Sex-specific associations between pregnancy zone protein and acute coronary syndrome: a case-control study

Pregnancy zone protein (PZP) is a highly glycosylated macromolecular protein involved in energy metabolism, fibrinolysis, and immunomodulation. However, its association with acute coronary syndrome (ACS), particularly regarding sex differences, remains to be fully elucidated.

ACS patients were enrolled from the Department of Cardiology, and control subjects were recruited from the Health Examination Department. Plasma levels of PZP were quantified using a sandwich enzyme-linked immunosorbent assay (ELISA). Spearman's correlation was used to analyze the association between PZP levels and clinical variables. The association of PZP with ACS was assessed using logistic regression models, with PZP levels analyzed as a continuous variable, and subsequently categorized into binary and quartile groupings. Potential confounding variables were selected based on the disjunctive cause criterion and were adjusted for in the logistic regression models.

In this study, we enrolled 1170 participants, comprising 721 men and 449 women. Plasma PZP exhibited marked sexual dimorphism, with concentrations much higher in women than in men (median [IQR]: 3.46[1.87, 5.88] vs. 0.26[0.10, 0.52] µg/mL; P < 0.01). Among men, PZP levels were significantly elevated in ACS patients compared to controls (median [IQR]: 0.29[0.12, 0.55] vs. 0.15[0.06, 0.32] µg/mL; P < 0.01), whereas no difference was observed in women (median [IQR]: 3.45[1.82, 5.99] vs. 3.48[2.26, 4.89] µg/mL; P = 0.95). Correlation analyses revealed distinct sex-specific patterns: in men, PZP correlated positively with age and inversely with estimated glomerular filtration rate (eGFR), whereas in women, only a weak positive correlation with high-density lipoprotein cholesterol (HDL-C) was observed. In multivariable logistic regression, higher PZP was independently associated with ACS in men across all modeling strategies-continuous (fully adjusted OR 5.90, 95% CI 1.59-24.98; P = 0.011), dichotomized using the Youden-derived cutoff (> 0.25 µg/mL; OR 1.87, 95% CI 1.02-3.50; P = 0.045), and quartile-based (top vs. bottom quartile; OR 4.79, 95% CI 1.74-15.26; P = 0.004)-but no significant association was found in women (fully adjusted continuous OR 1.06, 95% CI 0.86-1.31; P = 0.589).

This study establishes that circulating PZP exhibits extreme sexual dimorphism and demonstrates its male-specific association with ACS through absolute quantification. Our findings highlight the necessity of sex-stratified analysis in cardiovascular biomarker research. These findings warrant prospective validation to determine whether PZP has any role in sex-stratified cardiovascular risk assessment, as well as future studies to clarify its temporal dynamics and sex-specific mechanisms.