Efficacy and Safety of Rosuvastatin 5 mg in Combination with Fenofibric Acid 135 mg in Patients with Mixed Dyslipidemia – A Phase 3 Study

Background

Patients with mixed dyslipidemia characterized by elevated low-density lipoprotein cholesterol (LDL-C), elevated triglycerides (TG), and reduced high-density lipoprotein cholesterol (HDL-C) often require combination therapy to improve multiple lipid and nonlipid parameters. This phase 3, multicenter, randomized, double-blind study evaluated the efficacy and safety of rosuvastatin 5 mg coadministered with fenofibric acid 135 mg in patients with mixed dyslipidemia.

Methods

A total of 760 patients with TG?≥?150 mg/dL, HDL-C <40 mg/dL (<50 mg/dL for women), and LDL-C?≥?130 mg/dL were randomized for a 12-week treatment period to rosuvastatin 5 mg, fenofibric acid 135 mg, or rosuvastatin 5 mg + fenofibric acid 135 mg. The primary efficacy comparisons were mean percentage changes in HDL-C and TG (rosuvastatin + fenofibric acid vs. rosuvastatin monotherapy), and LDL-C (rosuvastatin + fenofibric acid vs. fenofibric acid monotherapy).

Results

Treatment with rosuvastatin + fenofibric acid resulted in statistically significant greater improvements in HDL-C (23.0% vs. 12.4%; P?P?P?Conclusion In conclusion, rosuvastatin 5 mg + fenofibric acid 135 mg resulted in comprehensive improvements in the lipid profile of patients with mixed dyslipidemia without unanticipated adverse events.     

Long-Term Efficacy of Adding Fenofibric Acid to Moderate-Dose Statin Therapy in Patients with Persistent Elevated Triglycerides

Objective

The objective of this study was to evaluate the long-term efficacy of adding fenofibric acid to moderate-dose statin therapy in patients at goal for low-density lipoprotein cholesterol (LDL-C) but with persistent hypertriglyceridemia.

Methods

This is a post hoc analysis of a subset of patients (N?=?92) with mixed dyslipidemia treated with moderate-dose statin (rosuvastatin 20 mg, simvastatin 40 mg, or atorvastatin 40 mg) for 12 weeks in three controlled trials who had achieved LDL-C <100 mg/dL but whose triglycerides remained >200 mg/dL, and had fenofibric acid 135 mg added to the moderate-dose statin in a 52-week open-label extension study. Lipid and apolipoprotein (Apo) values and the proportion of patients meeting individual and combined treatment targets with combination therapy were determined at scheduled visits during the 52-week study and compared with baseline (start of extension study).

Results

Addition of fenofibric acid to moderate-dose statin for 52 weeks resulted in significant (P?P?=?0.007), and LDL-C?+?non–HDL-C?+?ApoB?+?HDL-C?+?triglycerides (25.6% vs 0.0%) than at baseline.

Conclusions

The addition of fenofibric acid to moderate-dose statin in patients whose LDL-C was optimal but whose triglycerides remained >200 mg/dL led to additional improvements in non–HDL-C, ApoB, HDL-C, and triglycerides that resulted in greater proportions of patients attaining optimal levels of the individual parameters as well as simultaneously achieving optimal levels of these parameters and LDL-C.

     

Triglyceride-to-HDL cholesterol ratio

Objective

This study aimed to explore the association between the triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio and the severity of coronary heart disease (CHD). It also evaluated the clinical role of the TG/HDL-C ratio in predicting in-hospital CHD events and the long-term prognosis of CHD patients.

Methods

According to the results of coronary angiography examinations, 317 patients were enrolled in the study and classified into a CHD group (n=233) and a control group (n=84). The TG/HDL-C ratio was calculated at baseline. The CHD group was then further classified into cases of single-branch stenosis (n=79), double-branch stenosis (n=73), and multi-branch stenosis (n=81). The Gensini score was calculated for each group to analyze the relationship between the TG/HDL-C ratio and the severity of CHD.

Results

The TG/HDL-C ratio in the CHD group was significantly higher than in the normal group (P?<?0.001). The TG/HDL-C ratio was positively correlated with the Gensini score. The ratio was significantly higher in patients with new-onset heart failure than in those without heart failure events (P?<?0.05). An average 3-year follow-up showed that the serum TG/HDL-C ratios of patients with adverse events were significantly higher than other patients (P?<??0.01).

