1
|
Kessler EL, Dal Canto E, Diez-Benavente E, van Ommen AM, Kapteijn D, Glade MC, Bekkering S, Haitjema S, Valstar G, Cramer MJ, Rutten FH, Teske AJ, Menken R, Hofstra L, den Ruijter HM, Riksen NP, de Jager SCA. Non-classical monocytes are associated with functional markers of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction. Int J Cardiol 2025; 429:133161. [PMID: 40088950 DOI: 10.1016/j.ijcard.2025.133161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 02/13/2025] [Accepted: 03/12/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND Inflammatory conditions such as obesity and diabetes are linked to intermediate/non-classical monocyte activation, contributing to left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF). OBJECTIVE To investigate whether circulating monocyte subtypes and their activity are associated with the presence LVDD and HFpEF. METHODS We analyzed peripheral blood mononuclear cells (PBMCs) from 73 patients with or without LVDD/HFpEF. Cytokine secretion was measured post-stimulation, and gene expression was assessed via RNA sequencing. Monocyte subtypes were characterized using flow cytometry, and macrophage polarization was evaluated. We also examined the relationship between immunological markers and echocardiographic indicators of LVDD. RESULTS Among the participants, 24 were controls, 23 had LVDD, and 26 had HFpEF. PBMCs from LVDD patients secreted significantly less Interleukin-6 compared to controls (2053 ± 708 pg/mL vs 12,273 ± 3357 pg/mL, p = 0.008). RNA sequencing indicated increased estrogen receptor pathway activity in LVDD. HFpEF patients exhibited a 1.5-fold increase in intermediate monocytes and a significant rise in non-classical monocytes compared to controls. Stimulated macrophages from LVDD and HFpEF patients showed less CD206/CD80 expression, indicating a shift towards M2-macrophage polarization. Notably, higher non-classical monocyte counts correlated with lower E' septal velocity, suggesting an association with diastolic impairment (β = -0.15, p = 0.041). CONCLUSIONS LVDD and HFpEF are associated with a shift towards non-classical monocyte subtypes and higher numbers of non-classical monocytes are associated with signs of diastolic impairment. These findings highlight the importance of the inflammatory component in LVDD and HFpEF.
Collapse
Affiliation(s)
- Elise L Kessler
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Laboratory for Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Utrecht Regenerative Medicine Center, Circulatory Health Laboratory, University, Utrecht, the Netherlands
| | - Elisa Dal Canto
- Laboratory for Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Ernest Diez-Benavente
- Laboratory for Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Anne-Mar van Ommen
- Laboratory for Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Daniek Kapteijn
- Laboratory for Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Marleen C Glade
- Laboratory for Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Siroon Bekkering
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Saskia Haitjema
- Central Diagnostic Laboratory, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Gideon Valstar
- Laboratory for Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Maarten J Cramer
- Clinical Cardiology Department, University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Frans H Rutten
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Arco J Teske
- Clinical Cardiology Department, University Medical Center Utrecht, Utrecht University, the Netherlands
| | - Roxana Menken
- Cardiology Centers of the Netherlands, the Netherlands
| | | | - Hester M den Ruijter
- Laboratory for Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Niels P Riksen
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Saskia C A de Jager
- Laboratory for Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Utrecht Regenerative Medicine Center, Circulatory Health Laboratory, University, Utrecht, the Netherlands.
| |
Collapse
|
2
|
Myachina TA, Butova XA, Simonova RA, Volzhaninov DA, Kochurova AM, Kopylova GV, Shchepkin DV, Khokhlova AD. The Contractile Function of Ventricular Cardiomyocytes Is More Sensitive to Acute 17β-Estradiol Treatment Compared to Atrial Cardiomyocytes. Cells 2025; 14:561. [PMID: 40277887 PMCID: PMC12026394 DOI: 10.3390/cells14080561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 04/26/2025] Open
Abstract
17β-estradiol (E2) is the most active metabolite of estrogen with a wide range of physiological action on cardiac muscle. Previous studies have reported E2 effects predominantly for the ventricles, while the E2 impact on the atria has been less examined. In this study, we focused on the direct E2 effects on atrial and ventricular contractility at the cellular and molecular levels. Single atrial and ventricular cardiomyocytes (CM) from adult (24 weeks-old) female Wistar rats were incubated with 10 nM E2 for 15 min. Sarcomere length and cytosolic [Ca2+]i transients were measured in mechanically non-loaded CM, and the tension-length relationship was studied in CM mechanically loaded by carbon fibers. The actin-myosin interaction and sarcomeric protein phosphorylation were analyzed using an in vitro motility assay and gel electrophoresis with Pro-Q Diamond phosphoprotein stain. E2 had chamber-specific effects on the contractile function of CM with a pronounced influence on ventricular CM. The characteristics of [Ca2+]i transients did not change in both atrial and ventricular CM. However, in ventricular CM, E2 reduced the amplitude and maximum velocity of sarcomere shortening and decreased the slope of the passive tension-length relationship that was associated with increased TnI and cMyBP-C phosphorylation. E2 treatment accelerated the cross-bridge cycle of both atrial and ventricular myosin that was associated with increased phosphorylation of the myosin essential light chain. This study shows that E2 impairs the mechanical function of the ventricular myocardium while atrial contractility remains mostly preserved. Hormonal replacement therapy (HRT) with estrogen is by far the most effective therapy for treating climacteric symptoms experienced during menopause. Here we found a chamber specificity of myocardial contractile function to E2 that should be taken into account for the potential side effects of HRT.
Collapse
Affiliation(s)
- Tatiana A. Myachina
- Institute of Immunology and Physiology UrB RAS, 620049 Yekaterinburg, Russia; (T.A.M.); (R.A.S.); (D.A.V.); (D.V.S.)
| | - Xenia A. Butova
- Institute of Immunology and Physiology UrB RAS, 620049 Yekaterinburg, Russia; (T.A.M.); (R.A.S.); (D.A.V.); (D.V.S.)
| | - Raisa A. Simonova
- Institute of Immunology and Physiology UrB RAS, 620049 Yekaterinburg, Russia; (T.A.M.); (R.A.S.); (D.A.V.); (D.V.S.)
| | - Denis A. Volzhaninov
- Institute of Immunology and Physiology UrB RAS, 620049 Yekaterinburg, Russia; (T.A.M.); (R.A.S.); (D.A.V.); (D.V.S.)
| | - Anastasia M. Kochurova
- Institute of Immunology and Physiology UrB RAS, 620049 Yekaterinburg, Russia; (T.A.M.); (R.A.S.); (D.A.V.); (D.V.S.)
| | - Galina V. Kopylova
- Institute of Immunology and Physiology UrB RAS, 620049 Yekaterinburg, Russia; (T.A.M.); (R.A.S.); (D.A.V.); (D.V.S.)
| | - Daniil V. Shchepkin
- Institute of Immunology and Physiology UrB RAS, 620049 Yekaterinburg, Russia; (T.A.M.); (R.A.S.); (D.A.V.); (D.V.S.)
- Institute of Natural Sciences and Mathematics, Ural Federal University, 620026 Yekaterinburg, Russia
| | | |
Collapse
|
3
|
Hikoso S. Significance and perspective of establishing a female animal model for heart failure with preserved ejection fraction. Hypertens Res 2025; 48:1631-1633. [PMID: 39871004 DOI: 10.1038/s41440-024-02094-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 12/21/2024] [Indexed: 01/29/2025]
Affiliation(s)
- Shungo Hikoso
- Department of Cardiovascular Medicine, Nara Medical University, Kashihara, Japan.
| |
Collapse
|
4
|
Dushay J, Rickers ES, Wang E, Gilman J, Zhang Y, Blankstein R, Gervino EV, Jerosch‐Herold M, Veves A. Effects of Age and Sex on Systemic Inflammation and Cardiometabolic Function in Individuals With Type 2 Diabetes. J Am Heart Assoc 2025; 14:e037863. [PMID: 39846296 PMCID: PMC12074762 DOI: 10.1161/jaha.124.037863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 12/05/2024] [Indexed: 01/24/2025]
Abstract
BACKGROUND Systemic inflammation, aging, and type 2 diabetes (T2D) lead to varying degrees of cardiovascular dysfunction and impaired aerobic exercise capacity. This study evaluates the impact of inflammation and sex differences on coronary and peripheral vascular function and exercise capacity in older individuals with and without T2D. METHODS Older individuals (aged≥65 years) underwent biochemical and tissue inflammatory phenotyping, cardiopulmonary exercise testing, cardiovascular magnetic resonance imaging, and vascular reactivity testing. Correlation and regression analyses determined the effects of systemic inflammation, older age, and sex on cardiovascular health, stratified by T2D status. RESULTS For the 133 recruited individuals (44% women; median age, 71±7 years, 41% with T2D), the presence of T2D most significantly increased the white blood cell count (P=0.004; P.adj.=0.140) among markers of systemic inflammation. White blood cell count was comparable in men and women. Hyperemic myocardial blood flow and flow-mediated and flow-independent nitroglycerin-induced brachial artery dilation were significantly impaired in men but not women with T2D. Peak oxygen consumption during exercise was lower with T2D (P=0.021), and overall reduced in women compared with men (P=0.002). Across all participants, both peak oxygen consumption during exercise and hyperemic myocardial blood flow were significantly impaired with increased white blood cell count. Women showed more adverse myocardial remodeling assessed by extracellular volume than men (P=0.008), independently of T2D status. CONCLUSIONS The pathophysiological manifestations of T2D on vascular function and aerobic exercise capacity are distinct in older men and women, and this may reflect underlying differences in vascular and myocardial aging in the presence of T2D.
Collapse
Affiliation(s)
- Jody Dushay
- Division of EndocrinologyBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonMA
| | - Eva S. Rickers
- Department of RadiologyBrigham and Women’s Hospital, Harvard Medical SchoolBostonMA
- Medical FacultyUniversity of Cologne, and Department of Neurology, University Hospital CologneCologneGermany
| | - Enya Wang
- Rongxiang Xu Center for Regenerative Therapeutics, Microcirculation Lab, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA
| | - Jessica Gilman
- Rongxiang Xu Center for Regenerative Therapeutics, Microcirculation Lab, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA
| | - Ying Zhang
- Rongxiang Xu Center for Regenerative Therapeutics, Microcirculation Lab, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA
- Currently at Department of EndocrinologyThe Third People’s Hospital of ShenzhenShenzhenGuangdongChina
| | - Ron Blankstein
- Division of CardiologyBrigham and Women’s Hospital, Harvard Medical SchoolBostonMA
| | - Ernest V. Gervino
- Division of CardiologyBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonMA
| | | | - Aristidis Veves
- Rongxiang Xu Center for Regenerative Therapeutics, Microcirculation Lab, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA
| |
Collapse
|
5
|
Wu X, Li J, Xu Z, Feng Y. Gender differences in the prognostic impact of uric acid in patients with heart failure and preserved ejection fraction. BMC Cardiovasc Disord 2025; 25:29. [PMID: 39825228 PMCID: PMC11742201 DOI: 10.1186/s12872-025-04481-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 01/06/2025] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND Uric acid has been identified as an independent predictor of poor outcomes in patients with heart failure with preserved ejection fraction (HFpEF). However, the impact of gender differences on this association is not fully explored. METHODS This retrospective cohort study included hospitalized patients with HFpEF from June 2018 to October 2022. The primary outcome was a composite endpoint, defined as the occurrence of all-cause mortality and heart failure readmission. Kaplan-Meier survival analysis and stratified Cox regression examined the combined effect of gender and uric acid on the composite endpoint, and restricted cubic spline curves were applied to visualize the relationship. RESULTS The study included 547 patients, with 267 females and 280 males. In the entire cohort, each mg/dL increase in uric acid was associated with a 4% increase in the risk of the composite endpoint (HR: 1.04, 95%CI:1.01-1.09). This association was more pronounced in females, with a 9% increase in the risk of the composite endpoint per mg/dL increase in uric acid (95%CI: 1.02-1.17). Restrict cubic spline curves analysis demonstrated a significant linear correlation between increasing uric acid levels and higher risk of the composite endpoint in female patients (P = 0.028). Kaplan-Meier analysis revealed higher survival probabilities for females compared to males (P = 0.002). However, survival rates for females with high uric acid levels were similar to those for males with high uric acid levels. CONCLUSIONS Baseline serum uric acid levels are significantly associated with the composite endpoint in patients with HFpEF, particularly among females.
Collapse
Affiliation(s)
- Xuefeng Wu
- Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106, Zhongshan 2 Road, Yuexiu District, Guangzhou, 510080, China
- Department of Cardiology, The First People's Hospital of Foshan, No. 81, North Lingnan Avenue, Chancheng District, Foshan, Guangdong Province, 528000, China
| | - Jianming Li
- Department of Cardiology, The First People's Hospital of Foshan, No. 81, North Lingnan Avenue, Chancheng District, Foshan, Guangdong Province, 528000, China
| | - Zhaoyan Xu
- Department of Cardiology, The First People's Hospital of Foshan, No. 81, North Lingnan Avenue, Chancheng District, Foshan, Guangdong Province, 528000, China.
| | - Yingqing Feng
- Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106, Zhongshan 2 Road, Yuexiu District, Guangzhou, 510080, China.
| |
Collapse
|
6
|
Sivasinprasasn S, Chattipakorn K, Pratchayasakul W, Chattipakorn SC, Chattipakorn N. N-Acetylcysteine enhances low-dose estrogen efficacy against ischemia-reperfusion injury in estrogen-deprived obese insulin-resistant rats. Menopause 2025; 32:81-90. [PMID: 39626181 DOI: 10.1097/gme.0000000000002452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2024]
Abstract
OBJECTIVES Postmenopausal women are at higher risk of metabolic syndrome and cardiovascular disease, which are aggravated by obesity. Although estrogen provides cardiometabolic protection, chronic high-dose treatment could be harmful. This study investigated the efficacy of combined N-acetylcysteine (NAC) and low-dose estrogen treatment against cardiometabolic dysfunction in female estrogen-deprived obese rats with cardiac ischemia-reperfusion (I/R) injury. METHODS Bilateral ovariectomized (O) female Wistar rats were fed a high-fat diet (H) for 12 weeks. Then, rats were treated for 4 weeks with one of the following: vehicle (OH; sesame oil), regular-dose estrogen (E; 50 μg/kg/d), low-dose estrogen (e; 25 μg/kg/d), NAC (N; 100 mg/kg/d), or combined low-dose estradiol with NAC (eN). All rats then underwent cardiac I/R injury, and the left ventricle (LV) function and mitochondrial function were investigated (n = 6/group). Statistical analysis was performed by one-way ANOVA followed by Fisher's least significant difference post hoc test. RESULTS Body weight, visceral fat, plasma glucose, and plasma cholesterol were significantly increased with impaired LV function and heart rate variability in OH rats. OH-E rats had decreased plasma insulin and Homeostatic Model Assessment for Insulin Resistance index. Both OH-E and OH-eN rats had similarly improved heart rate variability and LV function. During cardiac I/R, OH-E and OH-eN rats had preserved left ventricular ejection fraction, stroke volume, and attenuated arrhythmias. Impaired cardiac mitochondrial function and infarct size were similarly reduced in OH-E and OH-eN rats. CONCLUSIONS Combined NAC and low-dose estrogen treatment shares similar efficacy as regular-dose estrogen in attenuating cardiac dysfunction, cardiac mitochondrial dysfunction, and protecting the heart against I/R injury in estrogen-deprived obese insulin-resistant rats.
