The effect of L-thyroxine replacement therapy on lipid based cardiovascular risk in subclinical hypothyroidism

The aim of our study was to assess the changes in serum lipid profiles after replacement therapy with L-T4 in patients with subclinical hypothyroidism (SCH), and to see whether there is an improvement in dyslipidemia based cardiovascular risk. Thirty non-smoker pre-menopausal women with newly diagnosed SCH (TSH between 4 and 10 microIU/ml) were involved in our study; twenty-six euthyroid healthy subjects were used as control group. TSH, free T3 (FT3), free T4 (FT4), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were measured before and after 6 months of L-T4 (50-100 microg/ day) therapy. TSH levels were targeted as < 2.0 microIU/ml. LDL-C was calculated using the Friedewald formula, while the cardiovascular risk was assessed with the TC/HDL-C ratio. Pre-treatment serum TC and LDL-C concentrations in SCH patients were significantly higher than those of euthyroid subjects (199.8 +/- 22.2 vs 181.5 +/- 24.6 mg/dl, p < 0.01; 146.3 +/- 26.1 vs 124.8 +/- 12 mg/dl, p < 0.001, respectively). TC, LDL-C levels and the TC/HDL-C ratio were reduced significantly after 6-month replacement therapy (-21.1 +/- 34.4 mg/dl or -10.5%, p < 0.01; -21.5 +/- 30.3 mg/dl or -14.7%, p < 0.001, respectively; and TC/HDL-C from 4.8 +/- 0.6 to 4.1 +/- 0.5 mg/dl, p < 0.01), while body mass index (BMI) values did not change. In conclusion, even mild elevations of TSH are associated with changes in lipid profile significant enough to raise the cardiovascular risk ratio, and these changes are corrected once the patients have been rendered euthyroid.     

Relation of coronary artery calcium identified by electron beam tomography to serum lipoprotein levels and implications for treatment

This study was designed to determine whether the National Cholesterol Education Program (NCEP) lipid guidelines accurately identify subclinical atherosclerosis and whether low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels are related to the extent and prematurity of coronary artery disease (CAD) as determined by electron beam tomography (EBT). Out of personal concern for CAD risk, 930 consecutive asymptomatic subjects, without clinical CAD and on no lipid-lowering agents, underwent EBT. Calcium score and percentile were correlated with total cholesterol (TC), LDL-C, HDL-C, triglycerides, and demographic parameters. A calcium score of > 0 (EBT+) was found in 55% of patients; 45% of patients had a 0 score (EBT-). Mean age (58.0 +/- 10.5 vs 49.3 +/- 9.7 years, p = 0.0001), TC (218 +/- 39 vs 211 +/- 41 mg/dl, p = 0.006), LDL-C (136 +/- 36 vs 127 +/- 27 mg/dl, p = 0.005), and TC/HDL-C (4.6 +/- 1.4 vs 4.2 +/- 1.5, p = 0.0001) were significantly higher and HDL-C (52.2 +/- 17.6 vs 55.4 +/- 19.3 mg/dl, p = 0.008) lower in the EBT+ compared with EBT- group. In the EBT+ group, 75.1% of subjects had LDL-C < 160 mg/dl and would not be advised to use lipid-lowering medications according to NCEP guidelines. In subjects with LDL-C < 160 mg/dl, 51.8% of subjects were EBT+, as were 46.1% of those with LDL-C < 100 mg/dl. There were no significant differences in the calcium scores throughout the entire range of all lipid parameters; calcium percentiles were virtually identical within lipid value subgroups. We conclude that asymptomatic patients with EBT-defined subclinical atherosclerosis are not reliably identified by NCEP guidelines, and TC, LDL-C, HDL-C, TC/HDL-C, and triglyceride levels do not correlate with either the extent or prematurity of calcified plaque burden.     

