Increase in hs-troponin I associated with higher risk of CVD in individuals without CVD history
High-Sensitivity Troponin I and Incident Coronary Events, Stroke, Heart Failure Hospitalization, and Mortality in the ARIC Study
Introduction and methods
Individuals with cardiac conditions and risk factors without established CVD often have low levels of cardiac troponin I (TnI) and T (TnT), which can now be detected with high sensitivity assays (hs-TnI and hs-TnT). Lower detection threshold for cardiac troponins has resulted in potential use as a biomarker in subjects without CVD. In previous community-based studies, detectable levels of cardiac troponins have been associated with incidence of coronary heart disease [CHD], heart failure [HF] and CV mortality [1-3].
In this study, the association between baseline hs-TnI and risk of incident CVD was examined in individuals without history of CVD in the ARIC study (Atherosclerosis Risk in Communities). Furthermore, it was assessed whether hs-TnI and hs-TnT were independent risk markers for incident CVD and whether adding hs-TnI and hs-TnT to the Pooled Cohort Equation (PCE) model improved risk prediction.
The ARIC study is a large, predominantly biracial prospective cohort of middle-aged and older individuals, recruited from 4 US communities in 1987-1989. In this study, 8121 participants were included from ARIC visit 4 (1996-1998). Outcomes were total incident CHD (including fatal CHD, definite or probable MI and silent MI), incident stroke, incident HF hospitalization, all-cause mortality, incident ASCVD, and incident global CVD. Median follow-up was ~15 years for all end points.
- In quintile analyses with adjustment for traditional risk factors, increased hs-TnI (highest quintile, hs-TnI ≥3.8 ng/L) was associated with greater incident CHD (HR 2.20, 95%CI: 1.64–2.95), ischemic stroke (HR 2.99, 95%CI: 2.01–4.46), ASCVD (HR 2.36, 95%CI: 1.86–3.00), HF hospitalization (HR 4.20, 95%CI: 3.28–5.37), global CVD (HR 3.01, 95%CI: 2.50–3.63), and all-cause mortality (HR 1.83, 95%CI: 1.56–2.14), compared to quintile 1 (hs-TnI ≤1.3 ng/L, all P-trend for linearity <0.0001).
- In continuous analyses with adjustment for risk factors, increase in Hs-TnI (per natural log) was associated with greater risk of ASCVD (HR, 1.41; 95% CI, 1.32–1.51), HF hospitalization (HR, 1.57; 95% CI, 1.48–1.67), and global CVD (HR, 1.46; 95% CI, 1.39– 1.54), and for each of the individual outcome measures.
- In continuous analyses by race and sex, hs-TnI had a stronger association in white participants than in black participants for ischemic stroke (HR 1.56, 95%CI:1.38–1.76 vs. HR, 1.22, 95%CI: 1.00–1.48), ASCVD (HR 1.50, 95%CI: 1.38– 1.62 vs HR 1.24, 95%CI: 1.09–1.41), HF hospitalization (HR 1.63, 95%CI: 1.52–1.75 vs HR 1.46, 95%CI: 1.30–1.63), and global CVD (HR 1.54, 95%CI: 1.45–1.63 vs HR 1.31, 95%CI: 1.19–1.44). Associations between hs-TnI and CHD was stronger in women than men (HR 1.54, 95%CI: 1.36–1.74 vs HR: 1.29, 95%CI: 1.15–1.45).
- Moderate correlation was observed between hs-TnI and hs-TnT (Spearman rank correlation R=0.47 [P<0.0001]).
- In individuals in the highest tertiles of both hs-TnI (≥2.9 ng/L) and hs-TnT (≥7 ng/L) levels, association with outcomes were the strongest when compared with individuals with one elevated troponin (in the highest tertile) but not the other.
- Addition of hs-TnI to the PCE model resulted in modest, statistically significant improvement in risk prediction for ASCVD, global CVD, and HF hospitalization. Adding hs-TnT to the PCE model with hs-TnI further improved risk prediction for all outcome measures.
Measurements of hs-TnI in a population of individuals without history of CVD in the ARIC study showed that higher hs-TnI levels were associated with increased risk of ASCVD, global CVD, incident CHD, ischemic stroke, HF hospitalization and all-cause mortality, with significant interactions by race and sex. There was a modest correlation between hs-TnI and hs-TnT and association with outcomes was strongest when both hs-TnI and hs-TnT were highest. Addition of hs-TnI and hs-TnT to the PCE model improved risk prediction for both ASCVD and global CVD events.