Conclusion

The TG/HDL-C ratio is predictive of the severity of CHD. It could also help predict in-hospital new-onset heart failure incidents of CHD patients.     

Lipid changes on hormone therapy and coronary heart disease events in the Heart and Estrogen/progestin Replacement Study (HERS)

Background

Despite the effect of lowering low-density lipoprotein cholesterol (LDL-C) levels and raising high-density lipoprotein cholesterol (HDL-C) levels, combination hormone therapy did not reduce the incidence of coronary heart disease (CHD) events in the Heart and Estrogen/progestin Replacement Study (HERS). To explore possible mechanisms, we examined the association between lipid changes and CHD outcomes among women assigned to hormone therapy.

Methods

HERS participants were postmenopausal women with previously diagnosed CHD who were randomly assigned to receive conjugated estrogens and medroxyprogesterone or identical placebo and then followed-up for an average of 4.1 years. Among women assigned to hormone therapy, associations between baseline-to-year-1 lipid level changes and CHD events were compared with the associations observed for baseline lipids using multivariate proportional hazards models.

Results

Among women assigned to hormone therapy, CHD events were independently predicted by baseline LDL-C levels (relative hazard [RH] 0.94 per 15.6 mg/dL decrease, 95% CI 0.88-1.01) and HDL-C levels (RH 0.89 per 5.4 mg/dL increase, 95% CI 0.81-0.99), but not by triglyceride levels (RH 1.01 per 13.2mg/dL increase, 95% CI 0.97-1.06). CHD events were marginally associated with first-year reductions in LDL-C levels (RH 0.95 per 15.6mg/dL decrease, 95% CI 0.86-1.04), and were not associated with increases in HDL-C levels ( RH 1.03 per 5.4 mg/dL increase, 95% CI 0.91-1.16) or triglyceride levels (RH 1.01 per 13.2 mg/dL increase, 95% CI 0.98-1.05).

Conclusion

Changes in lipid levels with hormone therapy are not predictive of CHD outcomes in women with heart disease in the HERS trial.     

Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin

Background

Despite the efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C) levels, many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction. The cholesterol absorption inhibitor, ezetimibe, has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins. This study was performed to compare the efficacy and safety of ezetimibe (10 mg) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease (CHD) and are not at their LDL-C goal on the starting dose of atorvastatin.

Methods

This was a 14-week, multicenter, randomized, double-blind, active-controlled study conducted in 113 clinical research centers in 21 countries. Participants were adults with heterozygous familial hypercholesterolemia (HeFH), CHD, or multiple (≥2) cardiovascular risk factors, and a LDL-C level ≥130 mg/dL after a 6- to10-week dietary stabilization and atorvastatin (10 mg/day) open-label run-in period. Eligible subjects continued to receive atorvastatin (10 mg) and were randomized to receive blinded treatment with ezetimibe (10 mg/day; n = 305) or an additional 10 mg/day of atorvastatin (n = 316). The atorvastatin dose in both groups was doubled after 4 weeks, 9 weeks, or both when the LDL-C level was not at its goal (≤100 mg/dL), so that patients receiving combined therapy could reach 40 mg/day and patients receiving atorvastatin alone could reach 80 mg/day. The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14. A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy.

Results

The proportion of subjects reaching their target LDL-C level goal of ≤100 mg/dL was significantly higher in the co-administration group than in the atorvastatin monotherapy group (22% vs 7%; P <.01). At 4 weeks, levels of LDL-C, triglycerides, and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin (LDL-C −22.8% versus −8.6%; P <.01). The combination regimen had a safety and tolerability profile similar to that of atorvastatin alone.

Conclusions

The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone.     

