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. 2020 Sep;51(9):2770-2777.
doi: 10.1161/STROKEAHA.120.029452. Epub 2020 Aug 19.

Cardiac Troponin I and Incident Stroke in European Cohorts: Insights From the BiomarCaRE Project

Stephan Camen  1   2 , Tarja Palosaari  3 , Jaakko Reinikainen  3 , Ngoc Anh Sprünker  1 , Teemu Niiranen  3   4 , Francesco Gianfagna  5   6 , Julie K K Vishram-Nielsen  7   8 , Simona Costanzo  9 , Stefan Söderberg  10 , Luigi Palmieri  11 , Marco Ferrario  5 , Annette Peters  12   13   14 , Erkki Vartiainen  3 , Maria Benedetta Donati  9 , Chiara Donfrancesco  11 , Rossana Borchini  5 , Christin Susanna Börschel  1 , Simona Giampaoli  11 , Augusto Di Castelnuovo  6 , Christina Magnussen  1   2 , Frank Kee  15 , Wolfgang Koenig  16   14   17 , Stefan Blankenberg  1   2 , Giovanni de Gaetano  9 , Hugh Tunstall-Pedoe  18 , Susanne Rospleszcz  12   13 , Torben Jørgensen  7   19   20 , Tanja Zeller  1   2 , Kari Kuulasmaa  3 , Allan Linneberg  7   21 , Veikko Salomaa  3 , Licia Iacoviello  5   9 , Renate B Schnabel  1   2 ; BiomarCaRE Consortium
Affiliations

Cardiac Troponin I and Incident Stroke in European Cohorts: Insights From the BiomarCaRE Project

Stephan Camen et al. Stroke. 2020 Sep.

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.

Keywords: cohort studies; epidemiology; risk assessment; stroke; troponin.

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Conflict of interest statement

Dr Di Castelnuovo reports grants from the European Foundation for Alcohol Research as the coapplicant of the ongoing study supported by a research grant (id. EA1767) unrelated to the current study. Dr Kee reports funding from grants of the UK Clinical Research Collaboration and from the Wellcome Trust unrelated to the current work. Dr Schnabel reports personal fees from BMS/Pfizer and lecture and advisory board fees unrelated to the current study. Dr Blankenberg reports research funding from Abbott Diagnostics, Bayer, SIEMENS, Singulex, and Thermo Fisher. He further received honoraria for lectures from Abbott, Abbott Diagnostics, AstraZeneca, Bayer, AMGEN, Medtronic, Pfizer, Roche, SIEMENS Diagnostics, SIEMENS, and Thermo Fisher and as member of Advisory Boards and for consulting for Bayer, Novartis, and Thermo Fisher. Dr Costanzo reports funding from an ERAB grant (id. EA1767) and personal fees as a member of the Organizing Committee and speaker for the Ninth European Beer and Health Symposium (Bruxelles 2019) and for given lecture at the 13th European Nutrition Conference (FENS 2019, Dublin), all unrelated to the current work. Dr Söderberg reports personal fees from Actelion, Ltd. Dr Salomaa has received honoraria from Novo Nordisk and Sanofi for consultations. He also has ongoing research collaboration with Bayer AG (all unrelated to the present study). Dr Koenig reports personal fees from AstraZeneca, Novartis, Pfizer, The Medicines Company, DalCor, Kowa, Amgen, Corvidia, Berlin-Chemie, Sanofi, Bristol-Myers Squibb, and Daichii-Sankyo and nonfinancial support by grants from Abbott, Roche Diagnostics, Beckmann, and Singulex, all unrelated to the current study. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
Hazard ratios (HRs) and 95% CIs for high-sensitivity cardiac troponin I (hsTnI) categories. The presented HRs are based on a sex-stratified Cox regression analyses with adjustment for cohort, body mass index, systolic blood pressure, total and high-density lipoprotein cholesterol level, antihypertensive medication, diabetes mellitus, and daily smoking (model 2).
Figure 2.
Figure 2.
Kaplan-Meier curves of stroke-free survival according to high-sensitivity cardiac troponin I (hsTnI) categories. Numbers below the curves represent individuals at risk for the different hsTnI categories at a certain age. Note that the y axes are truncated at 0.8. Given P values are for the comparison of the highest and the lowest hsTnI categories.
Figure 3.
Figure 3.
Hazard ratio (HR) for the highest vs the lowest category of high-sensitivity cardiac troponin I (hsTnI) across cohorts. This figure displays the HRs and 95% CIs (adjusted as in model 2; Table 2) for the highest vs the lowest category of hsTnI in the separate and overall cohorts for overall stroke. Note that the x axis is truncated at 5, since the 95% CI was much wider in 2 cohorts (Moli-sani and PRIME [Prospective Epidemiological Study of Myocardial Infarction]). KORA indicates Cooperative Health Research in the Region of Augsburg; and SHHEC, Scottish Heart Health Extended Cohort.
See this image and copyright information in PMC

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