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Ranjbari S, Almahmeed W, Kesharwani P, Sahebkar A. Advancements in biosensor technologies for fibrinogen detection in cardiovascular disorders. Talanta 2024; 280:126687. [PMID: 39126966 DOI: 10.1016/j.talanta.2024.126687] [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: 01/06/2024] [Revised: 08/04/2024] [Accepted: 08/06/2024] [Indexed: 08/12/2024]
Abstract
Rapid and accurate identification of cardiovascular diseases (CVDs) are crucial for timely medical interventions and improved patient outcomes. Fibrinogen (Fib) has emerged as a valuable biomarker for CVDs, playing a significant role in their early detection. Elevated levels of Fib are associated with an increased risk of developing CVD, highlighting its importance for more precise diagnosis and effective treatment strategies. In recent years, significant advancements have been made in developing biosensor-based approaches for detecting Fib, offering high sensitivity and specificity. This review aims to explore the impact of Fib on cardiovascular conditions, assess the current advancements, and discuss the future potential of biosensors in Fib research for diagnosing cardiovascular disorders. Furthermore, we evaluate various biosensor techniques, including optical, electrochemical, electronic, and gravimetric methods, in terms of their utility for measuring Fib in clinical samples such as serum, plasma, whole blood, and other body fluids. A comparative analysis of these techniques is conducted based on their performance characteristics. By providing a comprehensive overview of the relationship between Fib and cardiovascular ailments, this review aims to clarify the advancements in biosensor technology for Fib detection. The comparison of different biosensor techniques will aid researchers and clinicians in selecting the most suitable approach for their specific diagnostic needs. Ultimately, integrating biosensors into clinical practice has the potential to revolutionize the detection and management of CVDs, leading to improved patient care and outcomes.
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Affiliation(s)
- Sara Ranjbari
- Applied Biomedical Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Wael Almahmeed
- Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Song Y, Wang M, Li Y, Lian Y. The evaluation value of atherogenic index of plasma and high-sensitivity C-reactive protein for the degree of coronary artery lesion in premature coronary artery disease. BMC Cardiovasc Disord 2024; 24:410. [PMID: 39107719 PMCID: PMC11301844 DOI: 10.1186/s12872-024-04014-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 06/26/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Premature coronary artery disease (PCAD) is prevailing. We aimed to investigate the evaluation value of atherogenic index of plasma (AIP) and high-sensitivity C-reactive protein (hs-CRP) for the occurrence and severity of coronary artery lesion in PCAD patients. METHODS PCAD (PACD group)/non-PCAD (control group) patients were enrolled. The coronary artery lesion degree was evaluated using Gensini score (GS). PCAD patients were allocated into the low/medium/high GS groups, with general clinical baseline data analyzed. Plasma hs-CRP/AIP levels were compared in PCAD patients with different disease degree. Correlations between plasma hs-CRP/AIP with Gensini score, independent risk factors affecting the occurrence of PCAD, and the predictive value of hs-CRP/AIP/their combination for the occurrence and degree of PCAD were evaluated by Spearman correlation analysis/Logistic multivariate regression/receiver operating characteristic (ROC) curve. The differences in the area under the curve (AUC) were compared using MedCalc-Comparison of ROC curves. RESULTS Plasma hs-CRP/AIP levels in the PCAD group were increased. Plasma hs-CRP/AIP levels varied significantly among PCAD patients with different disease degree. Plasma hs-CRP/AIP levels were markedly positively correlated with the Gensini score. Smoking history/homocysteine/fasting blood-glucose/hs-CRP/AIP were all independent risk factors affecting PCAD occurrence. The AUC of hs-CRP and AIP combination predicting the occurrence of PCAD was 0.950 (90.80% sensitivity/93.33% specificity). hs-CRP/AIP combination assisted in predicting the disease degree in PCAD patients. CONCLUSIONS AIP and hs-CRP are independent risk factors for the occurrence of PCAD, and their combination has high predictive value for PCAD occurrence and disease degree, which are both positively correlated with coronary artery lesion degree.
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Affiliation(s)
- Yuwei Song
- Department of General Practice, Heping Hospital Affiliated to Changzhi Medical College, 110 Yan'an South Road, Luzhou District, Changzhi, Shanxi Province, 046000, China
| | - Mengmeng Wang
- Department of General Practice, Heping Hospital Affiliated to Changzhi Medical College, 110 Yan'an South Road, Luzhou District, Changzhi, Shanxi Province, 046000, China
| | - Yijun Li
- Department of General Practice, Heping Hospital Affiliated to Changzhi Medical College, 110 Yan'an South Road, Luzhou District, Changzhi, Shanxi Province, 046000, China
| | - Yajun Lian
- Department of General Practice, Heping Hospital Affiliated to Changzhi Medical College, 110 Yan'an South Road, Luzhou District, Changzhi, Shanxi Province, 046000, China.
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Chen S, Li Z, Li H, Zeng X, Yuan H, Li Y. RNA Sequencing of Whole Blood in Premature Coronary Artery Disease: Identification of Novel Biomarkers and Involvement of T Cell Imbalance. J Cardiovasc Transl Res 2024; 17:638-647. [PMID: 38038868 DOI: 10.1007/s12265-023-10465-8] [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: 08/09/2023] [Accepted: 11/17/2023] [Indexed: 12/02/2023]
Abstract
Serum biomarkers were explored based on the peripheral blood gene expression profiles of premature coronary artery disease (PCAD). RNA sequencing (RNA-Seq) was used to detect PCAD-specific differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (RT-PCR) was used to validate the most significant DEGs, and enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the effect on corresponding serum proteins. Fifty-nine PCAD-specific DEGs were identified. Functional analysis showed positive regulation of T cell-mediated cytotoxicity, regulation of T cell-mediated immunity, and the regulation of alpha-beta T cell proliferation which were enriched in PCAD. RT-PCR validated the significant difference in the expression of BAG6, MUC5B, and APOA2 between PCAD and late-onset coronary artery disease (LCAD) patients. ELISA validation showed serum MUC5B increased dramatically in PCAD when compared to LCAD. Our study found T cells contribute to the occurrence of PCAD, and the inflammatory factor MUC5B may be a novel serum marker in PCAD patients.
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Affiliation(s)
- Si Chen
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People's Republic of China
- State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Zhan Li
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People's Republic of China
- State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Haolong Li
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People's Republic of China
- State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Xiaoli Zeng
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Hui Yuan
- Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yongzhe Li
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People's Republic of China.
- State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
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Khoja A, Andraweera PH, Lassi ZS, Padhani ZA, Ali A, Zheng M, Pathirana MM, Aldridge E, Wittwer MR, Chaudhuri DD, Tavella R, Arstall MA. Modifiable and Non-Modifiable Risk Factors for Premature Coronary Heart Disease (PCHD): Systematic Review and Meta-Analysis. Heart Lung Circ 2024; 33:265-280. [PMID: 38365496 DOI: 10.1016/j.hlc.2023.12.012] [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: 07/21/2023] [Revised: 12/01/2023] [Accepted: 12/07/2023] [Indexed: 02/18/2024]
Abstract
AIM We aimed to compare the prevalence of modifiable and non-modifiable coronary heart disease (CHD) risk factors among those with premature CHD and healthy individuals. METHODS PubMed, CINAHL, Embase, and Web of Science databases were searched (review protocol is registered in PROSPERO CRD42020173216). The quality of studies was assessed using the National Heart, Lung and Blood Institute tool for cross-sectional, cohort and case-control studies. Meta-analyses were performed using Review Manager 5.3. Effect sizes for categorical and continuous variables, odds ratio (OR) and mean differences (MD)/standardised mean differences (SMD) with 95% confidence intervals (CI) were reported. RESULTS A total of n=208 primary studies were included in this review. Individuals presenting with premature CHD (PCHD, age ≤65 years) had higher mean body mass index (MD 0.54 kg/m2, 95% CI 0.24, 0.83), total cholesterol (SMD 0.27, 95% CI 0.17, 0.38), triglycerides (SMD 0.50, 95% CI 0.41, 0.60) and lower high-density lipoprotein cholesterol (SMD 0.79, 95% CI: -0.91, -0.68) compared with healthy individuals. Individuals presenting with PCHD were more likely to be smokers (OR 2.88, 95% CI 2.51, 3.31), consumed excessive alcohol (OR 1.40, 95% CI 1.05, 1.86), had higher mean lipoprotein (a) levels (SMD 0.41, 95% CI 0.28, 0.54), and had a positive family history of CHD (OR 3.65, 95% CI 2.87, 4.66) compared with healthy individuals. Also, they were more likely to be obese (OR 1.59, 95% CI 1.32, 1.91), and to have had dyslipidaemia (OR 2.74, 95% CI 2.18, 3.45), hypertension (OR 2.80, 95% CI 2.28, 3.45), and type 2 diabetes mellitus (OR 2.93, 95% CI 2.50, 3.45) compared with healthy individuals. CONCLUSION This meta-analysis confirms current knowledge of risk factors for PCHD, and identifying these early may reduce CHD in young adults.
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Affiliation(s)
- Adeel Khoja
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia; The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia; Cardiology Unit, Northern Adelaide Local Health Network, Adelaide, SA, Australia.
| | - Prabha H Andraweera
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia; The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia; Cardiology Unit, Northern Adelaide Local Health Network, Adelaide, SA, Australia
| | - Zohra S Lassi
- The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia; School of Public Health, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
| | - Zahra A Padhani
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia; The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia
| | - Anna Ali
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia; The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia
| | - Mingyue Zheng
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia; School of Health and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Maleesa M Pathirana
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia; The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia; Cardiology Unit, Northern Adelaide Local Health Network, Adelaide, SA, Australia
| | - Emily Aldridge
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia; The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia; Cardiology Unit, Northern Adelaide Local Health Network, Adelaide, SA, Australia
| | - Melanie R Wittwer
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia; Cardiology Unit, Northern Adelaide Local Health Network, Adelaide, SA, Australia
| | - Debajyoti D Chaudhuri
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia; Cardiology Unit, Northern Adelaide Local Health Network, Adelaide, SA, Australia
| | - Rosanna Tavella
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia; Department of Cardiology, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia
| | - Margaret A Arstall
- Cardiology Unit, Northern Adelaide Local Health Network, Adelaide, SA, Australia; Medical Specialties, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA, Australia
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Chen S, Li Z, Li H, Zeng X, Yuan H, Li Y. Novel lipid biomarkers and ratios as risk predictors for premature coronary artery disease: A retrospective analysis of 2952 patients. J Clin Hypertens (Greenwich) 2023; 25:1172-1184. [PMID: 37986641 PMCID: PMC10710552 DOI: 10.1111/jch.14751] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 10/23/2023] [Accepted: 10/30/2023] [Indexed: 11/22/2023]
Abstract
This study examined the associations between emerging lipid biomarkers (small dense low-density lipoprotein cholesterol [sdLDL-C), lipoprotein(a) [Lp(a)], and free fatty acids [FFA]), two ratios (sdLDL-C/LDL-C and the triglyceride-glucose [TyG) index), and the Gensini score (GS) in patients with premature coronary artery disease (PCAD) in relation to the extent of coronary stenosis. The authors evaluated a cohort of 2952 individuals undergoing coronary angiography (CAG), encompassing those with PCAD (n = 1749), late-onset coronary artery disease (LCAD; n = 328), and non-coronary artery disease (non-CAD; n = 575). Noteworthy differences were observed in the levels of the novel lipid biomarkers and ratio indexes among the PCAD, LCAD, and non-CAD groups (p < .05). Multiple logistic regression analyses pinpointed Lp(a) (OR = 2.62, 95% CI 1.22-5.63, p = .014) and the TyG index (OR = 2.53, 95% CI 1.08-5.93, p = .033) as independent risk factors for PCAD. Furthermore, these biomarkers and ratio indexes discerned substantial distinctions among PCAD patients with varying GS (p < .05). Consequently, these markers can proficiently anticipate the gravity of coronary artery stenosis (GS > 40) in PCAD patients, as evidenced by the ROC analysis. In conclusion, sdLDL-C, Lp(a), FFA, and the sdLDL-C/LDL-C and TyG indexes have considerable potential as risk and diagnostic markers for coronary artery stenosis in individuals afflicted with PCAD.
