Current Atherosclerosis Reports最新文献

Purpose of review: Globally, the prevalence of metabolic disorders is rising. Elevated low-density lipoprotein (LDL) cholesterol is a hallmark of familial hypercholesterolemia, one of the most prevalent hereditary metabolic disorders and another one is Diabetes mellitus (DM) that is more common globally, characterised by hyperglycemia with low insulin-directed glucose by target cells. It is still known that low-density lipoprotein cholesterol (LDL-C) increases the risk of cardiovascular disease (CVD). LDL-C levels are thought to be the main therapeutic objectives.

Recent findings: The primary therapy for individuals with elevated cholesterol levels is the use of statins and other lipid lowering drugs like ezetimibe for hypercholesterolemia. Even after taking statin medication to the maximum extent possible, some individuals still have a sizable residual cardiovascular risk. To overcome this proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors-monoclonal antibodies (mAbs) are a novel class of systemic macromolecules that have enhanced LDL-C-lowering efficacy. Along with this other inhibitor are used like Angiopoeitin like 3 inhibitors. Research on both humans and animals has shown that anti-CD3 antibodies can correct autoimmune disorders like diabetes mellitus. Individuals diagnosed with familial hypercholesterolemia (FH) may need additional treatment options beyond statins, especially when facing challenges such as statin tolerance or the inability of even the highest statin doses to reach the desired target cholesterol level. Here is the summary of PCSK9, ANGPTL-3 and CD3 inhibitors and their detailed information. In this review we discuss the details of PCSK9, ANGPTL-3 and CD3 inhibitors and the current therapeutic interventions of using the monoclonal antibodies in case of the metabolic disorder. We further present the present studies and the future prospective of the same.

Purpose of review: To provide perspective on the current development status, and potential future role, of obicetrapib, a third-generation cholesterylester transfer protein (CETP) inhibitor. Obicetrapib has received recent attention following positive Phase II clinical trial data and initiation of Phase III trials for the treatment of dyslipidemia and atherosclerotic cardiovascular disease (ASCVD).

Recent findings: The ROSE and ROSE2 trials are Phase II studies that examined the lipid lowering effects of obicetrapib in patients on pre-existing high-intensity statin therapy. Obicetrapib significantly reduced key dyslipidemia biomarkers including low density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) while increasing high-density lipoprotein cholesterol (HDL-C). Four phase III clinical trials, including a cardiovascular outcomes trial, are ongoing. Preliminary data for obicetrapib shows favorable effects on dyslipidemia, which could theoretically lead to a decrease in ASCVD clinical events. Short-term safety data in preliminary studies shows no significant safety signals.

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.

Summary

While recommendations from professional societies are increasingly aggressive, additional risk reduction could be achieved by setting more even ambitious LDL cholesterol goals.

Purpose of review: In this review, we aimed to summarize the different aspects of the field of cardio-rheumatology, the role of the cardio-rheumatologist, and future research in the field.

Recent findings: Cardio-rheumatology is an emerging subspecialty within cardiology that focuses on addressing the intricate relationship between systemic inflammation and cardiovascular diseases. It involves understanding the cardiovascular impact of immune-mediated inflammatory diseases on the heart and vascular system. A cardio-rheumatologist's role is multifaceted. First, they should understand the cardiac manifestations of rheumatological diseases. They should also be knowledgeable about the different immunotherapies available and side effects. Additionally, they should know how to utilize imaging modalities, either for diagnosis, prognosis, or treatment monitoring. This field is constantly evolving with new research on both treatment and imaging of the effects of inflammation on the cardiovascular system.

Purpose of review: The risk of incident atherosclerotic cardiovascular disease (ASCVD) in primary prevention is typically lower than in secondary prevention. However, there is a spectrum of risk among individuals undergoing primary prevention with the risk in some individuals approaching those of secondary prevention. We review the clinical conditions wherein the risk in primary prevention is similar to that observed in secondary prevention.

Recent findings: Among individuals without established ASCVD, coronary artery calcium (CAC) scores ≥ 300 AU are associated with ASCVD event rates similar to secondary prevention populations. CAC score ≥ 1,000 AU are associated with an ASCVD risk seen in very high-risk secondary prevention populations. Interpretation of these observations must however consider differences in the risk reduction strategies. Current guidelines dichotomize ASCVD prevention into primary and secondary prevention, but certain primary prevention patients have an ASCVD risk equivalent to that of secondary prevention populations. Identifying higher risk primary prevention populations will allow for better risk mitigation strategies.

Purpose of review: This review seeks to provide important information on each of the major domains of social determinants of health (SDOH) in the context of atherosclerotic cardiovascular disease.

Recent findings: SDOH can be classified into five domains: social and community context, health care access and quality, neighborhood and built environment, economic stability, and education access and quality. SDOH are major drivers for cardiovascular health outcomes that exceed the impact from traditional risk factors, and explain inequities in health outcomes observed across different groups of individuals. SDOH profoundly impacts healthcare's receipt, delivery, and outcomes. Many patients fall within various disenfranchised groups (e.g., identify with minority race, low socioeconomic status, low educational attainment, LGBTQ+), which impact overall health status and care. Learning to understand, recognize, and address SDOH as the driving force of disparities are critical for achieving health equity in the prevention and adequate treatment of ASCVD.

