Current Atherosclerosis Reports最新文献

Purpose of review: To discuss the history of cardiovascular outcomes trials of cholesteryl ester transfer protein (CETP) inhibitors and to describe obicetrapib, a next-generation, oral, once-daily, low-dose CETP inhibitor in late-stage development for dyslipidemia and atherosclerotic cardiovascular disease (ASCVD).

Recent findings: Phase 1 and 2 trials have evaluated the safety and lipid/lipoprotein effects of obicetrapib as monotherapy, in conjunction with statins, on top of high-intensity statins (HIS), and with ezetimibe on top of HIS. In ROSE2, 10 mg obicetrapib monotherapy and combined with 10 mg ezetimibe, each on top of HIS, significantly reduced low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, total LDL particles, small LDL particles, small, dense LDL-C, and lipoprotein (a), and increased HDL-C. Phase 3 pivotal registration trials including a cardiovascular outcomes trial are underway. Obicetrapib has an excellent safety and tolerability profile and robustly lowers atherogenic lipoproteins and raises HDL-C. As such, obicetrapib may be a promising agent for the treatment of ASCVD.

Purpose of review: To highlight that body fat depletion (the Yin paradigm) with glucose-lowering treatments (the Yang paradigm) are associated with metabolic benefits for patients with type 2 diabetes mellitus (T2DM).

Recent findings: The sodium-glucose cotransporter-2 inhibitor-mediated sodium/glucose deprivation can directly improve glycemic control and kidney outcome in patients with T2DM. The glucose deprivation might also promote systemic fatty acid β-oxidation to deplete ectopic/visceral fat and thereby contribute to the prevention of cardiovascular diseases. As with metabolic surgery, bioengineered incretin-based medications with potent anorexigenic and insulinotropic efficacy can significantly reduce blood glucose as well as body weight (especially in the ectopic/visceral fat depots). The latter effects could be a key contributor to their cardiovascular-renal protective effects. In addition to a healthy diet, the newer glucose-lowering medications, with body fat reduction effects, should be prioritized when treating patients with T2DM, especially for those with established cardiovascular/renal risks or diseases.

Purpose of Review

In this review, we discuss contemporary and emerging approaches for risk stratification and management of excess adiposity for the primary and secondary prevention of cardiovascular disease.

Recent Findings

Obesity is simultaneously a pandemic-scale disease and major risk factor for the incidence and progression of a wide range of cardiometabolic conditions, but risk stratification and treatment remain clinically challenging. However, sex-, race-, and ethnicity-sensitive anthropometric measures, body composition–focused imaging, and health burden–centric staging systems have emerged as important facilitators of holistic risk prediction. Further, expanding therapeutic approaches, including comprehensive lifestyle programs, anti-obesity pharmacotherapies, device/endoscopy-based interventions, metabolic surgery, and novel healthcare delivery resources offer new empowerment for cardiovascular risk reduction in individuals with obesity.

Summary

Personalized risk stratification and weight management are central to reducing the lifetime prevalence and impact of cardiovascular disease. Further evidence informing long-term safety, efficacy, and cost-effectiveness of novel approaches targeting obesity are critically needed.

Purpose of Review

Pharmacoequity refers to the goal of ensuring that all patients have access to high-quality medications, regardless of their race, ethnicity, gender, or other characteristics. The goal of this article is to review current evidence on disparities in access to cardiovascular drug therapies across sociodemographic subgroups, with a focus on heart failure, atrial fibrillation, and dyslipidemia.

Recent Findings

Considerable and consistent disparities to life-prolonging heart failure, atrial fibrillation, and dyslipidemia medications exist in clinical trial representation, access to specialist care, prescription of guideline-based therapy, drug affordability, and pharmacy accessibility across racial, ethnic, gender, and other sociodemographic subgroups.

Summary

Researchers, health systems, and policy makers can take steps to improve pharmacoequity by diversifying clinical trial enrollment, increasing access to inpatient and outpatient cardiology care, nudging clinicians to increase prescription of guideline-directed medical therapy, and pursuing system-level reforms to improve drug access and affordability.

Purpose of Review

The role of the inhibition of ANGPTL3 in severe or refractory hypercholesterolemia is well documented, less in severe hyperTG. This review focuses on the preclinical and clinical development of ApoC-III inhibitors and ANGPTL3, 4, and 3/8 complex inhibitors for the treatment of severe or refractory forms of hypertriglyceridemia to prevent cardiovascular disease or other morbidities.

Recent Findings

APOC3 and ANGPTL3 became targets for drug development following the identification of naturally occurring loss of function variants in families with a favorable lipid profile and low cardiovascular risk. The inhibition of ANGPTL3 covers a broad spectrum of lipid disorders from severe hypercholesterolemia to severe hypertriglyceridemia, while the inhibition of ApoC-III can treat hypertriglyceridemia regardless of the severity.

Summary

Preclinical and clinical data suggest that ApoC-III inhibitors, ANGPTL3 inhibitors, and inhibitors of the ANGPTL3/8 complex that is formed postprandially are highly effective for the treatment of severe or refractory hypertriglyceridemia. Inhibition of ANGPTL3 or the ANGPTL3/8 complex upregulates LPL and facilitates the hydrolysis and clearance of triglyceride-rich lipoproteins (TRL) (LPL-dependent mechanisms), whereas ApoC-III inhibitors contribute to the management and clearance of TRL through both LPL-dependent and LPL-independent mechanisms making it possible to successfully lower TG in subjects completely lacking LPL (familial chylomicronemia syndrome). Most of these agents are biologicals including monoclonal antibodies (mAb), antisense nucleotides (ASO), small interfering RNA (siRNA), or CRISPR-cas gene editing strategies.

