High-sensitivity troponins for outcome prediction in the general population: a systematic review and meta-analysis

Background: High-sensitivity (hs) assays allow to measure cardiac troponin T and I (cTnT/I) even in healthy individuals. The higher hs-cTn values, the higher the ongoing cardiomyocyte damage, and then reasonably the risk of developing symptomatic cardiac disease. Methods: We retrieved all studies evaluating the prognostic value of hs-cTnT or I in the general population. We calculated pooled hazard ratio (HR) values for all-cause and cardiovascular death, cardiovascular events and heart failure (HF) hospitalization. Results: We included 24 studies for a total of 203,202 subjects; 11 studies assessed hs-cTnT and 14 hs-cTnI. One standard deviation (SD) increase in baseline hs-cTn was associated with a 23% higher risk of all-cause death (HR 1.226, 95% CI 1.083-1.388, p<0.001, I-2=88.5%); all these studies measured hs-cTnI. In an exploratory analysis on 3 studies with 25,760 subjects, hs-cTn predicted cardiovascular death (HR 1.822, 95% CI 1.241-2.674, p=0.002, I-2=87.2%). After synthesizing 9 studies with 58,565 subjects, hs-cTn predicted cardiovascular events (HR 1.328, 95% CI 1.167-1.513, p<0.001, I-2=93.8%). Both hs-cTnT (HR 1.627, 95% CI 1.145-2.311, p<0.001) and hs-cTnI (HR 1.260, 95% CI 1.115-1.423, p<0.001; p for interaction <0.001). Furthermore, in 10 studies with 61,467 subjects, hs-cTn predicted HF hospitalization (HR 1.493, 95% CI 1.368-1.630, p<0.001, I-2=76.6%). Both hs-cTnT (HR 1.566, 95% CI 1.303-1.883, p<0.001) and hs-cTnI (HR 1.467, 95% CI 1.321-1.628, p<0.001) were associated with HF hospitalization (p for interaction <0.001). Conclusions: hs-cTn values hold strong prognostic value in subjects from the general population, predicting the risk of all-cause and cardiovascular mortality, cardiovascular events, and HF hospitalization.