Collapse
Affiliation(s)
| | - Kenneth Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | | | | |
Collapse
|
7
|
Araújo J. Diastolic Dysfunction and Renal Disease: Analysis, Mechanisms, and Different Perspectives. Cureus 2025; 17:e76959. [PMID: 39906471 PMCID: PMC11793875 DOI: 10.7759/cureus.76959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2024] [Indexed: 02/06/2025] Open
Abstract
Over the past few decades, heart failure with preserved ejection fraction has established itself as an individual clinical entity. Although it is associated with a better prognosis, it offers high resistance to classic treatment techniques, and the frequency of hospitalizations and mortality rates are comparable to cases of heart failure with reduced ejection fraction. Heart failure often leads to death and morbidity, and there has recently been a growing interest in studying the relationship between cardiac and renal function due to epidemiological evidence indicating that even a modest deterioration in renal function is a considerable risk factor in patients with heart failure, myocardial infarction or in the context of cardiovascular surgery. In fact, studies have proven that patients with chronic kidney disease have a cardiovascular risk about 10 times higher than a population of the same age, sex, and race without it. Before writing this review, research literature on heart failure with preserved ejection fraction and chronic kidney disease was reviewed. Studies have shown that in patients with chronic kidney disease, heart failure is mostly caused by the presence of left ventricular diastolic dysfunction, with aggravating comorbidities such as high blood pressure and coronary heart disease. A possible underlying mechanism may be the excessive activation of the renin-angiotensin-aldosterone system, which is known to be a determinant in the onset of profibrotic factors. In fact, it is known that, in patients with chronic heart failure, the renin-angiotensin-aldosterone system is activated, and it has even been shown that the activity of increased plasma renin levels directly contributes to mortality. Angiotensin II promotes cardiac remodeling, and aldosterone may increase myocardial fibrosis, which is a marker of diastolic dysfunction and cardiac necrosis, acting as an endogenous bioactive factor involved in the process of vascular calcification. On the other hand, the development of diastolic dysfunction in patients with chronic kidney disease may result from disorders of metabolism. Besides, evidence indicates that individuals with 25-hydroxyvitamin D deficiency have an increased risk of developing various cardiovascular conditions, such as hypertension, peripheral vascular disease, myocardial infarction, diabetes mellitus, heart failure, and even death. In recent studies, it has been described that the direct effect of vitamin D on cardiomyocytes consists essentially in the acceleration of myocardial relaxation, leading to the hypothesis that it causes a determining effect on diastolic function. Currently, both heart failure with preserved ejection fraction and chronic kidney disease are very prevalent and are closely linked to several other factors, including disturbances in phospho-calcium metabolism and variations in serum vitamin D levels. Although the concept of heart failure began to be explored a few decades ago, further studies are required in order to explain the factors that created the controversy behind the concept of diastolic dysfunction. This review aims precisely to identify the areas that lack further investigation, which can be essential to the development of more effective treatments and subsequently obtain better outcomes.
Collapse
Affiliation(s)
- Joana Araújo
- Family Medicine, Unidade Local de Saúde do Alto Minho, Viana do Castelo, PRT
| |
Collapse
|
8
|
Agarwal S, Farhat K, Khan MS, DeSimone CV, Deshmukh A, Munir MB, Asad ZUA, Stavrakis S. Sex differences in atrial fibrillation ablation outcomes in patients with heart failure. J Interv Card Electrophysiol 2024; 67:1807-1819. [PMID: 38811501 DOI: 10.1007/s10840-024-01833-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 05/21/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND There is a lack of data on the impact of sex on the outcomes of patients with heart failure (HF) undergoing atrial fibrillation (AF) ablation. We aimed to analyze the association of sex with outcomes of atrial fibrillation ablation in patients with heart failure. METHODS The National Readmissions Database (NRD) was analyzed from 2016 to 2019 to identify patients ≥ 18 years old with heart failure (HF) undergoing AF ablation. The outcomes of interest included peri-procedural complications, in-hospital mortality, resource utilization, and unplanned 1-year readmissions. The final cohort was divided into patients with HFrEF and HFpEF and outcomes were compared between males and females in both cohorts. RESULTS A total of 23,277 patients with HF underwent AF ablation between 2016 and 2019, of which 14,480 had HFrEF and 8,797 had HFpEF. Among patients with HFrEF, 61.6% were males and 38.4% were females whereas, among patients with HFpEF, 35.4% were males and 64.6% were females. On a multivariable-adjusted analysis, in patients with HFrEF, there was no difference in the odds of in-hospital mortality, peri-procedural complications, or 1-year HF-related/AF-related/all-cause readmissions between males and females. In patients with HFpEF, females had a higher risk 1-year HF-related readmissions (adjusted hazards ratio: 1.46; 95% CI: 1.13-1.87; p = 0.01), without any difference in the 1-year AF-related/all-cause readmissions, in-hospital mortality, or peri-procedural complications. CONCLUSION Our results show that females with HFrEF undergoing AF ablation have similar outcomes whereas females with HFpEF have higher 1-year HF readmissions with no difference in the other outcomes, compared to males.
Collapse
Affiliation(s)
- Siddharth Agarwal
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Kassem Farhat
- Department of Internal Medicine, Yale School of Medicine, Waterbury, CT, USA
| | - Muhammad Salman Khan
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | | | | | - Muhammad Bilal Munir
- Division of Cardiovascular Medicine, University of California Davis, Sacramento, CA, USA
| | - Zain Ul Abideen Asad
- Department of Cardiology, University of Oklahoma Health Sciences Center, 800 Stanton L Young Blvd, Suite 5400, Oklahoma City, OK, 73104, USA
| | - Stavros Stavrakis
- Department of Cardiology, University of Oklahoma Health Sciences Center, 800 Stanton L Young Blvd, Suite 5400, Oklahoma City, OK, 73104, USA.
| |
Collapse
|
9
|
Kovács Á, Zhazykbayeva S, Herwig M, Fülöp GÁ, Csípő T, Oláh N, Hassoun R, Budde H, Osman H, Kaçmaz M, Jaquet K, Priksz D, Juhász B, Akin I, Papp Z, Schmidt WE, Mügge A, El-Battrawy I, Tóth A, Hamdani N. Sex-specific cardiovascular remodeling leads to a divergent sex-dependent development of heart failure in aged hypertensive rats. GeroScience 2024; 46:4543-4561. [PMID: 38656649 PMCID: PMC11336029 DOI: 10.1007/s11357-024-01160-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Accepted: 04/09/2024] [Indexed: 04/26/2024] Open
Abstract
INTRODUCTION The prevalence of heart failure with preserved ejection fraction (HFpEF) is continuously rising and predominantly affects older women often hypertensive and/or obese or diabetic. Indeed, there is evidence on sex differences in the development of HF. Hence, we studied cardiovascular performance dependent on sex and age as well as pathomechanisms on a cellular and molecular level. METHODS We studied 15-week- and 1-year-old female and male hypertensive transgenic rats carrying the mouse Ren-2 renin gene (TG) and compared them to wild-type (WT) controls at the same age. We tracked blood pressure and cardiac function via echocardiography. After sacrificing the 1-year survivors we studied vascular smooth muscle and endothelial function. Isolated single skinned cardiomyocytes were used to determine passive stiffness and Ca2+-dependent force. In addition, Western blots were applied to analyse the phosphorylation status of sarcomeric regulatory proteins, titin and of protein kinases AMPK, PKG, CaMKII as well as their expression. Protein kinase activity assays were used to measure activities of CaMKII, PKG and angiotensin-converting enzyme (ACE). RESULTS TG male rats showed significantly higher mortality at 1 year than females or WT male rats. Left ventricular (LV) ejection fraction was specifically reduced in male, but not in female TG rats, while LV diastolic dysfunction was evident in both TG sexes, but LV hypertrophy, increased LV ACE activity, and reduced AMPK activity as evident from AMPK hypophosphorylation were specific to male rats. Sex differences were also observed in vascular and cardiomyocyte function showing different response to acetylcholine and Ca2+-sensitivity of force production, respectively cardiomyocyte functional changes were associated with altered phosphorylation states of cardiac myosin binding protein C and cardiac troponin I phosphorylation in TG males only. Cardiomyocyte passive stiffness was increased in TG animals. On a molecular level titin phosphorylation pattern was altered, though alterations were sex-specific. Thus, also the reduction of PKG expression and activity was more pronounced in TG females. However, cardiomyocyte passive stiffness was restored by PKG and CaMKII treatments in both TG sexes. CONCLUSION Here we demonstrated divergent sex-specific cardiovascular adaptation to the over-activation of the renin-angiotensin system in the rat. Higher mortality of male TG rats in contrast to female TG rats was observed as well as reduced LV systolic function, whereas females mainly developed HFpEF. Though both sexes developed increased myocardial stiffness to which an impaired titin function contributes to a sex-specific molecular mechanism. The functional derangements of titin are due to a sex-specific divergent regulation of PKG and CaMKII systems.
Collapse
Affiliation(s)
- Árpád Kovács
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44801, Bochum, Germany
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary
| | - Saltanat Zhazykbayeva
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44801, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, 44801, Bochum, Germany
| | - Melissa Herwig
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44801, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, 44801, Bochum, Germany
| | - Gábor Á Fülöp
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary
| | - Tamás Csípő
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary
| | - Nikolett Oláh
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary
| | - Roua Hassoun
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44801, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, 44801, Bochum, Germany
| | - Heidi Budde
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44801, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, 44801, Bochum, Germany
| | - Hersh Osman
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44801, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, 44801, Bochum, Germany
| | - Mustafa Kaçmaz
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44801, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, 44801, Bochum, Germany
- HCEMM-SU Cardiovascular Comorbidities Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, 1089, Hungary
| | - Kornelia Jaquet
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44801, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, 44801, Bochum, Germany
| | - Dániel Priksz
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary
| | - Béla Juhász
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary
| | - Ibrahim Akin
- University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany
| | - Zoltán Papp
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary
- Research Centre for Molecular Medicine, University of Debrecen, Debrecen, 4032, Hungary
| | - Wolfgang E Schmidt
- Department of Medicine I, St. Josef Hospital, UK RUB, Ruhr University Bochum, 44801, Bochum, Germany
| | - Andreas Mügge
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44801, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, 44801, Bochum, Germany
- Department of Cardiology and Angiology, Bergmannsheil University Hospitals, UK RUB, Ruhr University of Bochum, 44789, Bochum, Germany
| | - Ibrahim El-Battrawy
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44801, Bochum, Germany
- Department of Cardiology and Angiology, Bergmannsheil University Hospitals, UK RUB, Ruhr University of Bochum, 44789, Bochum, Germany
| | - Attila Tóth
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary
- Research Centre for Molecular Medicine, University of Debrecen, Debrecen, 4032, Hungary
| | - Nazha Hamdani
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, 44801, Bochum, Germany.
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, 44801, Bochum, Germany.
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, 44801, Bochum, Germany.
- HCEMM-SU Cardiovascular Comorbidities Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, 1089, Hungary.
- Department of Physiology, Cardiovascular Research Institute, Maastricht University, 6229, ER, Maastricht, The Netherlands.
| |
Collapse
|
10
|
Krittanawong C, Britt WM, Rizwan A, Siddiqui R, Khawaja M, Khan R, Joolharzadeh P, Newman N, Rivera MR, Tang WHW. Clinical Update in Heart Failure with Preserved Ejection Fraction. Curr Heart Fail Rep 2024; 21:461-484. [PMID: 39225910 DOI: 10.1007/s11897-024-00679-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/02/2024] [Indexed: 09/04/2024]
Abstract
PURPOSE OF REVIEW To review the most recent clinical trials and data regarding epidemiology, pathophysiology, diagnosis, and treatment of heart failure with preserved ejection fraction with an emphasis on the recent trends in cardiometabolic interventions. RECENT FINDINGS Heart failure with preserved ejection fraction makes up approximately half of overall heart failure and is associated with significant morbidity, mortality, and overall burden on the healthcare system. It is a complex, heterogenous syndrome and clinical trials, to this point, have not revealed quite as many effective treatment options when compared to heart failure with reduced ejection fraction. Nevertheless, there is an expanding amount of data insight into the pathogenesis of this disease and the potential for newer therapies and management strategies. Heart failure with preserved ejection fraction pathology has been found to be linked to abnormal energetics, myocyte hypertrophy, cell signaling, inflammation, ischemia, and fibrosis. These mechanisms also intricately overlap with the significant comorbidities often associated with heart failure with preserved ejection fraction including, but not limited to, atrial fibrillation, chronic kidney disease, hypertension, obesity and coronary artery disease. Treatment of this disease, therefore, should focus on the management and strict regulation of these comorbidities by pharmacologic and nonpharmacologic means. In this review, a clinical update is provided reviewing the most recent clinical trials and data regarding epidemiology, pathophysiology, diagnosis, and treatment of heart failure with preserved ejection fraction with an emphasis on the recent trend in cardiometabolic interventions.
Collapse
Affiliation(s)
| | - William Michael Britt
- Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Affan Rizwan
- Baylor College of Medicine, Houston, TX, 77030, USA
| | - Rehma Siddiqui
- Department of Internal Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA
| | - Muzamil Khawaja
- Division of Cardiology, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Rabisa Khan
- Department of Internal Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA
| | - Pouya Joolharzadeh
- John T Milliken Department of Medicine, Division of Cardiovascular Disease, Barnes-Jewish Hospital, St Louis, United States
| | - Noah Newman
- Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Mario Rodriguez Rivera
- Advanced Heart Failure and Transplant, Barnes-Jewish Hospital Washington University in St Louis School of Medicine, St.Louis, MO, USA
| | - W H Wilson Tang
- Kaufman Center for Heart Failure Treatment and Recovery, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH, 44195, USA
| |
Collapse
|
11
|
Wang J, Chen Y. Age at menopause and risk of ischaemic stroke: a systematic review and meta-analysis. Eur J Prev Cardiol 2024; 31:1595-1605. [PMID: 38700014 DOI: 10.1093/eurjpc/zwae156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 03/05/2024] [Accepted: 04/20/2024] [Indexed: 05/05/2024]
Abstract
AIMS Despite ischaemic stroke having much importance as one of the top 10 causes of death in older women, there are limited data on age at menopause and ischaemic stroke. We performed a systematic review and meta-analysis to estimate the effect of age at menopause on ischaemic stroke. METHODS AND RESULTS We screened four databases (PubMed, Cochrane, Web of Science, and EMBASE databases) up to 17 July 2023. This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered with PROSPERO (CRD42023444245). Data extraction and quality assessment were independently undertaken by two reviewers. A random-effects model was used for meta-analysis using Revman5.4 to calculate the risk ratio of the incidence of ischaemic stroke. Heterogeneity was assessed using I2. Meta-regression and assessment for bias were performed. Out of 725 records identified, 10 studies were included in the qualitative synthesis and the quantitative meta-analysis. The pooled incidence rate for ischaemic strokes which age at menopause before 43 years old was 1.22 [95% confidence interval (CI): 1.02-1.46]. The pooled incidence rate of early menopause was 1.26 (95% CI: 1.07-1.48) for ischaemic stroke. The incidence rate of ischaemic stroke for women with early menopause may be in an environment with a high incidence for a long time. CONCLUSION This meta-analysis suggests that early menopause is associated with an increased risk of ischaemic stroke. Age at onset of menopause before 43 years old may be the cut-off value of increased risk of ischaemic stroke.
