Atherosclerotic cardiovascular disease (ASCVD) remains the leading global cause of morbidity and mortality, even in the era of aggressive low-density lipoprotein cholesterol (LDL-C) lowering. This persistent residual risk has prompted a reevaluation of atherogenic lipid markers, with non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (Apo B) emerging as superior indicators of the total atherogenic particle burden. Unlike LDL-C, non-HDL-C includes cholesterol from all atherogenic lipoproteins, while Apo B reflects the total number of atherogenic particles regardless of cholesterol content. Their clinical relevance is underscored in populations with diabetes, obesity, and hypertriglyceridemia, where LDL-C may not adequately reflect cardiovascular risk. This review explores the biological, clinical, and genetic foundations of non-HDL-C and Apo B as critical tools for risk stratification and therapeutic targeting. It highlights discordance analysis, inflammatory mechanisms in atherogenesis, the influence of metabolic syndromes, and their utility in specific populations, including those with chronic kidney disease and children with familial hypercholesterolemia. Additionally, the role of lipoprotein (a), glycation in diabetes, and hypertriglyceridemia are examined as contributors to residual risk. Clinical trials and genetic studies support Apo B and non-HDL-C as more robust predictors of cardiovascular events than LDL-C. Current guidelines increasingly endorse these markers as secondary or even preferred targets in complex lipid disorders. The incorporation of Apo B and non-HDL-C into routine clinical practice, especially for patients with residual risk, represents a paradigm shift toward personalized cardiovascular prevention. The review concludes with recommendations for guideline integration, emerging therapies, and future directions in biomarker-driven cardiovascular risk management.

Obesity and type 2 diabetes mellitus (T2DM) are global health crises with significant morbidity and mortality. Retatrutide, a novel triple receptor agonist targeting glucagon-like peptide-1 (GLP-1), Glucose-Dependent Insulinotropic Polypeptide (GIP), and glucagon receptors, represents a groundbreaking advancement in obesity and T2DM pharmacotherapy. This review synthesizes findings from preclinical and clinical studies, highlighting retatrutide’s mechanisms, efficacy, and safety profile. Retatrutide’s unique molecular structure enables potent activation of GLP-1, GIP, and glucagon receptors, leading to significant weight reduction, improved glycemic control, and favorable metabolic outcomes. Animal studies demonstrate retatrutide’s ability to delay gastric emptying, reduce food intake, and promote weight loss, with superior efficacy compared to other incretin-based therapies. Phase I and II clinical trials corroborate these findings, showing dose-dependent weight loss, reductions in Glycated Hemoglobin (HbA1c) levels, and improvements in liver steatosis and diabetic kidney disease. Common adverse effects are primarily gastrointestinal and dose-related. Ongoing Phase III trials, such as the TRIUMPH studies, aim to further evaluate retatrutide’s long-term safety and efficacy in diverse patient populations. While retatrutide shows immense promise, considerations regarding cost and the quality of weight loss beyond BMI reduction warrant further investigation. Retatrutide heralds a new era in obesity and T2DM treatment, offering hope for improved patient outcomes.

Diabetes mellitus (DM) is a global health challenge that contributes to numerous complications. As a chronic metabolic disorder, DM leads to persistent microvascular and macrovascular damage, ultimately impairing the function of multiple organ systems. Cardiovascular diseases (CVD), including heart failure (HF), are among the most serious diabetes-related outcomes, accounting for substantial morbidity and mortality worldwide. Traditionally, diabetic HF has been attributed to coexisting conditions such as hypertensive heart disease or coronary artery disease. However, a high prevalence of HF is observed in individuals with DM even in the absence of these comorbidities. In recent years, the phenomenon of diabetes-induced HF has attracted considerable scientific interest. Gaining insight into the mechanisms by which diabetes elevates HF risk and drives key molecular and cellular alterations is essential for developing effective strategies to prevent or reverse these pathological changes. This review consolidates current evidence and recent advances regarding the cellular and molecular pathways underlying diabetes-related HF.

Lipid lowering, with the use of statins after an acute coronary syndrome (ACS), is a cornerstone, well-established strategy for the secondary prevention of ischemic events in this high-risk cohort. In addition to the positive effect on lipid levels, statins have also been linked to improved atherosclerotic plaque characteristics, such as plaque regression and inflammation reduction, associated with the extent of reduction in LDL-C. The recent emergence of PCSK9 inhibitors for the management of dyslipidemia and the more extensive lipid lowering provided by these agents may provide better prevention for ACS patients when initiated after the ACS event. Several trials have evaluated the immediate post-ACS initiation of PCSK9 inhibitors, which has shown, to date, beneficial results. Furthermore, PCSK9 inhibitors have been linked with positive plaque remodeling and associated mortality benefits, which makes their use in the initial management strategy of such patients appealing. Therefore, in this review, we will analyze the rationale behind immediate lipid lowering after an ACS, report the evidence of PCSK9 inhibition immediately after the ACS event and the available data on plaque stabilization, and discuss treatment algorithms and clinical perspectives for the use of these agents in this clinical setting.

Obesity and hypertension have become an international health issue, with detrimental consequences on patients. Obesity and hypertension share common pathophysiological mechanisms, such as overactivity of the renin–angiotensin–aldosterone and the sympathetic nervous systems, insulin resistance, and disruption of the leptin pathway. Approved therapies for obesity and overweight include phentermine/topiramate, orlistat, naltrexone/bupropion, the glucagon-like peptide-1 receptor agonists liraglutide and semaglutide, tirzepatide, and bariatric surgery. This review gives the clinical data in a thorough manner and explains in detail how each of the previously mentioned therapies affects blood pressure levels.

Background: Patients with severe mitral regurgitation and cardiogenic shock demonstrate a poor prognosis. Mitral transcatheter edge‐to‐edge repair could alter patient management. Methods and Results: We systematically reviewed PubMed/Medline, Scopus, and Cochrane Library until January 2023, including studies assessing transcatheter edge‐to‐edge repair in patients with severe mitral regurgitation and cardiogenic shock. Studies with <5 patients were excluded. The primary outcome was device success and all‐cause death, while secondary outcomes included myocardial infarction, stroke, and heart failure hospitalization rates at 30‐day and intermediate‐term follow‐up. A fixed‐effects meta‐analysis was used to estimate pooled rates. Risk of bias was assessed with the Newcastle–Ottawa Scale. A total of 24 studies and 5428 patients were included, with a mean age of 71.2±3.3 years and a high mean Society of Thoracic Surgery score (15.2±8.9). Device success was achieved in 86% (95% CI, 85%–87%) and mitral regurgitation ≤2+ in 89% (95% CI: 88%–90%). The 30‐day all‐cause mortality rate was 14% (95% CI, 13%–15%). Stroke, myocardial infarction, and heart failure hospitalization rates were 2% (95% CI, 1%–2%), 15% (95% CI, 13%–18%), and 9% (95% CI, 8%–10%), respectively. Patients with acute myocardial infarction had similar device success (81% [95% CI, 74%–87%]), a 30‐day mortality rate of 20% (95% CI, 16%–25%), and intermediate‐term mortality rate of 14% (95% CI, 9%–19%). In non–myocardial infarction populations, the 30‐day mortality rate was 13% (95% CI, 13%–14%), and the intermediate‐term mortality rate was 35% (95% CI, 34%–36%). Conclusions: In patients with mitral regurgitation and cardiogenic shock, transcatheter edge‐to‐edge repair is associated with favorable 30‐day and intermediate‐term outcomes. Limitations, including the observational design of included studies and considerable heterogeneity, necessitate further research in this setting.