Hormone replacement therapy in postmenopausal women with specific risk factors for coronary artery disease
Introduction
In industrialised countries coronary artery disease (CAD) is the major cause of death in women. The mortality rate from CAD is about 3–4 fold that related to cancer. The risk of developing atherothrombotic CAD is associated with various factors. Modulation of these factors is a potential tool for the primary and secondary prevention of CAD, and may therefore be of great importance for the cardiovascular health in the individual, but it may also have a substantial socio-economic impact.
In women as compared to men, the incidence of CAD is low before the age of 50. In contrast, in women older than 50, CAD risk strongly increases, indicating that the postmenopausal oestrogen deficiency state is a major risk factor in the development of CAD. Moreover, young ovariectomised women also suffer from an increased risk of dying from CAD [1], which supports the hypothesis that loss of ovarian function increases CAD risk.
Accumulating evidence supports the suggested cardiovascular protective role of postmenopausal hormone replacement therapy (HRT) 2, 3. Many epidemiological studies and several meta-analyses have reported a 50% lower incidence of CAD in oestrogen users compared with non-users [4], and comparable data have recently been published for combined oestrogen–progestogen users [5]. In addition, experimental studies in monkeys [6], in rabbits and rats have demonstrated that hormone administration reduces the arterial cholesterol accumulation.
The cardiovascular protective influence of HRT appears to be of special benefit in women at high risk for CAD 7, 8, 9, 10, 11, 12. In the Lipid Research Clinic study, Bush et al. [7]reported a stronger reduction in CAD mortality in oestrogen-using hyperlipidaemic women compared with oestrogen-using normo-lipidaemic women. Ross et al. [8]demonstrated, in oestrogen-using women, that CAD mortality was relatively more reduced in heavy smokers when compared with non-smoking women. Ten-year mortality in oestrogen-using versus non-using women with angiographically proven CAD was more reduced in women with severe coronary stenosis than in women with normal angiography [9].
Section snippets
Risk factors
An increasing number of factors have been identified which influence the risk of developing CAD. For many years, most attention was given to the impact on CAD risk due to changes in serum lipids and lipoproteins, and it was demonstrated that postmenopausal women have a more atherogenic lipid profile when compared with premenopausal women. Furthermore, HRT was found to have favourable effects on the lipid profile reflected by a reduction in the atherogenic LDL-cholesterol and an increase in the
Blood pressure
The effects of HRT on blood pressure have scarcely been investigated. Most studies have reported no change or a small decrease in systolic and diastolic blood pressures 13, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91. Proposed mechanisms to explain these observations are vasodilation [92], possibly related to calcium antagonistic effects of oestrogens [93], and inhibition of the angiotensin-converting-enzyme [94].
Conclusions
Based on the literature presently available, there is strong evidence that cholesterol, Lp(a) and homocysteine, as important predictors for occlusive arterial disease, can be favourably modulated by HRT, and that the strongest reductions can be achieved in women with the highest concentrations.
Although clinical trials still need to demonstrate the impact of lowering concentrations of homocysteine and Lp(a), HRT appears to be a promising risk reduction strategy in this respect.
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