Effects of atorvastatin on oxidized low-density lipoprotein, low-density lipoprotein subfraction distribution, and remnant lipoprotein in patients with mixed hyperlipoproteinemia

Atorvastatin (10 to 20 mg/day) was administered for 3 months to 15 outpatients (average age 58 +/- 4 years) with hypercholesterolemia accompanied by hypertriglyceridemia without hypolipemic treatment. Changes in lipid profile, particularly oxidized low-density lipoprotein (LDL) (malondialdehyde LDL), subfractions of LDL, and remnant lipoprotein (RLP) cholesterol, were examined before and after administration. In addition, the influence of atorvastatin on lipoprotein(a) (known to be an independent risk factor for atherosclerosis), asymmetric dimethylarginine (known to be an endogenous inhibitor of nitric oxide synthase), and homocysteine (methionine metabolite) was also investigated. Administration of atorvastatin significantly decreased serum total cholesterol, LDL cholesterol, and triglycerides. Conversely, a significant increase in high-density lipoprotein cholesterol was shown. In LDL subfractions, large, buoyant LDL fractions were not influenced by treatment with atorvastatin (before administration, 99 +/- 14 mg/dl; after administration, 91 +/- 6 mg/dl, shown as a cholesterol content in each subfraction), but a marked decrease in small, dense LDL fractions (p <0.001) (before administration, 119 +/- 17 mg/dl; after administration, 43 +/- 10 mg/dl) was shown. Moreover, oxidized LDL was significantly decreased (p < 0.01) (before administration, 169 +/- 13 U/L; after administration, 119 +/- 10 U/L) and RLP cholesterol also was significantly decreased (p <0.01) (before administration, 11.9 +/- 2.0 mg/dl; after administration, 6.0 +/- 0.9 mg/dl) with atorvastatin treatment. No significant change was observed in fasting plasma glucose, hemoglobin A1c, lipoprotein(a), asymmetric dimethylarginine, homocysteine, and so on. These data suggest that administration of relatively low doses of atorvastatin to patients with hypercholesterolemia accompanied with hypertriglyceridemia results in a decrease not only in LDL cholesterol and triglycerides, but also in oxidized LDL and RLP cholesterol, with an increase in high-density lipoprotein cholesterol. Furthermore, small, dense LDL decreased with a shift in LDL subfractions to large, buoyant fractions, and these changes are considered to be involved in the inhibition of the onset and progression of atherosclerosis.     

Differential effect of atorvastatin and fenofibrate on plasma oxidized low-density lipoprotein, inflammation markers, and cell adhesion molecules in patients with type 2 diabetes mellitus

Type 2 diabetes mellitus is associated with elevated plasma triglyceride levels, low high-density lipoprotein cholesterol, and a high incidence of cardiovascular disease. Hydroxymethylglutaryl-coenzyme A reductase inhibitors and fibrates are frequently used in the treatment of diabetic dyslipidemia, but their specific impact on the inflammation processes involved in atherosclerosis remains to be fully characterized. The objective of this 2-group parallel study was to investigate the differential effects of a 6-week treatment with either atorvastatin 20 mg/d alone (n = 19) or micronized fenofibrate 200 mg/d alone (n = 19) on inflammation, cell adhesion, and oxidation markers in type 2 diabetes mellitus subjects with marked hypertriglyceridemia. In addition to the expected changes in lipid levels, atorvastatin decreased plasma levels of C-reactive protein (-26.9%, P = .004), soluble intercellular adhesion molecule 1 (-5.4%, P = .03), soluble vascular cell adhesion molecule 1 (-4.4%, P = .008), sE-selectin (-5.7%, P = .02), matrix metalloproteinase 9 (-39.6%, P = .04), secretory phospholipase A(2) (sPLA(2)) (-14.8%, P = .04), and oxidized low-density lipoprotein (-38.4%, P < .0001). On the other hand, fenofibrate had no significant effect on C-reactive protein levels and was associated with reduced plasma levels of sE-selectin only (-6.0%, P = .04) and increased plasma levels of sPLA(2) (+22.5%, P = .004). These results suggest that atorvastatin was potent to reduce inflammation, oxidation, and monocyte adhesion in type 2 diabetes mellitus subjects with marked hypertriglyceridemia, whereas fenofibrate decreased sE-selectin levels only and was associated with an elevation of sPLA(2) levels.     

