Sex differences in vascular endothelial function in predicting cardiovascular events in hypertensive patients

The prevalence of cardiovascular morbidity and mortality is higher in females than in males, probably for different pathogenetic mechanisms operating in the onset and progression of atherosclerotic vascular disease. Endothelial dysfunction is also recognized as an important and independent predictor of cardiovascular events. Thus, we designed this study to detect possible differences in endothelial function between sexes and their effect on cardiovascular prognosis. We enrolled 844 Caucasian hypertensives (451 males and 393 females, aged 49.5 + 10.9 years). Endothelial function was investigated by strain-gauge plethysmography. Compared with males, females showed a significantly lower endothelium-dependent vasodilation (acetylcholine-stimulated peak percent increase 268  ± 1113 vs 309 ± 108% increase from basal). During the follow-up period of 9.3 ± 3.2 years, 252 new fatal and non-fatal cardiovascular outcomes (3.20%) occurred: 151 coronary (1.92%), 61 cerebrovascular (0.77%), and 40 deaths (0.51%), with a higher incidence in females than in males [MACE (3.79 vs 2.68%; P = 0.001) and coronary events (2.24 vs 1.69%; P = 0.035), cerebrovascular events (0.93 vs 0.64%; P = 0.135) and all-cause mortality (0.63 vs 0.40%; P = 0.155)]. In multivariate Cox regression analysis, endothelial function resulted an independent predictor of MACE (HR = 0.82; 95% CI 0.73-0.952) and coronary events (HR = 0.81; 95% CI 0.69-0.95), together with hs-CRP, age, LDL-cholesterol and triglyceride in the whole population, and in females and males, separately. These results were also confirmed in ROC analysis, that demonstrated a different cut-off value of endothelial function between groups (275% for males, 214% for females). Our results confirm, in hypertensive patients, the existence of significant differences between sexes in the occurrence of cardiovascular events, probably attributable to a lower vasodilating property of vascular endothelium in females.