Phenotypic predictors of response to simvastatin therapy among African-Americans and Caucasians: the Cholesterol and Pharmacogenetics (CAP) Study

Although statins are effective lipid-lowering agents, the phenotypic and demographic predictors of such lowering have been less well examined. We enrolled 944 African-American and white men and women who completed an open-label, 6-week pharmacogenetics trial of 40 mg of simvastatin. The phenotypic and demographic variables were examined as predictors of the change in lipids and lipoproteins using linear regression analysis. On average, treatment with simvastatin lowered low-density lipoprotein (LDL) cholesterol by 54 mg/dl and increased high-density lipoprotein (HDL) cholesterol by 2 mg/dl. Compared with African-Americans, whites had a 3-mg/dl greater LDL reduction and a 1-mg/dl higher HDL elevation, independent of other variables, including baseline lipoprotein levels (p <0.01). Multivariate analyses revealed moderate subgroup differences, with older participants having a larger decrease in LDL cholesterol and apolipoprotein B levels compared with younger participants (p <0.001), women having larger increases in HDL than men (p <0.01), nonsmokers having larger decreases in LDL and triglyceride levels compared with smokers (p <0.05), those with hypertension having smaller decreases in apolipoprotein B than those without hypertension (p <0.05), and those with a larger waist circumference having a diminished lowering of triglycerides in response to treatment with simvastatin (p <0.01). In conclusion, treatment with simvastatin produced favorable lipid and lipoprotein changes among all participants. The magnitude of the lipid and lipoprotein responses, however, differed among participants according to a number of phenotypic and demographic characteristics.     

Antioxidants, lipid peroxidation and lipoproteins in primary hypertension

The antioxidants and lipid peroxidation products are being extensively studied because of their potential importance and pathogenetic role in several non-communicable diseases like cardiovascular diseases and cancer, but the data on hypertension is scanty. Therefore, the present study aimed to assess the levels of lipid peroxidation and antioxidants besides dislipidemia changes among 32 newly diagnosed male hypertensives by comparing them with an equal sample of normotensives. Significant increase in serum lipid peroxide levels and decrease in antioxidant enzyme superoxide dismutase and vitamins E and A were observed among hypertensives than the controls. Hypertensives had higher total cholesterol, low-density lipoprotein cholesterol, triglycerides, body mass index and low high-density lipoprotein cholesterol levels than normotensives. The percentage prevalence of hypercholesterolemia, hypertriglyceridemia, low high-density lipoprotein cholesterol and obesity was higher in study subjects. Obese hypertensives had significantly higher levels of lipid peroxides and lipids with no change in antioxidant status than normal-weight hypertensives. Our results suggest that hypertensive patients may have elevated lipid peroxidation, lipids and reduced protection from antioxidants, which may contribute to the propensity in such patients to develop cardiovascular diseases, and to correct this, antioxidant supplementation besides weight reduction may be helpful to reduce the severity of burden.     

Serum leptin levels in marasmic children and the relationship between leptin and lipid profile

BACKGROUND AND AIMS: Leptin and dyslipidemia are risk factors for cardiovascular disease. We measured leptin and lipid levels, and examined whether there is an effect of leptin on lipid profile in marasmic children. METHODS: Fifty children (25 marasmic, 25 healthy) aged between 0.3 and 2.5 years were evaluated. Leptin levels were compared with lipid profile in marasmic and healthy children. The relationships between leptin and sex, body mass index and lipid profile were investigated in marasmic children. RESULTS: In the marasmic group, body mass index, leptin, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol levels were lower (p < 0.0001, p < 0.0001, p < 0.0001, p = 0.01, respectively), and triglyceride levels higher than in the control group. In females, leptin was correlated positively with high-density lipoprotein cholesterol (p = 0.002), and inversely correlated with the triglyceride level (p = 0.003). In males, a positive correlation was found between leptin and low-density lipoprotein cholesterol (p = 0.026). In female patients, body mass index, leptin and high-density lipoprotein cholesterol levels were lower (p < 0.0001, for all) when compared to their female controls. In male patients, body mass index, leptin, high-density lipoprotein and low-density lipoprotein cholesterol levels were lower (p < 0.0001, p = 0.031, p = 0.002, p = 0.017, respectively) than those in their male controls. CONCLUSION: As a result, we found low leptin (an independent cardiovascular risk factor) levels, but dyslipidemia in our marasmic patients. Dyslipidemia may be a risk factor for cardiovascular complications in marasmic children in the future.     