微粒化非诺贝特对Ⅳ型高脂血症患者血清低密度脂蛋白亚组份再分布的作用

目的　观察微粒化非诺贝特对IV型高脂血症患者血清低密度脂蛋白 (LDL)亚组份再分布的作用。方法　口服微粒化非诺贝特 2个月 ( 2 0 0mg ,每晚 1粒 ) ,共治疗患者 2 6例 ,对治疗后出现血清LDL 胆固醇水平升高 15 %以上的共 12例患者 ,进一步用超速离心法观察药物对血清LDL亚组份 (LDL1∶1 0 2 5g/ml～ 1 0 3 4g/ml,LDL2 ∶1 0 3 4g/ml～ 1 0 4 4g/ml和LDL3∶1 0 4 4g/ml～ 1 0 63g/ml)再分布的作用。结果　微粒化非诺贝特治疗后 ,血清甘油三酯 (TG)水平平均下降 5 3 4 %～ 64 4 % (P <0 0 0 1) ,LDL 胆固醇明显升高 3 7 3 %～ 79 4 % (P <0 0 0 1) ,总胆固醇、高密度脂蛋白 胆固醇水平无明显改变。治疗前患者的LDL亚组份分布以小而密LDL3为主 [LDL3占总LDL的 ( 3 4 7± 8 6) % ],分布曲线呈多峰、不均一态分布 ;治疗后LDL3比例显著降低 [降低 ( 3 5 0± 2 7 3 ) % ,P <0 0 0 1]、LDL2 显著升高 [升高 ( 4 6 9± 2 9 0 ) % ,P <0 0 0 1],LDL亚组份分布曲线转向单峰、较均一态分布。治疗后LDL颗粒的化学组成构成比 ( % )发生较大变动 ,其中TG %显著降低 (P <0 0 1) ,胆固醇酯 %和蛋白质 %不同程度增高 ,游离胆固醇 %和磷脂 %无明显变化。结论　微粒化非诺贝特能明显的降低IV型高脂血症患者血浆甘油     

Effects of atorvastatin therapy on the low-density lipoprotein subfraction, remnant-like particles cholesterol, and oxidized low-density lipoprotein within 2 weeks in hypercholesterolemic patients.

The short- and intermediate-term pleiotropic effects of atorvastatin were investigated in 18 hypercholesterolemic patients, as well as the temporal differences in these pleiotropic effects. Atorvastatin was given for 3 months and fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS), fibrinolytic parameters, and flow-mediated dilation of the brachial artery (FMD) were measured at baseline and after 2 weeks and 3 months of therapy. Atorvastatin reduced the total cholesterol (273+/-34 vs 188+/-31 mg/dl, p<0.0001), low-density lipoprotein-cholesterol (LDL-C: 174+/-28 vs 111+/-23 mg/dl, p<0.0001), small, dense LDL-C (34+/-22 vs 18+/-20%, p<0.01), remnant-like particles cholesterol (RLP-C: 8.8+/-6.0 vs 5.1+/-2.6 mg/ml, p<0.01), and TBARS (3.3+/-1.0 vs 3.1+/-0.9 nmol/ml, p<0.05) after 2 weeks. Atorvastatin decreased the concentration of small, dense LDL-C again after 3 months (8+/-13%, p<0.0001). The plasma concentrations of the fibrinolytic parameters did not change significantly after 3 months of atorvastatin therapy. FMD increased significantly after 2 weeks (5.6+/-2.1 vs 6.3+/-2.0%, p<0.01) and additionally increased after 3 months of therapy (8.3+/-1.9%, p<0.0001). There were no correlations between the pleiotropic effects and the improvement in the lipid profile. The results indicate some short-term pleiotropic effects of atorvastatin therapy within 2 weeks, which may be important with respect to the early benefits of statin therapy.     

