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Background and Aims: Familial hypercholesterolaemia (FH) is a highly prevalent monogenic disorder characterized by elevated LDL cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Sex disparities in diagnosis, lipid-lowering therapy, and achieved lipid levels have emerged worldwide, resulting in barriers to care in FH. A systematic review was performed to investigate sex-related disparities in treatment, response, and lipid target achievement in FH (PROSPERO, CRD42022353297)., Methods: MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases were searched from inception to 26 April 2023. Records were eligible if they described sex differences in the treatment of adults with FH., Results: Of 4432 publications reviewed, 133 met our eligibility criteria. In 16 interventional clinical trials (eight randomized and eight non-randomized; 1840 participants, 49.4% females), there were no differences between males and females in response to fixed doses of lipid-lowering therapy, suggesting that sex was not a determinant of response. Meta-analysis of 25 real-world observational studies (129 441 participants, 53.4% females) found that females were less likely to be on lipid-lowering therapy compared with males (odds ratio .74, 95% confidence interval .66-.85). Importantly, females were less likely to reach an LDL-C < 2.5 mmol/L (odds ratio .85, 95% confidence interval .74-.97). Similarly, treated LDL-C levels were higher in females. Despite this, male sex was associated with a two-fold greater relative risk of major adverse cardiovascular events including myocardial infarction, atherosclerotic cardiovascular disease, and cardiovascular mortality., Conclusions: Females with FH were less likely to be treated intensively and to reach guideline-recommended LDL-C targets. This sex bias represents a surmountable barrier to clinical care., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Hyperlipidemia, obesity and gut dysbiosis are pivotal risk factors for atherosclerotic cardiovascular disease (ACVD). Supplementation of Akkermansia muciniphila (AKK) has also been proven to be effective in the prevention and treatment of obesity and other metabolic disorders. Here we found that AKK was more abundant in healthy control than ACVD patients via metagenomic sequencing on fecal samples. Subsequently, we investigated the role and underlying mechanism of AKK on obesity-associated atherosclerosis. AKK intervention partially reversed the exacerbation of atherosclerotic lesion formation in ApoE -/- mice by improving dyslipidemia. Interestingly, replenishment with AKK significantly enhanced cardiac function and reduced the body weight. It also reduced pro-inflammatory cytokine IL-6 and increased anti-inflammatory IL-10 in the circulation. Additionally, AKK colonization dramatically regulated gut microbiota and increased the abundance of Lactobacillaceae. Our findings have provided novel insights into the therapeutic potential of AKK as a beneficial microbe for treating atherosclerotic-associated cardiovascular diseases., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: This review presents the risks and benefits of very low LDL cholesterol and the safety of using lipid-lowering therapy to achieve these levels., Recent Findings: A growing body of literature suggests that lower LDL cholesterol levels are associated with a reduced risk of cardiovascular disease. Further, achieving these levels with pharmaceuticals is remarkably safe. Although statins may slightly increase the risk of diabetes mellitus and hemorrhagic stroke, the benefits outweigh the risks. While recommendations from professional societies are increasingly aggressive, additional risk reduction could be achieved by setting more even ambitious LDL cholesterol goals., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The role of lipoprotein (a), or Lp(a), in the development of obstructive coronary artery disease (CAD) and high-risk plaque (HRP) among primary prevention patients with stable chest pain is unknown. We sought to evaluate the relationship of Lp(a), independent of low-density lipoprotein cholesterol (LDL-C), with the presence of obstructive CAD and HRP in an attempt to improve understanding of the residual risk imparted by Lp(a) on CAD., Methods: We performed a secondary analysis among PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) Trial participants who had coronary computed tomographic angiography (CTA) performed and Lp(a) data available. Lp(a) concentration was analyzed as a binary variable with elevated Lp(a) defined as ≥50 mg/dL. "Stenosis ≥ 50%" was defined as ≥50% coronary artery stenosis in any epicardial vessel, and "Stenosis ≥ 70%" was defined as ≥70% coronary artery stenosis in any epicardial vessel and/or ≥50% left main coronary artery stenosis. HRP was defined as presence of plaque on CTA imaging with evidence of positive remodeling, low CT attenuation, or napkin ring sign. Multivariate logistic regression models were constructed to evaluate the association between Lp(a) and the outcomes of obstructive CAD and HRP stratified by LDL-C ≥100 mg/dL vs. <100 mg/dL., Results: Of the 1,815 patients who underwent CTA and had Lp(a) data available, those with elevated Lp(a) were more commonly female and Black than those with lower Lp(a). Elevated Lp(a) was associated with both Stenosis ≥ 50% (OR 1.57, 95% CI 1.14-2.15, p=0.005) and Stenosis ≥ 70% (OR 2.05, 95% CI 1.34-3.11, p=0.0008) in multivariate models, and this relationship was not modified by LDL-C ≥100 mg/dL vs. <100 mg/dL (interaction p>0.4). Elevated Lp(a) was not associated with HRP when adjusted for obstructive CAD., Conclusions: This study of patients without known CAD found that elevated Lp(a) ≥50 mg/dL was independently associated with the presence of obstructive CAD regardless of controlled vs. uncontrolled LDL-C, but was not independently associated with HRP when Stenosis ≥ 50% or ≥ 70% was accounted for. Further research is warranted to delineate the role of Lp(a) in the residual risk for ASCVD that patients may have despite optimal LDL-C lowering., Competing Interests: Declaration of competing interest Dr. Shah reports research grants from Amgen, Janssen, Eli Lily, Novartis, and National Institutes of Health, and service as a consultant/advisor for Merck, Amgen, Norvartis, and New Amsterdam Pharma. Dr. Ferencik reports consulting fees from Cleerly, HeartFlow, Elucid, Siemens Healthineers, and BioMarin, and stock options from Elucid, and is a member of an advisory board for Cleerly. Dr. Lu reports research funding to his institution from the American Heart Association, AstraZeneca, Ionis, Johnson & Johnson Innovation, Kowa Pharmaceuticals America, MedImmune, National Academy of Medicine, National Heart, Lung, and Blood Institute, and Risk Management Foundation of the Harvard Medical Institutions outside the submitted work. Dr. Foldyna reports research grants from National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL170877, 5P30DK040561), AstraZeneca, Cleerly Health, MedImmune, and MedTrace. Dr. Pagidipati reports research support from Alnylam, Amgen, Bayer, Boehringer Ingelheim, Eggland's Best, Eli Lilly, Novartis, Novo Nordisk, Merck; service on consultation/advisory panels for Amgen, Bayer, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Esperion, AstraZeneca, Merck, Novartis, and Novo Nordisk; service as an Executive Committee member for trials sponsored by Novo Nordisk and by Amgen and by AstraZeneca; service on a Data and Safety Monitoring Board for trials sponsored by Johnson & Johnson and Novartis; and service on a medical advisory board for Miga Health. The remaining authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background: Dyslipidemia remains the major cause of atherosclerotic cardiovascular disease (ASCVD). Lipid management in patients with increased cardiovascular (CV) risk needs improvement across Europe, and data gaps are noticeable at the country level., Hypothesis: We described the current treatment landscape in Belgium, hypothesizing that lipid management in patients with ASCVD remains inadequate and aiming to understand the reasons., Methods: Using data from an anonymized primary care database in Belgium derived from 494 750 individuals, we identified those with any CV risk factor between November 2019 and October 2022 and described the clinical features of patients with ASCVD. The main outcomes were the proportion of patients (i) receiving lipid-lowering therapies (LLTs), (ii) per low-density lipoprotein cholesterol (LDL-C) threshold, stratified per LLT, (iii) reaching the 2021 ESC recommended LDL-C goals, and (iv) LDL-C reduction per type of LLT was also determined., Results: Among 40 888 patients with very high CV risk, 24 859 had established ASCVD. Most patients with ASCVD were either receiving monotherapy (59.6%) or had no documented LLT (25.1%). Further, 64.2% of those with no documented LLT exhibited LDL-C levels ≥ 100 mg/dL. Among common treatment options, one of the greatest improvements in LDL-C levels was achieved with combination therapy of statin and ezetimibe, reducing LDL-C levels by 41.5% (p < 0.0001). Yet, in this group, 24.8% of patients had still LDL-C levels ≥ 100 mg/dL and only 20.7% were at goal., Conclusion: Our study emphasizes the importance of developing strategies to help patients achieve their LDL-C goals, with a focus on supporting the implementation of combination LLT in routine clinical practice., (© 2024 Novartis Pharma NV/SA. Clinical Cardiology published by Wiley Periodicals LLC.)

Introduction: Despite decades of research clearly illustrating the direct link between low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk, LDL-C goal attainment rates are remarkably low in both the primary and secondary prevention settings., Areas Covered: Herein we detail: (1) the low rates of LDL-C goal attainment; (2) despite guidelines clearly outlining indications of use, there is suboptimal initiation, intensification, and persistence of lipid lowering therapy, especially combination therapy; (3) key clinician-related factors contributing to this gap include inconsistent risk assessments, clinical inertia, and barriers to health access; (4) LDL-C reduction is associated with reductions in risk for cardiovascular events. Increasing LDL-C goal attainment rates should be a high public health priority., Expert Opinion: There is an urgent need to rethink dyslipidemia management. Opportunities exist to overcome LDL-C goal attainment barriers, which necessitates a concerted effort from patients, clinicians, health systems, payors, pharmaceutical companies, and public health advocates. LDL-C measurement should be a performance metric for health systems. In addition, upfront use of combination therapy and polypill formulations should be encouraged. Engaging pharmacists to support drug therapy and adherence is crucial. Leveraging telehealth and electronic medical record (EMR) functionalities can enhance these efforts and ensure more effective implementation.

