Abstract
Abstract Background Stroke is a common cause of death and a leading cause of disability and morbidity. Stroke risk assessment remains a challenge but circulating biomarkers may improve risk prediction. Controversial evidence is available on the predictive ability of troponin concentrations and the risk of stroke in the community. Furthermore, reports on the predictive value of troponin concentrations for different stroke subtypes (ischemic and hemorrhagic) are scarce. Methods High-sensitivity cardiac troponin I (hsTnI) concentrations were assessed in 82,881 individuals (median age 50.7 years, 49.7% men) free of stroke or myocardial infarction at baseline from nine prospective European community cohorts. Multiple imputations were used to handle missing data. We used Cox proportional hazards regression to determine relative risks, followed by measures of discrimination and reclassification using 10-fold cross-validation to control for over-optimism. Follow-up was based upon linkage with national hospitalization registries and causes of death registries. Results Over a median follow-up of 12.7 years, 3,033 individuals were diagnosed with incident non-fatal or fatal stroke (N=1,654 ischemic strokes, N=612 hemorrhagic strokes, N=767 indeterminate strokes). In multivariable regression models hsTnI concentrations were associated with overall stroke (hazard ratio (HR) per one standard deviation increase 1.16, 95% confidence interval (CI) 1.10–1.21), ischemic stroke (HR 1.15, 95% CI 1.09–1.21) and hemorrhagic stroke (HR 1.10, 95% CI 1.01–1.21). Adding hsTnI concentrations to classical cardiovascular risk factors (C-indices 0.808, 0.840 and 0.735 for overall, ischemic and hemorrhagic stroke, respectively) increased the C-index significantly, but modestly. In individuals with an intermediate ten-year risk (5–20%) the net reclassification improvement for overall stroke was 0.039 (p=0.010). Conclusions Elevated hsTnI concentrations are associated with an increased risk of incident stroke in the community, irrespective of stroke subtype. Adding hsTnI concentrations to classical risk factors only modestly improved estimation of 10-year risk of stroke in the overall cohort, but might be of some value in individuals at an intermediate risk. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): The BiomarCaRE Project is funded by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no.HEALTH-F2-2011-278913. This project has received further funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 648131).
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