Prediabetes, obesity and risk for incident atherosclerotic cardiovascular disease: A large-scale contemporary cohort study

Background: Prediabetes is a highly prevalent metabolic state associated with the development of type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). Early identification and management of prediabetes and obesity are critical to mitigate this risk, particularly in younger adults. However, contemporary large-scale data on the interplay of prediabetes, obesity, and cardiovascular outcomes across the adult lifespan remains limited. Methods: at baseline. The primary outcome was incident ASCVD, a composite of myocardial infarction, stroke, or revascularization procedures. Outcomes were tracked over 5 years and analyzed using multivariable Cox proportional hazards models, adjusted for demographic and clinical covariates and stratified by age group. Results: The final cohort comprised 1358,882 individuals (mean age of 52.5 years; 55.8% women) of whom 688,575 (50.7%) had prediabetes at baseline. In the cohort19.2% had both prediabetes and obesity, 31.5% had prediabetes without obesity, 12.2% did not have prediabetes but had obesity, and 37.1% had neither. Over a mean follow-up period of 4.1 years, prediabetes was independently associated with a 21% increased risk of ASCVD after full adjustment (Hazard Ratio [HR] 1.21; 95% CI, 1.18-1.25). This association was strongest among younger adults (ages 18-34: HR 1.54; 95% CI, 1.18-2.02). Fully adjusted, HRs for 5-year ASCVD risk were 1.32 (95% CI 1.28-1.37) for individuals with prediabetes and obesity, and 1.22 (95% CI 1.18-1.26) for those with prediabetes without obesity, compared to the reference group without prediabetes or obesity. Conclusion: In a large, contemporary cohort study, prediabetes was independently associated with a significantly increased 5-year risk of ASCVD. The relative risk was most pronounced among young adults and those with obesity. These findings underscore a critical window for implementing targeted strategies to mitigate cardiovascular risk early during metabolic dysregulation.