Different definitions of the metabolic syndrome and risk for recurrent cardiovascular disease.
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Journal Article↗
Biomedical subjects
W Virgil Brown
Publications and source records attributed to W Virgil Brown.
Antiretroviral therapy in HIV-positive women is associated with increased apolipoproteins and total cholesterol.
OBJECTIVES: Dyslipidemia has become a common problem in HIV disease, especially in patients on combination antiretroviral (ARV) therapy. However, little data are available to evaluate lipid abnormalities in women on ARV therapy. METHODS: Using a cross-sectional design, the prevalence of abnormal plasma lipid and lipoprotein concentrations as well as other biomarkers for vascular disease was determined in 184 HIV-positive women from 2 HIV clinics in Atlanta during 2002. RESULTS: Most of the women were African American (89%), with median age of 41 years (range 21-72); 6% were diabetic, 44% smoked, and 67% were overweight. ARV therapy defined the comparison groups that included treatment with a protease inhibitor (PI)-based regimen for more than 3 months in 76 (41%), treatment with a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen for more than 3 months in 38 (20%), and no ARV therapy for the past 3 months in 70 (38%). Women being treated with a PI or NNRTI had higher total cholesterol and triglyceride levels than patients on no therapy (P < 0.05 for each). Women treated with either PIs or NNRTIs had significantly higher apolipoprotein B and apolipoprotein C-III levels than patients on no therapy (P < 0.01 for each). CONCLUSIONS: In this cross-sectional study of HIV-infected women, either PI or NNRTI therapy elevated levels of total cholesterol and specific apolipoproteins. These findings, on a background of an older population with additional risk factors of smoking, obesity, and diabetes, may lead to future atherosclerotic events in these patients.
Adult↗
Usefulness of arterial compliance in the thigh in predicting exercise capacity in individuals without coronary heart disease.
This study examined the relation between arterial compliance of the lower extremities and aerobic capacity in patients with a broad spectrum of cardiovascular risk but without overt coronary heart disease (CHD). Local arterial compliance was noninvasively measured in the thigh and calf in 104 men and 99 women using air plethysmography. Subjects also underwent maximal exercise treadmill testing as a measure of aerobic capacity. In univariate analysis, age (r = -0.49, p <0.001), systolic blood pressure at rest (r = -0.27, p <0.001), pulse pressure (r = -0.39, p <0.001), total cholesterol (r = -0.25, p <0.001), triglycerides (r = -0.025, p <0.001), non-high-density lipoprotein cholesterol (r = -0.23, p <0.001), high-sensitivity C-reactive protein (r = -0.21, p = 0.002), and low-density lipoprotein cholesterol (r = -0.15, p = 0.03) all demonstrated a significant inverse association with treadmill time. Thigh and calf compliance demonstrated a significant positive association with treadmill time (r = 0.48, p <0.001; r = 0.46, p <0.001). In multivariate analysis, thigh compliance (p = 0.003), age (p <0.001), gender (p = 0.005), and triglycerides (p = 0.017) were independent predictors of treadmill time. In conclusion, thigh compliance measured with a simple-to-use, fully automated device independently predicts aerobic fitness in patients with a wide range of cardiovascular risk but without CHD.
Arteries↗
Comparison of the relation of triglyceride-rich lipoproteins and muscular artery compliance in healthy women versus healthy men.
To determine whether structural features or concentrations of plasma lipoproteins are predictive of arterial compliance in healthy women versus healthy men, cohorts of 111 men and 112 women with a wide range of 10-year risks for coronary artery disease were selected using assessments based on the Framingham Heart Study. Age ranges were restricted to 35 to 69 years for men and 45 to 79 years for women. Lipid-lowering drugs or any evidence of vascular disease was cause for exclusion. Fasting lipoprotein analysis and arterial compliance measurements in thigh and calf were completed in all patients. Plasma triglyceride levels were the most powerful predictor of compliance in women. Weaker but significant relations were observed between plasma non-high-density lipoprotein cholesterol, apolipoprotein-B, and apolipoprotein-CIII. In contrast, the only significant predictor of compliance in men was body weight. Thus, the major lipid predictors of arterial stiffness in women are concentrations of triglyceride-rich lipoproteins. These results are consistent with previous findings that triglyceride measurements are more strongly related to clinical vascular events in women than in men.