Comparison of effects of simvastatin alone versus fenofibrate alone versus simvastatin plus fenofibrate on lipoprotein subparticle profiles in diabetic patients with mixed dyslipidemia (from the Diabetes and Combined Lipid Therapy Regimen study)

Diabetes mellitus is a strong risk factor for atherosclerosis and is often characterized by dyslipidemia. Besides acting on traditional lipids, statins and fibrates may also exert beneficial effects on various pro- and antiatherogenic lipid subparticles. This analysis was undertaken to evaluate combination therapy on lipid subparticles in the Diabetes and Combined Lipid Therapy Regimen (DIACOR) study. Patients with type 2 diabetes mellitus and no histories of coronary heart disease were evaluated (n = 498). Eligible patients underwent a 6- to 8-week washout period of all lipid-lowering medications and were enrolled if they demonstrated mixed dyslipidemia (having >or=2 of the following 3 lipid parameters: low-density lipoprotein [LDL] cholesterol >or=100 mg/dl, triglycerides >or=200 mg/dl, and high-density lipoprotein cholesterol <40 mg/dl). Patients were randomized to simvastatin 20 mg, fenofibrate 160 mg, or combined simvastatin 20 mg and fenofibrate 160 mg. Lipid subparticles were assessed 12 weeks after randomization by the Vertical Auto Profile II method. A total of 300 patients (mean age 61.6 +/- 11.5 years, 55% men) were randomized. Combination therapy was superior in lowering LDL cholesterol pattern B (-33.9 mg/dl) and dense very low-density lipoprotein cholesterol (-10.0 mg/dl) and increasing high-density lipoprotein3 (+2.3 mg/dl) and exerted the greatest change in altering the LDL cholesterol size profile. A potential effect on lipoprotein(a) (-0.5 mg/dl) was also found. For those with triglycerides >170 mg/dl, combination therapy was superior in lowering dense very low density lipoprotein cholesterol (-10.7 mg/dl) and LDL cholesterol pattern B (-35.8 mg/dl), the lipids that tend to be formed in the presence of elevated triglycerides. In conclusion, in this trial of mixed dyslipidemic patients with diabetes, combination therapy was more effective in changing a variety of other cardiovascular risk markers.     

Magnitude and characteristics of residual lipid risk in patients with a history of coronary revascularization: the ICP-bypass study

Introduction and objectives

Residual lipid risk has been defined as the excess of cardiovascular events observed in patients with adequate control of low-density lipoprotein cholesterol and has been mainly attributed to high-density lipoprotein cholesterol and triglycerides. The aim of our study was to describe the clinical features and the magnitude and characteristics associated with residual lipid risk in patients with a history of coronary revascularization.

Methods

Multicenter, observational, cross-sectional study of patients with a history of coronary revascularization. Residual lipid risk was defined as the presence of high-density lipoprotein cholesterol <40 mg/dL and/or triglycerides >150 mg/dL in patients with low-density lipoprotein cholesterol <100 mg/dL.

Results

We included 2292 patients with a mean age of 65.5 (12.4) years; 94.1% were receiving no statin therapy and 4.8% no lipid therapy. Statin-only therapy (74%) was the most common strategy, followed by combination with ezetimibe (17%). The prevalence of high-density lipoprotein cholesterol <40 mg/dL was 35.8%, hypertriglyceridemia 38.9%, and low-density lipoprotein cholesterol >100 mg/dL 44.9%; the residual lipid risk group included 29.9% of all patients. This patient group had a similar clinical profile except for slightly lower mean age, higher incidence of diabetes, and higher proportion of men. Multivariate analysis identified positive associations of diabetes and male sex with residual lipid risk; current smoking, male sex, and fibrate therapy were associated with high-density lipoprotein cholesterol <40 mg/dL; current smoking, abdominal obesity, and fibrate therapy were associated with hypertriglyceridemia.