Objective: Rest-activity rhythm is an essential behavior for human health. However, the association between rest-activity rhythm and atherosclerotic cardiovascular disease (ASCVD) risk remains unclear. Therefore, this study aimed to elucidate the association., Methods: This study included 87,039 participants from the UK Biobank who had 7-day accelerometry data and were free of ASCVD at baseline. Relative amplitude was calculated as the difference between the most active continuous 10-h period (M10) and the least active continuous 5-h period (L5) in 24 h, and lower relative amplitude indicated the disruption of rest-activity rhythm. Cox proportional hazard model was used to examine the association of relative amplitude with ASCVD. Further, the linear association between relative amplitude and arterial stiffness measurements, including arterial stiffness index (ASI) and carotid intima-media thickness (cIMT), was examined., Results: During a mean follow-up period of 6.80 ± 1.10 years, 2798 ASCVD cases were identified. A dose-response relationship was observed between relative amplitude and ASCVD risk (P for trend<0.001). The adjusted hazard ratio, for the highest vs the lowest quintile of relative amplitude, was 1.54 (95 % confidence interval: 1.31, 1.79). Further, we found significant association of lower relative amplitude with ASI and cIMT. The onset timing of M10 at ≤06:00, 09:00, 10:00, or ≥11:00, as opposed to the reference time of 07:00, was associated with higher ASCVD risk., Conclusions: Low rest-activity rhythm amplitude was associated with a higher risk of ASCVD. Rest-activity rhythm amplitude may provide a method to identify individuals at risk of ASCVD in public health and clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Systemic low-grade inflammation, measured by plasma high-sensitivity C-reactive protein (hsCRP) levels, is an important risk factor for atherosclerotic cardiovascular disease (ASCVD). To date, however, it is unknown whether plasma hsCRP is associated with adverse histological plaque features., Methods: Plaques were derived during carotid endarterectomy. Patients with hsCRP levels ≥2 mg/L were evaluated for pro-inflammatory and adverse plaque characteristics, as well as future ASCVD events, and compared with patients with low hsCRP levels. Logistic and linear regression analyses in addition to subdistribution hazard ratios were conducted, adjusted for cardiovascular risk factors., Results: A total of 1096 patients were included, of which 494 (46.2 %) had hsCRP levels ≥2 mg/L. Elevated hsCRP levels 2 mg/L were independently associated with levels of plaque interleukin 6, beta coefficient of 109.8 (95 % confidence interval (CI): 33.4, 186.5; p = 0.005) pg/L, interleukin 8 levels, 194.8 (110.4, 378.2; p = 0.03) pg/L and adiponectin plaque levels, -16.8 (-30.1, -3.6; p = 0.01) μg/L, compared with plaques from patients with low hsCRP levels. Histological analysis revealed increased vessel density in high hsCRP patients, odds ratio (OR) of 1.57 (1.20, 2.09; p = 0.001), larger lipid core, 1.35 (1.02, 1.73; p = 0.04), and increased macrophage content, 1.32 (1.02, 1.73; p = 0.04). Over a 3-year follow-up period, hsCRP levels ≥2 mg/L were associated with a hazard ratio of 1.81 (1.03, 3.16; p = 0.04) for coronary artery disease event risk., Conclusions: The distinct inflammatory and histological features observed in carotid plaques among individuals with hsCRP levels ≥2 mg/L underscore the utility of plasma hsCRP as a potent identifier for patients harboring high-risk plaques., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Randomized clinical trials (RCTs) of PCSK9 monoclonal antibody(mAb) specifically for Chinese patients have been limited. This multi-center RCT is to clarify the efficacy and safety of a novel mAb, Ebronucimab, in Chinese patients. Patients diagnosed with primary hypercholesterolemia, including Heterozygous Familial Hypercholesterolemia, or mixed dyslipidemia, were categorized by ASCVD risk and randomly assigned at a ratio of 2:1:2:1 to receive Ebronucimab 450 mg or matching placebo every 4 weeks (Q4W), or Ebronucimab 150 mg or matching placebo every 2 weeks (Q2W). The primary outcome was the percentage change of LDL-C from baseline to week 12 for all groups. The least squares mean reduction difference (95 %CI) in LDL-C from baseline to week 12 of Ebronucimab 450 mg Q4W and Ebronucimab 150 mg Q2W groups versus the placebo group was -59.13 (-64.103, -54.153) (Adjusted p<0.0001) and -60.43 (-65.450, -55.416) (Adjusted p<0.0001), respectively. Meanwhile, the Ebronucimab group exhibited notably high rates in reaching LDL-C goals of each cardiovascular risk stratification. In addition, Ebronucimab effectively improved other lipid panel. During the double-blind treatment period, relatively frequently reported adverse events (AEs) were injection site reactions (ISR), urinary tract infection, and hyperuricemia (Incidence rate are 6.9 %, 4.8 % and 3.5 %). Among treatment-associated AEs, only injection site reactions (ISR) occurred more in the dose groups. In conclusion, Ebronucimab, with either 450 mg Q4W or 150 mg Q2W doses, demonstrated significant efficacy in lowering serum LDL-C level with a favorable safety and immunogenicity profile among hypercholesterolemic patients., Competing Interests: Declaration of Competing Interest Binge Yu, Guoqin Wang, Fang Xu, Dongmei Lu, Zhimei He, Benchao Chen, Lei Ma, Max Wang, Baiyong Li, and Michelle Xia are employees of Akeso Pharmaceutical (Guangzhou) Co., Ltd. The remaining co-authors have nothing to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Aim: The objective of our study was to examine the association between composite dietary antioxidant index (CDAI) and atherosclerotic cardiovascular disease (ASCVD) in adults., Methods and Results: Data was gathered from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018. To examine the connection between CDAI and ASCVD, multiple logistic regression analyses were performed. Restricted cubic splines were utilized to examine non-linear correlations, and the inflection point was identified using a two-piecewise linear regression approach. Subgroup analyses were performed to demonstrate stability of results. A total of 44,494 individuals were included in the study. The multivariate logistic regression model was fully adjusted and revealed an odds ratio of 0.968 (95% CI: 0.959-0.978; P < 0.001) for the correlation between CDAI and ASCVD. Furthermore, individuals in the highest quartile of CDAI exhibited a decreased risk of ASCVD compared to those in the lowest quartile [0.716 (0.652-0.787); P < 0.001]. Moreover, restricted cubic spline (RCS) analysis revealed non-linear relationship between CDAI and ASCVD, with inflection point at -0.387. The analysis of subgroups showed that the importance of CDAI remained consistent among various age, sex, race, body mass index (BMI), and physical activity., Conclusions: Our research revealed an inverse and non-linear relationship between CDAI and ASCVD in adults. The implications of these findings are significant for future studies and the formulation of dietary guidelines., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite effective low-density lipoprotein cholesterol-targeted therapies. This review explores the crucial role of inflammation in the residual risk of ASCVD, emphasizing its impact on atherosclerosis progression and plaque stability. Evidence suggests that high-sensitivity C-reactive protein (hsCRP), and potentially other inflammatory biomarkers, can be used to identify the inflammatory residual ASCVD risk phenotype and may serve as future targets for the development of more efficacious therapeutic approaches. We review the biological basis for the association of inflammation with ASCVD, propose new therapeutic strategies for the use of inflammation-targeted treatments, and discuss current challenges in the implementation of this new treatment paradigm for ASCVD., (© 2024. The Author(s).)

