The relationship between remnant-like particle cholesterol (RLP-C) and cardiovascular disease risk and prognosis has been established, but its effect on the prognosis of ischemic heart failure (IHF) patients undergoing percutaneous coronary intervention (PCI) remains uncertain.

In this study, 2036 patients with IHF who underwent PCI were included. Patients were categorized into tertiles based on their RLP-C levels. The primary outcome was major adverse cardiovascular events (MACE). Kaplan-Meier survival analysis was used to assess the incidence of MACE and other outcomes. Multivariate Cox regression models were employed to investigate the correlation between RLP-C and the studied outcomes. The nonlinear relationship between RLP-C and MACE was examined through the restricted cubic spline (RCS). Subgroup analyses were performed and interactions were assessed.

The study results showed a clear association between higher RLP-C levels and an increased incidence of MACE in the participants. This association was validated by Kaplan-Meier analyses. The multivariate Cox regression demonstrated RLP-C was an independent risk factor for MACE, whether assessed as a continuous variable[hazard ratio (HR), 95% confidence interval (CI): 1.50, 1.15-1.98, p = 0.003] or categorized into tertiles[HR, 95% CI: 2.57, 2.03-3.26, p < 0.001, tertile 3 vs tertile 1]. A nonlinear relationship between RLP-C and MACE was observed, indicating that the risk of MACE increased with higher RLP-C levels(Nonlinear p < 0.001). This association remained consistent across various subgroups, as no significant interactions were found.

There was an independent and positive correlation between RLP-C and MACE in patients with IHF who underwent PCI.

Patients with peripheral artery disease (PAD) still experience excessive rates of fatal cardiovascular events. In this context, the relevance of co-existing extracranial carotid artery disease (ECAD) on outcome in patients with PAD is unclear. Thus, this study elucidates long-term outcome effects of the presence of both atherosclerotic entities for further risk stratification.

A total of 669 patients from the Lip-LEAD study with symptomatic PAD (Fontaine stage 2-4) were evaluated for ECAD (internal carotid artery stenosis >50%) with ultrasonography within 6 months after endovascular repair for PAD. Outcome was assessed with a long-term follow-up period with a maximum of 10 years.

Patients presenting with ECAD (n = 245, 36.7%) exhibited worse hemodynamic parameters of PAD than those without (ankle-brachial index (ABI). (0.53 (0.37-0.68) vs. 0.57 (0.47-0.68), p = 0.009; toe-brachial index (TBI) (0.50 (0.36-0.63) vs. 0.55 (0.42-0.70), p = 0.005). Significant correlations between grade of carotid stenosis and ABI as well as TBI were present (r=-0.190, p < 0.001; r=-0.219, p < 0.001). Cox-regression analyses revealed worse outcome in patients with ECAD for both all-cause and cardiovascular (CV)-mortality after multivariable adjustment for traditional CV risk-factors [1.48 (2.02-2.17); 2.10 (1.19-3.69)].

Patients with additional ECAD to symptomatic PAD exhibited an unfavourable long-term outcome in comparison to those without. The results suggest that the additional presence of ECAD highlights a highly vulnerable cohort of patients with symptomatic PAD at risk for further fatal CV events and thus should be considered for further diagnostic evaluation and stronger risk modification initiatives.

Protein energy wasting (PEW) is prevalent in adult maintenance hemodialysis (MHD) patients. Concurrently, cardiovascular diseases (CVD) remain a leading cause of mortality in MHD patients. However, the relationship between PEW and CVD in MHD patients remains unclear.

We conducted a retrospective cohort study at Shanghai East Hospital. According to the inclusion and exclusion criteria, a total of 210 adult MHD patients were finally enrolled. Patients were categorized into two groups based on PEW diagnostic criteria, including 122 patients (58.1%) with PEW and 88 patients (41.9%) without PEW. We further analyzed the incidence of major adverse cardiovascular events (MACE) and all-cause mortality in one year, along with their risk factors.

MACE incidence was significantly higher in the PEW group compared with the non-PEW group (p = 0.015). Multivariate Cox regression showed PEW, CVD, high N-terminal pro-B-type natriuretic peptide (NT-proBNP) and low Kt/V urea were the risk factors of MACE. Age ≥ 65 years and high NT-proBNP were the risk factors of all-cause death. Among patients aged ≥ 65 years, PEW was associated with a higher risk of all-cause death (p = 0.043). Total cholesterol < 3.4 mmol/L, albumin < 38 g/L and prealbumin < 280 mg/L were the thresholds for MACE incidence in MHD patients with PEW.

Adult MHD patients with PEW had an increased risk of MACE and all-cause mortality. Strategies aimed at optimizing total cholesterol, albumin, and prealbumin levels may improve cardiovascular outcomes in adult MHD patients with PEW.

Naringin, a flavonoid, has high antioxidant activity and hypolipidemic pharmacological effects. In this study, an animal model of dyslipidemia was established by feeding Apoe-/- mice a high-fat diet for 4 weeks. Subsequently, the mice were administered Naringin via gavage at doses of 50 mg/(kg·d), 100 mg/(kg·d), or 200 mg/(kg·d) for an additional 4 weeks. The research utilized liquid chromatography-mass spectrometry (LC-MS) metabolomics in conjunction with analyses of serum oxidative stress markers, Hematoxylin-eosin staining, Masson's trichome staining, and immunohistochemical staining. Naringin treatment reduced serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol concentrations (P<.05), reversed disorders of vascular structure and morphology, increased serum nicotinamide adenine dinucleotide phosphate hydride and glutathione concentrations (P<.05), reduced serum peroxynitrite concentrations (P<.05), promoted aortic endothelial nitric oxide synthase protein expression and inhibited aortic prolyl isomerase-1 protein expression. Twenty differentiated metabolites were obtained from the serum by LC-MS assay, followed by 16 differential metabolic pathways after enrichment. Among the metabolic pathways, glycolysis/gluconeogenesis, the pentose phosphate pathway, purine metabolism, ascorbate metabolism, and aldarate metabolism are the most relevant metabolic pathways by which naringin reduces oxidative stress. Our findings suggest that naringin can reduce oxidative stress levels associated with dyslipidemia through multiple metabolic pathways, protect vascular endothelial function, and thus providing a novel and promising natural medicine for treating dyslipidemia.

Skin cancers are the most common cancers in Caucasians, and their incidence is rising. Although metabolic and anthropometric markers play a role in cancer development, the relationship between metabolic and anthropometric changes in skin cancer remains unclear. This study aimed to examine possible associations between these changes and the risk of skin cancer.

Participants without prior skin cancer history from the Northern Netherlands representative of the general population were included. Histopathology data were obtained from the Dutch Nationwide Pathology Database. Adjusted Cox regression analyzed associations between metabolic changes and time to pathology-confirmed skin cancer incidence over a 7-year follow-up, assessing overall skin cancer risk and subtypes, including melanoma and nonmelanoma skin cancer.