Purpose of review: Current guidelines for primary and secondary prevention of cardiovascular events in adults up to age 75 years are well-established. However, recommendations for lipid-lowering therapies (LLT), particularly for primary prevention, are inconclusive after age 75. In this review, we focus on adults ≥ 75 years to assess low-density lipoprotein-cholesterol (LDL-C) as a marker for predicting atherosclerotic cardiovascular disease (ASCVD) risk, review risk assessment tools, highlight guidelines for LLT, and discuss benefits, risks, and deprescribing strategies.

Recent findings: The relationship between LDL-C and all-cause mortality and cardiovascular outcomes in older adults is complex and confounded. Current ASCVD risk estimators heavily depend on age and lack geriatric-specific variables. Emerging tools may reclassify individuals based on biologic rather than chronologic age, with coronary artery calcium scores gaining popularity. After initiating LLT for primary or secondary prevention, target LDL-C levels for older adults are lacking, and non-statin therapy thresholds remain unknown, relying on evidence from younger populations. Shared decision-making is crucial, considering therapy's time to benefit, life expectancy, adverse events, and geriatric syndromes. Deprescribing is recommended in end-of-life care but remains unclear in fit or frail older adults. After an ASCVD event, LLT is appropriate for most older adults, and deprescribing can be considered for those approaching the last months of life. Ongoing trials will guide statin prescription and deprescribing among older adults free of ASCVD. In the interim, for adults ≥ 75 years without a limited life expectancy who are free of ASCVD, an LLT approach that includes both lifestyle and medications, specifically statins, may be considered after shared decision-making.

Purpose of the review: This review aims to assess the variability in considering hypercholesterolemia for cardiovascular risk stratification in the general population. Recent literature on the integration of hypercholesterolemia into clinical risk scores and its interaction with other risk factors will be explored.

Recent findings: The impact of hypercholesterolemia on risk estimation varies among different cardiovascular risk calculators. Elevated lipid levels during early life stages contribute to atherosclerotic plaque development, influencing disease severity despite later treatment initiation. The interplay between low-density lipoprotein cholesterol (LDLc), inflammatory markers and non-LDL lipid parameters enhances cardiovascular risk stratification. Studies have also examined the role of coronary artery calcium (CAC) score as a negative risk marker in populations with severe hypercholesterolemia. Furthermore, polygenic risk scores (PRS) may aid in diagnosing non-monogenic hypercholesterolemia, refining cardiovascular risk stratification and guiding lipid-lowering therapy strategies. Understanding the heterogeneity in risk estimation and the role of emerging biomarkers and imaging techniques is crucial for optimizing cardiovascular risk prediction and guiding personalized treatment strategies in individuals with hypercholesterolemia.

Purpose of review: Evaluation of social influences on cardiovascular care requires a comprehensive analysis encompassing economic, societal, and environmental factors. The increased utilization of electronic health registries provides a foundation for social phenotyping, yet standardization in methodology remains lacking. This review aimed to elucidate the primary approaches to social phenotyping for cardiovascular risk stratification through electronic health registries.

Recent findings: Social phenotyping in the context of cardiovascular risk stratification within electronic health registries can be separated into four principal approaches: place-based metrics, questionnaires, ICD Z-coding, and natural language processing. These methodologies vary in their complexity, advantages and limitations, and intended outcomes. Place-based metrics often rely on geospatial data to infer socioeconomic influences, while questionnaires may directly gather individual-level behavioral and social factors. Z-coding, a relatively new approach, can capture data directly related to social determinant of health domains in the clinical context. Natural language processing has been increasingly utilized to extract social influences from unstructured clinical narratives-offering nuanced insights for risk prediction models. Each method plays an important role in our understanding and approach to using social determinants data for improving population cardiovascular health. These four principal approaches to social phenotyping contribute to a more structured approach to social determinant of health research via electronic health registries, with a focus on cardiovascular risk stratification. Social phenotyping related research should prioritize refining predictive models for cardiovascular diseases and advancing health equity by integrating applied implementation science into public health strategies.

Purpose of review: Major Depressive Disorder (MDD) is characterized by persistent symptoms such as fatigue, loss of interest in activities, feelings of sadness and worthlessness. MDD often coexist with cardiovascular disease (CVD), yet the precise link between these conditions remains unclear. This review explores factors underlying the development of MDD and CVD, including genetic, epigenetic, platelet activation, inflammation, hypothalamic-pituitary-adrenal (HPA) axis activation, endothelial cell (EC) dysfunction, and blood-brain barrier (BBB) disruption.

Recent findings: Single nucleotide polymorphisms (SNPs) in the membrane-associated guanylate kinase WW and PDZ domain-containing protein 1 (MAGI-1) are associated with neuroticism and psychiatric disorders including MDD. SNPs in MAGI-1 are also linked to chronic inflammatory disorders such as spontaneous glomerulosclerosis, celiac disease, ulcerative colitis, and Crohn's disease. Increased MAGI-1 expression has been observed in colonic epithelial samples from Crohn's disease and ulcerative colitis patients. MAGI-1 also plays a role in regulating EC activation and atherogenesis in mice and is essential for Influenza A virus (IAV) infection, endoplasmic reticulum stress-induced EC apoptosis, and thrombin-induced EC permeability. Despite being understudied in human disease; evidence suggests that MAGI-1 may play a role in linking CVD and MDD. Therefore, further investigation of MAG-1 could be warranted to elucidate its potential involvement in these conditions.