Response by Jia et al to Letter Regarding Article, “High-Sensitivity Troponin I and Incident Coronary Events, Stroke, Heart Failure Hospitalization, and Mortality in the ARIC Study”

Li and colleagues noted in their letter that there were significant differences in cardiac risk factors across high-sensitivity troponin I (hs-TnI) quantiles in our study. Specifically, higher quantiles were associated with more risk factors. This should not come as a surprise because hs-TnI reflects subclinical myocardial injury. Thus, risk factors known to contribute to clinical cardiovascular disease (CVD) are also likely to be associated with subclinical disease. However, we show that elevated hs-TnI is associated with incident clinical CVD events and mortality independent of traditional risk factors in adjusted regression models. The covariates used for adjustment were prespecified. In particular, we aimed to demonstrate that elevated hs-TnI was independently associated with incident CVD events beyond variables included in the Pooled Cohort Equation and added incremental predictive value beyond the Pooled Cohort Equation. We believe this provided clinical relevance because the Pooled Cohort Equation is currently widely adopted in the United States and recommended by the American Heart Association/American College of Cardiology guidelines for risk stratification in primary prevention. We also included other variables in further adjustment models such as body mass index and estimated glomerular filtration rate, which are important in analyses of incident heart failure events. Last, many covariables such as total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol are interrelated, and care must be taken to choose covariables strategically in adjustment models to avoid overadjustment.