Adult↗
Understanding physician and consumer attitudes concerning cholesterol management: results from the National Lipid Association surveys.
Two online surveys commissioned by the National Lipid Association (NLA) were conducted to determine the current attitudes of physicians and consumers regarding cholesterol and heart disease. Physicians and consumers from preexisting independent panels were randomly invited to participate in the online surveys that were open from January 26 to 30, 2004. Both physicians (n = 200) and consumers (n = 600) agreed that high cholesterol and coronary artery disease (CAD) are significant health risks. Physicians reported the primary barriers for patients being prescribed cholesterol-lowering medication as patient fear of side effects (61%) and reluctance to take prescription medications (52%). While most physicians were aware of and felt they adhered to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, considerably fewer thought the same of other physicians. The consumer survey focused on untreated moderate-risk patients (an approximate 10% to 20% 10-year risk of myocardial infarction and cardiac death) because this group is often undertreated. Untreated moderate-risk patients reported that their physicians did not advise them to take prescription cholesterol-lowering drugs (51%) and that they were trying to control their cholesterol with diet and exercise (58%). Consumers believe they are taking an increased role in their own health management and decision making. Current attitudes of physicians and consumers are similar with regard to their recognition of the significance of cholesterol and CAD for health, but differ with regard to why patients do not take prescription medications.
Adult↗
The National Lipid Association surveys of consumers, physicians, and pharmacists regarding an over-the-counter statin in the United States: is this a good idea?
Surveys commissioned by the National Lipid Association (NLA) were conducted to determine the current attitudes and perceptions of physicians, consumers, and pharmacists regarding the impact of an over-the-counter (OTC) statin. Individuals from preexisting independent databases were randomly invited to participate in the online surveys that were open from January 26 to 30, 2004 for physicians and consumers and from March 1 to 12, 2004 for pharmacists. The results of these surveys indicate that consumers and pharmacists are more positive regarding the idea of an OTC statin, whereas physicians are more guarded. Concerns of both physicians and pharmacists included the discontinuation by patients of their prescription cholesterol-lowering therapy without consulting their physician, safety issues such as potential drug interactions and side effects, and patient ability to self-manage OTC statins. Consumers interested in purchasing an OTC statin reported that they would consult their physician before doing so, and pharmacists were interested in supporting consumers who use OTC statins. Although such support would require further training and time, pharmacists believed that they could facilitate consumer self-care programs and follow-up with physicians.
Anticholesteremic Agents↗
Clinical Chemistry journal has contributed to progress in lipid and lipoprotein testing for fifty years.
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Chemistry, Clinical↗
Relationship between arterial stiffness and subclinical aortic atherosclerosis.
BACKGROUND: Noninvasive measures of arterial compliance may be useful for the detection of subclinical atherosclerosis. METHODS AND RESULTS: Measures of calf and thigh arterial compliance (MaxV50) were recorded in 267 subjects who also underwent MRI of the distal aorta to quantify distal aorta atherosclerosis. The average of calf and thigh MaxV50 was strongly predictive of extent of aortic atherosclerosis and risk of being in the top quartile of aortic atherosclerosis after adjustment for the Framingham Coronary Risk Score (FCRS) or the combination of the FCRS and C-reactive protein (P<0.0001). The areas under the receiver operating curves predicting the top quartile of gender-specific aortic atherosclerosis were 0.57, 0.60, and 0.75 for models containing the FCRS, the FCRS and C-reactive protein, and the FCRS, C-reactive protein, and the average of calf and thigh MaxV50. CONCLUSIONS: Lower-extremity arterial compliance may identify subjects with extensive subclinical atherosclerosis. Further studies examining the potential value of arterial stiffness as a screening tool to guide initiation of more aggressive preventive interventions are warranted.
Adult↗
Polyunsaturated fatty acids acutely suppress antibodies to malondialdehyde-modified lipoproteins in patients with vascular disease.
