Prevention of atherosclerosis progression in asymptomatic healthy elderly.

This review focuses on the role of lipid-lowering, blood pressure-lowering, antithrombotic drugs and diet and their place in the prevention and treatment of atherosclerosis in middle-aged and elderly men and woman. The major emphasis is on noninvasive assessment of the extent of atherosclerotic plaque and the importance of following plaque progression or regression by use of noninvasive ultrasound. With these data, we can demonstrate to both patients and physicians the value, at any age, of treating hypertension and abnormal blood lipids.

Carotid intimal medial thickness in human immunodeficiency virus-infected women: effects of protease inhibitor use, cardiac risk factors, and the metabolic syndrome.

CONTEXT: Little is known regarding carotid intimal medial thickness (IMT) in HIV-infected women and the risk factors for subclinical atherosclerosis in this population, including antiretroviral therapy and the metabolic syndrome. OBJECTIVE: Our objective was to assess carotid IMT in relationship to HIV status and antiretroviral therapy in HIV-infected women in comparison with healthy age- and body mass index (BMI)-matched control subjects. SETTING AND SUBJECTS: The study took place at an academic medical center and included 97 HIV-infected women compared with 86 age- and BMI-matched healthy control subjects. MAIN OUTCOME MEASURES: We assessed carotid IMT, metabolic syndrome, and risk factors for increased IMT. RESULTS: Carotid IMT was not increased in HIV-infected women [0.62 mm (0.57-0.68); median (IQR)] compared with non-HIV-infected women [0.61 mm (0.55-0.68)] matched for age and BMI (P = 0.07) but was increased significantly among HIV patients receiving a protease inhibitor (PI) [0.65 (0.59-0.71) mm] vs. non-PI-treated patients [0.61 (0.57-0.66) mm] (P < 0.05) and vs. control subjects [0.61 (0.55-0.68) mm] (P < 0.05). The prevalence of metabolic syndrome was significantly increased among the HIV-infected women compared with control subjects and particularly in PI- vs. non-PI-treated HIV patients (45 vs. 19%, P = 0.001). Metabolic syndrome score correlated with IMT among non-HIV patients but not among the HIV group. Individual risk factors most strongly associated with IMT in multivariate regression modeling in the control group were age and waist-to-hip ratio, and among the HIV group age and waist circumference. CONCLUSIONS: These data demonstrate increased carotid IMT in HIV-infected women receiving PI therapy, which may be due to associated metabolic abnormalities related to PI therapy or more direct effects of this medication class on the vasculature. Additional studies of the mechanisms by which PI uses results in subclinical atherosclerosis are needed.

Effects of obesity, body composition, and adiponectin on carotid intima-media thickness in healthy women.

CONTEXT: Increased common carotid intima-media thickness (IMT) is predictive of coronary artery disease and stroke. OBJECTIVE: In this study, we investigated common carotid IMT by obesity category in a cohort of healthy women without previously known cardiovascular disease. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURES: One hundred healthy women (aged 24-59 yr) from the general community enrolled in an observational study conducted at an academic medical center participated in the study. B-mode ultrasound imaging of the common carotid arteries was used to measure common carotid IMT in 99 subjects. Fat distribution was determined by computed tomography. Hormonal and inflammatory parameters related to cardiovascular disease and obesity were measured. RESULTS: IMT was higher in obese [body mass index (BMI) >or= 30 kg/m(2)], compared with overweight women (BMI >or= 25 and < 30 kg/m(2)) [0.69 mm, interquartile range (IQR) 0.60-0.75 mm] vs. 0.62 mm [IQR 0.56-0.68 mm), P = 0.044] and in comparison with lean women (BMI < 25 kg/m(2)) [0.69 mm (IQR 0.60-0.75 mm) vs. 0.59 mm (IQR 0.54-0.67 mm), P = 0.016]. In multivariate modeling, age (beta = 0.0050 mm change in IMT per year of age, P = 0.003), smoking (beta = 0.0044 mm change in IMT per pack-year, P = 0.046), and sc abdominal adiposity (beta = 0.00026 mm change in IMT per square centimeter, P = 0.010) were positively associated with IMT, whereas adiponectin (beta = -0.0042 mm change in IMT per milligram per liter, P = 0.045) was negatively associated with IMT. Visceral adiposity (beta = 0.00048 mm change in IMT per square centimeter, P = 0.092) was not significantly associated with IMT after adjusting for age, race, smoking, sc abdominal adiposity, and adiponectin. CONCLUSIONS: Obesity is associated with increased common carotid IMT in young and middle-aged women. Adiponectin and sc abdominal adiposity are associated with carotid IMT in this population.

Atherin: a newly identified, lesion-specific, LDL-binding protein in human atherosclerosis.