Out of 97,106 participants, 4,195 (4.3%) developed skin cancer. Decrease and increase in body mass index (BMI) were both associated with lower skin cancer risk: adjusted HRs (aHR) of 0.88 (0.80-0.98) and 0.78 (0.72-0.86), respectively. Triglyceride and waist-to-hip ratio decreases were also associated with lower risk: aHR: 0.89 (0.80-0.98) and 0.89 (0.83-0.98), respectively. Increase in Hemoglobin A1c (HbA1c) was associated with a higher risk in individuals below the age of 45 years at baseline: aHR: 1.21 (1.01-1.45). Subtype analysis showed an increase in BMI was associated with lower melanoma risk: aHR: 0.72 (0.58-0.91).

Changes in BMI and decrease in triglycerides and waist-to-hip ratio are related to lower skin cancer risk, whereas an increase in HbA1c may elevate risk in individuals younger than 45 at baseline. These findings highlight the importance of non-sunlight-related risk factors for skin cancer prevention and the need for further research into underlying mechanisms.

This study contributes to the broader understanding of how metabolic health impacts skin cancer development, offering potential avenues for targeted prevention strategies.

While statins are effective at managing lipid levels, there is growing evidence for new-onset diabetes mellitus (NODM). The insulin signalling pathway (ISP) inhibited by statins is one of the potential mechanisms; however, most studies have been limited to in vitro settings. Therefore, this study aimed to identify the genetic associations within the ISP-related genes and NODM.

We performed a retrospective analysis of samples collected prospectively from February 2021 to May 2021. Among ISP-related genes, we selected 11 candidate genes (IGF1, IGF2, IGF1R, INSR, IRS1, IRS2, PIK3CA, PIK3CB, PIK3R1, AKT1 and AKT2). An additional analysis was conducted comparing patients with DM prior to statin therapy and controls to determine whether the single nucleotide polymorphisms (SNPs) are specific to statin.

A total of 602 patients were analysed, including 71 (11.8%) with statin-induced NODM. After adjustment, IGF1R rs2715439, INSR rs1799817, INSR rs2059807 and PIK3R1 rs3730089 were found to be independently associated with NODM. In an additional analysis, all SNPs that demonstrated an association with statin-induced NODM lost their significance in patients with DM prior to statin therapy.

This study revealed the ISP-related genetic effects, specifically involving genes such as INSR, IGF1R and PIK3R1, in the development of statin-induced NODM. Our findings suggest a potential mechanism of statin-induced NODM related to ISP-related genetic variants.

As a major regulator of LDL receptor (LDLR) activity and thus of LDL-cholesterol (LDL-C) levels, proprotein convertase subtilisin/kexin type 9 (PCSK9) represents an obvious therapeutic target for lipid lowering. The PCSK9 inhibitors, alirocumab and evolocumab, are human monoclonal antibodies (mAbs) that act outside the cell by complexing circulating PCSK9 and thus preventing its binding to the LDLR. In contrast, inclisiran, a small interfering RNA (siRNA), inhibits hepatic synthesis of PCSK9, thereby resulting in reduced amounts of the protein inside and outside the cell. Both approaches result in decreased plasma LDL-C concentrations and improved cardiovascular outcomes. Marginally superior LDL-C reduction (≈ 60 %) is achieved with mAbs as compared to the siRNA (≈ 50 %); head-to-head comparisons are required to confirm between-class differences in efficacy. Both drug classes have shown variability in LDL-C lowering response between individuals in waterfall analyses. Whereas mAb-mediated inhibition leads to a compensatory increase in plasma PCSK9 levels, siRNA treatment reduces them. These agents differ in their pharmacokinetic and pharmacodynamic features, which may translate into distinct clinical opportunities under acute (e.g. acute coronary syndromes) as compared to chronic conditions. Both drug classes provide additional reduction in LDL-C levels (up to 50 %) beyond those achieved with statin therapy, facilitating attainment of guideline-recommended LDL-C goals in high and very high-risk patients. Additional PCSK9 inhibitors, including an oral macrocyclic peptide, a small PCSK9 binding protein and a novel small molecule, plus hepatic gene editing of PCSK9, are under development. This review critically appraises pharmacological strategies to target PCSK9 either inside or outside the cell.

Views on the etiopathogenesis of atherosclerosis are subject to evolution. In addition to the classic well-known risk factors, new ones related to mental state, social life and environment are being discovered. Both acute and chronic stress stimulate inflammatory processes. Due to the change in lifestyle and eating habits, the accumulation of risk factors in childhood is an increasing problem. Knowledge of risk factors allows for effective primary prevention of cardiovascular diseases. The effectiveness of prevention increases when the activities cover the largest possible part of the society, and access to a doctor is easy. Therefore, government programs are being implemented offering patients easier access to diagnostics of cardiovascular diseases at the level of primary health care, which enables faster identification of people at the greatest cardiovascular risk. Easier access to primary care and a good doctor-patient relationship improve patient compliance. In this situation, the importance of the family doctor as a key link in the diagnosis, prevention and treatment of cardiovascular diseases is increasing.

The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" incorporates new evidence since the "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction" and the corresponding "2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes" and the "2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction." The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" and the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization" retire and replace, respectively, the "2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease."

A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality globally, significantly influenced by modifiable risk factors, particularly hypercholesterolemia. Despite the availability of effective lipid-reducing drugs, achieving the low-density lipoprotein cholesterol (LDL-C) target levels remains a significant challenge in clinical practice, contributing to persistently high rates of cardiovascular events. The intEgrated multidiscipliNary pathway for large-scale maNagement of dyslipidemiA in high-risk patients (ENNA) Project was designed to address the alarming rates of suboptimal lipid management in patients at high and very-high risk in the province of Enna, Sicily. This program aims to optimize LDL-C control through an integrated care model that fosters collaboration among pharmacists, general practitioners, and cardiologists, ultimately promoting a patient-centered approach to therapy. The patients who are eligible are identified using data-driven methods through prescription claims, laboratory results, and hospital discharge data, facilitated by local pharmacies. General practitioners play a crucial role as the primary care providers for initiating or optimizing lipid-reducing therapy, whereas cardiologists are involved in managing more complex cases requiring specialized intervention. The primary objective of the ENNA Project is to increase the percentage of patients at great risk in whom LDL-C targets are achieved, improving overall lipid management and therapeutic adherence.

To date, no meta-analysis has reported on the role of transdermal estrogens combined with Medroxyprogesterone Acetate (MPA) in relation to cardiovascular disease (CVD) risk factors in postmenopausal women. To fill this knowledge gap, a meta-analysis of randomized controlled trials (RCTs) was conducted to assess the effects of transdermal estrogens and MPA on CVD risk factors in postmenopausal women.

A systematic literature search was conducted in major databases including PubMed/Medline, Web of Science, SCOPUS, and Embase, from inception to 12 February 2025. The combination of Medical Subject Headings (MeSH) and non-MeSH keywords was used.