Effect of improving glycemic control in patients with type 2 diabetes mellitus on low-density lipoprotein size, electronegative low-density lipoprotein and lipoprotein-associated phospholipase A2 distribution

The aim of this study was to determine the effect of intensified hypoglycemic therapy in patients with type 2 diabetes mellitus on the distribution of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity between high-density lipoprotein and low-density lipoprotein (LDL) and its relation with the lipid profile and other qualitative properties of LDL. Forty-two patients with type 2 diabetes on the basis of poor glycemic control and normal or near normal LDL cholesterol were recruited. Lifestyle counseling and pharmacologic hypoglycemic therapy were intensified to improve glycemic control, but lipid-lowering therapy was unchanged. At 4 ± 2 months, glycosylated hemoglobin had decreased by a mean of 2.1%, but the only effect on the lipid profile were statistically significant decreases in nonesterified fatty acids and apolipoprotein B concentration. LDL size increased and the proportion of electronegative LDL decreased significantly. In parallel, total Lp-PLA2 activity decreased significantly, promoting a redistribution of Lp-PLA2 activity toward a higher proportion in high-density lipoprotein. Improvements in glycemic control led to more marked changes in Lp-PLA2 activity and distribution in patients with diabetes who had not received previous lipid-lowering therapy. In conclusion, optimizing glycemic control in patients with type 2 diabetes promotes atheroprotective changes, including larger LDL size, decreased electronegative LDL, and a higher proportion of Lp-PLA2 activity in high-density lipoprotein.     

Effects of long-term fenofibrate therapy on cardiovascular events in people with type 2 diabetes mellitus

Conclusions The authors of the FIELD study conclude that the result of this large and scientifically rigorous study provides information to help guide clinicians on the future use of fenofibrate in patients with type 2 diabetes. They state the “results are likely to be of particular importance among patients without previous cardiovascular disease where both the prevention of non-fatal macrovascular events and microvascular complications are judged important.” I do not believe the results of the FIELD trial support an expanded role of fenofibrate therapy for patients with diabetes. To suggest we use fenofibrate as primary prevention in diabetic patients because a post hoc analysis of the FIELD study demonstrated no benefit in patients with known heart disease and modest benefit in patients without known heart disease is scientifically invalid and biologically implausible. To suggest we use fenofibrate to reduce microvascular disease will require a clinical trial designed to look at those specific endpoints. At present, there is no evidence to suggest that therapy with fenofibrate is superior to generic gemfibrozil. The clinical utility of fenofibrate in patients with more severe hypertriglyceridemia or in combination with statin therapy will remain to be demonstrated in a well-designed clinical trial.     

Oxidized low-density lipoprotein is negatively correlated with lecithin-cholesterol acyltransferase activity in type 2 diabetes mellitus

IntroductionIt is now believed that the oxidative modification of plasma lipoproteins enhance their atherogenicity in patients with type 2 diabetes. Because a variety of highly reactive lipid peroxidation products can transfer from oxidized low-density lipoprotein (ox-LDL) to high-density lipoprotein -cholesterol, the authors evaluated the association between ox-LDL and lecithin-cholesterol acyl-transferase (LCAT) activity, a key enzyme in reverse cholesterol transport and HDL remodeling.MethodsA total of 45 patients with diabetes and 45 age-, sex- and body mass index-matched healthy adult volunteers were enrolled. Fasting blood samples were obtained, and plasma glucose, lipid profile, creatinine, insulin, ox-LDL and LCAT activity were measured. Homeostasis model assessment of insulin resistance was also calculated.ResultsPatients with diabetes, compared with healthy participants, had a significantly higher ox-LDL (17.16 ± 3.75 U/L versus 7.93 ± 1.92 U/L, P < 0.001) and lower LCAT activity (73.7 ± 9.1 μmol/L/hr versus 88.7 ± 4.5 μmol/L/hr, P < 0.001). The higher level of LCAT activity completely disappeared after adjustment for ox-LDL. LCAT activity had a significant (P < 0.001) inverse correlation with ox-LDL (r = -0.77) in patients with diabetes and healthy participants (r =-0.75).ConclusionLCAT activity is significantly decreased in type 2 diabetes. The lower LCAT activity in type 2 diabetes might be through ox-LDL mechanism. ox-LDL may adversely affect high-density lipoprotein -cholesterol metabolism by reducing LCAT activity.     