Conclusions

In daily clinical practice, almost one-third of patients with a history of coronary revascularization have low-density lipoprotein cholesterol <100 mg/dL plus low high-density lipoprotein cholesterol and/or hypertriglyceridemia, a concept known as residual lipid risk.Full English text available from: www.revespcardiol.org     

Design and baseline characteristics of the simvastatin and ezetimibe in aortic stenosis (SEAS) study

Aortic valve stenosis and atherosclerotic disease have several risk factors in common, in particular, hypercholesterolemia. Histologically, the diseased valves appear to have areas of inflammation much like atherosclerotic plaques. The effect of lipid-lowering therapy on the progression of aortic stenosis (AS) is unclear, and there are no randomized treatment trials evaluating cardiovascular morbidity and mortality in such patients. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) Study is a randomized, double-blind, placebo-controlled, multicenter study of a minimum 4 years' duration investigating the effect of lipid lowering with ezetimibe/simvastatin 10/40 mg/day in patients with asymptomatic AS with peak transvalvular jet velocity 2.5 to 4.0 m/s. Primary efficacy variables include aortic valve surgery and ischemic vascular events, including cardiovascular mortality, and second, the effect on echocardiographically evaluated progression of AS. The SEAS Study randomly assigned 1,873 patients (age 68+/-10 years, 39% women, mean transaortic maximum velocity 3.1+/-0.5 m/s) from 173 sites. Other baseline characteristics were mean blood pressure of 145+/-20/82+/-10 mm Hg (51% hypertensive); 55% were current or previous smokers; and most were overweight (mean body mass index 26.9 kg/m2). At baseline, mean total cholesterol was 5.7+/-1.0 mmol/L (222 mg/dl), low-density lipoprotein cholesterol was 3.6+/-0.9 mmol/L (139 mg/dl), high-density lipoprotein cholesterol was 1.5+/-0.4 mmol/L (58 mg/dl), and triglycerides were 1.4+/-0.7 mmol/L (126 mg/dl). The SEAS Study is the largest randomized trial to date in patients with AS and will allow determination of the prognostic value of aggressive lipid lowering in such patients.     

Hostility and physiological risk in the National Heart, Lung, and Blood Institute Family Heart Study

BACKGROUND: The present analyses investigated possible pathways for earlier reported associations in the National Heart, Lung, and Blood Institute Family Heart Study between hostility and coronary and carotid end points. METHODS: The cross-sectional design recruited 535 women and 491 men with average familial risk for coronary heart disease and 1950 women and 1667 men with high familial coronary risk from 3 prospective ongoing studies at 4 sites. Recruitment of high-risk participants was based on family risk score. Average-risk participants came from a randomly selected group. Outcome measures were plasminogen activator inhibitor type 1 (PAI-1), homocysteine, fibrinogen, fasting glucose, blood pressure, high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein cholesterol, and "lipid metabolic disorder" (LMD) (defined as systolic blood pressure >/=140 mm Hg or diastolic blood pressure >/=90 mm Hg); fasting glucose >/=126 mg/dL (>/=7.0 mmol/L) or the use of diabetes medications; body mass index (calculated as weight in kilograms divided by the square of height in meters) >/=30; triglycerides >/=250 mg/dL (>/=2.8 mmol/L), high-density lipoprotein cholesterol <40 mg/dL (<1.0 mmol/L) in men and <50 mg/dL (<1.3 mmol/L) in women; and low-density lipoprotein cholesterol level >/=130 mg/dL (>/=3.4 mmol/L). RESULTS: After adjustment for age and risk-related behaviors, hostility was significantly associated with glucose level and LMD in high-risk women, with LMD in average-risk women, with PAI-1 and LMD in high-risk men, and with fibrinogen level in average-risk men. CONCLUSIONS: Associations between hostility and physiological risk were only partially accounted for by health behaviors, suggesting that further investigation of mechanistic pathways is warranted.     