A total of 14 trials were included in the meta-analysis. The combined eligible trials found that transdermal estrogens combined with MPA significantly decreased total cholesterol (TC) (WMD: -13.37 mg/dL, 95% CI: -21.54 to -5.21, p = 0.001), low density lipoprotein cholesterol (LDL-C) (WMD: -12.17 mg/dL, 95% CI: -23.26 to -1.08, p = 0.031), and apolipoprotein B (ApoB) (WMD: -7.26 mg/dL, 95% CI: -11.48 to -3.03, p = 0.001) compared to the control. No statistically significant associations were observed between transdermal estrogens combined with MPA on triglyceride (TG), high density lipoprotein cholesterol (HDL-C), lipoprotein(a) (Lp(a)), and apolipoprotein A1 (ApoAI).

Based on the results of the current meta-analysis, transdermal estrogens combined with oral MPA administration had a beneficial effect on certain CVD risk factors in postmenopausal women, as evidenced by the significant reductions in TC, LDL-C, and ApoB.

Evolocumab has shown significant reductions in low-density lipoprotein cholesterol (LDL-C) levels and incident cardiovascular events among acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Nonetheless, the potential modification of evolocumab's effectiveness by baseline inflammatory risk remains unclear. We aimed to assess evolocumab's effectiveness based on baseline neutrophil-to-lymphocyte ratio (NLR) and evaluate residual inflammatory and cholesterol-related risks across varying on-treatment NLR and LDL-C levels.

This multicentric, retrospective analysis enrolled consecutive patients with ACS undergoing PCI and exhibiting elevated LDL-C at the First Affiliated Hospital of Zhengzhou University and Zhongda Hospital Southeast University between March 2019 and August 2021. Patients were categorized into evolocumab and standard-of-care treatment groups based on evolocumab administration. Hazard ratios for the primary composite outcome-including myocardial infarction, ischemic stroke, cardiac death, unplanned coronary revascularization, and hospitalization due to unstable angina-comparing baseline NLR quartiles were computed using multivariable Cox regression. We assessed evolocumab's impact on the primary outcome across median-based NLR dichotomization and evaluated the outcome across 1-month NLR and LDL-C levels.

The median baseline NLR was 2.99 (IQR: 2.14-4.69), remaining stable following evolocumab therapy. Each NLR quartile increase heightened the risk of primary outcome by 29% (95% CI, 17-42%; P < 0.01). The relative risk reductions with evolocumab were consistent across NLR categories (P-interaction > 0.05), but absolute risk reductions were higher in high-NLR patients (2.9% vs. 6.2%). Residual inflammatory and cholesterol risks, indicated by on-treatment NLR and LDL-C, independently correlated with the primary outcome (P < 0.001).

Higher baseline NLR is associated with increased cardiovascular risk in ACS/PCI patients. Relative risk reductions with evolocumab were consistent across NLR categories, while absolute risk reductions were more significant in high-NLR patients. Minimized risk is observed in patients with the lowest on-treatment NLR and LDL-C levels.

With aging of the population, atherosclerotic diseases have increased in Japan, with acute coronary syndrome (ACS) a significant cause of morbidity and mortality. In Kagoshima Prefecture, ACS mortality rates exceed the national average, reflecting challenges in lipid management and access to care.

The Optimal Therapy for All Kagoshima Acute Coronary Syndrome (OK-ACS) Registry, initiated in April 2022, enrolled 2,328 ACS patients across Kagoshima. This study evaluated the impact of a standardized lipid management pathway, the "Kagoshima Style," on low-density lipoprotein cholesterol (LDL-C) control and guideline adherence, as well as the regional profile of ACS in Kagoshima. The pathway was implemented at all percutaneous coronary intervention facilities to optimize lipid management and secondary prevention. LDL-C levels decreased significantly (P<0.0001) from admission to discharge and at 3 months (113.3±39.9, 74.6±28.0, and 69.2±25.9 mg/dL, respectively), with no difference according to place of residence. The proportion of patients with LDL-C <70 mg/dL increased from 12% at admission to 59% at 3 months. Maximum tolerated doses of high-intensity statin use increased from 7% at baseline to 9.3% after pathway implementation. Geographic disparities were evident, with patients from isolated islands experiencing delayed treatment access.

The Kagoshima Style pathway improved lipid management, reducing LDL-C and enhancing guideline adherence. This interim analysis provides insights into lipid management and regional disparities in patients with ACS across Kagoshima prefecture.

In the MI-GENES clinical trial (URL: https://www.clinicaltrials.gov; Unique identifier: NCT01936675), participants at intermediate risk of coronary heart disease (CHD) were randomized to receive a Framingham risk score (Framingham risk score group, n=103) or an integrated risk score (integrated risk score group [IRSg], n=104) that additionally included a polygenic risk score. After 6 months, IRSg participants had higher statin initiation and lower low-density lipoprotein cholesterol. We conducted a post hoc 10-year follow-up analysis to investigate whether disclosure of a polygenic risk score for CHD was associated with a reduction in major adverse cardiovascular events (MACE).

Participants were followed from randomization in October 2013 to September 2023 to ascertain MACE, testing for CHD, and changes in risk factors. The primary outcome was time to first MACE, defined as cardiovascular death, nonfatal myocardial infarction, coronary revascularization, and nonfatal stroke. Statistical analyses included Cox proportional hazards regression and linear mixed-effects models.

We followed all participants who completed the trial, 100 in Framingham risk score group and 103 in IRSg (mean age at the end of follow-up, 68.2±5.2; 48% male). During a median follow-up of 9.5 years, 9 MACEs occurred in Framingham risk score group and 2 in IRSg (hazard ratio, 0.20 [95% CI, 0.04-0.94]; P=0.042). In Framingham risk score group, 47 (47%) underwent at least 1 diagnostic test for CHD, compared with 30 (29%) in IRSg (hazard ratio, 0.51 [95% CI, 0.32-0.81]; P=0.004). A higher proportion of IRSg participants were on statin therapy during the first 4 years postrandomization and had a greater reduction in low-density lipoprotein cholesterol for up to 3 years postrandomization. No significant differences were observed between 2 groups in other traditional cardiovascular risk factors during follow-up.

Disclosure of an integrated risk score that included a polygenic risk score to individuals at intermediate risk for CHD was associated with lower MACE incidence after 10 years, likely due to higher statin initiation, leading to lower low-density lipoprotein cholesterol levels.

Atherosclerosis remains the leading cause of death worldwide and is characterized by the accumulation of plaque beneath the endothelium. MicroRNA-145-5p (miR-145), which is downregulated in atherosclerosis, has been shown to mitigate plaque development by promoting the contractile vascular smooth muscle cell (VSMC) phenotype. Previously, our lab found that miR-145 micelles conjugated with MCP-1 peptides were able to inhibit atherosclerosis by targeting diseased VSMC via C-C chemokine receptor 2 (CCR2). Diseased endothelial cells similarly express CCR2; however, the impact of miR-145 micelles on endothelial cell function has not been explored. Thus, in this study, the in vitro therapeutic effects of miR-145 micelles in modulating the endothelium during atherosclerosis are evaluated. To that end, the MCP-1 peptide density on the micelle surface was first optimized for activated endothelial cell binding, followed by loading miR-145 into micelles with the optimal MCP-1 ratio. Following characterization, miR-145 micelle treatment of activated endothelial cells resulted in efficient miR-145 transfection, upregulation of atheroprotective genes, and suppression of atherogenic genes. Furthermore, the treatment enhanced the integrity of endothelial tight junctions and reduced monocyte migration. This work establishes miR-145 micelles as an effective nanotherapeutic for restoring endothelial cell health in cardiovascular disease for the first time.

