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Background: High triglycerides (TG)/low high-density lipoprotein cholesterol (HDL-C)(TG > or =1.60 and HDL-C < or =1.18 mmol/L) and ischemic ST-T changes in the resting electrocardiogram (ECG) are both strong risk factors of ischemic heart disease (IHD) in men without clinical cardiovascular diseases. This study tested the hypothesis that men free of clinical IHD with high TG/low HDL-C and resting ischemic ECG changes would have a particularly poor prognosis with respect to IHD., Methods: We conducted a cohort study of 2906 men, aged 53 to 74 years, without overt IHD at baseline., Results: During 8 years, IHD developed in 229 men; 61 cases were fatal. Of the risk factors recorded, ischemic ECG changes and high TG/low HDL-C were the strongest risk factors of IHD. Compared with men without high TG/low HDL-C and without ischemic ECG changes, age-adjusted relative risk of total IHD (95% CI) was 3.5 (1.7-7.2) in men with both high TG/low HDL-C and ischemic ECG changes; the corresponding value for fatal IHD was 11.2 (4.9-25.8). Adjusted for conventional risk factors, the interaction term high TG/low HDL-C x ischemic ECG changes was a significant predictor of IHD death, with a relative risk of 2.6 (1.0-6.9)., Conclusions: In men free of clinical IHD, ischemic ECG changes were significantly more predictive of fatal IHD in men with high TG/low HDL-C, indicating an adverse synergistic effect of these 2 risk factors.