The incidence of cardiometabolic disease is increasing globally, with a trend toward younger age of onset. Among these, atherosclerotic cardiovascular disease is a leading cause of mortality worldwide. Despite the efficacy of traditional lipid-lowering drugs, such as statins, in reducing low-density lipoprotein cholesterol levels, a significant residual risk of cardiovascular events remains, which is closely related to unmet triglyceride (TG) targets. The clinical application of current TG-lowering Western medicines has certain limitations, necessitating alternative or complementary therapeutic strategies. Traditional Chinese medicine (TCM) and plant-derived natural products, known for their safety owing to their natural origins and diverse biological activities, offer promising avenues for TG regulation with potentially fewer side effects. This review systematically summarises the mechanisms of TG metabolism and subsequently reviews the regulatory effects of TCM and plant-derived natural products on TG metabolism, including the inhibition of TG synthesis (via endogenous and exogenous pathways), promotion of TG catabolism, regulation of fatty acid absorption and transport, enhancement of lipophagy, modulation of the gut microbiota, and other mechanisms. In conclusion, through a comprehensive analysis of recent studies, this review consolidates the multifaceted regulatory roles of TCM and plant-derived natural products in TG metabolism and elucidates their potential as safer, multi-target therapeutic agents in managing hypertriglyceridemia and mitigating cardiovascular risk, thereby providing a basis for new drug development., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest that pertain to this work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Lipoprotein(a) [Lp(a)] is a well-recognized risk factor for atherosclerotic cardiovascular disease (ASCVD). Few data are available on the distribution of Lp(a) levels among subjects at different cardiovascular risk and in subjects with monogenic and polygenic dyslipidemias (familial hypercholesterolemia, FH and familial hypobetalipoproteinemia type 1, FHBL1). The aim of this study was to investigate the distribution of Lp(a) plasma levels in subjects with high and low LDL-C levels (FH and FHBL1) and in the general population., Methods and Results: The study cohorts included 356 hypercholesterolemic patients, 212 carrying a FH causative mutation, 144 with clinical FH (mutation negative - FHneg), 52 FHBL1 and 797 free-living subjects. Lp(a) levels were significantly higher in FH subjects (both FH and FHneg) (median 12.46 mg/dl and 14.0 mg/dl, respectively) compared with FHBL1 and free-living subjects (7.68 mg/dl and 7.18 mg/dl, respectively). More, Lp(a) levels were similar in FH subjects carrying LDLR defective and null mutations and FHneg. Subjects at high and very high CV risk exhibited significant higher Lp(a) levels (median 10.68 mg/dl and 9.20 mg/dl, respectively) compared with low and moderate CV risk (median 5.72 mg/dl and 7.80 mg/dl, respectively) (p < 0.0008)., Conclusions: FH subjects exhibit higher Lp(a) levels than FHBL1 and general population. Lp(a) slightly contribute to hypercholesterolemia in FH patients. Subjects at high and very high CV risk exhibited significant higher Lp(a) levels compared with low and moderate CV risk. Combined evaluation of Lp(a) levels in FH subjects with other traditional risk factors could identify very high-risk individuals who may benefit from early aggressive treatments to avoid premature CV events., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Olpasiran, a small interfering RNA (siRNA), blocks lipoprotein(a) (Lp(a)) production by preventing translation of apolipoprotein(a) mRNA. In phase 2, higher doses of olpasiran every 12 weeks (Q12W) reduced circulating Lp(a) by >95%., Objectives: This study sought to assess the timing of return of Lp(a) to baseline after discontinuation of olpasiran, as well as longer-term safety., Methods: OCEAN(a)-DOSE (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction-DOSE Finding Study) was a phase 2, dose-finding trial that enrolled 281 participants with atherosclerotic cardiovascular disease and Lp(a) >150 nmol/L to 1 of 4 active doses of olpasiran vs placebo (10 mg, 75 mg, 225 mg Q12W, or an exploratory dose of 225 mg Q24W given subcutaneously). The last dose of olpasiran was administered at week 36; after week 48, there was an extended off-treatment follow-up period for a minimum of 24 weeks., Results: A total of 276 (98.2%) participants entered the off-treatment follow-up period. The median study exposure (treatment combined with off-treatment phases) was 86 weeks (Q1-Q3: 79-99 weeks). For the 75 mg Q12W dose, the off-treatment placebo-adjusted mean percent change from baseline in Lp(a) was -76.2%, -53.0%, -44.0%, and -27.9% at 60, 72, 84, and 96 weeks, respectively (all P < 0.001). The respective off-treatment changes in Lp(a) for the 225 mg Q12W dose were -84.4%, -61.6%, -52.2%, and -36.4% (all P < 0.001). During the extension follow-up phase, no new safety concerns were identified., Conclusions: Olpasiran is a potent siRNA with prolonged effects on Lp(a) lowering. Participants receiving doses ≥75 mg Q12W sustained a ∼40% to 50% reduction in Lp(a) levels close to 1 year after the last dose. (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction-DOSE Finding Study [OCEAN(a)-DOSE]; NCT04270760)., Competing Interests: Funding Support and Author Disclosures The OCEAN(a)-DOSE study was funded by Amgen. Dr O’Donoghue has received grant funding through Brigham and Women’s Hospital from Novartis, Amgen, AstraZeneca, and Janssen; and has received honoraria from Novartis, Amgen, AstraZeneca, and Janssen. Dr Rosenson has received institutional grant funding from Amgen, Arrowhead, Lilly, Novartis, and Regeneron; has received consulting fees from Amgen, Arrowhead, CRISPER Therapeutics, Lilly, Novartis, Precision Biosciences, Regeneron, and Ultragenyx; has received nonpromotional speaker fees from Amgen and Kowa; and has held stock in MediMergent. Dr López is an employee of Amgen; and/or has owned Amgen stock or stock options. Dr Lepor has received grant support from Amgen, Novartis, Regeneron, New Amsterdam, Merck, Arrowhead, and AstraZeneca; and has received speaker and/or consulting fees from Amgen, Novartis, Regeneron, Merck, AstraZeneca, and Boehringer Ingelheim. Dr Baum has received consulting fees from Altimmune, Amgen, Axcella, Boehringer Ingelheim, Lilly, Esperion, Ionis, Madrigal, Merck, Novartis, and Regeneron; and has received speaker fees from Amgen, Lilly, and Regeneron. Dr Gaudet has received grants and personal fees from Amgen during the conduct of the study; has received grants from Acasti, Kowa, Uniqure, Sanofi, Aegerion, Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Ceapro, Dalcor, Esperion, Arrowhead, Regeneron, Akcea, Allergan, Amryt, Ionis, Novartis, Novo Nordisk, Pfizer, Lilly, and The Medicine Company, outside the submitted work; and has received personal fees from Arrowhead, Regeneron, Akcea, Allergan, Amryt, Ionis, Novartis, Novo Nordisk, Pfizer, Lilly, CRISPR Therapeutics, Saliogen, and Ceapro, outside the submitted work. Dr Knusel is an employee of Amgen; and/or has owned Amgen stock or stock options. Ms Kuder has served as a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Ms Murphy has served as a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Dr H. Wang is an employee of Amgen; and/or has owned Amgen stock or stock options. Dr Wu is an employee of Amgen; and/or has owned Amgen stock or stock options. Dr Shah is an employee of Amgen; and has owned Amgen stock. Dr J. Wang is an employee of Amgen; and has owned Amgen stock. Dr Wilmanski is an employee of Amgen; and has owned Amgen stock. Dr Sohn is an employee of Amgen; and/or has owned Amgen stock or stock options; and has existing or pending patents related to olpasiran. Dr Kassahun is an employee of Amgen; and/or has owned Amgen stock or stock options; and has existing or pending patents related to olpasiran. Dr Sabatine has received research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, Inc, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Ionis, Merck, Novartis, Pfizer, Saghmos Therapeutics, and Verve Therapeutics; has served as a consultant for Amgen, AMPEL BioSolutions, Anthos Therapeutics, Inc, AstraZeneca, Beren Therapeutics, Boehringer Ingelheim, Dr Reddy’s Laboratories, Fibrogen, Merck, Moderna, Novo Nordisk, Precision BioSciences, and Silence Therapeutics; and has served as a member of the TIMI Study Group, which has also received institutional research grant support through Brigham and Women’s Hospital from ARCA Biopharma, Janssen Research and Development, Siemens Healthcare Diagnostics, Softcell Medical Limited, Regeneron, Roche, and Zora Biosciences. Dr Stout has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Why lower low-density lipoprotein cholesterol (LDL-C) was associated with a decreased atherosclerotic cardiovascular disease (ASCVD) risk but an increased hemorrhagic stroke (HS) risk in hypertensive adults remains unclear. We examined whether the inverse LDL-C-HS association partly arises from its effect on ASCVD. We estimated separable effects of LDL-C on HS outside (i.e., separable direct effect) or only through its effect on ASCVD (i.e., separable indirect effect) in hypertensive adults from the Chinese Multi-provincial Cohort Study. We quantified such effects using numbers needed to treat (NNT) to prevent or cause an extra HS based on the restricted mean event-free time till a 25-year follow-up. LDL-C $<$ 70 mg/dL was not associated with an increased HS risk compared to LDL-C $\ge$ 70 mg/dL regarding total and separable direct effects. However, a small separable indirect effect (i.e., NNT to harm: 9722 participants) was noted and validated via a series of sensitivity analyses. Moreover, modified effects were observed, particularly in the 35-49-year age group, men, and those with SBP $\ge$ 140 mm Hg. These results suggest the inverse LDL-C-HS association in hypertensive adults is partly due to its effect on ASCVD. A better understanding of such associations would provide more enlightening into stroke prevention., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Idiopathic inflammatory myopathies (IIM) confer an increased risk of morbidity from atherosclerotic cardiovascular disease (ASCVD). While ASCVD risk has been studied in other countries, these results may not be applicable to patients with dermatomyositis (DM) and polymyositis (PM) in the United States. This retrospective analysis of a cohort of patients identified by ICD code from TriNetX investigated the incidence of ASCVD after International Classification of Disease (ICD) codes of DM, PM, dermatopolymyositis (DPM) or juvenile dermatomyositis (JDM)., Method: Patients were identified by entry of two ICD codes separated by at least 6 months, according to their first diagnosis code; ASCVD was defined as first ICD code for myocardial infarction, ischemic stroke, transient ischemic attack, or peripheral arterial disease. Cox proportional hazards regression modeled time from first IIM ICD code to ASCVD event., Results: A total of 35,554 patients were identified with the mean age at first IIM code of 54 and 26.1% were male. The most common comorbidity for all groups except JDM was hyperlipidemia (39.9%) though 79.2% of patients were on no cholesterol lowering medication. ASCVD occurred in 30.4% of patients with PM, 24.3% of patients with DM and 0.9% of patients with JDM. Patients with PM had a median time to event of 9.7 years (95% Confidence interval (CI) 9.1, 10.7) and 14.3 years (95% CI 12.6, 14.8) for DM. This study demonstrates that ASCVD is a comorbidity occurring after a median of 12.5 years (95% CI 11.9, 13.6) in patients with IIM., Conclusions: ASCVD appears to be a long-term complication for IIM patients occurring in nearly a quarter of US patients without prior ASCVD with at least two ICD codes for IIM, with a median time to event of 12.5 years. There appears to be a practice gap in the recognition and treatment of hyperlipidemia in these patients. Key Points • Hyperlipidemia was a common comorbidity identified in patients with IIM though most patients were not on cholesterol lowering medication. • Development of ASCVD appears to be a long-term complication for patients with IIM in the United States., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

In recent years, the prevalence and fatality rates of atherosclerotic cardiovascular disease have not only shown a consistent rise that cannot be ignored, but have also become a pressing social health problem that requires urgent attention. While interventional surgery and drug therapy offer significant therapeutic results, they often come with common side effects. Geniposide, an active component extracted from the Chinese medicine Gardenia jasminoides Ellis, shows promise in the management of cardiac conditions. This review comprehensively outlines the underlying pharmacological mechanisms by which geniposide exerts its effects on atherosclerosis. Geniposide exhibits a range of beneficial effects including alleviating inflammation, inhibiting the development of macrophage foam cells, improving lipid metabolism, and preventing platelet aggregation and thrombosis. It also demonstrates mitochondrial preservation, anti-apoptotic effects, and modulation of autophagy. Moreover, geniposide shows potential in improving oxidative stress and endoplasmic reticulum stress by maintaining the body's antioxidant and oxidative balance. Additionally, this review comprehensively details the biological properties of geniposide, including methods of extraction and purification, as well as its pharmacokinetics and toxicological characteristics. It further discusses the clinical applications of related biopharmaceuticals, emphasizing the potential of geniposide in the prevention and treatment of atherosclerotic cardiovascular diseases. Furthermore, it highlights the limitations of current research, aiming to provide insights for future studies., (© 2024. The Author(s).)

Various symptoms have been reported to persist beyond the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred to as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 are largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction is a strong candidate explaining the induction of long COVID-19. The angiotensin-converting enzyme 2 (ACE2), the entry receptor for SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for atherosclerotic cardiovascular disease (ASCVD) and a history of ASCVD raise the risk of severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with the development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in the development of ASCVD. We consider the influence of long COVID-19 on the development of chronic kidney disease (CKD) and ASCVD. Future assessments of the outcomes of long COVID-19 in patients resulting from therapeutic interventions that improve endothelial function may imply the significance of endothelial dysfunction in the development of long COVID-19.