Variable effects of weight loss on serum lipids and lipoproteins in obese patients

After a 500 calorie diet and 6 months of low fat, maintenance diet, weight, serum lipid, and lipoprotein levels were compared to baseline in 46 obese patients. Mean weight decreased by 25.9 percent (29.2 kg). Mean total (TC) and low density lipoprotein cholesterol (LDL-C), and triglycerides (TG) decreased by 5.5 percent (12.1 mg/dl), 11 percent (15.5 mg/dl) and 23.6 percent (34.5 mg/dl); mean high density lipoprotein cholesterol (HDL-C) increased by 20.6 percent (10.3 mg/dl) and TC/HDL-C decreased by 25 percent (1.2), P less than 0.01. Females and males had equal increases in HDL-C. The decrease in TG and TC in patients who continued to lose 4.2 kg during the 6 month maintenance period was significantly greater than in those who regained 7.8 kg (P less than 0.015). Greater changes in HDL-C and TC/HDL-C occurred in younger individuals (r = -0.35 and r = -0.37); in those with more abnormal initial values (r = -0.60, r = 0.64); and for HDL-C, a larger increase occurred in those with greater weight loss (r = 0.32; P less than 0.04).     

Obese children lipid profile: effects of hypocaloric diet and aerobic physical exercise

Diet and exercise help improve obese adults' lipid profile. However, their effect on obese children, the aim of the present study, is poorly known. Fifty obese children were studied into 2 paired groups: Group D (1,500 - 1,800 kcal diet: 55% carbohydrate, 30% fat, 15% protein), and Group DE (same diet + aerobic physical activity 1 hour/day 3 times a week). After 5 months BMI, triglycerides, total cholesterol (TC) and fractions were assessed. No change in triglycerides, TC and low-density lipoprotein cholesterol (LDL-C) levels were reported in both groups. However, high-density lipoprotein cholesterol (HDL-C) increased (+10.3%; p< 0.01) only in DE Group. Screening patients with TC > 170 mg/dL, LDL-C > 110 mg/dL and HDL-C < 35 mg/dL we had: similar reduction for TC in both groups (-6.0% x -6.0%; p= ns), LDL-C reduction in both groups (-14.2% x -13.5%; p= ns), and HDL-C increase only in DE Group (+10.0%; p< 0.05). CONCLUSIONS: 1) Hypocaloric diet (HD) + exercise, rather than diet only, increase obese children's HDL-C levels irrespective of baseline levels; 2) HD only and HD + exercise lead to TC and LDL-C reduction in obese children with TC and LDL-C above normal values.     

Secular trends in blood lipid disorders among adolescents: population study in Novosibirsk (1989-2003)

Hyperlipidemia is a known risk factor of coronary artery disease. The reduction of elevated serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in childhood may reduce cardiovascular morbidity and mortality in adulthood. Aim of the study was to assess prevalence and trends in lipid profile and lipid disorders in adolescent population in Novosibirsk (1989-2003). METHODS: Four cross-sectional surveys of school children aged 14-17 years in 1989 (n=656), in 1994 (n=620), in 1999 (n=626) and in 2003 (n=667) were carried out. Total sample was 2569 (1214 males and 1355 females). Blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) were measured by enzymatic methods. LDL-C was calculated with Friedwald's formula. Associations of blood lipids with age, sex, year of study, body mass index (kg/m2), blood pressure and main nutrients of diet were measured by GLM method. Prevalence of dyslipidemia was evaluated with NCEP-peds criteria. Diet was estimated using 24-hour dietary recall. RESULTS: During the 15-year period (1989-2003) mean serum TC decreased from 175 to 162 mg/dl in males and from 191 to 175 mg/dl in females (p < 0.001). Average levels of LDL-C also fell significantly during this period, but no changes in HDL-C levels were found. Females had significantly higher mean TC and LDL-C than did males at all surveys (p < 0.001). According to NCFP-peds criteria prevalence of high TC (200 mg/dl und more) during the period (1989-2003) significantly decreased from 22% to 8% (p < 0.01) in males and from 32% to 17% (p < 0.05) in females. Frequencies of low HDL-C (< 40 mg/dl) also decreased in boys and girls (p < 0.05 for both gender groups). Significant regression coefficients for TC controlled by age, sex and year of study were revealed with body mass index, diastolic blood pressure and triceps skinfolds. Trends in diet during the period showed significant decrease of total energy and basic nutrient intakes (proteins, fats and carbohydrates). CONCLUSION: During the period of socioeconomic reforms in Russia (1989-2003) the lipid profile and prevalence of atherogenic dislipidemias in adolescents of Novosibirsk significantly changed following the changes of body mass index and diet.     