Prolonged retention of LDL in focal, atherosclerosis-prone areas of arteries is a primary event in atherogenesis. To determine whether unrecognized LDL-binding proteins participate in this process, we generated a cDNA expression library from deendothelialized rabbit aorta, a model for early atherosclerosis that shows striking focal LDL retention in healing lesions. Library screening identified a previously unknown, highly conserved, 56kDa LDL-binding protein that we call atherin. Confocal microscopy of human arteries shows that atherin is present only in atherosclerotic lesions, not in normal intima. Within lesions, atherin is found both in the extracellular compartment and within foam cells. Essentially all extracellular atherin, as well as atherin within foam cells, co-localizes with LDL across the entire spectrum of human disease, from early lesions to advanced plaques. Our results suggest that focal arterial LDL accumulation may be initiated and maintained by binding between LDL and atherin, and that atherin may play a central role in atherogenesis by immobilizing LDL in the arterial wall.

Increased cardiovascular disease risk indices in HIV-infected women.

Little is known regarding cardiovascular disease risk indices in HIV-infected women. This study investigated cardiovascular disease risk indices in 100 consecutively recruited HIV-infected women and 75 healthy female control subjects. Subjects were recruited from hospital- and community-based health care providers. C-reactive protein (CRP), interleukin-6 (IL-6), adiponectin, lipid, and glucose levels were the main outcome measures. CT scan, dual-energy x-ray absorptiometry (DXA), and anthropometry were used to assess body composition. Although similar in age, weight, and racial composition, HIV-infected women demonstrated higher CRP (4.6 +/- 0.7 vs. 2.3 +/- 0.4 mg/L, P = 0.007), IL-6 (2.7 +/- 0.2 vs. 1.8 +/- 0.1 pg/mL, P = 0.02), triglyceride (1.84 +/- 0.21 vs. 0.85 +/- 0.05 mM, P = 0.0002), 2-hour glucose after oral glucose challenge (6.88 +/- 0.22 vs. 5.72 +/- 0.17 mM, P = 0.0003), and fasting insulin (81 +/- 8 vs. 45 +/- 2 pM, P = 0.0002) and lower high-density lipoprotein cholesterol (1.17 +/- 0.03 vs. 1.45 +/- 0.05 mM, P < 0.0001) and adiponectin (5.4 +/- 0.3 vs. 7.6 +/- 0.5 mg/L, P = 0.0001) levels compared with the control population. HIV-infected women had more abdominal visceral fat and less extremity fat by CT and DXA scan and demonstrated a higher waist-to-hip ratio (WHR) than the control population. Within the HIV group, CRP and other indices were significantly related to body composition in stepwise regression models. Among all subjects, WHR, but not HIV status, was significantly related to CRP and other cardiovascular disease risk indices. HIV-infected women demonstrate significantly increased risk factors for cardiovascular disease in association with abnormal fat distribution.

Localization of (99m)Tc-Labeled ApoB Synthetic Peptide in Arterial Lesions of an Experimental Model of Spontaneous Atherosclerosis.

We have previously shown that after administration of (123)I-SP-4 (a synthetic ApoB peptide fragment) to Watanabe heritable hyperlipidemic (WHHL) rabbits that foci of tracer uptake can be identified by external gamma camera imaging which correspond to regions of the aortas found to contain abundant atherosclerotic lesions at postmortem evaluation. Because (99m)Tc is preferred over (123)I for scintigraphic imaging, we prepared a (99m)Tc-labeled form of the SP-4 peptide, designated (99m)Tc-P199. To assess the feasibility of detecting atherosclerotic lesions using (99m)Tc-P199 and to compare the relative uptake of the (99m)Tc-labeled and radioiodinated peptides by such lesions, an admixture of (99m)Tc-199 and (125)I-SP-4 was administered to 11 WHHL and 2 normal rabbits. These animals were imaged for up to 3 h and were sacrificed 3--4 h after injection. The extent of aortic lesion involvement and radiotracer uptake were quantitatively compared by planimetric analysis of photographs of the endothelial surface, (99m)Tc-P199 ex vivo images and (125)I-SP-4 autoradiograms of the excised aortas. Pairwise correlation coefficients for planimetric analysis were as follows: photographs versus ex vivo images, r = 0.83, p = 0.003; photographs versus autoradiograms, r = 0.87, p = 0.001; ex vivo images versus autoradiograms, r = 0.83, p = 0.003. (99m)Tc-199 in vivo gamma camera images revealed relatively weak focal aortic uptake in 8 of 11 WHHL rabbits manifesting aortic lesions, and focal carotid artery uptake in 4 of 6 WHHL rabbits manifesting carotid lesions. Neither aortic nor carotid foci were visualized in the normal rabbits. We conclude that (99m)Tc-199 localizes specifically in atherosclerotic lesions and may be useful for external imaging of atherosclerosis.