Risk of Coronary Artery Disease Associated With Transitions in Metabolic Health in a Clinical Cohort of 69 272.

BACKGROUND: The effect of recent onset metabolic dysfunction on coronary artery disease (CAD) risk is poorly understood. We developed a large data set linking metabolic phenotypes and clinical outcomes to quantify CAD risks associated with adverse metabolic transition. METHODS: Clinical parameters, measures of metabolic dysfunction components (diabetes, hypertension, elevated triglycerides, and low high-density lipoprotein) and incident CAD were curated in a clinical cohort from a single quaternary medical center. Associations between body weight, metabolic abnormalities, and changes in metabolic health status were assessed for prevalent and incident CAD. RESULTS: Increasing body mass index category, presence of metabolic dysfunction (>2 components), and number of metabolic abnormalities were associated with prevalent CAD among 844 841 individuals. In time-to-event analyses (N=69 272), ~38% of subjects initially free of any metabolic dysfunction abnormality developed ≥1 abnormality over a 3-year run-in period. All metabolic abnormalities, whether new-onset or preexisting, significantly increased 10-year CAD event probability, and there was a progressive increase in 10-year CAD risk with increasing burden of metabolic abnormalities. In models adjusting for metabolic dysfunction, 10-year CAD risk increased for individuals with body mass index >25 kg/m2 (hazard ratio, 3.8). Compared with individuals with a body mass index of 25 kg/m2, any short-term weight gain or loss of >5% increased or decreased CAD risk, respectively, in individuals with a body mass index of 35 kg/m2. CONCLUSIONS: In a large clinical cohort, the transition to metabolic dysfunction is common, occurs rapidly, and significantly increases incident CAD risk. The effect of body weight and weight loss on CAD risk is nonlinear. Interventions to prevent progression to metabolic dysfunction are needed.