Evaluation of an ultrasound method to study early atherosclerotic changes in the arterial wall. A three-year study in men at high risk for cardiovascular disease

Abstract

The aim of the first experimental work was to identify the anatomical correlates to the different echo interfaces in ultrasound images of the carotid artery and to describe principles for accurate and valid measurements of arterial wall and lumen dimensions. Furthermore, to develop and describe a computerized method for measurement of intima-media thickness (IMT) and lumen diameter. The aims of the clinical part of the study was first to evaluate the whether hypertensive patients at high risk of cardiovascular disease had larger far wall common carotid IMT than a control group and to relate the IMT to signs or symptoms of atherosclerotic disease. A 3-year follow up study was then performed in the high risk group to analyze if a favorable change in risk factors, caused by a risk factor modification program, might beneficially affect ultrasound assessed IMT or plaques in the carotid artery in comparison with usual care. Furthermore, to evaluate ultrasound measurements of IMT and plaque occurrence in the femoral artery in relation to symptoms of claudicatio intermittens and ankle-arm index. Finally, to evaluate the presence of possible myocardial ischemia according to different exercise ECG and 24-h Holter monitoring criteria and the relationship to common carotid IMT in the high risk hypertensive group and a group at low cardiovascular risk. We concluded from the in vitro ultrasound imaging experiments that lumen and IMT of the far wall were accessible for quantitative measurements. A computerized system for measurements of wall thickness and lumen diameter was developed. Studies of inter- and intra-observer variability showed a satisfactory reproducibility for measurements of both carotid and femoral IMT. The IMT and lumen diameter of the common carotid artery were increased in the high risk hypertensive patients in comparison to a control group and the IMT was related to plaque status in the carotid artery region. Occurrence of moderate to large plaque formations in the carotid artery was related to clinically manifest cardiovascular disease. Though favorable changes in risk factors occurred, there was no difference in IMT and plaque status between the intervention and usual care groups after 3 years. Fasting insulin at baseline was related to the increase in IMT during follow-up. The femoral artery study suggested that the sonographic variables were valuable indicators of atherosclerotic disease and that subclinical atherosclerosis in the femoral artery was more common in the patients than earlier known. The exercise ECG study showed that heart rate adjusted ST criteria were more sensitive in detecting possible myocardial ischemia than standard criteria. The ST/HR slope and rate recovery loop completed each other and abnormal changes were related to an increased IMT. The contribution of standard criteria and Holter monitoring to diagnosis were insignificant. A new quantitative method to assess the rate recovery loop was described. In summary, new computer-aided ultrasound methods has been presented, suitable for direct evaluation of early subclinical atherosclerosis in large superficial arteries as the carotid and femoral arteries. These methods are useful tools in evaluating IMT in cross-sectional and prospective studies. Exercise ECG testing should be analyzed by heart rate adjusted criteria, their validity is supported by their association with an increased IMT