Improvement of the lipid profile during long-term administration of pindolol and hydrochlorothiazide in patients with hypertension

The effect of the combined administration of pindolol (10 or 20 mg daily) and hydrochlorothiazide (50 mg daily) on the serum lipid and lipoprotein levels of 34 hypertensive patients was investigated for 6 to 18.5 months (mean 13.3). Placebo control data were compared with the results obtained during treatment periods in each patient by paired t tests. Mean levels of high-density lipoprotein cholesterol increased by 17% (p less than 0.01), low-density lipoprotein cholesterol decreased by 4% (p less than 0.01) and the high-density lipoprotein: low-density lipoprotein cholesterol ratio increased by 28% (p less than 0.01). Total serum cholesterol, serum triglycerides and very low-density lipoprotein cholesterol showed no statistically significant changes from control values. These findings suggest that the long-term administration of this beta blocker combined with a diuretic results in serum lipid changes considered beneficial in the evaluation of risk factors for coronary artery disease.     

Peroxisome proliferator-activated receptor gamma gene locus is related to body mass index and lipid values in healthy nonobese subjects

The peroxisome proliferator-activated receptor gamma (PPARgamma) gene has been implicated in morbid obesity and is important to lipid and carbohydrate metabolism. However, the relevance of gene variations in healthy nonobese subjects has not been defined. We recruited monozygotic and dizygotic healthy nonobese twin subjects to test the hypothesis that the PPARgamma gene is important to body mass index and lipid concentrations in healthy nonobese subjects. Both linkage and association strategies were used in the same dizygotic twins. The PPARgamma gene locus was linked (P<0.01) to high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and body mass index as quantitative traits. A biallelic variant in the PPARgamma gene was associated with high-density lipoprotein cholesterol and body mass index (P<0.05). We also looked for linkage between the same variables and the retinoic X receptor gene locus. This locus was linked to total and low-density lipoprotein cholesterol as well as triglycerides. We conclude that the PPARgamma gene is highly relevant to lipid metabolism and body mass index, not only in the morbidly obese but also in healthy nonobese subjects. The same appears to be true for its binding partner. Sequencing these genes in twins would serve to identify gene variations contributing to body mass index and lipid concentrations in healthy nonobese subjects.     

Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naive cohort

OBJECTIVES: With the use of potent antiretroviral therapy in patients with HIV disease, changes in lipid parameters and glucose homeostasis have been noted. However, these effects have been difficult to interpret because of the varied demographic and treatment characteristics of the cohorts and the complexity of differentiating the effect of HIV disease from that of the drugs used in its treatment. This study was designed to explore these issues. METHODS: Demographic information and fasting blood samples were collected from 419 antiretroviral-naive HIV-1-infected patients. RESULTS: The average age of the participants was 38.2 years, with 21% being female, 60% being African American, and 14% having a history of injection drug use. The mean CD4 lymphocyte count was 216 cells/microL, the mean baseline log10 HIV viral load was 4.98 HIV-1 RNA copies/mL, and 26% of patients had a history of AIDS-defining events. Women and African Americans had significantly higher levels of high-density lipoprotein (HDL) cholesterol, and older age was associated with higher total cholesterol levels. Lower CD4 lymphocyte counts and higher HIV RNA levels were independently associated with lower HDL cholesterol levels. Additionally, higher HIV RNA level was associated with lower levels of low-density lipoprotein (LDL) cholesterol and higher levels of very-low-density lipoprotein (VLDL) cholesterol and triglycerides. A history of AIDS-defining events was associated with higher total cholesterol, VLDL cholesterol and triglyceride concentrations. With respect to glucose homeostasis, a higher CD4 lymphocyte count was associated with less evidence of insulin resistance. However, a higher body mass index was associated with higher lipid levels and with more evidence of insulin resistance. CONCLUSIONS: Both HIV disease and demographic characteristics were found to influence lipid values and glucose homeostasis in the absence of antiretroviral treatment. More advanced HIV disease was associated with less favourable lipid and glucose homeostatic profiles. The independent association between HIV RNA levels and various lipid parameters suggests that viral replication had a direct effect on lipid levels. Interpretation of the effects of various HIV treatment regimen and drugs on metabolic parameters must take into account the stage of HIV disease and the demographic characteristics of the population studied.     

Magnitude and management of hypercholesterolemia in the adult population of Spain, 2008-2010: The ENRICA Study

Introduction and objectives

Only a few studies have reported nationwide population-based data on the magnitude and control of hypercholesterolemia. This work examines the prevalence and management of hypercholesterolemia in Spain.

Methods

Cross-sectional study conducted from June 2008 to October 2010 on 11 554 individuals representative of the population aged ≥18 years in Spain. Study participants provided 12-h fasting blood samples, which were analyzed in a central laboratory with standardized methods.

