Increased levels of plasma troponins and natriuretic peptides in the general population are associated with increased future risk of cardiovascular disease, but only limited information exists on these biomarkers and stroke occurrence. In a prospective epidemiological study, the Atherosclerosis Risk in Communities (ARIC) Study, we tested the hypothesis that high-sensitivity troponin T (TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are associated positively with incidence of stroke. We measured plasma high-sensitivity TnT and NT-proBNP in 10,902 men or women initially free of stroke and followed them for a mean of 11.3 years for stroke occurrence (n=507). Analyses were performed using proportional hazards modeling. Both biomarkers were associated positively with total stroke, nonlacunar ischemic, and especially, cardioembolic stroke, but not with lacunar or hemorrhagic stroke. After adjustment for other stroke risk factors, the hazard ratio (95% CI) per one SD greater increment of natural log-transformed TnT was 1.23 (1.13, 1.35) for total stroke, 1.27 (1.15, 1.40) for total ischemic stroke, and 1.36 (1.14, 1.62) for cardioembolic stroke. Likewise, the hazard ratio per one SD greater natural log-transformed NT-proBNP, was 1.37 (1.26, 1.49) for total stroke, 1.39 (1.27, 1.53) for total ischemic stroke, and 1.95 (1.67, 2.28) for cardioembolic stroke. The hazard ratios for jointly high values of TnT (≥0.013 ug/L) and NT-proBNP (≥155.2 pg/mL), versus neither biomarker high, were 2.70 (1.92, 3.79) for total stroke and 6.26 (3.40, 11.5) for cardioembolic stroke, and somewhat stronger for NT-proBNP than TnT. Strikingly, approximately 58% of cardioembolic strokes occurred in the highest quintile of pre-stroke NT-proBNP (versus 3% occurring in the lowest quintile), and 32% of cardioembolic strokes occurred in participants who had both NT-proBNP in the highest quintile and were known by ARIC to have atrial fibrillation sometime before their cardioembolic stroke occurrence. In conclusion, in the general population, elevated plasma TnT and NT-proBNP concentrations are associated with increased risk of cardioembolic and other nonlacunar ischemic strokes.
Novel Hemostatic Factor Levels and Risk of Ischemic Stroke: The Atherosclerosis Risk in Communities (ARIC) Study