Baseline values but not treatment-induced changes in carotid intima-media thickness predict incident cardiovascular events in treated hypertensive patients: findings in the European Lacidipine Study on Atherosclerosis (ELSA).

BACKGROUND: Baseline carotid intima-media thickness (IMT) and plaques are considered predictors of cardiovascular events, but whether they maintain predictive value in treated hypertensive patients and whether time-related (or treatment-induced) IMT changes are additional predictors are unknown. METHODS AND RESULTS: Analyses were performed of the data from the European Lacidipine Study on Atherosclerosis (ELSA), a large, randomized, intervention trial in which 2334 hypertensive patients from 7 European countries were followed up under effective antihypertensive treatment for 3.75 years. Kaplan-Meier curves indicated progressively lower survival free of any type of outcome except stroke, with increasing baseline IMT quartiles or increasing IMT values, even after adjustment for major baseline risk factors. Incidence of any outcome except stroke also was related to baseline number of carotid plaques. However, when both baseline and on-treatment IMT values were entered in Cox proportional-hazards models, differences in IMT compared with baseline did not predict cardiovascular outcomes. Although on-treatment rather than baseline IMT values significantly entered some of the proportional-hazards models, baseline and on-treatment IMTs were highly correlated, and therefore these results are inconclusive. CONCLUSIONS: ELSA shows that carotid intima-media thickening and plaques are important added risks of cardiovascular outcomes in a treated hypertensive population independently of blood pressure and traditional risk factors. However, the analysis failed to show a predictive role of treatment-dependent IMT changes. These negative conclusions should be tempered by the limitations inherent in the smallness of these changes compared with the large individual differences in baseline IMTs.

The association of myeloperoxidase promoter polymorphism with carotid atherosclerosis is abolished in patients with type 2 diabetes.

OBJECTIVES: Type 2 diabetes mellitus (DM) enhances the development of atherosclerosis and reduces the activity of the oxidative myeloperoxidase (MPO) enzyme. MPO gene has a functional promoter polymorphism -463G/A which leads to high- (GG) and low-expression (AG, AA) genotypes. DESIGN AND METHODS: We studied the association of MPO polymorphism with carotid artery intima-media thickness (IMT) in 198 randomly selected Finnish men of Caucasian origin, 161 non-diabetics and 37 with type 2 DM. Their carotid IMT was measured by high-resolution ultrasonography, and the overall mean IMT value was calculated. MPO genotypes were determined by the PCR-RFLP method. RESULTS: We found significant MPO genotype-by-study-group (control/DM) interactions with the overall mean IMT and internal carotid IMT (p=0.05 and p=0.04, respectively). Among non-diabetic subjects, the overall carotid IMT was 7.3% higher in subjects with the low-activity genotype when compared to the high-activity (G/G) group. The results remained significant after adjustment for total cholesterol and smoking (p=0.015). No similar genotypic association was found for the subjects with type 2 DM. CONCLUSIONS: This data suggests that in subjects with normal glucose metabolism, MPO gene variation may modify the carotid artery IMT.

Assessment of carotid intima-media thickness in subjects with ischemic cerebrovascular events undergoing endarterectomy.

BACKGROUND AND AIM: In clinical settings, the degree of lumen stenosis is the parameter used to select patients for carotid surgery. The present study was designed to measure carotid intima-media thickness (IMT), an indicator of atherosclerotic burden, in a sample of consecutive patients with ischemic cerebrovascular events referred for endarterectomy. METHODS AND RESULTS: Carotid endarterectomy specimens from 55 consecutive patients (age 66+/-10 years) admitted to hospital with recent documented atherothrombotic ischemic cerebrovascular events were compared with 24 carotid arteries from people (age 68+/-11 years) who had died from documented causes unrelated to cerebrovascular disease. Measurement of extracranial carotid atherosclerosis was made from three anatomically defined segments, using image-processing software. A total of 426 cross sections was analyzed. Increasing IMT measures were clearly associated with increased risk of an ischemic event. Single maximum IMT values of 2.33 mm (95% CI, 1.69-2.96) for the common carotid, 2.45 mm (95% CI, 1.97-2.93) for the bifurcation, and 2.23 (95% CI, 1.83-2.64) for the internal carotid were associated with a 75% probability of a cerebrovascular ischemic accident. Receiver operator characteristic curve analyses demonstrated that the diagnostic ability of IMT measurements performed at the level of internal carotid artery to separate cases from controls was greater than common carotid artery or bifurcation measurements. CONCLUSIONS: The present pathology study provides data on IMT in patients admitted to hospital for cerebrovascular accidents and referred for carotid endarterectomy.

