Abstract
AIMS: This study examined whether or not the coexistence of smoking and metabolic syndrome synergistically increases the risk of cardiovascular disease (CVD) beyond their individual effects. METHODS: This prospective cohort study included 68,743 workers from the Japan Epidemiology Collaboration on Occupational Health Study. The participants were categorized into four groups based on their smoking status and metabolic syndrome. Biological interactions were evaluated using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S). RESULTS: During a mean follow-up of 7.2 (range: 0.1-10.9) years, 346 participants developed CVD. Current smokers with metabolic syndrome had the highest CVD risk (hazard ratio: 6.45, 95% confidence interval [CI]: 4.73-8.80). Approximately 35% of CVD cases among individuals exposed to both factors were attributed to their biological interactions (RERI: 2.27, 95% CI: 0.56-3.98; AP: 0.35, 95% CI: 0.15-0.55; S: 1.71, 95% CI: 1.16-2.52). An analysis of CVD subtypes revealed a significant biological interaction for myocardial infarction (RERI: 5.14, 95% CI: 0.65-9.62; AP: 0.52, 95% CI: 0.26-0.78; S: 2.38, 95% CI: 1.22-4.62) but not for stroke (RERI: 1.34, 95% CI: -0.46-3.13; AP: 0.25, 95% CI: -0.03-0.53; S: 1.44, 95% CI: 0.89-2.34). CONCLUSION: Smoking and metabolic syndrome interact synergistically to elevate CVD risk, particularly for myocardial infarction. Targeting both factors is essential for CVD prevention.