Purpose of Review

The objective of this review is to shed light on the transformative potential of machine learning (ML) in coronary angiography. We aim to understand existing developments in using ML for coronary angiography and discuss broader implications for the future of coronary angiography and cardiovascular medicine.

Recent Findings

The developments in invasive and noninvasive imaging have revolutionized diagnosis and treatment of coronary artery disease (CAD). However, CAD remains underdiagnosed and undertreated. ML has emerged as a powerful tool to further improve image analysis, hemodynamic assessment, lesion detection, and predictive modeling. These advancements have enabled more accurate identification of CAD, streamlined workflows, reduced the need for invasive diagnostic procedures, and improved the diagnostic value of invasive procedures when they are needed. Further integration of ML with coronary angiography will advance the prevention, diagnosis, and treatment of CAD.

Summary

The integration of ML with coronary angiography is ushering in a new era in cardiovascular medicine. We highlight five use cases to leverage ML in coronary angiography: (1) improvement of quality and efficacy, (2) characterization of plaque, (3) hemodynamic assessment, (4) prediction of future outcomes, and (5) diagnosis of non-atherosclerotic coronary disease.

Purpose of review: Heterozygous familial hypercholesterolemia (HeFH) is the most common monogenic autosomal dominant disorder. However, the condition is often underdiagnosed and undertreated. The objective of this review is to provide an update on the risk stratification in patients with HeFH, incorporating new cardiovascular imaging techniques, various biomarkers, and genetic studies.

Recent findings: The diagnosis of HeFH places patients in a high cardiovascular risk category due to the increased incidence of premature atherosclerotic cardiovascular disease. However, the level of risk varies significantly among different individuals with HeFH. Achieving an optimal stratification of cardiovascular risk is crucial for establishing appropriate and accurate treatment and management strategies. Different new tools such as risk scores have emerged in recent years, aiding physicians in assessing the risk stratification for HeFH using imaging, biomarkers, and genetics. This review emphasizes that not all patients with HeFH face the same cardiovascular risk. By utilizing different assessment tools, we can identify those who require more intensive monitoring, follow-up, and treatment.

Purpose of review: The focus of this article is to highlight the importance of the small GTPase, Ras-associated protein 1 (Rap1), in proprotein convertase subtilisin/kexin type 9 (PCSK9) regulation and atherosclerosis and type 2 diabetes etiology and discuss the potential therapeutic implications of targeting Rap1 in these disease areas.

Review findings: Cardiometabolic disease characterized by obesity, glucose intolerance, dyslipidemia, and atherosclerotic cardiovascular disease remain an important cause of mortality. Evidence using mouse models of obesity and insulin resistance indicates that Rap1 deficiency increases proatherogenic PCSK9 and low-density lipoprotein cholesterol levels and predisposes these mice to develop obesity- and statin-induced hyperglycemia, which highlights Rap1's role in cardiometabolic dysfunction. Rap1 may also contribute to cardiovascular disease through its effects on vascular wall cells involved in the atherosclerosis progression. Rap1 activation, specifically in the liver, could be beneficial in the prevention of cardiometabolic perturbations, including type 2 diabetes, hypercholesterolemia, and atherosclerosis.

Purpose of review: This review seeks to define caregiver practices that impact childhood eating behaviors and identify ways to utilize these relationships to prevent childhood obesity.

Recent findings: Childhood obesity, which correlates with adult obesity and increased cardiovascular risk, is increasing in prevalence and severity. Caregivers play a significant role in shaping a child's eating behaviors and their predisposition to obesity. Maternal influences during pregnancy and infancy impact a child's future food preferences. Caregiver feeding styles (authoritarian, authoritative, indulgent, and uninvolved) are associated with distinct effects on children's eating behaviors and self-regulation. Authoritative feeding styles promote child autonomy while setting boundaries in the feeding environment. Early caregiver education and coaching regarding nutrition and feeding practices is beneficial to establishing healthy eating behaviors for children. Various caregivers, including parents, grandparents, siblings, teachers, and others, influence a child's eating habits at different stages of development. These caregivers can both positively and negatively impact a child's diet. Comprehensive interventions involving these various caregivers to promote healthy eating practices in children is ideal. Such interventions should be sensitive to cultural and environmental factors. Childhood obesity is a complex issue with long-term health effects. Early intervention using comprehensive approaches including all caregivers, community support, and public policies to address the social determinants of health will be beneficial. Future research should focus on valid outcome measures and equitable interventions that encompass all aspects of a child's life.

Purpose of review: To review current evidence, discuss key knowledge gaps and identify opportunities for development, validation and application of polysocial risk scores (pSRS) for cardiovascular disease (CVD) risk prediction and population cardiovascular health management.

Recent findings: Limited existing evidence suggests that pSRS are promising tools to capture cumulative social determinants of health (SDOH) burden and improve CVD risk prediction beyond traditional risk factors. However, available tools lack generalizability, are cross-sectional in nature or do not assess social risk holistically across SDOH domains. Available SDOH and clinical risk factor data in large population-based databases are under-utilized for pSRS development. Recent advances in machine learning and artificial intelligence present unprecedented opportunities for SDOH integration and assessment in real-world data, with implications for pSRS development and validation for both clinical and healthcare utilization outcomes. pSRS presents unique opportunities to potentially improve traditional "clinical" models of CVD risk prediction. Future efforts should focus on fully utilizing available SDOH data in large epidemiological databases, testing pSRS efficacy in diverse population subgroups, and integrating pSRS into real-world clinical decision support systems to inform clinical care and advance cardiovascular health equity.