Aims: To assess the association of air pollution exposure at different time scales with arterial stiffness in participants with and without atherosclerotic cardiovascular disease (ASCVD)., Methods: We measured participants' arterial stiffness with brachial-ankle pulse wave velocity (baPWV) from October 2016 to January 2020. Concentrations of air pollutants including fine particles < 2.5 μm aerodynamic diameter (PM 2.5 ), inhalable particles < 10 μm aerodynamic diameter (PM 10 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), carbon monoxide (CO), and ozone (O 3 ) measured by fixed ambient air monitoring stations were collected for short- (7-day) and long-term (365-day) exposure assessment. We used generalized estimating equations (GEEs) to analyze and further explored the modification effects between ASCVD and air pollutants., Results: Seven hundred sixty-five participants were finally included and four hunderd sixty (60.1%) participants had a history of ASCVD. Based on the partial regression coefficients (β) and 95% confidence intervals (95% CI) calculated from GEEs using linear regression, each 10 μg/m 3 increase in long-term exposure to PM 2.5 and PM 10 was associated with 31.85 cm/s (95% CI, 17.97 to 45.73) and 35.93 cm/s (95% CI, 21.01 to 50.84) increase in baPWV. There was no association between short-term exposure to air pollution and arterial stiffness. Although no significant interaction effect was observed between air pollution and ASCVD, baPWV showed a greater increment in the subgroup without ASCVD., Conclusion: Long-term exposure to air pollution is closely associated with higher arterial stiffness in participants with and without ASCVD. Reducing air pollution exposure is essential in the primary and secondary prevention of ASCVD., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The relationship between epilepsy and risk of acute myocardial infarction (AMI) is not fully understood. Evidence from the Stockholm Heart Study indicates that the risk of AMI is increased in people with epilepsy. This study aims to analyze the temporal trends in prevalence, adverse clinical outcomes, and risk factors of AMI in patients with epilepsy (PWE)., Methods: Patients aged 18 years or older, diagnosed with epilepsy with or without AMI and hospitalized from January 1, 2008, to December 31, 2017, were identified from the National Inpatient Sample (NIS) database. The Cochran-Armitage trend test and logistic regressions were conducted using SAS 9.4. Odds ratios (ORs) were generated for multiple variables., Results: A total of 8,456,098 inpatients were eligible for our analysis, including 181,826 comorbid with AMI (2.15%). The prevalence of AMI diagnosis in PWE significantly increased from 1,911.7 per 100,000 hospitalizations in 2008 to 2,529.5 per 100,000 hospitalizations in 2017 ( P trend  < 0.001). Inpatient mortality was significantly higher in epilepsy patients with AMI compared to those without AMI (OR = 4.61, 95% CI: 4.54 to 4.69). Factors significantly associated with AMI in PWE included age (≥75 years old vs. 18 ~ 44 years old, OR = 3.54, 95% CI: 3.45 to 3.62), atherosclerosis (OR = 4.44, 95% CI: 4.40 to 4.49), conduction disorders (OR = 2.21, 95% CI: 2.17 to 2.26), cardiomyopathy (OR = 2.11, 95% CI: 2.08 to 2.15), coagulopathy (OR = 1.52, 95% CI: 1.49 to 1.54), dyslipidemia (OR = 1.26, 95% CI: 1.24 to 1.27), peptic ulcer disease (OR = 1.23, 95% CI: 1.13 to 1.33), chronic kidney disease (OR = 1.23, 95% CI: 1.22 to 1.25), smoking (OR = 1.20, 95% CI: 1.18 to 1.21), and weight loss (OR = 1.20, 95% CI: 1.18 to 1.22)., Conclusion: The prevalence of AMI in PWE increased during the decade. Mortality rates were high among this population, highlighting the need for comprehensive attention to prophylaxis for risk factors and early diagnosis of AMI in PWE by physicians., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pan, Xu, Wu, Chen, Luo, Chen, Yu, Qin and He.)

Background: The longitudinal relation between coronary artery disease (CAD) polygenic risk score (PRS) and long-term plaque progression and high-risk plaque (HRP) features is unknown., Objectives: The goal of this study was to investigate the impact of CAD PRS on long-term coronary plaque progression and HRP., Methods: Patients underwent CAD PRS measurement and prospective serial coronary computed tomography angiography (CTA) imaging. Coronary CTA scans were analyzed with a previously validated artificial intelligence-based algorithm (atherosclerosis imaging-quantitative computed tomography imaging). The relationship between CAD PRS and change in percent atheroma volume (PAV), percent noncalcified plaque progression, and HRP prevalence was investigated in linear mixed-effect models adjusted for baseline plaque volume and conventional risk factors., Results: A total of 288 subjects (mean age 58 ± 7 years; 60% male) were included in this study with a median scan interval of 10.2 years. At baseline, patients with a high CAD PRS had a more than 5-fold higher PAV than those with a low CAD PRS (10.4% vs 1.9%; P < 0.001). Per 10 years of follow-up, a 1 SD increase in CAD PRS was associated with a 0.69% increase in PAV progression in the multivariable adjusted model. CAD PRS provided additional discriminatory benefit for above-median noncalcified plaque progression during follow-up when added to a model with conventional risk factors (AUC: 0.73 vs 0.69; P = 0.039). Patients with high CAD PRS had an OR of 2.85 (95% CI: 1.14-7.14; P = 0.026) and 6.16 (95% CI: 2.55-14.91; P < 0.001) for having HRP at baseline and follow-up compared with those with low CAD PRS., Conclusions: Polygenic risk is strongly associated with future long-term plaque progression and HRP in patients suspected of having CAD., Competing Interests: Funding Support and Author Disclosures Dr Nurmohamed is supported by grants from the Dutch Heart Foundation (Dekker grant number 03-007-2023-0068) and European Atherosclerosis Society (2023). Dr Fahed is supported by grants K08HL161448 and R01HL164629 from the National Heart, Lung, and Blood Institute. Dr Nurmohamed has received research funding/speaker fees from Cleerly, Daiichi Sankyo, and Novartis; and is co-founder of Lipid Tools. Dr Choi has received grant support from Cleerly Inc and GW Heart and Vascular Institute; has equity in Cleerly, Inc; and reports consulting with Siemens Healthineers. Dr Natarajan has received investigator-initiated grants from Allelica, Amgen, Apple, AstraZeneca, Boston Scientific, and Novartis; has received personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, GV, HeartFlow, Novartis, and Roche/Genentech; is a co-founder of TenSixteen Bio; is a scientific advisory board member of Esperion Therapeutics, Preciseli, and TenSixteen Bio; and reports spousal employment at Vertex Pharmaceuticals. Drs Earls and Min are employees of and hold equity in Cleerly Inc. Dr Stroes has received lecturing/advisory board fees from Amgen, Novartis, Esperion, Sanofi-Regeneron, and Akcea. Dr Knaapen has received research grants from HeartFlow, Inc and Cleerly Inc. Dr Reeskamp is cofounder of Lipid Tools; and has received speaker fees from Novartis, Daiichi Sankyo, and Ultragenyx. Dr Fahed is co-founder of Goodpath. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: With atherosclerotic cardiovascular disease (ASCVD) cases increasing in Indonesia, there is a growing need to identify high-risk patients for recurrent cardiovascular events. Risk stratification could guide optimal secondary preventive therapy. Understanding the ASCVD direct inpatient costs could further provide insight in reducing the economic burden that comes with Indonesia's high number ASCVD cases. However, there is a significant gap in Indonesian large-scale research on both of these valuable data. Employing the SMART-REACH model, we can profile the risk of recurrent cardiovascular events in Indonesian ASCVD patients., Objectives: Utilize the SMART-REACH model to estimate 10-year and lifetime risk of cardiovascular events in Indonesian ASCVD patients and describe the direct inpatient cost of ASCVD., Methods: This descriptive cross-sectional study gathered data from 3,209 ASCVD patients aged 45-80 from two major cardiovascular centers using purposive sampling. Participants were patients admitted between January 2020 and March 2023 with ST-elevated myocardial infarct (STEMI), non-ST-elevated myocardial infarct (NSTEMI), and chronic coronary syndrome (CCS) requiring elective percutaneous coronary intervention (PCI). The SMART-REACH risk estimation model required clinical data upon admission, laboratory results within the first 24 h of admission, and cardiovascular medication prescribed upon discharge. The SMART-REACH model is a Fine and Gray competing risk model incorporating cardiovascular risk factors that estimates individual 10-year and lifetime risk for recurrent cardiovascular events which includes myocardial infarction, stroke, or vascular death. Direct inpatient cost profiling totaled all medical expenses incurred from ASCVD diagnosis admission to discharge. Results were reported descriptively with subgroup analyses., Results: The cohorts (mean age 60.15 ± 8.6 years) were predominantly male [ n  = 2,537 (79.1%)], hypertensive [ n  = 2,267 (70.6%)], and diagnosed with STEMI [ n  = 1,732 (54%)]. The SMART-REACH model calculated a mean 10-year risk of 30.2% (95% CI 29.7-30.6) and a lifetime risk of 62.5% (95% CI 62.1-62.9). The direct inpatient cost of ASCVD patients includes a median 3,033 USD, with highest median costs in the STEMI subgroup (3,270 USD)., Conclusions: A significant number of Indonesian ASCVD patients exhibited notably high 10-year and lifetime risks of experiencing a major cardiovascular event. Combined with the direct inpatient cost, therapy optimization is crucially needed to mitigate these risks and further cost burden., Competing Interests: The authors declare that this study received funding from Novartis Indonesia. The funder was involved in the creation of ideas and study design, but was not involved further in data collection, analysis, interpretation, and the writing of this article., (© 2024 Dwiputra, Desandri, Hartopo, Juzar, Alkatiri, Zuhdi, Ramadhan, Kenconosari, Phowira and Widyantoro.)

Background: Serum lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population, its association with ASCVD incidence in Chinese maintenance hemodialysis (MHD) patients remains unclear. We aimed to evaluate the relationship between Lp(a) levels and ASCVD incidence among MHD patients in Beijing, China., Methods: This retrospective, observational cohort study included MHD patients at Beijing Tongren Hospital from January 1, 2013 to December 1, 2020, and followed until December 1,2023. The primary outcome was ASCVD occurrence. Kaplan-Meier survival analysis was used to evaluate ASCVD-free survival in MHD patients, with stratification based on Lp(a) levels. Cox regression analyses were conducted to assess the association between Lp(a) levels and the occurrence of ASCVD., Results: A total of 265 patients were enrolled in the study. The median follow-up period were 71 months.78 (29.4%) participants experienced ASCVD events, and 118 (47%) patients died, with 58 (49.1%) deaths attributed to ASCVD. Spearman rank correlation analyses revealed positive correlations between serum Lp(a) levels and LDL-c levels, and negative correlations with hemoglobin, triglyceride, serum iron, serum creatinine, and albumin levels. Multivariate Cox regression analysis showed that Lp(a) levels ≥ 30 mg/L, increased age, decreased serum albumin levels, and a history of diabetes mellitus were significantly associated with ASCVD incidence., Conclusions: This study demonstrated an independent and positive association between serum Lp(a) levels and the risk of ASCVD in MHD patients, suggesting that serum Lp(a) could potentially serve as a clinical biomarker for estimating ASCVD risk in this population., (© 2024. The Author(s).)

