Current Atherosclerosis Reports最新文献

Purpose of review: This review synthesises current evidence on the cardiovascular disease (CVD) burden among young people living with HIV. It explores myocardial and vascular pathology, evaluates the role of advanced imaging, and highlights critical gaps in understanding the mechanisms driving HIV-associated CVD in this population.

Recent findings: Emerging data suggest that HIV-associated CVD in youth may be predominantly driven by non-atherosclerotic mechanisms, including direct myocardial injury, fibrosis, and remodelling, rather than traditional coronary atherosclerosis. Imaging studies have revealed subclinical myocardial changes such as increased left ventricular mass and reduced strain. Vascular studies show inconsistent findings. However, longitudinal data and multimodal imaging approaches remain scarce, particularly in high-burden regions like Africa. Young adults with HIV face a significant burden of cardiovascular pathology, often subclinical and poorly understood. The prevailing paradigm focused on atherosclerosis may not fully apply to this group, especially in African settings. There is an urgent need for longitudinal, mechanistic research to inform tailored clinical strategies and policy interventions aimed at reducing long-term cardiovascular morbidity in young people with HIV.

Purpose of review: Dysfunction of the ATP-binding cassette G5/G8 heterodimier (ABCG5/G8) leads to sitosterolemia, a condition in which premature atherosclerosis is often observed, thereby linking elevated circulating phytosterols to atherogenicity. Conversely, consumption of phytosterols reduces circulating cholesterol levels and, in animal studies, is anti-atherogenic. The debate over phytosterols' benefits vs. harms continues without consensus. Two key issues remain: despite extensive research, the etiology of premature atherosclerosis in sitosterolemia is still uncertain, and discussion of phytosterol atherogenicity has not been grounded in quantitative evidence, hindering true risk assessment.

Recent findings: In this review, we conducted a meta-analysis of circulating cholesterol and phytosterol levels prior to medical interventions in individuals with sitosterolemia. The analysis revealed that severe hypercholesterolemia manifests in the first decade of life but declines rapidly into adulthood, suggesting the presence of hypercholesterolemia-induced atherosclerotic cardiovascular disease (ASCVD). Although ABCG5/G8-deficient animal models recapitulate the symptoms of sitosterolemia, including hematologic abnormalities and organ dysfunction, increased atherogenicity has not been observed in these models. By contrast, the consumption of phytosterol-supplemented foods minimally influences circulating phytosterol levels in the general population and lowers circulating cholesterol levels by approximately 10%. Mendelian randomization studies have indicated an association between circulating phytosterol levels and ASCVD risk; however, genetic background, sterol absorption efficiency, and metabolic disturbances modulate these levels, potentially confounding the interpretation of such associations. This review reframes the phytosterol atherogenicity debate through quantitative assessment and clarifies longstanding uncertainties about phytosterol safety, thus contributing to evidence-based risk evaluation and supporting informed clinical and dietary recommendations.

Purpose of review: Apolipoprotein C-III (apoC-III) is a central regulator of triglyceride metabolism. Elevated triglyceride levels are associated with increased risk of acute pancreatitis and atherosclerotic cardiovascular disease (ASCVD).

Recent findings: Conventional triglyceride-lowering therapies, such as fibrates and omega-3 fatty acids, have limited efficacy in reducing triglycerides and in reducing the risk of pancreatitis or ASCVD in patients with severe hypertriglyceridemia. ApoC-III inhibits lipoprotein lipase and impairs clearance of both triglyceride-rich and cholesterol-rich lipoproteins. Novel therapies targeting APOC3 mRNA to reduce triglycerides, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), achieve greater triglyceride reductions than standard agents. Volanesorsen and olezarsen, both ASOs, are approved as an adjunct to diet to reduce triglycerides in familial chylomicronemia syndrome (FCS) in different regions. Plozasiran, an siRNA, is in late-stage clinical development. Indirect cross-trial comparisons were performed, aligned by timepoint and outcome measures, and indicate comparable efficacy of olezarsen and plozasiran in patients with chylomicronemia. APOC3 inhibition is now an established therapeutic approach for reducing the risk of acute pancreatitis in FCS, with three agents, volanesorsen, olezarsen, and plozasiran, demonstrating efficacy. However, its role in ASCVD prevention remains unproven. This review evaluates current APOC3 - targeted therapies for FCS, including available comparative data, and synthesizes the emerging literature on the potential of APOC3 inhibition to reduce the burden of acute pancreatitis in broader populations with severe hypertriglyceridemia, as well as its potential role in ASCVD risk reduction.