Results

In the whole population, 50.5% had hypercholesterolemia (total cholesterol ≥200 mg/dL or drug treatment) and 44.9% high levels of low-density lipoprotein cholesterol (≥130 mg/dL or drug treatment), with no substantial sex-related differences. Moreover, 25.5% of men showed high-density lipoprotein cholesterol <40 mg/dL and 26.4% of women high-density lipoprotein cholesterol <50 mg/dL. Also, 23.2% of men and 11.7% of women had triglycerides ≥150 mg/dL. Frequency of dyslipidemia increased up to 65 years, except for low high-density lipoprotein cholesterol which did not vary with age. Among those with high low-density lipoprotein cholesterol, 53.6% knew of it and 44.1% of them received lipid-lowering treatment; among the latter, 55.7% had a controlled level (13.2% of all hypercholesterolemics). Control of high low-density lipoprotein cholesterol increased with age and with the number of visits to the specialist physician, but was lower among diabetics (odds ratio=0.38; 95% confidence interval, 0.28-0.53) and patients with cardiovascular disease (odds ratio=0.55; 95% confidence interval, 0.33-0.92).

Conclusions

About half of the Spanish population has elevated serum cholesterol; moreover, cholesterol control is poor, particularly among those with highest cardiovascular risk, such as diabetics or patients with cardiovascular disease.Full English text available from:www.revespcardiol.org     

Effectiveness of probucol in reducing plasma low-density lipoprotein cholesterol oxidation in hypercholesterolemia

Oxidized low-density lipoprotein (LDL) interacts with macrophages to induce intracellular cholesterol ester accumulation and foam cell formation. Probucol is a lipid-lowering drug with a well-known antioxidant action. The thiobarbituric acid (TBA)-reacting substances were measured as an index of plasma and LDL lipid peroxidation in a group of hypercholesterolemic patients compared with a normolipidemic control group. The effect of probucol treatment on plasma and LDL lipid peroxidation in the hypercholesterolemic group was also evaluated. Twenty-five patients (10 men and 15 women) with total cholesterol levels greater than 6.5 mmol/liter were given probucol for 24 weeks. Lipid and apoprotein measurements were obtained at 0, 12 and 24 weeks. TBA-reacting substances were also measured in plasma and the LDL fraction. Twenty-five normolipidemic subjects matched for sex, age and body mass index underwent complete blood analysis for purposes of comparison at week 0. Plasma, LDL and high-density lipoprotein cholesterol, and plasma apoproteins A-I and B significantly decreased after 12 and 24 weeks of probucol treatment. Hypercholesterolemic subjects (men and women) had significantly higher TBA-reacting substances in plasma and LDL than control subjects had (p less than 0.05). The amount of TBA-reacting substances in plasma and LDL showed a very significant decrease after probucol treatment (40 and 44%, respectively, after 24 weeks; p less than 0.05). This reduction was not related to age, sex or body mass index, and was greater than the decrease in lipids. These results support a potential role for probucol as a coadjuvant drug in any lipid-lowering antiatherogenic therapy.     

Obstructive sleep apnoea and its therapy influence high-density lipoprotein cholesterol serum levels.

Recent studies suggest an association of obstructive sleep apnoea (OSA) with cardiovascular risk factors, such as dyslipidaemia. The present study analyses the effects of OSA and its therapy on serum lipid concentrations in 470 OSA patients in a single centre study. Multivariate regression showed a significant association between the apnoea-hypopnoea index and high-density lipoprotein cholesterol (HDL-C) serum levels (n = 366), independent of age, sex, body mass index, diabetes and lipid lowering medication. There were no independent associations with total cholesterol, triglyceride and low-density lipoprotein cholesterol serum levels. During follow-up (6 months) with effective bilevel or continuous positive airway pressure therapy in 127 patients (lipoproteins: n = 86) without change in their lipid lowering therapy, the mean HDL-C serum level increased significantly by 5.8% from 46.9+/-15.8 to 49.6+/-15.3 mg x dL(-1) (mean+/-SD). An independent relationship was found between the change of apnoea-hypopnoea index and the change of high-density lipoprotein cholesterol or triglycerides, respectively. All patients with abnormal serum lipid/lipoprotein levels improved significantly under bilevel or continuous positive airway pressure therapy. This study demonstrates an influence of obstructive sleep apnoea and its therapy on high-density lipoprotein cholesterol levels.     

