European journal of clinical investigation · 2025
Obesity phenotypes and atherogenic dyslipidemias.
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Choe Hun Jee, Almas Talal, Neeland Ian J, Lim Soo, Després Jean-Pierre
Аннотация
BACKGROUND: Obesity and atherogenic dyslipidemias are interrelated disorders that substantially contribute to the development of atherosclerotic cardiovascular disease (ASCVD) and the broader cardiovascular-kidney-metabolic (CKM) syndrome. The heterogeneity of obesity, particularly the role of visceral, ectopic and dysfunctional adipose tissue, drives the dyslipidemia phenotype characterized by hypertriglyceridemia, reduced high-density lipoprotein cholesterol and elevated apolipoprotein B-containing lipoproteins.
METHODS: We review the epidemiological studies, imaging analyses, genetic data and clinical trial evidence linking obesity phenotypes with dyslipidemias and cardiovascular outcomes. We further evaluated lifestyle, pharmacological and surgical strategies targeting obesity-related lipid abnormalities.
RESULTS: Visceral and ectopic fat accumulation, rather than body mass index alone, strongly predicts adverse lipid patterns, insulin resistance and cardiovascular events. Atherogenic dyslipidemias contribute to substantial residual ASCVD risk despite low-density lipoprotein cholesterol lowering. Lifestyle interventions-including diet modification, physical activity and improved cardiorespiratory fitness-demonstrate favourable effects on lipid metabolism independent of weight loss. Traditional pharmacotherapies such as statins, fibrates and omega-3 fatty acids offer partial benefits, while novel incretin-based agents and dual or triple receptor agonists provide robust weight loss and metabolic improvements. Metabolic and bariatric surgery remains an effective approach for sustained weight reduction and remission of dyslipidemias in the appropriate patient and is increasingly integrated with pharmacotherapy.
CONCLUSIONS: Atherogenic dyslipidemias are a hallmark of high-risk obesity phenotypes and a major contributor to ASCVD within the CKM framework. Precision medicine approaches that incorporate obesity phenotyping, targeted treatment strategies and population-level interventions are needed to reduce the burden of dyslipidemias and their cardiovascular sequelae.
METHODS: We review the epidemiological studies, imaging analyses, genetic data and clinical trial evidence linking obesity phenotypes with dyslipidemias and cardiovascular outcomes. We further evaluated lifestyle, pharmacological and surgical strategies targeting obesity-related lipid abnormalities.
RESULTS: Visceral and ectopic fat accumulation, rather than body mass index alone, strongly predicts adverse lipid patterns, insulin resistance and cardiovascular events. Atherogenic dyslipidemias contribute to substantial residual ASCVD risk despite low-density lipoprotein cholesterol lowering. Lifestyle interventions-including diet modification, physical activity and improved cardiorespiratory fitness-demonstrate favourable effects on lipid metabolism independent of weight loss. Traditional pharmacotherapies such as statins, fibrates and omega-3 fatty acids offer partial benefits, while novel incretin-based agents and dual or triple receptor agonists provide robust weight loss and metabolic improvements. Metabolic and bariatric surgery remains an effective approach for sustained weight reduction and remission of dyslipidemias in the appropriate patient and is increasingly integrated with pharmacotherapy.
CONCLUSIONS: Atherogenic dyslipidemias are a hallmark of high-risk obesity phenotypes and a major contributor to ASCVD within the CKM framework. Precision medicine approaches that incorporate obesity phenotyping, targeted treatment strategies and population-level interventions are needed to reduce the burden of dyslipidemias and their cardiovascular sequelae.