Heterogeneity of low-density lipoprotein particle number in patients with type 2 diabetes mellitus and low-density lipoprotein cholesterol <100 mg/dl

Patients with type 2 diabetes mellitus have an increased risk of cardiovascular events even when treated to low-density lipoprotein (LDL) cholesterol goals. The purpose of this study was to determine how many diabetic patients with low LDL cholesterol have correspondingly low numbers of LDL particles (LDL-P) and the extent to which those achieving target levels of LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol might still harbor residual risk associated with increased LDL-P. Split-sample measurements of LDL cholesterol, non-HDL cholesterol, and nuclear magnetic resonance measured LDL-P were performed on plasma samples from 2,355 patients with type 2 diabetes seen in clinical practice and who had LDL cholesterol levels <100 mg/dl. Substantial heterogeneity of LDL-P was noted among patients with low or very low levels of LDL cholesterol. Of 1,484 patients with low LDL cholesterol (70 to 99 mg/dl), only 385 (25.9%) had low levels of LDL-P (<20th percentile of an ethnically diverse contemporary reference population), whereas 468 (31.6%) had LDL-P values >50th percentile (>1,300 nmol/L). Among the 871 patients with very low LDL cholesterol, i.e., <70 mg/dl, 349 (40.1%) had LDL-P levels >1,000 nmol/L (>20th percentile) and 91 (10.4%) had LDL-P levels >50th percentile. For patients with high triglyceride values (200 to 400 mg/dl), there was less discordance between LDL-P and non-HDL cholesterol than between LDL-P and LDL cholesterol. However, for those with triglyceride levels <200 mg/dl, LDL-P distributions were similarly wide for patients having achieved low or very low targets of LDL cholesterol or non-HDL cholesterol. In conclusion, these data demonstrate that patients with type 2 diabetes mellitus and LDL cholesterol levels <100 mg/dl are extremely heterogeneous with regard to LDL-P and, by inference, LDL-based cardiovascular risk.     

Effect of intensive lipid-lowering strategy on low-density lipoprotein particle size in patients with type 2 diabetes mellitus

A preponderance of small dense LDL particles is strongly associated with the occurrence of atherosclerotic disease. Although several studies have documented an increased prevalence of small dense LDL particles in diabetes mellitus no data are available to show the effect of lipid-lowering treatment upon the improvement of LDL particle size. In the present study we examined the effect of lipid-lowering treatment, following an intensive lipid-lowering strategy for 30 weeks pursuing ADA recommended target lipid levels, on LDL particle size in 50 type 2 diabetic patients with moderate hyperlipidemia. At week 0, 24 patients (48%) were characterized by small dense LDL phenotype pattern B. After the treatment period a shift towards normal LDL particle size was observed in 17 patients but seven patients (29%) showed the more atherogenic LDL subclass pattern B. After treatment, plasma HDL-cholesterol was significantly lower (P<0.05) in these patients compared to those who had LDL subclass pattern A. Multivariate regression analysis revealed VLDL-cholesterol or triglycerides and HDL(3)-cholesterol as independent determinants for LDL particle size. Change in HDL(2)-cholesterol was an independent determinant for change in LDL particle size. In conclusion, a strategy of intensive lipid-lowering, with the intention to reduce triglyceride levels below 1.7 mmol/l, may be insufficient to ensure improvement in LDL size in all patients.     

Effect of simvastatin and fenofibrate on cytokine release and systemic inflammation in type 2 diabetes mellitus with mixed dyslipidemia

