Peptide Predicts Cardiac Risk in Women With Unblocked Arteries

Medscape

11-06-2025

In women with angina pectoris but no obstructive coronary artery disease (ANOCA), a high concentration of pro-C-type natriuretic peptide (proCNP) is linked to a 73% increased risk for all-cause mortality. The substance also shows a positive association with atherosclerotic markers and a negative association with generalized inflammation.
METHODOLOGY:
The analysis focused on baseline associations between proCNP concentrations in plasma and clinical data in 1508 women with ANOCA, with exploratory analyses examining correlation patterns between proCNP and 185 cardiovascular plasma markers.
Primary outcomes included all-cause death and a composite endpoint of cardiovascular events. Hazard ratios (HRs) were adjusted for age and creatine concentration, which have been linked to proCNP-derived peptides in plasma.
TAKEAWAY:
A high concentration of proCNP (≥ 53.4 pmol/L) was associated with a diagnosis of hypertension ( P = .001) and diabetes mellitus ( P < .001), postmenopausal status ( P < .001), but not age.
= .001) and diabetes mellitus ( < .001), postmenopausal status ( < .001), but not age. The researchers identified 38 plasma markers significantly associated with proCNP, showing positive correlation with atherosclerotic markers and a negative correlation with pro-inflammatory markers.
Women with high concentrations of proCNP were at increased risk for all-cause mortality (crude HR, 1.73; 95% CI, 1.10-2.73; P = .02) and adjusted HR, 1.57; 95% CI, 0.99-2.49; P = .06).
= .02) and adjusted HR, 1.57; 95% CI, 0.99-2.49; = .06). No significant difference was found in rates of cardiovascular events between groups (crude HR, 1.08; 95% CI, 0.72-1.62; P = .71; and adjusted HR, 1.03; 95% CI, 0.68-1.56; P = .90).
IN PRACTICE:
'The association between high proCNP concentrations and diabetes in women is notable as diabetes is associated with an excess risk of > 40% of fatal ischemic heart disease in women compared with men,' the researchers reported. 'Our findings thus raise the question whether increases in proCNP among elderly women are part of an adaptive vascular response to cardiovascular risk factors after menopause. Taken together, the baseline associations of the present study show high proCNP concentration in women with ANOCA is associated with a cardiovascular risk profile independent of NT-proBNP and low-grade inflammation.'
SOURCE:
This study was led by Peter D. Mark, MD, PhD, of the University of Copenhagen, in Copenhagen, Denmark. It appears online in the July 1 issue of JACC: ADVANCES .
LIMITATIONS:
As only women were examined in this study, it was impossible to evaluate whether the findings would be mirrored in men with ANOCA. Biomarkers, except for proCNP and high-sensitivity C-reactive protein, were quantified as relative plasma levels rather than absolute concentrations, limiting the interpretation of the statistical analyses.
DISCLOSURES:
This study received support through the Danish Biotek program via a grant from the Danish Health Ministry. The senior author, Jens P. Goetze, has served as a consultant for Novo Nordisk on biochemical method development.