Collapse
Affiliation(s)
- Jie Wang
- Department of Obstetrics and Gynecology, Beijing Tiantan Hospital, Capital Medical University, 119 South Fourth Ring Road West, Fengtai District, Beijing 100070, China
| | - Ying Chen
- Department of Obstetrics and Gynecology, Beijing Tiantan Hospital, Capital Medical University, 119 South Fourth Ring Road West, Fengtai District, Beijing 100070, China
| |
Collapse
|
12
|
Colombo D, Mercurio V, Klersy C, Temporelli P, Rossi A, Carluccio E, La Rovere MT, Dini FLL, Nappi R, Acquaro M, Greco A, Turco A, Schirinzi S, Scelsi L, Ghio S. The influence of sex on heart failure mortality. J Cardiovasc Med (Hagerstown) 2024; 25:693-699. [PMID: 39083064 DOI: 10.2459/jcm.0000000000001656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/06/2024]
Abstract
AIMS Little research has investigated how sex may affect the prognosis of patients with chronic heart failure (HF). The present study was aimed at exploring sex-specific differences in prognosis in a cohort of patients with chronic HF, categorized according to severity of left ventricular dysfunction (HFrEF, HFmrEF and HFpEF), right ventricular (RV) dysfunction and ischemic (IHD) or nonischemic (no-IHD) etiology. METHODS This retrospective analysis included 1640 HF patients of whom 24% were females, 759 patients had IHD, 1110 patients had HFrEF, 147 patients had HFmrEF and 383 patients had HFpEF. The median follow-up period was 63 months (25th-75th 27-93). RESULTS In the no-IHD group, no statistically significant sex differences emerged regarding survival, regardless of age and severity of cardiac dysfunction. In contrast, in the IHD group, females had a significantly lower event rate than males in the age group between 65 and 79 years [hazard ratio (HR) 0.39; 95% confidence interval (CI): 0.86-0.18; P < 0.01]; in addition, a lower event rate was observed in females compared with males among patients with HFrEF (HR 0.47; 95% CI: 0.88-0.25; P < 0.01), among patients without RV dysfunction (HR 0.58; 95% CI: 1.02-0.33; P = 0.048) and among patients without diabetes (HR 0.44; 95% CI: 0.84-0.23; P < 0.01). CONCLUSION In nonischemic patients there was no difference between males and females in terms of survival whereas in patients with ischemic etiology survival was better in females among elderly patients, in HFrEF patients, in the absence of RV dysfunction and in the absence of diabetes.
Collapse
Affiliation(s)
- Davide Colombo
- Division of Cardiology - Fondazione IRCCS Policlinico S Matteo, Pavia
| | - Valentina Mercurio
- Department of Translational Medical Sciences, 'Federico II' University, Naples
| | - Catherine Klersy
- Biostatistics and Clinical Trial Center - Fondazione IRCCS Policlinico S Matteo
| | - Pierluigi Temporelli
- Istituti Clinici Scientifici Maugeri, IRCCS, Department of Cardiology, Istituto Scientifico di Veruno, Novara
| | | | - Erberto Carluccio
- Cardiology and Cardiovascular Pathophysiology, S. Maria della Misericordia Hospital, University of Perugia, Perugia
| | - Maria Teresa La Rovere
- Istituti Clinici Scientifici Maugeri, IRCCS, Department of Cardiology, Istituto Scientifico di Montescano, Pavia
| | | | - Rossella Nappi
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy. Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause, IRCCS San Matteo Foundation, Pavia, Italy
| | - Mauro Acquaro
- Division of Cardiology - Fondazione IRCCS Policlinico S Matteo, Pavia
| | - Alessandra Greco
- Division of Cardiology - Fondazione IRCCS Policlinico S Matteo, Pavia
| | - Annalisa Turco
- Division of Cardiology - Fondazione IRCCS Policlinico S Matteo, Pavia
| | - Sandra Schirinzi
- Division of Cardiology - Fondazione IRCCS Policlinico S Matteo, Pavia
| | - Laura Scelsi
- Division of Cardiology - Fondazione IRCCS Policlinico S Matteo, Pavia
| | - Stefano Ghio
- Division of Cardiology - Fondazione IRCCS Policlinico S Matteo, Pavia
| |
Collapse
|
13
|
Ahmed HA, Shaaban AA, Makled MN, Ibrahim TM. G protein-coupled estrogen receptor selective agonist, G1, improves the molecular and biochemical markers in a cisplatin mouse model of CKD. Chem Biol Interact 2024; 398:111065. [PMID: 38795875 DOI: 10.1016/j.cbi.2024.111065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 05/06/2024] [Accepted: 05/22/2024] [Indexed: 05/28/2024]
Abstract
Multiple cycles of cisplatin result in a permanent loss of kidney function with severe and life-limited chronic kidney disease (CKD) after successful cisplatin therapy. Recently, studies have showed that the activation of G-protein coupled estrogen receptor (GPER) could protect against kidney disease. This study aimed to test the potential of the G1 compound, a GPER selective agonist, to prevent CKD development after cisplatin therapy. Male C57BL/6 mice were exposed to 2 cycles of 2.5 mg/kg cisplatin in a regimen miming clinical exposure (1 injection daily for 5 days, followed by a 16-day recovery period between cycles). G1 (50 or 100 μg/kg) was administered daily for 6 weeks. G1 dose-dependently improved kidney function biomarkers (serum creatinine, creatinine clearance, and protein excretion) and histopathological changes compared to the cisplatin-treated group. Collagen 3 expression was dose-dependently decreased in G1-treated groups that was parallel to the reduction of fibrosis in Masson's trichrome-stained sections. G1 administration also increased total antioxidant capacity (TAC) and nuclear factor erythroid 2-related factor 2 (Nrf2) and reduced the level of malondialdehyde and the proinflammatory cytokine, tumor necrosis factor-α. In addition, G1 downregulated the expression of inflammasome NLRP3 and nuclear factor kappa B p65 (NF-κB p65) in a dose-dependent manner. In conclusion, these data suggest that G1 could be a new therapeutic tool for CKD prevention post cisplatin therapy. These effects might be mediated through the activation of Nrf2 and the inhibition of NF-κB/NLRP3 signaling.
Collapse
MESH Headings
- Animals
- Cisplatin/pharmacology
- Male
- Receptors, G-Protein-Coupled/agonists
- Receptors, G-Protein-Coupled/metabolism
- Mice, Inbred C57BL
- Mice
- Renal Insufficiency, Chronic/drug therapy
- Renal Insufficiency, Chronic/chemically induced
- Renal Insufficiency, Chronic/metabolism
- Renal Insufficiency, Chronic/pathology
- Disease Models, Animal
- Kidney/drug effects
- Kidney/metabolism
- Kidney/pathology
- Biomarkers/metabolism
- Receptors, Estrogen/metabolism
- NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
- NF-E2-Related Factor 2/metabolism
- NF-E2-Related Factor 2/agonists
- NF-kappa B/metabolism
- Oxidative Stress/drug effects
Collapse
Affiliation(s)
- Hala A Ahmed
- Pharmacology and Biochemistry Department, Faculty of Pharmacy, Delta University for Science and Technology, Egypt; Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt
| | - Ahmed A Shaaban
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt; Faculty of Pharmacy, Jerash University, Jerash, 26150, Jordan
| | - Mirhan N Makled
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt.
| | - Tarek M Ibrahim
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Egypt
| |
Collapse
|
14
|
Dushay J, Rickers ES, Wang E, Gilman J, Zhang Y, Blankstein R, Gervino EV, Jerosch-Herold M, Veves A. Effects of Age and Sex on Systemic Inflammation and Cardiometabolic Function in Individuals with Type 2 Diabetes. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.05.08.24307092. [PMID: 38766042 PMCID: PMC11100929 DOI: 10.1101/2024.05.08.24307092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
Objective Systemic inflammation, aging, and type 2 diabetes (T2DM) all contribute to the development of cardiovascular dysfunction and impaired aerobic exercise capacity but their interplay remains unclear. This study evaluates the impact of age, sex, and inflammation on coronary and peripheral vascular function and exercise capacity in elderly individuals with and without type 2 diabetes (T2DM). Research Design and Methods Elderly individuals (age ≥65 years) underwent biochemical and tissue inflammatory phenotyping, cardiopulmonary exercise testing (CPET), cardiovascular magnetic resonance (CMR) imaging, and vascular reactivity testing. Correlation and regression analyses determined the effects of systemic inflammation, older age, and sex on cardiovascular health, stratified by T2DM status. Results For the 133 recruited individuals (44% female; median age 71, IQR=7 years, 41% with T2DM) the presence of T2DM did not have an effect on most blood serum inflammatory markers and skin biopsies. Hyperemic myocardial blood flow (hMBF), flow-mediated, and flow-independent nitroglycerin induced brachial artery dilation were significantly impaired in males, but not females with T2DM. Peak VO2 was lower with T2DM (p=0.022), mostly because of the effect of T2DM in females. Females showed more adverse myocardial remodeling assessed by extracellular volume (p=0.008), independent of T2DM status. Conclusions Our findings suggest that the pathophysiological manifestations of T2DM on vascular function and aerobic exercise capacity are distinct in elderly males and females and this may reflect underlying differences in vascular and myocardial aging in the presence of T2DM.
Collapse
|
15
|
Bos EME, Tol JTM, de Boer FC, Schenk J, Hermanns H, Eberl S, Veelo DP. Differences in the Incidence of Hypotension and Hypertension between Sexes during Non-Cardiac Surgery: A Systematic Review and Meta-Analysis. J Clin Med 2024; 13:666. [PMID: 38337360 PMCID: PMC10856734 DOI: 10.3390/jcm13030666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/12/2024] [Accepted: 01/20/2024] [Indexed: 02/12/2024] Open
Abstract
Background: Major determinants of blood pressure (BP) include sex and age. In youth, females have lower BP than males, yet in advanced age, more pronounced BP increases result in higher average BPs in females over 65. This hypothesis-generating study explored whether age-related BP divergence impacts the incidence of sex-specific intraoperative hypotension (IOH) or hypertension. Methods: We systematically searched PubMed and Embase databases for studies reporting intraoperative BP in males and females in non-cardiac surgery. We analyzed between-sex differences in the incidence of IOH and intraoperative hypertension (primary endpoint). Results: Among 793 identified studies, 14 were included in this meta-analysis, comprising 1,110,636 patients (56% female). While sex was not associated with IOH overall (females: OR 1.10, 95%CI [0.98-1.23], I2 = 99%), a subset of studies with an average age ≥65 years showed increased exposure to IOH in females (OR 1.17, 95%CI [1.01-1.35], I2 = 94%). One study reported sex-specific differences in intraoperative hypertension, with a higher incidence in females (31% vs. 28%). Conclusions: While sex-specific reporting on intraoperative BP was limited, IOH did not differ between sexes. However, an exploratory subgroup analysis offers the hypothesis that females of advanced age may face an increased risk of IOH, warranting further investigation.
Collapse
Affiliation(s)
- Elke M. E. Bos
- Department of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; (E.M.E.B.)
| | - Johan T. M. Tol
- Department of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; (E.M.E.B.)
| | - Fabienne C. de Boer
- Department of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; (E.M.E.B.)
| | - Jimmy Schenk
- Department of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; (E.M.E.B.)
- Department of Intensive Care, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Henning Hermanns
- Department of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; (E.M.E.B.)
| | - Susanne Eberl
- Department of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; (E.M.E.B.)
| | - Denise P. Veelo
- Department of Anaesthesiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; (E.M.E.B.)
| |
Collapse
|
16
|
Fumagalli C, Zocchi C, Cappelli F, Celata A, Tassetti L, Sasso L, Zampieri M, Argirò A, Marchi A, Targetti M, Berteotti M, Maurizi N, Mori F, Livi P, Baldini K, Tomberli A, Girolami F, Favilli S, Mecacci F, Olivotto I. Impact of pregnancy on the natural history of women with hypertrophic cardiomyopathy. Eur J Prev Cardiol 2024; 31:3-10. [PMID: 37531614 DOI: 10.1093/eurjpc/zwad257] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 07/26/2023] [Accepted: 07/31/2023] [Indexed: 08/04/2023]
Abstract
AIMS Whether pregnancy is a modifier of the long-term course and outcome of women with hypertrophic cardiomyopathy (HCM) is unknown. We assessed the association of pregnancy with long-term outcomes in HCM women. METHODS AND RESULTS Retrospective evaluation of women with HCM from 1970 to 2021. Only women with pregnancy-related information (pregnancy present or absent) and a follow-up period lasting ≥1 year were included. The peri-partum period was defined as -1 to 6 months after delivery. The primary endpoint was a composite for major adverse cardiovascular events [MACE: cardiovascular death, sudden cardiac death, appropriate defibrillator shock and heart failure (HF) progression]. Overall, 379 (58%) women were included. There were 432 pregnancies in 242 (63%) patients. In 29 (7.6%) cases, pregnancies (n = 39) occurred after HCM diagnosis. Among these, three carrying likely pathogenic sarcomeric variants suffered MACEs in the peri-partum period. At 10 ± 9 years of follow-up, age at diagnosis [hazard ratio (HR) 1.034, 95% confidence interval (CI) 1.018-1.050, P < 0.001] and New York Heart Association (NYHA) class (II vs. I: HR 1.944, 95% CI 0.896-4.218; III vs. I: HR 5.291, 95% CI 2.392-11.705, P < 0.001) were associated with MACE. Conversely, pregnancy was associated with reduced risk (HR 0.605; 95% CI 0.380-0.963, P = 0.034). Among women with pregnancy, multiple occurrences did not modify risk. CONCLUSIONS Pregnancy is not a modifier of long-term outcome in women with HCM and mostly occurs before a cardiac diagnosis. Most patients tolerate pregnancy well and do not show a survival disadvantage compared to women without. Pregnancy should not be discouraged, except in the presence of severe HF symptoms or high-risk features.
Collapse
Affiliation(s)
- Carlo Fumagalli
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
- Department of Advanced Medical and Surgical Sciences, University of Campania 'Luigi Vanvitelli', Piazza Miraglia, 2, Naples 80138, Italy
| | - Chiara Zocchi
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Francesco Cappelli
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Anastasia Celata
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Luigi Tassetti
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Laura Sasso
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Mattia Zampieri
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Alessia Argirò
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Alberto Marchi
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Mattia Targetti
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Martina Berteotti
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Niccolò Maurizi
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Fabio Mori
- Obstetrics and Gynecology Unit, Careggi University Hospital, Florence, Italy
| | - Paola Livi
- Obstetrics and Gynecology Unit, Careggi University Hospital, Florence, Italy
| | - Katia Baldini
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Alessia Tomberli
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
| | - Francesca Girolami
- Pediatric Cardiology, Meyer Children's University Hospital, Florence, Italy
| | - Silvia Favilli
- Pediatric Cardiology, Meyer Children's University Hospital, Florence, Italy
| | - Federico Mecacci
- Obstetrics and Gynecology Unit, Careggi University Hospital, Florence, Italy
| | - Iacopo Olivotto
- Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla, 3, Florence 50134, Italy
- Pediatric Cardiology, Meyer Children's University Hospital, Florence, Italy
| |
Collapse
|
17
|
Han BG, Pak D, Kim JS, Sohn Y. The moderating effect of fluid overload on the relationship between the augmentation index and left ventricular diastolic function in patients with CKD. Sci Rep 2024; 14:480. [PMID: 38177252 PMCID: PMC10767097 DOI: 10.1038/s41598-023-50746-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 12/24/2023] [Indexed: 01/06/2024] Open
Abstract
Increased vascular stiffness, fluid overload, and left ventricular diastolic dysfunction (LVDD) are common in patients with chronic kidney disease (CKD). We investigated the potential moderating effect of volume status in the relationship between arterial stiffness and left ventricular (LV) diastolic function in non-dialysis patients with stage 5 CKD. The radial augmentation index at a heart rate of 75 beats/min (rAIx75), overhydration/extracellular water (OH/ECW), and E/e´ ratio were concurrently measured in 152 consecutive patients. Each of these parameters reflects the status of vascular stiffness, fluid balance, and LV diastolic function, respectively. Hierarchical regression analysis demonstrated a significant interaction effect of OH/ECW for all patients (P = 0.015), even after controlling for confounders. In separate analyses, this interaction effect was particularly significant in women (P = 0.010), whereas its significance in patients with diabetes was marginally significant (P = 0.062). Our study suggested that fluid overload could be one of the more aggravating factors of LVDD in patients with CKD who have increased arterial stiffness. Therefore, it is advisable to conduct simultaneous assessments of vascular stiffness, fluid balance, and LV function, particularly in the specific groups mentioned earlier. Our results may serve as evidence applicable to patients with chronic heart failure.