Comparison of efficacy and safety of rosuvastatin versus atorvastatin in African-American patients in a six-week trial

The lipid-modifying effects of statin therapy in hypercholesterolemic African-Americans have not been well characterized. This study compared the efficacy and safety of rosuvastatin and atorvastatin treatment for 6 weeks in hypercholesterolemic African-American adults. In the African American Rosuvastatin Investigation of Efficacy and Safety (ARIES) trial (4522US/0002), 774 adult African-Americans with low-density lipoprotein cholesterol > or = 160 and < or = 300 mg/dl and triglycerides < 400 mg/dl were randomized to receive open-label rosuvastatin 10 or 20 mg or atorvastatin 10 or 20 mg for 6 weeks. At week 6, significantly greater reductions in low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B concentrations, as well as lipoprotein and apolipoprotein ratios, were seen with rosuvastatin versus milligram-equivalent atorvastatin doses (analysis of variance with Bonferroni-adjusted critical p < 0.017 for all comparisons). Rosuvastatin 10 mg also increased high-density lipoprotein cholesterol significantly more than atorvastatin 20 mg (p < 0.017). Although statistical comparisons were not performed, larger proportions of rosuvastatin-treated patients than atorvastatin-treated patients achieved National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. The median high-sensitivity C-reactive protein levels were significantly reduced statistically from baseline with rosuvastatin 20 mg and atorvastatin 20 mg among all patients and with rosuvastatin 10 and 20 mg and atorvastatin 20 mg in those patients with a baseline C-reactive protein level > 2.0 mg/L. The 2 study medications were well tolerated during the 6-week study period. In conclusion, rosuvastatin 10 and 20 mg improved the overall lipid profile of hypercholesterolemic African-Americans better than did milligram-equivalent doses of atorvastatin.     

Dyslipoproteinemia in systemic lupus erythematosus. Effect of corticosteroids

The increased incidence of atherosclerotic coronary artery disease in patients with systemic lupus erythematosus (SLE) may be due to a dyslipoproteinemia caused by corticosteroid administration. To determine whether lipoprotein lipid levels are abnormal in SLE and the relation of lipoprotein levels to corticosteroid use, lipid and apolipoprotein levels were measured in 46 female patients with SLE and 30 matched control subjects. The patients with SLE had higher levels of plasma triglyceride (134 versus 73 mg/dl; p less than 0.001), cholesterol (201 versus 168 mg/dl; p less than 0.001), and low-density lipoprotein cholesterol (121 versus 94 mg/dl; p less than 0.001) than control subjects. The levels of high-density lipoprotein cholesterol, high-density lipoprotein subfraction 3 cholesterol, and apolipoprotein Al were similar in the two groups, but high-density lipoprotein subfraction 2 cholesterol was lower in the patients with SLE (10.2 versus 18.2 mg/dl; p less than 0.001). When patients with SLE treated with prednisone (n = 32) were compared to patients with SLE not treated with prednisone (n = 14), the former had higher triglyceride (158 versus 87 mg/dl; p less than 0.001), cholesterol (214 versus 170 mg/dl; p less than 0.001), and low-density lipoprotein cholesterol (130 versus 103 mg/dl; p less than 0.001) levels. The patients with SLE not treated with prednisone had lipid levels similar to those in control subjects except that high-density lipoprotein cholesterol was lower (49.7 versus 59.0 mg/dl; p less than 0.05). The daily prednisone dosage in the treated patients with SLE correlated with levels of cholesterol (r = 0.38, p less than 0.02), high-density lipoprotein cholesterol (r = 0.40, p less than 0.02), and high-density lipoprotein subfraction 3 cholesterol (r = 0.47, p less than 0.01). Thus, female patients with SLE have a dyslipoproteinemia of the type that would place them at an increased risk for coronary artery disease. Corticosteroids, used in the treatment of SLE, seem to play a role in the pathogenesis of the observed lipoprotein abnormalities.     

