Cardiomyocyte injury assessed by a highly sensitive troponin assay and sudden cardiac death in the community: the Cardiovascular Health Study

Abstract

Objectives: This study sought to determine the association between markers of cardiomyocyte injury in ambulatory subjects and sudden cardiac death (SCD).

Background: The pathophysiology of SCD is complex but is believed to be associated with an abnormal cardiac substrate in most cases. The association between biomarkers of cardiomyocyte injury in ambulatory subjects and SCD has not been investigated.

Methods: Levels of cardiac troponin T, a biomarker of cardiomyocyte injury, were measured by a highly sensitive assay (hsTnT) 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.

Results: Over a median follow-up of 13.1 years, 246 participants had SCD. Baseline levels of hsTnT were significantly associated with SCD (hazard ratio [HR] for +1 log(hsTnT): 2.04, 95% confidence interval [CI]: 1.78 to 2.34]. This association persisted in covariate-adjusted Cox analyses accounting for baseline risk factors (HR: 1.30, 95% CI: 1.05 to 1.62), as well as for incident heart failure and myocardial infarction (HR: 1.26, 95% CI: 1.01 to 1.57). The population was also categorized into 3 groups based on baseline hsTnT levels and SCD risk [fully adjusted HR: 1.89 vs. 1.55 vs. 1 (reference group) for hsTnT ≥12.10 vs. 5.01 to 12.09 vs. ≤ 5.00 pg/ml, respectively; p trend = 0.005]. On serial measurements, change in hsTnT 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 to 1.06).

Conclusions: The findings suggest an association between cardiomyocyte injury in ambulatory subjects and SCD risk beyond that of traditional risk factors.

Keywords: CI; HR; MI; SCD; cardiac troponin T levels by a highly sensitive assay; confidence interval(s); general population; hazard ratio(s); hsTnT; myocardial infarction; myocytes; sudden cardiac death; sudden death.

Figure 1. Enrollment and analysis flow of the study population

hsTnT: Troponin T levels by highly sensitive assay.

Figure 2. Analysis performed to define low (≤ 5.00 pg/mL), intermediate (5.01–12.09 pg/mL) and high (≥ 12.10 pg/mL) risk categories of sudden cardiac death (SCD) based on Troponin T levels by a sensitive assay (hsTnT)

Figure shows hazard ratios (95% confidence interval) of SCD with increasing deciles (D1 to D10) of detectable hsTnT levels compared to subjects with undetectable levels (≤2.99 pg/ml).

Figure 3. Cumulative incidence of sudden cardiac death (SCD)

Cumulative incidence of SCD in participants of the Cardiovascular Health Study (n=4431) based on baseline levels of Troponin T levels by a sensitive assay (hsTnT).