Suboptimal lipid levels in clinical practice among Portuguese adults with dyslipidemia under lipid-lowering therapy: Data from the DISGEN-LIPID study

IntroductionCardiovascular disease (CVD) is the leading cause of morbidity and mortality in Portugal. Hypercholesterolemia has a causal role in atherosclerotic CVD. Guidelines recommend that cardiovascular (CV) risk reduction should be individualized and treatment goals identified. Low-density lipoprotein cholesterol (LDL-C) is the primary treatment target.MethodsDISGEN-LIPID was a cross-sectional observational study conducted in 24 centers in Portugal in dyslipidemic patients aged ≥40 years, on lipid-lowering therapy (LLT) for at least three months and with an available lipid profile in the previous six months.ResultsA total of 368 patients were analyzed: 48.9% men and 51.1% women (93.9% postmenopausal), of whom 73% had a SCORE of high or very high CV risk. One quarter had a family history of premature CVD; 31% had diabetes; 26% coronary heart disease; 9.5% cerebrovascular disease; and 4.1% peripheral arterial disease. Mean baseline lipid values were total cholesterol (TC) 189 mg/dl, LDL-C 116 mg/dl, high-density lipoprotein cholesterol (HDL-C) 53.5 mg/dl, and triglycerides (TG) 135 mg/dl. Women had higher TC (p<0.001), LDL-C (non-significant) and HDL-C (p<0.001), and lower TG (p=0.002); 57% of men and 63% of women had LDL-C>100 mg/dl (p=0.28), and 58% of men and 47% of women had LDL-C>70 mg/dl (p=0.933).ConclusionThese observational data show that, despite their high-risk profile, more than half of patients under LLT, both men and women, did not achieve the recommended target levels for LDL-C, and a large proportion also had abnormal HDL-C and/or TG. This is a renewed opportunity to improve clinical practice in CV prevention.     

Wives of patients with acute myocardial infarction are at an increased risk of developing coronary artery disease

BACKGROUND: The present study was carried out to investigate risk factors for developing coronary artery disease in wives of patients with acute myocardial infarction. SUBJECTS AND METHODS: Risk factors for developing coronary artery disease were investigated in 50 wives of patients who developed an acute myocardial infarction (group A) and were compared with those of 50 wives of normal healthy men (group B). The average age was 50.20 +/- 1.56 years (mean +/- SD) and 50.20 +/- 1.53 years for group A and group B respectively. The parameters assessed were: plasma cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), systolic and diastolic blood pressure, smoking habits and body mass index (BMI). RESULTS: The levels of LDL-C in the wives of patients with myocardial infarction were higher than those of the wives of normal healthy men (167.8 +/- 5.84 mg/dl and 148.4 +/- 4.85 mg/dl, respectively, P < 0.01). Moreover, HDL-C concentrations were lower in the wives of the patients (51.34 +/- 0.92 mg/dl) than in the wives of the healthy men (58.14 +/- 1.39 mg/dl), (P < 0.001). Finally, TG levels were higher in the wives of the patients (132.2 +/- 7.9 mg/dl) than in the wives of the normal healthy men (96.9 +/- 5.94 mg/dl) (P < 0.01). CONCLUSIONS: Although plasma lipid levels themselves were not excessively high, the wives of patients with an acute myocardial infarction are at a higher risk of developing coronary artery disease than the wives of normal healthy men, in the long term, due to higher levels of LDL-C and TG as well as lower levels of HDL-C.     

Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia and coronary heart disease: secondary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT).