Purpose of review: Cardiac computed tomography (CCT) is now an essential noninvasive imaging modality for evaluating a broad range of cardiovascular conditions. This review summarizes the most recent recommendations from the American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC), providing an updated overview of the evolving role of CCT in risk assessment, chest pain evaluation, structural heart disease, arrhythmias, and perioperative management.

Recent findings: Compared to prior guidelines issued between 2008 and 2015, the number of CCT-related recommendations has significantly increased from 42 to 51 in the ACC/AHA guidelines, and from 20 to 31 in the ESC guidelines. This growth reflected the broadening role of CCT in the assessment of coronary artery disease, acute and stable chest pain, valvular and congenital heart disease, arrhythmias, and perioperative risk stratification. Additionally, the review highlighted emerging applications such as CT-derived fractional flow reserve (FFR-CT) and CCT-guided planning for structural interventions. By consolidating and contextualizing current recommendations, this work underscores the vital and continuously evolving role of CCT in cardiovascular practice.

Purpose of review: Discuss the effects of menopause and menopause hormone therapy (MHT) on cardiovascular risk, and propose a structured, person-centered framework for cardiovascular risk assessment when initiating MHT.

Recent findings: The risk of atherosclerotic heart disease accelerates during the menopause transition due to hormonal, metabolic, and vascular changes. Both menopause and MHT affect cardiovascular risk factors (i.e. blood pressure, lipids, insulin resistance) and cardiovascular events (i.e. myocardial infarction and stroke). Early clinical trial evidence demonstrated that oral synthetic MHT, including conjugated equine estrogen (CEE) with medroxyprogesterone acetate (MPA), is associated with increased coronary heart disease and stroke risk, particularly in older, postmenopausal women. Contemporary formulations such as low-dose transdermal estrogen and micronized progesterone have lower cardiovascular risk. A personalized assessment when initiating MHT should consider age, time since menopause, baseline cardiovascular (CV) risk, and choice of MHT formulation. Assessment of baseline CV risk should include a comprehensive review of traditional CV risk factors and consideration of risk-enhancing factors (including female-specific risk factors) and imaging for subclinical atherosclerosis (i.e. coronary artery calcium scoring) to provide a person-centered risk assessment. Menopause is an important period to implement prevention strategies to reduce future incidence CVD. A structured, individualized approach that accounts for the timing, formulation and delivery of MHT can optimize cardiovascular safety. This review provides a framework for personalized decision-making and highlights the need for further research to clarify MHT's impact on long-term CV outcomes.

Purpose of review: This review explores the role of artificial intelligence (AI) in visceral adipose tissue (VAT) and ectopic fat imaging. It aims to evaluate how AI may be used to enhance the efficiency and accuracy of cardiovascular disease (CVD) risk assessment. It addresses key questions regarding AI's capabilities in risk prediction, segmentation, and integration with large volume data for CVD risk assessment.

Recent findings: Recent studies demonstrate that AI, powered by deep learning models, significantly improve VAT and ectopic fat segmentation. AI can also be used to facilitate early detection of cardiometabolic risks and allows integration of imaging with clinical data for a more personalized approach to medicine. Emerging applications include AI-enabled telehealth and continuous monitoring through wearable technologies. AI is transforming VAT and ectopic fat imaging by enabling more precise, personalized, and scalable assessments of fat distribution and cardiovascular risk. While challenges remain, such as model interpretability, future research will likely focus on refining algorithms and expanding AI's clinical applications, potentially redefining obesity and CVD risk management.

Purpose of review: Cardiovascular disease (CVD) continues to exact a heavy toll across the Middle East and North Africa. We analyzed Global Burden of Disease 2021 data to characterize trends in CVD mortality, disability‑adjusted life‑years (DALYs), and incidence from 1990 to 2021, identify leading risk factors, and highlight country‑level disparities that inform policy action.

Recent findings: Age‑standardized CVD death rates declined by 31% and DALY rates by 36% over three decades, while incidence fell only 8%. Progress was highly uneven: Lebanon and Qatar cut DALYs by > 60%, whereas Libya's burden rose and Egypt still records > 12 000 DALYs per 100,000. Metabolic risks including obesity, hypertension, dyslipidemia, and hyperglycemia accounted for nearly half of 2021 DALYs. This contribution outweighed that of behavioral and environmental risks, despite sizeable declines in tobacco use and air-pollution exposure. Countries with robust data systems and universal coverage achieved the fastest gains; conflict‑affected or lower‑income states lagged markedly. Although regional CVD burden is trending downward, persistent heterogeneity and the rising dominance of metabolic risk highlight an urgent need for prevention‑centered, context‑specific strategies. Strengthening primary care, expanding registries, integrating digital health and environmental surveillance, and fostering cross‑country collaboration will be critical to sustain and equalize cardiovascular progress across the Middle East and North Africa.