Collapse
Affiliation(s)
- Byoung-Geun Han
- Department of Nephrology, Yonsei University Wonju College of Medicine, Kang-Won, Wonju, Korea
| | - Daewoo Pak
- Division of Data Science, Yonsei University, Kang-Won, Wonju, Korea
| | - Jae-Seok Kim
- Department of Nephrology, Yonsei University Wonju College of Medicine, Kang-Won, Wonju, Korea
| | - Yujin Sohn
- Department of Infectious Disease, Yonsei University Wonju College of Medicine, Kang-Won, Wonju, Korea.
| |
Collapse
|
18
|
Masuda M, Matsuda Y, Uematsu H, Sugino A, Ooka H, Kudo S, Fujii S, Asai M, Okamoto S, Ishihara T, Nanto K, Tsujimura T, Hata Y, Higashino N, Nakao S, Mano T. Clinical impact of left atrial remodeling pattern in patients with atrial fibrillation: Comparison of volumetric, electrical, and combined remodeling. J Cardiovasc Electrophysiol 2024; 35:171-181. [PMID: 38018401 DOI: 10.1111/jce.16129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/12/2023] [Accepted: 10/28/2023] [Indexed: 11/30/2023]
Abstract
INTRODUCTION Atrial fibrillation (AF) is accompanied by various types of remodeling, including volumetric enlargement and histological degeneration. Electrical remodeling reportedly reflects histological degeneration. PURPOSE To clarify the differences in determinants and clinical impacts among types of remodeling. METHODS This observational study included 1118 consecutive patients undergoing initial ablation for AF. Patients were divided into four groups: minimal remodeling (left atrial volume index [LAVI] < mean value and no low-voltage area [LVA], n = 477); volumetric remodeling (LAVI ≥ mean value and no LVA, n = 361); electrical remodeling (LAVI < mean value and LVA presence, n = 96); and combined remodeling (LAVI ≥ mean value and LVA presence, n = 184). AF recurrence and other clinical outcomes were followed up for 2 and 5 years, respectively. RESULTS Major determinants of each remodeling pattern were high age for electrical (odds ratio = 2.32, 95% confidence interval = 1.68-3.25) and combined remodeling (2.57, 1.88-3.49); female for electrical (3.85, 2.21-6.71) and combined remodeling (4.92, 2.90-8.25); persistent AF for combined remodeling (7.09, 3.75-13.4); and heart failure for volumetric (1.71, 1.51-2.53) and combined remodeling (2.21, 1.30-3.75). Recurrence rate after initial ablation increased in the order of minimal remodeling (20.1%), volumetric (27.4%) or electrical remodeling (36.5%), and combined remodeling (50.0%, p < .0001). A composite endpoint of heart failure, stroke, and death occurred in the order of minimal (3.4%), volumetric (7.5%) or electrical (8.3%), and combined remodeling (15.2%, p < .0001). CONCLUSION Volumetric, electrical, and combined remodeling were each associated with a unique patient background, and defined rhythm and other clinical outcomes.
Collapse
Affiliation(s)
- Masaharu Masuda
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Yasuhiro Matsuda
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Hiroyuki Uematsu
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Ayako Sugino
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Hirotaka Ooka
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Satoshi Kudo
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Subaru Fujii
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Mitsutoshi Asai
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Shin Okamoto
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Takayuki Ishihara
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Kiyonori Nanto
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Takuya Tsujimura
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Yosuke Hata
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Naoko Higashino
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Sho Nakao
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| | - Toshiaki Mano
- Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Hyogo, Japan
| |
Collapse
|
19
|
Lau L, Wiebe N, Ramesh S, Ahmed S, Klarenbach S, Carrero JJ, Stenvinkel P, Thorand B, Senior P, Tonelli M, Bello AK. Associations of Estradiol With Mortality and Health Outcomes in Patients Undergoing Hemodialysis: A Prospective Cohort Study. Can J Kidney Health Dis 2023; 10:20543581231209233. [PMID: 37928249 PMCID: PMC10624074 DOI: 10.1177/20543581231209233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 09/16/2023] [Indexed: 11/07/2023] Open
Abstract
Background Both lower and higher estradiol (E2) levels have been associated with increased mortality among women with kidney failure. However, robust data are still lacking. Objective We investigated the interaction of diabetes and age on linear and nonlinear associations between E2 levels, adverse outcomes, and health-related quality of life (HRQOL) in Canadian women undergoing hemodialysis (HD). Design Population-based cohort study; data from Canadian Kidney Disease Cohort Study (CKDCS). Setting & patients A total of 427 women undergoing HD enrolled in the CKDCS. Measurements Baseline E2 (in pmol/L) and E2 tertiles (<38 pmol/L, 38-95 pmol/L, >95 pmol/L). Methods Cox-proportional hazards used for all-cause and cardiovascular disease (CVD) mortality. Fine-Gray models used for incident CVD. Mixed models used for Health Utilities Index Mark 3 (HUI3), Kidney Disease Quality of Life Physical Component Scores (KDQOL12-PCS), and Mental Component Scores (KDQOL12-MCS). Results Over a median follow-up of 3.6 (interquartile range [IQR]: 1.6-7.5) years, 250 (58.6%) participants died; 74 deaths (29.6%) were CV-related. Among 234 participants without prior CV events, 80 (34.2%) had an incident CVD event. There were no significant linear associations between E2 and all-cause mortality, CVD mortality, and incident CVD. However, E2 showed a significant concave association with all-cause mortality, but not with CVD mortality and incident CVD. Among patients aged ≥63 years, higher E2 levels were associated with lower HUI3 scores, mean difference (MD) = -0.062 per 1 - SD pmol/L, 95% confidence interval (CI) = -0.112 to -0.012, but the opposite was observed in younger patients (<63 years) in whom higher E2 levels were associated with higher HUI3 scores (MD = 0.032 per 1 - SD pmol/L, 95% CI = 0.008-0.055), Pinteraction = .045. No associations were observed among E2, KDQOL12-PCS (MD = -0.15 per 1 - SD pmol/L, 95% CI = -1.15 to 0.86), and KDQOL12-MCS (MD = -0.63 per 1 - SD pmol/L, 95% CI = -1.82 to 0.57). Limitations Unmeasured confounding and small sample size. Conclusions The association between E2 and all-cause mortality may be nonlinear, while no association was observed for CVD mortality, incident CVD, KDQOL12-PCS, and KDQOL12-MCS. Furthermore, the association between serum E2 and HUI3 was modified by age: Higher levels were associated with higher utility among women aged <63 years and the converse observed among older women.
Collapse
Affiliation(s)
- Lina Lau
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- International Helmholtz Research School for Diabetes, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig Maximilians Universität München, Germany
- Department of Medicine, University of Alberta, Edmonton, Canada
| | - Natasha Wiebe
- Department of Medicine, University of Alberta, Edmonton, Canada
| | | | - Sofia Ahmed
- Department of Medicine, University of Calgary, AB, Canada
| | | | - Juan-Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Peter Stenvinkel
- Renal Unit, Department of Clinical Sciences and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Barbara Thorand
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig Maximilians Universität München, Germany
- German Center for Diabetes Research, Neuherberg, Germany
| | - Peter Senior
- Department of Medicine, University of Alberta, Edmonton, Canada
| | | | - Aminu K. Bello
- Department of Medicine, University of Alberta, Edmonton, Canada
| |
Collapse
|
20
|
Ho JS, Wong JJ, Gao F, Wee HN, Teo LLY, Ewe SH, Tan RS, Ching J, Chua KV, Lee LS, Koh WP, Kovalik JP, Koh AS. Adverse cardiovascular and metabolic perturbations among older women: 'fat-craving' hearts. Clin Res Cardiol 2023; 112:1555-1567. [PMID: 36651997 DOI: 10.1007/s00392-023-02156-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Accepted: 01/09/2023] [Indexed: 01/19/2023]
Abstract
BACKGROUND Despite known sex-based differences in cardiovascular aging, differences in aging biology are poorly understood. We hypothesize that circulating metabolites studied cross-sectionally with cardiac aging may be associated with cardiovascular changes that distinguish cardiac aging in women. METHODS A population-based cohort of community men and women without cardiovascular disease from Singapore underwent detailed clinical and echocardiography examinations. Cross-sectional associations between cardiac functional characteristics and metabolomics profiles were examined. RESULTS Five hundred sixty-seven adults (48.9% women) participated. Women were younger (72 ± 4.4 years vs 73 ± 4.3 years, p = 0.022), had lower diastolic blood pressures (71 ± 11.0 mmHg vs 76 ± 11.2 mmHg, p < 0.0001, and less likely to have diabetes mellitus (18.0% vs 27.6%, p = 0.013) and smoking (3.8% vs 34.5%, p < 0.001). Body mass indices were similar (24 ± 3.8 kg/m2 vs 24 ± 3.4 kg/m2, p = 0.29), but women had smaller waist circumferences (81 ± 10.1 cm vs 85 ± 9.2 cm, p < 0.001). Women had a significantly higher E/e' ratios (10.9 ± 3.4 vs 9.9 ± 3.3, p = 0.007) and mitral A peak (0.86 ± 0.2 m/s vs 0.79 ± 0.2 m/s, p < 0.001) than men. Among women, lower E/e' ratio was associated with higher levels of C16 (OR 1.019, 95%CI 1.002-1.036, p = 0.029), C16:1 (OR 1.06, 95%CI 1.006-1.118, p = 0.028), serine (OR 1.019, 95%CI 1.002-1.036, p = 0.025), and histidine (OR 1.045, 95%CI 1.013-1.078, p = 0.006). Lower mitral A peak was associated with higher levels of histidine (OR 1.039, 95%CI 1.009-1.070, p = 0.011), isoleucine (OR 1.013, 95%CI 1.004-1.021, p = 0.004), and C20 (OR 1.341, 95%CI 1.067-1.684, p = 0.012). CONCLUSION Impairments in diastolic functions were more frequent among older women compared to men, despite lower prevalence of vascular risk factors and preserved cardiac structure. Cardiac aging in women correlated with metabolites involved in fatty acid oxidation and tricyclic acid cycle fuelling.
Collapse
Affiliation(s)
- Jien Sze Ho
- National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Jie Jun Wong
- National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore
| | - Fei Gao
- National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | | | - Louis L Y Teo
- National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - See Hooi Ewe
- National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Ru-San Tan
- National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Jianhong Ching
- Duke-NUS Medical School, Singapore, Singapore
- KK Research Centre, KK Women's and Children's Hospital, Singapore, Singapore
| | | | | | - Woon-Puay Koh
- Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore
| | - Jean-Paul Kovalik
- Duke-NUS Medical School, Singapore, Singapore
- Singapore General Hospital, Singapore, Singapore
| | - Angela S Koh
- National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore.
- Duke-NUS Medical School, Singapore, Singapore.
| |
Collapse
|
21
|
Chen Y, Wang A, Zhang X, Xia F, Zhao X. Effect of age at menopause and menopause itself on high sensitivity C-reactive protein, pulse wave velocity, and carotid intima-media thickness in a Chinese population. Medicine (Baltimore) 2023; 102:e35629. [PMID: 37861482 PMCID: PMC10589532 DOI: 10.1097/md.0000000000035629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Accepted: 09/22/2023] [Indexed: 10/21/2023] Open
Abstract
Potential associations between menopause, age at menopause, and clinical indicators related to cardiovascular disease (CVD) have not been elucidated. To identify the risk of CVD early and contribute to its prevention and intervention, the present study used relevant biomarkers to evaluate the risk of CVD among pre- and postmenopausal women. An overall population of 816 women (aged 40-60 y) was evaluated as premenopause, natural early menopause, or natural late menopause (ages ≤ 48 and ≥52 y), with ages 49-51 years as reference (natural menopause). High-sensitivity C-reactive protein, carotid intima-media thickness, and brachial-ankle pulse wave velocity were measured. Triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) of the postmenopausal group were each significantly higher than that of the premenopausal. However, the 3 menopausal groups were similar regarding hypertension, diabetes, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. In the logistic regression model, the CRP, brachial-ankle pulse wave velocity, and carotid intima-media thickness levels were similar among the premenopause and early and late menopause groups. These results were unchanged after further adjustment for multiple confounders including age, smoking, drinking, salt intake habits, presence of hypertension, or diabetes mellitus. Menopause itself is a more important risk factor for CVD compared with menopause that begins at early or late age.
Collapse
Affiliation(s)
- Ying Chen
- Department of Obstetrics and Gynecology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Anxin Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Xiaoli Zhang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Fengqin Xia
- Department of Obstetrics and Gynecology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Xingquan Zhao
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| |
Collapse
|
22
|
Sciatti E, Coccia MG, Magnano R, Aakash G, Limonta R, Diep B, Balestrieri G, D'Isa S, Abramov D, Parwani P, D'Elia E. Heart Failure Preserved Ejection Fraction in Women: Insights Learned from Imaging. Heart Fail Clin 2023; 19:461-473. [PMID: 37714587 DOI: 10.1016/j.hfc.2023.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/17/2023]
Abstract
While the prevalence of heart failure, in general, is similar in men and women, women experience a higher rate of HFpEF compared to HFrEF. Cardiovascular risk factors, parity, estrogen levels, cardiac physiology, and altered response to the immune system may be at the root of this difference. Studies have found that in response to increasing age and hypertension, women experience more concentric left ventricle remodeling, more ventricular and arterial stiffness, and less ventricular dilation compared to men, which predisposes women to developing more diastolic dysfunction. A multi-modality imaging approach is recommended to identify patients with HFpEF. Particularly, appreciation of sex-based differences as described in this review is important in optimizing the evaluation and care of women with HFpEF.
Collapse
Affiliation(s)
- Edoardo Sciatti
- Cardiology Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | | | | | - Gupta Aakash
- Division of Cardiology, Department of Medicine, Loma Linda University Health, Loma Linda, CA, USA
| | - Raul Limonta
- School of Medicine and Surgery, Milano Bicocca University, Milano, Italy
| | - Brian Diep
- Division of Cardiology, Department of Medicine, Loma Linda University Health, Loma Linda, CA, USA
| | | | - Salvatore D'Isa
- Cardiology Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Dmitry Abramov
- Division of Cardiology, Department of Medicine, Loma Linda University Health, Loma Linda, CA, USA
| | - Purvi Parwani
- Division of Cardiology, Department of Medicine, Loma Linda University Health, Loma Linda, CA, USA
| | - Emilia D'Elia
- Cardiology Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy.
| |
Collapse
|
23
|
Masuda M, Matsuda Y, Uematsu H, Sugino A, Ooka H, Kudo S, Fujii S, Asai M, Iida O, Okamoto S, Ishihara T, Nanto K, Tsujimura T, Hata Y, Toyoshima T, Higashino N, Nakao S, Mano T. Gender Differences in Atrial Fibrosis and Cardiomyopathy Assessed by Left Atrial Low-Voltage Areas During Catheter Ablation of Atrial Fibrillation. Am J Cardiol 2023; 203:37-44. [PMID: 37481810 DOI: 10.1016/j.amjcard.2023.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 06/20/2023] [Accepted: 07/04/2023] [Indexed: 07/25/2023]
Abstract
Atrial myocardial degeneration predisposes to atrial fibrillation (AF), ischemic stroke, and heart failure. Studies suggest the presence of gender differences in atrial myocardial degeneration. This study aimed to delineate gender differences in the prevalence, predictors, and prognostic impact of left atrial low-voltage areas (LVAs). This observational study included 1,488 consecutive patients who underwent initial ablation for AF. Voltage mapping was performed after pulmonary vein isolation during sinus rhythm. LVAs were defined as regions where bipolar peak-to-peak voltage was <0.50 mV. LVA prevalence was higher in women (38.7%) than in men (16.0%). High age, persistent form of AF, diabetes mellitus, and a large left atrium were shown to be common predictors in both gender categories. Heart failure and history of stroke/thromboembolic events were men-specific predictors of LVA existence. Women experienced more AF recurrence than men (31.1% vs 25.7%, p = 0.027). LVA existence was significantly associated with increased AF recurrence in each gender category, with a respective hazard ratio, 95% confidence interval, and p value of 2.45, 1.87 to 3.22, and <0.0001 in men and 1.82, 1.33 to 2.49, and <0.0001 in women. In conclusion, LVA was more frequent in women than men, and predicted frequent AF recurrence irrespective of gender category.