Clinical evidence exists for LDL-cholesterol lowering by plant sterols, bergamot extract and artichoke leaf extract individually but their effect when combined is unknown. This study investigated the effects of a novel nutraceutical combining plant sterols, bergamot extract, artichoke leaf extract and hydroxytyrosol (referred to as 'Cholesterol Balance'), on serum LDL-cholesterol (primary outcome), other cardiometabolic and oxidative stress markers in adults with hypercholesterolaemia.

Healthy adults (n = 42, 18-<66 years, body mass index [BMI] >18.5-<35 kg/m2), with mild hypercholesterolaemia (LDL-cholesterol ≥2.5-<5 mmol/L) and low CVD risk participated in a 4-month double-blind randomised placebo-controlled trial. Participants consumed either 3 capsules/day Cholesterol Balance (providing 375 mg Bergavit40™, 150 mg Altilix™, 1.8 g phytosterols, and 50 mg of Hydrovas10™ daily) or placebo. Outcomes were assessed at baseline, 2- and 4-months.

There was no evidence that Cholesterol Balance affected serum LDL-cholesterol compared to placebo (adjusted mean difference [95 % CI] at 4 months between treatments, -0.12 [-0.34, 0.11] mmol/L, p = 0.307). None of the secondary outcomes, including total cholesterol, HDL-cholesterol, triglycerides, non-HDL-cholesterol, total cholesterol:HDL-cholesterol ratio, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), ApoB:ApoA1 ratio, plasma oxidised LDL, serum malondialdehyde, HbA1c, blood pressure or safety markers showed a significant difference between groups.

While safe to consume, a nutraceutical containing plant sterols, bergamot extract, artichoke leaf extract and hydroxytyrosol did not show evidence of improving serum LDL-cholesterol, or any other lipid and oxidative stress markers in adults with mild hypercholesterolaemia. Further research is needed to determine if ingredients in the complex formulation interact or interfere with LDL-cholesterol lowering mechanisms.

Progress in the management of myocardial infarction (MI) has led to reductions in cardiac mortality. The aim of this study was to describe the temporal trends in the relative proportions of cardiac death (CD) and non-cardiac death (NCD) in an Australian cohort with MI following in-hospital stay, then at 6 and 12 months as well as long-term follow-up.

Retrospective study at a single large tertiary referral hospital in Queensland. Outcome data were obtained from the state births/deaths/marriages registry. A total of 3464 consecutive patients with MI were included.

The mean age of patients was 63.3 ± 13.8 years, 70.6% were males, and 28.2% were ST-elevation MIs. At a median follow-up of 4.5 years, there were 551 deaths (15.9%), with 200 (5.8%) classified as CD, 332 (9.6%) classified as NCD and 20 (0.5%) classified as indeterminate. In-hospital death occurred in 75 patients (2.2%). The relative proportions of cumulative CD to NCD in those with classifiable deaths (CD:NCD ratio) following in-hospital stay, then at 6, 12 and 18 months as well as long-term follow-up were: 79%:21%, 62%:38%, 53%:47% and 38%:62% respectively. Of those patients who survived their index hospitalisation, subsequent cardiac deaths accounted for only 29.7% of total deaths.

NCD outstrips CD at long-term follow-up in contemporary patients with MI, with the majority of deaths beyond hospital discharge attributable to NCD. The long-term risk of residual cardiac mortality was less than 30% in hospital survivors. Similar to considering the impact of cardiac events in cancer survivorship, the burden of non-cardiac events in MI survivorship needs to be considered.

Hypercholesterolemia is a significant and modifiable risk factor for cardiovascular disease (CVD), with Low-Density Lipoprotein Cholesterol (LDL-C) being the primary target for lipid-lowering therapies in both primary and secondary prevention. This review aims to explore the efficacy of statin therapy in women, its safety and application during pregnancy, and treatment disparities that contribute to undertreatment of dyslipidemia in women.

Statins has demonstrated efficacy in reducing LDL-C and CVD risk in women. However, women are less likely to achieve LDL-C targets compared to men, largely due to undertreatment and delays in initiating therapy, often influenced by sex-specific factors. The unique considerations of lipid management during pregnancy, including suspension of statin therapy, present additional challenges in achieving optimal lipid control in high-risk women. Evidence also points to systemic disparities in healthcare delivery and treatment allocation, further exacerbating undertreatment of dyslipidemia among women. While LDL-C lowering remains a cornerstone of CVD prevention, women face distinct challenges in achieving lipid goals due to biological, clinical, and healthcare disparities. Addressing these barriers, including improving timely initiation of statins and addressing gaps in care during pregnancy, is essential to enhance the dyslipidemia management and reduce CVD risk in women.

The reduction of LDL cholesterol lowers the risk of coronary and cerebrovascular events in individuals without manifest cardiovascular diseases. In Germany, statins at the expense of statutory health insurance had only been permitted for patients with atherosclerosis-related diseases or those at high cardiovascular risk (over 20 percent event probability within the next 10 years, calculated using one of the "available risk calculators"). However, international guidelines recommend lower risk thresholds for the use of statins.

The health and economic impacts of different risk thresholds for statin use in primary prevention within the German population are estimated for thresholds of 7.5, 10, and 15 percent over 10 years, based on the US Pooled Cohort Equation (PCE) which is valid for Germany, using Markov models.

Cost-effectiveness increases with a rising risk threshold, while individual benefit decreases with age at the start of treatment. The use of statins at a risk of 7.5 percent or more is cost-effective at any age (cost per QALY between 410 and 2100 Euros). In none of the examined scenarios does the proportion of the population qualifying for statin therapy exceed 25 percent.

Lowering the threshold for statin therapy to a risk of 7.5 percent of either non-fatal myocardial infarction, coronary heart disease death, non-fatal or fatal stroke would align statin prescription in Germany with international standards. There is no urgent rationale for applying age-stratified risk thresholds.

The associations between screen time exposure, blood lipids, and Atherosclerotic Cardiovascular Disease (ASCVD) incidence have been less studied. We aimed to examine the associations of exposure to screen time with blood total cholesterol (TC), HDL-C, LDL-C, triglycerides (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and ASCVD risk score, and risk of subsequent ASCVD incidence.

