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. 2023 Jun 13;147(24):1798-1808.
doi: 10.1161/CIRCULATIONAHA.123.064386. Epub 2023 Apr 28.

Sex Differences in Cardiac Troponin Trajectories Over the Life Course

Marie de Bakker  1 , Atul Anand  2 , Martin Shipley  3 , Takeshi Fujisawa  2 , Anoop S V Shah  4 , Isabella Kardys  1 , Eric Boersma  1 , Eric J Brunner  3 , Nicholas L Mills  2   5 , Dorien M Kimenai  2
Affiliations

Sex Differences in Cardiac Troponin Trajectories Over the Life Course

Marie de Bakker et al. Circulation. .

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.

Keywords: cardiovascular diseases; population health; risk assessment; sex; troponin.

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Conflict of interest statement

Disclosures Dr Shah has received honoraria from Abbott Diagnostics. Dr Mills has acted as a consultant for Abbott Diagnostics, Siemens Healthineers, Roche, and LumiraDx. The other authors have no conflicts of interest.

Figures

Figure 1.
Figure 1.
Sex-specific cardiac troponin trajectories. A, The sex-specific average trajectory of cardiac troponin over the middle to late adulthood life course. B, The sex-specific average relative increase in cardiac troponin from 46 years onwards. The solid red line depicts the average trajectory of cardiac troponin in women and the solid blue line depicts the average trajectory of cardiac troponin in men. The dashed lines represent the 95% CIs.
Figure 2.
Figure 2.
Sex-specific association between clinical characteristics and cardiac troponin. A, The sex-specific association between repeated measures of clinical characteristics and cardiac troponin in univariable linear mixed-effects analyses. B, The sex-specific association between repeated measures of clinical characteristics and cardiac troponin in a multivariable linear mixed-effects analysis. The multivariable model included all of the clinical characteristics evaluated.
Figure 3.
Figure 3.
Sex-specific association between cardiac troponin level and change over time and primary outcome. Group 1 = baseline level < median and change < median; Group 2 = baseline level < median and change ≥ median; Group 3 = baseline level ≥ median and change < median; and Group 4 = baseline level ≥ median and change ≥ median. Log-rank test was used for between group comparisons. The estimated sex-specific median baseline level of cardiac troponin = 2.4 ng/L in women and 3.8 ng/L in men. The estimated sex-specific median change in cardiac troponin level equals a 4.4% increase per year in women and a 3.5% increase per year in men. The primary outcome is a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.
Figure 4.
Figure 4.
Sex-specific association between cardiac troponin level and change over time and death from any cause. Group 1 = baseline level < median and change < median; Group 2 = baseline level < median and change ≥ median; Group 3 = baseline level ≥ median and change < median; and Group 4 = baseline level ≥ median and change ≥ median. Log-rank test was used for between group comparisons. The estimated sex-specific median baseline level of cardiac troponin = 2.4 ng/L in women and 3.8 ng/L in men. The estimated sex-specific median change in cardiac troponin level equals a 4.4% increase per year in women and a 3.5% increase per year in men.
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