Collapse
Affiliation(s)
- Masaharu Masuda
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan.
| | - Yasuhiro Matsuda
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Hiroyuki Uematsu
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Ayako Sugino
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Hirotaka Ooka
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Satoshi Kudo
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Subaru Fujii
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Mitsutoshi Asai
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Osamu Iida
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Shin Okamoto
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Takayuki Ishihara
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Kiyonori Nanto
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Takuya Tsujimura
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Yosuke Hata
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Taku Toyoshima
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Naoko Higashino
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Sho Nakao
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| | - Toshiaki Mano
- Cardiovascular Center, Kansai Rosai Hospital Cardiovascular Center, Amagasaki, Japan
| |
Collapse
|
24
|
Kundu S, Acharya SS. Study on depletion of ovarian function and late-life chronic diseases in India. Int J Gynaecol Obstet 2023; 162:1057-1067. [PMID: 37158425 DOI: 10.1002/ijgo.14818] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 01/28/2023] [Accepted: 04/12/2023] [Indexed: 05/10/2023]
Abstract
OBJECTIVE The current study aims to understand premature and early menopausal age in association with chronic conditions. METHODS The present cross-sectional study analyzed nationally representative data from LASI (Longitudinal Aging Study in India) from 2017 to 2018. Bivariate analysis including cross-tabulation and χ2 tests were performed. Further multiple regression analysis was performed, using the generalized linear model of logit link. RESULTS Approximately 2533 (8%) older women reported that they had experienced premature menopause (before age 40), while 3889 (12.4%) reported having early menopause (age 40-44). The likelihood of a woman with premature menopause developing cardiovascular diseases (CVDs) is 15% higher (adjusted odds ratio [AOR], 1.15; P < 0.05) than those who do not experience premature menopause, while women with early menopause have a 13% higher risk (AOR, 1.13; P < 0.05). For women who experienced premature menopause and were also smokers, the probability of developing CVDs was higher. Other chronic diseases such as bone or joint problems, diabetes, and eye vision problems were also shown to be significant health problems among women who had premature ovarian failure. CONCLUSION Our results show significant association between women with premature or early depletion of ovarian function and chronic health conditions such as cardiovascular diseases, bone or joint problems, vision problems, and neurological or psychiatric disorders at their later life ages. Comprehensive strategies in the form of lifestyle changes may regulate hormonal levels and allow the body to reach menopause at the appropriate age.
Collapse
Affiliation(s)
- Sampurna Kundu
- Centre of Social Medicine and Community Health, Jawaharlal Nehru University, New Delhi, India
| | | |
Collapse
|
25
|
Zhu F, Qi H, Bos M, Boersma E, Kavousi M. Female Reproductive Factors and Risk of New-Onset Heart Failure: Findings From UK Biobank. JACC. HEART FAILURE 2023; 11:1203-1212. [PMID: 37086244 DOI: 10.1016/j.jchf.2023.02.019] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 02/17/2023] [Accepted: 02/21/2023] [Indexed: 04/23/2023]
Abstract
BACKGROUND A comprehensive evaluation of woman-specific risk factors in relation to incident heart failure (HF) is limited. OBJECTIVES This study sought to investigate the association of multiple female reproductive factors with the risk of HF. METHODS Between 2007 and 2010, 229,026 women (mean age: 56.5 years) without prevalent HF from the UK Biobank cohort were included and followed until December 2020. The relation between (self-reported) reproductive factors and HF was analyzed using Cox proportional hazards models with adjustment for potential confounding. RESULTS Menarche at age <12 years, compared to age 12-13 years, carried a 9% larger risk of HF (HR: 1.09 [95% CI: 1.01-1.18]). Younger age at menopause was associated with a higher risk of HF (HRage <45 y vs 50-51 y: 1.15 [95% CI: 1.03-1.28]; HRage 45-49 y vs 50-51 y: 1.11 [95% CI: 1.01-1.23]). Younger maternal age at first live birth (HRage <21 y vs 24-26 y: 1.42 [95% CI: 1.28-1.59]; HRage 21-23 y vs 24-26 y: 1.14 [95% CI: 1.03-1.26]) and at last live birth (HRage <26 y vs 29-31 y: 1.19 [95% CI: 1.07-1.33]) were associated with higher risk of HF. Compared to women with 1 or 2 children, having 3 or 4 children (HR: 1.09 [95% CI: 1.02-1.17]) or >4 children (HR: 1.24 [95% CI: 1.05-1.47]) was associated with higher HF risk. Experiencing miscarriages or abortions was not significantly associated with incident HF, whereas experiencing 1 stillbirth and recurrent stillbirths conferred a 20% and 43% larger risk of HF, respectively, compared to no stillbirth. CONCLUSIONS The findings emphasize the importance of female reproductive history in the assessment of HF risk.
Collapse
Affiliation(s)
- Fang Zhu
- Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Hongchao Qi
- Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Biostatistics, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Maxime Bos
- Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Eric Boersma
- Department of Cardiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Maryam Kavousi
- Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands.
| |
Collapse
|
26
|
Han BG, Seol JH, Choi S, Shin D, Kim JS, Kim YH. Comparing Left Ventricular Diastolic Function between Peritoneal Dialysis and Non-Dialysis Patients with Stage 5 Chronic Kidney Disease: A Propensity Score-Matched Analysis. J Clin Med 2023; 12:5092. [PMID: 37568494 PMCID: PMC10420270 DOI: 10.3390/jcm12155092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 07/25/2023] [Accepted: 08/01/2023] [Indexed: 08/13/2023] Open
Abstract
Patients with chronic kidney disease (CKD) have a high incidence of left ventricular diastolic dysfunction (LVDD), which increases the risk of heart failure and mortality. We assessed fluid overload as an independent risk factor for LVDD in patients with decreased kidney function and compared its impact on the E/e' ratio as a parameter for assessing left ventricular diastolic functions between patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and those with non-dialysis CKD stage 5 (CKD5) using propensity score matching (PSM). After PSM, 222 patients (CAPD, n = 111; CKD5, n = 111) were included. Fluid balance was assessed using bio-impedance spectroscopy and LVDD was determined by echocardiography based on an E/e' ratio of >15. The CKD5 group had a significantly higher E/e' ratio (p = 0.002), while fluid overload (OH/ECW) did not differ significantly between the groups. In the CAPD group, there were no significant differences in OH/ECW between patients with and without LVDD (p = 0.517). However, in the CKD5 group, patients with LVDD showed a significantly higher OH/ECW (p = 0.001). In a regression analysis investigating factors associated with the E/e' ratio, OH/ECW was not significantly associated with the E/e' ratio in the CAPD group (p = 0.087), but in the CKD5 group, it was independently correlated (p = 0.047). The factors closely associated with LVDD varied depending on dialysis dependence. While fluid overload independently influenced LVDD in non-dialysis patients, it was not statistically significant in patients with CAPD. Early assessment and management of volume status are crucial in addressing LVDD in patients with advanced-stage CKD.
Collapse
Affiliation(s)
- Byoung-Geun Han
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (B.-G.H.)
| | - Jae Hee Seol
- Department of Pediatrics, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea
| | - Sooyeon Choi
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (B.-G.H.)
| | - Donghui Shin
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (B.-G.H.)
| | - Jae-Seok Kim
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea; (B.-G.H.)
| | - Yong Hyuk Kim
- Department of Pediatrics, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea
| |
Collapse
|
27
|
Visniauskas B, Kilanowski-Doroh I, Ogola BO, Mcnally AB, Horton AC, Imulinde Sugi A, Lindsey SH. Estrogen-mediated mechanisms in hypertension and other cardiovascular diseases. J Hum Hypertens 2023; 37:609-618. [PMID: 36319856 PMCID: PMC10919324 DOI: 10.1038/s41371-022-00771-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 10/06/2022] [Accepted: 10/18/2022] [Indexed: 06/08/2023]
Abstract
Cardiovascular disease (CVD) is the leading cause of death globally for men and women. Premenopausal women have a lower incidence of hypertension and other cardiovascular events than men of the same age, but diminished sex differences after menopause implicates 17-beta-estradiol (E2) as a protective agent. The cardioprotective effects of E2 are mediated by nuclear estrogen receptors (ERα and ERβ) and a G protein-coupled estrogen receptor (GPER). This review summarizes both established as well as emerging estrogen-mediated mechanisms that underlie sex differences in the vasculature during hypertension and CVD. In addition, remaining knowledge gaps inherent in the association of sex differences and E2 are identified, which may guide future clinical trials and experimental studies in this field.
Collapse
Affiliation(s)
- Bruna Visniauskas
- Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA
| | | | - Benard O Ogola
- Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA
| | - Alexandra B Mcnally
- Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA
| | - Alec C Horton
- Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA
| | - Ariane Imulinde Sugi
- Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA
| | - Sarah H Lindsey
- Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA.
- Tulane Center of Excellence in Sex-Based Biology and Medicine, New Orleans, LA, USA.
- Tulane Brain Institute, New Orleans, LA, USA.
| |
Collapse
|
28
|
Egami Y, Nohara H, Kawanami S, Sugae H, Ukita K, Kawamura A, Nakamura H, Yasumoto K, Tsuda M, Okamoto N, Matsunaga-Lee Y, Yano M, Nishino M, Tanouchi J. Impact of a Novel Score to Predict Left Ventricular Diastolic Dysfunction After Catheter Ablation of Nonparoxysmal Atrial Fibrillation With Preserved Ejection Fraction. Am J Cardiol 2023; 200:128-134. [PMID: 37321025 DOI: 10.1016/j.amjcard.2023.04.045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 03/30/2023] [Accepted: 04/28/2023] [Indexed: 06/17/2023]
Abstract
The impact of catheter ablation of atrial fibrillation (AFCA) on left ventricular (LV) diastolic function is still unknown. This study aimed to develop a novel risk score to predict LV diastolic dysfunction (LVDD) 12 months after AFCA (12-month LVDD) and to evaluate whether the risk score was associated with cardiovascular events (cardiovascular death, transient ischemic attack/stroke, myocardial infarction, or heart failure hospitalization). We studied 397 patients with nonparoxysmal AF with preserved ejection fraction who underwent initial AFCA (age: 69 years, women: 32%). LVDD was diagnosed if more than 2 of 3 variables (average E/e' ratio >14, septal e' velocity <7 cm/s or lateral e' velocity <10 cm/s, and tricuspid valve regurgitation velocity >2.8 m/s) were present. The 12-month LVDD was observed in 89 patients (23%). A total of 4 preprocedural variables (woman, average E/e' ratio ≥9.6, age ≥74 years, and left atrial diameter ≥50 mm [WEAL]) were identified as predictors of 12-month LVDD on multivariable analysis. We developed a WEAL score. The prevalence of 12-month LVDD increased as WEAL scores increased (p <0.001). There was a statistically significant difference in cardiovascular events-free survival between those at high risk (WEAL score: 3 or 4) and those at low risk (WEAL score: 0, 1, or 2). (86.6% vs 97.2%, log-rank p = 0.009). The WEAL score before AFCA is useful to predict 12-month LVDD after AFCA in patients with nonparoxysmal AF with preserved ejection fraction and is associated with cardiovascular events after AFCA.
Collapse
Affiliation(s)
- Yasuyuki Egami
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | - Hiroaki Nohara
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | - Shodai Kawanami
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | - Hiroki Sugae
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | - Kohei Ukita
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | - Akito Kawamura
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | - Hitoshi Nakamura
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | - Koji Yasumoto
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | - Masaki Tsuda
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | - Naotaka Okamoto
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | | | - Masamichi Yano
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| | - Masami Nishino
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan.
| | - Jun Tanouchi
- Division of Cardiology, Osaka Rosai Hospital, Sakai, Osaka, Japan
| |
Collapse
|
29
|
Piťha J, Vaněčková I, Zicha J. Hypertension after the Menopause: What Can We Learn from Experimental Studies? Physiol Res 2023; 72:S91-S112. [PMID: 37565415 PMCID: PMC10660576 DOI: 10.33549/physiolres.935151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 06/07/2023] [Indexed: 12/01/2023] Open
Abstract
Hypertension is the most prevalent cardiovascular disease of the adult population and is closely associated with serious cardiovascular events. The burden of hypertension with respect to vascular and other organ damage is greater in women. These sex differences are not fully understood. The unique feature in women is their transition to menopause accompanied by profound hormonal changes that affect the vasculature that are also associated with changes of blood pressure. Results from studies of hormone replacement therapy and its effects on the cardiovascular system are controversial, and the timing of treatment after menopause seems to be important. Therefore, revealing potential sex- and sex hormone-dependent pathophysiological mechanisms of hypertension in experimental studies could provide valuable information for better treatment of hypertension and vascular impairment, especially in postmenopausal women. The experimental rat models subjected to ovariectomy mimicking menopause could be useful tools for studying the mechanisms of blood pressure regulation after menopause and during subsequent therapy.
Collapse
Affiliation(s)
- J Piťha
- Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
| | | | | |
Collapse
|
30
|
Zhazykbayeva S, Hassoun R, Herwig M, Budde H, Kovács Á, Mannherz HG, El-Battrawy I, Tóth A, Schmidt WE, Mügge A, Hamdani N. Oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction rats. Front Cardiovasc Med 2023; 10:1157398. [PMID: 37363100 PMCID: PMC10285478 DOI: 10.3389/fcvm.2023.1157398] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 05/26/2023] [Indexed: 06/28/2023] Open
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a complex cardiovascular insufficiency syndrome presenting with an ejection fraction (EF) of greater than 50% along with different proinflammatory and metabolic co-morbidities. Despite previous work provided key insights into our understanding of HFpEF, effective treatments are still limited. In the current study we attempted to unravel the molecular basis of sex-dependent differences in HFpEF pathology. We analyzed left ventricular samples from 1-year-old female and male transgenic (TG) rats homozygous for the rat Ren-2 renin gene (mRen2) characterized with hypertension and diastolic dysfunction and compared it to age-matched female and male wild type rats (WT) served as control. Cardiomyocytes from female and male TG rats exhibited an elevated titin-based stiffness (Fpassive), which was corrected to control level upon treatment with reduced glutathione indicating titin oxidation. This was accompanied with high levels of oxidative stress in TG rats with more prominent effects in female group. In vitro supplementation with heat shock proteins (HSPs) reversed the elevated Fpassive indicating restoration of their cytoprotective function. Furthermore, the TG group exhibited high levels of proinflammatory cytokines with significant alterations in apoptotic and autophagy pathways in both sexes. Distinct alterations in the expression of several proteins between both sexes suggest their differential impact on disease development and necessitate distinct treatment options. Hence, our data suggested that oxidative stress and inflammation distinctly drive diastolic dysfunction and remodeling in female and male rats with HFpEF and that the sex-dependent mechanisms contribute to HF pathology.