SLCO1B1c.388A＞G多态性对于中国缺血性卒中患者阿托伐他汀降脂和抗动脉粥样硬化作用的影响

目的 探讨溶质载体有机阴离子转运体家族1B1(solute carrier organic anion transporterfamily member l B1,SLCO1 B1)基因c.388A＞G多态性对中国缺血性卒中患者阿托伐他汀降脂和抗动脉粥样硬化作用的影响.方法 前瞻性纳入基线低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)＞ 1.8 mmol/L的缺血性卒中患者,口服阿托伐他汀(20 mg/d)治疗12个月,分别在治疗前后检测血脂和双侧颈动脉内膜-中膜厚度(carotid intima-media thickness,CIMT).比较SLCO1 B1基因c.388A＞G基因型组之间CIMT的差异.结果 共纳入71例缺血性卒中患者,其中AA基因型5例,AG基因型31例,GG基因型35例;A等位基因频率为28.9％,G等位基因频率为71.1％.所有患者治疗后总胆固醇、三酰甘油和LDL-C均较治疗前显著降低,而高密度脂蛋白胆固醇显著升高(P均＜0.001),但CIMT无显著改变(P=0.475).GG基因型组LDL-C＜ 1.8 mmol/L或LDL-C下降≥50％的患者比例显著高于AG+AA基因型组(74.29％对44.44％;x2=6.540,P=0.011).结论 SLCO1B1基因c.388A＞G多态性会影响阿托伐他汀的降脂效果,GG基因型组的降脂效果优于AG+AA基因型组;SLCO1 B1基因c.388A＞G多态性对阿托伐他汀抗动脉粥样硬化疗效无影响,但可能与随访时间过短有关.     

Rare LPL gene variants attenuate triglyceride reduction and HDL cholesterol increase in response to fenofibric acid therapy in individuals with mixed dyslipidemia

Objective

Individuals with mixed dyslipidemia have elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), and increased risk for coronary disease. Fibrate therapy is commonly used to lower TG and increase HDL-C. Common genetic variants are known to affect the response to fibrate therapy. We sought to identify rare genetic variants (frequency ≤ 1%) in genes involved in TG and HDL-C metabolism that affect the response to fenofibric acid (FA) therapy.

Methods

Four genes with a major role in HDL-C and TG metabolism APOA1, APOC2, APOC-III and LPL were sequenced in 2385 participants with mixed dyslipidemia in a randomized, double-blind, active-controlled study comparing therapy with FA alone, in combination with statins, or statin alone. Rare variants collapsing or SKAT methods were used for the analysis.

Results

Synonymous rare variants in the LPL gene were significantly associated with absolute HDL-C change (P = 9 × 10⁻⁴) and TG percent change (P = 6.76 × 10⁻⁴) in those treated with FA only. Participants with these rare variants had a 2 mg/dL increase in HDL-C and 39 mg/dL decrease in TG as compared to 6.2 mg/dL increase in HDL-C and 100 mg/dL decrease in TG in those without these variants. Rare variants in the APOC-III gene were associated with a modest 3 mg/dL less reduction in APOB (P = 8.72 × 10⁻⁴) in those receiving FA and statin.

Conclusion

In individuals with mixed dyslipidemia rare synonymous variants within LPL gene were associated with attenuated response to FA therapy while APOCIII rare variants were associated with a modest effect on APOB response to FA-statin therapy. These results should be replicated in a similar clinical trial for further confirmation.     

Efficacy and Safety of Tolvaptan in Heart Failure Patients with Sustained Volume Overload despite the Use of Conventional Diuretics: A Phase III Open-Label Study

Objective  

The objective of this study was to assess the proportion of patients with type 2 diabetes mellitus (T2DM) attaining individual and combined targets of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), non-HDL-C, and apolipoprotein B (ApoB) after treatment with rosuvastatin (R) + fenofibric acid (FA) compared with corresponding-dose R monotherapy.     

硝苯地平控释片与阿托伐他汀对高血压患者颈动脉内膜中层厚度及血管内皮功能的影响

目的比较观察单用硝苯地平控释片、阿托伐他汀与硝苯地平控释片联用及阿托伐他汀与培哚普利联用对原发性高血斥患者颈动脉内膜中层厚度（CIMT）和血管内皮功能的影响及临床意义。方法选择126例心血管危险分层中危以上的1、2级高血压患者,随机分为钙通道阻滞剂（calcium—channel blocker,CCB）组（40例）,他汀＋血管紧张素转化酶抑制剂（angiotensin—converting enzyme inhibitor,ACEI）组（43例）及他汀＋CCB组（43例）,分别于用药前和用药24周后测量血压,测定空腹静脉血总胆同醇（TC）、甘油二三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆同醇（HDL—C）,以超声观察CIMT及肱动脉内皮依赖性舒张功能（FMD）的变化。结果三组收缩乐和舒张压均显著降低,他汀＋CCB组的收缩斥和舒张压下降更为显著。他汀＋ACEI组及他汀＋CCB组的TC和LDL—C均明显下降：三组FMD均显著改善,CIMT均显著减少,并且治疗后他汀＋CCB组与另两组比较,差异均有统计学意义。结论硝苯地平控释片与阿托伐他汀在降压、降脂、降低CIMT及改善血管内皮功能方面有协同作用。     