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Affiliation(s)
- Si Chen
- Department of Clinical LaboratoryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- State Key Laboratory of ComplexSevere and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- Department of Clinical LaboratoryBeijing Anzhen HospitalCapital Medical UniversityBeijingChina
| | - Zhan Li
- Department of Clinical LaboratoryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- State Key Laboratory of ComplexSevere and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Haolong Li
- Department of Clinical LaboratoryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- State Key Laboratory of ComplexSevere and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Xiaoli Zeng
- Department of Clinical LaboratoryBeijing Anzhen HospitalCapital Medical UniversityBeijingChina
| | - Hui Yuan
- Department of Clinical LaboratoryBeijing Anzhen HospitalCapital Medical UniversityBeijingChina
| | - Yongzhe Li
- Department of Clinical LaboratoryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- State Key Laboratory of ComplexSevere and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
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Krzesińska A, Nowak M, Mickiewicz A, Chyła-Danił G, Ćwiklińska A, Koper-Lenkiewicz OM, Kamińska J, Matowicka-Karna J, Gruchała M, Jankowski M, Fijałkowski M, Kuchta A. Lipoprotein(a) As a Potential Predictive Factor for Earlier Aortic Valve Replacement in Patients with Bicuspid Aortic Valve. Biomedicines 2023; 11:1823. [PMID: 37509461 PMCID: PMC10376971 DOI: 10.3390/biomedicines11071823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/16/2023] [Accepted: 06/23/2023] [Indexed: 07/30/2023] Open
Abstract
Bicuspid aortic valve (BAV) affects 0.5-2% of the general population and constitutes the major cause of severe aortic valve stenosis (AVS) in individuals ≤70 years. The aim of the present study was to evaluate the parameters that may provide information about the risk of AVS developing in BAV patients, with particular emphasis on lipoprotein(a) (Lp(a)), which is a well-recognized risk factor for stenosis in the general population. We also analyzed the impact of autotaxin (ATX) and interleukin-6 (IL-6) as parameters potentially related to the pathomechanism of Lp(a) action. We found that high Lp(a) levels (>50 mg/dL) occurred significantly more frequently in patients with AVS than in patients without AVS, both in the group below and above 45 years of age (p = 0.036 and p = 0.033, respectively). Elevated Lp(a) levels were also strictly associated with the need for aortic valve replacement (AVR) at a younger age (p = 0.016). However, the Lp(a) concentration did not differ significantly between patients with and without AVS. Similarly, we observed no differences in ATX between the analyzed patient groups, and both ATX activity and concentration correlated significantly with Lp(a) level (R = 0.465, p < 0.001 and R = 0.599, p < 0.001, respectively). We revealed a significantly higher concentration of IL-6 in young patients with AVS. However, this observation was not confirmed in the group of patients over 45 years of age. We also did not observe a significant correlation between IL-6 and Lp(a) or between CRP and Lp(a) in any of the analyzed groups of BAV patients. Our results demonstrate that a high level of Lp(a), greater than 50 mg/dL, may be a significant predictive factor for earlier AVR. Lp(a)-related parameters, such as ATX and IL-6, may be valuable in providing information about the additional cardiovascular risks associated with developing AVS.
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Affiliation(s)
- Aleksandra Krzesińska
- Department of Clinical Chemistry, Medical University of Gdańsk, 80-211 Gdańsk, Poland
| | - Maria Nowak
- 1st Department of Cardiology, Medical University of Gdańsk, 80-211 Gdańsk, Poland
| | - Agnieszka Mickiewicz
- 1st Department of Cardiology, Medical University of Gdańsk, 80-211 Gdańsk, Poland
| | - Gabriela Chyła-Danił
- Department of Clinical Chemistry, Medical University of Gdańsk, 80-211 Gdańsk, Poland
| | - Agnieszka Ćwiklińska
- Department of Clinical Chemistry, Medical University of Gdańsk, 80-211 Gdańsk, Poland
| | - Olga M Koper-Lenkiewicz
- Department of Clinical Laboratory Diagnostics, Medical University of Białystok, 15-269 Białystok, Poland
| | - Joanna Kamińska
- Department of Clinical Laboratory Diagnostics, Medical University of Białystok, 15-269 Białystok, Poland
| | - Joanna Matowicka-Karna
- Department of Clinical Laboratory Diagnostics, Medical University of Białystok, 15-269 Białystok, Poland
| | - Marcin Gruchała
- 1st Department of Cardiology, Medical University of Gdańsk, 80-211 Gdańsk, Poland
| | - Maciej Jankowski
- Department of Clinical Chemistry, Medical University of Gdańsk, 80-211 Gdańsk, Poland
| | - Marcin Fijałkowski
- 1st Department of Cardiology, Medical University of Gdańsk, 80-211 Gdańsk, Poland
| | - Agnieszka Kuchta
- Department of Clinical Chemistry, Medical University of Gdańsk, 80-211 Gdańsk, Poland
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Lipoprotein(a) in Atherosclerotic Diseases: From Pathophysiology to Diagnosis and Treatment. Molecules 2023; 28:molecules28030969. [PMID: 36770634 PMCID: PMC9918959 DOI: 10.3390/molecules28030969] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 01/12/2023] [Accepted: 01/17/2023] [Indexed: 01/21/2023] Open
Abstract
Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a). Increased Lp(a) levels are an independent, heritable causal risk factor for atherosclerotic cardiovascular disease (ASCVD) as they are largely determined by variations in the Lp(a) gene (LPA) locus encoding apo(a). Lp(a) is the preferential lipoprotein carrier for oxidized phospholipids (OxPL), and its role adversely affects vascular inflammation, atherosclerotic lesions, endothelial function and thrombogenicity, which pathophysiologically leads to cardiovascular (CV) events. Despite this crucial role of Lp(a), its measurement lacks a globally unified method, and, between different laboratories, results need standardization. Standard antilipidemic therapies, such as statins, fibrates and ezetimibe, have a mediocre effect on Lp(a) levels, although it is not yet clear whether such treatments can affect CV events and prognosis. This narrative review aims to summarize knowledge regarding the mechanisms mediating the effect of Lp(a) on inflammation, atherosclerosis and thrombosis and discuss current diagnostic and therapeutic potentials.
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Ugovšek S, Šebeštjen M. Lipoprotein(a)—The Crossroads of Atherosclerosis, Atherothrombosis and Inflammation. Biomolecules 2021; 12:biom12010026. [PMID: 35053174 PMCID: PMC8773759 DOI: 10.3390/biom12010026] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 12/22/2021] [Accepted: 12/23/2021] [Indexed: 12/14/2022] Open
Abstract
Increased lipoprotein(a) (Lp(a)) levels are an independent predictor of coronary artery disease (CAD), degenerative aortic stenosis (DAS), and heart failure independent of CAD and DAS. Lp(a) levels are genetically determinated in an autosomal dominant mode, with great intra- and inter-ethnic diversity. Most variations in Lp(a) levels arise from genetic variations of the gene that encodes the apolipoprotein(a) component of Lp(a), the LPA gene. LPA is located on the long arm of chromosome 6, within region 6q2.6–2.7. Lp(a) levels increase cardiovascular risk through several unrelated mechanisms. Lp(a) quantitatively carries all of the atherogenic risk of low-density lipoprotein cholesterol, although it is even more prone to oxidation and penetration through endothelia to promote the production of foam cells. The thrombogenic properties of Lp(a) result from the homology between apolipoprotein(a) and plasminogen, which compete for the same binding sites on endothelial cells to inhibit fibrinolysis and promote intravascular thrombosis. LPA has up to 70% homology with the human plasminogen gene. Oxidized phospholipids promote differentiation of pro-inflammatory macrophages that secrete pro-inflammatory cytokines (e. g., interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α). The aim of this review is to define which of these mechanisms of Lp(a) is predominant in different groups of patients.
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Affiliation(s)
- Sabina Ugovšek
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia;
| | - Miran Šebeštjen
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia;
- Department of Cardiology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Department of Vascular Diseases, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Correspondence:
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Gue YX, Jeong YH, Farag M, Spinthakis N, Gorog DA. Precision Treatment in ACS-Role of Assessing Fibrinolysis. J Clin Med 2021; 10:jcm10050929. [PMID: 33804303 PMCID: PMC7957496 DOI: 10.3390/jcm10050929] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/17/2021] [Accepted: 02/18/2021] [Indexed: 11/24/2022] Open
Abstract
Despite advancements in pharmacotherapy and interventional strategies, patients with acute coronary syndrome (ACS) remain at risk of recurrent thrombotic events. In addition to an enhanced tendency to thrombus formation, impairment in the ability to naturally dissolve or lyse a developing thrombus, namely impaired endogenous fibrinolysis, is responsible for a major part of this residual risk regardless of optimal antiplatelet medication. Global assessment of endogenous fibrinolysis, including a point-of-care assay, can identify patients with ACS at persistent high cardiovascular risk and might play an important role in allowing the personalisation of potent antithrombotic therapy to enhance fibrinolytic status, providing precision treatment of ACS to improve long-term outcome.
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Affiliation(s)
- Ying X. Gue
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool L14 3PE, UK;
- Department of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK; (M.F.); (N.S.)
| | - Young-Hoon Jeong
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Cardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon 51472, Korea;
| | - Mohamed Farag
- Department of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK; (M.F.); (N.S.)
| | - Nikolaos Spinthakis
- Department of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK; (M.F.); (N.S.)
| | - Diana A. Gorog
- Department of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK; (M.F.); (N.S.)
- National Heart and Lung Institute, Imperial College, London SW3 6LY, UK
- Correspondence:
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10
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Cardiovascular and Metabolic Consequences of Liver Transplantation: A Review. ACTA ACUST UNITED AC 2019; 55:medicina55080489. [PMID: 31443295 PMCID: PMC6722584 DOI: 10.3390/medicina55080489] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Revised: 08/03/2019] [Accepted: 08/09/2019] [Indexed: 12/14/2022]
Abstract
Liver transplantation (LT) is considered the curative treatment option for selected patients who suffer from end-stage or acute liver disease or hepatic malignancy (primary). After LT, patients should be carefully monitored for complications that may appear, partially due to immunosuppressive therapy, but not entirely. Cardiovascular diseases are frequently encountered in patients with LT, being responsible for high morbidity and mortality. Patients with underlying cardiovascular and metabolic pathologies are prone to complications after the transplant, but these complications can also appear de novo, mostly associated with immunosuppressants. Metabolic syndrome, defined by obesity, hypertension, dyslipidemia, and hyperglycemia, is diagnosed among LT recipients and is aggravated after LT, influencing the long-term survival. In this review, our purpose was to summarize the current knowledge regarding cardiovascular (CV) diseases and the metabolic syndrome associated with LT and to assess their impact on short and long-term morbidity and mortality.
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Kolkenbeck-Ruh A, Woodiwiss AJ, Monareng T, Sadiq E, Mabena P, Robinson C, Motau TH, Stevens B, Manyatsi N, Tiedt S, Dembskey R, Abdool-Carrim T, Veller M, Cassimjee I, Modi G, Hale M, Norton GR. Complementary Impact of Carotid Intima-Media Thickness With Plaque in Associations With Noncardiac Arterial Vascular Events. Angiology 2019; 71:122-130. [PMID: 31303025 DOI: 10.1177/0003319719862681] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The ability of carotid intima-media thickness (IMT) to predict risk beyond plaque is controversial. In 952 participants (critical limb ischemia [CLI] or stroke, n = 473; community, n = 479), we assessed whether relationships with events for IMT complement the impact of plaque in young patients depending on the extent of thrombotic versus atherosclerotic disease. The extent of atherosclerotic versus thrombotic occlusion was determined in 54 patients with CLI requiring amputations. Thrombotic occlusion in CLI was associated with younger age (P < .0001) and less plaque (P = .02). Independent relations between plaque and CLI were noted in older (>50 years; P < .005 to <.0001) but not younger (P > .38) participants, while independent relations between plaque and stroke (P < .005 to <.0001) and between IMT and CLI (P < .0001) were noted in younger participants. Although in performance (area under the receiver operating curve) for event detection, IMT thresholds failed to add to plaque alone in older patients (0.680 ± 0.020 vs 0.664 ± 0.017, P = .27), IMT improved performance for combined stroke and CLI detection when added to plaque in younger patients (0.719 ± 0.023 vs 0.631 ± 0.026, P < .0001). Because in younger participants the high prevalence of thrombotic occlusion in CLI is associated with less plaque, IMT adds information in associations with arterial vascular events.