A sedentary lifestyle, low levels of physical activity and fitness, poor dietary patterns, and psychosocial stress are strongly associated with increased morbidity and mortality from atherosclerotic cardiovascular disease (ASCVD). Conversely, engaging in regular physical activity, maintaining optimal fitness levels, adhering to a heart-healthy dietary pattern, effectively managing body weight, ensuring adequate sleep, implementing stress-reduction strategies, and addressing psychosocial risk factors are associated with a reduced risk of ASCVD. This comprehensive review synthesizes current evidence from large observational studies and randomized controlled trials on lifestyle factors as determinants of ASCVD health. It also briefly reviews mechanistic insights into how factors such as low shear stress, increased reactive oxygen species production, chronic inflammation, platelets and coagulation activation, endothelial dysfunction, and sympathetic hyperactivity contribute to the initiation and exacerbation of ASCVD risk factors. These include obesity, hyperglycemia, type 2 diabetes, hypertension, and dyslipidemia, subsequently leading to the development and progression of atherosclerosis, ultimately resulting in chronic ASCVD or acute cardiovascular events. To bridge the translational gap between epidemiologic and trial-based evidence and clinical practice, practical recommendations are summarized to facilitate the translation of scientific knowledge into actionable interventions to promote ASCVD health. Acknowledged is the gap between the evidence-based knowledge and adoption within healthcare systems, which remains a crucial objective in advancing cardiovascular health at the population level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Atherosclerotic cardiovascular disease (ASCVD) remains the most common cause of death in women. Pregnancy is an exposure unique to women leading to significant changes in maternal cardiovascular function. However, studies of the relationship between the number of pregnancies and ASCVD are rare. We aimed to clarify the association between the number of pregnancies and ASCVD. Methods: In this cross-sectional study, we used publicly available data from the National Health and Nutrition Examination Survey from 1999 to 2018. The number of pregnancies was divided into 0 (reference), 1, 2-3, 4-5, or ≥6, to create more stable estimates. A multiple logistic regression approach was used to examine the correlation between pregnancy and ASCVD in women aged 45 years or older who reported no menstruation in the past 12 months due to menopause, as well as in those aged 55 years or older, encompassing various age groups. We also separately estimated the association between the exposure of pregnancy and individual components of ASCVD. Results: In this study, age-adjusted data showed that women with six or more pregnancies had a doubled risk (odds ratio [OR]: 2.07) of ASCVD. The risk remained elevated at 1.69 times in women with four to five pregnancies and further increased to 1.90 times in women with six or more pregnancies, after adjusting for social factors. Similar patterns were observed when considering reproductive health and cardiovascular risk factors. Across the full population, every model that accounted for these variables consistently indicated that with an increasing number of pregnancies, we observed higher ORs for ASCVD risk (all p values <0.05). Conclusions: A higher number of pregnancies was associated with a higher risk of ASCVD after menopause, especially among women aged 45-64 years. Moreover, this association is particularly significant in the risk of stroke, cardiovascular heart disease, and heart attack.

Background: Studies assessing equity in the prevention of atherosclerotic cardiovascular disease (ASCVD) for Latinos living in the USA collectively yield mixed results. Latino persons are diverse in many ways that may influence cardiovascular health. The intersection of Latino nativity and ASCVD prevention is understudied., Objective: To determine whether disparities in ASCVD screening, detection, and prescribing differ for US Latinos by country of birth., Design: A retrospective cohort design utilizing 2014-2020 electronic health record data from a network of 320 community health centers across 12 states. Analyses occurred October 1, 2022, to September 30, 2023., Participants: Non-Hispanic White and Latino adults age 20-75 years, born in Cuba, Dominican Republic, El Salvador, Guatemala, Honduras, Mexico, and the USA., Exposures: Ethnicity and country of birth., Main Measures: Outcome measures included prevalence of statin eligibility, of having insufficient data to establish eligibility, odds of having a documented statin prescription, and rates of statin prescriptions and refills. We used covariate-adjusted logistic and generalized estimating equations logistic and negative binomial regressions to generate absolute and relative measures., Key Results: Among 108,672 adults, 23% (n = 25,422) were statin eligible for primary or secondary prevention of ASCVD using American College of Cardiology/American Heart Association guidelines. Latinos, born in and outside the USA were more likely eligible than Non-Hispanic White patients were (US-born Latino OR = 1.55 (95% CI = 1.37-1.75); non-US-born Latino OR = 1.63 (95% CI = 1.34-1.98)). The eligibility criteria that was met differed by ethnicity and nativity. Latinos overall were less likely missing data to establish eligibility and differences were again observed by specific non-US country of origin. Among those eligible, we observed no statistical difference in statin prescribing between US-born Latinos and non-Hispanic White persons; however, disparities varied by specific non-US country of origin., Conclusion: Efforts to improve Latino health in the USA will require approaches for preventing and reversing cardiovascular risk factors, and statin initiation that are Latino subgroup specific., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Aims: Familial Hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism that causes an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Although early diagnosis and treatment of FH can significantly improve the cardiovascular prognosis, this disorder is underdiagnosed and undertreated. For these reasons the Italian Society for the Study of Atherosclerosis (SISA) assembled a Consensus Panel with the task to provide guidelines for FH diagnosis and treatment., Data Synthesis: Our guidelines include: i) an overview of the genetic complexity of FH and the role of candidate genes involved in LDL metabolism; ii) the prevalence of FH in the population; iii) the clinical criteria adopted for the diagnosis of FH; iv) the screening for ASCVD and the role of cardiovascular imaging techniques; v) the role of molecular diagnosis in establishing the genetic bases of the disorder; vi) the current therapeutic options in both heterozygous and homozygous FH. Treatment strategies and targets are currently based on low-density lipoprotein cholesterol (LDL-C) levels, as the prognosis of FH largely depends on the magnitude of LDL-C reduction achieved by lipid-lowering therapies. Statins with or without ezetimibe are the mainstay of treatment. Addition of novel medications like PCSK9 inhibitors, ANGPTL3 inhibitors or lomitapide in homozygous FH results in a further reduction of LDL-C levels. LDL apheresis is indicated in FH patients with inadequate response to cholesterol-lowering therapies., Conclusion: FH is a common, treatable genetic disorder and, although our understanding of this disease has improved, many challenges still remain with regard to its identification and management., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

This study aims to investigated the association between sedentary behavior (SB) and predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk and determine whether the associations differ by how the behavior is accumulated, in US middle-aged and older adults. Cross-sectional data were derived from national health and nutrition examination survey (NHANES) 2003-2006. Seven-day wearing of accelerometer was used to assess SB pattern, exported as total SB, bouts of 1-9, 10-29, 30-59 and ≥ 60 min SB. Predicted 10-year ASCVD risk was calculated using validated pooled cohort equations. Linear regression was used to estimate adjusted coefficients. A total of 2327 participants were enrolled with mean age of 56.9 and mean predicted 10-year ASCVD risk of 10.7%. We observed significant associations of total SB and its longer accumulated patterns with higher 10-year predicted ASCVD risk, in a linear fashion and independent of a list of covariates. A 30 min increment per day of total SB, bouts in 10-29, bouts in 30-59 and bouts in ≥ 60 min were associated with 0.14, 0.14, 0.23 and 0.12% higher multivariable-adjusted 10-year predicted ASCVD risk. There are significant associations of total SB as well as its longer accumulated patterns with higher 10-year predicted ASCVD risk, independent of a list of covariates and in a linear fashion. The result indicates that reducing total sedentary time and interrupting long duration of prolonged SB, could be meaningful to for public guideline to lessen the personal and public health burden of cardiovascular health., (© 2024. The Author(s).)

The congenital anomalous origin of the right coronary artery (AORCA) with an incongruous course is a rare malformation that can manifest as exertional chest pain, syncope, arrhythmias, heart failure, and sudden cardiac death. We present a case of a 42-year-old male with a history of hypercholesterolemia who presented with chest pain and dizziness upon exertion for two weeks. The physical examination was unremarkable, and the patient was hemodynamically stable. Initial blood tests were normal. Electrocardiogram (ECG) showed sinus bradycardia at 56 bpm without ST or T wave changes. A cardiac stress test indicated antero-apical inducible ischemia with a moderate probability of stress-induced ischemia. Computed tomography angiography (CTA) revealed an AORCA with a high interarterial course between the pulmonary artery and the aorta. Subsequent left heart catheterization confirmed the anomalous origin and revealed atherosclerotic disease. This anomaly was identified as the cause of the patient's symptoms due to the compression of the right coronary artery (RCA). The patient was treated with aspirin and statin and underwent successful internal mammary artery-RCA bypass grafting. Postoperatively, the patient's symptoms resolved, and there were no further episodes of chest pain., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bilal et al.)

