Key result
Higher plasma pregnancy zone protein linked to ~490% higher ACS risk in men, not women.
Why the study?
The association between pregnancy zone protein and acute coronary syndrome, particularly regarding sex differences, remained to be fully elucidated.
Is plasma pregnancy zone protein (PZP) associated with acute coronary syndrome, and does this association differ by sex?
Case-Control (n=1,170)
No
Is plasma pregnancy zone protein (PZP) associated with acute coronary syndrome, and does this association differ by sex?
Effect estimate: OR 5.90 (95% CI 1.59-24.98)
p-value: p=0.011
Plasma pregnancy zone protein exhibits extreme sexual dimorphism and is independently associated with acute coronary syndrome in men but not in women.
PZP-ACS association limited to men is hypothesis-generating; leaves open sex-specific biomarker utility pending prospective studies.
Background 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. Methods 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. Results 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). Conclusions 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.
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Shen et al. (2026) conducted a case-control in Acute coronary syndrome (n=1,170). Plasma pregnancy zone protein (PZP) vs. Non-ACS controls was evaluated on Association of continuous plasma PZP levels with acute coronary syndrome in men (OR 5.90, 95% CI 1.59-24.98, p=0.011). Higher plasma pregnancy zone protein levels were independently associated with acute coronary syndrome in men (OR 5.90), whereas no significant association was observed in women.
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