Antibodies to malondialdehyde (MDA)-modified low-density lipoprotein (LDL) are transiently reduced during the postprandial period in patients with atherosclerotic heart disease. Previous experiments using mixed meals high in fat have found reductions of approximately 20% within 2 hours. This study was designed to reveal if this phenomenon was due uniquely to saturated fats. Using a standardized immunoassay for the detection of circulating levels of autoantibodies (AAbs) against MDA-modified LDL, we examined the acute changes in AAb levels during 6 hours of postprandial lipemia in 10 men with known atherosclerotic heart disease. Each subject was given 4 meals 1 week apart. Three of the meals differed in content of saturated fat, monounsaturated fat, and polyunsaturated fat. A fat-free meal with equivalent carbohydrate and equivalent protein was also administered. The study was double blinded and the meals were administered in random order. Only the meal enriched with polyunsaturated fatty acids caused the reduction in antibodies to MDA-LDL. This decrease was statistically significant from baseline at 1 hour (p <0.05), 2 hours (p <0.004), and 3 hours (p <0.02), with the nadir occurring at 2 hours. Polyunsaturated fatty acids are the major stimulus for causing a reduction in the AAbs to MDA-LDL during postprandial lipemia. These results strongly suggest that fat in chylomicrons may be a major source of oxidized lipids in the blood of patients with arteriosclerosis.
Aged↗
Apolipoprotein C-III protein concentrations and gene polymorphisms in type 1 diabetes: associations with lipoprotein subclasses.
Serum apolipoprotein C-III (apoCIII) concentration and apoCIII gene polymorphisms have been shown to be a risk factor for cardiovascular disease; however, the underlying mechanisms remain unclear. In addition, no studies have been performed that address these issues in type 1 diabetes. The current study investigated apoCIII protein and apoCIII gene variation in a normotriglyceridemic (82 +/- 57 mg/dL) population of patients with type 1 diabetes, the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) cohort. Blood samples were obtained in 409 patients after an overnight fast. Serum apoCIII concentration was highly correlated with multiple changes in lipids and lipoproteins that resulted in an adverse cardiovascular disease risk profile. Higher apoCIII concentrations were associated (P < .0001) with increased triglycerides (r = 0.78), total (r = 0.61) and low-density lipoprotein (LDL) (r = 0.40) cholesterol, apoA-I (r = 0.26), and apoB (r = 0.50), and these relationships persisted after controlling for age, gender, body mass index (BMI), and hemoglobin A1c (HbA1c). Nuclear magnetic resonance (NMR) lipoprotein subclass analyses demonstrated that apoCIII was correlated with an increase in very-low-density lipoprotein (VLDL) subclasses (P = .0001). There also was a highly significant positive relationship between serum apoCIII concentration and the LDL particle concentration in both men (r = 0.49, P = .001) and women (r = 0.40, P = .001), and a highly significant negative relationship between serum apoCIII levels and average LDL particle size in both men (r = -0.37, P = .001) and women (r = -0.22, P = .001) due primarily to an augmentation in the small L1 subclass (r = 0.42, P = .0001). Neither the T(-455) --> C polymorphism affecting an insulin response element in the apoCIII gene promoter nor a SacI polymorphism in the 3'UTR were associated with any alterations in circulating apoCIII concentrations, serum lipids, apolipoprotein concentrations, lipoprotein composition, or parameters measured by NMR lipoprotein subclass analyses. In summary, elevated apoCIII concentration was associated with risk factors for cardiovascular disease in normolipidemic type 1 diabetic patients through associated changes in lipoprotein subfraction distributions, which were independent of apoCIII genotype.
3' Untranslated Regions↗
Study of lipid and apolipoprotein binding interactions using vesicle affinity capillary electrophoresis.
Vesicle affinity capillary electrophoresis (VCE), a newly developed technique, was designed to assess the effect of physicochemical properties of apolipoprotein (apo) on the binding to lipoproteins, under physiological conditions (phosphate-saline buffer system at pH 7.4 and 37 degrees C), using vesicle as a model. The technique results in similar lipid binding properties of apo CIII (CIII) and its peptides compared to other techniques. It also offers a fast and more sensitive tool in determining the lipid affinity of apos in a unique system simulating the dynamic binding properties of apo in vivo. A noncompetitive binding model is used to determine the multiple binding properties of CIII and its peptides to vesicle. The VCE binding constants are dependent on temperature, physicochemical properties of the protein (hydrophobicity and charge), and nature of the vesicle. The vesicles used in the VCE experiments described here have been fully characterized and found to be stable under different temperatures (4 and 37 degrees C) and voltage conditions. Migration behavior of CIII and related peptides is reported in terms of relative mobility in order to correct for variability in viscosity at different vesicle concentrations. The VCE method provides very precise data on the migration time from 0.1 to 3.3% RSD at the highest concentration of vesicle. The model and current data have been used to determine VCE binding constants and protein-to-lipid binding ratios. The model predicts that higher lipid affinity (K(B)), protein-lipid binding ratio (n), and lower protein concentration result in a shift of the binding isotherm toward a lower concentration range of vesicle. A higher vesicle mobility, reflecting the size and charge of the vesicle, results in a larger separation window between the migration time of the free protein and the complex. The value of VCE for structure-function studies and drug design for peptides and proteins that are strongly bound to lipids has been illustrated.