Marked low-density lipoprotein cholesterol reduction below current national cholesterol education program targets provides the greatest reduction in carotid atherosclerosis

BACKGROUND: Current National Cholesterol Education Program (NCEP) guidelines recognize low-density lipoprotein cholesterol (LDL-C) below 100 mg/dl as an optimal level. Evidence supporting this is scant. Both LDL-C and C reactive protein (CRP) are known correlates of atherosclerosis progression. HYPOTHESIS: We examined the effect of final LDL-C and CRP obtained with statin therapy on carotid intima-media thickness (CIMT), a valid surrogate for clinical benefit of lipid-lowering therapies. METHODS: In a randomized, single-center trial, 161 patients were assigned to statin therapy of different potencies (pravastatin 40 mg, n = 82; atorvastatin 80 mg, n = 79). The effects on CIMT were assessed in relationship to LDL-C and CRP levels obtained after 12 months of therapy. RESULTS: Changes in CIMT were directly related to the final LDL-C level obtained on statin therapy after 12 months (R = 0.219, p = 0.015). Carotid intima-media thickness regression was seen in 61% of the subjects in the lowest quartile of final LDL-C (< 70 mg/dl) versus 29% of the subjects with the highest quartile of final LDL-C (> or = 114 mg/dl, p = 0.008). No threshold value was seen, with more favorable effects on absolute change in CIMT with lower values of LDL-C (decrease in CIMT of 0.06 +/- 0.17 mm in the lowest quartile compared with an increase of 0.06 +/- 0.09 in the highest quartile of LDL-C, p = 0.008). On-treatment LDL and CRP concentrations both below the group median values were associated with the greatest likelihood of CIMT regression. CONCLUSIONS: Regression of carotid atherosclerosis is directly related to the absolute LDL-C level on statin therapy. The greatest regression was obtained with an LDL-C < 70 mg/dl, supporting marked LDL-C reduction to levels below current NCEP guidelines.     

Efficacy and safety of rosuvastatin and atorvastatin in patients with hypercholesterolemia and a high risk of coronary heart disease: a randomized, controlled trial

Background

This double-blind, multicenter, randomized trial compared rosuvastatin and atorvastatin for reducing low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia and a high risk of coronary heart disease.

Methods

After a 6-week dietary lead-in period, patients with LDL-C levels ≥160 and <250 mg/dL and triglyceride levels ≤400 mg/dL were randomly assigned to 24 weeks' treatment in 1 of 3 groups, each with forced dose titrations at 12 and 18 weeks. Starting and titrated doses for each group were rosuvastatin 5, 20, and 80 mg (n = 127); rosuvastatin 10, 40, and 80 mg (n = 128); and atorvastatin 10, 40, and 80 mg (n = 128).

Results

At 24 weeks, LDL-C was reduced significantly more with 80 mg rosuvastatin (combined rosuvastatin group) than with atorvastatin 80 mg (60% vs 52% [P < .001]). At 12 weeks, rosuvastatin 5 and 10 mg reduced LDL-C significantly more than atorvastatin 10 mg (40% [P < .01], 47% [P < .001] vs 35%). At 18 weeks, LDL-C reductions were also significantly greater in both rosuvastatin groups than in the atorvastatin group (52% [P < .01], 59% [P < .001] vs 47%). Consequently, more patients receiving rosuvastatin achieved LDL-C goals. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoproteins B and A-I, and all lipid ratios were more favorably modified by rosuvastatin at 24 weeks (P < .01). Effects of the 2 agents on triglycerides were similar.

Conclusions

Rosuvastatin was more efficacious than atorvastatin in modifying lipids in patients with hypercholesterolemia and a high coronary heart disease risk.     

Independent Contribution of A1C, Systolic Blood Pressure, and LDL Cholesterol Control to Risk of Cardiovascular Disease Hospitalizations in Type 2 Diabetes: An Observational Cohort Study

BACKGROUND

Cardiovascular disease (CVD) prevention in diabetes requires broad-based treatment of dyslipidemia, hypertension, and hyperglycemia. The independent contribution of all combinations of risk factor control to CVD risk has not been evaluated.

OBJECTIVE

To estimate the independent association of control of glycosylated hemoglobin (A1C), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) with risk of cardiovascular disease hospitalization.