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Affiliation(s)
- Andrea Kolkenbeck-Ruh
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Angela J Woodiwiss
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Talib Monareng
- School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Eitzaz Sadiq
- School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Philanathi Mabena
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Chanel Robinson
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Tshegofatso H Motau
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Belinda Stevens
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Nomvuyo Manyatsi
- School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Scott Tiedt
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Reinhard Dembskey
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Talib Abdool-Carrim
- School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Martin Veller
- School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Ismail Cassimjee
- School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Girish Modi
- School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Martin Hale
- School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Gavin R Norton
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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12
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Osadnik T, Osadnik K, Pawlas N, Strzelczyk J, Kasperczyk J, Poloński L, Gąsior M. Metabolic and genetic profiling of young adults with and without a family history of premature coronary heart disease (MAGNETIC). Study design and methodology. Arch Med Sci 2019; 15:590-597. [PMID: 31110523 PMCID: PMC6524187 DOI: 10.5114/aoms.2018.75895] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 03/22/2018] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION First-degree relatives of individuals with premature coronary artery disease (CAD) are at increased risk of CAD. The research hypothesis of this project assumes that there are differences in the metabolic profiles between individuals with and without a positive family history (FH) of premature CAD. MATERIAL AND METHODS The study group will comprise healthy patients (n = 500) aged 18-35 years with a FH of premature CAD, and the control group (n = 500) will consist of healthy subjects without a FH of premature CAD. Blood tests assessing the lipid profile will be carried out. Patients will respond to a questionnaire regarding FH and dietary habits. Measurement of carotid intima media thickness will be performed. Analysis of single-nucleotide polymorphisms (SNPs) associated with premature CAD will be carried out for every patient. Metabolomic profiling will be performed using a high-sensitivity Bruker AVANCE II 600 MHz NMR spectroscope. RESULTS The results of this study will include a comparison of metabolic profiles assessed by 1H-NMR spectroscopy in the study and control groups and the results of analyses of the relationship between the metabolic profiles and genetic risk score calculated based on evaluated SNPs associated with premature CAD. CONCLUSIONS This study will deepen our knowledge of the aetiopathogenesis of atherosclerosis by identifying metabolic patterns associated with a positive FH of premature CAD. Obtaining a detailed FH will enable adjustments for major risk factors of premature CAD in the proband's first-degree relatives. This research project also provides a chance to discover new biomarkers associated with the risk of premature CAD.
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Affiliation(s)
- Tadeusz Osadnik
- Department of Pharmacology, Medical University of Silesia, School of Medicine with the Division of Dentistry, Zabrze, Poland
- 2 Department of Cardiology, Silesian Centre for Heart Diseases, Zabrze, Poland
| | - Kamila Osadnik
- Department of Pharmacology, Medical University of Silesia, School of Medicine with the Division of Dentistry, Zabrze, Poland
| | - Natalia Pawlas
- Department of Pharmacology, Medical University of Silesia, School of Medicine with the Division of Dentistry, Zabrze, Poland
- Institute of Occupational Medicine and Environmental Health, Sosnowiec, Poland
| | - Joanna Strzelczyk
- Department of Medical and Molecular Biology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Poland
| | - Janusz Kasperczyk
- Centre of Polymer and Carbon Materials, the Polish Academy of Sciences, Zabrze, Poland
| | - Lech Poloński
- 2 Department of Cardiology, Silesian Centre for Heart Diseases, Zabrze, Poland
| | - Mariusz Gąsior
- Third Department of Cardiology, SMDZ in Zabrze, Medical University of Silesia, Katowice, Poland
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13
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Kolkenbeck-Ruh A, Woodiwiss AJ, Naran R, Sadiq E, Robinson C, Motau TH, Monareng T, Mabena P, Manyatsi N, Gazwa PZ, Abdool-Carrim T, Majane OHI, Veller M, Modi G, Norton GR. Carotid intima-media thickness, but not chronic kidney disease independently associates with noncardiac arterial vascular events in South Africa. J Hypertens 2019; 37:795-804. [PMID: 30817461 DOI: 10.1097/hjh.0000000000001921] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
AIM Although chronic kidney disease (CKD) as determined from estimated glomerular filtration rate (eGFR) is recommended for risk prediction by current hypertension guidelines, the equations to derive eGFR may not perform well in black Africans. We compared whether across the adult lifespan, eGFR or CKD are as closely associated with noncardiac arterial vascular events, as carotid intima-media thickness (IMT), in Africa. METHODS In 1152 black South Africans [480 with noncardiac arterial events (294 with critical lower limb ischemia, 186 with stroke) of which 37% were premature] and 672 age, sex and ethnicity-matched controls from a randomly selected community sample, we assessed relations between eGFR, CKD or carotid IMT (B-mode ultrasound) and arterial events. RESULTS From 20 years until old age, with or without adjustments, IMT was increased in those with as compared with without events (P < 0.01 at each decade of age). However, at any decade of age across the adult lifespan neither creatinine concentrations, nor eGFR were altered in those with arterial events (P > 0.28). Although IMT was strongly and independently associated with the odds of an event [odds ratio per 1 SD (0.171 mm) effect = 2.19, confidence interval = 1.75-2.78, P < 0.0001], neither creatinine concentrations (P = 0.89), modification of diet in renal disease-derived (P = 0.07), nor Chronic Kidney Disease Epidemiology Collaboration-derived [odds ratio per 1 SD (22.5 ml/min per 1.73 m) effect = 1.06, confidence interval = 0.89-1.27, P = 0.51] eGFR were independently associated with the odds of an event. Although many with premature events had an increased IMT (63%), few with either premature events (8%) or with events at an older age (21%) had CKD and CKD had a poor performance (0.539 ± 0.011) and low sensitivity (16%) for event detection. CONCLUSION In black South Africans, despite carotid IMT strongly associating with noncardiac arterial vascular events (stroke and critical lower limb ischaemia) consistently across the adult lifespan, few with events have CKD and CKD fails to associate with events.
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Affiliation(s)
| | - Angela J Woodiwiss
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology
| | - Ravi Naran
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology
| | - Eitzaz Sadiq
- Department of Neurology, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand Medical School, Johannesburg, South Africa
| | - Chanel Robinson
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology
| | - Tshegofatso H Motau
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology
| | - Taalib Monareng
- Department of Neurology, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand Medical School, Johannesburg, South Africa
| | - Philanathi Mabena
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology
| | - Nomvuyo Manyatsi
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology
| | - Pitchou Z Gazwa
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology
| | - Talib Abdool-Carrim
- Department of Neurology, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand Medical School, Johannesburg, South Africa
| | | | - Martin Veller
- Department of Neurology, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand Medical School, Johannesburg, South Africa
| | - Girish Modi
- Department of Neurology, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand Medical School, Johannesburg, South Africa
| | - Gavin R Norton
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology
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14
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Andreenko EY, Yavelov IS, Loukianov ММ, Vernohaeva AN, Drapkina OM, Boytsov SA. Ischemic Heart Disease in Subjects of Young Age: Current State of the Problem. Features of Etiology, Clinical Manifestation and Prognosis. ACTA ACUST UNITED AC 2018; 58:24-34. [PMID: 30625075 DOI: 10.18087/cardio.2018.11.10195] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Accepted: 11/24/2018] [Indexed: 11/18/2022]
Abstract
In addition to conventional risk factors in young patients with ischemic heart disease (IHD) numerous other risk factors including genetics play an important role in its causation. Molecular genetic testing is recommended for the detection of monogenic diseases with a high risk of developing IHD, such as familial hypercholesterolemia. In majority ofyoung patients, the first manifestation of IHD is an acute coronary syndrome. Young patients with IHD more often have normal coronary arteries or single-vessel coronary disease, and in up to 20% of them cause of myocardial ischemia is not related to atherosclerosis. In general, young patients with IHD have better prognosis. However, there are sex differences in IHD outcomes the prognosis of patients with premature IHD and reason for this is still unclear.
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Affiliation(s)
- E Yu Andreenko
- National Medical Research Center for Preventive Medicine.
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15
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Gupta MD, Girish MP, Sarkar PG, Gupta A, Kategari A, Bansal A, Saijpaul R, Batra V, Rain M, Tyagi S, Pasha Q. Role of ApoE gene polymorphism and nonconventional biochemical risk factors among very young individuals (aged less than 35 years) presenting with acute myocardial infarction. Indian Heart J 2018; 70 Suppl 3:S146-S156. [PMID: 30595248 PMCID: PMC6310748 DOI: 10.1016/j.ihj.2018.08.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 08/09/2018] [Accepted: 08/12/2018] [Indexed: 12/11/2022] Open
Abstract
Background Incidence rate of acute myocardial infarction (MI) has increased in younger population over the years. The young patients have a different risk profile, presentation, and prognosis than the elderly. Hence, it is essential to understand the risk factors in young patients for proper treatment. Methods Apolipoprotein E (ApoE) polymorphism and biochemicals such as total cholesterol, serum triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein(a), insulin, interleukin-6, homocysteine, fibrinogen, and highly sensitive C-reactive protein were investigated in very young MI (yMI patients; age ≤ 35 years; n = 125), in old MI (oMI patients; age >35 and < 80 years; n = 111), and healthy controls (age ≤35 years; n = 103). Results HDL-C was significantly lower in yMI patients than in controls (p = 2.63E-04) and oMI patients (p = 1.29E-05). ApoA1 was also lowest in yMI patients, but significant only in comparison to controls (p = 2.62E.04). The yMI group had the highest ratios of total cholesterol:HDL-C (p = 0.027 in yMI patients versus controls and p = 0.018 in yMI patients versus oMI patients), LDL-C:HDL-C (p = 0.002 in yMI patients versus controls and p = 0.005 in yMI patients versus oMI patients), and ApoB:ApoA1 (p = 8.75E-05 in yMI patients versus controls and p > 0.05 in yMI patients versus oMI patients). No significant pattern of ApoE polymorphisms was observed. Conclusion The lower level of HDL-C and ApoA1 and higher ratios of total cholesterol:HDL-C, LDL-C:HDL-C, and ApoB:ApoA1 are risk factors for MI in young patients.
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Affiliation(s)
- Mohit D Gupta
- GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India; Safdarjung Hospital and Vardhman Institute of Medical Sciences, New Delhi, India.