Apolipoproteins↗
Efficacy of rosuvastatin compared with other statins at selected starting doses in hypercholesterolemic patients and in special population groups.
A total of 5 randomized, double-blind trials in patients with hypercholesterolemia were prospectively designed to allow pooling of plasma lipid data after 12 weeks of treatment. The purpose was (1) to compare rosuvastatin 5 and 10 mg with atorvastatin 10 mg (data from 3 of the 5 trials); (2) to compare rosuvastatin 5 and 10 mg with simvastatin 20 mg and pravastatin 20 mg (data from 2 of the 5 trials); and (3) to summarize overall efficacy and subset analyses of rosuvastatin data from all 5 trials. Rosuvastatin 5 mg (n = 390) and 10 mg (n = 389) reduced low-density lipoprotein (LDL) cholesterol significantly more than did atorvastatin 10 mg (n = 393) (41.9% and 46.7% vs 36.4%, both p <0.001). Treatment with rosuvastatin 5 mg (n = 240) and 10 mg (n = 226) also resulted in significantly greater reductions in LDL cholesterol compared with both simvastatin 20 mg (n = 249) and pravastatin 20 mg (n = 252) (40.6% and 48.1% vs 27.1% and 35.7%, all p <0.001). Significant differences favoring rosuvastatin 10 mg were also observed for total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, apolipoprotein (apo) B, and apo A-I versus atorvastatin 10 mg, and for total cholesterol, HDL cholesterol, triglycerides, non-HDL cholesterol, and apo B versus simvastatin 20 mg and pravastatin 20 mg. Analyses of all the rosuvastatin 10 mg data (n = 615) from the 5 trials in subgroups defined by age > or =65 years, female sex, postmenopausal status, hypertension, atherosclerosis, type 2 diabetes, and obesity showed that rosuvastatin had consistent efficacy across patient subgroups.
Adult↗
Importance of high-density lipoprotein cholesterol and triglyceride levels in coronary heart disease.
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Biomarkers↗
Cholesterol absorption inhibitors: defining new options in lipid management.
Although many studies have documented that reduction of plasma cholesterol levels decreases the risk of coronary artery disease, it remains the most common cause of death in the Western world. Current therapeutic options are effective in lowering cholesterol, especially in clinical trials, but clinical application is not optimized for many reasons. Dietary restriction for long-term management of hypercholesterolemia is helpful but usually insufficient to reduce low-density lipoprotein cholesterol (LDL-C) to goal levels. Powerful drugs are available, but these are often insufficient to meet the clinical demands for cholesterol-lowering therapy. Phytosterols and phytostanols have been partially effective by providing some inhibition of absorption of cholesterol. Compounds that specifically and more effectively block intestinal absorption of dietary and biliary cholesterol should provide a significant new agent for altering lipoprotein concentrations favorably. Ezetimibe is the first of this class of compounds that act at the gut epithelium to reduce cholesterol absorption in the milligram dose range markedly. Clinical studies indicate that ezetimibe effectively decreases LDL-C by 15 to 20% as monotherapy, with a favorable safety profile. Moreover, results from preliminary clinical trials indicate that ezetimibe given concomitantly with a statin provides additive efficacy. The combination represents a new approach to lipid management, achieving greater LDL-C and triglyceride reductions and greater improvements in HDL-C than statin monotherapy. This could offer another important option in clinical practice for management of hypercholesterolemic patients.
Anticholesteremic Agents↗
Reaching goal: conquering the treatment gaps in dyslipidemia management.
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Cholesterol, LDL↗
Benefits of statin therapy in patients with special risks: coronary bypass surgery, stable coronary disease, and acute coronary syndromes.
