Metabolic health is a stronger determinant than obesity for cardiovascular disease incidence: a meta-analysis of longitudinal cohort studies.

Overweight and obesity are established risk factors for cardiovascular diseases (CVDs), yet heterogeneity in metabolic health among individuals with varied body mass index (BMI) complicates risk assessment. This systematic-review and meta-analysis of cohort studies investigated the risk of combined BMI-metabolic health phenotypes in relation to CVDs. PubMed and Scopus were searched up to January 2025. Metabolic phenotypes were defined as individuals with metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obesity (MHO), and their metabolically unhealthy counterparts, were analyzed for associations with CVD, coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). Hazard ratios (HRs) and 95%confidence intervals (95% CIs) were pooled using random-effects models. Fifty-one publications (44 studies) were included. Compared with MHNW individuals, individuals with metabolically unhealthy obesity exhibited significantly higher risks across all cardiovascular outcomes with HRs of 2.10 (1.85-2.40) for CVD, 1.97 (1.71-2.27) for CHD, 2.20 (1.75-2.76) for MI, 1.55 (1.38-1.78) for stroke, and 2.05 (1.65-2.54) for HF. There was a positive dose-response relationship between both higher BMI and poor metabolic health and risk of CVD, CHD, MI, and HF incidence, however, associations for metabolically unhealthy normal weight subjects often exceeded that of metabolically healthy obese subjects. For stroke, poor metabolic health appears to be a primary determinant of risk. In conclusion, worsening metabolic health and higher BMI independently associated with increased CVD, CHD, MI, and HF risk, with their combination posing the greatest risk, while stroke risk was mainly associated with metabolic health.