Artery Wall Imaging and Effects of Postmenopausal Estrogen Therapy

Sammanfattning: Postmenopausal estrogen therapy, initiated early in the menopause, seems to protect against development of atherosclerosis and cardiovascular diseases. This thesis concerns studies of artery wall thickness and arterial stiffness estimated by noninvasive ultrasound techniques in long-term estrogen treated postmenopausal women who initiated therapy at the time of the menopause.A noninvasive 25 MHz high-frequency ultrasound technique was validated in the imaging of superficial arteries by using an animal model. Ultrasound estimates of the artery wall layers obtained in vivo in the pig were compared to ex-vivo histomorphometry. Valid estimates of total artery wall and media thickness were found for the most superficial arteries. Adventitia thickness was underestimated and intima thickness overestimated in this animal model when non-atherosclerotic vessels were imaged.To validate the clinical usefulness of separately estimating the artery wall layers in the human, the carotid artery wall was imaged in elderly subjects. Separate estimates of intima thickness, media thickness and intima/media ratio differed significantly between subjects with and without atherosclerosis and CVD, indicating that this noninvasive high-frequency ultrasound method might be a strong tool in monitoring changes in artery wall morphology associated with aging and development of atherosclerosis.The investigation of intima thickness, media thickness and intima/media ratio of the carotid and femoral arteries in long-term estrogen treated postmenopausal women showed a maintenance of a thin intima and a preservation of media thickness and intima/media ratio at values similar to those obtained in women of fertile age. By comparing estrogen-users with age-matched postmenopausal nonusers, long-term estrogen therapy initiated at the time of the menopause seemed to counteract the increase in intima and decrease in media thickness associated with aging and development of atherosclerosis. The preservation of the artery wall morphology into older age might be a mechanism for the well-documented cardioprotective effects of estrogen when therapy is initiated early after menopause. However, long-term estrogen therapy showed no substantial effects on the age-related changes in arterial stiffness estimated at the aorta, carotid and femoral arteries, suggesting that any long-term cardioprotective effect that estrogen therapy may have is unlikely to be mediated by an impact on arterial stiffness.