Hyperlipidemias: Stein JH

Dubé MP, Stein JH, Aberg JA, Fichtenbaum CJ, Gerber JG, Tashima KT, Henry WK, Currier JS, Sprecher D, Glesby MJ, Anonymous00228, Anonymous00229. · Indiana University, Indianapolis, USA. · Clin Infect Dis. · Pubmed #12942391 No free full text.

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Stein JH, McBride PE. · No affiliation provided · J Cardiopulm Rehabil. · Pubmed #17135856 No free full text.

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Stein JH. · Section of Cardiovascular Medicine, University of Wisconsin Medical School, Madison, WI 53792, USA. · J Acquir Immune Defic Syndr. · Pubmed #15671795 No free full text.

Abstract: 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.

Stein JH. · Section of Cardiovascular Medicine, University of Wisconsin Medical School, Clinical Science Center, Madison, WI 53792, USA. · Prog Cardiovasc Dis. · Pubmed #12638093 No free full text.

Abstract: Human immunodeficiency virus protease inhibitors are associated with metabolic abnormalities that may increase risk of atherosclerotic vascular disease, including dyslipidemia, insulin resistance, and central obesity. Dyslipidemia, characterized by hypercholesterolemia and hypertriglyceridemia, small low- and high-density lipoprotein particles, and in some cases lipoprotein(a) excess, can be severe and has been associated with endothelial dysfunction and carotid atherosclerosis. The mechanisms underlying protease inhibitor-associated dyslipidemia have not been elucidated completely, but appear to involve hepatic overproduction of very low-density lipoproteins and to a lesser extent, impaired clearance. Insulin resistance appears to mediate part of the adverse lipoprotein changes observed in patients taking protease inhibitors. Ongoing epidemiological and surrogate endpoint studies are investigating the atherogenicity of these medications. Until the risk associated with use of protease inhibitors is better understood, identifying patients at high risk for adverse vascular events such as heart attacks, cardiac death, and stroke is a high priority. This article reviews the lipid and lipoprotein abnormalities associated with use of protease inhibitors, possible mechanisms for protease inhibitor-associated dyslipidemia, its potential atherogenicity, and use of the National Cholesterol Education Program Adult Treatment Panel III Guidelines for the management of patients with dyslipidemia.

Carlsson CM, Stein JH. · University of Wisconsin Department of Medicine and Center for Women's Health and Women's Health Research, 2500 Overlook Terrace, Madison, WI 53705, USA. · Curr Womens Health Rep. · Pubmed #12215309 No free full text.

Abstract: Coronary heart disease (CHD) is the leading cause of death in women aged 60 years and older, yet 40% of this group believe they are unlikely to have a heart attack. Recent data show that the lack of a low-risk lifestyle may account for approximately 82% of coronary events in women. Underappreciation of CHD risk may prevent aging women from making significant changes in dietary habits, activity levels, and tobacco use to decrease their risk. In addition, many physicians may not treat cardiovascular risk factors aggressively in middle-aged and older women, despite data from primary and secondary prevention trials supporting the efficacy of interventions. This article addresses age-related changes in cardiovascular risk factors in women, with a focus on lifestyle interventions.

Carlsson CM, Carnes M, McBride PE, Stein JH. · Preventive Cardiology Program, University of Wisconsin Medical School, Madison 53792, USA. · J Am Geriatr Soc. · Pubmed #10591243 No free full text.

Abstract: OBJECTIVES: To summarize and critically review clinical trial data regarding dyslipidemia as a risk factor for coronary heart disease (CHD) and the efficacy and safety of lipid-lowering interventions in older adults. Based on these data, clinical recommendations for diagnosing and managing dyslipidemia in older adults are provided. METHODS: Peer-reviewed journal articles were identified by a MEDLINE search and a review of journal article references. Studies that were performed exclusively in subjects older than 65 years or that included a large subgroup of older adults were included. CONCLUSIONS: Elevated low density lipoprotein and total cholesterol levels are independent risk factors for CHD events in patients aged older than 65 years. Older adults have a higher risk of mortality attributable to hypercholesterolemia. Diet and lipid-lowering medications safely and effectively lower cholesterol levels in this age group. Exercise increases high-density lipoprotein cholesterol levels and decreases triglyceride levels. If accompanied by weight loss, exercise may reduce low-density lipoprotein and total cholesterol levels. Improving lipid levels in older adults with CHD decreases the risk of future coronary events by up to 45%, and significant effects on outcome measures may be observed within 2 years of the initiation of therapy.