The incidence of atherosclerotic cardiovascular disease is increasing globally, especially in low- and middle-income countries, despite significant efforts to reduce traditional risk factors. Premature subclinical atherosclerosis has been documented in association with several viral infections. The magnitude of the recent COVID-19 pandemic has highlighted the need to understand the association between SARS-CoV-2 and atherosclerosis. This review examines various pathophysiological mechanisms, including endothelial dysfunction, platelet activation, and inflammatory and immune hyperactivation triggered by SARS-CoV-2 infection, with specific attention on their roles in initiating and promoting the progression of atherosclerotic lesions. Additionally, it addresses the various pathogenic mechanisms by which COVID-19 in the post-acute phase may contribute to the development of vascular disease. Understanding the overlap of these syndromes may enable novel therapeutic strategies. We further explore the need for guidelines for closer follow-up for the often-overlooked evidence of atherosclerotic cardiovascular disease among patients with recent COVID-19, particularly those with cardiometabolic risk factors., Competing Interests: This study was supported by the 10.13039/100006492National Institute of Allergy and Infectious Diseases (NIAID)/10.13039/100000002National Institutes of Health (NIH) grant K24AI143447 to Dr Karakousis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Recent evidence has linked changes in plasma lecithin-cholesterol acyltransferase (LCAT) and paraoxonase-1 (PON-1) levels with increased risk for development of premature atherosclerotic cardiovascular disease (ASCVD) in different populations. However, studies on this in Nigeria and sub-Saharan Africa are scarce., Objective: This study assessed the association between reduced plasma LCAT and PON-1 levels and an increased risk of ASCVD, and their potential as biomarkers for ASCVD., Methods: Atherosclerotic cardiovascular disease patients and healthy controls were randomly selected for this cross-sectional case-control study from the Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria, between March 2022 and March 2023. Plasma LCAT and PON-1 were determined by sandwich enzyme-linked immunosorbent assay, while the lipid profile was measured by spectrophotometry., Results: A total of 153 ASCVD patients (mean age: 52.92 ± 10.24 years) and 50 healthy controls (mean age: 46.96 ± 11.05 years) were included in the analyses. Stastistically significant increases were observed in the mean body weight, hip circumference, waist circumference, waist-to-hip ratio, body mass index, diastolic and systolic blood pressure (all p ≤ 0.001), and pulse rate ( p = 0.003) compared to the control values. Statistically significant increases were also observed in the mean plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol (all p ≤ 0.001). In contrast, the mean plasma high-density lipoprotein cholesterol, LCAT, and PON-1 ( p ≤ 0.001) were notably reduced compared to the control values., Conclusion: The present study provides supportive evidence that changes in plasma LCAT and PON-1 could predispose individuals to risk of premature ASCVD., What This Study Adds: Plasma LCAT and PON-1 may serve as independent markers or complement other established cardiovascular disease markers to discriminate the risk of ASCVD when it is unclear., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Background: There is paucity of data on the prevalence of novel and traditional cardiovascular risk factors in young women with atherosclerotic cardiovascular disease (ASCVD) in the Middle East. We sought to evaluate clinical profiles and prevalence of novel and traditional risk factors in Middle Eastern young women with ASCVD compared with age-matched controls., Methods: Women 18-50 years of age who have ASCVD were enrolled and each was aged-matched with two women with no ASCVD. Prevalence of novel and traditional risk factors was compared in the two groups. Multivariable analyzes examined the independent association of 16 factors with ASCVD., Results: Of 627 young women enrolled mean age 44.1 ± 5.2 years; 209 had ASCVD and 418 served as controls. Women with ASCVD had significantly higher prevalence of five of the studied traditional risk factors (hypertension, type 2 diabetes [T2D], smoking, low-density lipoprotein cholesterol serum levels, and family history of premature ASCVD [FHx]) than women with no ASCVD. Additionally, of the 11 novel and psychosocial risk factors studied, four showed significantly higher prevalence in young women with ASCVD (preterm delivery, hypertensive disease of pregnancy gestational diabetes, and low level of education). Multivariable analyzes showed hypertension, T2D, smoking, FHx, persistent weight gain after pregnancy and low level of education were independently associated with ASCVD., Conclusions: In this study of young Middle Eastern women; traditional risk factors as well as persistent weight gain after pregnancy were more prevalent in women with ASCVD compared with controls.The study is registered with ClinicalTrials.gov, unique identifier number NCT04975503., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

During the past 30 years, several developments have occurred in the antiplatelet field, including the role of aspirin in primary prevention of atherosclerotic cardiovascular disease. There have been several attempts to develop antiplatelet drugs more effective and safer than aspirin and a shift in emphasis from efficacy to safety, advocating aspirin-free antiplatelet regimens after percutaneous coronary intervention. Evidence supporting a chemopreventive effect of low-dose aspirin against colorectal (and other digestive tract) cancer has also strengthened. The aim of this article is to revisit the role of aspirin in the prevention of atherothrombosis across the cardiovascular risk continuum, in view of developments in the antiplatelet field. The review will offer a clinical perspective on aspirin's mechanism of action, pharmacokinetics, and pharmacodynamics. This will be followed by a detailed discussion of its clinical efficacy and safety., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a), and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses the diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Competing Interests: Funding Support and Author Disclosures FINEARTS-HF was sponsored by Bayer AG. DELIVER was sponsored by AstraZeneca. PARAGON-HF was sponsored by Novartis. TOPCAT was sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Health. I-PRESERVE was sponsored by Bristol Myers Squibb and Sanofi. Dr Claggett has received personal fees from Alnylam, Cardior, Cardurion, Corvia, Cytokinetics, CVRx, Intellia, and Rocket outside the submitted work. Dr McCausland has received research grants from NIDDK, Satellite Healthcare, Fifth Eye, Novartis, and Lexicon paid directly to his institution; has received expert witness fees from Rubin-Anders Scientific; and has received consulting fees from GlaxoSmithKline and Zydus Therapeutics. Dr Anand has received consultancy fees from Amgen, ARCA, AstraZeneca, Boehringer Ingelheim, Boston Scientific, LivaNova, Novartis, Rockwell Medical, and Zensun. Dr Desai has received honoraria for consulting or speaking from Abbott, AstraZeneca, Alnylam Pharmaceuticals, Avidity Biopharma, Axon Therapeutics, Bayer, Biofourmis, Boston Scientific, GlaxoSmithKline, Medpace, Medtronic, Merck, New Amsterdam Pharma, Novartis, Parexel, Regeneron, River2Renal, Roche, scPharmaceuticals, Verily, Veristat, and Zydus; and has received institutional research grant support from Abbott, Alnylam, AstraZeneca, Bayer, Novartis, and Pfizer. Dr Jhund received speaker fees from Novartis, AstraZeneca, Alkem metabolomics, Sun Pharmaceuticals and ProAdWise Communications; his employer, University of Glasgow has been paid for his time working on clinical trials by Novartis, AstraZeneca, Bayer, and NovoNordisk; has received grants from Analog Devices Inc, Boehringer Ingelheim, and Roche Diagnostics outside the submitted work, and is Director GCTP Ltd. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Novo Nordisk and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and has served as cofounder and nonexecutive director of Us2.ai. Dr Pfeffer has received research grant support (via institution) from Lexicon and Novartis; is a consultant to Alnylam Pharmaceuticals, Apnimed, AstraZeneca, Boehringer Ingelheim, Eli Lilly Alliance, DalCor, Intellia, NHLBI CONNECTs (Master Protocol Committee), Novartis, and Novo Nordisk; and holds equity in DalCor. Dr Pitt has served as a consultant for Bayer, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lexicon, Anacardia, and G3 Therapeutics; has served as a consultant and has received stock options or stocks from Sea Star Medical, Vifor, scPharmaceuticals, SQ Innovation, KBP Biosciences, Sarfez, Cereno Scientific, Prointel, and Brainstorm Medical; and holds a U.S. Patent (9931412-site-specific delivery of eplerenone to the myocardium) and a U.S. Patent pending (63/045,783 histone modulating agents for the prevention and treatment of organ damage). Dr Zannad has received personal fees from steering committees during the conduct of the study; has received personal fees from Boehringer, Bristol Myers Squibb, CVRx, Cardior, Cereno, Cellprothera, Merck, Owkin, Roche, and Northsea, outside the submitted work; has stock options from G3 Therapeutics; has equities from Cereno, Cardiorenal, and Eshmoun Clinical research; and is a founder of CVCT. Dr Zile has received research funding from Novartis; and has served as a consultant for Novartis, Abbott, Boston Scientific, CVRx, EBR, Endotronix, Ironwood, Merck, Medtronic, and Myokardia V Wave. Dr Bomfim Wirtz, Mr Lay-Flurrie, and Dr Viswanathan are full-time employees of Bayer AG. Dr McMurray has received committee and/or employee fees from AstraZeneca, Novartis, Amgen, Bayer, Cardurion, Cytokinetics, GSK, and KBP Biosciences; and has received personal fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals Ltd, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals & Pharmaceuticals Ltd, Lupin Pharmaceuticals, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, Translational Medicine Academy, Alynylam Pharmaceuticals, Bayer, BMS, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, River 2 Renal Corp, Global Clinical Trial Partners Ltd, and George Clinical PTY Ltd outside the submitted work. Dr Solomon has received research grants from Alexion, Alnylam Pharmaceuticals, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Boston Scientific, Cytokinetics, Edgewise, Eidos, Gossamer, GlaxoSmithKline, Ionis, Eli Lilly, MyoKardia, NIH/NHLBI, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Eli Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. Dr Vaduganathan has received research grant support, has served on advisory boards, or has had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and has participated on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: The coexistence of multiple standard modifiable risk factors (SMuRFs),classical and novel risk factors (RFs) for atherosclerotic cardiovascular disease (ASCVD) is common in the Middle East (ME). There is a paucity of data on the coexistence of these RFs in ME young women., Aim: Comparing the prevalence and the statistical patterns of the SMuRFs, classical and novel RFs in target population., Methods: In this case-control (1:2) study, consecutive young women aged 18-50 years were enrolled in 12 centers (July 2021 to October 2023). Prevalence and coexistence of 19 RFs were compared between cases with ASCVD and their controls. The RFs included SMuRFs (hypertension, type 2 diabetes, dyslipidemia, and cigarette smoking), other classical RF (obesity, family history of premature ASCVD, and physical inactivity), novel RFs and social determinants of health (health insurance, place of residence, depression, and level of education)., Results: The study included 627 subjects; 209 had ASCVD (median age 46 years, IQR 49-42 years) and 418 controls (median age 45 years, IQR 48-41 years). The presence of 1-2 RFs; (ASCVD: 63.2%, Control: 54.1%, p=0.037) and 3-4 RFs; (ASCVD: 27.8%, Control: 3.3%, p < 0.001) SMuRFs was more prevalent in women with ASCVD. Similarly, the presence of 4-5 RFs; (ASCVD: 40.7%, Control: 14.6%, p<0.001), and 6-7 (ASCVD: 10.5%, Control: 1%, p < 0.001). The classical RF were also significantly common in these women. The distribution of multiple novel RF was not statistically significant across both groups. Finally, regarding the socioeconomic RFs in women with ASCVDs, the presence of 1-2 RFs (ASCVD: 59.8%, Control: 76.1%, p < 0.001) was significantly less common while the presence of 3-4 RFs (ASCVD: 39.2%, Control: 21.8%, p < 0.001) was vastly more common., Conclusion: An elevated rate of coexistence of classical RF in the case group, mainly socioeconomic and SMuRFs. By managing them primary and secondary ASCVDs prevention attained., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Al-Shudifat et al.)