Efficacy and safety of a potent new selective cholesterol absorption inhibitor,ezetimibe, in patients with primary hypercholesterolemia

The efficacy and safety of ezetimibe, a new cholesterol absorption inhibitor, was evaluated in this randomized, double-blind, placebo-controlled trial of 892 patients with primary hypercholesterolemia. After > or =2 weeks on the National Cholesterol Education Program (NCEP) Step I or a stricter diet and a 4- to 8-week single-blind placebo lead-in, patients with low-density lipoprotein (LDL) cholesterol 130 to 250 mg/dl and triglycerides < or =350 mg/dl were randomized 3:1 to receive ezetimibe 10 mg or placebo orally each morning for 12 weeks. The primary efficacy end point was the percent reduction in direct plasma LDL cholesterol from baseline to end point. A total of 434 men and 458 women (ages 18 to 85 years) received randomized treatment (666 ezetimibe 10 mg, 226 placebo). Demographics and baseline characteristics were similar between treatment groups. Ezetimibe significantly reduced direct LDL cholesterol by a mean of 16.9%, compared with an increase of 0.4% with placebo (p <0.01). Subgroup analysis indicated that response to ezetimibe was generally consistent across all subgroups, regardless of risk-factor status, gender, age, race, or baseline lipid profile. Ezetimibe effects on LDL cholesterol occurred early (2 weeks) and persisted throughout the 12-week treatment period. Compared with placebo, ezetimibe 10 mg also significantly improved calculated LDL cholesterol, apolipoprotein B, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and HDL(3) cholesterol (p <0.01). Ezetimibe was well tolerated. There were no differences in laboratory or clinical safety parameters, or gastrointestinal, liver, or muscle side effects from that of placebo. Ezetimibe 10 mg/day is well tolerated, reduces LDL cholesterol approximately 17%, and improves other key lipid parameters.     

Common INSIG2 polymorphisms are associated with age-related changes in body size and high-density lipoprotein cholesterol from young adulthood to middle age

Insulin-induced gene 2 (INSIG2) plays an important role in the regulation of cholesterol and fatty acids synthesis. A polymorphism, rs7566605, located 10 kilobases upstream of the INSIG2 gene, was identified in a genomewide association study of obesity. We conducted an association study of 12 INSIG2 tag-single nucleotide polymorphisms with longitudinal measures of body size (body mass index and waist circumference) and lipid metabolism (plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides levels). We investigated their interaction with age in 4304 Coronary Artery Risk Development in Young Adults participants (49.5% blacks, 50.5% whites) followed prospectively for 20 years. rs7566605 was not associated with variation in body size or lipid metabolism at any age in either racial group. However, rs1352083 and rs10185316 were associated with age-related decline in high-density lipoprotein cholesterol in whites (P = .0005 and .04, respectively). A similar trend was observed in blacks who consistently maintained a body mass index less than 25 kg/m² over the study period. These data support a role of INSIG2 sequence variation in the regulation of cholesterol metabolism.     

Comparison of modifiable determinants of lipids and lipoprotein levels among African-Americans, Hispanics, and Non-Hispanic Caucasians > or =65 years of age living in New York City.

Information on determinants of plasma lipids and lipoproteins and how these factors would differ among race/ethnic groups in elderly populations is scarce. We studied cross-sectionally the distribution and predictors of lipids and lipoproteins in 1,118 free-living elderly subjects (> or =65 years of age), in a multiethnic urban community (22% non-Hispanic Caucasian, 34% African-American, and 44% Hispanic). Mean levels of total cholesterol, total/high-density lipoprotein (HDL) cholesterol ratio, and triglycerides decreased with increasing age (p <0.001). Low-density lipoprotein cholesterol and total cholesterol were lower among men, whereas women had higher levels of HDL cholesterol (p <0.001). Hispanics had lower low-density lipoprotein cholesterol, total cholesterol, and HDL cholesterol levels, whereas African-Americans had a lower total/HDL cholesterol ratio and triglyceride levels along with higher HDL cholesterol levels (p <0.001). Diabetes was more prevalent among Hispanics and African-Americans (p = 0.002), and body mass index was higher in African-Americans (p = 0.009). Hispanics were less likely to drink alcohol (p <0.0001), but more likely to drink larger amounts of coffee (p <0.0001). A greater proportion of African-Americans were active smokers (p <0.001). In multivariate regression models, body mass index was a significant independent predictor of total cholesterol (beta = 0.74, p <0.001). Waist circumference predicted lower HDL cholesterol levels (0.57 mg/dl lower per inch, p <0.001) and a higher total/HDL cholesterol ratio (beta = 0.05, p <0.001). Alcohol intake (>2 g/day) predicted higher HDL cholesterol (beta = 6.20, p <0.001). Diabetic status predicted lower HDL cholesterol (beta = -2.47, p <0.05), higher total/HDL cholesterol ratio (beta = 0.35, p <0.001), and triglycerides (beta = 37.10, p <0.001). Physical activity, coffee intake, and a calorie-adjusted atherogenicity index did not show independent predictive value. These findings indicate that obesity, alcohol intake, and diabetes mellitus are potentially modifiable independent determinants of lipids and lipoprotein levels in an elderly multiethnic population.     

