Key result
Inflammatory marker SERPINA3 predicts ~34% higher mortality in males, whereas D-dimer predicts female mortality.
Why the study?
Sex differences in the prognostic role of inflammatory and thrombo-fibrinolytic markers in relation to cardiovascular disease were investigated.
Do inflammatory and thrombotic biomarkers predict long-term mortality differently in male versus female patients with suspected coronary chest pain?
Observational
Do inflammatory and thrombotic biomarkers predict long-term mortality differently in male versus female patients with suspected coronary chest pain?
There are significant sex differences in the prognostic utility of cardiovascular risk markers, with inflammatory markers predicting mortality in men and thrombotic markers predicting mortality in women.
Supports sex-specific biomarker interpretation for prognosis in suspected CAD; leaves open the need for outcome trials before clinical adoption.
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: /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.
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Nilsen et al. (2025) conducted an observational in Chest pain of suspected coronary origin. Inflammatory and thrombotic cardiovascular risk markers vs. Sex differences (males vs females) was evaluated on All-cause mortality (HR 1.34, 95% CI 1.16-1.56, p=<0.0001). Inflammatory markers like SERPINA3 predicted 7-year all-cause mortality in males (HR 1.34; 95% CI 1.16-1.56; p<0.0001), whereas thrombo-fibrinolytic markers like D-dimer predicted it in females.
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