Stein JH, Merwood MA, Bellehumeur JL, Aeschlimann SE, Korcarz CE, Underbakke GL, Mays ME, Sosman JM. · University of Wisconsin Atherosclerosis Imaging Research Program, University of Wisconsin Medical School, Madison 53792, USA. · Am Heart J. · Pubmed #15077088 No free full text.

Abstract: 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.

Carlsson CM, Papcke-Benson K, Carnes M, McBride PE, Stein JH. · University of Wisconsin Medical School, Madison, Wisconsin 53792, USA. · Drugs Aging. · Pubmed #12390056 No free full text.

Abstract: INTRODUCTION: Concerns about the effects of HMG-CoA reductase inhibitors ('statins') on health-related quality of life may contribute to their underuse in older adults with and at risk for cardiovascular disease. These concerns also may prevent clinicians from enrolling older patients in clinical trials assessing the efficacy of statins as a preventive therapy for Alzheimer's disease. OBJECTIVE: To determine the effects of pravastatin and tocopherol (vitamin E), alone and in combination, on health-related quality of life in older adults. STUDY DESIGN: Double-blind, randomised, placebo-controlled, crossover study. PARTICIPANTS: Forty-one community-dwelling men and women aged > or = 70 years with low-density lipoprotein-cholesterol (LDL-C) > or = 3.62 mmol/L (140 mg/dl) participated. METHODS: Subjects received pravastatin for 6 months then pravastatin plus tocopherol for an additional 6 months (group 1), or tocopherol for 6 months then pravastatin plus tocopherol for an additional 6 months (group 2). Dosages were pravastatin 20 mg daily and tocopherol 400 IU daily. MAIN OUTCOME MEASURES: The following health-related quality-of-life measures were assessed at baseline, after 6 months and after 1 year: health perception, depression, physical function, cognitive function and sleep behaviour. In addition, data on adverse effects and laboratory abnormalities were obtained. RESULTS: Pravastatin reduced levels of total cholesterol (-21%, p < 0.001) and LDL-C (-29%, p < 0.001). Health-related quality-of-life scores, physical adverse effects, muscle enzyme levels and liver function tests did not change after 12 months of therapy with pravastatin, tocopherol or their combination. CONCLUSION: Both pravastatin and tocopherol have a good safety profile, are well tolerated and do not adversely affect health-related quality of life in older patients with hypercholesterolaemia. Given the significant beneficial cardiovascular effects of statin therapy in older adults and the potential role of statins in prevention of Alzheimer's disease, concerns about adverse effects on quality of life should not deter use of these medications in this population.

Stein JH, Carlsson CM, Papcke-Benson K, Aeschlimann SE, Bodemer A, Carnes M, McBride PE. · University of Wisconsin Medical School, Madison, Wisconsin, USA. · J Am Coll Cardiol. · Pubmed #11738278 No free full text.

Abstract: OBJECTIVES: The goal of this study was to determine the long-term effects of statins and antioxidant vitamins on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia. BACKGROUND: Lipid-lowering therapy and antioxidant vitamins improve endothelium-dependent vasodilation in young and middle-aged adults with hypercholesterolemia, but their effects in older adults are not known. METHODS: Two double-blind, placebo-controlled studies were performed in individuals > or =70 years old with low-density lipoprotein cholesterol (LDL-C) > or =140 mg/dl. In the first study, 37 subjects were randomized to receive (group 1) pravastatin for six months then pravastatin and vitamin E for six additional months or (group 2) vitamin E for six months, then pravastatin and vitamin E for six additional months. In the second study, additional 17 subjects sequentially received simvastatin for six months, then simvastatin and vitamins C and E for six additional months. Flow-mediated vasodilation of the brachial artery was measured by high-resolution ultrasound. RESULTS: At baseline, subjects in both studies were similar in age (mean +/- SD, 75.8 +/- 4.2 years), gender, systolic blood pressure, total cholesterol (261.6 +/- 37.4 mg/dl), LDL-C (180.3 +/- 28.1 mg/dl), high-density lipoprotein cholesterol and triglycerides levels. Flow-mediated vasodilation was severely impaired (2.2 +/- 3.9%). Both statins reduced total and LDL-C levels (p < 0.001); however, neither statin, antioxidant vitamin regimen nor the combination of statins and antioxidant vitamins improved flow-mediated vasodilation of the brachial artery. At baseline, nitroglycerin-mediated vasodilation also was impaired (10.7 +/- 5.6%) and did not change in either study. CONCLUSIONS: Older adults with hypercholesterolemia have impaired flow-mediated vasodilation of the brachial artery that does not improve after one year of therapy with statins and antioxidant vitamins, despite significant lipid-lowering.

