Subclinical atherosclerosis in multiple vascular beds: an index of atherosclerotic burden evaluated in postmenopausal women
Introduction
Although symptoms of coronary artery disease (CAD) in women occur 10–15 years later than in men [1], CAD is still a leading cause of death in women over age 60 [2]. We have previously shown that women with elevated premenopausal risk factors have a greater extent of carotid intima-media thickness at postmenopause [3], [4]. This suggests that women at risk to develop atherosclerosis can be identified during their premenopausal years, opening the opportunity for delay or prevention of cardiovascular disease through early modification of risk factors.
The carotid arteries are easily and accurately evaluated using ultrasound. Carotid ultrasound is used repeatedly as a non-invasive measure of atherosclerosis in general [5], and as a surrogate for coronary atherosclerosis in a number of clinical trials of cholesterol lowering [6], [7], [8]. The moderate correlation between carotid and coronary atherosclerosis [9] is of a similar magnitude to the correlation between two different coronary arteries [10].
Electron beam tomography (EBT) now allows the non-invasive evaluation of the coronary arteries directly by providing a quantitative measure of coronary calcification. Coronary calcification relates to the degree of atherosclerosis found on pathological exam [11], and also predicts incident cardiovascular events [12], [13], [14]. In addition, EBT allows evaluation of the aorta for quantification of vascular calcification.
The Healthy Women Study (HWS) is a longitudinal study of risk factors for coronary heart disease in women as they progress through the peri and postmenopausal years. Women were recruited starting in 1983 and now are an average of 8 years postmenopause. These women underwent carotid ultrasound and EBT to evaluate the extent of atherosclerosis in the coronary, aorta and carotid arteries. This report evaluates the degree to which measures of subclinical atherosclerosis in these vascular beds correlate with each other and reports the risk factors associated with atherosclerosis in each of these vascular beds. A subclinical disease scale, which aggregates information from each of these measures is described and associated with risk factors.
Section snippets
Healthy Women Study
Detailed descriptions of the HWS have been previously published [15], [16]. Beginning in 1983, 541 premenopausal women aged 42–50 years, living in Pittsburgh, PA were recruited. Eligible women had diastolic blood pressures (BPs) less than 100 mmHg, were free from chronic disease requiring medication (including BP medication), were not taking hormone replacement therapy (HRT) and were menstruating within 3 months of the baseline examination. These women were followed until they ceased cycling
Results
Coronary and aortic calcification data are available for a total of 274 women. At the time of EBT testing, their average age was 59 years, they were an average of 8 years postmenopause, and 50% were taking HRT. At baseline, prior to menopause, the average cholesterol was 184 mg/dl, average HDL was 60 mg/dl, average LDL was 108 mg/dl, average BMI was 25 kg/m2, and average systolic BP was 108 mmHg. Approximately 26% were current smokers at baseline. These characteristics are similar to women who
Discussion
This study demonstrates that different measures of subclinical atherosclerosis are correlated with one another, even in a healthy population of middle-aged women. Traditional cardiovascular risk factors were related to disease in each vascular bed, underscoring that atherosclerosis is a systemic disease affecting the vascular system as a whole. A higher prevalence of measurable disease was found in the aorta and carotid arteries than in the coronary arteries, suggesting that disease can be
Acknowledgements
This project was funded by NHLBI grant numbers HL28266 and HL40962. This research was done under the tenure of an Established Investigatorship from the American Heart Association (KST).
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