JACC: Advances (Jul 2025)
Pro-C-Type Natriuretic Peptide in Women With Angina Pectoris and No Obstructive Coronary Artery Disease
Abstract
Background: Circulating C-type natriuretic peptides (CNPs) predict adverse outcome in women presenting with ST-elevation myocardial infarction. Objectives: The purpose of this study was to determine the prognostic impact of a high proCNP concentration in women with angina pectoris but no obstructive coronary artery disease (ANOCA). Methods: In a prospective cohort of women with ANOCA, we assessed the baseline associations between proCNP concentrations in plasma and clinical data. Moreover, we performed exploratory partial least squares regression (PLS) analyses for correlation patterns of proCNP with 185 cardiovascular plasma markers. We included 1,508 women in baseline/follow-up analyses and 1,598 women in PLS analyses. Follow-up analyses included all-cause death and a composite endpoint of cardiovascular events, where we calculated HR estimates from crude and adjusted (age, creatinine) Cox proportional hazards models. Results: A high proCNP concentration (223 women) was associated with hypertension (P = 0.001), diabetes mellitus (P < 0.001), and postmenopausal status (P < 0.001) but not age (P = 0.13). PLS analyses showed that proCNP concentrations were positively associated with atherosclerotic markers and negatively associated with pro-inflammatory markers. For high proCNP, we found an increased risk of all-cause mortality (HRcrude: 1.73 [95% CI: 1.10-2.73]; P = 0.02 and HRadjusted: 1.57 [95% CI: 0.99-2.49]; P = 0.06), whereas hazard rates of cardiovascular events were comparable (HRcrude: 1.08 [95% CI: 0.72-1.62]; P = 0.71 and HRadjusted: 1.03 [95% CI: 0.68-1.56]; P = 0.90). Conclusions: In women with ANOCA, a high circulating proCNP concentration is associated with a distinct cardiovascular risk profile beyond pro-inflammatory biomarkers and an increased risk of all-cause mortality.