| | - M P Girish
- GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India; Safdarjung Hospital and Vardhman Institute of Medical Sciences, New Delhi, India
| | - Prattay G Sarkar
- GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India; Safdarjung Hospital and Vardhman Institute of Medical Sciences, New Delhi, India
| | - Amit Gupta
- GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India; Safdarjung Hospital and Vardhman Institute of Medical Sciences, New Delhi, India
| | - Anand Kategari
- GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India; Safdarjung Hospital and Vardhman Institute of Medical Sciences, New Delhi, India
| | - Ankit Bansal
- GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India; Safdarjung Hospital and Vardhman Institute of Medical Sciences, New Delhi, India
| | - Rajni Saijpaul
- Safdarjung Hospital and Vardhman Institute of Medical Sciences, New Delhi, India
| | - Vishal Batra
- GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India; Safdarjung Hospital and Vardhman Institute of Medical Sciences, New Delhi, India
| | - Manjari Rain
- Institute of Genomics and Integrative Biology, New Delhi, India
| | - Sanjay Tyagi
- GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India; Safdarjung Hospital and Vardhman Institute of Medical Sciences, New Delhi, India
| | - Qadar Pasha
- Institute of Genomics and Integrative Biology, New Delhi, India
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16
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Jung RG, Motazedian P, Ramirez FD, Simard T, Di Santo P, Visintini S, Faraz MA, Labinaz A, Jung Y, Hibbert B. Association between plasminogen activator inhibitor-1 and cardiovascular events: a systematic review and meta-analysis. Thromb J 2018; 16:12. [PMID: 29991926 PMCID: PMC5987541 DOI: 10.1186/s12959-018-0166-4] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 03/05/2018] [Indexed: 12/17/2022] Open
Abstract
Background Small studies have implicated plasminogen activator inhibitor-1 (PAI-1) as a predictor of cardiovascular events; however, these findings have been inconsistent. We sought out to examine the potential role of PAI-1 as a marker for major adverse cardiovascular events (MACE). Methods We systematically reviewed all indexed studies examining the association between PAI-1 and MACE (defined as death, myocardial infarction, or cerebrovascular accident) or restenosis. EMBASE, Web of Science, Medline, and the Cochrane Library were searched through October 2016 to identify relevant studies, supplemented by letters to authors and review of citations. Studies reporting the results of PAI-1 antigen and/or activity levels in association with MACE in human subjects were included. Results Of 5961 articles screened, we identified 38 articles published between 1991 to 2016 that reported PAI-1 levels in 11,557 patients. In studies that examined PAI-1 antigen and activity levels, 15.1% and 29.6% of patients experienced MACE, respectively. Patients with MACE had higher PAI-1 antigen levels with a mean difference of 6.11 ng/mL (95% CI, 3.27-8.96). This finding was similar among patients with and without known coronary artery disease. Comparatively, studies that stratified by PAI-1 activity levels were not associated with MACE. In contrast, studies of coronary restenosis suggest PAI-1 antigen and activity levels are negatively associated with MACE. Conclusions Elevated plasma PAI-1 antigen levels are associated with MACE. Definitive studies are needed to ascertain if PAI-1 acts simply as a marker of risk or if it is indeed a bona fide therapeutic target. Electronic supplementary material The online version of this article (10.1186/s12959-018-0166-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Richard G Jung
- 1CAPITAL Research Group, University of Ottawa Heart Institute, 40 Ruskin Street, H-4238, Ottawa, ON K1Y 4W7 Canada.,2Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON Canada.,3Vascular Biology and Experimental Medicine Laboratory, University of Ottawa Heart Institute, Ottawa, ON Canada
| | - Pouya Motazedian
- 1CAPITAL Research Group, University of Ottawa Heart Institute, 40 Ruskin Street, H-4238, Ottawa, ON K1Y 4W7 Canada
| | - F Daniel Ramirez
- 1CAPITAL Research Group, University of Ottawa Heart Institute, 40 Ruskin Street, H-4238, Ottawa, ON K1Y 4W7 Canada.,4Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON Canada.,5School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON Canada
| | - Trevor Simard
- 1CAPITAL Research Group, University of Ottawa Heart Institute, 40 Ruskin Street, H-4238, Ottawa, ON K1Y 4W7 Canada.,2Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON Canada.,3Vascular Biology and Experimental Medicine Laboratory, University of Ottawa Heart Institute, Ottawa, ON Canada.,4Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON Canada
| | - Pietro Di Santo
- 1CAPITAL Research Group, University of Ottawa Heart Institute, 40 Ruskin Street, H-4238, Ottawa, ON K1Y 4W7 Canada.,4Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON Canada
| | - Sarah Visintini
- 6Berkman Library, University of Ottawa Heart Institute, Ottawa, ON Canada
| | - Mohammad Ali Faraz
- 1CAPITAL Research Group, University of Ottawa Heart Institute, 40 Ruskin Street, H-4238, Ottawa, ON K1Y 4W7 Canada
| | - Alisha Labinaz
- 1CAPITAL Research Group, University of Ottawa Heart Institute, 40 Ruskin Street, H-4238, Ottawa, ON K1Y 4W7 Canada
| | - Young Jung
- 7Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON Canada
| | - Benjamin Hibbert
- 1CAPITAL Research Group, University of Ottawa Heart Institute, 40 Ruskin Street, H-4238, Ottawa, ON K1Y 4W7 Canada.,2Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON Canada.,3Vascular Biology and Experimental Medicine Laboratory, University of Ottawa Heart Institute, Ottawa, ON Canada.,4Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON Canada
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17
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Ramesh G, Sai NVB, Gururaj P, Bhupal R, Patel N. Association of metabolic syndrome and level of hs-CRP, Lp(a), and serum ferritin in young Asian patients (≤45 years) with acute myocardial infarction. Interv Med Appl Sci 2018; 10:65-69. [PMID: 30363361 PMCID: PMC6167620 DOI: 10.1556/1646.10.2018.14] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Aims This study was aimed to determine the levels of hs-CRP, serum ferritin, and Lp(a) and to study the prevalence of metabolic syndrome (MetS) in young patients (≤45 years) with and without acute myocardial infarction (AMI). Methods This was a cross-sectional, case–control study conducted at a tertiary care center in India. Equal number of patients with matched age and sex (n = 51) were included in case group (with AMI) and in control group (without AMI). Subjects were assessed for the presence of MetS as per modified ATP III criteria. The hs-CRP, Lp(a), and serum ferritin were also measured. Results The prevalence of MetS was found to be 62.74% in case group, whereas 33.33% in control group with decreased HDL level as the most prevalent parameter. The hs-CRP level was found to be 15.35 ± 8.27 mg/dl in case group and 1.85 ± 1.05 mg/dl in control group and Lp(a) was 33.84 ± 23.69 mg/dl in case group and 19.68 ± 10.39 mg/dl in control group. No significant difference was observed in the serum ferritin level in case (264.2 ± 40.6 ng/dl) and control (225.51 ± 45.35 ng/dl) groups. Conclusion From this study, we can conclude that the assessment of these novel risk factors [hs-CRP, Lp(a), and MetS] may be used for the risk estimation and can help to prevent future mortality and morbidity due to CVD.
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Affiliation(s)
- Gadepalli Ramesh
- Department of Cardiology, Yashoda Hospital, Secunderabad, Telangana, India
| | | | - Pramod Gururaj
- Department of Cardiology, Yashoda Hospital, Secunderabad, Telangana, India
| | - Reddy Bhupal
- Department of Cardiology, Yashoda Hospital, Secunderabad, Telangana, India
| | - Nilesh Patel
- Department of Cardiology, Yashoda Hospital, Secunderabad, Telangana, India
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18
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Milgrom A, Lee K, Rothschild M, Makadia F, Duhon G, Min S, Wang P, Glueck CJ. Thrombophilia in 153 Patients With Premature Cardiovascular Disease ≤Age 45. Clin Appl Thromb Hemost 2018; 24:295-302. [PMID: 28401801 PMCID: PMC6714667 DOI: 10.1177/1076029617703481] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
We assessed contributions of thrombophilia to premature cardiovascular disease (CVD) events (≤ age 45) in 153 patients. Test results of thrombophilia-hypofibrinolysis were obtained in 153 patients with CVD ≤ age 45, 110 healthy normal controls, and 110 patients who had venous thromboembolism (VTE) without CVD. Of the 153 patients with CVD, 121 (79%) had sustained myocardial infarction, 70 (46%) had coronary artery stenting, and 53 (35%) had coronary artery bypass grafts. The first CVD events occurred at ages >20 to 35 in 47 patients and at ages >35 to 45 in 106 patients. At study entry, median low-density lipoprotein cholesterol was 126 mg/dL, 56 (37%) smoked, 56 (37%) had hypertension, and 56 (37%) were diabetic. Cases differed from normal controls for high factor VIII (10 [22%] of 45 vs 7 of 103 [7%], P = .007), high homocysteine (32 [21%] of 151 vs 5 [5%] of 107, P = .0002), low free protein S (5 [11%] of 44 vs 2 [2%] of 96, P = .032), high anticardiolipin antibodies (ACLA) IgM (11 [9%] of 129 vs 2 [2%] of 109, P = .024), high lipoprotein (a) [Lp(a)] (46 [30%] of 151 vs 21 [19%] of 110, P = .038), and the lupus anticoagulant (4 [11%] of 37 vs 2 [2%] of 110, P = .035). There were no differences ( P > .05) between cases and VTE controls except free protein S and Lp(a). Free protein S was more often low in VTE controls (24 [28%] of 85 vs 5 [11%] of 44, P = .03) and Lp(a) was more often high in cases (46 [30%] of 151, VTE controls 12 [17%] of 71, P = .032). In 153 patients with premature CVD ≤ age 45, thrombophilia was pervasive (high factor VIII, homocysteine, ACLA IgM, low free protein S, high Lp(a), and lupus anticoagulant), evidencing thrombotic contribution to premature CVD. Moreover, thrombophilia in patients with premature CVD was comparable to VTE controls, emphasizing the pervasive nature of thrombophilia in premature CVD.
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Affiliation(s)
- Alexander Milgrom
- Department of Graduate Medical Education and Research, Internal Medicine Residency Program, Jewish Hospital of Cincinnati, Cincinnati, OH, USA
| | - Kevin Lee
- Department of Graduate Medical Education and Research, Internal Medicine Residency Program, Jewish Hospital of Cincinnati, Cincinnati, OH, USA
| | - Matan Rothschild
- Department of Graduate Medical Education and Research, Internal Medicine Residency Program, Jewish Hospital of Cincinnati, Cincinnati, OH, USA
| | - Frini Makadia
- Department of Graduate Medical Education and Research, Internal Medicine Residency Program, Jewish Hospital of Cincinnati, Cincinnati, OH, USA
| | - Greg Duhon
- Department of Graduate Medical Education and Research, Internal Medicine Residency Program, Jewish Hospital of Cincinnati, Cincinnati, OH, USA
| | - Sarah Min
- Department of Graduate Medical Education and Research, Internal Medicine Residency Program, Jewish Hospital of Cincinnati, Cincinnati, OH, USA
| | - Ping Wang
- Department of Graduate Medical Education and Research, Internal Medicine Residency Program, Jewish Hospital of Cincinnati, Cincinnati, OH, USA
| | - Charles J. Glueck
- Department of Graduate Medical Education and Research, Internal Medicine Residency Program, Jewish Hospital of Cincinnati, Cincinnati, OH, USA
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19
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Rallidis LS, Pavlakis G, Foscolou A, Kotakos C, Katsimardos A, Drosatos A, Zolindaki M, Panagiotakos DB. High levels of lipoprotein (a) and premature acute coronary syndrome. Atherosclerosis 2017; 269:29-34. [PMID: 29258004 DOI: 10.1016/j.atherosclerosis.2017.12.011] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Revised: 11/20/2017] [Accepted: 12/06/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIMS High levels of lipoprotein(a) [Lp(a)] are associated with increased risk of acute coronary syndrome (ACS). We explored whether Lp(a) exhibits a stronger association with premature ACS. METHODS A case-control study was conducted; 1457 patients with a history of ACS (54.8 ± 13 years, 86% males) and 2090 age-sex matched adults free of cardiovascular disease were enrolled. Bio-clinical characteristics [risk factors, low-density lipoprotein-cholesterol, Lp(a)] were derived through standard procedures. RESULTS A 10 mg/dL increase in Lp(a) was associated with 4% (95% CI, 1.01 to 1.02) higher likelihood of having ACS in younger (<45 years) and 2% (95% CI, 1.01 to 1.02) higher likelihood in middle-aged (45-60 years) individuals. Adjusting for common risk factors, elevated Lp(a), i.e. >50 mg/dL, was still associated with increased likelihood of ACS in younger adults (<45 years) (OR = 2.88, 95% CI, 1.7 to 4.6) and in middle aged ones (45 and 60 years) (OR = 2.06, 95% CI, 1.4 to 3.2), but not in older participants (>60 years) (OR = 1.31, 95% CI, 0.8 to 2.4). CONCLUSIONS Lp(a) seems to be an independent risk factor for ACS in individuals <45 years, and high Lp(a) levels increase by ∼3folds the risk for ACS. The association is preserved but is less in middle-aged individuals (45-60 years) and is abolished >60 years.
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Affiliation(s)
- Loukianos S Rallidis
- Second Department of Cardiology, University General Hospital Attikon, Athens, Greece.
| | | | - Alexandra Foscolou
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
| | | | - Andreas Katsimardos
- Second Department of Cardiology, University General Hospital Attikon, Athens, Greece
| | - Alexandros Drosatos
- Second Department of Cardiology, University General Hospital Attikon, Athens, Greece
| | - Maria Zolindaki
- Biochemistry Laboratory, General Hospital of Nikea, Piraeus, Greece
| | - Demosthenes B Panagiotakos
- Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece; Faculty of Health, University of Canberra, Australia; School of Allied Health, College of Science, Health and Engineering, LA TROBE University, Australia
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20
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Musthafa QA, Abdul Shukor MF, Ismail NAS, Mohd Ghazi A, Mohd Ali R, M Nor IF, Dimon MZ, Wan Ngah WZ. Oxidative status and reduced glutathione levels in premature coronary artery disease and coronary artery disease. Free Radic Res 2017; 51:787-798. [PMID: 28899235 DOI: 10.1080/10715762.2017.1379602] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Identifying patients at risk of developing premature coronary artery disease (PCAD) which occurs at age below 45 years old and constitutes approximately 7-10% of coronary artery disease (CAD) worldwide remains a problem. Oxidative stress has been proposed as a crucial step in the early development of PCAD. This study was conducted to determine the oxidative status of PCAD in comparison to CAD patients. PCAD (<45 years old) and CAD (>60 years old) patients were recruited with age-matched controls (n = 30, each group). DNA damage score, plasma malondialdehyde (MDA) and protein carbonyl content were measured for oxidative damage markers. Antioxidants such as erythrocyte glutathione (GSH), oxidised glutathione (GSSG), and glutathione peroxidase activity (GPx), superoxide dismutase (SOD) and catalase (CAT) were also determined. DNA damage score and protein carbonyl content were significantly higher in both PCAD and CAD when compared to age-matched controls while MDA level was increased only in PCAD (p<.05). In contrast, GSH, GSH/GSSG ratio, α-tocotrienol isomer, and GPx activity were significantly decreased, but only in PCAD when compared to age-matched controls. The decrease in GSH was associated with PCAD (OR = 0.569 95%CI [0.375 - 0.864], p = .008) and cut-off values of 6.69 μM with areas under the ROC curves (AUROC) 95%CI: 0.88 [0.80-0.96] (sensitivity of 83.3%; specificity of 80%). However, there were no significant differences in SOD and CAT activities in all groups. A higher level of oxidative stress indicated by elevated MDA levels and low levels of GSH, α-tocotrienol and GPx activity in patients below 45 years old may play a role in the development of PCAD and has potential as biomarkers for PCAD.
