In this study, women between the ages of 40 and 60 years with untreated stage 1 hypertension exhibited poorer endothelial function, as indicated by smaller brachial artery FMD responses, compared to their male counterparts. In contrast, non-endothelium dependent vasodilation, assessed by the GTND response, was comparable between genders supporting the interpretation that women with hypertension exhibit an impairment of vascular endothelial function rather than a generalized vascular smooth muscle dysfunction.24
These findings may be particularly relevant given that women have a higher sensitivity threshold than men for impaired FMD being indicative of the presence of CAD11
and that reduced endothelial function has been found to be associated with an increased risk of cardiovascular events in women without CAD but not men.12
In accordance with the results of the current study, FMD was lower in women compared to men after adjustment for baseline artery diameter in 2265 adults (aged 24–39 years) participating in The Cardiovascular Risk in Young Finns Study.25
In a subgroup analysis of 224 pairs of women and men matched for identical baseline artery diameter, men continued to show larger FMD responses than women (8.2%±4.7 vs 7.1%±4.7, p
=.004) even after adjustment for traditional cardiovascular risk factors.25
However, not all studies have reported similar gender differences in FMD responses. In healthy men and women FMD has been reported to be inversely related to age,23
with men experiencing a progressive decline in endothelial function after age 40, while women exhibited a more dramatic age-related decline in their early 50's.26
In a community sample (mean age 61±9 years), women demonstrated greater FMD responses than men up until 70 years of age;23
a study of older adults (mean age; 74.5±13.1 years) reported relatively impaired endothelial responses in women compared to men;27
and no gender differences in FMD responses were observed among individuals (mean age; 62±12 years) undergoing angiographic evaluation of CAD.12
These inconsistent findings suggest that age, population under study (clinical versus community), treatment with cardiovascular medications and adjustment for baseline artery diameter may play a role in the inconsistencies observed in the literature regarding gender-based differences in endothelial function. Our present findings in a middle aged (mean age 46±8 years) sample of untreated hypertensive women and men suggest that hypertension may also moderate the association between endothelial function and gender.
Anand and colleagues6
explored gender differences in cardiovascular risk factors using the INTERHEART database and found that hypertension was more strongly associated with first myocardial infarction in women (OR: 2.95; 95% CI:[ 2.66–3.28]) than in men (OR: 2.32; 95% CI: [2.16–2.48]) and the relationship was stronger for women less than 60 years of age (OR: 4.00; 95% CI: [3.31– 4.84]) compared to older women (OR: 2.84; 95% CI: [2.49–3.23]). The reasons for this gender disparity are not known but our present observations raise the possibility that hypertension may impart an increased cardiovascular risk in women because of its association with poorer endothelial function. In addition, because hypertension is less prevalent in younger (<45 years) women compared to men,28
the presence of hypertension in younger women may be indicative of more extensive impairment of endothelial function.
Although hypertension is an established cardiovascular risk factor that is associated with endothelial dysfunction,7–9
the mechanisms accounting for our observations of reduced endothelial function among hypertensive women remain to be clarified. Given that women have smaller conduit arteries than men,29, 30
it is possible that over time similar pressures in smaller arteries may have a more profound effect on the endothelium. On the other hand, high BP may be a manifestation of more severe endothelial dysfunction in women, requiring more vascular disease to “overcome” the tendency of women to have lower BP. Palatini and colleagues31
reported that untreated stage 1 hypertensive premenopausal women between 18 and 45 years of age had an increased risk of developing hypertensive end-organ damage (microalbuminuria and left ventricular hypertrophy) than men of the same age despite lower 24-hour SBP, BMI, triglycerides and glucose. The authors hypothesized that the negative consequences of a hypertensive BP may be greater for younger women given their general tendency to have lower BP than men of similar ages. Donahue et al.32
also examined biomarkers of endothelial function (E-selectin and soluble intracellular adhesion molecule-1) in women and men who progressed from normoglycemia to pre-diabetes. The female participants who developed pre-diabetes exhibited poorer endothelial function than the normoglycemic controls while no differences were found among the male participants. The authors suggest that the pre-diabetic state may diminish the cardioprotective effect of being female, predisposing women to greater cardiovascular risk than their male counterparts. In the present study, untreated hypertension may also play a similar role in negating the cardioprotective advantage among women.
Women have often been viewed as being at lower cardiovascular risk due to the presence of cardioprotective reproductive hormones during the premenopausal years. However, gender-specific differences exist in CVD.1–4, 33
Hypertension is more prevalent in younger (< 45 years) men and older (> 65 years) women28
and women more commonly have hypertension when diagnosed with acute coronary syndromes.4
The INTERHEART researchers reported that younger (< 60 years) hypertensive women had a greater risk of myocardial infarction than their older counterparts.6ENREF 7
In addition, Gierach et al.34
found that among women with coronary risk factors undergoing coronary angiography for suspected myocardial ischemia, SBP and pulse pressure were stronger risk factors for CAD in premenopausal women compared to postmenopausal women. The findings reinforce the need for enhanced CVD risk assessment and management in all hypertensive women.