Hyperlipidemia is primarily implicated in the progression of coronary heart disease (CHD) and its treatment is essential for patients with a history of CHD. Statins such as simvastatin, the lipid-lowering agents, are well-known for their ability to normalize patient's serum lipid levels. The Japan Lipid Intervention Trial study of simvastatin is the first nationwide investigation of the relationship between serum lipid levels and the development of CHD in Japanese patients with hypercholesterolemia. Of 5,127 patients, exclusively with a history of documented CHD at enrollment, 4,673 were treated with open-labeled simvastatin at an initial dose of 5-10 mg/day and were monitored for 6 years. The risk of coronary events tended to be higher in patients with a serum total cholesterol (TC) > or =240 mg/dl compared with total cholesterol <240 mg/dl. The concentration of low-density lipoprotein cholesterol (LDL-C) positively correlated and that of high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of CHD. Each 10 mg/dl decrease in LDL-C and each 10 mg/dl increase in HDL-C concentration reduced the risk of CHD by 8.0% (95% confidence interval 3.8-12.0) and 28.3% (95% CI 13.9-40.3), respectively. A reasonable therapeutic strategy to reduce CHD progression in patients with prior CHD under low-dose statin treatment might be regulating the serum LDL-C concentration to at least <120 mg/dl and HDL-C >40 mg/dl, respectively.     

Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels.

OBJECTIVES: This study was designed to evaluate the efficacy and safety of torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, in subjects with low high-density lipoprotein cholesterol (HDL-C) levels. BACKGROUND: Evidence suggests HDL-C is atheroprotective. A proven mechanism for increasing the level of HDL-C is the inhibition of CETP. METHODS: A total of 162 subjects with below-average HDL-C (men <44 mg/dl; women <54 mg/dl) who were not taking lipid-modifying therapy were randomized to double-blind treatment with torcetrapib 10, 30, 60, or 90 mg/day or placebo ( approximately 30 subjects per group). RESULTS: The percent change from baseline to Week 8 with torcetrapib (least-squares mean difference from placebo) was dose-dependent and ranged from 9.0% to 54.5% for HDL-C (p < or = 0.0001 for 30 mg and higher doses) and from 3.0% to -16.5% for low-density lipoprotein cholesterol (LDL-C) (p < 0.01 for 90-mg dose). Low-density lipoprotein cholesterol lowering was less in subjects with higher (>150 mg/dl) versus lower levels of baseline triglycerides; at 60 mg, the change in LDL-C was 0.1% versus -22.2% (p < 0.0001), respectively. Particle size for both HDL and LDL increased with torcetrapib. There were no dose-related increases in the frequency of adverse events. Significant blood pressure increases were noted in 2 of 140 subjects. CONCLUSIONS: Torcetrapib resulted in substantial dose-dependent elevations in HDL-C, accompanied by moderate decreases in LDL-C at the higher doses. Torcetrapib was generally well tolerated.     

Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia

OBJECTIVES: The purpose of this study was to assess the efficacy and safety of ezetimibe administered with simvastatin in patients with primary hypercholesterolemia. BACKGROUND: Despite the availability of statins, many patients do not achieve lipid targets. Combination therapy with lipid-lowering agents that act via a complementary pathway may allow additional patients to achieve recommended cholesterol goals. METHODS: After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =145 mg/dl to < or =250 mg/dl and triglycerides (TG) < or =350 mg/dl were randomized to one of the following 10 groups administered daily for 12 consecutive weeks: ezetimibe 10 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg plus simvastatin 10, 20, 40, or 80 mg; or placebo. The primary efficacy variable was percentage reduction from baseline to end point in direct LDL-C for the pooled ezetimibe plus simvastatin groups versus pooled simvastatin groups. RESULTS: Ezetimibe plus simvastatin significantly improved LDL-C (p < 0.01), high-density lipoprotein cholesterol (HDL-C) (p = 0.03), and TG (p < 0.01) compared with simvastatin alone. Ezetimibe plus simvastatin (pooled doses) provided an incremental 13.8% LDL-C reduction, 2.4% HDL-C increase, and 7.5% TG reduction compared with pooled simvastatin alone. Coadministration of ezetimibe and simvastatin provided LDL-C reductions of 44% to 57%, TG reductions of 20% to 28%, and HDL-C increases of 8% to 11%, depending on the simvastatin dose. Ezetimibe 10 mg plus simvastatin 10 mg and simvastatin 80 mg alone each provided a 44% LDL-C reduction. The coadministration of ezetimibe with simvastatin was well tolerated, with a safety profile similar to those of simvastatin and of placebo. CONCLUSIONS: When coadministered with simvastatin, ezetimibe provided significant incremental reductions in LDL-C and TG, as well as increases in HDL-C. Coadministration of ezetimibe with simvastatin was well tolerated and comparable to statin alone.     

Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia.

Hyperlipidemia is a well-established risk factor for primary coronary heart disease (CHD). Although simvastatin is known to lower serum lipid concentrations, the protective effect of such lipid-lowering therapy against primary CHD has not been established in Japanese patients with hypercholesterolemia. The Japan Lipid Intervention Trial was a 6-year, nationwide cohort study of 47,294 patients treated with open-labeled simvastatin (5-10 mg/day) and monitored by physicians under standard clinical conditions. The aim of the study was to determine the relationship between the occurrence of CHD and the serum lipid concentrations during low-dose simvastatin treatment. Simvastatin reduced serum concentrations of total cholesterol (TC), low-density lipoprotein- cholesterol (LDL-C) and triglyceride (TG), by 18.4%, 26.8% and 16.1% on average, respectively, during the treatment period. The risk of coronary events was higher when the average TC concentration was > or =240 mg/dl and the average LDL-C concentration was > or =160 mg/dl. The incidence of coronary events increased in the patients with TG concentration > or =300 mg/dl compared with patients with TG concentration <150 mg/dl. The high-density lipoprotein cholesterol (HDL-C) inversely correlated with the risk of coronary events. The J-curve association was observed between average TC or LDL-C concentrations and total mortality. Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC and LDL-C concentrations with low-dose statin. A reasonable strategy to prevent coronary events in Japanese hypercholesterolemic patients without prior CHD under low-dose statin treatment might be regulating the serum lipid concentrations to at least <240 mg/dl for TC, <160 mg/dl for LDL-C, <300 mg/dl for TG, and >40 mg/dl for HDL-C.     

Serum lipid comparison in patients treated by statins or fibrates: existence of bad HDL-C responders to statins

INTRODUCTION: Major cardiac events are strongly associated with high levels of low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C). The HDL-C target level (40 mg/dl) is often not achieved with statins. The aim of this study was to compare the proportions of patients achieving the HDL-C target levels after one year of treatment with statins or fibrates. Furthermore, a subgroup with low HDL-C levels during statin treatment was investigated and suggestions are made for a better management of these patients. METHODS: A survey of lipid levels, cardiovascular disease and risk factors in 120 outpatients treated with a statin or a fibrate for hyperlipidaemia (total cholesterol (TC) > 250 mg/dl or triglycerides (TG) > 200 mg/dl after diet). After one year of treatment the proportions of patients achieving the target levels for TC, LDL-C, HDL-C,TG,TC/HDL-C and LDL-C/HDL-C are compared for statins and fibrates. RESULTS: The proportions of patients achieving the target lipid levels with statins or fibrates are comparable except for HDL-C. Compared to the baseline, the proportion of patients achieving the HDL-C target level of 40 mg/dl increases only by 8.3% for statins and by 42.9% for fibrates. In total, 38.5% of the statin group had low HDL-C-levels after one year of treatment. Among these patients, eight were treated with a fibrate before the statin and six were treated with a fibrate afterwards. In those 14 patients, mean HDL-C increased during fibrate treatment by 48.5% and TC/HDL-C and LDL-C/HDL-C decreased by 25.7 and 26.5%, respectively as compared with statins. CONCLUSIONS: Patients with low levels of HDL-C during statin treatment had far better levels of HDL-C, TC/HDL-C and LDL-C/HDL-C with fibrates. A randomised double-blind crossover trial with simvastatin and fenofibrate has been initiated to corroborate these findings.     