Atherosclerotic cardiovascular disease (ASCVD) remains the major cause of premature death and disability; effective cardiovascular (CV) risk prevention is fundamental. The World Heart Federation (WHF) Cholesterol Roadmap provides a framework for national policy development and aims to achieve ASCVD prevention. At the invitation of the WHF, a group of experts from the Portuguese Society of Cardiology (SPC), addressed the cholesterol burden at nationally and discussed possible strategies to include in a Portuguese cholesterol roadmap. The literature review showed that the cholesterol burden in Portugal is high and especially uncontrolled in those with the highest CV risk. An infographic scorecard was built to include in the WHF collection, for a clear idea about CV risk and cholesterol burden in Portugal, which would also be useful for health policy advocacy. The expert discussion and preventive strategies proposal followed the five pillars of the WHF document: awareness improvement; population-based approaches for CV risk and cholesterol; risk assessment/population screening; system-level approaches; surveillance of cholesterol and ASCVD outcomes. These strategies were debated by all the expert participants, with the goal of creating a national cholesterol roadmap to be used for advocacy and as a guide for CV prevention. Several key recommendations were outlined: include all stakeholders in a multidisciplinary national program; create a structured activities plan to increase awareness in the population; improve the quality of continuous CV health education; increase the interaction between different health professionals and non-health professionals; increment the referral of patients to cardiac rehabilitation; screen cholesterol levels in the general population, especially high-risk groups; promote patient self-care, engage with patients' associations; use specific social networks to spread information widely; create a national database of cholesterol levels with systematic registry of CV events; redefine strategies based on the evaluation of results; create and involve more patients' associations - invert the pyramid order. In conclusion, ASCVD and the cholesterol burden remain a strong global issue in Portugal, requiring the involvement of multiple stakeholders in prevention. The Portuguese cholesterol roadmap can provide some solutions to help urgently mitigate the problem. Population-based approaches to improve awareness and CV risk assessment and surveillance of cholesterol and ASCVD outcomes are key factors in this change. A call to action is clearly needed to fight hypercholesterolemia and ASCVD burden., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

Shared decision-making (SDM) and multidisciplinary team-based care delivery are recommended across several cardiology clinical practice guidelines. However, evidence for benefit and guidance on implementation are limited. Informed consent, the use of patient decision aids, or the documentation of these elements for governmental or societal agencies may be conflated as SDM. SDM is a bidirectional exchange between experts: patients are the experts on their goals, values, and preferences, and clinicians provide their expertise on clinical factors. In this Expert Panel perspective, we review the current state of SDM in team-based cardiovascular care and propose best practice recommendations for multidisciplinary team implementation of SDM., Competing Interests: Dr Perpetua has been a consultant for Edwards Lifesciences and is a consultant for Abbott Vascular. Ms. Palmer is a consultant for Edwards Lifesciences. Dr Beckman is a consultant for Norvartis, Janssen, and JanOne. Dr Keegan is a consultant for Edwards Lifesciences and Abbott Vascular. Dr Guibone is a consultant for Medtronic and Abbott Vascular. Dr Lauck is a consultant for Edwards Lifesciences. Dr Le has received research grant funding from Janssen and is a consultant for 10.13039/100008272Novartis. Dr Lindman is supported by R01AG073633 from the 10.13039/100000002National Institutes of Health and has been a consultant for and received investigator-initiated research grants from 10.13039/100006520Edwards Lifesciences. Dr Wyman has been a consultant for Edwards Lifesciences and Boston Scientific. Dr Gulati has been a consultant for Esperion, Boehringer Ingelheim, and Medtronic. There was no funding support for this expert panel. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Lipid-related risk and residual cardiovascular risk remain high in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). Significant treatment gaps exist in implementation of pluripotent and effective therapies that reduce these risks., Objective: This study evaluates the efficacy and impact of a dedicated, standalone cardiometabolic clinic designed to address treatment gaps through streamlined management and optimization of treatment strategies., Methods: We retrospectively collected data from the first 400 patients with T2D and ASCVD who underwent treatment at the clinic and presented for at least one follow-up visit. These patients were primarily managed for their cardiometabolic risks and received intensified lipid-lowering therapies, including adjunct non-statin therapies., Results: Significant findings included increased use of glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) to 84 % and 65 %, respectively, with 94 % of patients eventually on one therapy and 55 % on dual therapy. Increases in lipid-lowering therapies led to 89 % of patients achieving low-density lipoprotein cholesterol levels below patient-specific thresholds for intensification., Conclusion: This care model effectively manages high-risk patient needs, achieving significant intensification of lipid-lowering therapies and broad use of cardiometabolic drugs, and highlights the clinic's potential to serve as a model for similar high-risk populations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Taher Modarressi reports a relationship with Novo Nordisk Inc that includes: board membership and consulting or advisory. Taher Modarressi reports a relationship with Eli Lilly and Company that includes: speaking and lecture fees. Taher Modarressi reports a relationship with AstraZeneca Pharmaceuticals LP that includes: speaking and lecture fees. Taher Modarressi reports a relationship with Novartis Pharmaceuticals Corporation that includes: board membership. Taher Modarressi reports a relationship with Abbott Laboratories that includes: speaking and lecture fees. Taher Modarressi reports a relationship with CRISPR Therapeutics that includes: consulting or advisory. Taher Modarressi reports a relationship with Amgen Inc that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction: Patients with type 2 diabetes (T2DM) are at high risk of atherosclerotic cardiovascular disease (ASCVD) and cardiovascular death. Cardiovascular protection is a key objective in T2DM., Areas Covered: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have proven their efficacy in reducing major cardiovascular events in high-risk patients with T2DM in placebo-controlled trials, a finding confirmed in observational studies compared with other glucose-lowering agents. Overall, GLP-1RAs have a good safety profile associated with a favorable benefit/risk ratio for the management of T2DM, even if their cost-effectiveness might be questionable. International guidelines recommend GLP-1RAs as preferred glucose-lowering agents in patients with ASCVD and as a valuable alternative in overweight/obese patients with T2DM. However, real-life studies worldwide revealed that only a minority of patients receive a GLP-1RA, despite a positive trend for increased prescriptions in recent years. Surprisingly, however, fewer patients with established ASCVD are treated with these cardioprotective antihyperglycemic agents versus patients without ASCVD., Expert Opinion: The reasons for GLP-1RA underuse in clinical practice are multiple. Multifaceted and coordinated interventions targeting all actors of the health-care system must be implemented to stimulate the adoption of GLP-1RAs as part of routine cardiovascular care among patients with T2DM, especially in those with ASCVD.

Background and Aims: It has been reported that maresin 1 (MaR1) is able to protect against the development of atherogenesis in cellular and animal models. This study was performed to investigate whether plasma MaR1 is associated with the risk of atherosclerotic cardiovascular disease (ASCVD) at the population level., Methods and Results: The study included 2822 non-ASCVD participants from a community-based cohort who were followed for about 8 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for ASCVD events according to baseline MaR1 quartiles were calculated using the Cox proportional hazards model. During follow-up, a total of 290 new ASCVD cases were identified. The restricted cubic spline analysis indicated a linear dose-response association between plasma MaR1 and incident ASCVD. In addition, the adjusted-HR (95% CI) for ASCVD events associated with one standard deviation increase in MaR1 was 0.79 (0.68-0.91). Moreover, the adjusted-HRs (95% CIs) for ASCVD events associated with the second, third and fourth quartiles versus the first quartile of plasma MaR1 were 1.00, 1.04 (0.76, 1.42), 0.88 (0.64, 1.22) and 0.58 (0.41, 0.84), respectively. Mediation analyses showed that the association between MaR1 and incident ASCVD was partially mediated by small dense low-density lipoprotein cholesterol, with a mediation proportion of 9.23%. Further, the net reclassification improvement and integrated discrimination improvement of ASCVD risk were significantly improved when MaR1 was added to basic model established by conventional risk factors (all p < 0.01)., Conclusions: Elevated plasma MaR1 concentrations are associated with a lower risk of ASCVD development., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Polycystic ovary syndrome (PCOS) is a common endocrinopathy worldwide with a heterogeneous clinical presentation including reproductive, metabolic, and endocrine elements. However, the assessment and management of PCOS remains inconsistent, with many women undiagnosed and untreated. We now also understand that the management of PCOS should extend throughout a woman's lifespan as many elements of the syndrome persist after menopause. Management has traditionally focused on the treatment of hyperandrogenism and oligomenorrhea. Women with PCOS often have dyslipidemia, hypertension, obesity, and metabolic syndrome, which may be worsened by the hormonal abnormalities, and are therefore at higher risk for cardiovascular disease morbidity and mortality, a risk that increases after menopause. While treatment with hormonal therapy, in particular combined oral contraceptives, may improve cardiovascular risk factors, management plans should incorporate specific diagnosis and management of these factors, if present, because of the strong contribution to the risk for atherosclerotic cardiovascular disease. Given the complexities of the syndrome, optimal management often requires a multi-disciplinary approach including the lipid and cardiometabolic specialist to provide counseling and support for lifestyle modification along with pharmacologic therapy as indicated to address the full range of any reproductive, endocrine, and cardiometabolic abnormalities., Competing Interests: Declaration of competing interest Merle Myerson Consultant, Novartis Rodis Paparodis none Robert Block research support: Novartis, Ionis, Amgen Dean Karalis consultant, Novartis Guy Mintz Janssen Pharmaceuticals (Speaker), Esperion (Advisory Board) Eliot Brinton Research: Regeneron. Consultant/advisor: 89bio, Amarin, Amgen, Amryt, CSL Behring, Immunovant, Merck, New Amsterdam, Regeneron. Speakers’ bureau: Amarin, Amgen, Amryt, CSL Behring Robert Wild May Health (Consultant), Mass General Partners (Biostatistical Consultant), Quest (contract for lipid measurement), (Copyright © 2024. Published by Elsevier Inc.)