Different relation between 24-h blood pressure and distensibility at different peripheral arteries. Data from the European Lacidipine Study on Atherosclerosis (ELSA).

INTRODUCTION: The European Lacidipine Study on Atherosclerosis (ELSA) has been planned to investigate the effect of reduction in office and ambulatory blood pressure by lacidipine versus atenolol on carotid artery wall thickness in mild to moderate essential hypertensive patients with no metabolic abnormalities. One prespecified sub-study of ELSA focused on measurements of arterial distensibility in the carotid as well as in the radial artery to determine the relationship of functional arterial properties with office versus ambulatory blood pressure (BP) values as well as the correspondence between functional and structural arterial alterations. METHODS: The sub-study was conducted on 124 patients recruited in four centres (Monza-Milan, Paris, Grenoble and Glasgow). BP was measured both by a mercury sphygmomanometer and by 24-h ambulatory monitoring. Common carotid artery wall thickness was measured by certified sonographers as described in the main study. Common carotid and radial artery distensibility were obtained by echotracking techniques, which allowed to relate changes in arterial diameter with systo-diastolic BP changes. RESULTS: Carotid artery wall distensibility showed (1) a negative correlation with office and more so 24-h average systolic BP (r = -0.45 and -0.58, P < 0.008 and 0.001) but not with office or 24-h diastolic BP) and (2) a negative correlation with the corresponding wall thickness (r = -0.47, P < 0.005). In contrast, at the radial artery level distensibility and thickness showed no correlation with each other and with BP. Carotid (but not radial) artery distensibility also correlated with ambulatory systolic BP variability but the correlation was lost after adjustment for age and mean BP values. CONCLUSION: These data suggest that stiffening of large elastic artery is reflected more by ambulatory than office BP elevations, systolic BP being much more important than diastolic. Alterations of large elastic arteries function is related to structural wall changes. Functional and structural properties of middle-size muscle arteries are independent of BP.

Cardiovascular risk profile of asymptomatic healthy young adults with increased carotid artery intima-media thickness: the Bogalusa Heart Study.

OBJECTIVE: The cardiovascular (CV) risk profile of healthy young adults was studied at the extreme 5th percentiles of carotid intima-medial thickness (IMT) as measured by B-mode ultrasonography in different segments of the carotid artery. METHODS: Anthropometric variables, blood pressure, laboratory data, family history health habits were collected from 518 individuals (mean age 32 years). Individuals in the top and bottom 5th percentiles of IMT of carotid bulb or bifurcation area (n = 22) and the common carotid (n = 25) segments were examined for presence of risk factors. Univariate analyses compared the two groups, t tests, and chi-square tests were performed. RESULTS: The common carotid segment top and bottom percentiles of IMT differed with respect to age (p < 0.000), BMI (p < 0.001). In contrast, carotid bulb segment top and bottom percentiles differed with respect to age, (p = 0.001), BMI (p = 0.004), HDL cholesterol (p 0.006), LDL cholesterol (p = 0.023), ECG diagnosis (p = 0.016), smoking status (p = 0.004). The individuals in the top 5th percentile of IMT of the bifurcation area were more obese (BMI > 30), hypertensive (BP > 140/90 or on medications), dyslipidemic (LDL > 130 mg/dl, triglycerides > 150, HDL < 40 mg/dl), and more often had an abnormal ECG, and a history of smoking. CONCLUSION: The observed deleterious effect of CV risk factors on IMT of the carotid artery, a surrogate measure of coronary atherosclerosis, underscores the risk factor profile history in youth. The prevalence of multiple risk factors among those in the top 5th percentile of IMT was significantly higher with respect to the carotid bulb segment only (p = 0.000), suggesting more sensitivity to the risk factor burden compared with the common carotid segment. These observations have important implications in preventive cardiology.