Neurohormonal response is associated with mortality in women with STEMI.

Abstract

Background: The prognosis after ST-elevation myocardial infarction (STEMI) continues to be worse in women. We hypothesize that sex-based differences in neurohormonal response may be a contributor to sex-specific differences in mortality risk.

Aims: To investigate whether the association between sex and mortality could in part be explained by levels of neurohormonal activation in patients with STEMI.

Methods: 1892 consecutive STEMI patients from two tertiary heart centers were included. Admission neurohormonal activation defined as pro-atrial natriuretic peptide (proANP) and mid-regional proadrenomedullin (MR-proADM) was measured in blood drawn prior to acute coronary angiography. The primary endpoint was 1-year mortality stratified according to sex and biomarker level.

Results: Of 1782 (94%) with biomarkers available, 476 (27%) of patients were women. They were older (68 vs. 62 years), had longer symptom-to-angiography delay (211 vs. 181 min), and displayed a higher crude one-year mortality rate (12 vs 7.4%, p<0.001) compared to men. The neurohormonal response was higher in women compared to men (median (IQR) proANP 1050 (IQR 671-1591) vs. 772 (492-1294) pmol/L, p<0.001); MR-proADM 0.80 (0.63-1.03) vs. 0.70 (0.58-0.89) nmol/L, p<0.001). In women, a level at or above the median was independently associated with a significantly higher mortality risk when adjusting for age, left ventricular ejection fraction (LVEF), diabetes, heart failure, symptom onset to coronary angiography (CAG), left-sided culprit lesion, obesity, renal dysfunction, primary percutaneous intervention (PCI), admission systolic blood pressure, and multi vessel disease (HR proANP 6.05, 95%CI 1.81-20.3, p=0.004; HR MR-proADM 3.49, 95%CI 1.42-8.62, p=0.007). In men, there was an independent prognostic association for proANP but not for MR-proADM (HR proANP 2.38, 95%CI 1.18-4.81, p=0.015; HR MR-proADM 1.74, 95%CI 0.89-3.40, p=0.11).

Conclusion: In STEMI patients who are women, increased admission neurohormonal activation was significantly and independently associated with increased mortality compared to men. Neurohormonal activation may contribute to some of the differences in mortality between men and women.