Abstract
IMPORTANCE: Atherosclerotic cardiovascular disease remains the leading cause of global morbidity and mortality. Identifying early markers of subclinical atherosclerosis is critical for predicting major adverse cardiovascular events (MACE) and improving prevention strategies. Carotid intima-media thickness (cIMT) is a well-established surrogate marker of atherosclerosis, but the impact of cardiometabolic risk factor burden on cIMT and future MACE risk is not fully understood. OBJECTIVE: To assess the association between cIMT and the risk of MACE, and to evaluate the relationship between a composite cardiometabolic-risk biomarker index and cIMT as well as future MACE risk. DESIGN: Prospective cohort study using data from the UK Biobank, with a median follow-up of 4.3 years. SETTING: Population-based study of 29,292 participants from the UK Biobank. PARTICIPANTS: Men and women aged 40 to 69 years (n=29,292) free from cardiovascular disease at baseline. Exclusions were made for those with prior coronary heart disease, myocardial infarction, and heart failure. EXPOSURES: Carotid intima-media thickness (cIMT) measured at baseline. A composite cardiometabolic-risk biomarker index (CRBI) was developed using HbA1c, total cholesterol ratio, and blood pressure. MAIN OUTCOMES AND MEASURES: The primary outcomes were the risk of MACE, including coronary heart disease (CHD), myocardial infarction (MI), and heart failure (HF). The association between cIMT, CRBI, and the risk of these events was evaluated using hazard ratios (HRs) and adjusted for confounders. RESULTS: Higher cIMT values (>800 µm) were predictive of increased risk for CHD (HR: 2.15 at 800 µm; 95 % CI: 1.07-4.31) and MI (HR: 2.46 at 800 µm; 95 % CI: 0.93-6.53). The cumulative burden of cardiometabolic risk factors, as measured by the CRBI score, was significantly associated with increased cIMT (β=44.38 µm for very high CRBI score; 95 % CI: 38.25-50.51; p < 0.001) and future MI risk (HR: 10.43 for very high CRBI score; 95 % CI: 3.18-34.24). Lifestyle factors such as smoking and physical activity were also correlated with higher cIMT, particularly in males. CONCLUSIONS: Carotid intima-media thickness is a strong predictor of coronary heart disease and myocardial infarction. The cumulative cardiometabolic-risk biomarker index offers additional predictive value for subclinical atherosclerosis and future cardiovascular events. These findings underscore the importance of comprehensive cardiometabolic health in CVD prevention strategies.