The Verapamil in Hypertension and Atherosclerosis Study (VHAS) : Results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness

Ultrasound high resolution B-mode imaging of human arteries allows in vivo an accurate and non-invasive determination of the thickness of the intimal-medial complex. A computer assisted procedure to measure this parameter at the level of common carotid arteries was developed. The average difference between duplicate thickness determinations was 4.6%. The thickness of the intimal medial complex of common carotid arteries was then measured in a group of hypercholesterolemic patients. This parameter was significantly greater in these patients as compared to controls (P less than 0.001). The prevalence of small plaques in the carotid arterial tree was also significantly increased in patients. Analysis of data showed that in controls, but not in patients, the thickness of the intimal medial complex increases with age (r = 0.46, P less than 0.05). Within the hypercholesterolemic group, intimal-medial complex values were greater in male patients and in smokers. It is concluded that the common carotid arteries of hypercholesterolemic patients show thickening of the intimal-medial complex. Cigarette smoking, male sex and age increase the extent of this modification. The determination of this parameter using a non-invasive technique may represent an important tool to monitor in vivo the progression and/or the regression of early atherosclerosis in man.

The Carotid Atherosclerosis Italian Ultrasound Study (CAIUS) was performed to test the effects of lipid lowering on the progression of carotid intima-media thickness (IMT) in 305 asymptomatic patients from a Mediterranean country. Eligibility included hypercholesterolemia (baseline means: low-density lipoprotein [LDL] = 4.68 mmol/L, high-density lipoprotein [HDL] = 1.37 mmol/L), and at least one 1.3 < IMT < 3.5 mm in the carotid arteries. Patients (mean age 55 years, 53% male) were assigned to pravastatin (40 mg/day, n = 151) or placebo (n not equal to 154). Ultrasound imaging was used to quantify IMT at baseline, and semiannually thereafter for up to 3 years. The mean of the 12 maximum IMTs (MMaxIMT), was calculated for each patient visit, and used to determine each patient's longitudinal progression slope. The intention-to-treat group difference in the MMaxIMT progression was chosen a priori as the primary end point. Five serious cardiovascular events (1 fatal myocardial infarction), and 7 drop-outs for cancer were registered. In the pravastatin group, LDL decreased -0.22 after 3 months versus -0.01 in the placebo group, and remained substantially unchanged afterward (-0.23 versus +0.01 at 36 months, respectively). Progression of the MMaxIMT was 0.009 +/- 0.0027 versus -0.0043 +/- 0.0028 mm/year (mean +/- SE, P < 0.0007) in the placebo and pravastatin groups, respectively. IMT progression slopes diverged after 6 months of treatment. Pravastatin stops the progression of carotid IMT in asymptomatic, moderately hypercholesterolemic men and women. This finding extends the beneficial effects of cholesterol lowering to the primary prevention of atherosclerosis in a population with relatively low cardiovascular event rates, and suggests that this benefit is mediated by specific morphological effects on early stages of plaque development.

The evolution of atherosclerosis can be studied before development of symptomatic plaque by evaluating morphologic changes of the intima-media (I-M) complex, seen on high-resolution ultrasonography of the arterial wall. These qualitative changes require large alterations in vessel wall appearance to recognize progression of atherosclerosis. It has been suggested that measurement of the thickness of the I-M complex may be a quantitative and more sensitive method of assessing these early atherosclerotic changes. High-resolution ultrasonography has been used to measure the thickness of the I-M complex in 140 symptom-free subjects. The mean thickness of the I-M complex of the common carotid arteries was linearly related to the age (r = 0.77; p < 0.001), pack-years of smoking (r = 0.39; p < 0.05), the systolic blood pressure (r = 0.51, p < 0.01), and to the arterial ultrasound score (r = 0.85). The arterial ultrasound score has previously been shown to correlate with the presence of asymptomatic myocardial ischemia and with the development of cardiovascular symptoms. The mean thickness of the I-M complex in subjects without plaque (in the common carotid or common femoral artery bifurcations) was significantly thinner than in subjects with plaque (p < 0.001). The thickness of the I-M complex of the common carotid arteries is a measure of the risk for the development of cardiovascular symptoms in symptom-free individuals.