Abstract
Background: Cardiac troponin concentrations are lower in women than men. We examined whether age- and risk factor-related changes in cardiac troponin over the life course differ by sex and if the trajectory of cardiac troponin was informative in respect of cardiovascular outcomes in women and men in the general population. Methods: In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on 3 occasions over a 15-year period. Using linear mixed-effects models, the sex-specific trajectories of cardiac troponin were evaluated, and the relationship with conventional cardiovascular risk factors determined. Using multistate joint models, the association between sex-specific trajectories of cardiac troponin and a composite outcome of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death was evaluated. Results: In 2142 women and 5151 men (mean, 58±7 and 57±7 years of age, respectively), there were 177 (8.3%) and 520 (10.1%) outcome events, respectively, during a median follow-up of 20.9 (25th to 75th percentile, 15.8-21.3) years. Cardiac troponin concentrations were persistently lower in women than in men (median baseline concentration: 2.4 [25th to 75th percentile, 1.7-3.6] ng/L versus 3.7 [25th to 75th percentile, 2.6-5.8] ng/L, respectively, P<0.001), with women exhibiting a relatively larger increase with advancing age as compared with men (Pinteraction<0.001). Apart from age, a significant and divergent interaction with sex was found for the association between cardiac troponin and body mass index (BMI) (Pinteraction=0.008) and diabetes (Pinteraction=0.003). During follow-up, cardiac troponin concentrations were associated to the outcome in both women and men (adjusted hazard ratio per 2-fold difference [95% CI, 1.34 (1.17-1.52) and 1.30 (1.21-1.40), respectively], Pinteraction=0.752). The slope of cardiac troponin was significantly associated with the outcome in women, but not in men (adjusted hazard ratio [95% CI, 2.70 (1.01-7.33) and 1.31 (0.62-2.75), respectively], Pinteraction=0.250). Conclusions: Trajectories of cardiac troponin differ between women and men in the general population, with differing associations to conventional risk factors and cardiovascular outcomes. Our findings highlight the importance of a sex-specific approach when serial cardiac troponin testing is applied for cardiovascular risk prediction.
| Original language | English |
|---|---|
| Pages (from-to) | 1798-1808 |
| Number of pages | 11 |
| Journal | Circulation |
| Volume | 147 |
| Issue number | 24 |
| DOIs | |
| Publication status | Published - 13 Jun 2023 |
Bibliographical note
Funding Information:The authors gratefully acknowledge the British Heart Foundation Cardiovascular Biomarker Laboratory, the University of Edinburgh for their expertise and assistance in this work, and the support of participants in the Whitehall II study.
Funding Information:
The Whitehall II Study has been supported by grants from the British Medical Research Council; British Economic and Social Research Council; British Heart Foundation (RG/16/11/32334); United Kingdom Health and Safety Executive; United Kingdom Department of Health; National Heart Lung and Blood Institute (HL36310), National Institutes of Health; National Institute on Aging R01AG056477, RF1AG062553), National Institutes of Health; Agency for Health Care Policy Research (HS06516); John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socio-Economic Status and Health; United Kingdom Stroke Association; and the United Kingdom Health and Safety Executive. The study was supported by an investigator-initiated study grant from the Siemens Healthineers to the University of Edinburgh. Dr de Bakker is supported by the Jaap Schouten Foundation. Dr Shah is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/19/17/34172). Dr Brunner’s research is supported by UKRI (ES/T014377/1). Dr Mills is supported by a Chair Award (CH/F/21/90010), a Programme Grant (RG/20/10/34966), and a Research Excellence Award (RE/18/5/34216) from the British Heart Foundation. Dr Kimenai is supported by Health Data Research UK which receives its funding from Health Data Research UK Ltd (HDR-5012), funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and the Wellcome Trust. The funders had no role in the study design, statistical analysis, or decision to submit this work to be considered for publication.
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