The aim of our study was to compare the effect of simvastatin and fenofibrate treatment on the secretory function of human monocytes and lymphocytes and on systemic inflammation in type 2 diabetes and to assess whether their coadministration is superior to treatment with only 1 of these drugs. One hundred ninety-six adult patients with recently diagnosed and previously untreated type 2 diabetes and mixed dyslipidemia, complying throughout the study with lifestyle intervention and treated with metformin, were randomized in a double-blind fashion to receive simvastatin (40 mg), fenofibrate (200 mg), simvastatin plus fenofibrate, or placebo for 90 days. Main outcome measurements were monocyte and lymphocyte release of proinflammatory cytokines and plasma levels of C-reactive protein. One hundred ninety patients completed the study. Simvastatin and fenofibrate decreased monocyte release of tumor necrosis factor-α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1 and lymphocyte release of interleukin-2, interferon-γ, and tumor necrosis factor-α, which was accompanied by a decrease in plasma C-reactive protein levels. Anti-inflammatory effects of fenofibrate partly correlated with the improvement in insulin sensitivity. Lymphocyte-suppressing, but not monocyte-suppressing, effect was stronger if these 2 agents were administered together. In conclusion, simvastatin and fenofibrate exhibit a similar effect on the secretory function of human monocytes and lymphocytes and on systemic inflammation in type 2 diabetic subjects with mixed dyslipidemia. This effect may be clinically relevant in the prevention of vascular complications in metformin- and diet-treated subjects with newly diagnosed diabetic dyslipidemia.     

Impact of low-density lipoprotein particle size on carotid intima-media thickness in patients with type 2 diabetes mellitus

Small low-density lipoprotein (LDL) particles and modifications to LDL such as glycation and oxidation have been linked to the pathogenesis of atherosclerosis in patients with diabetes. We investigated whether LDL particle size, or the levels of glycated LDL or malondialdehyde-modified LDL (MDA-LDL) are associated with carotid intima-media thickness (IMT) in patients with type 2 diabetes mellitus. One hundred seventy-two patients with type 2 diabetes mellitus were enrolled. Carotid IMT was measured by high-resolution ultrasound, and LDL particle size and serum glycated LDL and MDA-LDL levels were determined. The 3 variables were significantly correlated with one another. Univariate analyses defined statistically significant correlations of carotid IMT with LDL size, hemoglobin A(1c), glycated LDL, MDA-LDL, high-density lipoprotein (HDL) cholesterol, and age. The strongest association of IMT was with LDL size (r = -0.406, P < .0001), followed by that with HDL cholesterol (r = -0.225, P = .004). A stepwise multiple regression analysis revealed that LDL size and HDL cholesterol are independent predictors of carotid IMT. Neither glycated LDL nor MDA-LDL had a significant independent contribution to the severity of carotid IMT in the multivariate model. Low-density lipoprotein particle size, but not the glycated LDL or MDA-LDL level, was independently associated with carotid IMT in patients with type 2 diabetes mellitus regardless of antidiabetic and lipid-lowering medications. These results suggest that the measurement of LDL size may be more useful than quantification of modified LDLs for assessing atherosclerosis in patients with type 2 diabetes mellitus. Small LDL particles may be the most important predictor for the risk of cardiovascular disease in diabetic patients.     

Effect of atorvastatin on low-density lipoprotein subtypes in patients with different forms of hyperlipoproteinemia and control subjects

Atorvastatin is a potent hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor that decreases low-density lipoprotein (LDL) cholesterol and triglyceride concentrations, but little is known about its effects on LDL subtype distribution in different types of hyperlipoproteinemia. Thus, we evaluated the influence of atorvastatin (10 mg/d, 4 weeks) on lipid concentrations and LDL subtype distribution in patients with hypercholesterolemia (n = 9; LDL cholesterol, 227 +/- 30 mg/dL; triglycerides, 137 +/- 56 mg/dL), patients with type 2 diabetes and dyslipoproteinemia (n = 11; LDL cholesterol, 163 +/- 34 mg/dL; triglycerides, 260 +/- 147 mg/dL), and controls (n = 10; LDL cholesterol, 116 +/- 20 mg/dL; triglycerides, 130 +/- 47 mg/dL). Cholesterol concentration was determined in 7 LDL subfractions isolated by density gradient ultracentrifugation before and during atorvastatin treatment. Atorvastatin decreased LDL cholesterol (-36%, -28%, and -41%, all P <.01) and triglyceride (-4%, NS; -2%, NS; -24%, P <.05) concentrations but had little effect on high-density lipoprotein (HDL) cholesterol (-1%, NS; +10%, P <.05; +6%, NS) in hypercholesterolemic, diabetic, and control subjects, respectively. In all 3 groups, a significant reduction in cholesterol in each LDL subfraction was observed. Large-buoyant (LDL-1, LDL-2) and intermediate-dense (LDL-3, LDL-4) LDL were reduced more than small-dense (LDL-5 through LDL-7) LDL in hypercholesterolemic (-45%, -35%, and -32%, P <.05) and control subjects (-48%, -44%, and -25%, P <.05), but in diabetic patients cholesterol reduction was uniform in all LDL subtypes (-32%, -27%, and -29%, P =.45). Thus, atorvastatin decreases cholesterol concentration in all LDL subfractions in hypercholesterolemic, diabetic, and control subjects. However, the relative reduction of individual LDL subtypes differed between these groups. This finding suggests that the effect of atorvastatin on LDL subtype distribution depends on the type of underlying hyperlipoproteinemia.     

