Cardiovascular risk in patients with human immunodeficiency virus infection: incomplete data.
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Antiretroviral Therapy, Highly Active↗
Biomedical subjects
James H Stein
Publications and source records attributed to James H Stein.
Validation of a carotid intima-media thickness border detection program for use in an office setting.
BACKGROUND: A unique semiautomated border detection program (BDP) designed for use on a personal computer was evaluated to determine whether: (1) carotid intima-media thickness (CIMT) measurements were bioequivalent to a reference laboratory; and (2) it would allow a novice (NOV) reader with no medical training to accurately and reproducibly measure CIMT. METHODS: Far-wall CIMT was measured blindly and in duplicate by an experienced and NOV reader using BDP and by a reference laboratory. RESULTS: Mean CIMT using BDP was bioequivalent to the reference laboratory (two 1-sided T-test, P < .05) with small absolute differences (experienced 0.011 +/- 0.004 mm, NOV 0.022 +/- 0.004 mm). Reproducibility was high, with small coefficients of variation when used by either the experienced (3.1%) or NOV (7.8%) reader. CONCLUSION: CIMT measurements using BDP were accurate and reproducible. It was mastered easily by a NOV reader and appeared suitable for use in an office setting.
Adult↗
President's page: New York 1952 to Atlanta 2006: celebrating the cardiovascular community.
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Cardiology↗
Increased subclinical atherosclerosis in young adults with metabolic syndrome: the Bogalusa Heart Study.
OBJECTIVES: The purpose of this study was to investigate the association of metabolic syndrome (MetS) with subclinical atherosclerosis, determined by ultrasound carotid intima-media thickness (CIMT) measurements, in young adults. BACKGROUND: Metabolic syndrome is associated with subclinical atherosclerosis and increased cardiovascular risk in older and middle-aged adults; however, these associations have not been studied among young adults. METHODS: Non-diabetic subjects from Bogalusa Heart Study, a longitudinal study of atherosclerosis in young adults, underwent B-mode ultrasonography of the carotid arteries. Metabolic syndrome was defined with the National Cholesterol Education Program Adult Treatment Panel III (MetSNCEP) and World Health Organization (MetSWHO) definitions. CIMT and MetS associations were evaluated with multivariable regression and area under receiver-operator characteristic curve (AUC) analyses. RESULTS: Of 507 subjects (29% black, 39% male, mean [SD] age 32 [3] years), 67 (13%) had MetSNCEP and 65 (13%) had MetSWHO. Common (mean = 0.70 [0.11] mm vs. 0.66 [0.08] mm, p = 0.002) and internal CIMT (0.72 [0.21] mm vs. 0.68 [0.12] mm, p = 0.020) were higher among those with MetS(NCEP) than those without MetS(NCEP). Common (0.69 [0.11] mm vs. 0.66 [0.08] mm, p = 0.020) and internal CIMT (0.73 [0.23] mm vs. 0.68 [0.12] mm, p = 0.012) also were higher among those with MetSWHO than those without MetSWHO. Composite CIMT increased with the number of MetS components present (MetSNCEP r = 0.997, p < 0.001; MetSWHO r = 0.946, p = 0.053). Metabolic syndromeNCEP (AUC = 0.557, 95% confidence interval [CI] 0.513 to 0.601) and MetSWHO (AUC = 0.539, 95% CI 0.495 to 0.584) both predicted composite CIMT > or =75th percentile. CONCLUSIONS: In young adults, MetS is associated with increased atherosclerotic burden, and therefore, increased cardiovascular risk. These results support the importance of screening and early intervention in this population.
Adult↗
Advanced lipoprotein testing does not improve identification of subclinical atherosclerosis in young adults: the Bogalusa Heart Study.
