ISO-1 Endothelial dysfunction has been associated with most
Endothelial dysfunction has been associated with most of the established cardiovascular risk factors, such as hypercholesterolemia, hypertension, smoking, diabetes mellitus, a positive history of premature CAD and elevated ISO-1 homocysteine 4, 26, 27. Endothelial dysfunction is present in the preclinical stages of atherosclerosis and can be detected long before structural changes in the vessel wall are evident on angiography or ultrasound. Assessment of vascular endothelial function can therefore serve as an integrating index of cardiovascular disease risk factor burden, enabling the monitoring of ongoing atherogenic risk .
Endothelial dysfunction has been shown to be a reversible process; numerous interventions have been reported to improve endothelial function and modify cardiovascular risk (e.g. statins, angiotensin-converting enzyme inhibitors, antioxidants) 28, 29. Recent reports have also provided evidence for the prognostic significance of endothelial dysfunction; coronary endothelial dysfunction has been shown to represent an independent predictor of cardiovascular events in long-term follow-up in patients with and without CAD , even after adjustment for conventional risk factors . Nevertheless, the relationship between endothelial dysfunction and clinical outcome has not yet been established in a large prospective clinical trial.
Endothelial function can be assessed noninvasively with high-resolution ultrasound in the brachial artery to monitor changes in arterial diameter in response to increased blood flow, an important physiological stimulus for endothelial NO production 27, 29. More specifically, hand hyperemia induced by a five-minute pressure cuff arterial occlusion at the wrist causes an increase in local shear stress, stimulating endothelial NO release, which, in turn, induces dilation of the brachial artery . This endothelium-dependent, NO-mediated process is known as flow-mediated dilation (FMD).
FMD in the brachial artery has been used extensively to evaluate both the effects of risk factors on endothelial function 27, 29, 32, 33 and the short-term effects of therapeutic interventions 29, 32. FMD has also been shown to predict long-term cardiovascular events in patients with cardiovascular diseases 34, 35, 36. However, further research is needed before FMD is established as a valuable risk predictor in clinical practice.
Premature ovarian failure is associated with vascular endothelial dysfunction Natural menopause (>50 years of age) is associated with endothelial dysfunction 2, 37, 38. Endothelial dysfunction was also found in women older than 40 years who suffered acute endogenous estrogen deprivation following ovariectomy 39, 40. In these women, impaired endothelial function was present within one month after ovariectomy and was restored after three months of hormone therapy. Epidemiological studies suggest that women who experience POF are at increased risk for cardiovascular-related mortality 8, 9, 10, 11, 12, 13. We have demonstrated that young women with POF have significant endothelial dysfunction compared with age-matched women with normal ovarian function . Using FMD in the brachial artery, endothelial function was assessed in 18 women with POF (mean age 35.4 years) and in 20 age- and body mass index-matched premenopausal women (mean age 35.0 years). FMD was significantly lower in women with POF than in controls (mean±standard deviation: 3.06±4.33% versus 8.84±2.15%, respectively; P<0.0005), suggesting that the process of atherosclerosis starts very early in women with POF. Early onset of endothelial dysfunction associated with sex-steroid deficiency might contribute to the increased risk for cardiovascular disease in these women. In young women with normal ovarian function, estradiol production varies cyclically during their menstrual cycle, with the highest serum concentrations in the preovulatory phase and the lowest during menses. In normal young women, FMD has been found to vary during the menstrual cycle in relation to endogenous estradiol levels; low levels are associated with a relative decrease in FMD . Interestingly, a recent study demonstrated that premenopausal women have an increased vulnerability to coronary events during and immediately after menses (i.e. when endogenous estrogen concentrations are very low) . In addition, in premenopausal women with variant angina, it has been shown that the frequency of myocardial ischemia is highest and FMD lowest from the end of the luteal phase to the early follicular phase, when endogenous estradiol levels are lowest .