Abstract

Introduction: Elevated high-sensitive cardiac troponin T (hs-cTnT>14 ng/L) and low ankle-brachial index (ABI < 0.9) are known to be associated with cardiovascular diseases (CVD) but their joint effect on the risk of CVD events is unknown. Methods: We used data from the MESA and CHS among 10,900 participants free of CVD events at baseline (mean age 66.3 years, 44.7% males). Incident coronary heart disease (CHD) was defined as fatal or non-fatal myocardial infarction or revascularization and incident CVD was defined as CHD, transient ischemic attack, stroke, or atrial fibrillation. Hazard ratio (HR) and 95% CI was calculated from a Cox regression model. Interaction on the additive scale was assessed using relative excess risk due to interaction (RERI) and interaction on the multiplicative scale was assessed by Likelihood ratio (LR) test. Results: At baseline (2000-2002 for MESA and 1989-1990 for CHS), 10.2% of participants had elevated hs-cTnT and 7.5% had low ABI. During 26.1 years of total follow-up (median follow-up 18.4 years), there were 3,911 incident CVD events. The risk of CHD and CVD was higher in participants with both elevated hs-cTnT and low ABI [CHD HR: 2.1 (1.5, 2.9), CVD HR: 2.1 (1.7, 2.5)], only elevated hs-cTnT [CHD HR: 1.7 (1.4, 2.0), CVD HR: 1.6 (1.5, 1.8)], and only low ABI [CHD HR: 1.8 (1.5, 2.2), CVD HR: 1.5 (1.3, 1.7)] than those with unelevated hs-cTnT and normal ABI. Interaction on the multiplicative scale was observe in both adjusted and unadjusted models for CHD (unadjusted LR test p-value=0.002, adjusted LR test p-value=0.042) and only in unadjusted model for CVD (LR test p-value=0.001). No significant additive interaction was detected for both CHD and CVD (RERI p-value≥0.25 for unadjusted and adjusted models). Conclusion: Having both elevated cTnT and low ABI was associated more strongly with CVD events than only elevated cTnT or low ABI. Antagonistic multiplicative interaction was found indicating the observed joint effect of elevated cTnT and low ABI was smaller than the expected combined individual effects.

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