BACKGROUND: The clinical value of advanced lipoprotein testing relative to traditional lipid testing remains controversial. To date, no studies have evaluated associations between advanced lipoprotein testing and subclinical atherosclerosis in healthy young adults. OBJECTIVE: To determine whether advanced lipoprotein testing using vertical-spin density-gradient ultracentrifugation better predicts carotid intima-media thickness, a validated measure of subclinical atherosclerosis, than does traditional lipoprotein testing in asymptomatic young adults. DESIGN: Cross-sectional community-based study. SETTING: Bogalusa, Louisiana. PARTICIPANTS: 311 randomly selected adults from the Bogalusa Heart Study who were 20 to 38 years of age. MEASUREMENTS: The authors performed advanced lipoprotein testing using vertical-spin density-gradient ultracentrifugation, traditional testing using enzymatic methods, and Friedewald formula estimation of low-density lipoprotein cholesterol levels. A certified reader blinded to lipoprotein results determined carotid intima-media thickness by B-mode ultrasonography. C-statistics from area under the receiver-operating characteristic curves (AUCs) derived from multivariable regression models were compared. RESULTS: Lipid values obtained with advanced lipoprotein testing did not predict carotid intima-media thickness better than traditionally measured lipid values in 236 participants for whom all data were available. A model using traditional lipoprotein measures (AUC, 0.754 [95% CI, 0.690 to 0.812]) did not differ significantly from a model using advanced lipoprotein measures (AUC, 0.779 [CI, 0.662 to 0.871]) for prediction of carotid intima-media thickness (P > 0.2). Subclass pattern of LDL, lipoprotein(a) cholesterol, intermediate-density lipoprotein cholesterol, high-density lipoprotein cholesterol subclasses, and very-low-density lipoprotein subclasses did not improve the performance of models for prediction of carotid intima-media thickness. LIMITATIONS: The study was cross-sectional, cardiac events were not determined, and only 1 method of advanced lipoprotein testing was used. CONCLUSIONS: Advanced lipoprotein testing using vertical-spin density-gradient ultracentrifugation did not improve prediction of carotid intima-media thickness in young adults and may not be useful for assessing cardiovascular risk in this population.
Adult↗
Managing cardiovascular risk in patients with HIV infection.
Highly active antiretroviral therapy (HAART) improves the survival of patients with HIV infection; however, several observational studies have described associations between HIV infection, HAART, and cardiovascular disease. Important limitations of these studies included a low incidence of cardiovascular events, short duration of HAART exposure, and retrospective design. Nevertheless, the weight of evidence from observational and surrogate end point studies suggests that the dyslipidemia and other metabolic changes that are common in patients with HIV infection and those using HAART may be associated with increased cardiovascular risk. The Infectious Disease Society of America/Adults AIDS Clinical Trials Group guidelines for the evaluation and management of dyslipidemia recommend target lipid levels and treatment of dyslipidemia in patients with HIV infection. Although practitioners should consider dyslipidemia and cardiovascular risk when making plans for initiating or altering HAART therapy, maintaining viremic control should be the overriding factor, because short-term absolute rates of cardiovascular disease are significantly lower than death rates from AIDS in inadequately suppressed patients. This article reviews the cardiovascular risks in patients receiving HAART and discusses the implementation of the new guidelines.
Antiretroviral Therapy, Highly Active↗
Skin cholesterol content identifies increased carotid intima-media thickness in asymptomatic adults.
BACKGROUND: A noninvasive assay to measure skin Tc recently has become available for use in the outpatient setting as a cardiovascular (CV) risk prediction tool. The purpose of this study was to determine whether skin tissue cholesterol content (skin Tc) levels are associated with increased carotid intima-media thickness (CIMT) after adjusting for known CV risk factors and Framingham CV risk. METHODS: Consecutive patients without known vascular disease who were referred for determination of CIMT underwent B-mode ultrasonography of the carotid arteries and measurement of skin Tc using a noninvasive assay. Use of medications, cardiac risk factors, and Framingham 10-year CV risk were determined prospectively. Multivariable regression was used to determine predictors of increased CIMT. RESULTS: Among 81 subjects, the mean (SD) age was 55.6 (7.7) years and the mean skin Tc was 95.9 (18.3) U. Carotid intima-media thickness was significantly higher among individuals in the highest quartile of skin Tc (0.87 vs 0.76 mm, P = .011). In multivariable analyses, skin Tc was associated with increased CIMT even after adjusting for age, sex, glucose, systolic blood pressure, total/high-density lipoprotein cholesterol ratio, and use of lipid-lowering therapy (odds ratio [OR] per 10-unit increase = 1.590, 95% CI 1.525-1.658, P = .031). Skin Tc also was associated with increased CIMT after adjustment for Framingham risk (OR = 1.341, 95% CI 1.302-1.380, P = .048). CONCLUSIONS: Skin Tc is an easy-to-measure, noninvasive marker that can help identify subclinical atherosclerosis in asymptomatic middle-aged adults, even after controlling for risk factors and CV risk predicted by the Framingham model.