DESIGN

Non-concurrent longitudinal cohort study.

PATIENTS

The study included 26,636 patients with type 2 diabetes who were members of an integrated group model HMO with multiple A1C, SBP, and LDL-C measurements.

MAIN MEASURES

Patients were followed for a mean (SD) of 5.6 (2.5) years until they died or disenrolled, or until 31 December 2010. The outcome was a first-observed CVD hospitalization. Using the mean of all A1C, SBP, and LDL-C measures during follow-up, we created dichotomous categories of A1C control (< 7 %), SBP control (< 130 mmHg), and LDL-C control (< 100 mg/dL) to estimate the incidence rate of CVD hospitalization associated with all combinations of risk factor control adjusting for demographic and clinical characteristics.

KEY RESULTS

Patients with no controlled risk factors (18.2/1,000 person-years, 95 % CI 16.5?20.2) or with only A1C in control (16.9, 15.0?19.0) had the highest rate of CVD hospitalization, whereas those with all three risk factors controlled (7.2, 6.2?8.4) or with SBP and LDL-C in control (6.1, 5.1?7.2) had the lowest rates. Those with only SBP or LDL-C in control, A1C and SBP controlled, or A1C and LDL-C controlled had statistically similar incidence between the highest and lowest rates.

CONCLUSIONS

Maintaining SBP < 130 mmHg or LDL-C < 100 mg/dL was significantly associated with reduced CVD hospitalization risk, especially when both risk factors were well controlled. Maintaining A1C < 7 % was not independently associated with reduced CVD hospitalization risk.     

Prevalence of lipid abnormalities and cholesterol target value attainment in Egyptian patients presenting with an acute coronary syndrome

Background

Effective management of hyperlipidemia is of utmost importance for prevention of recurring cardiovascular events after an acute coronary syndrome (ACS). Indeed, guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level of <70?mg/dL for such patients. The Dyslipidemia International Study II (DYSIS II) – Egypt was initiated in order to quantify the prevalence and extent of hyperlipidemia in patients presenting with an ACS in Egypt.

Efficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia not Adequately Controlled with Current Lipid-Lowering Therapy: Design and Rationale of the ODYSSEY FH Studies

Background

Individuals with heterozygous familial hypercholesterolemia (heFH) have higher levels of low-density lipoprotein cholesterol (LDL-C) and are predisposed to premature cardiovascular disease. Alirocumab is a fully-human, monoclonal antibody targeted to proprotein convertase subtilisin/kexin type 9 currently in Phase 3 development for the treatment of hypercholesterolemia. Described here are three ODYSSEY Phase 3 trials, FH I (NCT01623115), FH II (NCT01709500) and HIGH FH (patients with heFH and LDL-C levels ≥160 mg/dL) (NCT01617655), in which alirocumab is further evaluated in the heFH population.

Methods

Multicenter, multinational, randomized, double-blind, placebo-controlled studies have been designed to evaluate efficacy and safety of alirocumab in more than 800 patients with heFH who are not adequately controlled with a maximally-tolerated stable daily dose of statin for ≥4 weeks prior to the screening visit, with or without other lipid-lowering therapy. Patients are randomized (2:1) to receive alirocumab or placebo via a 1-mL subcutaneous auto-injection every 2 weeks (Q2W) for 78 weeks. In studies FH I and II, if their Week 8 LDL-C level is ≥70 mg/dL, patients will undergo a dose uptitration from 75 to 150 mg alirocumab Q2W at Week 12. In HIGH FH, patients will receive alirocumab 150 mg Q2W throughout the entire treatment period. The primary efficacy endpoint in all three studies is the percent change in calculated LDL-C from baseline to Week 24.

Conclusions

The ODYSSEY FH studies are three Phase 3 studies aiming to further evaluate the efficacy and long-term safety of alirocumab as an effective therapeutic option for patients with heFH.     

