Overview of gender aspects of cardiac syndrome X

Cardiac syndrome X, a condition defined by the presence of angina-like chest pain, a positive response to stress testing and normal coronary arteriograms, has been shown to occur in approximately 20--30% of angina patients undergoing coronary arteriography. The prevalence of syndrome X is significantly higher in women compared to men. In the majority of patients with chest pain and normal coronary arteriograms, symptoms are likely to be non-cardiac in origin. However, myocardial ischaemia may be the pathogenic mechanism in a proportion of syndrome X patients. Indeed, the clinical characteristics, the ischaemic electrocardiographic findings and the presence of myocardial perfusion defects during stress testing are similar in syndrome X and coronary artery disease patients. Moreover, coronary sinus oxygen saturation abnormalities and pH changes, as well as myocardial lactate production and alterations of cardiac high energy phosphate are seen during stress testing in patients with syndrome X and appear to endorse an ischaemic origin of symptoms in at least a proportion of these individuals. Patients with chest pain and normal coronary arteries have abnormal vasodilatory coronary blood flow responses and an increased sensitivity of the coronary microcirculation to vasoconstrictor stimuli (microvascular angina). Microvascular endothelial dysfunction appears to be responsible for these coronary microcirculation abnormalities. Given the high prevalence of peri- and post-menopausal women in cardiac syndrome X, it has been hypothesized that oestrogen deficiency may play a major role in the pathogenesis of this condition. Oestrogen vasoactive properties involve endothelium-dependent effects and, in postmenopausal women, forearm vasodilatation induced by acetylcholine is potentiated by the acute local administration of intravenous oestradiol. This suggests that endothelium-dependent responses in the peripheral circulation may be modulated by steroid hormones. Impairment of endothelial function in post-menopausal women with syndrome X has been reported by various groups and it could be hypothesized that oestrogen deficiency may contribute to the development of microvascular angina through endothelial dysfunction and that exogenous oestrogen administration may have a beneficial effect in syndrome X patients. This article reviews current knowledge regarding the role of oestrogen deficiency in the pathogenesis of syndrome X and the potential therapeutic role of oestrogen replacement therapy in women with chest pain and normal coronary arteriograms