A nationwide sample of 7124 China Health and Nutrition Survey 2009 participants were followed up to 2015 for ASCVD incidence. The stationary screen time exposure was assessed through self-reported daily hours of using television, and computers. A total of 292 ASCVD events occurred during 35,310 follow-up person-years. Per 1-h increases in daily screen time exposure were associated with a higher 0.34% (0.12% to 0.56%), 0.47% (0.09% to 0.86%), and 0.51% (0.19% to 0.83%) increases in blood TC, LDL-C, and ApoB levels. A higher risk of incident ASCVD was associated with per log-transformed unit increase in blood LDL-C (adjusted HR = 1.51, 95% CI 1.04 to 2.18), and ApoB (adjusted HR = 1.80, 95% CI 1.12 to 2.92). The elevated blood TC, blood LDL-C, blood ApoA1 and ApoB levels significantly mediated the association between screen time exposure and ASCVD incidence. Urban dwellers, middle-aged adults, and females were particularly associated with a higher ASCVD risk with screen time exposure.

The results of this nationwide cohort supported the associations of screen time exposure with elevated blood LDL-C, and ApoB levels, which consistently contributed to an increased risk of subsequent ASCVD incidence.

Semaglutide has been shown to reduce cardiovascular events in non-diabetic patients with preexisting cardiovascular disease and overweight/obesity in the SELECT trial. Data on the applicability of these results to clinical practice are limited. We evaluated the eligibility for and practical implications of semaglutide in overweight/obese non-diabetic patients with recent acute coronary syndrome (ACS) from a contemporary real-world registry.

Patients from the multicenter START-ANTIPLATELET registry (NCT02219984) were stratified to investigate the proportion of patients eligible for semaglutide >60 days after discharge for ACS (post-acute phase), according to the SELECT trial eligibility criteria: age ≥ 45 years; body mass index ≥27 kg/m2; history of myocardial infarction (MI), stroke, or peripheral artery disease; no diabetes. Major adverse cardiovascular events (MACE), defined as a composite of all-cause death, MI, target vessel revascularization, or stroke, and net adverse clinical events (NACE), a composite of all-cause death, MI, stroke, or major bleeding, were assessed at 1-year follow-up.

The study population comprised 2940 consecutive ACS patients. At 60 days after discharge, 807 patients (27.4 %) met the SELECT eligibility criteria (SELECT-like group) and 2133 patients were ineligible (not-eligible group). At 1 year, incidence of MACE (4.6 % vs. 8.2 %; p = 0.004) and NACE (3.6 % vs. 7.6 %; p < 0.001) was lower in the SELECT-like group compared to the not-eligible group.

In a contemporary real-world registry, a significant proportion of post-ACS patients were eligible for semaglutide according to the SELECT trial criteria. Future studies are needed to evaluate the potential implications of semaglutide for secondary prevention.

Post-marketing regulatory data suggest a potential association between atorvastatin use and memory protection; however, findings from observational studies have been inconsistent and remain a subject of controversy.

This study aims to investigate the correlation between atorvastatin exposure and subjective memory deficits, with the objective of providing more precise safety and efficacy information for its clinical use.

We utilized two primary data sources: the National Health and Nutrition Examination Survey (NHANES) covering the years 2001 to 2018, and the Food and Drug Administration Adverse Event Reporting System (FAERS) spanning 2011 to 2018. We systematically analyzed the correlation between atorvastatin exposure and memory function using a range of statistical methods, including descriptive statistics, multivariate logistic regression, and receiver operating characteristic (ROC) curves.

In the analysis of the NHANES database, multivariate logistic regression modeling, after controlling for various factors such as demographic characteristics and lifestyle, revealed a significant association between atorvastatin use and a reduced risk of memory loss (OR = 0.47; 95% CI, 0.15-0.79; p = 0.004). This suggests that atorvastatin may offer a protective effect on memory. Conversely, our analysis of the FAERS database identified 15,277 reports of adverse reactions associated with atorvastatin, of which 401 were related to psychiatric adverse events, including memory loss. This finding indicates that while atorvastatin may not generally increase the risk of memory loss, some patients may still experience these side effects.

This study integrated data from NHANES and FAERS to provide a comprehensive analysis of the relationship between atorvastatin and memory function. On one hand, the NHANES findings support the potential benefits of atorvastatin in reducing the risk of memory loss. On the other hand, the FAERS data highlight specific cognitive side effects associated with the drug. Consequently, clinicians and patients should carefully consider both the potential benefits and risks of atorvastatin, taking into account individual patient differences and implementing appropriate monitoring strategies.

Hypertriglyceridemia is related to atherosclerotic cardiovascular risk and pancreatitis risk. The efficacy and safety of apolipoprotein C-III (APOC-III) inhibitors remains unclear.

To investigate the effects of APOC-III inhibitors on hypertriglyceridemia and its complications.

We systematically searched PubMed, Embase, and Cochrane Central databases from inception to May 2024 for randomized controlled trials (RCTs) comparing APOC-III inhibitors to placebo in patients with hypertriglyceridemia. We pooled percentage standardized mean difference (SMD) changes and risk ratio (RR) for continuous and binary outcomes, respectively, with 95 % confidence interval (CI). Subgroup analyses were performed with APOC-III inhibitors drugs doses (Olezarsen, Volanesorsen and Plozasiran), and primary and secondary hypertriglyceridemia.

10 RCTs with 1204 participants were included, of which 46 % were men. APOC-III inhibitors significantly reduced triglycerides (TG) (SMD: -60.56 %; 95 % CI -68.94 to -52.18; p < 0.00001), APOC-III (SMD: -75.44 %; 95 % CI -80.81 to -70.07; p < 0.00001) and non-HDL-c (SMD: -27.49 %; 95 % CI -34.16 to -20.82; p < 0.00001) levels. Consistent results were found for all subgroup analyses. APOC-III inhibitors were capable to normalize TG levels in patients with severe hypertriglyceridemia (RR: 7.92; 95 % CI 4.12 to 15.23; p < 0.00001). There was a significant increase in HDL-c (SMD: 43.92 %; 95 % CI 37.27 to 50.57; p < 0.00001) and LDL-c (SMD: 33.05 %; 95 % CI 9.08 to 57.01; p = 0.007) levels. There was a significant relative risk reduction in acute pancreatitis in the APOC-III inhibitors group (RR 0.17; 95 % CI 0.05 to 0.53; p = 0.007). Adverse events were similar in both groups.

APOC-III inhibitors improve TG levels and other lipid panel parameters, as well as reduce episodes of acute pancreatitis in patients with primary and secondary hypertriglyceridemia.