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Affiliation(s)
- Qurratu Aini Musthafa
- a Department of Biochemistry, Faculty of Medicine , Universiti Kebangsaan Malaysia Medical Centre , Cheras , Malaysia
| | - Muhd Faizan Abdul Shukor
- a Department of Biochemistry, Faculty of Medicine , Universiti Kebangsaan Malaysia Medical Centre , Cheras , Malaysia
| | - Noor Akmal Shareela Ismail
- a Department of Biochemistry, Faculty of Medicine , Universiti Kebangsaan Malaysia Medical Centre , Cheras , Malaysia
| | - Azmee Mohd Ghazi
- b National Heart Institute of Malaysia , Kuala Lumpur , Malaysia
| | - Rosli Mohd Ali
- b National Heart Institute of Malaysia , Kuala Lumpur , Malaysia
| | | | - Mohd Zamrin Dimon
- c Department of Medicine , UiTM Private Specialist Centre , Selangor , Malaysia
| | - Wan Zurinah Wan Ngah
- a Department of Biochemistry, Faculty of Medicine , Universiti Kebangsaan Malaysia Medical Centre , Cheras , Malaysia
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21
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Gue YX, Gorog DA. Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation. Int J Mol Sci 2017; 18:E1850. [PMID: 28841147 PMCID: PMC5618499 DOI: 10.3390/ijms18091850] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Revised: 08/21/2017] [Accepted: 08/21/2017] [Indexed: 12/13/2022] Open
Abstract
The processes of thrombosis and coagulation are finely regulated by endogenous fibrinolysis maintaining healthy equilibrium. When the balance is altered in favour of platelet activation and/or coagulation, or if endogenous fibrinolysis becomes less efficient, pathological thrombosis can occur. Arterial thrombosis remains a major cause of morbidity and mortality in the world despite advances in medical therapies. The role endogenous fibrinolysis in the pathogenesis of arterial thrombosis has gained increasing attention in recent years as it presents novel ways to prevent and treat existing diseases. In this review article, we discuss the role of endogenous fibrinolysis in platelet thrombus formation, methods of measurement of fibrinolytic activity, its role in predicting cardiovascular diseases and clinical outcomes and future directions.
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Affiliation(s)
- Ying X Gue
- Department of Cardiology, East and North Hertfordshire NHS Trust, Hertfordshire SG1 4AB, UK.
| | - Diana A Gorog
- Department of Cardiology, East and North Hertfordshire NHS Trust, Hertfordshire SG1 4AB, UK.
- Department of Postgraduate Medicine, University of Hertfordshire, Hertfordshire AL10 9AB, UK.
- National Heart & Lung Institute, Imperial College, London SW3 6LY, UK.
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22
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Radin M, Schreiber K, Costanzo P, Cecchi I, Roccatello D, Baldovino S, Bazzan M, Cuadrado MJ, Sciascia S. The adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) for risk stratification in young APS patients with acute myocardial infarction. Int J Cardiol 2017; 240:72-77. [PMID: 28385357 DOI: 10.1016/j.ijcard.2017.02.155] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Revised: 02/21/2017] [Accepted: 02/28/2017] [Indexed: 01/21/2023]
Abstract
BACKGROUND Young adults with acute myocardial infarction are a critical group to examine for the purpose of risk factor stratification and modification. In this study we aimed to assess the clinical utility of the adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) for the risk stratification of acute myocardial infarction in a cohort of young patients with antiphospholipid syndrome (APS). METHODS The analysis included 83 consecutive APS patients (≤50years old) who presented with arterial or venous thromboembolic events. Data on cardiovascular risk factors and antiphospholipid antibodies (aPL) positivity were retrospectively collected. The aGAPSS was calculated by adding the points corresponding to the risk factors, based on a linear transformation derived from the ß-regression coefficient as follows: 3 for hyperlipidaemia, 1 for arterial hypertension, 5 for aCL IgG/IgM, 4 for anti-b2 glycoprotein I IgG/IgM and 4 for LA. RESULTS Higher aGAPSS values were observed in patients with acute myocardial infarction when compared to the others [mean aGAPSS 11.9 (S.D. 4.15, range 4-18) Vs. mean aGAPSS 9.2 (S.D. 5.1, range 1-17); T test: p<0.05]. Significantly higher aGAPSS values were also seen in patients with acute coronary syndrome compared to patients with a history of peripheral or cerebrovascular arterial thrombotic events [mean aGAPSS 11.9 (S.D. 4.15, range 4-18) Vs. mean aGAPSS 6.7 (S.D. 5.7, range 1-17); T test: P<0.005]. CONCLUSIONS The aGAPSS is based upon a quantitative score and could aid risk stratifying APS patients younger than 50years for the likelihood of developing coronary thrombotic events and may guide pharmacological treatment for high-risk patients.
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Affiliation(s)
- M Radin
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, and SCDU Nephrology and Dialysis, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
| | - K Schreiber
- Department of Thrombosis and Haemophilia, Guy's and St Thomas' Hospital, London, United Kingdom; Department of Rheumatology, Copenhagen University Hospital, Copenhagen, Denmark
| | - P Costanzo
- Cardiology Departiment, S. Giovanni Bosco Hospital, Turin, Italy
| | - I Cecchi
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, and SCDU Nephrology and Dialysis, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
| | - D Roccatello
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, and SCDU Nephrology and Dialysis, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
| | - S Baldovino
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, and SCDU Nephrology and Dialysis, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
| | - M Bazzan
- UOSD Hematology and Thrombosis Unit, S. Giovanni Bosco Hospital, Turin, Italy
| | - M J Cuadrado
- Louise Coote Lupus Unit, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - S Sciascia
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, and SCDU Nephrology and Dialysis, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy.
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23
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Li Z, Huang J, Li N. Predictive and Prognostic Value of High-density Lipoprotein Cholesterol in Young Male Patients with Acute Myocardial Infarction. Chin Med J (Engl) 2017; 130:77-82. [PMID: 28051027 PMCID: PMC5221116 DOI: 10.4103/0366-6999.196581] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Background: The level of high-density lipoprotein cholesterol (HDL-C) is an important risk indicator and used in risk factor counting and quantitative risk assessment; however, the effect of HDL-C in young male patients with acute myocardial infarction (AMI) is unclear. The aim of this study was to investigate the effect of HDL-C in young male patients. Methods: We recruited 267 consecutive young male patients (≤44 years) diagnosed with AMI. Other 247 participants free from coronary heart disease were enrolled as controls. HDL-C levels of AMI patients and controls were evaluated to analyze the predictive value on AMI. According to the cutoff point of 1.04 mmol/L HDL-C, patients of AMI were divided into two subgroups (normal HDL-C group and low HDL-C group) and were followed up for 2 years. Clinical end points included all major adverse coronary events (MACEs): the main cause of death, nonfatal myocardial infarction, readmissions for acute coronary syndrome, arrhythmias, or revascularization. The prognostic value of HDL-C was evaluated using Cox regression according to MACE. Results: Patients of AMI had decreased proportion in normal HDL-C group compared to controls (47.2% vs. 57.9%; P = 0.017). Logistic regression analysis showed that there was an inverse relationship between HDL-C and AMI in young males. In the low HDL-C subgroup of AMI patients (n = 141), 34 (24.1%) patients experienced a MACE during the 2-year follow-up, compared with 15 (11.9%) patients in normal HDL-C subgroup (n = 126). The Cox regression analysis showed that HDL-C was an independent predictor of a MACE during the follow-up period (hazard ratio = 0.354, P = 0.006). Conclusion: HDL-C was an important parameter for predicting the risk and the clinical outcomes of AMI in young male patients.
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Affiliation(s)
- Zhao Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China
| | - Ji Huang
- Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China
| | - Nan Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China
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Aggarwal A, Srivastava S, Velmurugan M. Newer perspectives of coronary artery disease in young. World J Cardiol 2016; 8:728-734. [PMID: 28070240 PMCID: PMC5183972 DOI: 10.4330/wjc.v8.i12.728] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 10/03/2016] [Accepted: 11/02/2016] [Indexed: 02/06/2023] Open
Abstract
Coronary artery disease (CAD) occurring in less than 45 years of age is termed as young CAD. Recent studies show a prevalence of 1.2% of CAD cases in this age group. Ethnic wise south Asians especially Indians are more vulnerable to have CAD in young age group with a prevalence of 5% to 10%. Conventional risk factors such as smoking, diabetes, hypertension, obesity and family history seems to be as important as in older CAD subjects. But the prevalence of these risk factors seems to vary in younger subjects. By far the most commonly associated risk factor is smoking in young CAD. Several genes associated with lipoprotein metabolism are now found to be associated with young CAD like cholesterol ester transfer protein (CETP) gene, hepatic lipase gene, lipoprotein lipase gene, apo A1 gene, apo E gene and apo B. Biomarkers such as lipoprotein (a), fibrinogen, D-dimer, serum Wnt, gamma glutamyl transferase, vitamin D2 and osteocalcin are seems to be associated with premature CAD in some newer studies. In general CAD in young has better prognosis than older subjects. In terms of prognosis two risk factors obesity and current smoking are associated with poorer outcomes. Angiographic studies shows predominance of single vessel disease in young CAD patients. Like CAD in older person primary and secondary prevention plays an important role in prevention of new and further coronary events.
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25
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Reinstadler SJ, Eitel C, Thieme M, Metzler B, Poess J, Desch S, Thiele H, Eitel I. Comparison of Characteristics of Patients aged ≤45 Years Versus >45 Years With ST-Elevation Myocardial Infarction (from the AIDA STEMI CMR Substudy). Am J Cardiol 2016; 117:1411-6. [PMID: 26965019 DOI: 10.1016/j.amjcard.2016.02.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Revised: 02/08/2016] [Accepted: 02/08/2016] [Indexed: 12/12/2022]
Abstract
It is unknown whether the occurrence of ST-elevation myocardial infarction (STEMI) at a younger age is associated with differences in myocardial damage compared with older patients. We aimed to compare the infarct characteristics (area at risk [AAR], myocardial salvage index [MSI], infarct size [IS], microvascular obstruction [MVO]) and clinical outcome in patients aged ≤45 years and >45 years. We analyzed 795 patients with STEMI treated with primary percutaneous coronary intervention. All patients completed 12-month follow-up for the assessment of major adverse cardiac events (MACE). Left ventricular ejection fraction, AAR, MSI, IS, and MVO were determined by cardiac magnetic resonance imaging. Seventy-eight patients (9.8%) were aged 45 years or younger. Young patients were more likely to be male (p = 0.01), to be current smokers (p <0.001), and to have a family history of coronary artery disease (p = 0.05). Contrary, they had significantly lower prevalence of hypertension (p <0.001), diabetes (p <0.01), and 3-vessel disease (p <0.01). There were no significant differences in left ventricular ejection fraction (p = 0.36), AAR (p = 0.30), MSI (p = 0.34), IS (p = 0.29), or MVO (p = 0.58) between both groups. MACE rate was significantly lower in patients aged ≤45 years compared with patients aged >45 years (1.3% vs 7.5%, p = 0.04). After multivariate adjustment for clinical risk factors and cardiac magnetic resonance findings, age remained an independent predictor of MACE (hazard ratio 1.04, 95% CI 1.01 to 1.07, p = 0.03). In conclusion, infarct characteristics are not dependent on age in patients undergoing primary percutaneous coronary intervention for STEMI.
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Affiliation(s)
- Sebastian Johannes Reinstadler
- Department of Cardiology, Angiology, and Intensive Care Medicine, University Heart Center Lübeck, Medical Clinic II, University of Lübeck, Lübeck, Germany; German Centre for Cardiovascular Research (DZHK), Lübeck, Germany; University Clinic of Internal Medicine III, Department of Cardiology, and Angiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Charlotte Eitel
- Department of Cardiology, Angiology, and Intensive Care Medicine, University Heart Center Lübeck, Medical Clinic II, University of Lübeck, Lübeck, Germany; German Centre for Cardiovascular Research (DZHK), Lübeck, Germany
| | - Merle Thieme
- Department of Cardiology, Angiology, and Intensive Care Medicine, University Heart Center Lübeck, Medical Clinic II, University of Lübeck, Lübeck, Germany; German Centre for Cardiovascular Research (DZHK), Lübeck, Germany
| | - Bernhard Metzler
- University Clinic of Internal Medicine III, Department of Cardiology, and Angiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Janine Poess
- Department of Cardiology, Angiology, and Intensive Care Medicine, University Heart Center Lübeck, Medical Clinic II, University of Lübeck, Lübeck, Germany; German Centre for Cardiovascular Research (DZHK), Lübeck, Germany
| | - Steffen Desch
- Department of Cardiology, Angiology, and Intensive Care Medicine, University Heart Center Lübeck, Medical Clinic II, University of Lübeck, Lübeck, Germany; German Centre for Cardiovascular Research (DZHK), Lübeck, Germany
| | - Holger Thiele
- Department of Cardiology, Angiology, and Intensive Care Medicine, University Heart Center Lübeck, Medical Clinic II, University of Lübeck, Lübeck, Germany; German Centre for Cardiovascular Research (DZHK), Lübeck, Germany
| | - Ingo Eitel
- Department of Cardiology, Angiology, and Intensive Care Medicine, University Heart Center Lübeck, Medical Clinic II, University of Lübeck, Lübeck, Germany; German Centre for Cardiovascular Research (DZHK), Lübeck, Germany.