Collapse
Affiliation(s)
- Saltanat Zhazykbayeva
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, Germany
| | - Roua Hassoun
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, Germany
| | - Melissa Herwig
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, Germany
| | - Heidi Budde
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, Germany
| | - Árpád Kovács
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, Germany
| | - Hans Georg Mannherz
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany
- Department of Anatomy and Molecular Embryology, Ruhr University Bochum, Bochum, Germany
| | - Ibrahim El-Battrawy
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany
- Department of Cardiology and Angiology, Bergmannsheil University Hospitals, UK RUB, Ruhr University of Bochum, Bochum, Germany
| | - Attila Tóth
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- Research Centre for Molecular Medicine, University of Debrecen, Debrecen, Hungary
| | - Wolfgang E. Schmidt
- Department of Medicine I, St. Josef Hospital, UK RUB, Ruhr-University Bochum, Bochum, Germany
| | - Andreas Mügge
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, Germany
- Department of Cardiology and Angiology, Bergmannsheil University Hospitals, UK RUB, Ruhr University of Bochum, Bochum, Germany
| | - Nazha Hamdani
- Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, Germany
- Institut für Forschung und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany
- Department of Cardiology, St. Josef-Hospital, UK RUB, Ruhr University Bochum, Bochum, Germany
| |
Collapse
|
31
|
Amiri M, Ahmadi N, Hadaegh F, Mousavi M, Azizi F, Ramezani Tehrani F. Does the addition of serum antimüllerian hormone concentrations to the Framingham Risk Score and Pooled Cohort Equations improve the prediction of cardiovascular disease? Menopause 2023; 30:406-413. [PMID: 36720078 DOI: 10.1097/gme.0000000000002145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Abstract
The present study revealed that the addition of serum antimüllerian hormone concentrations to Framingham Risk Score and Pooled Cohort Equations could potentially improve the risk prediction of cardiovascular disease.
Objective
The current study aimed to examine the added value of serum antimüllerian hormone (AMH) concentration to the Framingham Risk Score (FRS) and Pooled Cohort Equations (PCE) in predicting the risk of cardiovascular disease (CVD) in women of reproductive age.
Methods
Women 30 years and older were considered eligible for this population-based prospective study. The univariate and multivariate Cox proportional hazard models were used to evaluate the association between the serum concentrations of AMH and the risk of CVD.
Results
In the enhanced model, which integrated AMH into FRS and PCE and was adjusted for family history of premature CVD, AMH showed a significant association with the risk of CVD during a 19-year follow-up of 800 women (hazard ratio, 0.77 [95% CI, 0.60-0.99] and hazard ratio, 0.64 [95% CI, 0.48-0.84], respectively). According to the likelihood-ratio test, the addition of AMH measurements to FRS and PCE could significantly improve the risk prediction of CVD (P = 0.02 and P < 0.001, respectively); however, the integration of this biomarker did not improve the classification of risk categories.
Conclusions
The present findings revealed that the addition of serum AMH concentrations to FRS and PCE could potentially improve the risk prediction of CVD.
Collapse
Affiliation(s)
- Mina Amiri
- From the Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Narjes Ahmadi
- Department of internal Medicine, School of Medicine, Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzad Hadaegh
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Mousavi
- From the Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fahimeh Ramezani Tehrani
- From the Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
32
|
Pizzato SB, Terraciano PB, Zanon P, Kuhl CP, Alves Garcez TN, Passos EP, Tirloni L, Berger M. Estrogen depletion modulates aortic prothrombotic signaling in normotensive and spontaneously hypertensive female rats. Mol Cell Endocrinol 2023; 561:111827. [PMID: 36494014 PMCID: PMC9812894 DOI: 10.1016/j.mce.2022.111827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 11/30/2022] [Accepted: 12/05/2022] [Indexed: 12/12/2022]
Abstract
AIM In this study, we investigated how platelets and aorta contribute to the creation and maintenance of a prothrombotic state in an experimental model of postmenopausal hypertension in ovariectomized rats. METHODS Bilateral ovariectomy was performed in both 14-week-old female spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. The animals were kept in phytoestrogen free diet. Vascular parameters, platelet, coagulation and aortic prothrombotic functions and mechanisms were assessed. RESULTS Exacerbated platelet aggregation was observed in both SHR and WKY animals after ovariectomy. The mechanism was related to aortic COX2 downregulation and reduction in AMP, ADP, and ATP hydrolysis in serum and platelets. A procoagulant potential was observed in plasma from ovariectomized rats and this was confirmed by kallikrein and factor Xa generation in aortic rings. Aortic rings derived from ovariectomized SHR presented a greater thrombin generation capacity compared to equivalent rings from WKY animals. The mechanism involved tissue factor and PAR-1 upregulation as well as an increase in extrinsic coagulation and fibrinolysis markers in aorta and platelets. Aortic smooth muscle cells pre-treated with a plasma pool derived from estrogen-depleted animals developed a procoagulant profile with tissue factor upregulation. This procoagulant profile was dependent on inflammatory signalling, since NFκB inhibition attenuated the procoagulant activity and tissue factor expression. CONCLUSIONS A prothrombotic phenotype was observed in both WKY and SHR ovariectomized rats being associated with platelet hyperreactivity and tissue factor upregulation in aorta and platelets. The mechanism involves proinflammatory signalling that supports greater thrombin generation in aorta and vascular smooth muscle cells.
Collapse
Affiliation(s)
- Sabrina Beal Pizzato
- Grupo de Reprodução e Farmacologia Celular, Laboratório de Bioquímica Farmacológica, Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA-UFRGS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências de Saúde: Ginecologia e Obstetrícia (PPGGO), Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Paula Barros Terraciano
- Programa de Pós-Graduação em Ciências de Saúde: Ginecologia e Obstetrícia (PPGGO), Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Grupo de Reprodução e Farmacologia Celular, Laboratório de Embriologia e Diferenciação Celular, Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA-UFRGS), Porto Alegre, RS, Brazil
| | - Pamela Zanon
- Grupo de Reprodução e Farmacologia Celular, Laboratório de Bioquímica Farmacológica, Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA-UFRGS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências de Saúde: Ginecologia e Obstetrícia (PPGGO), Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Cristiana Palma Kuhl
- Programa de Pós-Graduação em Ciências de Saúde: Ginecologia e Obstetrícia (PPGGO), Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Grupo de Reprodução e Farmacologia Celular, Laboratório de Embriologia e Diferenciação Celular, Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA-UFRGS), Porto Alegre, RS, Brazil
| | - Tuane Nerissa Alves Garcez
- Grupo de Reprodução e Farmacologia Celular, Laboratório de Embriologia e Diferenciação Celular, Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA-UFRGS), Porto Alegre, RS, Brazil; Unidade de Experimentação Animal, Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA-UFRGS), Porto Alegre, RS, Brazil
| | - Eduardo Pandolfi Passos
- Programa de Pós-Graduação em Ciências de Saúde: Ginecologia e Obstetrícia (PPGGO), Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Grupo de Reprodução e Farmacologia Celular, Laboratório de Embriologia e Diferenciação Celular, Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA-UFRGS), Porto Alegre, RS, Brazil; Departamento de Ginecologia e Obstetrícia, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Lucas Tirloni
- Tick-Pathogen Transmission Unit, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, Hamilton, MT, USA
| | - Markus Berger
- Grupo de Reprodução e Farmacologia Celular, Laboratório de Bioquímica Farmacológica, Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA-UFRGS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências de Saúde: Ginecologia e Obstetrícia (PPGGO), Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Tick-Pathogen Transmission Unit, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, Hamilton, MT, USA.
| |
Collapse
|
33
|
Janket SJ, Lee C, Surakka M, Jangam TG, Van Dyke TE, Baird AE, Meurman JH. Oral hygiene, mouthwash usage and cardiovascular mortality during 18.8 years of follow-up. Br Dent J 2023:10.1038/s41415-023-5507-4. [PMID: 36737459 PMCID: PMC9897600 DOI: 10.1038/s41415-023-5507-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Accepted: 11/01/2022] [Indexed: 02/05/2023]
Abstract
Aim(s) We tested the following hypotheses: would better oral hygiene self-care (OHS) influence cardiovascular (CVD) mortality? Will using mouthwash in addition to OHS affect CVD mortality? How does mouthwash usage impact the oral microbes?Design and methods Among 354 dentate subjects from the Kuopio Oral Health and Heart study, the association of OHS with CVD mortality was assessed using Cox regression analyses, adjusting for age, sex, smoking, dyslipidemia, diabetes, hypertension and education. Additionally, whether using mouthwash would affect this relationship was evaluated.Results In the multivariable-adjusted models, OHS was associated with a 51% reduction in the risk of CVD mortality (hazard ratio [HR] 0.49 [0.28-0.85]; p = 0.01). Even those who had coronary artery disease at baseline showed a marginally significant benefit (0.50 [0.24-1.06]; p = 0.07). However, mouthwash usage did not change OHS effects (HR = 0.49 [0.27-0.87]; p = 0.01), indicating no additional benefits nor detriments. All tested microbes trended to decrease with mouthwash usage in the short term, but none were statistically significant.Conclusion Good OHS significantly lowered the risk of CVD mortality relative to poor OHS. Mouthwash usage did not show any long-term harm or benefit on CVD mortality beyond the benefits rendered by brushing and flossing.
Collapse
Affiliation(s)
- Sok-Ja Janket
- The Forsyth Institute, Centre for Clinical and Translational Research, Cambridge, Massachusetts, USA.
| | - Caitlyn Lee
- Boston University Externship, Wheeler High School, Providence, Rhode Island, USA
| | - Markku Surakka
- Department of Maxillofacial Diseases, Kuopio University Hospital, Kuopio, Finland
| | | | - Thomas E Van Dyke
- The Forsyth Institute, Centre for Clinical and Translational Research, Cambridge, Massachusetts, USA
| | - Alison E Baird
- Department of Neurology, SUNY Downstate Medical Centre, Brooklyn, New York, USA
| | - Jukka H Meurman
- Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| |
Collapse
|
34
|
Mansur ADP, Del Carlo CH, Gonçalinho GHF, Avakian SD, Ribeiro LC, Ianni BM, Fernandes F, César LAM, Bocchi EA, Pereira-Barretto AC. Sex Differences in Heart Failure Mortality with Preserved, Mildly Reduced and Reduced Ejection Fraction: A Retrospective, Single-Center, Large-Cohort Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph192316171. [PMID: 36498244 PMCID: PMC9736433 DOI: 10.3390/ijerph192316171] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 12/01/2022] [Accepted: 12/02/2022] [Indexed: 05/27/2023]
Abstract
BACKGROUND Heart failure (HF) is one of the leading causes of death worldwide. Studies show that women have better survival rates than men despite higher hospitalizations. However, little is known about differences in mortality and predictors of death in women and men with HF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). METHODS From February 2017 to September 2020, mortality and predictors of death were analyzed in women and men with HF. Baseline data included clinical characteristics and echocardiographic findings. RESULTS A total of 11,282 patients, 63.9 ± 14.4 years, including 6256 (55.4%) males, were studied. Females were older, had a higher baseline mean left ventricular ejection fraction (LVEF) and lower left ventricular diastolic diameter. During follow-ups, 1375 (22%) men and 925 (18.4%) women died. Cumulative incidence of death was higher in men with HFrEF but similar for HFmrEF and HFpEF. Cox regression for death showed renal dysfunction, stroke, diabetes, atrial fibrillation, age, LVEF, valve disease, MI, and hypertensive CMP as independent death predictors for all HF patients. CONCLUSIONS Women had a better prognosis than men in HFrEF and similar mortality for HFmrEF and HFpEF, but sex was not an independent predictor of death for all HF subtypes.
Collapse
Affiliation(s)
- Antonio de Padua Mansur
- Serviço de Prevencao, Cardiopatia na Mulher e Reabilitação Cardiovascular, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, Brazil
| | - Carlo Henrique Del Carlo
- Hospital Dia, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, Brazil
| | - Gustavo Henrique Ferreira Gonçalinho
- Serviço de Prevencao, Cardiopatia na Mulher e Reabilitação Cardiovascular, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, Brazil
| | - Solange Desirée Avakian
- Unidade Clínica de Valvopatias, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, Brazil
| | | | - Barbara Maria Ianni
- Unidade Clínica de Miocardiopatias e Doenças da Aorta, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, Brazil
| | - Fábio Fernandes
- Unidade Clínica de Miocardiopatias e Doenças da Aorta, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, Brazil
| | - Luiz Antonio Machado César
- Unidade Clinica de Coronariopatias Cronicas, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, Brazil
| | - Edimar Alcides Bocchi
- Unidade Clinica de Insuficiencia Cardiaca, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, Brazil
| | - Antonio Carlos Pereira-Barretto
- Serviço de Prevencao, Cardiopatia na Mulher e Reabilitação Cardiovascular, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, Brazil
| |
Collapse
|
35
|
Algur K, Sakpal R. Premature menopausal women and risk of cardiovascular diseases in India: Longitudinal Aging Study in India, 2017-18. Health Care Women Int 2022; 45:1207-1219. [PMID: 36369776 DOI: 10.1080/07399332.2022.2141745] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 10/07/2022] [Accepted: 10/26/2022] [Indexed: 11/13/2022]
Abstract
Women who have premature menopause are increasing in number and there is a wide regional diversity across the World, including India. However, in India, the relationship between age at menopause and cardiovascular diseases is still unclear. To fill this research gap, we undertook the present study using data from the Longitudinal Aging Study of India (Wave1, 2017-18). Bivariate logistic regression with three different models controlling for socio-economic and demographic characteristics, reproductive history, nutritional status, and co-morbidities of CVDs was used to show the relationship between CVDs and premature menopause. In all three models, the adjusted odds of having CVDs were higher for premature menopausal women than for those who had menopause between the ages of 45-50. There is a need to understand menopausal problems and their risk factors. The government should initiate a reproductive and sexual health awareness program at the macro level and provide treatment for the same.
Collapse
Affiliation(s)
- Kisan Algur
- International Institute for Population Sciences, Mumbai, India
| | - Ruchita Sakpal
- International Institute for Population Sciences, Mumbai, India
| |
Collapse
|
36
|
High-normal diastolic blood pressure as a risk factor for left ventricular diastolic dysfunction in healthy postmenopausal women. Hypertens Res 2022; 45:1891-1898. [PMID: 36202980 DOI: 10.1038/s41440-022-01024-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 08/22/2022] [Accepted: 08/25/2022] [Indexed: 11/09/2022]
Abstract
Left ventricular (LV) diastolic dysfunction is associated with heart failure with preserved ejection fraction, and metabolic syndrome (MetS) is a risk factor. However, there is limited knowledge regarding the metabolic factors that contribute to LV dysfunction in postmenopausal women without comorbidities. This study aimed to analyze the relationship between LV diastolic dysfunction and MetS, as well as other cardiovascular risk factors, and to determine risks for LV diastolic dysfunction. Postmenopausal women without hypertension, diabetes mellitus, LV systolic dysfunction, or other heart diseases underwent physical examinations, including echocardiography. The study participants were diagnosed with LV diastolic dysfunction based on several echocardiographic parameters. Logistic regression analyses of LV diastolic dysfunction and cardiovascular risk factors were performed. Of the 269 postmenopausal women examined, 29 (10.7%) and 40 (14.9%) had MetS and LV diastolic dysfunction, respectively. Abnormal diastolic blood pressure (odds ratio, 3.6; 95% confidence interval, 1.16-10.9; P < 0.05) and age (odds ratio, 1.1; 95% confidence interval, 1.07-1.19; P < 0.01) were predictors of LV diastolic dysfunction. In healthy postmenopausal women, high-normal diastolic blood pressure was the only independent risk factor for LV diastolic dysfunction, and it thus may be a useful predictor of diastolic heart failure during routine physical examinations.
