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 StudyLiterature - Jia X, Sun W, Hoogeveen RC, et al. - Circulation 2019; DOI: 10.1161/CIRCULATIONAHA.118.038772
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.