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Abstract
OBJECTIVE The total burden of subclinical coronary atherosclerosis is significant in young adults. Serum lipoprotein-associated phospholipase A2 (Lp-PLA2) is an established predictor of morbidity and mortality because of cardiovascular disease. The aim of the present investigation was to evaluate the relationship between subclinical coronary atherosclerosis and serum Lp-PLA2 concentrations in a population of young adults. PATIENTS AND METHODS A total of 261 individuals younger than 45 years of age who had undergone coronary computed tomography angiography were evaluated. The study group included 101 patients in whom coronary computed tomography angiography detected subclinical coronary atherosclerosis; the control group included 160 sex-matched and age-matched healthy control patients. RESULTS Serum Lp-PLA2 levels were increased significantly in the study group patients compared with the control patients (15.42±11.88 vs. 8.06±4.32 ng/ml, P<0.001). Furthermore, a positive correlation was identified between the Lp-PLA2 levels and the total number of plaques and diseased arteries (r=0.495, P<0.001, and r=0.621, P<0.001, respectively). The presence of mixed plaque composition was also correlated with the Lp-PLA2 levels (r=0.657, P<0.001). Multivariate regression analysis identified four independently significant predictors of subclinical coronary atherosclerosis: high-sensitivity C-reactive protein levels, tobacco use, uric acid levels, and serum Lp-PLA2 levels. CONCLUSION The presence of subclinical coronary atherosclerosis is associated independently with Lp-PLA2, and it has potential utility as a novel indicator of cardiovascular disease risk in the young adult population.
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Ma X, Ji XM, Fu P, Ding YC, Xue Q, Huang Y. Coexistence of High Fibrinogen and Low High-density Lipoprotein Cholesterol Levels Predicts Recurrent Cerebral Venous Thrombosis. Chin Med J (Engl) 2016; 128:1732-7. [PMID: 26112712 PMCID: PMC4733709 DOI: 10.4103/0366-6999.159345] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND Cerebral venous thrombosis (CVT) may lead to serious neurological disorders; however, little is known about the risk factors for recurrent CVT. Our aim was to determine the association between elevated fibrinogen and decreased high-density lipoprotein cholesterol (HDL-C) levels with recurrent CVT. METHODS This retrospective cohort study included participants if they had a first episode of objectively defined CVT and were admitted to Xuan Wu Hospital, Capital Medical University from August 2005 to September 2009. Demographic and clinical variables were collected, as well as laboratory parameters, including plasma fibrinogen and HDL-C. Patients with CVT were followed for recurrent symptomatic CVT. Follow-up was through the end of September 2010. Potential predictors of recurrence were analyzed using Cox survival analysis. RESULTS At the end of the follow-up, 95 patients were eligible for the study. Twelve of 95 patients (12.6%) had recurred CVT. The median time of recurrence was 7 months (range: 1-39 months). Eight of these 12 (66.7%) experienced recurrence within the first 12 months after their initial CVT. The recurrence rate of CVT was 2.76 per 100 patient-years. Multivariate Cox regression analysis demonstrated that the coexistence of high fibrinogen (>4.00 g/L) and low HDL-C (<1.08 mmol/L) levels at baseline was the only independent predictor for recurrent CVT (hazard ratio: 4.69; 95% confidence interval: 1.10-20.11; P < 0.05). Of the twelve patients with recurrent CVT in our study, 7 (58.3%) had high fibrinogen plus low HDL-C levels. All 7 of these patients took warfarin for 3-12 months, and 6 of 7 had recurrent CVT after the discontinuation of anticoagulant treatment. CONCLUSIONS Concomitant high fibrinogen and low HDL-C levels may be associated with recurrence of CVT. The effect of potential risk factors related to atherothrombosis on recurrent CVT should be closely monitored.
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Affiliation(s)
- Xin Ma
- Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China
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Abstract
The prevalence of thrombophilia and dyslipidemia among young survivors of acute coronary syndrome has not been clearly defined. The purpose of the current study was to investigate the prevalence of multiple markers of thrombophilia and dyslipidemia in a cohort of consecutive young survivors of acute coronary syndrome. The study cohort included 156 consecutive young patients (men <45 and women <50 years), admitted to the intensive cardiac care unit with newly diagnosed acute coronary syndrome. Analysis included baseline, clinical and epidemiological characteristics, angiographic coronary anatomy, echocardiographic evaluation, extensive lipid and thrombophilia laboratory profiles, and in-hospital and 1-year clinical outcomes for all patients. Acute myocardial infarction was diagnosed in 142 (92 %) patients, of whom 108 (72 %) had ST-segment elevation. Eighteen (12 %) patients had no traditional risk factors. Low levels of high-density lipoprotein (<40 mg/dL) were found in 101 (65 %) patients, and 49 (34 %) patients had elevated levels of lipoprotein(a) (Lp(a)) (>30 mg/dL). Eighteen (12 %) patients were diagnosed with antiphospholipid antibody syndrome (APS), and 73 (47 %) had at least one laboratory finding consistent with thrombophilia. Patients with APS had significantly higher levels of Lp(a) (46 ± 32 vs. 29 ± 31 mg/dL, p = 0.005). APS is a common prothrombotic state found in young survivors of acute coronary syndrome. Lp(a) levels are elevated among APS patients who present with premature acute coronary syndrome.
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Gong P, Yang SH, Li S, Luo SH, Zeng RX, Zhang Y, Guo YL, Zhu CG, Xu RX, Li JJ. Plasma d-Dimer as a Useful Marker Predicts Severity of Atherosclerotic Lesion and Short-Term Outcome in Patients With Coronary Artery Disease. Clin Appl Thromb Hemost 2016; 22:633-40. [PMID: 26936933 DOI: 10.1177/1076029616634885] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Increased d-dimer is indicative of a hypercoagulable state and found to be associated with acute coronary syndromes. The present study aimed to evaluate whether plasma d-dimer levels could predict subsequent major clinical events in patients with coronary artery disease (CAD). First, 2209 angiographic-proven patients with CAD were consecutively enrolled. Then, all patients were subjected to follow up for an average of 18 months (ranged from 14 to 1037 days). The relationships of the plasma d-dimer with the severity of CAD and future clinical outcomes were evaluated. We found that plasma d-dimer was higher in patients with prior myocardial infarction (MI) than that in patients with nonprior MI (P = .006). Multivariate linear regression analysis suggested that the plasma d-dimer was linked to the severity of CAD assessed by Gensini score (β = 0.052, 95% confidence interval [CI]: 1.20-6.84, P = .005) even after adjusting for confounding factors. During the follow-up, 42 patients underwent prespecified outcomes. After adjustment for multiple variables in the Cox regression model, the d-dimer levels remained to be a potential predictor of total outcome (hazard ratio = 1.22, 95% CI: 1.09-1.37, P = .001). Therefore, plasma d-dimer levels appeared to be a useful predictor for the severity of CAD and the subsequent major clinical events.
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Affiliation(s)
- Ping Gong
- Center for Dyslipidemia and Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, XiCheng District, Beijing, China Department of Cardiology, The Fifth Hospital of Wuhan & Affiliated Guangci Hospital of Wuhan University, Wuhan, China
| | - Sheng-Hua Yang
- Center for Dyslipidemia and Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, XiCheng District, Beijing, China
| | - Sha Li
- Center for Dyslipidemia and Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, XiCheng District, Beijing, China
| | - Song-Hui Luo
- Department of Cardiology, The Fifth Hospital of Wuhan & Affiliated Guangci Hospital of Wuhan University, Wuhan, China
| | - Rui-Xiang Zeng
- Center for Dyslipidemia and Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, XiCheng District, Beijing, China
| | - Yan Zhang
- Center for Dyslipidemia and Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, XiCheng District, Beijing, China
| | - Yuan-Lin Guo
- Center for Dyslipidemia and Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, XiCheng District, Beijing, China
| | - Cheng-Gang Zhu
- Center for Dyslipidemia and Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, XiCheng District, Beijing, China
| | - Rui-Xia Xu
- Center for Dyslipidemia and Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, XiCheng District, Beijing, China
| | - Jian-Jun Li
- Center for Dyslipidemia and Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, XiCheng District, Beijing, China
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Tabakcı MM, Gerin F, Sunbul M, Toprak C, Durmuş Hİ, Demir S, Arslantaş U, Cerşit S, Batgerel U, Kargın R. Relation of Plasma Fibrinogen Level With the Presence, Severity, and Complexity of Coronary Artery Disease. Clin Appl Thromb Hemost 2016; 23:638-644. [PMID: 26865586 DOI: 10.1177/1076029616629210] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Relation of plasma fibrinogen levels with extent, severity, and complexity of coronary artery disease (CAD) in patients with stable angina pectoris (SAP) has not been adequately investigated. The aim of this study was to evaluate whether plasma fibrinogen level is associated with coronary complexity, severity, and extent assessed by SYNTAX (Synergy between percutaneous coronary intervention with TAXUS and Cardiac Surgery) score (SS). METHODS We enrolled 134 consecutive patients with SAP who underwent coronary angiography. Baseline serum fibrinogen levels were measured, and SS was calculated from the study population. The patients were classified into 3 groups by tertiles of SS (SS, control group = 0; intermediate group < 22; and high group ≥ 22). RESULTS Plasma fibrinogen levels demonstrated a stepwise increase from control group to high SS group. There was a strong correlation between fibrinogen and the SS ( r = .535, P < .001). Area under the receivers operating characteristic curve of fibrinogen was 0.72 (95% confidence interval [CI] 0.61-0.82; < .001) for predicting a high SS. Fibrinogen value higher than 411 mg/dL has a sensitivity of 75% and a specificity of 64% in prediction of high SS. In multivariate analyses, plasma fibrinogen was observed to be an independent predictor for high SS in patients with stable CAD (odds ratio [OR] 1.01; 95% CI, 1.01-1.02; P < .001). CONCLUSION Plasma fibrinogen is a readily measurable systemic inflammatory marker and is independently associated coronary severity and complexity in patients with CAD.
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Affiliation(s)
- Mehmet Mustafa Tabakcı
- 1 Cardiology Department, Kartal Koşuyolu Cardiovascular Research and Training Hospital, Istanbul, Turkey
| | | | - Murat Sunbul
- 3 Department of Cardiology, Medical Faculty, Marmara University, Istanbul, Turkey
| | - Cuneyt Toprak
- 1 Cardiology Department, Kartal Koşuyolu Cardiovascular Research and Training Hospital, Istanbul, Turkey
| | | | - Serdar Demir
- 1 Cardiology Department, Kartal Koşuyolu Cardiovascular Research and Training Hospital, Istanbul, Turkey
| | - Uğur Arslantaş
- 1 Cardiology Department, Kartal Koşuyolu Cardiovascular Research and Training Hospital, Istanbul, Turkey
| | - Sinan Cerşit
- 1 Cardiology Department, Kartal Koşuyolu Cardiovascular Research and Training Hospital, Istanbul, Turkey
| | - Ulaankhuu Batgerel
- 1 Cardiology Department, Kartal Koşuyolu Cardiovascular Research and Training Hospital, Istanbul, Turkey
| | - Ramazan Kargın
- 1 Cardiology Department, Kartal Koşuyolu Cardiovascular Research and Training Hospital, Istanbul, Turkey
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Abstract
The clinical relevance of lipoprotein(a) (Lp(a)) as a cardiovascular risk factor is currently underestimated. The aim of our study was to assess the influence of increased Lp(a) values on the development and severity of coronary artery disease (CAD).In our retrospective analysis of 31,274 patients, who were hospitalized for the first time, we compared patients with isolated increased Lp(a) (> 110 mg/dl) and normal Lp(a) (< 30 mg/dl), with increased Lp(a) concentrations (30-60 mg/dl, 61-90 mg/dl, 91-110 mg/dl), and in a third analysis with additionally increased LDL cholesterol and HbA1c values.Patients with high Lp(a) levels showed a significantly higher incidence of advanced CAD with a three-vessel disease being present in 50.2 vs. 25.1 %. Patients with high Lp(a) levels had a significantly more frequent history of myocardial infarction (34.6 vs. 16.6 %, p < 0.001), surgical myocardial revascularization (40.8 vs. 20.8 %, p < 0.001) and percutaneous coronary intervention (55.3 vs. 33.6 %, p < 0.001). In addition, there was a marked difference in gender to the disadvantage of male patients regarding development and severity of CAD. CAD risk (Odds ratio) was increased 5.5-fold in patients with Lp(a) ≥ 110 mg/dl. Additionally elevated LDL and HbA1c levels were not associated with increased manifestation and severity of CAD.High Lp(a) concentration leads to an increased manifestation and severity of coronary artery disease. Additional risk factors do not aggravate manifestation of CAD.