Stein JH, Klein MA, Bellehumeur JL, McBride PE, Wiebe DA, Otvos JD, Sosman JM. · Department of Medicine, University of Wisconsin Medical School, Madison, Wisconsin, USA. · Circulation. · Pubmed #11457741 links to  free full text

Abstract: BACKGROUND: Human immunodeficiency virus protease inhibitors (HIV PIs) are associated with hyperlipidemia, hyperglycemia, and obesity; however, it is not known whether they increase risk of atherosclerotic vascular disease. The purposes of this study were to characterize the lipoprotein abnormalities associated with use of HIV PIs in individuals with HIV infection and to determine the pathophysiological significance of these changes by assessing their effect on endothelial dysfunction. METHODS AND RESULTS: This was a cross-sectional study of 37 adults with HIV-1 infection who were receiving antiretroviral therapy. Twenty-two were taking HIV PIs (group 1); 15 were not (group 2). Lipids and lipoproteins were measured by enzymatic techniques and nuclear magnetic resonance spectroscopic analysis. Flow-mediated vasodilation (FMD) of the brachial artery was measured by high-resolution ultrasound. Subjects in both groups were similar in regard to age, time since diagnosis of HIV infection, and CD4 cell count. Group 1 subjects had higher total cholesterol (5.68 versus 4.42 mmol/L, P=0.007) and triglyceride (4.43 versus 1.98 mmol/L, P=0.009) levels, characterized by elevated levels of IDL and VLDL. Subjects in group 1 had impaired FMD (2.6+/-4.6%), indicative of significant endothelial dysfunction. Group 2 subjects had normal FMD (8.1+/-6.7%, P=0.005). In group 1, chylomicron, VLDL, IDL, and HDL cholesterol levels predicted FMD. CONCLUSIONS: Use of HIV PIs is associated with atherogenic lipoprotein changes and endothelial dysfunction. Because these metabolic and vascular changes predispose to atherosclerosis, monitoring and treatment of dyslipidemia in patients taking these medications is warranted.

Cullen MW, Stein JH, Gangnon R, McBride PE, Keevil JG. · Department of Internal Medicine, Mayo School of Graduate Medical Education, Rochester, MN. · Am Heart J. · Pubmed #18657658 No free full text.

Abstract: BACKGROUND: This study sought to evaluate national levels of elevated low-density lipoprotein cholesterol (LDL-C) before and after publication of the Adult Treatment Panel III (ATP III). The ATP III guidelines intensified LDL-C targets and defined additional high-risk conditions. These recommendations are expected to have a noticeable impact on US cholesterol levels. METHODS: Coronary heart disease (CHD) risk was determined per ATP III guidelines for US residents aged 20 to 79 years in the 1999 to 2000 and 2001 to 2002 surveys. For those at high risk, the LDL-C mean percentage <100 mg/dL and percentage > or =130 mg/dL, although not taking lipid-lowering therapy, were compared between the 2 surveys. In addition, subsets with and without CHD were evaluated. RESULTS: Of all high-risk US residents, the mean LDL-C dropped from 129 mg/dL in 1999 to 2000 to 120 mg/dL in 2001 to 2002 (P = .003). Those <100 mg/dL increased from 23% to 32% (P = .003). Those > or =130 mg/dL and not on medication dropped from 36% to 27% (P = .001). Goal achievement and improvements were more favorable in the subset with CHD compared with those at high risk due to high-risk equivalent conditions. CONCLUSIONS: The sharp increase in high-risk US residents at the goal and the drop in the untreated percentage of those above treatment threshold illustrate national improvements in the management of LDL-C for those at high coronary risk. High-risk subjects without CHD displayed less significant improvements, suggesting an opportunity for better recognition and management of these individuals.