Collapse
|
37
|
Shuaishuai D, Jingyi L, Zhiqiang Z, Guanwei F. Sex differences and related estrogenic effects in heart failure with preserved ejection fraction. Heart Fail Rev 2022:10.1007/s10741-022-10274-2. [PMID: 36190606 DOI: 10.1007/s10741-022-10274-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/20/2022] [Indexed: 11/04/2022]
Abstract
Heart failure with preserved ejection fraction (HFpEF) is an essential subtype of heart failure accounting for 40% of the total. However, the related pathological mechanism and drug therapy research have been stagnant for a long time. The direct cause of this dilemma is the heterogeneity of HFpEF. And some researchers believe that there is no common pathway to reach the origin of HFpEF; others argue that there is an unidentified unified pathophysiological process hidden beneath the ice surface. Aside from the debate, a series of clinical studies have shown that hypertension and obesity play a fundamental role in the pathogenesis of HFpEF. These results imply that there may be two parallel pathological processes interweaved in one disease, manifested as multiple coexistent pathological phenomena, like a shadow. Meanwhile, the prevalence of HFpEF in women is higher than in men in any given age group, especially prominent in elderly patients. These pathological processes and epidemiological data reflect gender differences, reminding us to shift our attention to estrogen. This article will review the parallel pathogenesis of HFpEF, and also introduce sex differences and the potential effect of estrogen in this condition below.
Collapse
Affiliation(s)
- Deng Shuaishuai
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,National Clinical Research Center for Chinese Acupuncture and Moxibustion, Tianjin, China
| | - Lin Jingyi
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,National Clinical Research Center for Chinese Acupuncture and Moxibustion, Tianjin, China
| | - Zhao Zhiqiang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.,National Clinical Research Center for Chinese Acupuncture and Moxibustion, Tianjin, China
| | - Fan Guanwei
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China. .,National Clinical Research Center for Chinese Acupuncture and Moxibustion, Tianjin, China.
| |
Collapse
|
38
|
Choi HR, Chang Y, Kim Y, Cho Y, Kang J, Kwon MJ, Kwon R, Lim GY, Kim KH, Kim H, Hong YS, Park J, Zhao D, Cho J, Guallar E, Park HY, Ryu S. Ideal Cardiovascular Health Metrics and Risk of Incident Early-Onset Vasomotor Symptoms Among Premenopausal Women. J Clin Endocrinol Metab 2022; 107:2666-2673. [PMID: 35596684 PMCID: PMC9387697 DOI: 10.1210/clinem/dgac327] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Indexed: 12/19/2022]
Abstract
CONTEXT The relationship of ideal cardiovascular health (CVH) behaviors with preventing early-onset vasomotor symptoms (VMSs) is unknown. OBJECTIVE We investigated the association between CVH metrics and the development of early-onset VMSs in premenopausal women. METHODS This cohort study included 2541 premenopausal women aged 42 to 52 years without VMSs at baseline. CVH metrics were defined according to the American Heart Association Life Simple 7 metrics. Owing to limited availability of dietary information, CVH metrics were scored from 0 (unhealthy) to 6 (healthy) and classified into 3 groups: poor (0-2), intermediate (3-4), and ideal (5-6) CVH. VMSs, including hot flashes and night sweats, were assessed using the Menopause-Specific Quality of Life questionnaire. Moderate/severe VMSs was defined as a score of 3 or more points (range, 0 to 6; 6 being most bothersome). RESULTS During a median follow-up of 4.5 years, 1241 women developed VMSs before menopause. After adjustment for age, parity, education level, and alcohol consumption, the hazard ratio (HR) (95% CI) for developing early-onset VMSs comparing poor CVH group to the ideal group was 1.41 (1.07-1.86). CVH scores were also inversely associated with moderate/severe VMSs in a dose-response manner (P for trend = .004); specifically, multivariable-adjusted HRs comparing intermediate and poor CVH groups to the ideal group were 1.20 (95% CI, 1.02-1.43) and 1.57 (95% CI, 1.08-2.29), respectively. CONCLUSION Unfavorable CVH metrics were significantly associated with an increased risk of early-onset VMSs and its more severe forms among premenopausal women.
Collapse
Affiliation(s)
- Hye Rin Choi
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 04514, Republic of Korea
- Institute of Medical Research, School of Medicine, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Yoosoo Chang
- Correspondence: Yoosoo Chang, MD, PhD, Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Samsung Main Bldg B2, 250, Taepyung-ro 2ga, Jung-gu, Seoul 04514, Republic of Korea.
| | - Yejin Kim
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 04514, Republic of Korea
| | - Yoosun Cho
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 04514, Republic of Korea
| | - Jeonggyu Kang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 04514, Republic of Korea
| | - Min-Jung Kwon
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 04514, Republic of Korea
- Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 04514, Republic of Korea
| | - Ria Kwon
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 04514, Republic of Korea
- Institute of Medical Research, School of Medicine, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Ga-Young Lim
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 04514, Republic of Korea
- Institute of Medical Research, School of Medicine, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Kye-Hyun Kim
- Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
| | - Hoon Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Yun Soo Hong
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
| | - Jihwan Park
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
| | - Di Zhao
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
| | - Juhee Cho
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 04514, Republic of Korea
- Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul 06355, Republic of Korea
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
| | - Eliseo Guallar
- Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
| | - Hyun-Young Park
- Department of Precision Medicine, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju 28159, Republic of Korea
| | - Seungho Ryu
- Correspondence: Seungho Ryu, MD, PhD, Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Samsung Main Bldg B2, 250, Taepyung-ro 2ga, Jung-gu, Seoul 04514, Republic of Korea.
| |
Collapse
|
39
|
Shamaki GR, Kesiena O, Markson F, Andrew M, Bob-Manuel T. Editorial of "Heart failure with normal LVEF in BIOSTAT-CHF" to International Journal of Cardiology". Int J Cardiol 2022; 366:63-64. [PMID: 35787434 DOI: 10.1016/j.ijcard.2022.06.069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 06/29/2022] [Indexed: 11/05/2022]
Affiliation(s)
| | | | | | - Murphy Andrew
- Pennsylvania hospital of the University of Pennsylvania Health System, PA, USA
| | | |
Collapse
|
40
|
Cheng L, Maboh RN, Wang H, Mao GW, Wu XY, Chen H. Naoxintong Capsule Activates the Nrf2/HO-1 Signaling Pathway and Suppresses the p38α Signaling Pathway Via Estrogen Receptors to Ameliorate Heart Remodeling in Female Mice With Postmenopausal Hypertension. J Cardiovasc Pharmacol 2022; 80:158-170. [PMID: 35500215 DOI: 10.1097/fjc.0000000000001285] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 04/06/2022] [Indexed: 11/25/2022]
Abstract
ABSTRACT Limited treatments are available for alleviating heart remodeling in postmenopausal hypertension. The cardioprotective effect of naoxintong (NXT) has been widely accepted. This study aimed to explore the effects of NXT on pathological heart remodeling in a postmenopausal hypertension mouse model in vivo and H9c2 cardiomyocytes in vitro. In vivo, ovariectomy combined with chronic angiotensin II infusion was used to establish the postmenopausal hypertension animal model. NXT significantly ameliorated cardiac remodeling as indicated by a reduced ratio of heart weight/body weight and left ventricle weight/body weight, left ventricular wall thickness, diameter of cardiomyocytes, and collagen deposition in the heart. NXT also significantly increased the expression of estrogen receptors (ERs) and downregulated the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2). In vitro, NXT treatment greatly suppressed angiotensin II-induced cardiac hypertrophy, cardiac fibrosis, and excessive oxidative stress as proven by reducing the diameter of H9c2 cardiomyocytes, expression of hypertrophy and fibrosis markers, intracellular reactive oxygen species, and oxidative enzymes. Mechanistically, NXT significantly upregulated the expression of ERs, which activated the Nrf2/HO-1 signaling pathway and inhibited the phosphorylation of the p38α pathway. Collectively, the results indicated that NXT administration might attenuate cardiac remodeling through upregulating the expression of ERs, which activated the Nrf2/HO-1 signaling pathway, inhibited the phosphorylation of the p38α signaling pathway, and reduced oxidative stress.
Collapse
Affiliation(s)
- Lan Cheng
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China ; and
| | - Rene Nfornah Maboh
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China ; and
| | - Huan Wang
- Hypertension Laboratory, Fujian Provincial Cardiovascular Disease Institute, Fujian Provincial Hospital, Fuzhou, China
| | - Gao-Wei Mao
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China ; and
| | - Xiao-Ying Wu
- Hypertension Laboratory, Fujian Provincial Cardiovascular Disease Institute, Fujian Provincial Hospital, Fuzhou, China
| | - Hui Chen
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China ; and.,Hypertension Laboratory, Fujian Provincial Cardiovascular Disease Institute, Fujian Provincial Hospital, Fuzhou, China
| |
Collapse
|
41
|
Daneii P, Neshat S, Mirnasiry MS, Moghimi Z, Dehghan Niri F, Farid A, Shekarchizadeh M, Heshmat-Ghahdarijani K. Lipids and diastolic dysfunction: Recent evidence and findings. Nutr Metab Cardiovasc Dis 2022; 32:1343-1352. [PMID: 35428541 DOI: 10.1016/j.numecd.2022.03.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 02/03/2022] [Accepted: 03/02/2022] [Indexed: 11/25/2022]
Abstract
AIM Diastolic dysfunction is the decreased flexibility of the left ventricle due to the impaired ability of the myocardium to relax and plays an important role in the pathogenesis of heart failure. Lipid metabolism is a well-known contributor to cardiac conditions, including ventricular function. In this article, we aimed to review the literature addressing the connections between lipids, their storage, and metabolism with left ventricular diastolic dysfunction. DATA SYNTHESIS We searched Google scholar, Pubmed, Embase and Researchgate for our keywords: "Diastolic function", "Fat" and "Lipid profile". Initially, 250 articles were selected by title and 84 of them were chosen as most relevant and directly reviewed. CONCLUSIONS Alterations of lipid metabolism in cardiac muscle and cardiac lipid content can occur in many conditions, including consumption of a high-fat diet, obesity, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). These conditions induce alterations in myocardial lipid metabolism, increase myocardial fat content and epicardial fat thickness and increase inflammation and oxidative stress which ultimately lead to cardiac lipotoxicity and diastolic dysfunction. The effects of lipids on diastolic function can differ based on gender. Lipid profile and metabolism are as important in the pathogenesis of diastolic dysfunction as they are in other cardiovascular disorders. A more careful look at cardiac lipid metabolism in molecular, histological and gross levels results in more precise understanding of its role in myocardial function and leads to development of potential treatments for diastolic dysfunction.
Collapse
Affiliation(s)
- Padideh Daneii
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Sina Neshat
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
| | | | - Zahra Moghimi
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
| | | | - Armita Farid
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Masood Shekarchizadeh
- Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Science, Iran
| | - Kiyan Heshmat-Ghahdarijani
- Heart Failure Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
| |
Collapse
|
42
|
Lau ES, Wang D, Roberts M, Taylor CN, Murugappan G, Shadyab AH, Schnatz PF, Farland LV, Wood MJ, Scott NS, Eaton CB, Ho JE. Infertility and Risk of Heart Failure in the Women's Health Initiative. J Am Coll Cardiol 2022; 79:1594-1603. [PMID: 35450577 PMCID: PMC9377329 DOI: 10.1016/j.jacc.2022.02.020] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 02/08/2022] [Indexed: 12/20/2022]
Abstract
BACKGROUND There is growing recognition that reproductive factors are associated with increased risk of future cardiovascular disease. Infertility has been less well studied, although emerging data support its association with increased risk of cardiovascular disease. Whether infertility is associated with future risk of heart failure (HF) is not known. OBJECTIVES This study sought to examine the development of HF and HF subtypes in women with and without history of infertility. METHODS We followed postmenopausal women from the Women's Health Initiative prospectively for the development of HF. Infertility was self-reported at study baseline. Multivariable cause-specific Cox models were used to evaluate the association of infertility with incident overall HF and HF subtypes (heart failure with preserved ejection fraction [HFpEF]: left ventricular ejection fraction of ≥50% vs heart failure with reduced ejection fraction [HFrEF]: left ventricular ejection fraction of <50%]). RESULTS Among 38,528 postmenopausal women (mean age: 63 ± 7 years), 5,399 (14%) participants reported a history of infertility. Over a median follow-up of 15 years, 2,373 developed incident HF, including 807 with HFrEF and 1,133 with HFpEF. Infertility was independently associated with future risk of overall HF (HR: 1.16; 95% CI: 1.04-1.30; P = 0.006). Notably, when examining HF subtypes, infertility was associated with future risk of HFpEF (HR: 1.27; 95% CI: 1.09-1.48; P = 0.002) but not HFrEF (HR: 0.97; 95% CI: 0.80-1.18). CONCLUSIONS Infertility was significantly associated with incident HF. This was driven by increased risk of HFpEF, but not HFrEF, and appeared independent of traditional cardiovascular risk factors and other infertility-related conditions. Future research should investigate mechanisms that underlie the link between infertility and HFpEF.
Collapse
Affiliation(s)
- Emily S Lau
- Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
| | - Dongyu Wang
- CardioVascular Institute and Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Mary Roberts
- Department of Family Medicine, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Christy N Taylor
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Gayathree Murugappan
- Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, California, USA
| | - Aladdin H Shadyab
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, California, USA
| | - Peter F Schnatz
- Department of Obstetrics and Gynecology, The Reading Hospital/Tower Health, Reading, Pennsylvania, USA
| | - Leslie V Farland
- Department of Epidemiology and Biostatistics, University of Arizona, Tucson, Arizona, USA; Department of Obstetrics and Gynecology, College of Medicine-Tucson, Tucson, Arizona, USA
| | - Malissa J Wood
- Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Nandita S Scott
- Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Charles B Eaton
- Department of Family Medicine, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Jennifer E Ho
- CardioVascular Institute and Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. https://twitter.com/JenHoCardiology
| |
Collapse
|
43
|
Reilingh A, van den Meiracker T, Bolijn R, Galenkamp H, van Charante EM, van der Schouw Y, van Valkengoed I. Is early menopause a potential criterion for cardiovascular risk screening to detect high risk in a multi-ethnic population? The Helius study. Maturitas 2022; 162:1-7. [DOI: 10.1016/j.maturitas.2022.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 03/03/2022] [Accepted: 03/06/2022] [Indexed: 10/18/2022]
|
44
|
Abstract
Heart failure affects over 2.6 million women and 3.4 million men in the United States with known sex differences in epidemiology, management, response to treatment, and outcomes across a wide spectrum of cardiomyopathies that include peripartum cardiomyopathy, hypertrophic cardiomyopathy, stress cardiomyopathy, cardiac amyloidosis, and sarcoidosis. Some of these sex-specific considerations are driven by the cellular effects of sex hormones on the renin-angiotensin-aldosterone system, endothelial response to injury, vascular aging, and left ventricular remodeling. Other sex differences are perpetuated by implicit bias leading to undertreatment and underrepresentation in clinical trials. The goal of this narrative review is to comprehensively examine the existing literature over the last decade regarding sex differences in various heart failure syndromes from pathophysiological insights to clinical practice.
