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Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individuals complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation.

Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone of reducing risk for atherosclerotic cardiovascular disease. Despite the approval of nonstatin therapies for LDL-C lowering over the past 2 decades, these medications are underused, and most patients are still not at guideline-recommended LDL-C goals. Barriers include poor adherence, clinical inertia, concern for side effects, cost, and complex prior authorization processes. With atherosclerotic cardiovascular disease-related mortality increasing globally, there remains a need for additional therapeutic options for lowering LDL-C as part of an atherosclerotic cardiovascular disease prevention strategy. Following the identification of PCSK9 (proprotein convertase subtilisin/kexin type 9) as a promising therapeutic target, inclisiran was developed using the natural process of RNA interference for robust, sustained prevention of hepatic PCSK9 synthesis. Twice-yearly maintenance subcutaneous inclisiran (following initial loading doses at Day 1 and Day 90) reduces circulating LDL-C levels by ≈50% versus placebo when added to maximally tolerated statins. Long-term safety and tolerability of inclisiran have been assessed, with studies underway to evaluate the effects of inclisiran on cardiovascular outcomes and to provide additional safety and effectiveness data. In 2021,

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • Rest-activity rhythm is an essential behavior for human health. • Low rest-activity rhythm amplitude was associated with higher ASCVD risk. • Early or late onset timing of 10h activity was associated with higher ASCVD risk. • Low rest-activity rhythm amplitude was associated with increased arterial stiffness. • Rest-activity rhythm amplitude could be a novel risk factor for ASCVD. [ABSTRACT FROM AUTHOR]

The objective of our study was to examine the association between composite dietary antioxidant index (CDAI) and atherosclerotic cardiovascular disease (ASCVD) in adults. 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. 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. • Our research revealed the association between composite dietary antioxidant index and atherosclerotic cardiovascular disease. • The composite dietary antioxidant index was negatively associated with atherosclerotic cardiovascular disease. • Our findings were significant for future studies and the formulation of dietary guidelines. [ABSTRACT FROM AUTHOR]

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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%. This study sought to assess the timing of return of Lp(a) to baseline after discontinuation of olpasiran, as well as longer-term safety. 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. 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. 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) [ABSTRACT FROM AUTHOR]

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. Highlights: Geniposide is an active iridoid glycoside compound extracted from the Chinese medicine Gardenia jasminoides Ellis. Geniposide can combat atherosclerosis through various mechanisms. Geniposide modulates immune cells and the reverse cholesterol transport, thereby limiting the formation of macrophage foam cells and improving lipid metabolism. The effects of geniposide on autophagy and apoptosis in VSMCs may be the emphasis of additional research. Whether geniposide can regulate the interaction between apoptosis and autophagy in CVD needs further investigation. Whether geniposide can target intestinal flora to inhibit atherosclerosis development needs further investigation. By selecting an appropriate route of administration and dosage regimen for geniposide, potential safety concerns can be effectively addressed. [ABSTRACT FROM AUTHOR]

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 (Ptrend < 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Despite many patients being on statins before optimisation most were under treated. • A pharmacist led service was implemented to optimise lipid lowering therapy. • Goal was secondary prevention target of non-HDL cholesterol < 97 mg/dl. • High intensity statin use increased from 39% before optimisation to 76% after review. • 41/216 (19%) of patients were at non-HDL target at baseline which improved to 92/137 (67%) after intervention. 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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

• Polycystic ovary syndrome (PCOS) is common worldwide. The syndrome refers to a group of disorders with multiple reproductive, metabolic, and endocrine elements. • PCOS affects women from fetal life throughout their lifespan, often decreasing reproductive ability and quality of life, and increasing other types of morbidity and mortality. It is often undiagnosed and untreated. • Management traditionally focuses on the treatment of hyperandrogenism and oligomenorrhea. Women with PCOS often have dyslipidemia, hypertension, obesity, and metabolic syndrome. Management plans should incorporate diagnosis and management of these factors, if present, because of the strong contribution to risk for atherosclerotic cardiovascular disease. • Understanding that the disease extends throughout life emphasizes the importance of continued screening for and treatment of risk factors to prevent cardiovascular disease throughout a woman's lifespan. • Given the complexities of the syndrome and heterogeneous manifestations, optimal management often requires a multi-disciplinary approach to provide counseling and support for lifestyle modification and addressing the full range of any reproductive, endocrine, and cardiometabolic abnormalities. 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. [ABSTRACT FROM AUTHOR]

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. Among persons with a CAC of ≥1,000, the authors sought to identify risk factors equating with very high-risk ASCVD mortality rates. 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). 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]). 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. [Display omitted] [ABSTRACT FROM AUTHOR]