Adult↗
Ultrasound-detected carotid plaque as a screening tool for advanced subclinical atherosclerosis.
BACKGROUND: There is great need for a simple, noninvasive tool that can be used in an office setting to screen for subclinical atherosclerosis. In patients referred for cardiovascular (CV) risk assessment, we evaluated the ability of ultrasound screening for carotid plaque to identify patients with advanced subclinical atherosclerosis. METHODS: Consecutive asymptomatic patients without vascular disease referred by their physician for measurement of the ankle-brachial pressure index and carotid intima-media thickness (CIMT) were included. Carotid intima-media thickness was measured using the standardized ultrasound protocol from the Atherosclerosis Risk in Communities (ARIC) study. Advanced atherosclerosis was defined as CIMT > or = 75th percentile for age, sex, and race in ARIC. RESULTS: The mean age of the 327 subjects was 55.4 years (SD 7.7 years). The 10-year Framingham CV risk was 5.1% (4.8%). In a multiple logistic regression model that included Framingham CV risk, ankle-brachial pressure index, and use of lipid-lowering medications, plaque presence significantly predicted advanced atherosclerosis (odds ratio 3.08, 95% CI 1.91-4.96, P < .001). In stepwise regression models that included age, body mass index, current tobacco use, family history of premature CV disease, fasting glucose, sex, systolic blood pressure, total/high-density lipoprotein cholesterol ratio, and use of antihypertensive and lipid-lowering medications, plaque presence independently predicted advanced atherosclerosis (P < .001). CONCLUSION: Ultrasound detection of carotid plaque helped identify asymptomatic patients with advanced subclinical atherosclerosis. Screening for carotid plaque is easier than determination of CIMT and may help detect asymptomatic patients at increased CV risk.
Carotid Artery Diseases↗
A semiautomated ultrasound border detection program that facilitates clinical measurement of ultrasound carotid intima-media thickness.
We have developed a novel, semiautomated carotid intima-media thickness (CIMT) border detection program (AUTO) and evaluated its measurement reproducibility and accuracy. Images from 6 carotid segments were acquired in 50 subjects, for a total of 300 segments. Mean and maximum CIMT values were measured blindly at a reference (REF) lab and in duplicate by experienced (EXP) and novice (NOV) readers using manual (MAN) and AUTO methods. Coefficients of variation for AUTO measurements of mean (3.2%) and maximum (4.1%) CIMT were low, and the AUTO method improved the NOV reader's reproducibility. Compared with the REF lab, mean (0.012 +/- 0.006 mm) and maximum (0.144 +/- 0.006 mm) CIMT biases were small and equivalent to those of the REF lab ( P < .001). The AUTO method shortened reading times by 35% to 46% ( P < .001). We conclude that our novel AUTO CIMT measurement program improved reproducibility and was accurate. Compared with MAN tracing, the AUTO method agreed better with the REF lab and decreased reading time.
Adult↗
Postprandial lipoprotein changes in patients taking antiretroviral therapy for HIV infection.
