Diet, Obesity and Cardiovascular Health: Molecular Mechanisms, Clinical Evidence and Future Perspectives

Background: Obesity and unhealthy dietary habits are among the leading modifiable determinants of cardiovascular disease, acting through biological mechanisms that extend far beyond excess body weight. Adipose tissue dysfunction, chronic low-grade inflammation, oxidative stress, endothelial impairment, mitochondrial dysfunction, and gut microbiota dysbiosis contribute to the development and progression of cardiometabolic disease. Consequently, nutrition should be regarded as a key biological modulator of cardiovascular risk, capable of influencing multiple interconnected metabolic and molecular pathways. Methods: This narrative review provides a critical and translational overview of the current evidence linking diet, obesity, and cardiovascular disease. We critically evaluated epidemiological studies, landmark randomized controlled trials, prospective cohort studies, meta-analyses, international guidelines, and relevant mechanistic investigations to examine the impact of major dietary patterns, obesity-related immunometabolic alterations, and emerging precision nutrition strategies on cardiovascular prevention and management. Results: Among currently available dietary models, the Mediterranean diet has one of the most extensive randomized evidence bases for cardiovascular prevention, including trials demonstrating reductions in major adverse cardiovascular events and other clinically relevant cardiovascular outcomes. Other healthy dietary patterns, including the Dietary Approaches to Stop Hypertension (DASH), healthy plant-based, and Nordic diets, consistently improve intermediate cardiometabolic outcomes, although evidence for hard cardiovascular endpoints is less robust. Conversely, Western dietary patterns characterized by high consumption of ultra-processed foods are associated with visceral adiposity, insulin resistance, vascular inflammation, mitochondrial dysfunction, endothelial injury, and increased cardiovascular risk. Conclusions: Contemporary evidence supports nutrition as a cornerstone of cardiovascular prevention and obesity management, with benefits may extend beyond weight reduction through modulation of key biological pathways involved in cardiometabolic disease.