Current Atherosclerosis Reports

PURPOSE OF REVIEW: This review provides an overview of genetic and non-genetic causes of premature coronary artery disease (pCAD). RECENT FINDINGS: pCAD refers to coronary artery disease (CAD) occurring before the age of 65 years in women and 55 years in men. Both genetic and non-genetic risk factors may contribute to the onset of pCAD. Recent advances in the genetic epidemiology of pCAD have revealed the importance of both monogenic and polygenic contributions to pCAD...

PURPOSE OF REVIEW: Heart failure (HF) is one of the main causes of cardiovascular mortality in the western world. Despite great advances in treatment, recurrence and mortality rates remain high. Soluble guanylate cyclase is an enzyme which, by producing cGMP, is responsible for the effects of vasodilation, reduction of cardiac pre- and after-load and, therefore, the improvement of myocardial performance. Thus, a new therapeutic strategy is represented by the stimulators of soluble guanylate cyclase (sGCs)...

PURPOSE OF REVIEW: In this review, we will discuss the data from early clinical studies of MK-0616 and summarize clinical trials of other oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. RECENT FINDINGS: The success of PCSK9 inhibition with monoclonal antibody injections has fueled the development of additional therapies targeting PCSK9, including oral formulations, the most advanced of which is MK-0616. MK-0616 is a novel, orally administered macrocyclic peptide that binds to PCSK9 and inhibits binding of PCSK9 to the LDL receptor, thereby decreasing plasma levels of LDL-C...

PURPOSE OF REVIEW: Here, we summarize the key findings from preclinical studies that tested the concept that editing of hepatic genes can lower plasma low-density lipoprotein (LDL)-cholesterol levels to subsequently reduce atherosclerotic cardiovascular disease risk. RECENT FINDINGS: Selective delivery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing tools targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to hepatocytes, i...

PURPOSE OF REVIEW: The objective of this review is to explore the role of genetics in cardiometabolic drug development. The declining costs of sequencing and the availability of large-scale genomic data have deepened our understanding of cardiometabolic diseases, revolutionizing drug discovery and development methodologies. We highlight four key areas in which genetics is empowering drug development for cardiometabolic disease: (1) identifying drug candidates, (2) anticipating drug target failures, (3) silencing and editing genes, and (4) enriching clinical trials...

PURPOSE OF REVIEW: Focused review highlighting ten select studies presented at the 2023 American Heart Association (AHA) Scientific Sessions. RECENT FINDINGS: Included studies assessed semaglutide and cardiovascular outcomes in overweight or obese patients without diabetes (SELECT); dapagliflozin in patients with acute myocardial infarction without diabetes (DAPA-MI); effects of dietary sodium on systolic blood pressure in middle-aged individuals (CARDIA-SSBP); long-term blood pressure control after hypertensive pregnancy with physician guided self-management (POP-HT); effect and safety of zilebesiran, an RNA interference therapy, for sustained blood pressure reduction (KARDIA-1); recaticimab add-on therapy in patients with non-familial hypercholesterolemia and mixed hyperlipidemia (REMAIN-2); efficacy and safety of lepodisiran an extended duration short-interfering RNA targeting lipoprotein(a); safety and pharmacodynamic effects of an investigational DNA base editing medicine that inactivates the PCSK9 gene and lowers LDL cholesterol (VERVE-101); automated referral to centralized pharmacy services for evidence-based statin initiation in high-risk patients; and effects of intensive blood pressure lowering in reducing risk of cardiovascular events (ESPRIT)...

PURPOSE OF REVIEW: Genetic, experimental, epidemiologic, and clinical data support the causal role of elevated levels of low-density lipoprotein cholesterol (LDL-C) in atherosclerosis and cardiovascular disease (CVD). The recommendations of the 2019 European guidelines are based on the concept of differential CV risk, which in turn defines the LDL-C goals that should be achieved. RECENT FINDINGS: The 2019 ESC/EAS guidelines for dyslipidaemia use the Systematic COronary Risk Evaluation (SCORE) model to assess CV risk, which provides a 10-year risk of fatal CV event...