Background/Objectives: Bempedoic acid (BA) is a novel lipid-lowering agent that reduces low-density lipoprotein cholesterol (LDL-c) and cardiovascular events. Limited real-world data on its effectiveness and safety are available. This study aimed to evaluate the utilization and clinical performance of BA in routine clinical practice. Moreover, an explorative pharmacoeconomic analysis was performed. Methods: We prospectively enrolled consecutive patients with dyslipidemia who started 180 mg BA, alone or with 10 mg ezetimibe, across five outpatient clinics in Campania Region, Italy from September to December 2023. Clinical and laboratory assessments, including lipid profile, hepatic function, and creatine phosphokinase levels, were performed at baseline and at least after one month follow-up. Side effects were recorded. Results: 111 patients (age 65 ± 9 years, 61% male) were included. At BA initiation, 70.3% were on maximally tolerated statin dosage and ezetimibe, 16.2% on ezetimibe alone, and 13.5% on PCSK9 inhibitors due to statin intolerance. BA significantly reduced LDL-c serum levels (89.9 ± 33.0 vs. 56 ± 27.6 mg/dL; p < 0.0001), with 46% achieving therapeutic targets. LDL-c decreased by 28% in patients on intensive statins/ezetimibe and by 45% in statin-intolerant patients, with reduced healthcare costs. Side effects were infrequent (10%) and reversible. Adherence was 99%, and persistence 90%. Conclusions: In our clinical pratice, BA was primarily used in high-risk patients with dyslipidemia who failed to reach LDL-c therapeutic target with statins/ezetimibe, and to a lesser extent, in statin-intolerant individuals. BA treatment enabled 54% to reach LDL-c therapeutic target. BA was well tolerated, and showed high adherence and persistence, contributing to cost savings.

Death in dyslipidemia is a significant health problem, dietary intervention plays an important role in this context.

Our study investigated the association between dietary patterns and all-cause mortality in individuals with dyslipidemia. This will lay a foundation for the relevant departments to develop more precise and targeted dietary strategies and help high-risk people with early prevention by adjusting their dietary patterns, which may reduce their mortality and reduce the medical burden.

This study included 5369 participants. Factor analysis identified distinct dietary patterns, each categorized into tertiles based on factor scores: low, medium, and high. Cox proportional hazards regression models were estimated the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between dietary patterns and all-cause mortality in individuals with dyslipidemia.

Over a median follow-up of 12.61 years, 365 deaths occurred among the 5369 participants. Four primary dietary patterns were identified. We found that compared to the lowest tertile, the highest tertile of the equilibrium pattern (HR=0.740, 95%CI: 0.565~0.969) and the aquatic products and poultry high loadings pattern (HR=0.757, 95%CI: 0.575~0.997) were negatively correlated with all-cause mortality. Conversely, the grain-tuber and vegetables high loadings pattern (HR=1.338, 95%CI: 1.031~1.737) was positively correlated with all-cause mortality. The oil and salt high loadings pattern (HR=0.973, 95%CI: 0.747~1.268) was not statistically significant.

The equilibrium pattern and the aquatic products and poultry high loadings pattern were linked to a lower risk of all-cause mortality among individuals with dyslipidemia, whereas the grain-tuber and vegetables high loadings pattern was linked to a higher risk. The results implying that adopting appropriate dietary pattern could provide survival benefit for individuals with dyslipidemia. However, this study has only considered dietary intake at baseline, and future research should consider the dynamic changes in dietary habits over time.

Achieving low-density lipoprotein cholesterol (LDL-C) levels is key to preventing atherosclerotic cardiovascular events. However, many high-risk cardiovascular patients still experience poor LDL-C goal attainment and receive suboptimal lipid-lowering therapy (LLT) prescriptions. Herein, we evaluated LLT prescription patterns, LDL-C goal attainment and cardiovascular mortality among this population group in Singapore.

This prospective observational cohort study included 555 patients with ischaemic heart disease (IHD) admitted to the hospital in 2020. The LLT prescriptions, corresponding LDL-C levels and cardiovascular outcomes were assessed over a 24-month period.

Most participants were male (82.3%), with 48.5% identified as Chinese. High-intensity statin prescriptions increased from 45.4% at hospital admission to 87.1% at discharge and remained stable at approximately 80% at 6, 12, and 24 months post-discharge. Combination LLT prescriptions increased from 12.3% at discharge to 33.8% by 24 months. Ezetimibe was the most commonly prescribed second-line LLT (40.8%), followed by inclisiran (1.09%) and anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibody therapies (0.87%). Over 24 months, LDL-C goal attainment rates were 22.1% for LDL-C < 1.4 mmol/L and 47.2% for LDL-C < 1.8 mmol/L. Multivariable Cox proportional hazards regression indicated that achieving LDL-C < 1.8 mmol/L goal was associated with a reduction in all-cause mortality at 24 months (hazard ratio 0.53, 95% confidence interval 0.30-0.94, P = 0.030).

Treatment gaps in lipid management persist in 80% of the study population, indicating that statin monotherapy alone is insufficient to achieve LDL-C goals. Greater efforts to improve LDL-C goal attainment rates in high-risk cardiovascular patients are imperative.

Ezetimibe is a safe and effective medication for achieving secondary prevention low-density lipoprotein-cholesterol (LDL-C) targets after acute coronary syndrome (ACS). We sought to examine ezetimibe prescribing after ACS and the effects of expanding the Australian Pharmaceutical Benefits Scheme eligibility criteria.

A retrospective analysis was performed for the rates and factors of ezetimibe eligibility and prescribing in ezetimibe-naive patients with ACS admitted to a single quaternary centre between May 2020 and September 2022. Eligibility rates were also assessed with tighter LDL-C targets and with modelling to identify patients unlikely to achieve targets with first-line care.

Of 757 patients with ACS with LDL-C >1.8 mmol/L, 94 were eligible for ezetimibe. This subgroup was highly comorbid but only 16 patients were prescribed ezetimibe. The univariate logistic regression identified statin contraindication (odds ratio 19.4; 95% confidence interval 4.58-103.9; p<0.001) and higher LDL-C (odds ratio 2.43 per 1 mmol/L; 95% confidence interval 1.44-4.67; p=0.03) as key predictors of prescribing. Of 956 patients with ACS with an LDL-C >1.4 mmol/L, tightening LDL-C targets from 1.8 to 1.4 mmol/L increased eligibility from 94 (9.8%) to 152 (16.0%) patients, whereas predictive modelling substantially expanded eligibility to 309 (32.3%) and 620 (64.9%) with the 1.8 mmol/L and 1.4 mmol/L targets, respectively.

In the acute setting after ACS, Australian Pharmaceutical Benefits Scheme restrictions limit ezetimibe to highly comorbid patients with a high risk of recurrent disease. Despite this, the prescribing rates were poor. Furthermore, a larger group of patients are discharged on treatments that are unlikely to achieve guideline-directed LDL-C targets. Rationalising eligibility criteria for ezetimibe would likely improve access to early and effective secondary prevention.

This study aimed to investigate the association between cardiovascular risk factors and major adverse cardiovascular events (MACE) in people with type 2 diabetes, while assessing potential changes over time.

Utilizing data from Danish registries, this study identified people with type 2 diabetes between 2002 and 2021 (n = 372 328) and subdivided them into two 10-year time periods: TP1: 2002-2011 and TP2: 2012-2021, and further categorized into cases and controls. Cases were defined as having suffered a first-time three-point MACE (nTP1 = 12 713, nTP2 = 8981) and matched 1:1 with controls on age, sex, and type 2 diabetes duration. Exposures were preselected diabetes complications and comorbidities.