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Kundu S, Parmar V, Ray S, Basu K, Saha M, Mukherjee A, Khanra D, Sonthalia N, Talukdar A. Predicting flow-mediated dilation of brachial artery in systemic lupus erythematosus patients by reproducible and operator-independent inflammatory and immunologic markers and development of a novel score. INDIAN JOURNAL OF RHEUMATOLOGY 2015. [DOI: 10.1016/j.injr.2015.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Variation of lipoprotein(a) plasma levels after premature myocardial infarction. Int J Cardiol 2015; 186:5-6. [DOI: 10.1016/j.ijcard.2015.03.211] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Accepted: 03/17/2015] [Indexed: 11/21/2022]
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Rallidis LS, Sakadakis EA, Tympas K, Varounis C, Zolindaki M, Dagres N, Lekakis J. The impact of smoking on long-term outcome of patients with premature (≤35years) ST-segment elevation acute myocardial infarction. Am Heart J 2015; 169:356-62. [PMID: 25728725 DOI: 10.1016/j.ahj.2014.12.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2014] [Accepted: 12/04/2014] [Indexed: 10/24/2022]
Abstract
BACKGROUND There are few data regarding the long-term prognosis of young survivors of acute myocardial infarction (AMI). We explored the long-term outcome in individuals who had sustained a premature ST-segment elevation AMI. METHODS We recruited 257 consecutive patients who had survived their first AMI ≤35years of age. Patients were followed up for up to 18years. Clinical end points included all major adverse coronary events (MACE): cardiac death, readmission for acute coronary syndrome, arrhythmias, or coronary revascularization due to clinical deterioration. RESULTS The most prevalent risk factor at presentation was smoking (93.7%). Follow-up data were obtained from 237 patients (32.2±3.7years old). The median follow-up period was 9.1years. During follow-up, 139 (58.6%) patients reported continuation of smoking. Ninety-one (38.4%) patients had recurrent MACE (13 deaths, 59 acute coronary syndromes, 2 arrhythmias, and 17 revascularizations). Multivariable Cox regression analysis showed that persistence of smoking, left ventricular ejection fraction (LVEF), and reperfusion therapy (fibrinolysis or primary coronary angioplasty) were independent predictors of MACE after adjustment for conventional risk factors. Continuation of smoking remained an independent predictor for MACE after additional adjustments for LVEF (hazard ratio 2.154, 95% CI 1.313-3.535, P=.002) or reperfusion treatment (hazard ratio 2.327, 95% CI 1.423-3.804, P=.001). Harrell c statistic showed that the model with persistent smoking had the best discriminatory power compared with models with LVEF or reperfusion treatment. CONCLUSIONS In the era of statins and reperfusion treatment, continuation of smoking is the strongest independent long-term predictor for recurrent MACE in young survivors of premature AMI.
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VanWagner LB, Lapin B, Levitsky J, Wilkins JT, Abecassis MM, Skaro AI, Lloyd-Jones DM. High early cardiovascular mortality after liver transplantation. Liver Transpl 2014; 20:1306-16. [PMID: 25044256 PMCID: PMC4213202 DOI: 10.1002/lt.23950] [Citation(s) in RCA: 158] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Accepted: 06/30/2014] [Indexed: 12/12/2022]
Abstract
Cardiovascular disease (CVD) contributes to excessive long-term mortality after liver transplantation (LT); however, little is known about early postoperative CVD mortality in the current era. In addition, there is no model for predicting early postoperative CVD mortality across centers. We analyzed adult recipients of primary LT in the Organ Procurement and Transplantation Network (OPTN) database between February 2002 and December 2012 to assess the prevalence and predictors of early (30-day) CVD mortality, which was defined as death from arrhythmia, heart failure, myocardial infarction, cardiac arrest, thromboembolism, and/or stroke. We performed logistic regression with stepwise selection to develop a predictive model of early CVD mortality. Sex and center volume were forced into the final model, which was validated with bootstrapping techniques. Among 54,697 LT recipients, there were 1576 deaths (2.9%) within 30 days. CVD death was the leading cause of 30-day mortality (40.2%), and it was followed by infection (27.9%) and graft failure (12.2%). In a multivariate analysis, 9 significant covariates (6 recipient covariates, 2 donor covariates, and 1 operative covariate) were identified: age, preoperative hospitalization, intensive care unit status, ventilator status, calculated Model for End-Stage Liver Disease score, portal vein thrombosis, national organ sharing, donor body mass index, and cold ischemia time. The model showed moderate discrimination (C statistic = 0.66, 95% confidence interval = 0.63-0.68). In conclusion, we provide the first multicenter prognostic model for the prediction of early post-LT CVD death, the most common cause of early post-LT mortality in the current transplant era. However, evaluations of additional CVD-related variables not collected by the OPTN are needed in order to improve the model's accuracy and potential clinical utility.
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Affiliation(s)
- Lisa B. VanWagner
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine
- Northwestern University Transplant Outcomes Research Collaborative, Northwestern University Feinberg School of Medicine
| | - Brittany Lapin
- Northwestern University Transplant Outcomes Research Collaborative, Northwestern University Feinberg School of Medicine
- Department of Surgery, Division of Organ Transplantation, Northwestern University Feinberg School of Medicine
| | - Josh Levitsky
- Department of Medicine, Division of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine
- Department of Surgery, Division of Organ Transplantation, Northwestern University Feinberg School of Medicine
| | - John T. Wilkins
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine
- Department of Medicine, Division of Cardiology, Northwestern University Feinberg School of Medicine
| | - Michael M. Abecassis
- Northwestern University Transplant Outcomes Research Collaborative, Northwestern University Feinberg School of Medicine
- Department of Surgery, Division of Organ Transplantation, Northwestern University Feinberg School of Medicine
| | - Anton I. Skaro
- Northwestern University Transplant Outcomes Research Collaborative, Northwestern University Feinberg School of Medicine
- Department of Surgery, Division of Organ Transplantation, Northwestern University Feinberg School of Medicine
| | - Donald M. Lloyd-Jones
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine
- Department of Medicine, Division of Cardiology, Northwestern University Feinberg School of Medicine
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Sonneveld MAH, de Maat MPM, Leebeek FWG. Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis. Blood Rev 2014; 28:167-78. [PMID: 24825749 DOI: 10.1016/j.blre.2014.04.003] [Citation(s) in RCA: 103] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Accepted: 04/14/2014] [Indexed: 01/08/2023]
Abstract
Von Willebrand Factor (VWF) plays an important role in hemostasis by mediating platelet adhesion and aggregation. Ultralarge VWF multimers are cleaved by ADAMTS13 in smaller, less procoagulant forms. An association between high VWF levels and cardiovascular disease has frequently been reported, and more recently also an association has been observed between low ADAMTS13 levels and arterial thrombosis. We reviewed the current literature and performed meta-analyses on the relationship between both VWF and ADAMTS13 with arterial thrombosis. Most studies showed an association between high VWF levels and arterial thrombosis. It remains unclear whether ADAMTS13 is a causal independent risk factor because the association between low ADAMTS13 and arterial thrombosis is so far only shown in case-control studies. Prospective studies are awaited. A causal role for ADAMTS13 is supported by mice studies of cerebral infarction where the infusion of recombinant human ADAMTS13 reduced the infarct size.
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Affiliation(s)
| | - Moniek P M de Maat
- Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Frank W G Leebeek
- Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
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Davidson L, Wilcox J, Kim D, Benton S, Fredi J, Vaughan D. Clinical features of precocious acute coronary syndrome. Am J Med 2014; 127:140-4. [PMID: 24332726 DOI: 10.1016/j.amjmed.2013.09.025] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2013] [Revised: 09/30/2013] [Accepted: 09/30/2013] [Indexed: 10/26/2022]
Abstract
BACKGROUND Acute coronary syndrome due to acute plaque rupture has been well described and is associated with established risk factors, including hypertension, diabetes mellitus, hyperlipidemia, and smoking. The prevalence of these risk factors in very young patients (aged ≤35 years) is not well known, and they may have other nontraditional risk factors. We hypothesized that acute coronary syndrome in very young patients may represent a thrombotic event independent of underlying atherosclerotic disease. METHODS We performed a dual-institution, retrospective study of consecutive patients aged ≤35 years who presented with acute coronary syndrome and underwent coronary angiography from January 2000 to December 2011. Standard demographics, risk factors, and detailed angiographic information were obtained. RESULTS A total of 124 patients met inclusion criteria. The mean age was 31 ± 4 years for both sexes. Approximately half (49%) of the patients were obese (body mass index ≥30 kg/m(2)); 90% of patients had at least 1 traditional risk factor, most commonly hyperlipidemia (63%) and smoking (60%); 52% of patients underwent re-vascularization, of which 94% were by percutaneous coronary intervention, and 42.9% of patients had intracoronary thrombus, of whom approximately one third had no detectable underlying coronary disease. CONCLUSIONS Very young patients with acute coronary syndrome tend to be obese, with a high prevalence of smoking and hyperlipidemia. The presence of thrombus in the absence of underlying coronary disease suggests a thromboembolic event or de novo thrombotic occlusion, which may reflect primary hemostatic dysfunction in a considerable number of these patients.
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Affiliation(s)
- Laura Davidson
- Northwestern University Feinberg School of Medicine, Chicago, Ill.
| | - Jane Wilcox
- Northwestern University Feinberg School of Medicine, Chicago, Ill
| | - David Kim
- Vanderbilt University Medical Center, Nashville, Tenn
| | | | - Joseph Fredi
- Vanderbilt University Medical Center, Nashville, Tenn
| | - Douglas Vaughan
- Northwestern University Feinberg School of Medicine, Chicago, Ill
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DUSP1 Gene Polymorphisms Are Associated with Obesity-Related Metabolic Complications among Severely Obese Patients and Impact on Gene Methylation and Expression. Int J Genomics 2013; 2013:609748. [PMID: 23986905 PMCID: PMC3748404 DOI: 10.1155/2013/609748] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2013] [Accepted: 07/11/2013] [Indexed: 01/04/2023] Open
Abstract
The DUSP1 gene encodes a member of the dual-specificity phosphatase family previously identified as being differentially expressed in visceral adipose tissue (VAT) of severely obese men with versus without the metabolic syndrome. Objective. To test the association between DUSP1 polymorphisms, obesity-related metabolic complications, gene methylation, and expression levels in VAT. Methods. The DUSP1 locus and promoter region were sequenced in 25 individuals. SNPs were tested for association with obesity-related complications in a cohort of more than 1900 severely obese individuals. The impact of SNPs on methylation levels of 36 CpG sites and correlations between DNA methylation and gene expression levels in VAT were computed in a subset of 14 samples. Results. Heterozygotes for rs881150 had lower HDL-cholesterol levels (HDL-C; P = 0.01), and homozygotes for the minor allele of rs13184134 and rs7702178 had increased fasting glucose levels (P = 0.04 and 0.01, resp.). rs881150 was associated with methylation levels of CpG sites located ~1250 bp upstream the transcription start site. Methylation levels of 4 CpG sites were inversely correlated with DUSP1 gene expression. Conclusion. These results suggest that DUSP1 polymorphisms modulate plasma glucose and HDL-C levels in obese patients possibly through alterations of DNA methylation and gene expression levels.
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Lymphocyte subset characterization in patients with early clinical presentation of coronary heart disease. J Thromb Thrombolysis 2013; 34:475-82. [PMID: 22903683 DOI: 10.1007/s11239-012-0761-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This study aimed to investigate lymphocyte populations in non-diabetic patients with early clinical presentation of coronary heart disease (CHD). Twenty-five consecutive middle-aged (<55 years) out-patients with CHD (acute myocardial infarction in the previous 3 months) and stable clinical conditions (>1 month) underwent venous blood sampling in order to determinate CD3+ (T-lymphocytes), CD19+ (B-lymphocytes), CD4+ (helper/inducer lymphocytes) and CD8+ (suppressor/cytotoxic lymphocytes) populations. Patients with diabetes, heart failure symptoms, recent revascularization (<30 days) were excluded. Twenty-five patients matched for age, gender and risk factors were enrolled as controls. All patients with CHD previously underwent coronary angiography. CHD patients showed lower CD3+ levels (70.96 ± 4.72 vs. 74.12 ± 4.93 %, p < 0.05) and CD8+ (37.80 ± 7.15 vs. 46.36 ± 5.22 %, p < 0.001) but higher CD4+ (37.32 ± 7.99 vs. 31.64 ± 4.72 %, p < 0.01) and CD4+/CD8+ ratio (1.06 ± 0.43 vs. 0.69 ± 0.13, p < 0.001). Difference in CD19+ levels was not statistically significant. Subjects with an impaired (≤55 %) left ventricular ejection fraction were characterized by lower levels of CD8+ (33.23 ± 7.04 vs. 43.76 ± 7.40 %, p < 0.05) and higher levels of CD4+ (38.31 ± 8.23 vs. 32.73 ± 6.08 %, p < 0.05) and CD4+/CD8+ ratio (1.06 ± 0.38 vs. 0.79 ± 0.34, p < 0.05). CD8+ levels inversely related to severity of coronary atherosclerosis (r = -0.37, p < 0.01). In conclusion, subjects with early clinical presentation of CHD are characterized by an altered CD4+/CD8+ ratio and lower CD3+ levels.