PURPOSE OF REVIEW: Bias in artificial intelligence (AI) models can result in unintended consequences. In cardiovascular imaging, biased AI models used in clinical practice can negatively affect patient outcomes. Biased AI models result from decisions made when training and evaluating a model. This paper is a comprehensive guide for AI development teams to understand assumptions in datasets and chosen metrics for outcome/ground truth, and how this translates to real-world performance for cardiovascular disease (CVD)...

PURPOSE OF REVIEW: Lipoprotein(a) is an important causal risk factor for cardiovascular disease but currently no available medication effectively reduces lipoprotein(a). This review discusses recent findings regarding lipoprotein(a) as a causal risk factor and therapeutic target in cardiovascular disease, it reviews current clinical recommendations, and summarizes new lipoprotein(a) lowering drugs. RECENT FINDINGS: Epidemiological and genetic studies have established lipoprotein(a) as a causal risk factor for cardiovascular disease and mortality...

PURPOSE OF REVIEW: Bempedoic acid is a novel therapeutic agent that is designed to reduce levels of low-density lipoprotein cholesterol (LDL-C). The purpose of this review is to provide the background for development of bempedoic acid, findings from clinical trials and to discuss clinical implications. RECENT FINDINGS: Bempedoic acid inhibits ATP citrate lyase within the liver and reduces cholesterol synthesis, with the potential to avoid muscle symptoms experienced by patients treated with statins...

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is associated with a significantly increased risk of cardiovascular disease (CVD). This review summarizes known risk factors, pathophysiological mechanisms, and current therapeutic possibilities, focusing on lipid-lowering therapy in CKD. RECENT FINDINGS: Novel data on lipid-lowering therapy in CKD mainly stem from clinical trials and clinical studies. In addition to traditional CVD risk factors, patients with CKD often present with non-traditional risk factors that include, e...

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PURPOSE OF REVIEW: This paper reviews the evidence why lipoprotein(a) (Lp(a)) is a causal risk factor for cardiovascular disease and how high Lp(a) concentrations should be managed now and with an outlook to the future. REVIEW FINDINGS: No optimal and widely available animal models exist to study the causality of the association between Lp(a) and cardiovascular disease. This has been a major handicap for the entire field. However, genetic studies turned the page...

PURPOSE OF REVIEW: Psychological health encompasses a constellation of negative and positive factors-i.e., psychosocial stress, depression, anxiety, trauma, loneliness and social isolation, anger and hostility, optimism, and a sense of purpose. This narrative review presents current evidence at the intersection of psychological health, risk of ischemic heart disease (IHD), and IHD-related outcomes, with an emphasis on associations in women. RECENT FINDINGS: For women, relations between psychological health and IHD reflect important sex and gender differences in biological and psychosocial factors...

PURPOSE OF REVIEW: Cardiometabolic diseases, which include obesity, type 2 diabetes, and cardiovascular diseases, constitute a worldwide health crisis of unparalleled proportions. The human gut microbiota has emerged as a prominent topic of inquiry in the search for novel treatment techniques. This review summarizes current research on the potential of addressing the gut microbiota to treat cardiometabolic disease. RECENT FINDINGS: Recent studies have highlighted a complex link between the gut microbiota and host physiology, shedding light on the several processes through which gut microorganisms impact metabolic health, inflammation, and cardiovascular function...

PURPOSE OF REVIEW: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of premature death. Lipid disorders, particularly elevated serum low-density lipoprotein cholesterol (LDL-C), contribute significantly to ASCVD. The risk of developing ASCVD is influenced by the duration of exposure to elevated LDL-C concentrations (cholesterol-years concept). Implementing lipid-lowering treatments based on the principles of "the earlier the better," "the lower the better," and "the longer the better" has been shown to reduce cardiovascular risk and significantly extend lifespan...

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...

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...

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...

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...