P4625On women with ST-elevation myocardial infarction: raised concentrations of pro-C-type natriuretic peptide predict increased one-year mortality

Abstract Introduction Endothelial C-type natriuretic peptide (CNP) contributes to the local regulation of vascular homeostasis including a vasodilatory function in the microcirculation when studied in animal models. Clinical investigations have shown that high concentrations of C-type natriuretic peptides in plasma are associated with adverse clinical outcome in subgroups of patients with cardiac disease. Purpose To determine the prognostic potential of pro-C-type natriuretic peptide (proCNP) measurement in plasma sampled on admission of patients with ST-elevation myocardial infarction (STEMI). Methods In 1760 patients (470 women, 1290 men) with confirmed STEMI, we measured proCNP concentration in plasma obtained on hospital admission before coronary angiography. We divided patients into groups of low, normal or raised proCNP concentrations based on lower and upper cut-off values of sex- and age-specific 95% reference intervals from a reference population (688 individuals). We estimated differences in baseline characteristics including medical history and determined the prognostic value of proCNP measurement by Kaplan-Meier plots including log-rank tests and Cox regression survival analyses (expressed as hazard ratio (HR) and 95% confidence interval). Results Raised proCNP concentrations in plasma were associated with a higher prevalence of hypertension (P<0.001), diabetes mellitus (P=0.009), and peripheral artery disease (P=0.023), and a higher one-year all-cause mortality rate compared with normal proCNP concentrations (Plog-rank = 0.009, HR: 1.6 (1.1–2.4)). However, when adjusted for sex, an interaction between sex and groups of normal vs. raised proCNP was found (P=0.030). In sex-stratified analyses only women with raised proCNP concentrations showed an increased one-year all-cause mortality rate (women: Plog-rank <0.001, HR: 2.6 (1.5–4.6), men: Plog-rank= 0.66, HR: 1.1 (0.6–1.9)). Furthermore, in women, stepwise increases of proCNP concentration in the upper range (proCNP concentration > median) were independently associated with increased risk of death within one year after adjusting for age, plasma concentrations of creatinine and proANP, and quartiles of plasma troponins (HR: 1.02 (1.00–1.05) per 1 pmol/L increase of proCNP, P=0.047). One-year all-cause mortality rates Conclusion In patients with STEMI, a raised concentration of proCNP from plasma sampled on admission was associated with a higher risk of death within one year. However, only women displayed this difference of mortality rate in sex-specific estimates. Moreover, stepwise increases of proCNP concentration in the upper range independently predicted a higher risk of one-year death in women following STEMI after adjusting for potential confounders.