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. 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). Elevated plasma MaR1 concentrations are associated with a lower risk of ASCVD development. • Elevated plasma MaR1 levels are significantly associated with a lower risk of ASCVD development. • The association between plasma MaR1 and ASCVD risk is partially mediated by serum sdLDL-c. • ASCVD risk reclassification is significantly improved by including MaR1 in the traditional risk factor-based model. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: percutaneous coronary intervention (PCI) has become the mainstay of treatment for atherosclerotic cardiovascular disease (ASCVD). Inflammatory factors have been shown to be involved in the initiation and progression of ASCVD. After PCI, the persistence of inflammation, especially the inflammation released at the target lesion, may affect the stability of non-target lesion plaques. Interleukin-6 (IL-6) is one of the most common inflammatory factors, however studies about the influence of IL-6 on the progression of non-target lesions (NTLs) of coronary artery are limited. This study investigated whether serum IL-6 levels can affect the progression of NTLs after coronary stent implantation. Methods: We performed a retrospective cohort study including 441 patients undergoing coronary angiography (CAG) and stent implantation, who had at least one NTL, between January 2019 and December 2021. They underwent followup CAG 9 to 12 months after PCI. Quartile grouping was based on serum IL-6 levels following readmission. The relationship between serum IL-6 levels and the progression of NTLs after coronary stent implantation was analyzed by using logistic regression analysis and restricted cubic spline regression. Predictive value of IL-6 on NTL progression was evaluated using the receiver operating characteristic (ROC) curve. Results: When compared to the first quartile (Q1) group, the probability of NTL progression was increased in Q2 (adjusted odds ratio (aOR) 3.06, 95% CI 1.29–7.29), Q3 (aOR 3.55, 95% CI 1.52–8.26), and Q4 group (aOR 7.51, 95% CI 3.30– 17.05), with a trend test p < 0.001. With the increase of IL-6 levels, the risk of progression of NTLs gradually increased, and there was a non-linear relationship between IL-6 and progression of NTLs (p < 0.001). The ROC curve showed that the critical value of the serum IL-6 level was 12.652 pg/mL (area under the curve is 0.673, sensitivity is 54.5%, specificity is 70.9%, p < 0.05). Conclusions: A high serum IL-6 level is an independent risk factor for the progression of NTLs after coronary stent implantation, and has certain predictive value for the progression of NTLs. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to clarify the real-world status of lipid management in outpatients with type 2 diabetes (T2DM) following the 2022 revision of the Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases. It also aimed to evaluate characteristics associated with the failure to achieve management targets. Materials and Methods: In this post-hoc analysis of a multicenter, cross-sectional study, we included Japanese outpatients with T2DM undergoing primary prevention of atherosclerotic cardiovascular diseases (ASCVD) who provided fasting blood samples. The frequency and determinants of achieving low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) targets were assessed. Results: Among 223 participants with a mean age of 67 and mean HbA1c of 7.1%, 61 had no history of peripheral arterial disease, microvascular complications, or smoking. Out of the 223 participants, 64.1% (95% CI: 57.6–70.1%) achieved the LDL-C target. In multivariate logistic regression analysis, being female (odds ratio [OR] 3.139, P = 0.0011), having diabetic nephropathy (OR 2.868, P = 0.0021), smoking (OR 2.292, P = 0.0281), and non-use of statins (OR 4.857, P < 0.0001) were independently associated with non-achievement. For non-HDL-C, 65.6% (95% CI: 58.1%–70.6%) of patients met the target. Having diabetic neuropathy (OR 2.428, P = 0.0054), smoking (OR 2.008, P = 0.0478), and non-use of statins (OR 2.277, P = 0.0112) were identified as factors associated with non-achievement. Conclusions: Low achievement rate of revised lipid management targets for ASCVD primary prevention in T2DM was unveiled. Assessing comorbidities, encouraging smoking cessation, and prioritizing statin use are considered. [ABSTRACT FROM AUTHOR]

ObjectivePersons with HIV (PWH) have increased risk for atherosclerotic cardiovascular disease (CVD). Despite this increased risk, perceived cardiovascular risk among PWH is low, and interventions that are known to be beneficial in the general population, such as statins, have low uptake in this population. We sought to develop a bank of text messages about (1) the association between HIV and CVD and (2) advice on reducing cardiovascular risk.MethodsWe developed an initial bank of 162 messages. We solicited feedback from 29 PWH recruited from outpatient clinics providing HIV care at a large urban tertiary medical center and a public hospital in San Francisco, California. Participants reviewed 7-10 messages each and rated message usefulness, readability, and potential impact on behavior on a scale from 1 (least) to 5 (most). We also collected open-ended feedback on the messages and data on preferences about message timing.ResultsThe average score for the messages was 4.4/5 for usefulness, 4.4/5 for readability, and 4.0/5 for potential impact on behavior. The text messages were iteratively revised based on participant feedback, and lowest-rated messages were removed from the message bank. The final message bank included 116 messages on diet (30.2%), physical activity (24.8%), tobacco (11.2%), the association between HIV and cardiovascular disease (9.5%), general heart health (6.9%), cholesterol (5.2%), blood pressure (4.3%), blood sugar (2.6%), sleep (2.6%), and weight (2.6%).ConclusionWe describe an approach for developing educational text messages on primary prevention of cardiovascular disease among PWH.

Abstract 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. Graphical Abstract

Abstract 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.