Comparing the effects of five different statins on the HDL subpopulation profiles of coronary heart disease patients

We compared the effects of five different statins (atorvastatin, simvastatin, pravastatin, lovastatin, and fluvastatin) on the lipid, lipoprotein, and apolipoprotein (apo) A-I-containing high-density lipoprotein (HDL) subpopulation profiles of 86 coronary heart disease (CHD) patients. Patients with established CHD, and low density lipoprotein (LDL) cholesterol (C)>130 mg/dl, and triglyceride (TG)<400 mg/dl, were treated with atorvastatin 20, 40, and 80 mg/day and one of the other four statins at 20, 40, and when available 80 mg/day in increasing doses (4 weeks of each dose) in a randomized crossover fashion. There was an 8-week placebo controlled washout period between different drug treatments. All five statins on each dose resulted in significant reductions in total- and LDL-C compared to placebo treatment. There were also decreases in plasma TG and increases in HDL-C and apoA-I concentrations, but not all treatments changed these parameters significantly. Each statin except fluvastatin improved the HDL subpopulation profile by increasing the concentrations of the large, cholesterol-rich, LpA-I alpha-1 and prealpha-1 HDL subpopulations. CHD patients have significantly lower concentration of the large, LpA-I alpha-1 HDL particles compared to controls. Our data indicate that statins which are the most effective in lowering LDL-C and TG are also the most effective agents in modifying the HDL subpopulation profile in CHD patients towards the patterns found in healthy individuals. The order of efficacy of statins in increasing alpha-1 HDL subpopulation was: atorvastatin, simvastatin, pravastatin, lovastatin and fluvastatin.     

Low-density lipoprotein cholesterol/apolipoprotein B ratio may be a useful index that differs in statin-treated patients with and without coronary artery disease: a case control study

Low density lipoproteins (LDLs) are heterogeneous aggregations of molecules of different particle sizes, and small-size LDLs are more potent risk factors for atherosclerosis. We examined the qualitative characteristics of LDLs in patients with stable coronary artery disease (CAD) receiving statin therapy. LDL-particle size was estimated based on the LDL-cholesterol/apolipoprotein B ratio (LDL-C/apoB) in 214 age-adjusted men receiving statin therapy. The LDL-C/apoB ratio was significantly lower in the CAD (+) group (n = 107) than in the CAD (-) group (n = 107) (median, 1.17 versus 1.19, P = 0.0095). LDL-C/apoB was significantly lower in patients with serum TG ≥ 150 mg/dL than in those with serum TG < 150 mg/dL, and in patients with serum HDL-C < 40 mg/dL than in those with serum HDL-C ≥ 40 mg/dL (1.06 versus 1.18, P = 0.012; 1.08 versus 1.22, P = 0.0023). Stepwise logistic regression analysis revealed that elevated serum TG was an independent predictor for smaller sizes of LDLs, both in the overall subjects (β : -0.165, P = 0.02) as well as in the subset with serum LDL-C < 100 mg/dL (β : -0.252, P = 0.011). This study demonstrated that not only the absolute serum LDL-C level, but also the qualitative characteristics of LDL may be monitored for secondary prevention of CAD. Such monitoring is particularly important in patients with elevated serum TG levels, which is associated with smaller sizes of LDL-particles.     

阿托伐他汀对高脂血症患者颈动脉内膜中层厚度及凝血系统的影响

目的　观察阿托伐他汀调脂同时对高脂血症患者颈动脉内膜中层厚度 (IMT)及凝血系统的影响。方法　选择高脂血症患者 35例为血脂紊乱组 ,口服阿托伐他汀 10mg·qd ,12周 ,血脂正常者 35例为正常对照组 ,分别对血脂紊乱组治疗前及 12周后两组进行血脂总胆固醇 (TC)、甘油三酯 (TG)、低密度脂蛋白胆固醇 (LDL C)、高密度脂蛋白胆固醇 (HDL C)、IMT、纤维蛋白原 (FIB)、凝血酶时间 (TT)、活化部分凝血酶时间 (APTT)、凝血酶原时间 (PT)检查。结果　与治疗前比较 ,血脂紊乱组治疗 12周后的TC、TG、LDL C、FIB均有显著降低 (P均 <0 0 1) ,HDL -C显著升高 (P <0 0 5 ) ,颈动脉IMT显著变薄 (P <0 0 5 ) ,TT、APTT均有显著延长 (P均 <0 0 1)。PT显著升高 (P <0 0 5 )。TC、TG、LDL C、HDL C、IMT、FIB、PT均接近血脂正常组各指标 ,比较无显著差异 (P >0 0 5 )。TT、APTT均超出血脂正常组 ,比较有显著差异 (P <0 0 5 )。结论　阿托伐他汀在有效调脂同时可发挥其非调脂作用 ,逆转或延迟颈动脉IMT的进程 ,并改善凝血系统。     