Patients attending vascular or diabetic foot clinics commonly have atherosclerotic disease, are at increased risk of cardiovascular disease (CVD), merit high-intensity lipid-modifying therapy to maintain secondary prevention targets and are often sub optimally treated in primary care. We set out to assess the impact of a pharmacist led lipid optimisation clinic in these patients in an area with high levels of social deprivation., Methods: We performed a clinical cohort study to assess the effectiveness of a pharmacist led clinic to optimise lipid lowering therapy by optimising of statin therapy and commencing additional lipid lowering therapy if applicable with monitoring of blood lipid profiles., Results: Of the 216 patients (166 [77%] on statins) triaged by the pharmacist, 175 (81%) had non-high-density lipoprotein (non-HDL) cholesterol levels above the target value of 97 mg/dL (2.5 mmol/L) with a mean non-HDL cholesterol level of 135.73 mg/dL (3.51 mmol/L). Pre optimisation by the prescribing clinical pharmacist 41/216 (19%) patients were at target with a mean non-HDL cholesterol of 135.5 mg/dL improving to 92/137 (67%) patients achieving the target non-HDL cholesterol level with a mean post optimisation non-HDL cholesterol of 94.35 mg/dL (2.44 mmol/L), odds ratio (OR) for being at target 8.67 (95% CI 5.30-14.20). The calculated low-density lipoprotein cholesterol levels (Friedewald) demonstrated a mean reduction of 35.19 (95% CI 29.23-41.38) mg/dL (0.91 [95% CI 0.76-1.07] mmol/L). Proportion on high intensity statin increased from 65 out of 166 (39%) to 129 of 170 (76%) at follow up (OR 4.89 [3.06-7.82]), equivalent to an number needed to treat = 3., Conclusions: A pharmacist led service in undertreated and clinically challenging vascular and diabetic foot patients in an area of high social deprivation produced significant improvements in utilization of high intensity statin and other lipid lowering therapies and attainment of lipid goals., Competing Interests: Declarations of competing interest None, (Copyright © 2024. Published by Elsevier Inc.)

Purpose of Review: Low-density lipoprotein (LDL) poses a risk for atherosclerotic cardiovascular disease (ASCVD). As LDL comprises various subtypes differing in charge, density, and size, understanding their specific impact on ASCVD is crucial. Two highly atherogenic LDL subtypes-electronegative LDL (L5) and Lp(a)-induce vascular cell apoptosis and atherosclerotic changes independent of plasma cholesterol levels, and their mechanisms warrant further investigation. Here, we have compared the roles of L5 and Lp(a) in the development of ASCVD., Recent Findings: Lp(a) tends to accumulate in artery walls, promoting plaque formation and potentially triggering atherosclerosis progression through prothrombotic or antifibrinolytic effects. High Lp(a) levels correlate with calcific aortic stenosis and atherothrombosis risk. L5 can induce endothelial cell apoptosis and increase vascular permeability, inflammation, and atherogenesis, playing a key role in initiating atherosclerosis. Elevated L5 levels in certain high-risk populations may serve as a distinctive predictor of ASCVD. L5 and Lp(a) are both atherogenic lipoproteins contributing to ASCVD through distinct mechanisms. Lp(a) has garnered attention, but equal consideration should be given to L5., (© 2024. The Author(s).)

The role of lipoprotein (a) [Lp(a)] in cerebrovascular disease is a topic of importance. In this narrative review, pertinent studies have been leveraged to comprehensively examine this relationship from diverse perspectives.Lp(a) shares structural traits with low-density lipoprotein cholesterol. Lp(a) is synthesized by hepatocytes, and its plasma levels are genetically determined by the LPA gene, which produces apolipoprotein (a).Numerous epidemiological studies have confirmed the positive correlation between elevated serum Lp(a) levels and the occurrence or recurrence of cerebrovascular events, especially ischemic strokes, in adults. It should be noted that the correlation strength varies among studies and is marginal in Mendelian randomization studies.Regarding pediatric patients, screening is currently limited to those with a relevant medical history. Lp(a) seems to play a significant role in the pathogenesis of arterial ischemic stroke in children because environmental thrombotic and atherogenic factors are generally not present.Phase 3 trials of novel Lp(a) targeting agents, such as pelacarsen and olpasiran, are anticipated to demonstrate their efficacy in reducing the incidence of stroke. Given the richness of the literature, new guidelines regarding Lp(a) screening and management in targeted populations are warranted to provide more effective primary and secondary prevention., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Background: Although a coronary artery calcium (CAC) of ≥1,000 is a subclinical atherosclerosis threshold to consider combination lipid-lowering therapy, differentiating very high from high atherosclerotic cardiovascular disease (ASCVD) risk in this patient population is not well-defined., Objectives: Among persons with a CAC of ≥1,000, the authors sought to identify risk factors equating with very high-risk ASCVD mortality rates., Methods: The authors studied 2,246 asymptomatic patients with a CAC of ≥1,000 from the CAC Consortium without a prior ASCVD event. Cox proportional hazards regression modelling was performed for ASCVD mortality during a median follow-up of 11.3 years. Crude ASCVD mortality rates were compared with those reported for secondary prevention trial patients classified as very high risk, defined by ≥2 major ASCVD events or 1 major event and ≥2 high-risk conditions (1.4 per 100 person-years)., Results: The mean age was 66.6 years, 14% were female, and 10% were non-White. The median CAC score was 1,592 and 6% had severe left main (LM) CAC (vessel-specific CAC ≥300). Diabetes (HR: 2.04 [95% CI: 1.47-2.83]) and severe LM CAC (HR: 2.32 [95% CI: 1.51-3.55]) were associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95% CI: 0.7-0.9), although higher rates were observed for diabetes (1.4 [95% CI: 0.8-1.9]), severe LM CAC (1.3 [95% CI: 0.6-2.0]), and both diabetes and severe LM CAC (7.1 [95% CI: 3.4-10.8])., Conclusions: Among asymptomatic patients with a CAC of ≥1,000 without a prior index event, diabetes, and severe LM CAC define very high risk ASCVD, identifying individuals who may benefit from more intensive prevention therapies across several domains, including low-density lipoprotein-cholesterol lowering., Competing Interests: Funding Support and Author Disclosures This project was supported in part by a research grant from the National Institutes of Health (NIH)-National Heart, Lung, and Blood Institute (NHLBI) [L30 HL110027]. Dr Blaha has received grants from the National Institutes of Health, U.S. Food and Drug Administration, American Heart Association, and Aetna Foundation; grants and personal fees from Amgen; and personal fees from Sanofi, Regeneron, Novartis, Bayer, and Novo Nordisk outside the submitted work. Dr Dzaye has received support from National Institutes of Health grant T32 HL007227. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Emerging evidence highlights the pivotal roles of long non-coding RNAs (lncRNAs) in lipid metabolism. Apoprotein C3 (ApoC3) is a well-established therapeutic target for hypertriglyceridemia and exhibits a strong association with cardiovascular disease. However, the exact mechanisms via which the lncRNAs control ApoC3 expression remain unclear., Methods: We identified a novel long noncoding RNA (lncRNA), GM47544, within the ApoA1/C3/A4/A5 gene cluster. Subsequently, the effect of GM47544 on intracellular triglyceride metabolism was analyzed. The diet-induced mouse models of hyperlipidemia and atherosclerosis were established to explore the effect of GM47544 on dyslipidemia and plaque formation in vivo. The molecular mechanism was explored through RNA sequencing, immunoprecipitation, RNA pull-down assay, and RNA immunoprecipitation., Results: GM47544 was overexpressed under high-fat stimulation. GM47544 effectively improved hepatic steatosis, reduced blood lipid levels, and alleviated atherosclerosis in vitro and in vivo. Mechanistically, GM47544 directly bound to ApoC3 and facilitated the ubiquitination at lysine 79 in ApoC3, thereby facilitating ApoC3 degradation via the ubiquitin-proteasome pathway. Moreover, we identified AP006216.5 as the human GM47544 transcript, which fulfills a comparable function in human hepatocytes., Conclusions: The identification of GM47544 as a lncRNA modulator of ApoC3 reveals a novel mechanism of post-translational modification, with significant clinical implications for the treatment of hypertriglyceridemia and atherosclerosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: To test whether dietary magnesium is associated with 10-year risk of a first hard atherosclerotic cardiovascular disease event., Methods: In this cross-sectional study, a total of 2980 participants, aged 40 to 79 years, from the National Health and Nutrition Examination Survey 1999-2018 were analyzed. The association between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease (ASCVD) event was assessed following adjustment for clinical risk factors, including sex, age, race, educational level, body mass index (BMI), alcohol drinking, smoking, systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension treated or not, diabetes and low density lipoprotein cholesterol (LDL-C), total energy and dietary fiber. We performed multivariate linear regression models and smooth curve fittings to evaluate the associations between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease event., Results: We observed a significant inverse association between dietary magnesium and predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event (β=-0.01, [95% CI: -0.01, -0.00], P = 0.0256). We divided the 10-year risk into two categories, with a statistically significant reduction of ASCVD risk when the 10-year risk ≥7.5% (β=-0.01, [95% CI: -0.01, -0.00], P = 0.0440)., Conclusions: Dietary magnesium intake was inversely associated with the predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The association between dietary magnesium (Mg) intake and the risk of atherosclerotic cardiovascular disease (ASCVD) remains uncertain. We aimed to examine the associations of dietary Mg intake with the risk of ASCVD events and mortality in individuals with and without type 2 diabetes., Methods: A total of 149,929 participants (4603 with type 2 diabetes) from the UK Biobank were included in the analyses. The hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models. Furthermore, interactions of dietary Mg intake with type 2 diabetes status were examined on multiplicative and additive scales., Results: During a median follow-up of 12.0 and 12.1 years, 7811 incident ASCVD events and 5000 deaths (including 599 ASCVD deaths) were documented, respectively. There were significantly negative associations between sufficient dietary Mg intake (equal to or greater than the recommended daily intake) and the risk of ASCVD incidence (HR 0.63 [95 % CI 0.49;0.82]), ASCVD mortality (0.45 [0.24;0.87]), and all-cause mortality (0.71 [0.52;0.97]) in participants with type 2 diabetes, whereas no significant association was observed in participants without type 2 diabetes (1.01 [0.94;1.09] for ASCVD incidence; 1.25 [0.93;1.66] for ASCVD mortality; 0.97 [0.88;1.07] for all-cause mortality). Multiplicative and additive interactions of dietary Mg intake with type 2 diabetes status were both observed., Conclusion: Sufficient dietary Mg intake was significantly associated with lower risks of ASCVD events and mortality in individuals with type 2 diabetes but not in those without type 2 diabetes. Our findings provide insight into the importance of dietary Mg intake for reducing modifiable cardiovascular burden in individuals with type 2 diabetes, which may inform future personalized dietary guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)