Sex differences in the effect of physical activity on hemostasis in coronary artery disease

Abstract Introduction Although sex differences in coronary artery disease (CAD) are recognised, the biological basis is unclear, particularly regarding potential differences in hemostasis, which plays a central role in the pathophysiology of the disease. Cardiac rehabilitation improves exercise capacity and prognosis in patients with CAD; however, its impact on hemostasis has not yet been elucidated. Purpose To evaluate sex-related differences in overall hemostatic potential (OHP), overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) before and after cardiac rehabilitation in patients with CAD in real-world clinical practice. Methods We included patients referred for a structured cardiac rehabilitation programme (36 sessions, 2–3 times weekly) within 90 days after acute myocardial infarction. Fasting blood samples were collected at recruitment and after completion of rehabilitation. OHP and OCP were quantified using established protocols, OFP was calculated: OFP=(OHP–OCP)/OCP×100 (%). We compared hemostatic potentials between men and women and examined linear correlations with sex, age and cardiovascular risk factors. Multivariate linear regression models included sex, arterial hypertension and hyperlipidaemia for prediction of hemostatic potentials at baseline and their change during rehabilitation. Results Of 107 included participants, 21 were women (19.6%). Age and cardiovascular risk factors did not differ between groups (p0.05). Women had higher baseline OHP than men (9.5±3.1 vs 7.8±2.5; p=0.013), while baseline OCP and OFP did not differ significantly (p=0.73 and p=0.123; Figure 1). At follow-up, women had higher OHP and OCP than men (9.6±3.04 vs 7.6±2.42; p=0.002 and 26.4±4.00 vs 23.37±4.30; p=0.005, respectively). Over the course of rehabilitation, a significant increase in OFP was observed in men (mean change 2.0±7.23; p=0.02), but not in women (p=0.591). All other hemostatic changes were non-significant (p0.05). Univariate linear regression showed an association between arterial hypertension and OCP at baseline (β=3.81; p=0.001) and follow-up (β=2.30; p=0.026). Hyperlipidaemia was associated with both OHP and OCP at both time points (for OHP: β=1.99; p0.001 and β=1.34; p=0.017; for OCP: β=3.37; p=0.001 and β=2.97; p=0.001). Female sex was associated with higher OHP at both time points (β=1.69; p=0.013 and β=2.03; p = 0.002) and with higher OCP at follow-up only (β=3.08; p=0.005). In multivariate analysis, sex and hyperlipidaemia were significant predictors of OHP and OCP at baseline and follow-up (Table 1), whereas arterial hypertension was associated only with OCP at both time points. Conclusion Our study shows that women with CAD have increased coagulation compared to men. Cardiac rehabilitation programme increases fibrinolysis in men but not in women. Our results further confirm sex differences in CAD pathophysiology and support the need for a sex specific approach to research, diagnostic and treatment in CAD.Figure 1.For image description, please refer to the figure legend and surrounding text. Table 1.For image description, please refer to the figure legend and surrounding text.