瑞舒伐他汀治疗中国高胆固醇血症患者疗效和安全性的随机双盲多中心对照研究

目的评价瑞舒伐他汀治疗中国高胆固醇血症患者的疗效和安全性。方法采用随机、双盲、多中心研究。患者经6周筛选后符合LDL—C≥4．14mmol／L（160mg／dl）,〈6．50mmol／L（250mg／dl）、TG〈4．52mmol／L（400mg／dl）者以2：1随机接受瑞舒伐他汀10mg／d或阿托伐他汀10mg／d治疗。12周后瑞舒伐他汀组LDL-C未达到ATPⅢ治疗目标者,予瑞舒伐他汀20mg延续治疗8周。结果304例进入随机治疗阶段,瑞舒伐他汀10mg／d组201例,阿托伐他汀10mg／d组103例。意向治疗人群290例,符合方案人群263例。瑞舒伐他汀组治疗12周后血LDL—C显著下降,下降幅度为45．6％,显著大于阿托伐他汀组的39．0％（P〈0．001）。瑞舒伐他汀组患者LDL—C达标率也较阿托伐他汀组（78．0％比72．7％）有增高趋势,且在高危人群中优势更为明显（56．5％比35．0％）,但差异未达到统计学意义。瑞舒伐他汀降低TG（-22．8％）以及升高HDL-C（＋6．6％）和ApoA-1（＋12．5％）的幅度与阿托伐他汀组差别无统计学意义（分别为-16．6％。＋4．3％和＋9．8％）。29例患者接受20mg／d瑞舒伐他汀延续治疗,22例完成治疗患者中10例（45．5％）LDL—C达标。研究中未发现药物相关的严重不良反应事件。结论本组研究显示瑞舒伐他汀10mg降低LDL-C的疗效优于同等剂量的阿托伐他汀,治疗3个月安全性与之类似。     

低密度脂蛋白胆固醇/高密度脂蛋白胆固醇、甘油三酯/高密度脂蛋白胆固醇和尿酸与冠心病的关系

目的探讨低密度脂蛋白胆固醇(LDL-C)/高密度脂蛋白胆固醇(HDL-C)、甘油三脂(TG)/HDL-C和血尿酸(UA)与冠心病的关系。方法检测203例经冠脉造影确诊的冠心病患者(冠心病组)和61例冠脉造影正常者(对照组)的血清总胆固醇、TG、LDL-C、HDL-C、UA含量,计算LDL-C/HDL-C、TG/HDL-C的比值。结果冠心病组的总胆固醇、LDL-C、LDL-C/HDL-C比值较对照组均显著升高,HDL-C显著降低(P<0.05)。而TG及TG/HDL-C比值两组间无显著差异。结论LDL-C/HDL-C和UA对冠心病有一定的预测价值,而TG/HDL-C比值的预测价值尚待研究。     

Aerobic exercise and lipids and lipoproteins in patients with cardiovascular disease: a meta-analysis of randomized controlled trials

PURPOSE: Use the meta-analytic approach to examine the effects of aerobic exercise on lipids and lipoproteins in adults with cardiovascular disease (CVD). METHODS: Studies were retrieved via electronic databases, review of reference lists from retrieved articles, including reviews, and hand searching. Inclusion criteria were: (1) randomized controlled trials, (2) aerobic exercise >or=4 weeks as an intervention, (3) studies published in English language only between January 1, 1955 and January 1, 2005, (4) studies published in journals or as dissertations or master's theses, (5) human subjects >or=18 years, (6) all subjects diagnosed with some type of CVD, and (7) pre and post data available for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). Random-effects models were used for data analysis. RESULTS: Of the more than 3,000 studies reviewed, a total of 10 representing 1,260 subjects (580 exercise, 680 control) were included in our analysis. There was a statistically significant increase of 9% in HDL-C (mean +/- SEM, 3.7 +/- 1.3 mg/dL; 95% CI, 1.2 to 6.1 mg/dL) and a statistically significant decrease of 11% in TG (-19.3 +/- 5.4 mg/dL; 95% CI, -30.1 to -8.5 mg/dL), but no statistically significant decreases in TC or LDL-C (TC, -8.8 +/- 6.8 mg/dL; 95% CI, -22.3 to 4.7 mg/dL; LDL-C, -7.7 +/- 6.0 mg/dL; 95% CI, -19.5 to 4.2 mg/dL). CONCLUSIONS: The present findings suggest that chronic aerobic exercise increases HDL-C and decreases TG in adults, especially men, with CVD.