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Reibis R, Treszl A, Wegscheider K, Bestehorn K, Karmann B, Völler H. Disparity in risk factor pattern in premature versus late-onset coronary artery disease: a survey of 15,381 patients. Vasc Health Risk Manag 2012; 8:473-81. [PMID: 22930639 PMCID: PMC3425343 DOI: 10.2147/vhrm.s33305] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND There are few data available regarding the specificity and modifiability of major cardiovascular (CV) risk factors in patients with premature versus (vs) late-onset coronary artery disease (CAD). This study was designed to analyze and compare these risk factors. PATIENTS AND METHODS Data from 15,381 consecutive patients (mean age, 62.3 ± 11.7 years; female, 33.8%) hospitalized with CAD were collected from a large-scale registry (Transparency Registry to Objectify Guideline-Oriented Risk Factor Management) and analyzed. The patients were divided into two groups, depending on age at inclusion: group 1 patients (n = 5725; mean age, 50.5 ± 7.2 years) were males aged < 55 years and females aged < 65 years; group 2 patients (n = 9656; mean age, 69.4 ± 7.4 years) were males aged > 55 years and females aged > 65 years and had a low-density lipoprotein cholesterol level of >100 mg/dL on admission to cardiac rehabilitation. Besides the conventional risk factors, lipoprotein(a) concentrations and glucose tolerance were measured facultatively. Univariate (chi-square test) and multivariate logistic regression models were used. RESULTS Cigarette smoking (group 1 at 31.5% vs group 2 at 9.4%; P < 0.001), family history of CAD (group 1 at 43.6% vs group 2 at 26.5%; P < 0.001), and dyslipidemia (group 1 at 92.7% vs group 2 at 91.8%; P < 0.001) were dominant risk factors in the younger group. Arterial hypertension (group 1 at 71.4% vs group 2 at 87.0%; P < 0.001) and diabetes (group 1 at 23.5% vs group 2 at 30.1%; P < 0.001) were dominant risk factors in the older group. Impaired glucose tolerance and diabetes were less frequent in the younger group (P(trend) = 0.038), and identical lipoprotein(a) concentration levels of >30 mg/dL were found in both groups (8.0%; P = 0.810). Modification of lipid profile and blood pressure was more effective in the younger group (low-density lipoprotein cholesterol < 100 mg/dL: group 1 at 66.3% vs group 2 at 61.1%; systolic blood pressure < 140 mmHg: group 1 at 91.7% vs group 2 at 83.0%; P < 0.001). CONCLUSION CV risk factors differ markedly between premature and non-premature CAD. Cardiac rehabilitation provides an opportunity to reinforce secondary prevention after acute coronary syndrome.
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Affiliation(s)
- Rona Reibis
- Department of Cardiology, Klinik am See, Rehabilitation Center of Cardiovascular Diseases, Rüdersdorf, Germany.
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Mulders TA, Maurissen LFA, Meyer Z, Hameeteman M, van der Donk C, Kroon AA, Ferreira I, Stehouwer CDA, Hackeng TM, Pinto-Sietsma SJ. A positive family history for premature cardiovascular disease identifies patients prone to recurrent arterial thrombotic events. Eur J Prev Cardiol 2011; 19:1465-73. [DOI: 10.1177/1741826711422989] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Ties A Mulders
- University Medical Centre, Maastricht, The Netherlands
- Academic Medical Centre, Amsterdam, The Netherlands
| | | | - Zainna Meyer
- University Medical Centre, Maastricht, The Netherlands
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Tousoulis D, Papageorgiou N, Androulakis E, Briasoulis A, Antoniades C, Stefanadis C. Fibrinogen and cardiovascular disease: genetics and biomarkers. Blood Rev 2011; 25:239-45. [PMID: 21652129 DOI: 10.1016/j.blre.2011.05.001] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Several prospective epidemiological studies and clinical observations provided evidence regarding fibrinogen and coronary artery disease (CAD). Many of these studies firmly correlate fibrinogen with CAD. However, it is uncertain whether this relation is causal or reflects genetic variability and residual confounding by other risk factors. Several polymorphisms on fibrinogen chain genes affect its levels, however only few of the genetic variants are associated with increased cardiovascular risk. As regards the role of fibrinogen in myocardial infarction (MI) studies indicate that genetic variations have at best a modest impact on the process resulting in MI. Therefore, the screening of fibrinogen genes might not be useful for the assessment of the risk of MI. However, the findings that specific genotypes lead to specific differences in fibrinogen levels, but may not be linked to cardiovascular risk, complicates the hypothesis of causality of fibrinogen in the pathogenesis of cardiovascular disease.
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Affiliation(s)
- Dimitris Tousoulis
- Athens University Medical School, Hippokration Hospital,Vasilissis Sofias 114, 115 28, Athens, Greece.
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Abstract
AbstractHypofibrinolysis as measured with overall clot lysis assays is associated with risk of arterial thrombosis. Individual components of the fibrinolytic system, however, have not been studied extensively in relation to arterial disease, or results of studies were inconsistent. The relation between plasminogen and α2-antiplasmin levels and cardiovascular risk factors and the association between plasminogen, α2-antiplasmin, tissue-plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) and risk of myocardial infarction was investigated in the Study of Myocardial Infarctions Leiden (555 men with a first myocardial infarction and 635 controls). α2-antiplasmin was associated with age and lipid levels, whereas plasminogen correlated with lipids, C-reactive protein, and smoking. Increased levels of all fibrinolytic factors were associated with myocardial infarction. Age-adjusted odds ratios (ORs; 95% confidence interval) for quartile 4 compared with 1 were 1.7 (1.2-2.3) for plasminogen, 1.9 (1.3-2.6) for α2-antiplasmin, 1.7 (1.2-2.3) for t-PA, and 1.7 (1.2-2.4) for PAI-1. After adjusting for cardiovascular risk factors, only α2-antiplasmin levels remained associated with risk (OR, 1.4; [1.0-2.0]). t-PA and PAI-1 levels predominantly reflected lipid levels, whereas plasminogen reflected the inflammatory state. Concluding, elevated α2-antiplasmin levels are independently associated with risk of myocardial infarction. t-PA, PAI-1, and plasminogen levels appear to reflect other cardiovascular risk factors.
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Prognostic value of plasma fibrinolysis activation markers in cardiovascular disease. J Am Coll Cardiol 2010; 55:2701-9. [PMID: 20538163 DOI: 10.1016/j.jacc.2009.11.095] [Citation(s) in RCA: 86] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2009] [Revised: 10/26/2009] [Accepted: 11/02/2009] [Indexed: 11/24/2022]
Abstract
The pivotal role of hypoactive endogenous fibrinolysis in the occurrence of thrombotic cardiovascular events is now well-recognized. To evaluate the diagnostic and prognostic role of impaired fibrinolysis, plasma fibrinolysis markers have been investigated in large prospective studies in both healthy individuals and patients with established coronary disease. Antigen and activity levels of components of the fibrinolytic system were measured by immunoassays, which replaced earlier global fibrinolysis tests. This review covers 45 studies in nearly 50,000 subjects, examining the association between plasma markers of fibrinolysis and coronary artery disease, to establish the usefulness of these markers in predicting future cardiovascular events. The predictive value of plasma levels of tissue-type plasminogen activator, platelet activator inhibitor-1, plasmin-antiplasmin complex, D-dimer, thrombin activatable fibrinolysis inhibitor, and lipoprotein(a) for major adverse cardiac events is highly variable and conflicting, especially after adjusting for conventional risk factors, judging from the published data in the last decade. The value of fibrinolysis activity markers is very limited in aiding diagnosis and risk stratification in the individual patient, on the basis of the weak prognostic values obtained in some studies and the lack of power in others. The physiological limitations of such markers in reflecting endogenous fibrinolysis is discussed. The emerging novel global assays of fibrinolysis will require large-scale clinical trials before their prognostic power or superiority to multiple biomarker measurements can be evaluated.
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Snell-Bergeon JK, West NA, Mayer-Davis EJ, Liese AD, Marcovina SM, D'Agostino RB, Hamman RF, Dabelea D. Inflammatory markers are increased in youth with type 1 diabetes: the SEARCH Case-Control study. J Clin Endocrinol Metab 2010; 95:2868-76. [PMID: 20371668 PMCID: PMC2902077 DOI: 10.1210/jc.2009-1993] [Citation(s) in RCA: 106] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
CONTEXT Increased inflammation may contribute to type 1 diabetes (T1D) complications. OBJECTIVE The objective of the study was to investigate the association of inflammation with obesity, hyperglycemia and dyslipidemia in youth with T1D. DESIGN This was a cross-sectional study of youth with and without T1D. SETTING The study was conducted in Colorado and South Carolina. PATIENTS SEARCH Case-Control participants with T1D [n = 553, mean age 15 yr (range 10-22), median duration 2.7 yr] and without diabetes [n = 215, mean age 15 yr (range 10-22)]. INTERVENTION This was an observational study. MAIN OUTCOME MEASURES IL-6, high-sensitivity C-reactive protein (hsCRP), fibrinogen, and leptin were measured. RESULTS Inflammatory markers were evaluated by diabetes status, quartiles of glycated hemoglobin, and obesity using multiple linear regression analyses, adjusted for age, sex, study site, race/ethnicity, T1D duration, body mass index, and pubertal status. Compared with controls, youth with T1D had higher IL-6 and fibrinogen levels at all levels of glycemia and obesity, and hsCRP levels were significantly higher in youth with T1D in the top three quartiles of glycated hemoglobin (> or = 7.2%) and among normal-weight subjects. Leptin was lower in youth with poor glycemic control. Higher hsCRP and fibrinogen were correlated with higher total and LDL cholesterol, and apolipoprotein B in youth with T1D, whereas higher fibrinogen was correlated with higher LDL and apolipoprotein B in controls. CONCLUSIONS T1D is characterized by excess inflammation, independent of adiposity and glycemic control. Even T1D youth in good glycemic control had higher levels of IL-6 and fibrinogen than controls. Elevated inflammatory markers were associated with an atherogenic lipid profile, which may contribute to accelerated atherosclerosis in youth with T1D.
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Affiliation(s)
- Janet K Snell-Bergeon
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, P.O. Box 6511, Mail Stop A-140, Aurora, Colorado 80045, USA.
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Haas MJ, Mooradian AD. Regulation of high-density lipoprotein by inflammatory cytokines: establishing links between immune dysfunction and cardiovascular disease. Diabetes Metab Res Rev 2010; 26:90-9. [PMID: 20047197 DOI: 10.1002/dmrr.1057] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Coronary artery disease is a primary co-morbidity in metabolic diseases such as metabolic syndrome, diabetes and obesity. One contributing risk factor for coronary artery disease is low high-density lipoprotein-cholesterol (HDLc). Several factors influence steady-state HDLc levels, including diet, genetics and environment. Perhaps more important to coronary artery disease is factors that attribute to the dynamics of reverse cholesterol transport, storage, and excretion of excess cholesterol. HDLc biogenesis, clearance and innate ability to serve as a cholesterol acceptor and transporter all contribute to HDLc's function as a negative regulator of cardiovascular disease. With the recent failure of torcetrapid, focus is being placed on HDLc biology and its role in various metabolic diseases. Low HDLc levels are often associated with an increased state of background inflammation. Recently, several syndromes with clear pro-inflammatory components have been shown to be inversely correlated with low HDLc levels in the absence of obesity, diabetes and metabolic syndrome. Early studies with HDLc during the acute-phase response suggest that HDLc is substantially physically modified during acute infection and sepsis, and recent studies show that HDLc is physically modified by chronic pro-inflammatory disease. In this review, several of these connections are described and cytokine signalling related to HDLc is examined.
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Affiliation(s)
- Michael J Haas
- Department of Medicine, University of Florida College of Medicine, 653-1 West Eighth Street, Jacksonville, FL 32209, USA.
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Premature coronary artery disease in young patients: an uncommon but growing entity. Int J Cardiol 2009; 144:131-2. [PMID: 19174320 DOI: 10.1016/j.ijcard.2008.12.150] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2008] [Accepted: 12/13/2008] [Indexed: 02/08/2023]
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