Sex-specific mortality prediction by pro-C-type natriuretic peptide measurement in a prospective cohort of patients with ST-elevation myocardial infarction.

Abstract

To determine the predictive value of pro-C-type natriuretic peptide (pro-CNP) measurement in plasma sampled on admission from patients presenting with ST-elevation myocardial infarction (STEMI). Prospective cohort study. Two University Hospitals in Denmark. 1760 consecutive patients (470 females and 1290 males) with confirmed STEMI. The main outcome was all-cause mortality at 1 year after presentation and the primary measure was pro-CNP concentration in plasma at admission in all patients and longitudinal measurements in a consecutive subgroup of 287 patients. A reference population (n=688) defined cut-off values of increased pro-CNP concentrations. In all patients, an increased pro-CNP concentration was associated with a higher all-cause mortality after 1 year (HR 1.6, 95% CI 1.1 to 2.4, P_logrank=0.009) including an interaction of sex (p=0.03). In separate sex-stratified analyses, female patients showed increased all-cause mortality (HR_{1 year} 2.6, 95% CI 1.5 to 4.6), P_logrank <0.001), whereas no differences were found in male patients (HR_{1 year} 1.1, 95% CI 0.7 to 1.9, P_logrank=0.66). After adjusting for potential risk factors, we found increased pro-CNP concentrations≥the median value to be independently associated with increased risk of mortality in female patients within 1 year (HR per 1 pmol/L increase: 1.04, 95% CI 1.01 to 1.06, p=0.007). Moreover, we found indications of sex differences in pro-CNP concentrations over time (higher pro-CNP in males (4.4, 95% CI -0.28 to 9.1 pmol/L, p=0.07) and interaction of sex and time (p=0.13)), and that hypertension was independently associated with higher pro-CNP (4.5, 95% CI 0.6 to 8.4 pmol/L, p=0.03). In female but not male patients presenting with STEMI, high concentrations of pro-CNP (≥median) at admission independently indicate a higher risk of all-cause mortality. The findings are remarkably specific for female patients, suggesting a different vascular phenotype beyond traditional measures of coronary artery flow compared with male patients.