Seasonal variation of serum high density lipoprotein cholesterol levels in men

To determine if there are seasonal variations in serum high density lipoprotein cholesterol (HDL-C), the concentration of HDL-C was measured monthly for 12 consecutive months in 31 healthy men and 24 male inpatients with schizophrenia. In addition to HDL-C, total cholesterol (TC) and triglyceride (TG) concentrations in serum were assayed, and low density lipoprotein cholesterol (LDL-C) was estimated by calculation. Mean serum HDL-C levels of schizophrenic patients were significantly low compared with those of healthy controls, 35 +/- 12 and 49 +/- 11 mg/dl, respectively. The TC levels of schizophrenic patients were significantly higher in January and March as compared with August. The HDL-C levels in summer and autumn were significantly lower than those in winter and spring in both healthy men and schizophrenic patients. The concentration of LDL-C was significantly high in September and October as compared with April in healthy men. In patients with schizophrenia, LDL-C level seemed higher in January and March as compared with August.     

Cholesterol paradox in patients with paroxysmal atrial fibrillation

Hypercholesterolemia is a major risk factor for coronary heart disease (CHD), but the associations among lipids, lipoproteins and paroxysmal atrial fibrillation (PAF) have not yet been reported. The associations among lipids, lipoproteins and PAF were examined in a case-control study, in which cases and controls were defined as those with/without definite ECG-detectable PAF, respectively. CHD patients were excluded from the study. The mean values of serum total cholesterol (TC), triglyceride (TG) and high density lipoprotein-cholesterol (HDL-C), after adjusting for age and gender, in patients with PAF were lower than those in patients without PAF (175 +/- 4 mg/dl vs. 190 +/- 3 mg/dl, 104 +/- 7 mg/dl vs. 123 +/- 6 mg/dl, 46.0 +/- 1.7 mg/dl vs. 51.8 +/- 1.4 mg/dl, respectively), as assessed by an analysis of covariance. After controlling for age and gender, TC, TG and HDL-C (all in quartiles) were inversely and linearly (p < 0.05) associated with the percentage of patients with PAF, as assessed by a multiple logistic regression analysis. The associations between TC or TG and PAF varied with the HDL-C level: significant when HDL-C was low (p < 0.05), but not when HDL-C was high. The odds ratio (relative risk of PAF) for patients with both low TC or TG and low HDL-C was 4.08 (95% CI: 1.81-9.57) times or 9. 40 (3.25-32.0) times higher (p < 0.01) than that for patients with high TC or TG and high HDL-C, respectively. In conclusion, low serum levels of TC and TG were found in PAF patients, while reduced HDL-C may cause PAF. Hypolipoproteinemia including low HDL-C may affect atrial vulnerability and cause atrial fibrillation.     

Aerobic exercise and lipids and lipoproteins in children and adolescents: a meta-analysis of randomized controlled trials

OBJECTIVE: Use the meta-analytic approach to examine the effects of aerobic exercise on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) in children and adolescents. STUDY DESIGN: Randomized controlled trials which were limited to aerobic exercise >or=4 weeks in children and adolescents 5-19 years of age. RESULTS: Twelve outcomes representing 389 subjects were available for pooling. Using random-effects modeling, a trend for statistically significant decreases of 12% was found for TG (X +/-S.E.M., -11.0+/-6.1mg/dl; 95% CI, -22.8-0.8 mg/dl) with no statistically significant changes for TC, HDL-C, and LDL-C. Decreases in LDL-C were associated with increased training intensity (r=-0.89; 99% CI, -0.99 to -0.04) and older age (r=-0.90; 99% CI, -0.99 to -0.25) while increases in HDL-C were associated with lower initial HDL-C (r=-0.75; 99% CI, -0.94 to -0.80). Statistically significant decreases in TG were observed in overweight/obese subjects with a trend for increases in HDL-C (TG, X +/-S.E.M., -23.9+/-7.0mg/dl; 95% CI, -37.6 to -10.1mg/dl; HDL-C, X +/-S.E.M., 4.0+/-2.3mg/dl; 95% CI, -0.5-8.5mg/dl). CONCLUSIONS: Aerobic exercise decreases TG in overweight/obese children and adolescents.     

