Arterial stiffness in women, during the menopausal transition and beyond, as a predictor of cardiac disease: an assessment of the contribution of hormonal factors

Abstract Background Cardiovascular disease (CVD) in women remains the major cause of mortality, accounting for one third of all deaths. Although similar numbers of men and women die of CVD, onset in women occurs approximately 10 years later. It has been hypothesised that the endogenous sex steroids, primarily oestrogen, are cardioprotective and are responsible, in part, for this delay in CVD. Menopause is associated with a deterioration in many conditions recognised as CVD risk factors. However, the precise mechanisms by which menopause might increase cardiovascular risk remain largely unexplained It has been established through a number of studies that arterial stiffness is a better marker of cardiovascular risk than conventional risk factors. There has been no definitive answer as to whether menopause specifically accelerates the age-related increase in arterial stiffness. In addition, if menopause does accelerate the age-related increase in arterial stiffness, it needs to be established whether this response is a direct effect of oestrogen withdrawal or an indirect effect due to an increase of atherosclerotic risk factors as a result of oestrogen withdrawal through the menopause transition. The measurement of pulse wave velocity (PWV) using non-invasive techniques is well documented and widely accepted as the simplest, most robust and most easily reproducible method of determining arterial stiffness. In particular, carotid-femoral PWV is a direct measurement that corresponds to the propagative model of the arterial system. Aortic pulse wave velocity (PWV) and Augmentation index (AIx) are independent predictors of adverse cardiovascular events, including mortality. Aims To establish whether oestrogen withdrawal through the menopause transition contributes to an increase in arterial stiffness; to show that a non-invasive measure of pulse wave analysis (PWA) and pulse wave velocity (PWV) employing applanation tonometry can be used in routine clinical practice as a more effective marker of arterial disease and prognosis in women than conventional measures of brachial systolic pressure and fasting lipids; to formulate intervention strategies supported and justified by these data. Methods The subjects were recruited as part of a longitudinal assessment of age-related changes in a random sample of urban women from Brisbane. The sample consisted of 468 women, distributed over 4 age groups, 40-49, 50-59, 60-69 and 70-79 years. Each subject had PWA and PWV performed non-invasively using applanation tonometry, measured at entry into the study and repeated 3-4 years later. Results In multiple linear regression models, age was the predominant correlate of increasing augmentation pressure (AP) (P<0.0001), augmentation index (AIx) (P<0.0001), augmentation index adjusted to a heart rate of 75 (AIx@75) (P<0.0001) and pulse wave velocity (PWV) (P<0.0001). Analysis of covariance showed no significant difference in adjusted-mean of AP, AIx or PWV between menopause groups (pre, peri, post). Adjusted-mean of AP and PWV was comparable between women on hormone therapy (n=130) and non-users (n = 338). Menopause per se does not appear to alter gradual age-dependent changes in arterial stiffness and central pressure augmentation. Conclusion The null results in the present study suggest that the fall in endogenous sex steroids at the time of menopause, although associated with complex biologic effects, has no effect on arterial stiffness as measured by PWV and AIx. Key risk factors that should be controlled in menopausal woman include hypertension (a particularly powerful risk factor), dyslipidaemia, obesity and other components of the metabolic syndrome, with the prevention and control of diabetes a high priority. Arterial stiffness is recognised as an independent marker of CV risk. The present study therefore suggests that rather than focusing primarily on the lowering on brachial blood pressure, consideration should also be given to identifying menopausal women at risk of CV morbidity and mortality using non-invasive techniques to assess central arterial stiffness.