Joint effect of highly-sensitive cardiac troponin T and ankle-brachial index on incident cardiovascular events: The MESA and CHS

BACKGROUND: Elevated highly-sensitive cardiac troponin-T (hs-cTnT≥14 ng/L) and low ankle-brachial index (ABI<0.9) are risk factors for atherosclerotic cardiovascular diseases (ASCVD) but their joint effect on the risk of ASCVD events is unknown. METHODS: We used data from the two population-based cohort studies, the Multi-Ethnic study of Atherosclerosis (MESA) and Cardiovascular Heart Study (CHS) among 10,897 participants free of CVD events at baseline (mean age 66.3 years, 44.7% males). Incident ASCVD was defined as CHD (fatal/non-fatal MI or revascularization), transient ischemic attack, or stroke,. 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 a median follow-up of 13.6 years (interquartile range, 7.5–14.7 years), there were 2590 incident ASCVD and 1542 incident CHD events. The hazard of CHD and ASCVD was higher in participants with both elevated hs-cTnT and low ABI [HR(95% CI): CHD: 2.04 (1.45, 2.88), ASCVD: 2.05 (1.58, 2.66)] than those with only elevated hs-cTnT [CHD: 1.65 (1.37, 1.99), ASCVD: 1.67 (1.44, 1.99)] or only low ABI [CHD: 1.87 (1.52, 2.31), ASCVD: 1.67 (1.42, 1.97)]. Antagonistic multiplicative interaction was observed for CHD (LR test p-value=0.042) but not for ASCVD (LR test p-value =0.08). No significant additive interaction was detected for CHD and ASCVD (RERI p-value ≥0.23). CONCLUSION: The observed joint effect of elevated cTnT and low ABI on ASCVD risk was smaller (i.e., antagonistic interaction) than that expected by the combined independent effects of each risk factor.