Randomized dose-response study of rosuvastatin in Japanese patients with hypercholesterolemia

Rosuvastatin is a novel statin that has been shown to produce large dose-dependent reductions in low-density lipoprotein cholesterol (LDL-C) in Western hypercholesterolemic patients. Rosuvastatin dose response was assessed in a randomized, double-blind phase II trial in which 112 Japanese patients with fasting LDL-C > 160 and < 220 mg/dl and triglycerides < 300 mg/dl received placebo or rosuvastatin 1, 2.5, 5, 10, 20, or 40 mg once daily for 6 weeks. LDL-C change from baseline showed a linear dose response (p < 0.0001 for slope of regression line) over the rosuvastatin dose range, with each doubling of dose producing an additional 5.12% reduction. Mean reductions (least-squares mean percentage change from baseline from ANOVA) in LDL-C were 35.8% to 66.0% and significantly different from placebo at all doses (p < 0.0001). Linear dose response was also observed for total cholesterol (TC) and apolipoprotein (apo) B, but not for triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), or apo A-I or A-II. Mean changes at 6 weeks were - 25.5 to - 45.1% for TC, - 16.0 to - 26.2% for TG, + 7.5 to + 12.8% for HDL-C, - 31.9 to - 57.8% for apo B, + 5.5 to + 10.0% for apo A-I, and + 0.4 to + 8.1% for apo A-II. Rosuvastatin was well tolerated. Although there was some suggestion of increased frequency of treatment-related adverse events at higher doses, there were no clear dose relationships in safety parameters. Only one patient withdrew from the study because of a treatment-related adverse event. No patients had clinically significant elevations in liver transaminases or creatine kinase. Rosuvastatin produces good dose-related reductions in LDL-C and beneficial changes in other lipid fractions in Japanese hypercholesterolemic patients and is well tolerated.     

早期应用大剂量阿托伐他汀对急性冠状动脉综合征患者C反应蛋白的影响

目的探讨阿托伐他汀对急性冠状动脉综合征(ACS)患者血清C-反应蛋白(CRP)水平的影响。方法66例ACS患者随机分为常规治疗组(30例)和阿托伐他汀治疗组(36例),30例健康人为对照组。阿托伐他汀治疗组于常规治疗基础上加用阿托伐他汀40mg/d,疗程为两周。两组均于治疗前和治疗结束时测定血清CRP、血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)浓度。结果阿托伐他汀组治疗两周后,CRP、TC、TG、LDL-C较治疗前下降(P<0.05￣0.01)。常规组治疗前后无明显变化(P>0.05)。阿托伐他汀组治疗后CRP与TC、LDL-C水平变化无相关性。结论在ACS早期给予大剂量阿托伐他汀治疗,使CRP水平下降,可能有利于抑制炎症反应,稳定斑块。     

Low-density lipoprotein cholesterol: association with mortality and hospitalization in hemodialysis patients

BACKGROUND/AIMS: Hypocholesterolemia is a common finding in hospitalized elderly people, critically ill surgical patients, septic patients and end-stage renal disease patients. The different effect of lipid subfractions on patients with end-stage renal disease has never been demonstrated. We aim to study the effect of lipid subfractions on hospitalization and mortality in maintenance hemodialysis (MHD) patients. METHODS: Lipid subfractions, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured in 210 patients with MHD in a single dialysis center. Patients were stratified into three groups based on the tertiles of lipid levels, and differences in patient characteristics and survival were evaluated. RESULTS: Of a total of 22 deceased patients in our MHD cohort, infection-related mortality (50%) was higher than cardiovascular-related mortality (18.2%). Significant differences (p < 0.05) in the duration and frequency of hospitalization and in mortality events were observed when patients were divided into different subgroups according to the tertiles of baseline TC and LDL-C levels. Patients with lower LDL had significantly lower levels of albumin, TC and TG. The LDL-C tertiles were similar in terms of age, hypertension, diabetes, biochemical results, hematocrit, adequacy of hemodialysis and normalized protein catabolism rate. Both TC and LDL-C predicted survival (p < 0.001), but not TG and HDL-C in the Kaplan-Meier model. The Cox proportional hazard model demonstrated that baseline serum LDL-C was the best lipid subfraction in predicting all-cause death with an adjusted hazard ratio (95% confidence interval) for each 10 mg/dl of 0.752 (0.631-0.898; p = 0.002). CONCLUSIONS: We firstly demonstrated that lipid subfractions, including TC and LDL-C, predict poor outcomes in a MHD cohort with high infection-related mortality.     

