Atherosclerosis and the menopause

Abstract

Atherosclerosis is the process whereby atheromatous plaques develop in large and medium-sized arteries. In premenopausal women plaque formation is a very rare event in the absence of high risk factors. In the perimenopausal period simple atheromatous plaques formation occurs in the early stages. With the ageing process and years from menopause, late-stage complicated plaques result. The menopause is characterized by a steep rise in the atherogenous lipid profile. Following the climacteric, blood pressure rises increasing the occurrence of hypertension. Pro-atherogenic circulating haemostatic factors such as fibrinogen, plasmogen activator-1, factor VII, homocysteine and von Willebrand factor all increase after the menopause. As evidenceof a chronic inflammatory process following the menopause hs-C reactive protein increases after the menopause. The pathogenesis of atherosclerosis appears to initiate from an inflammatory reaction following injury to the endothelium due to shear forces on the vessel wall. Through the presence of adhesion molecules, monocytes are recruited into the endothelium and later differentiate into macrophages. In the presence of chronic inflammation more lipid is deposited followed by smooth muscle proliferation in the vessel wall. Collagen and proteoglycans are produced at the site of the atherosclerotic plaque as part of the ongoing chronic inflammatory process. With further accumulation of connective tissue, calcium deposition ensues resulting in end-stage atheromatous plaque formation. Complicated plaque formation is irreversible and does not appear to be amenable to treatment with lipid reducing agents such as the lipostatins and oestrogens. Conversely early simple plaques formation may be modulated by lipid-reducing drugs and this has also been demonstrated with hormone replacement therapy given during the climacteric or early after the menopause. Hormone replacement therapy appears to favourably modulate the surrogates for atherosclerosis possibly attenuating cardiovascular disease in postmenopausal women.