June 19, 2008 Postmenopausal women are at an increased risk of developing coronary artery disease, yet recent research studies have sometimes resulted in conflicting data regarding how best to treat or minimize the effects of the disease.
"Although it is commonly understood that postmenopausal women, particularly those with early menopause, have an increased risk of developing coronary artery disease and it was thought that hormone replacement therapy (HRT) would help to remedy this, some well-known clinical investigations, such as the Heart and Estrogen/progestin Replacement Study (HERS), were unable to demonstrate an improved outcome in postmenopausal women using HRT," said Thomas Schindler, M.D., chief of nuclear cardiology at the University Hospitals of Geneva, Geneva, Switzerland. "The exact mechanism behind this increased risk, however, remains uncertain."
As women age, researchers have noted that changes occur in the walls of the blood vessels--making it more likely for plaque and blood clots to form--and in the level of lipids (fats) in the blood. According to Dr. Schindler, some of the factors putting women at risk are an accumulation of body fat, insulin resistance, inflammation, dyslipidemia (disruption of lipid metabolism) and increases in arterial blood pressure. Another important factor for postmenopausal women is the deprivation of naturally occurring estrogen.
In a recent study, researchers evaluated the effect of long-term hormone replacement therapy with estrogen, mostly combined with progestin, on heart vessel function in 48 postmenopausal women who had been treated for coronary risk factors, such as hypercholesterolemia (high blood cholesterol) or arterial hypertension. The women were divided into groups according to HRT: Group 1 comprised 18 women who were on HRT at baseline and at follow-up positron emission tomography (PET) assessment of coronary endothelial function (the inner lining of the coronary vessels); group 2 comprised 18 women who were not on HRT; and group 3 comprised 12 women who were on HRT at baseline, but not at follow-up PET exam.
During the PET exam, the study participants underwent cold pressor testing (the immersion of the hand into a slush of ice water), which provokes the release of nitric oxide (NO) from the inner lining of the vessels (the vascular endothelium). The release of NO causes a relaxation of the vascular smooth muscle cells with a subsequent dilation of the vessel, resulting in an increase in blood flow to the heart. Apart from this vasodilatory effect, NO helps to protect heart vessels from the initiation and development of atherosclerosis (or heart vessel disease) by exerting numerous antiatherosclerotic and antithrombotic effects. If risk factors for coronary artery disease diminish normal functioning of the vascular endothelium and, thus, the bio-availability of artery-protective NO, a coronary artery disease process may be initiated and/or proceed.
"In the current study, a normal function of the coronary endothelium was indicated by a PET-measured flow increase in the heart vessels during sympathetic stimulation with cold-pressor testing, while an impaired increase, absence or even decrease in flow indicated a functional abnormality of the coronary endothelium," said Dr. Schindler.
"Given that preventive medical treatment of coronary risk factors, such as statins (cholesterol-lowering agents) or angiotensin-coverting enzyme inhibitors, usually improves coronary endothelial function, it is not known whether HRT, which commonly promotes the release of endothelial-derived NO in postmenopausal women with already medically treated coronary risk factors, might still exert an additional protective effect on the function of the coronary endothelium and, thus, the development of coronary artery disease," he added.
Applying PET, the researchers found that HRT widely maintained coronary endothelial function, while those postmenopausal women without HRT experienced a worsening in the endothelium function. In addition, postmenopausal women who gave up HRT during the observational period demonstrated the most severe drop in the coronary endothelial function.
"We concluded that in postmenopausal women on HRT, the vascular lining is benefited, which may help protect against the development of atherosclerosis," said Dr. Schindler.
He also stressed that further research is needed to test whether or not HRT replacement in postmenopausal women will result in an improved clinical outcome.
According to the American Heart Association, cardiovascular disease (CVD) is the largest single cause of death among women, accounting for one third of all deaths. In 2004, 461,152 females in the United States died from CVD, 7.2 million had coronary heart disease (CHD) and 3.3 million had a stroke.
Scientific Paper 508: T. H. Schindler, Nuclear Cardiology and Cardiovascular Center, Geneva, Geneva, Switzerland; R. Campisi, D. Dorsey, J. Sayre, H. R. Schelbert, Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, Calif., "Beneficial Long-term Effect of Hormone Replacement Therapy on Coronary Vasomotion in Postmenopausal Women With Treated Coronary Risk Factors," SNM's 55th Annual Meeting, June 14-18, 2008.
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