Several major clinical studies have examined the impact of lipid lowering in patients with and without coronary heart disease and have demonstrated that lowering lipid levels can successfully and significantly delay the onset of cardiovascular events. Although epidemiologic studies and small clinical trials have suggested that more aggressive and sustained lowering of low-density lipoprotein cholesterol (LDL-C) to < 100 mg/dl (2.6 mmol/l) can result in reductions in cardiovascular events in these populations, reducing LDL-C to these concentrations has only recently been shown in larger clinical trials. However, few clinical trials have been conducted in patients with certain special high risks, such as those who have had a recent revascularization procedure or have experienced an acute coronary event. Three trials examined the short- and long-term clinical benefits of aggressive lipid lowering in patients who underwent coronary artery bypass surgery (Post-CABG), were candidates for angioplasty (AVERT), or were hospitalized for acute coronary syndromes (MIRACL).
Acute Disease↗
Arterial compliance adds to conventional risk factors for prediction of angiographic coronary artery disease.
BACKGROUND: Arterial compliance is related to left ventricular hypertrophy and risk for cardiovascular disease events; however, its association with coronary artery stenosis remains uncertain. We sought to assess the relation between lower extremity arterial compliance and presence of angiographically defined coronary artery disease. METHODS: Lower extremity arterial compliance was measured with the use of a noninvasive air plethysmography technique in 376 subjects undergoing routine diagnostic coronary angiography. RESULTS: Measures of calf arterial compliance were significantly associated with the presence of one or more stenoses > or =50% compared with no stenoses, even after adjustment for age, sex, smoking, diabetes, hypertension, hypercholesterolemia, and obesity (P =.03). Measures of thigh arterial compliance were also lower in subjects with disease, although this association did not reach statistical significance (P =.07). Receiver operator curves illustrate the incremental predictive ability of calf arterial compliance over and above age, sex, and conventional risk factors. CONCLUSIONS: Lower extremity arterial compliance is associated with presence of significant coronary stenoses in a cardiac catheterization laboratory referral population. This observation lends support for additional efforts to determine the utility of vascular stiffness measures in both clinical and pre-clinical populations to guide treatment and prevention efforts.
Adult↗
Ezetimibe.
Ezetimibe is the first of a new class of drugs that specifically reduces the intestinal absorption of cholesterol. The drug is absorbed into the intestinal epithelial cell and remains associated in great part with the apical cell membrane where it is believed to interfere with the putative sterol transporter system. This apparently prevents both free cholesterol and plant sterols (phytosterols) from being transported into the cell from the intestinal lumen. The mechanism is very different from the reduction produced by phytosterol esters and phytostanol esters that have been documented previously as interfering with the micellar presentation of sterols to the cell surface. The drug is rapidly absorbed and glucuronidated in the intestinal cell before secretion into the blood. Ezetimibe is avidly taken up by the liver from the portal blood and excreted into the bile, resulting in low peripheral blood concentrations. The glucuronide conjugate is hydrolyzed and absorbed and is equally effective in inhibiting sterol absorption. This enterohepatic recycling is responsible for a half-life in the body of more than 20 h. The principle medical benefit appears to be a reduction in low-density lipoprotein cholesterol (LDLc). There is also a reduction in the cholesterol content of chylomicrons, which may provide some reduction in the atherogenic potential of the plasma lipoprotein pool. Triglycerides fall moderately and a modest rise in high-density lipoprotein cholesterol (HDLc) has been consistently observed in groups of treated patients. The maximum mean reduction of LDL cholesterol is approximately 20-25% in small studies at the maximal dose tested of 40 mg/day and the reduction is usually in the 16-20% range at the dosage of 10 mg/day. Most subsequent studies have been completed with the 10 mg/day dose. The medication is effective as a single daily dose due to its long residence time in the body. Combinations of ezetimibe with all available statins have been completed and demonstrate LDLc reductions of approximately 25% as additive effects to any statin dose alone. There are also small additional increases in HDL (2-3%) and reductions in triglycerides (10-15%). Additive effects to statin therapy have also been documented in patients with homozygous familial hypercholesterolemia. Reduction of plant sterols has been demonstrated in phytosterolemia, offering the first drug treatment for this rare inherited disease.
Anticholesteremic Agents↗