Purpose of review: This review provides a comprehensive and scholarly examination of glucagon-like peptide-1 receptor (GLP-1R) agonists, tracing their evolution from glycemic control agents in diabetes mellitus (DM) to multifaceted therapeutics with expanding indications in cardiovascular, renal, and metabolic health. We explore the underlying biological mechanisms, summarize clinical trial evidence, and highlight emerging applications in non-diabetic populations. Recent developments underscore the relevance of GLP-1R agonists in addressing the complex interplay of cardiovascular-kidney-metabolic (CKM) syndrome, microvascular dysfunction, and metabolic-associated steatohepatitis (MASH). We also discuss combination therapies and strategies to mitigate muscle mass loss during treatment and calls for targeted research, improved clinical education, and policy reforms to optimize the translational potential of GLP-1R agonists in both individualized care and population health.

Recent findings: Diabetes mellitus currently affects over 422 million individuals worldwide, with projections indicating a rise to 783 million by 2045, representing 10.5% of the global adult population. Common comorbidities include chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD), which collectively impact nearly one-third of individuals with DM. The growing prevalence of metabolic disease, CKD, and ASCVD have prompted investigation into the role of GLP-1R agonists in mitigating cardiovascular and metabolic risks, particularly within the framework of Cardiovascular-Kidney-Metabolic (CKM) Syndrome, irrespective of diabetic status. Emerging evidence, foundational science, and transformative knowledge of mechanisms of action further support the expansion of therapeutic indications for this drug class. Although GLP-1R agonists were originally developed for glycemic control in DM, their mechanistic versatility has enabled broader application across a spectrum of cardiovascular, cerebrovascular and metabolic disorders. This review traces the trajectory of their development and highlights opportunities for more expansive translational use in both clinical and population health settings. We also address current barriers to implementation and evidence-based use, ongoing clinical trials, and future directions, including combination therapies that may enhance efficacy and patient outcomes.

Purpose of the review: This review summarizes current evidence on the use of serial coronary computed tomography angiography (CCTA) to monitor the effects of lipid-lowering therapies (LLTs)-including statins, PCSK9 inhibitors, and icosapent ethyl-on coronary plaque regression.

Recent findings: Serial CCTA enables detailed anatomic assessment of plaque characteristics including luminal stenosis, total plaque volume, calcified plaque, non-calcified plaque, and high-risk plaque features. Functional imaging with Fractional Flow Reserve from Computed Tomography and inflammatory assessment via perivascular fat attenuation index and pericoronary adipose tissue improve disease characterization. Together, these complementary tools provide a comprehensive evaluation of both the structural and biological aspects of coronary atherosclerosis, enhancing risk stratification and monitoring of therapeutic response to LLT. Serial CCTA is a valuable noninvasive tool for monitoring the effects of LLTs on coronary plaque progression aiding in risk stratification. However, wider clinical adoption is limited by cost, radiation exposure, contrast-related risks, and technical challenges in some patient populations.

Purpose of review: To discuss the role of self-DNA in activating the cytosolic DNA-sensing proteins (CDSPs) and inducing low-grade inflammation in the vessel wall in coronary atherosclerosis.

Recent findings: The cytosolic self-DNA, released from the nuclear or mitochondrial DNA in response to internal and external stressors, is sensed by the cytosolic CDSPs, which activate a cascade of molecular events that lead to the expression of interferon-stimulated genes and pro-inflammatory cytokines. The focus of this review is on the cGMP-cAMP synthase (CGAS) - stimulator of interferon response cGAMP interactor 1 (STING1) pathway. Activation of the CGAS-STING1 pathway has been documented in the coronary arteries in human patients with atherosclerosis. Likewise, experimental data implicate the activation of the CGAS-STING1 pathway in response to cytosolic self-DNA in the pathogenesis of atherosclerosis and cardiac remodeling, as well as clinical outcomes after myocardial infarction. Genetic and pharmacological inhibition of the CGAS-STING1 pathway, by and large, has shown salubrious effects in attenuating atherosclerosis and improving cardiac function and prolonging survival after myocardial infarction in experimental models. The data support the pathogenic role of the cytosolic self-DNA, released from the nuclear and/or mitochondrial genomes in response to the DNA-damaging agents, in inducing a low-grade inflammation in the vessel wall and contributing to the pathogenesis of coronary atherosclerosis and cardiac remodeling post-myocardial infarction. Whether the salubrious effects of targeting the CGAS-STING1 pathway, observed in the experimental models, would extend to human patients with coronary atherosclerosis or myocardial infarction is an open empirical question that awaits being tested after careful consideration of the potential fortuitous effects.