OBJECTIVE: Dyslipidemia is common among patients receiving antiretroviral therapy for HIV infection. The purpose of this study was to determine whether postprandial lipemia contributes to the dyslipidemia observed in HIV-positive patients taking antiretroviral therapy. METHODS AND RESULTS: A standardized fat load was administered to 65 subjects (group 1 35 HIV-positive subjects receiving protease inhibitors [PIs]; group 2 20 HIV-positive subjects not receiving PIs; group 3 10 HIV-negative controls). Serum triglycerides, retinyl palmitate, and lipoproteins were measured using enzymatic and nuclear magnetic resonance spectroscopic techniques. Compared with HIV-negative controls, peak postprandial retinyl palmitate and large very low-density lipoprotein (VLDL) levels occurred later in both HIV-positive groups, and a delayed decrease in serum triglycerides was observed. However, postprandial areas under the curve (AUCs) for triglycerides, retinyl palmitate, chylomicrons, and large VLDL were similar. Postprandial AUCs for intermediate-density lipoproteins (IDLs) and low-density lipoproteins (LDLs) were higher in group 1 than groups 2 and 3 (all P<0.035). CONCLUSIONS: Postprandial clearance of triglyceride-rich lipoproteins is delayed in HIV-positive individuals receiving antiretroviral therapy. Compared with HIV-positive individuals not on PIs, those taking PIs do not have increased postprandial triglyceride-rich lipoproteins but do have increased postprandial IDLs and LDLs. An oral fat load was administered to 55 HIV-positive and 10 HIV-negative individuals. Postprandial clearance of triglyceride-rich lipoproteins was delayed in HIV-positive individuals. Compared with HIV-positive subjects not on PIs, those taking PIs do not have increased postprandial triglyceride-rich lipoproteins but do have increased postprandial intermediate-density and low-density lipoproteins.
Adult↗
Distribution and cross-sectional age-related increases of carotid artery intima-media thickness in young adults: the Bogalusa Heart Study.
BACKGROUND AND PURPOSE: Reference values and age-related changes of carotid intima-media thickness (CIMT) have not been described in a community-based sample of young asymptomatic adults. CIMT measurements from the Bogalusa Heart Study, a study of the natural history of atherosclerosis in young adults and children, were used to characterize age-, race-, and sex-specific CIMT distributions and yearly rates of change. METHODS: Age-, sex-, and race-specific CIMT percentile values and cross-sectional changes with age were estimated using B-mode carotid ultrasound images from 519 young adults (mean age 32 years, 61% female, 29% black). Nomograms of CIMT percentiles between the ages of 25 and 40 years are provided in 5-year increments. RESULTS: CIMT was thickest in the carotid bulb and increased linearly with age, most rapidly in the bulb. With age, composite CIMT increased most slowly in white females and most rapidly in white males. Sample size estimates projected that 268 to 462 subjects are needed to detect CIMT changes > or =0.010 mm/year. CONCLUSIONS: These estimated CIMT distributions and percentiles can serve as reference values for assessment of subclinical atherosclerosis in young adults. The observed age-related differences in CIMT can be used to plan epidemiological and clinical trials investigating atherosclerosis and anti-atherosclerotic interventions.
Adult↗
Vascular age: integrating carotid intima-media thickness measurements with global coronary risk assessment.
BACKGROUND: An imaging test that quantifies atherosclerotic burden and that can be integrated with existing risk stratification paradigms would be a very useful clinical tool. HYPOTHESIS: Measurement of carotid intima-media thickness (CIMT) is feasible in a clinical setting. Such measurements can be integrated into coronary risk assessment models. METHODS: Carotid intima-media thickness was measured by B-mode ultrasound in 82 consecutive patients without manifest atherosclerotic vascular disease. The values were used to determine "vascular age" (VA) based on nomograms from the Atherosclerosis Risk in Communities study. Vascular age was substituted for chronological age and standard and vascular age-adjusted 10-year coronary heart disease (CHD) risk estimates were compared. RESULTS: The mean chronological age was 55.8 +/- 9.0 years. The mean VA using CIMT was 65.5 +/- 18.9 years (p < 0.001). The Framingham 10-year hard CHD risk estimate was 6.5 +/- 4.9%. Substituting CIMT-derived VA for chronological age increased the 10-year CHD risk estimate to 8.0 +/- 6.8% (p < 0.001). Of 14 subjects initially at intermediate risk, 5 (35.7%) were reclassified as higher risk and 2 (14.3%) were reclassified as lower risk. Significant predictors of reclassification were tobacco use, high-density lipoprotein cholesterol, systolic blood pressure, and low-density lipoprotein cholesterol. CONCLUSIONS: Measurement of CIMT, a noninvasive estimate of current atherosclerotic burden, is feasible in a clinical setting and can be integrated into CHD risk assessment models. Determining VA using CIMT values may help individualize the age component of population-based CHD risk estimates. This strategy should be tested in a large trial with hard clinical endpoints.
Adult↗
Effects of pravastatin on lipoproteins and endothelial function in patients receiving human immunodeficiency virus protease inhibitors.