Collapse
Affiliation(s)
| | - Anna Beale
- Department of Cardiology, Alfred Hospital, Melbourne, Australia
| | | | | | - Uri Elkayam
- Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California
| | - Carolyn S.P. Lam
- National Heart Centre Singapore and Duke-National University of Singapore
| | - Eileen Hsich
- Department of Cardiology, Cleveland Clinic, Cleveland, Ohio
| |
Collapse
|
45
|
Mirinezhad MR, Ghazizadeh H, Aghsizadeh M, Zamiri Bidary M, Naghipour A, Hasanzadeh E, Yaghooti-Khorasani M, Ebrahimi Dabagh A, Moghadam MRSF, Sheikh Andalibi N, Naseri Far Z, Esmaily H, Ferns GA, Hamzehloei T, Pasdar A, Ghayour-Mobarhan M. The relationship between genetic variants associated with primary ovarian insufficiency and lipid profile in women recruited from MASHAD cohort study. BMC Womens Health 2022; 22:2. [PMID: 34996442 PMCID: PMC8742392 DOI: 10.1186/s12905-021-01550-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Accepted: 11/23/2021] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND AND AIM Primary Ovarian Insufficiency (POI) is defined by the occurrence of menopause before the age of 40 years. It is often associated with cardiovascular disease (CVD). The purpose of this study was to explore the relationship between POI-associated genotypes cardiometabolic disorder risk factors. METHODS One hundred seventeen women with POI and one hundred eighty-three healthy women without POI were recruited in this study. DNA was extracted and analyzed using ASO-PCR or Tetra ARMS-PCR. Lipid profiles were also assessed. RESULTS Multivariate logistic regression analysis showed that individuals with GG vs. TT genotype of the rs1046089 SNP were more likely to have a higher serum LDL (p = 0.03) compared to the control group. There was also a significant association between low serum HDL and rs2303369 and rs4806660 SNP genotypes in the POI group. In the POI group, the percentage of those with high total cholesterol was lower in those with a CC genotype compared to those with a TT genotype (p = 0.03). CONCLUSION Some SNPs reported to be associated with POI appear to be independently associated with dyslipidemia. These results may be helpful to identify subjects with POI who may be susceptible to CVD.
Collapse
Affiliation(s)
- Mohammad Reza Mirinezhad
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamideh Ghazizadeh
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Metabolic Syndrome Research Center, 99199-91766, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maliheh Aghsizadeh
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Metabolic Syndrome Research Center, 99199-91766, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Alireza Naghipour
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elahe Hasanzadeh
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Ali Ebrahimi Dabagh
- Department of Nutrition Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
| | | | | | - Zeynab Naseri Far
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Habibollah Esmaily
- Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton and Sussex Medical School, Falmer, Brighton, BN1 9PH, Sussex, UK
| | - Tayebeh Hamzehloei
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alireza Pasdar
- Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Division of Applied Medicine, Medical School, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
- Metabolic Syndrome Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Majid Ghayour-Mobarhan
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Metabolic Syndrome Research Center, 99199-91766, Mashhad, Iran.
| |
Collapse
|
46
|
Maluleke TT, Millen AME, Michel FS. The effects of estrogen deficiency and aging on myocardial deformation and motion in normotensive female rats. Menopause 2021; 29:89-95. [PMID: 34905750 DOI: 10.1097/gme.0000000000001884] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Estrogen deficiency is associated with left ventricular (LV) dysfunction in postmenopausal women and ovariectomized rats. Whether the relationship between estrogen deficiency and LV dysfunction is independent of cardiovascular disease (CVD) risk factors remains uncertain. This study assessed the effects of short-term and long-term estrogen deficiency on cardiac structure and function using conventional and speckle tracking echocardiography, independent of traditional CVD risk factors. METHODS Female Sprague-Dawley rats were divided into short-term (6 wks) ovariectomized (n = 9), short-term sham-operated (n = 10), long-term (6 mo) ovariectomized (n = 8), and long-term sham-operated (n = 9) groups. Cardiac geometry, systolic and diastolic function, and myocardial deformation and motion were measured using echocardiography. RESULTS Ovariectomy had no effect on conventional echocardiography measures of cardiac structure or function. Compared with short-term, long-term groups had reduced LV internal diameter (false discovery rate [FDR] adjusted P = 0.05) and impaired relaxation (e'; FDR adjusted P = 0.0005) independent of body mass and blood pressure (BP). Global longitudinal strain was impaired in ovariectomized compared with sham-operated rats (FDR adjusted P = 0.05), but not after adjusting for body mass and BP (FDR adjusted P = 0.16). Global longitudinal strain (FDR adjusted P = 0.05), strain rate (FDR adjusted P = 0.002), and velocity (FDR adjusted P = 0.04) were impaired in long-term compared with short-term groups. Global longitudinal strain rate remained impaired after adjustments for body mass and BP (FDR adjusted P = 0.02). CONCLUSIONS Estrogen deficiency does not independently cause cardiac remodeling, LV dysfunction, or impaired myocardial deformation. Traditional CVD risk factors accompanying estrogen deficiency may account for cardiac remodeling and dysfunction observed in postmenopausal women.
Collapse
Affiliation(s)
- Tshiamo T Maluleke
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | | | | |
Collapse
|
47
|
Zhang X, Li T, Cheng HJ, Wang H, Ferrario CM, Groban L, Cheng CP. Chronic GPR30 agonist therapy causes restoration of normal cardiac functional performance in a male mouse model of progressive heart failure: Insights into cellular mechanisms. Life Sci 2021; 285:119955. [PMID: 34520767 DOI: 10.1016/j.lfs.2021.119955] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 08/21/2021] [Accepted: 09/08/2021] [Indexed: 01/22/2023]
Abstract
AIMS G protein-coupled estrogen receptor 30 (GPR30) activation by its agonist, G1, exhibits beneficial actions in female with heart failure (HF). Recent evidence indicates its cardiovascular benefits may also include male as well. However, whether and how GPR30 activation may limit HF progression and have a salutary role in males is unknown. We hypothesized that chronic G1 treatment improves LV and cardiomyocyte function, [Ca2+]i regulation and β-adrenergic reserve, thus limiting HF progression in male. MAIN METHODS We compared left ventricle (LV) and myocyte function, [Ca2+]i transient ([Ca2+]iT) and β-AR modulation in control male mice (12/group) and isoproterenol-induced HF (150 mg/kg s.c. for 2 days). Two weeks after isoproterenol injection, HF mice received placebo, or G1 (150 μg/kg/day s.c. mini-pump) for 2 weeks. KEY FINDINGS Isoproterenol-treated mice exhibited HF with preserved ejection fraction (HFpEF) at 2-weeks and progressed to HF with reduced EF (HFrEF) at 4-weeks, manifested by significantly increased LV time constant of relaxation (τ), decreased EF and mitral flow (dV/dtmax), which were accompanied by reduced myocyte contraction (dL/dtmax), relaxation (dR/dtmax) and [Ca2+]iT. Acute isoproterenol-superfusion caused significantly smaller increases in dL/dtmax, dR/dtmax and [Ca2+]iT. G1 treatment in HF increased basal and isoproterenol-stimulated increases in EF and LV contractility of EES. Importantly, G1 improved basal and isoproterenol-stimulated dL/dtmax, dR/dtmax and [Ca2+]iT to control levels and restored normal cardiac β-AR subtypes modulation. SIGNIFICANCE Chronic G1 treatment restores normal myocyte basal and β-AR-stimulated contraction, relaxation, and [Ca2+]iT, thereby reversing LV dysfunction and playing a rescue role in a male mouse model of HF.
Collapse
Affiliation(s)
- Xiaowei Zhang
- Department of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States of America
| | - Tiankai Li
- Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States of America; Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Heng-Jie Cheng
- Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
| | - Hao Wang
- Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
| | - Carlos M Ferrario
- Department of Surgery, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
| | - Leanne Groban
- Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
| | - Che Ping Cheng
- Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
| |
Collapse
|
48
|
Trongtorsak A, Polpichai N, Thangjui S, Kewcharoen J, Yodsuwan R, Devkota A, Friedman HJ, Estrada AQ. Gender-Related Differences in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis. Pulse (Basel) 2021; 9:38-46. [PMID: 34722354 DOI: 10.1159/000517618] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 05/29/2021] [Indexed: 12/21/2022] Open
Abstract
Background Gender-related differences in phenotypic expression and outcomes have been established in many cardiac conditions; however, the impact of gender in hypertrophic cardiomyopathy (HCM) remains unclear. We conducted a systematic review and meta-analysis to assess the differences in clinical outcomes between female and male HCM patients. Methods We searched MEDLINE and EMBASE from inception to October 2020. Included were cohort studies that compared outcomes of interest including all-cause mortality, HCM-related mortality, and worsening heart failure (HF) or HF hospitalization between male and female. Data from each study were combined using the random effects model to calculate pooled odds ratio (OR) with 95% confidence interval (CI). Results Eleven retrospective cohort studies with a total of 9,427 patients (3,719 females) were included. Female gender was significantly associated with an increased risk of all-cause mortality (pooled OR = 1.63, 95% CI: 1.26-2.10, p ≤ 0.001), HCM-related mortality (pooled OR = 1.47, 95% CI: 1.08-2.01, p = 0.015), and worsening HF or HF hospitalization (pooled OR = 2.05, 95% CI: 1.76-2.39, p ≤ 0.001). Conclusions Female gender was associated with a worse prognosis in HCM. These findings suggest the need for improved care in women including early identification of disease and more possible aggressive management. Moreover, gender-based strategy may benefit in HCM patients.
Collapse
Affiliation(s)
- Angkawipa Trongtorsak
- Internal Medicine Residency Program, AMITA Health Saint Francis Hospital, Chicago, Illinois, USA
| | - Natchaya Polpichai
- Faculty of Medicine Songklanagarin Hospital, Prince of Songkla University, Songkhla, Thailand
| | - Sittinun Thangjui
- Internal Medicine Residency Program, Bassett Healthcare Network, New York, New York, USA
| | - Jakrin Kewcharoen
- Internal Medicine Residency Program, University of Hawaii, Honolulu, Hawaii, USA
| | - Ratdanai Yodsuwan
- Internal Medicine Residency Program, Bassett Healthcare Network, New York, New York, USA
| | - Amrit Devkota
- Internal Medicine Residency Program, AMITA Health Saint Francis Hospital, Chicago, Illinois, USA
| | - Harvey J Friedman
- Department of Pulmonary Medicine and Critical Care, AMITA Health Saint Francis Hospital, Chicago, Illinois, USA
| | - Alfonso Q Estrada
- Department of Cardiovascular Medicine, AMITA Health Saint Francis Hospital, Chicago, Illinois, USA
| |
Collapse
|
49
|
Kim GH, Park YJ. Accelerated diastolic dysfunction in premenopausal women with rheumatoid arthritis. Arthritis Res Ther 2021; 23:247. [PMID: 34560895 PMCID: PMC8461933 DOI: 10.1186/s13075-021-02629-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 09/12/2021] [Indexed: 12/18/2022] Open
Abstract
Background Disturbances of diastolic function precede systolic heart failure and, although clinically silent, represent the earliest sign of cardiac involvement. Diastolic dysfunction (DD) is associated with age, gender (female), and hypertension. However, little is known about the age-specific incidence rates and risk factors for DD in patients with rheumatoid arthritis (RA). Methods We used standard two-dimensional/Doppler echocardiography to screen for the presence of diastolic dysfunction in 61 patients with RA and 107 healthy subjects. All participants were premenopausal women with no history of hypertension. DD includes an impaired relaxation with or without increased left ventricular (LV) filling pressures, pseudonormal filling, and restrictive filling based on parameters measured using echocardiography. Results The two groups were similar with respect to age (P=0.269). Patients with RA had significantly higher LV mass index, LV filling pressure, and lower E/A velocity than controls. All patients had preserved ejection fraction (EF ≥50%). DD was more common in patients with RA at 47% compared to 26% in the controls (P=0.004). Women with RA in the 30- to 49-year age range were over 3.5 times more likely to have DD than those of similar age in the control group (OR=3.54; 95% CI 1.27 to 9.85). Among patients with RA, high CRP levels were independently associated with DD even after adjustment for cardiovascular risk factors (P=0.009). Conclusions In premenopausal women with RA, DD is much more common and the age of onset is reduced. Early screening of myocardial function may provide an opportunity for preventing future cardiovascular disease. Supplementary Information The online version contains supplementary material available at 10.1186/s13075-021-02629-1.
Collapse
Affiliation(s)
- Gee Hee Kim
- Division of Cardiology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Yune-Jung Park
- Division of Rheumatology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea.
| |
Collapse
|
50
|
Sun X, Wang H, Hodge H, Wright KN, Ahmad S, Ferrario CM, Groban L. Amplifying effect of chronic lisinopril therapy on diastolic function and the angiotensin-(1-7) Axis by the G1 agonist in ovariectomized spontaneously hypertensive rats. Transl Res 2021; 235:62-76. [PMID: 33915312 DOI: 10.1016/j.trsl.2021.04.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 04/07/2021] [Accepted: 04/13/2021] [Indexed: 10/21/2022]
Abstract
G protein-coupled estrogen receptor (GPER) activation by G1 attenuates diastolic dysfunction from estrogen loss, which may be partly due to suppression of angiotensin II pathological actions. We aimed to determine the independent effects of 8 weeks of G1 (100 µg/kg/d, subcutaneous pellet), ACE-inhibition (ACEi; lisinopril 10 mg/kg, drinking water), or combination therapy versus vehicle in the ovariectomized (OVX) spontaneously hypertensive rat (SHR) on cardiac function and morphometrics (echocardiography), serum equilibrium of angiotensins (mass spectroscopy) and cardiac components of the RAS (Western blotting). G1 alone and when combined with ACEi enhanced myocardial relaxation (é: 30 and 17%) and diastolic wall strain (DWS: 76 and 68%) while reducing relative wall thickness (RWT: 20 and 33%) and filling pressures (E/é: 30 and 37%). Cardiac expression levels of Mas receptor (Mas-R) and ACE2 also increased in the presence of G1. Strong antihypertensive effects of lisinopril monotherapy were associated with reductions in RWT, collagen deposition and E/é without overtly altering é or DWS. Chronic ACEi also increased cardiac levels of Mas-R and AT1-R and tilted the circulating RAS toward the formation of Ang-(1-7), which was amplified in the presence of G1. In vitro studies further revealed that an inhibitor to prolyl endopeptidase (PEP), but not to neprilysin, significantly reduced serum Ang-(1-7) levels in G1-treated rats, suggesting that G1 might be increasing Ang-(1-7) formation via PEP. We conclude that activating GPER with G1 augments components of the cardiac RAS and improves diastolic function without lowering blood pressure, and that lisinopril-induced blood pressure control and cardiac alterations in OVX SHR are permissive in facilitating G1 to augment Ang-(1-7) in serum, thereby strengthening its cardioprotective benefits.
Collapse
Affiliation(s)
- Xuming Sun
- Department of Anesthesiology, Wake Forest School of Medicine, Winston Salem, North Carolina
| | - Hao Wang
- Department of Anesthesiology, Wake Forest School of Medicine, Winston Salem, North Carolina; Department of Internal Medicine-Molecular Medicine, Wake Forest School of Medicine, Winston Salem, North Carolina
| | - Hunter Hodge
- Department of Anesthesiology, Wake Forest School of Medicine, Winston Salem, North Carolina
| | - Kendra N Wright
- Department of Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina
| | - Sarfaraz Ahmad
- Department of Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina
| | - Carlos M Ferrario
- Department of Surgery, Wake Forest School of Medicine, Winston Salem, North Carolina; Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston Salem, North Carolina
| | - Leanne Groban
- Department of Anesthesiology, Wake Forest School of Medicine, Winston Salem, North Carolina; Department of Internal Medicine-Molecular Medicine, Wake Forest School of Medicine, Winston Salem, North Carolina.
| |
Collapse
|