Biomedical subjects
Publications and source records attributed to James H Stein.
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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.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: Cigarette smoking has been associated with increased plasma homocysteine levels. Although hyperhomocysteinemia may mediate some of the adverse cardiovascular consequences of smoking cigarettes, the effects of smoking cessation and smoking reduction on homocysteine levels have not been evaluated previously. HYPOTHESIS: The purpose of this study was to determine the effects of smoking cessation and smoking reduction on plasma homocysteine levels. METHODS: Fifty-one healthy subjects who smoked 35.9 +/- 6.4 cigarettes daily were randomized to continue smoking, reduce smoking to 4-8 cigarettes daily, or to stop smoking. A nicotine inhaler and individualized counseling were provided as aids to smoking cessation. RESULTS: In subjects who quit smoking, homocysteine levels decreased by 11.6%, from 8.58 +/- 2.31 to 7.53 +/- 2.26 micromol/l (p = 0.013). Significant changes in homocysteine levels were not observed in subjects who reduced smoking or continued to smoke. CONCLUSION: A "harm reduction" strategy of reducing cigarette use may not be sufficient for reducing the vascular risk associated with smoking cigarettes.
In this chapter, we have reviewed many of the steps necessary for effective CHD risk reduction. The first step in the office setting is to assess the individual CHD risk. This combines the evaluation of current CHD or a "secondary risk equivalent" with the counting of risk factors and in many cases, the absolute risk calculation. The next steps are to consider each of the major modifiable risk factors (hypertension, dyslipidemia, diabetes mellitus, smoking status) to set goals for each and then work to achieve those goals through lifestyle changes and medication therapy. We reviewed each of these risk factors in detail and then turned to a discussion of emerging risk factors that may help "fine-tune" the risk assessment in some borderline cases. We also discussed additional non-invasive testing that is available to the clinician to help refine the assessment of current burden of disease. Finally, we discuss some of the barriers that exist on both a global and local level to effective treatment of CHD risk factors.
To investigate the effects of non-ECG-triggered imaging during ultrasound studies of endothelial function, brachial artery diameters were measured throughout the cardiac cycle at rest, during reactive hyperemia, and after administration of nitroglycerin. R-wave-triggered imaging using a 7.5-MHz ultrasound transducer with acquisition every 41.7-66.7 ms was performed in 24 subjects. Cardiac cycle-related variation was computed as the maximum per cent change from the end-diastolic diameter. The range of possible errors in flow-mediated dilation (FMD) and nitroglycerin-mediated vasodilation that may result from ignoring cyclic variations in diameter was determined for each condition. True FMD, true nitroglycerin-mediated vasodilation, and the maximum and minimum values that could be erroneously calculated for FMD if timing was ignored all differed dramatically (p < 0.05). The range of apparent FMD values that could be measured was nearly three times the true FMD value. Ignoring temporal position within the cardiac cycle artifactually increased calculated FMD into the normal range, despite truly impaired FMD. Peak arterial dilation occurred before end-systole and greater baseline vessel compliance was associated with greater FMD. Brachial arterial diameters vary significantly throughout the cardiac cycle. The magnitude of this variation is similar to the arterial dilation induced by reactive hyperemia and nitroglycerin, making ECG-triggered imaging mandatory for accurate and reproducible clinical and research measurements of artery diameters and FMD. Measurement of diameters at end-diastole may be preferred to other time-points in the cardiac cycle.
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.
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.
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.
New cases of Human Immunodeficiency Virus (HIV) infection are becoming more prevalent in Wisconsin. As advances in HIV treatment have improved patient survival, more individuals are living with this disease. Consequently, previously uncommon manifestations, such as cardiac complications, are likely to be encountered in clinical practice more often. In general, cardiac manifestations in patients with HIV infection are clinically subtle in their initial stages. Symptoms are usually nonspecific; however, dyspnea is very common and may be overlooked or attributed to pulmonary diseases and opportunistic infections. Cardiac abnormalities in HIV infection may involve any of the structures of the heart including pericardium, myocardium, and endocardium. Furthermore, HIV infection is associated with pulmonary hypertension, cardiac neoplasms, and use of potentially cardiotoxic medications. This article reviews the clinical cardiac manifestations currently seen in patients with HIV infection. Most of the cardiac complications were identified in the era before highly-active antiretroviral therapy, however, new complications have also been observed. To further reduce morbidity and mortality caused by HIV, early recognition and prompt intervention of cardiac diseases is extremely important. Further delineation of the natural history and clinical trials of the treatment of cardiac complications in patients with HIV infection are need given recent advances in antiretroviral therapy.
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.
Although positive troponin-I (TnI) assays have been reported in patients with pulmonary embolism (PE), TnI levels in patients with suspected PE have not been evaluated systematically. The purpose of this study was to evaluate the diagnostic utility of TnI measurements in patients with suspected PE. Consecutive patients with suspected PE were identified in whom nuclear ventilation/perfusion (V/Q) scans were performed and TnI levels were measured. TnI levels in patients with and without positive V/Q scans were compared by use of t tests. After categorizing TnI levels as positive (TnI-pos, > or = 0.40 ng/mL) or negative, chi-square tests were used to relate these values to V/Q scan results. Separate comparisons were made for subjects with high-probability V/Q scans (V/Q-high, > or = 90% likelihood of PE) and intermediate- or high-probability V/Q scans (V/Q-pos, > or = 50% likelihood of PE). The mean TnI level in the 10 subjects with V/Q-high scans was 0.39 +/-0.79 ng/mL. The mean TnI level in the 81 subjects without V/Q-high scans was 0.36 +/-0.66 ng/mL (p=0.89). TnI levels did not differ between the 22 V/Q-pos subjects and the 69 subjects with negative V/Q scans (p = 0.86). A positive TnI in the setting of V/Q-pos had a sensitivity of 32%, specificity of 71%, positive predictive value of 26%, and a negative predictive value = 77% (chi-square = 0.06, p = 0.80). Elevated TnI levels are not associated with positive V/Q scans. The TnI assay is not a useful test in patients suspected of having PE, unless used to exclude myocardial ischemia or infarction.