BACKGROUND: Although recommended as initial therapy for patients with dyslipidemia who are taking human immunodeficiency virus protease inhibitors (HIV PIs), the effects of pravastatin on lipoproteins and arterial reactivity have not been elucidated. The purpose of this study was to determine the effects of pravastatin on lipoprotein subfractions and endothelial function in patients with dyslipidemia who are receiving HIV PIs. METHODS: This was a placebo-controlled, double-blind, crossover study comparing pravastatin (40 mg) to placebo in 20 patients who were taking HIV PIs. Lipoprotein subfractions were measured with nuclear magnetic resonance spectroscopic analysis. Flow-mediated vasodilation (FMD) of the brachial artery was evaluated with high-resolution ultrasound scanning. RESULTS: At baseline, subjects had an increased concentration of low-density lipoprotein (LDL) particles (1756 +/- 180 nmol/L), which tended to be small (19.9 +/- 0.2 nm), a low concentration of large high-density lipoproteins (HDL; 0.94 +/- 0.07 mmol/L), and an increased concentration of large very low-density lipoproteins (VLDL; 1.90 +/- 0.58 mmol/L). FMD was impaired (4.5% +/- 1.1%). Compared with placebo, pravastatin resulted in a 20.8% reduction in LDL particles (P =.030), a 26.7% reduction in small LDL (P =.100), and a 44.9% reduction in small VLDL (P =.023). Total and non-HDL cholesterol levels decreased by 18.3% (P <.001) and 21.7% (P <.001), respectively. FMD tended to increase in patients receiving pravastatin (0.7% +/- 0.6%); however, the difference between treatment phases was not statistically significant (P =.080). CONCLUSIONS: This is the first double-blind, placebo-controlled study of the effects of statin therapy on lipids, lipoprotein subfractions, and endothelial function in patients taking HIV PIs. Pravastatin reduced concentrations of atherogenic lipoproteins, particularly those most associated with future coronary events.
Adult↗
Effects of multivitamins and low-dose folic acid supplements on flow-mediated vasodilation and plasma homocysteine levels in older adults.
BACKGROUND: Hyperhomocysteinemia is associated with aging, endothelial dysfunction, and increased risk of coronary heart disease in older adults; however, the effects of homocysteine-lowering therapy on vascular reactivity in older persons are unknown. The objective of this study was to determine the effects of multivitamins (MV) and folic acid (FA) supplements on flow-mediated vasodilation (FMD) in older adults. METHODS: Individuals > or =70 years old with homocysteine levels > or =10 micromol/L were recruited for this 40-week, prospective, single-blinded study. All subjects were treated sequentially, with each of the following daily therapies for 10 weeks: (1) placebo, (2) MV (400 microg FA, 6 mg vitamin B6, 25 microg vitamin B12), (3) placebo, then (4) MV + FA (total FA, 1400 microg). FMD, folate intake, and laboratory values were measured at each visit. Investigators were blinded to subject treatment phase when measuring vessel diameters and calculating FMD. RESULTS: Twenty subjects (mean +/- SEM age, 78.0 +/- 1.2 [range, 70 to 88] years, 9 women) completed the MV and 17 completed the MV + FA interventions. FMD was impaired at baseline (2.0% +/- 1.2%). During the 40-week study, homocysteine levels decreased by 1.4 +/- 0.9 micromol/L (p(trend) = 0.034) from a baseline of 12.8 +/- 0.6 micromol/L; however, FMD did not change significantly (p(trend) = 0.874). FMD did not improve after therapy with MV alone (3.0% +/- 0.9% [week 10] vs 2.4% +/- 1.1% [week 20], P =.716) or with MV + FA (2.6% +/- 0.9% [week 30] vs 1.9% +/- 0.7% [week 40], P =.484). CONCLUSIONS: At doses commonly prescribed in clinical practice, MV and FA supplements did not improve FMD in older adults with hyperhomocysteinemia.
Aged↗
Carotid intima-media thickness and vascular age: you are only as old as your arteries look.
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Adult↗
Noninvasive assessment of coronary flow reserve by echocardiography: technical considerations.
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Contrast Media↗
American Society of Echocardiography recommendations for use of echocardiography in clinical trials.
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Cardiovascular Diseases↗
Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medical Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group.
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Adult↗