Fewer were affected by MACE during TP2 compared to TP1 (p < 0.001). Diabetes complications associated with MACE were nephropathy (ORTP1 = 1.54, 95% CI 1.30-1.83, ORTP2 = 1.47, 95% CI 1.20-1.79), neuropathy (ORTP1 = 2.02, 95% CI 1.84-2.21 ORTP2 = 1.58, 95% CI 1.44-1.73) and retinopathy (ORTP1 = 1.10, 95% CI 0.98-1.23, ORTP2 = 1.38, 95% CI 1.17-1.63). Comorbidities associated with MACE included hypertension (ORTP1 = 1.30, 95% CI 1.22-1.38 ORTP2 = 1.31, 95% CI 1.22-1.41), atrial flutter or fibrillation (ORTP1 = 1.46, 95% CI 1.35-1.58, ORTP2 = 1.37, 95% CI 1.26-1.50), heart failure (ORTP1 = 1.53, 95% CI 1.401.67-, ORTP2 = 1.37, 95% CI 1.23-1.54) and hypercholesterolemia (ORTP1 = 1.13, 95% CI 1.07-1.20, ORTP2 = 1.02, 95% CI 0.96-1.10). Hypercholesterolemia (p = 0.038) and neuropathy (p = 0.038) exhibited a significant decrease in association with MACE between the time periods.

The prevalence of first-time MACE decreased over time, despite a relatively stable prevalence of type 2 diabetes. Several diabetes-related complications and comorbidities were significantly associated with MACE. The associations of neuropathy and hypercholesterolemia with MACE lessened over time, suggesting potential improvements in risk management or treatment strategies.

Elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with atherosclerotic cardiovascular diseases. Inclisiran, a small interfering RNA, has been observed to effectively and sustainably reduce LDL-C in large randomized controlled trials (RCTs); however, real-world data on its short-term efficacy and use are limited. This study aims to assess the efficacy and safety of inclisiran in a real-life population within one month from the first administration.

This observational, single-center, retrospective cohort study included patients affected by dyslipidemia who could not achieve their LDL-C target despite a maximum tolerated oral lipid-lowering therapy (LLT). 284 mg Inclisiran was subcutaneously administered. Blood samples were collected before the inclisiran administration and at week and one month afterward with the aim toevaluate achievement of LDL-C targets at these time intervals (primary endpoint) and reduction in LDL-C levels (secondary endpoint).

From September 2022 to December 2023, inclisiran was administered to 33 patients at Mater Salutis Hospital. After exclusion of two patients due to statin therapy modification or discontinuation during follow-up, a final number of 31 patients were included. At a median follow-up of 32 (IQ1-3 30-37) days, 21 (67.7 %) patients reached their LDL-C target (primary endpoint). At 7 days, LDL-C mean value decreased from 123.6 ± 42.1 mg/dl to 97.9 ± 53.6 mg/dl, (p < 0.001), with a 29.9 ± 20.6 % reduction. At 32 days, LDL-C mean value declined to 58.5 ± 42.8 mg/dl (p < 0.001), with a 56.9 ± 20.9 % reduction.

In a real-life single center population, inclisiran safely led to LDL-C target achievement within one month. Significantly reduction of LDL-C levels were already present in the early days after the first administration.

In patients undergoing percutaneous coronary intervention (PCI), personalised medicine is key to the secondary prevention of ischaemic and bleeding events. To provide an extensive overview of the quality of secondary prevention and of personalised medicine, a consortium in the southeastern region of the Netherlands has created a PCI registry: the South-East Netherlands Heart Registry (Zuid-Oost Nederland Hart Registratie, ZON-HR).

To visualise and improve personalised secondary prevention post-PCI, focussing on key elements such as antiplatelet treatment, cholesterol management and comorbidities such as diabetes mellitus.

A prospective multicentre registry of all consecutive patients undergoing PCI at 4 participating PCI centres and 3 referral centres.

Interventional procedures and concomitant pharmaceutical treatment are performed in accordance with the guidelines. The ZON-HR promotes risk stratification after PCI using a simplified protocol for a personalised antiplatelet strategy.

Demographics, laboratory values, baseline procedural characteristics and pharmaceutical treatment data are collected. Outcomes include thromboembolic and bleeding complications and medication changes. Data are pseudonymised, and a clinical event committee will review 20% of the adverse events (randomly selected).

This registry represents the entire PCI population and visualises gaps in secondary prevention. Weaknesses are the collection of outcomes and medication changes using mostly patient-reported outcomes.

The ZON-HR is a comprehensive PCI registry that provides baseline and follow-up data of a large PCI cohort in the southeastern region of the Netherlands. The ZON-HR aims to improve secondary prevention after PCI and augment personalised treatment that focusses on key elements of secondary prevention.

Liver fibrosis progression is influenced by older age and cardiometabolic risk factors such as obesity and is associated with an increased risk of cardiovascular events. While statins may protect against cardiovascular complications, their effects in elderly individuals with obesity and liver fibrosis are unclear.

The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) database was used to evaluate the effect of pravastatin on major adverse cardiovascular events in an elderly population (>70 years). Subjects were categorized by BMI: lean (<25 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2). Liver fibrosis was assessed using the FIB-4 index: low risk (<2.0), intermediate risk (2.0-2.66) and high risk (≥2.67). Time-to-event data were analysed using the Cox proportional hazards model, adjusted for confounders and compared the placebo and pravastatin groups.

A total of 5.804 subjects were included. In the placebo group, the highest risk group (high FIB-4 and obesity) had a significantly higher hazard ratio for (non-)fatal stroke (HR 2.74; 95% CI 1.19-6.29) compared to the low FIB-4, lean BMI group. This risk disappeared in the same pravastatin group. Pravastatin did not affect other cardiovascular endpoints. All-cause mortality was significantly higher in subjects with lean weight and high FIB-4 on placebo (HR 1.88; 95% CI 1.14-3.11), but not on pravastatin (HR .58; 95% CI .28-1.20).

Elderly individuals with obesity and liver fibrosis are at higher risk for (non-)fatal stroke, which is reduced with pravastatin. Pravastatin also potentially lowers all-cause mortality in subjects with lean weight and liver fibrosis.

To determine whether preoperative LDL-C concentration affects the risk of perioperative major adverse cardiovascular or cerebrovascular events (MACCE) after noncardiac surgery.

Single center retrospective cohort study.

Hospital (including medical and surgical floor, intensive care unit) and patient disposition location (including the patient's home or any other receiving facility).

43,348 non-cardiac surgeries at NYU Langone Health between January 2016 and September 2020.

Patients were grouped based on preoperative LDL-C.

Complete serum lipid panel obtained within one year prior to the date of noncardiac surgery and rate of perioperative MACCE, defined as a composite of in-hospital non-fatal myocardial infarction, in-hospital acute ischemic stroke, myocardial injury after noncardiac surgery, and death from any cause within 30 days of surgery.

Perioperative MACCE occurred in 1093 patients (2.5 %) overall. After multivariable adjustment, odds of MACCE were significantly lower in patients with higher (≥100 mg/dL) versus lower (<100 mg/dL) LDL-C (adjusted odds ratio [aOR] 0.783, 95 % CI, 0.660-0.926]).