Stein JH, Merwood MA, Bellehumeur JB, McBride PE, Wiebe DA, Sosman JM. · University of Wisconsin Medical School, 600 Highland Ave, G7/341 CSC (MC 3248) Madison, WI 53792, USA. · Arterioscler Thromb Vasc Biol. · Pubmed #15576636 links to  free full text

Abstract: 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.

Stein JH, Wu Y, Kawabata H, Iloeje UH. · Department of Medicine, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA. · Am J Cardiol. · Pubmed #12888129 No free full text.

Abstract: Although human immunodeficiency virus (HIV) protease inhibitors (PIs) improve survival in patients with HIV infection, many patients receiving PIs develop hyperlipidemia, which may increase risk of future coronary events. The purpose of this study was to estimate the changing prevalence of lipid-lowering therapy (LLT) in patients with HIV and to evaluate its association with the use of HIV PIs. This was a cross-sectional study of adults with HIV infection who were registered in the Medicaid of California (MEDI-CAL) administrative claims database. Frequencies of HIV-related and dyslipidemia diagnoses were determined from International Classification of Diseases-9th Edition codes. Use of lipid-lowering and antiretroviral medications was determined by National Drug Codes. Multivariate statistical techniques were used to evaluate trends in use of PIs and lipid-lowering medications from January 1996 to June 2002. The number of HIV-infected patients in MEDI-CAL ranged from 15,764 in 1996 to 13,349 in 2000. The prevalence of LLT use among HIV-infected patients on PIs increased by sixfold (1.7% to 10.6%, p <0.05), and in 2000, exceeded use in the overall MEDI-CAL population (p = 0.09). The increasing rate of LLT in patients taking PIs was greater than in HIV-infected patients not on PIs and in MEDI-CAL (p = 0.002). In multivariate models, increasing age (odds ratio 2.30) and use of PIs (odds ratio 2.08) predicted use of LLT (p <0.001). Thus, in patients taking HIV PIs, use of LLT increased more than sixfold, at a faster rate than in the general population. It has not been proved that use of LLT in HIV-infected patients taking PIs improves survival.

Stein JH, Carlsson CM, Papcke-Benson K, Einerson JA, McBride PE, Wiebe DA. · University of Wisconsin Medical School, Madison, WI 53792, USA. · Clin Chem. · Pubmed #11805009 links to  free full text

Abstract: BACKGROUND: Although total cholesterol concentrations measured by portable lipid analyzers have acceptable bias and precision in young and middle-aged adults, clinically relevant differences in HDL-cholesterol (HDL-C) and triglyceride values have been described. Furthermore, the accuracy of portable lipid analyzers in older hyperlipidemic individuals, who have a high incidence of coronary heart disease, has not been validated. This study determined the biases and variability in portable lipid measurements in older patients with hypercholesterolemia and related them to National Cholesterol Education Program Adult Treatment Panel III guidelines. METHODS: Participants were > or =70 years of age with fasting serum LDL-cholesterol (LDL-C) concentrations > 1.40 g/L. Fasting fingerstick samples were analyzed on a Cholestech L.D.X desktop analyzer. Antecubital venous samples were analyzed in a proficiency-certified clinical laboratory. RESULTS: Portable measurements systematically overestimated triglycerides (0.296 g/L; P <0.001) and HDL-C (0.015 g/L; P = 0.026). LDL-C concentrations were underestimated (0.043 g/L; P = 0.046). Total and non-HDL cholesterol calculations based on the portable lipid device provided unbiased estimates, but wide variability was present. Significant variability in lipid determinations limited their clinical usefulness in individual patients, especially because 2 SD of the mean bias between the laboratory and the portable determinations of LDL-C and non-HDL cholesterol exceeded the 0.30 g/L cutoff that defines treatment targets in the current lipid guidelines. CONCLUSIONS: Lipid values obtained from portable lipid analyzers may be useful for screening, but they should not be used to make clinical decisions regarding the diagnosis and management of dyslipidemia in individual patients.

Stein JH, Carlsson CM. · No affiliation provided · Circulation. · Pubmed #11815445 links to  free full text

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