Cardiac Troponin I and Incident Stroke in European Cohorts

Abstract

Background and Purpose: 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 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 9 prospective European community cohorts. 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 overoptimism. 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, 3033 individuals were diagnosed with incident nonfatal or fatal stroke (n=1654 ischemic strokes, n=612 hemorrhagic strokes, and n=767 indeterminate strokes). In multivariable regression models, hsTnI concentrations were associated with overall stroke (hazard ratio per 1-SD increase, 1.15 [95% CI, 1.10–1.21]), ischemic stroke (hazard ratio, 1.14 [95% CI, 1.09–1.21]), and hemorrhagic stroke (hazard ratio, 1.10 [95% CI, 1.01–1.20]). Adding hsTnI concentrations to classical cardiovascular risk factors (C indices, 0.809, 0.840, and 0.736 for overall, ischemic, and hemorrhagic stroke, respectively) increased the C index significantly but modestly. In individuals with an intermediate 10-year risk (5%–20%), the net reclassification improvement for overall stroke was 0.038 ( P =0.021). 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.

Cardiac Troponin I and Risk of Stroke: A Mendelian Randomization Study

“… 33 On the other hand, circulating cTnI can serve as a predictor of stroke, as observational studies have shown. 7 , 8 A novel biomarker-based stroke risk score with the introduction of cTnI was well calibrated and performed better than the extensively used CHA2DS2-VASc score. 10 Nowadays, developed biosensors for cTnI detection are being promoted to aid early management decisions in acute strokes.…”

“…It is a protein found in the cardiomyocytes and released into the bloodstream following myocardial injury. Elevated circulating cTnI level has been associated with a high risk of ischemic stroke, with hazard ratios ranging from 1.14 to 2.99 per 1-SD increase in cTnI [7][8][9] in the general population. Furthermore, circulating cTnI has also been included in the ABC (age, biomarkers, clinical history) stroke score for predicting stroke in patients with atrial fibrillation.…”

High sensitivity troponins: A potential biomarkers of cardiovascular risk for primary prevention

“…Elevated cTnI concentrations are associated with an increased risk of the incidence of stroke in the community, irrespective of the subtype. Adding cTnI concentrations to classical risk factors only modestly improved the estimation of the 10-year risk of stroke in the overall cohort, but might be of some value in individuals at an intermediate risk ( 56 ).…”

Serum biomarkers, including nitric oxide metabolites (NOx), for prognosis of cardiovascular death and acute myocardial infarction in an ESSE-RF case–control cohort with 6.5-year follow up

“…The panel included serum levels of 8 experimental markers: angiopoietin-like protein 3 (ANGPTL3), proprotein convertase subtilisin/kexin type (PCSK9), circulating total nitrate and nitrite ions (NOx), endothelin-1, leptin, adiponectin, galectin-3, and cardiac troponin I (cTnI). Most of these markers were not extensively validated but were previously demonstrated to be associated with cardiovascular risk in numerous studies and are directly or indirectly related to various aspects of cardiovascular pathology 3 . ANGPTL3 and PCSK9 participate in lipoprotein metabolism, which is associated with atherogenesis and development of cardiovascular lesions 4 , 5 .…”