In a large cohort of patients undergoing non-cardiac surgery at a major academic health system in New York City, lower LDL-C concentrations were not associated with a lower incidence of perioperative MACCE. Further investigation into modifiable perioperative cardiovascular risk factors is needed to improve perioperative outcomes.

Hypertension and hypercholesterolemia often occur in the same individuals, increasing the risk of major cardiovascular (CV) outcomes, including myocardial infarction, stroke, CV death, as well as other CV complications. Concomitant management of these condition now represent a crucial step to reduce individual global CV risk and improve CV disease prevention in daily clinical practice. Given the high prevalence of hypertension and hypercholesterolemia in general population and their impact on health status, several pharmacological options are currently available to achieve the recommended therapeutic targets. These drugs, mostly including statins, ezetimibe, bempedoic acid, proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors and inclisiran, can be used either in monotherapies or in combination therapies, with different clinical indications, therapeutic efficacy and tolerability profile. Decision among different drug classes and dosages, as well as choice between monotherapy or combination therapy (fixed or free), largely depend on individual global CV risk profile and therapeutic targets of low-density lipoprotein (LDL) cholesterol levels to be achieved under pharmacological therapy. The present consensus document represents an update of the previous document published on 2022 and endorsed by the Italian Society of Hypertension (SIIA) and the Italian Society of Cardiovascular Prevention (SIPREC). Here we propose a novel paradigm for the treatment of the patients with hypertension and hypercholesterolemia at high or very high cardiovascular risk. In addition, the pharmacological properties, and the clinical efficacy of novel agents recently approved for a tailored therapy of hypercholesterolemia in patients with atherosclerotic CV disease, including PCSK9 inhibitors and bempedoic acid, will be summarized.

Lerodalcibep, a small binding anti-PCSK9 protein (adnectin), showed effective LDL cholesterol reduction in heterozygous familial hypercholesterolaemia. We aimed to assess the safety and efficacy of lerodalcibep and evolocumab in a globally diverse homozygous familial hypercholesterolaemia population.

This phase 3, randomised, open-label, crossover, non-inferiority study consisted of two 24-week treatment periods separated by an 8-week washout. The study was conducted in 12 lipid clinics in six countries (India, Israel, Norway, South Africa, Türkiye, and the USA). Patients aged 10 years or older with genetically confirmed homozygous familial hypercholesterolaemia were randomly assigned by computer-generated randomisation scheme performed centrally via interactive response technology to either monthly lerodalcibep 300 mg (1·2 mL subcutaneous injection) or monthly evolocumab 420 mg (subcutaneous 9 min infusion of 3·5 mL) for 24 weeks (period A) followed by an 8-week washout and then crossed over to the alternate therapy for the next 24 weeks (period B). The trial was open label, but all efficacy parameters were masked to patients, study staff, and the sponsor from randomisation. The primary efficacy endpoint was the percent change from baseline (day 1 of period A) in LDL cholesterol concentration to week 24 for period A and B. The intention-to-treat (ITT) population, defined as all randomly assigned patients, was used for the primary analysis. The safety population included all patients who received any study medication. The margin used to establish non-inferiority was 6%. The trial is registered with ClinicalTrials.gov (NCT04034485) and EudraCT (2019-003611-62), and has now finished.

Patients were enrolled from Nov 11, 2019, to July 2, 2021, and the final study visit took place on Aug 8, 2022. Of 82 patients screened, 66 entered period A (ITT population). The mean age was 28·7 years (SD 15·2); 20 (30%) of 66 were paediatric patients; 36 (55%) of 66 were female and 30 (45%) of 66 were male; and the mean baseline LDL cholesterol was 10·59 mmol/L (SD 4·37). Mean LDL cholesterol reduction by ITT analysis at week 24 was -4·9% (SE 3·5) on lerodalcibep compared with -10·3% (3·5) on evolocumab; the mean difference between treatments was 5·4% (95% CI -0·2 to 11·1), which did not show non-inferiority at the prespecified 6% margin. LDL cholesterol response varied considerably across the patient population but was generally similar in the same patients with both lerodalcibep and evolocumab. When averaged across all monthly visits, LDL cholesterol response was -9·1% (SE 3·2) on lerodalcibep and -10·8% (3·2) on evolocumab. Importantly, genotyping and free PCSK9 suppression were not predictive of response. Both drugs were well tolerated, with no treatment-related serious adverse events. Injection site reactions were reported in one (2%) of 65 patients on lerodalcibep and 15 (24%) of 62 patients on evolocumab.

The LDL cholesterol response was highly variable, but generally similar in patients treated with both lerodalcibep and evolocumab. Importantly, the study showed the inability to predict response based on genotyping, reinforcing the rationale for PCSK9 inhibition in all patients with homozygous familial hypercholesterolemia and continuing its use in responders.

LIB Therapeutics.

The genetic determinants of low-density lipoprotein cholesterol (LDL-C) levels in blood have been predominantly explored in European populations and remain poorly understood in Middle Eastern populations. We investigated the genetic architecture of LDL-C variation in Qatar by conducting a genome-wide association study (GWAS) on serum LDL-C levels using whole genome sequencing data of 13,701 individuals (discovery; n = 5,939, replication; n = 7,762) from the population-based Qatar Biobank (QBB) cohort. We replicated 168 previously reported loci from the largest LDL-C GWAS by the Global Lipids Genetics Consortium (GLGC), with high correlation in allele frequencies (R2 = 0.77) and moderate correlation in effect sizes (Beta; R2 = 0.53). We also performed a multi-ancestry meta-analysis with the GLGC study using MR-MEGA (Meta-Regression of Multi-Ethnic Genetic Association) and identified one novel LDL-C-associated locus; rs10939663 (SLC2A9; genomic control-corrected P = 1.25 × 10-8). Lastly, we developed Qatari-specific polygenic score (PGS) panels and tested their performance against PGS derived from other ancestries. The multi-ancestry-derived PGS (PGS000888) performed best at predicting LDL-C levels, whilst the Qatari-derived PGS showed comparable performance. Overall, we report a novel gene associated with LDL-C levels, which may be explored further to decipher its potential role in the etiopathogenesis of cardiovascular diseases. Our findings also highlight the importance of population-based genetics in developing PGS for clinical utilization.

Dyslipidemia is a metabolic disorder characterized by quantitative and/or qualitative abnormalities in serum lipid levels. Elevated serum cholesterol levels can modify the turnover and recruitment of ionic channels in myocytes and cellular homeostasis, including those of inflammatory cells. Experimental and clinical data indicate that inflammation is implicated in the pathophysiology of atrial remodeling, which is the substrate of atrial fibrillation (AF). Data about the association between increased lipid serum levels and AF are few and contrasting. Lipoprotein (a), adiposity, and inflammation seem to be the main drivers of AF; in contrast, low-density lipoproteins, high-density lipoproteins and triglycerides are not directly involved in AF onset. The present review aimed to describe the pathophysiological link between dyslipidemia and AF, the efficacy of lipid-lowering therapies in atherosclerotic cardiovascular disease (ASCVD) patients with and without AF, and the impact of lipid-lowering therapies on AF incidence.