Sex-related differences in the prognostic utility of inflammatory and thrombotic cardiovascular risk markers in patients with chest pain of suspected coronary origin

Abstract

Background: α1-antichymotrypsin (SERPINA3), high sensitivity C-reactive protein (hsCRP) and pentraxin 3 (PTX3) are acute phase proteins triggered by inflammation, whereas D-dimer, fibrin monomer and α2-antiplasmin are thrombo-fibrinolytic markers. Sex differences in relation to cardiovascular disease were investigated. Methods: A total of 871 consecutive patients (61.0 % males; females: 77.3 years, males 69.1 years) were included. Of these, 380 were diagnosed with an acute myocardial infarction (MI). Stepwise Cox regression models, applying normalized continuous loge/SD values, were fitted for the biomarkers with all-cause mortality, MI and stroke, respectively, and a composite endpoint within 7 years as the dependent variables. Results: Except for α2-antiplasmin, all biomarkers were significantly associated with all-cause mortality and the combined endpoint in the univariate analysis. None of the inflammatory biomarkers predicted all-cause mortality in females after multivariable adjustment but were significant predictors in males (SERPINA3: HR 1.34 (95 %CI 1.16–1.56), p < 0.0001. hsCRP: HR 1.19 (95 %CI 1.02–1.38), p = 0.027. PTX3: HR 1.22 [95 %CI 1.04–1.44], p = 0.018. The p-value for interaction suggests a sex difference in the prognostic weighting of SERPINA3 (p = 0.015). None of the thrombo-fibrinolytic biomarkers predicted all-cause mortality in males after adjustment, but D-dimer and fibrin monomer were significant predictors of all-cause mortality in females (HR 1.51 [1.29–1.78], p < 0.0001, and HR 1.28 [1.08–1.53] p = 0.005, respectively). A trend towards interaction for D-dimer (p = 0.07) may suggest a sex difference in its prognostic weighting. Conclusion: SERPINA3, hsCRP and PTX3 predicted long-term all-cause mortality in males but not in females. The opposite relationship was observed for D-dimer and fibrin monomer.

Keywords

• Gender/sex
• Biomarkers
• SERPINA3
• D-dimer
• acute coronary syndrome (ACS)
• cardiovascular disease (CVD) events/mortality