Lp(a) lipoprotein and lipids in patients with rheumatoid arthritis: serum levels and relationship to inflammation

Objectives Changes in lipid profiles, Lp(a) lipoprotein, and acute phase reactants are associated with early atherosclerosis in rheumatoid arthritis (RA). The associations of Lp(a) levels with atherosclerotic disorders, diabetes, RA, and renal diseases suggest that Lp(a) might be involved in autoimmune reactions.Methods Eighty-seven women with RA diagnosed according to American Rheumatism Association criteria (mean age 45.4±9.4 years) were recruited and 50 healthy women (mean age 44±10.7 years) included as a control group. Serum Lp(a), total cholesterol (TC), triglyceride (TG), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and C-reactive protein levels were analyzed.Results In the RA and C groups, serum Lp(a) levels were 39.2±20.6 mg/dl and 14.8±9.7 mg/dl, respectively (P<0.001). The TC levels were 188.4±41.8 mg/dl and 185.3±19.3 mg/dl (P>0.05), TG levels were 124.5±50.1 mg/dl and 94.6±24.9 mg/dl (P<0.01), HDL-C levels were 40.0±7.4 mg/dl and 52.8±4.8 mg/dl (P<0.01), and LDL-C levels were 123.4±24.6 mg/dl and 113.3±21.1 mg/dl (P>0.05). While serum CRP levels showed a positive correlation with Lp(a), they correlated negatively with HDL-C levels (r=0.83 and P<0.0001, r=–0.49 and P<0.0001, respectively). It was meaningful that Lp(a) correlated negatively with serum HDL-C level (r=–0.36, P<0.001).Conclusions It is suggested that higher serum Lp(a), lower HDL-C, higher TG level, and a high ratio of TC/HDL-C might show high risk of atherosclerosis. Inflammation in RA may cause changes in HDL-C and Lp(a) metabolisms.     

Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels on a background of atorvastatin.

OBJECTIVES: This study sought to evaluate the efficacy and safety of torcetrapib in patients with low high-density lipoprotein cholesterol (HDL-C) levels receiving background atorvastatin. BACKGROUND: Elevating HDL-C levels may reduce the residual cardiovascular risk that is observed in patients treated with statin therapy. Torcetrapib (a cholesteryl ester transfer protein inhibitor) increases HDL-C and decreases low-density lipoprotein cholesterol (LDL-C). METHODS: This was a multicenter, double-blind, randomized trial. Patients with below-average HDL-C (men <44 mg/dl; women <54 mg/dl) who were eligible for statin therapy according to National Cholesterol Education Program Adult Treatment Panel III guidelines or who had LDL-C >130 mg/dl at screening entered an 8-week run-in period with atorvastatin 20 mg/day before randomization (n = 174) to torcetrapib 10, 30, 60, or 90 mg/day or placebo for 8 weeks. Atorvastatin was continued during treatment with torcetrapib. RESULTS: After 8 weeks, the percent change from baseline with torcetrapib (least-squares mean difference from placebo) ranged from 8.3% to 40.2% for HDL-C (p < or = 0.0001 for 30-mg and higher doses) and from 0.6% to -18.9% for LDL-C (p < 0.01 for 60-mg and 90-mg doses). Particle size for both HDL and LDL increased with torcetrapib. The incidence of all-causality and treatment-related adverse events was similar across placebo and torcetrapib treatment groups with no evidence of a dose-related response. In some treatment groups, small increases in systolic and diastolic blood pressures were noted. CONCLUSIONS: In statin-eligible patients, torcetrapib plus background atorvastatin resulted in substantial, dose-dependent increases in HDL-C, accompanied by additional decreases in LDL-C beyond those seen with atorvastatin alone. Torcetrapib plus atorvastatin was generally well tolerated.