Impact of sex on the prognostic value of high-sensitivity cardiac troponin I in the general population: The HUNT study

BACKGROUND: A new, high-sensitivity assay for cardiac troponin I (hs-cTnI) permits evaluation of the prognostic value of cardiac troponins within the reference interval. Men have higher hs-cTnI concentrations than women, but the underlying pathophysiological mechanisms and prognostic implications are unclear. The aim of this study was to assess the potential impact of sex on the association between hs-cTnI and cardiovascular death. METHODS: By use of the Architect STAT High-Sensitive Troponin assay, we measured hs-cTnI in 4431 men and 5281 women aged >20 years participating in the prospective observational Nord-Trøndelag Health Study (HUNT). RESULTS: hs-cTnI was detectable in 98.5% of men and 94.7% of women. During a mean follow-up period of 13.9 years, 708 cardiovascular deaths were registered. hs-cTnI was associated with the incidence of cardiovascular death [adjusted hazard ratio (HR) per 1 SD in log hs-cTnI 1.23 (95% CI 1.15-1.31)], with higher relative risk in women than men [HR 1.44 (1.31-1.58) vs 1.10 (1.00-1.20); P _interacti_on < 0.001]. This finding was mediated by both lower risk associated with low hs-cTnI concentrations in women than in men and higher risk associated with high concentrations of hs-cTnI in women than in men. Male sex was associated with a higher risk of cardiovascular death [HR 1.28 (1.11-1.49)], but after adjustment for hs-cTnI, this association disappeared [HR 0.87 (0.75-1.02)]. CONCLUSIONS: The prognostic value of hs-cTnI concentrations in the general population is stronger in women than in men. Subtle impairment of cardiovascular status may contribute to higher hs-cTnI concentrations in men, reflecting sex-dependent differences in cardiovascular risk.