Cardiomyocyte Injury Assessed by a Highly Sensitive Troponin Assay and Sudden Cardiac Death in the Community: The Cardiovascular Health Study

Study Questions:

What is the association between markers of cardiomyocyte injury in ambulatory subjects and sudden cardiac death (SCD)?

Methods:

Levels of cardiac troponin T (cTnT), a biomarker of cardiomyocyte injury, were measured by a highly sensitive assay (hs-TnT) in 4,431 ambulatory participants in the Cardiovascular Health Study, a longitudinal community-based prospective cohort study. Serial measures were obtained in 3,089 subjects. All deaths, including SCD, were adjudicated by a central events committee. Covariate adjusted Cox models were employed to study the association of baseline hs-TnT levels and SCD risk.

Results:

Over a median follow-up of 13.1 years, 246 participants had SCD. Baseline levels of hs-TnT interval (CI), 1.78-2.34]. This association persisted in covariate-adjusted Cox analyses accounting for baseline risk factors (HR, 1.30; 95% CI, 1.05-1.62), as well as for incident heart failure and myocardial infarction (HR, 1.26; 95% CI, 1.01-1.57). The population was also categorized into three groups based on baseline hs-TnT levels and SCD risk [fully-adjusted HRs, 1.89 vs. 1.55 vs. 1 (reference group) for hs-TnT ≥12.10 vs. 5.01-12.09 vs. ≤5.00 pg/ml, respectively; Ptrend = 0.005]. On serial measurements, change in hs-TnT levels was also associated with SCD risk (fully-adjusted HR for +1 pg/ml per year increase from baseline, 1.03; 95% CI, 1.01-1.06).

Conclusions:

The authors concluded that there is an association between cardiomyocyte injury in ambulatory subjects and SCD risk beyond that of traditional risk factors.

Perspective:

In this study of a community-based population, there was a significant graded association between cTnT levels measured by a highly sensitive assay and long-term risk of SCD. The association between hs-TnT levels and SCD risk persisted in covariate adjusted analyses accounting for an extensive number of risk factors including low ejection fraction, and incident heart failure and myocardial infarction, suggesting that cardiomyocyte injury increases SCD risk beyond the effect of these covariates. These observations suggest that cTn levels in ambulatory subjects may reflect an ongoing myocardial injury-remodeling process, which may result in structural cardiac abnormalities that may in turn predispose to SCD. However, additional research is indicated to address the mechanisms underlying these associations and validate these findings.

Keywords: Myocardial Infarction, Follow-Up Studies, Heart Defects, Congenital, Risk Factors, Heart Diseases, Proportional Hazards Models, Biomarkers, Heart Failure, Cardiovascular Diseases, Myocytes, Cardiac, Death, Sudden, Cardiac, Troponin


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