Background: This study assessed sex-specific time-associated changes in the impact of risk factors on coronary artery disease (CAD) mortality in a general population over long-term follow-up. Methods and Results: A prospective longitudinal cohort study was conducted on representative Japanese populations followed up for 29 years. Data from 8,396 participants (3,745 men, 4,651 women) were analyzed. The sex-specific multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of 4 risk factors (smoking, diabetes, serum total cholesterol [TC], and systolic blood pressure [SBP]) for CAD mortality were calculated at baseline and at 10, 15, 20, 25, and 29 years of follow-up. In men, smoking (HR 3.23; 95% CI 1.16-9.02) and a 1-SD increase in TC (HR 1.82; 95% CI 1.29-2.57) were strongly associated with a higher risk of CAD in the first 10 years, but this association decreased over time. Diabetes (HR 2.30; 95% CI 1.37-3.85) and a 1-SD increase in SBP (HR 1.23; 95% CI 1.00-1.50) were strongly correlated with a higher risk of CAD after 29 years). In women, diabetes was correlated with CAD after 20 years (HR 2.53; 95% CI 1.19-5.36) and this correlation persisted until after 29 years (HR 2.47; 95% CI 1.40-4.35). Conclusions: The duration of follow-up needed for the accurate assessment of risk factors for CAD mortality varies according to risk factor and sex.
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