Control of Lipids at Baseline in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial

In order to examine lipids, a major treatment parameter in those with diabetes and heart disease, the authors analyzed baseline data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. The study consisted of 2368 participants with type 2 diabetes and coronary artery disease from 49 sites in 6 countries (2295 provided lipid measurements). Fifty-nine percent of participants had a low-density lipoprotein (LDL) cholesterol level <100 mg/dL. Levels of total, LDL, and non–high-density lipoprotein (HDL) cholesterol and triglycerides differed by age group (younger than 55, 55–64, and 65 years and older); they were lowest in those aged 65 years. Women had higher total, LDL, and non-HDL cholesterol values. Education was associated with lower total, LDL, and non-HDL cholesterol levels. LDL cholesterol and triglyceride values were lower in the United States and Canada. Adjustment for age, sex, education level, randomization year, and medication did not eliminate these differences. Geographic variation was seen and was not fully accounted for by demographic or treatment characteristics (all P values <.05).     

Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials

BACKGROUND: Low-carbohydrate diets have become increasingly popular for weight loss. However, evidence from individual trials about benefits and risks of these diets to achieve weight loss and modify cardiovascular risk factors is preliminary. METHODS: We used the Cochrane Collaboration search strategy to identify trials comparing the effects of low-carbohydrate diets without restriction of energy intake vs low-fat diets in individuals with a body mass index (calculated as weight in kilograms divided by the square of height in meters) of at least 25. Included trials had to report changes in body weight in intention-to-treat analysis and to have a follow-up of at least 6 months. Two reviewers independently assessed trial eligibility and quality of randomized controlled trials. RESULTS: Five trials including a total of 447 individuals fulfilled our inclusion criteria. After 6 months, individuals assigned to low-carbohydrate diets had lost more weight than individuals randomized to low-fat diets (weighted mean difference, -3.3 kg; 95% confidence interval [CI], -5.3 to -1.4 kg). This difference was no longer obvious after 12 months (weighted mean difference, -1.0 kg; 95% CI, -3.5 to 1.5 kg). There were no differences in blood pressure. Triglyceride and high-density lipoprotein cholesterol values changed more favorably in individuals assigned to low-carbohydrate diets (after 6 months, for triglycerides, weighted mean difference, -22.1 mg/dL [-0.25 mmol/L]; 95% CI, -38.1 to -5.3 mg/dL [-0.43 to -0.06 mmol/L]; and for high-density lipoprotein cholesterol, weighted mean difference, 4.6 mg/dL [0.12 mmol/L]; 95% CI, 1.5-8.1 mg/dL [0.04-0.21 mmol/L]), but total cholesterol and low-density lipoprotein cholesterol values changed more favorably in individuals assigned to low-fat diets (weighted mean difference in low-density lipoprotein cholesterol after 6 months, 5.4 mg/dL [0.14 mmol/L]; 95% CI, 1.2-10.1 mg/dL [0.03-0.26 mmol/L]). CONCLUSIONS: Low-carbohydrate, non-energy-restricted diets appear to be at least as effective as low-fat, energy-restricted diets in inducing weight loss for up to 1 year. However, potential favorable changes in triglyceride and high-density lipoprotein cholesterol values should be weighed against potential unfavorable changes in low-density lipoprotein cholesterol values when low-carbohydrate diets to induce weight loss are considered.