Effect of ciprofibrate on lipoprotein metabolism and oxidative stress parameters in patients with type 2 diabetes mellitus and atherogenic lipoprotein phenotype

The effect of ciprofibrate therapy on plasma lipids and lipoproteins, HDL and LDL subfraction profile, fractional esterification rate of HDL cholesterol (FER_HDL) and the resistance of LDL and serum lipids to oxidation was studied in 24 males with type 2 diabetes and atherogenic lipoprotein phenotype (ALP). We also examined the effect of ciprofibrate therapy on oxidative DNA damage in peripheral lymphocytes. No differences in glucose, HbA1C and BMI levels were found after three months of ciprofibrate therapy. Ciprofibrate significantly decreased total cholesterol and triglyceride levels by 5.5% and 50% (p = 0.05; 0.001, respectively) and increased HDL-cholesterol levels by 8.5% (p = 0.05). FER_HDL and LDL subfraction profile were also favorably affected, However, no effect on HDL subclasses was found. There were no statistically significant differences in lipid resistance to oxidation measured in serum and in LDL (lag time and V_max) before and after therapy. No significant effect of ciprofibrate was found on oxidative DNA damage. The evaluation of the relationship between oxidative damage purines with lag time in LDL and maximal rate of serum lipid oxidation showed significant correlations after therapy (r = −0.58; 0.47, p = 0.01; 0.05, respectively), but only trends before starting ciprofibrate treatment. Type 2 diabetes mellitus represents a complex metabolic disorder expressed in glucose and lipoprotein disturbances and increased oxidative stress. Ciprofibrate therapy favorably affected major features of lipid abnormalities of diabetic patients, but the level of oxidative stress assessed by in vitro and in vivo methods was not changed. The evaluation of expected logical correlations between the parameters of lipoprotein metabolism, lipid resistance in serum and LDL, and oxidative DNA damage showed that those correlations were more relevant and significant after ciprofibrate treatment and were not related with glucose homeostasis. Received: 13 March 2000 / Accepted in revised form: 7 November 2000     

Effect of 6-month supervised exercise on low-density lipoprotein apolipoprotein B kinetics in patients with type 2 diabetes mellitus

Although low-density lipoprotein (LDL) cholesterol is often normal in patients with type 2 diabetes mellitus, there is evidence for a reduced fractional catabolic rate and consequently an increased mean residence time (MRT), which can increase atherogenic risk. The dyslipidemia and insulin resistance of type 2 diabetes mellitus can be improved by aerobic exercise, but effects on LDL kinetics are unknown. The effect of 6-month supervised exercise on LDL apolipoprotein B kinetics was studied in a group of 17 patients with type 2 diabetes mellitus (mean age, 56.8 years; range, 38-68 years). Patients were randomized into a supervised group, who had a weekly training session, and an unsupervised group. LDL kinetics were measured with an infusion of 1-¹³C leucine at baseline in all groups and after 6 months of exercise in the patients. Eight body mass index-matched nondiabetic controls (mean age, 50.3 years; range, 40-67 years) were also studied at baseline only. At baseline, LDL MRT was significantly longer in the diabetic patients, whereas LDL production rate and fractional clearance rates were significantly lower than in controls. Percentage of glycated hemoglobin A_1c, body mass index, insulin sensitivity measured by the homeostasis model assessment, and very low-density lipoprotein triglyceride decreased (P < .02) in the supervised group, with no change in the unsupervised group. After 6 months, LDL cholesterol did not change in either the supervised or unsupervised group; but there was a significant change in LDL MRT between groups (P < .05) that correlated positively with very low-density lipoprotein triglyceride (r = 0.51, P < .04) and negatively with maximal oxygen uptake, a measure of fitness (r = −0.51, P = .035), in all patients. The LDL production and clearance rates did not change in either group. This study suggests that a supervised exercise program can reduce deleterious changes in LDL MRT.     

Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.

This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol > or =4.14 mmol/L (160 mg/dl) and < 6.47 mmol/L (250 mg/dl) and triglycerides < or =4.52 mmol/L (400 mg/dl) were randomized to 12 weeks of once-daily placebo (n = 132), rosuvastatin 5 mg (n = 128), rosuvastatin 10 mg (n = 129), or atorvastatin 10 mg (n = 127). The primary efficacy end point was percent change in LDL cholesterol. Secondary efficacy variables were achievement of National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II), ATP III, and European Atherosclerosis Society LDL cholesterol goals and percent change from baseline in high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein B, and apolipoprotein A-I. Rosuvastatin 5 and 10 mg compared with atorvastatin 10 mg were associated with greater LDL cholesterol reductions (-40% and -43% vs 35%; p <0.01 and p <0.001, respectively) and HDL cholesterol increases (13% and 12% vs 8%, p <0.01 and p <0.05, respectively). Total cholesterol and apolipoprotein B reductions and apolipoprotein A-I increases were also greater with rosuvastatin; triglyceride reductions were similar. Rosuvastatin 5 and 10 mg were associated with improved achievement in ATP II (84% in both rosuvastatin groups vs 73%) and ATP III (84% and 82% vs 72%) LDL cholesterol goals, and rosuvastatin 10 mg was more effective than atorvastatin in achieving European Atherosclerosis Society LDL cholesterol goals. Both treatments were well tolerated.     

Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus

This study evaluated the effects of rosiglitazone therapy on lipids and the efficacy and safety of rosiglitazone in combination with atorvastatin in patients with type 2 diabetes mellitus. Three-hundred thirty-two patients entered an 8-week, open-label, run-in treatment phase with rosiglitazone 8 mg/day, and 243 were randomized to a 16-week, double-blinded period of continued rosiglitazone plus placebo, atorvastatin 10 mg/day, or atorvastatin 20 mg/day. With rosiglitazone alone, a modest increase in low-density lipoprotein (LDL) cholesterol (9%), a shift in LDL phenotype from dense to large buoyant subfractions (52% of patients), and an increase in total high-density lipoprotein (HDL) cholesterol levels (6%), predominantly in HDL(2) levels (13%), occurred from week 0 to week 8. When atorvastatin was added, there was a further increase in HDL(3) (5%) and expected significant reductions (p <0.0001) in LDL cholesterol (-39%), apolipoprotein B (-35%), and triglyceride levels (-27%). Glycemic control achieved with rosiglitazone alone was not adversely affected by add-on atorvastatin. The combination was well tolerated compared with placebo. To conclude, in addition to the beneficial effects of rosiglitazone on glycemic control, rosiglitazone and atorvastatin in combination achieved 2 goals: the reduction of LDL cholesterol to <100 mg/dl and the removal of small dense LDL in patients with type 2 diabetes mellitus.     

Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels

Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipoprotein (HDL) and its subclasses. Our purpose in this post hoc subanalysis of an open-label study was to compare the effects of daily oral doses of rosuvastatin 40 mg with atorvastatin 80 mg over a 6-week period on direct LDL cholesterol and small dense LDL (sdLDL) cholesterol in 271 hyperlipidemic men and women versus baseline values. Rosuvastatin was significantly (p<0.01) more effective than atorvastatin in decreasing sdLDL cholesterol (-53% vs -46%), direct LDL cholesterol (-52% vs -50%), total cholesterol/HDL cholesterol ratio (-46% vs -39%), and non-HDL cholesterol (-51% vs -48%), The magnitude of these differences was modest, and the 2 statins caused similar decreases in triglyceride levels (-24% and -26%). In conclusion, our data indicate that the 2 statins, given at their maximal doses, significantly and beneficially alter the entire spectrum of lipoprotein particles, but that rosuvastatin is significantly more effective than atorvastatin in lowering direct LDL cholesterol and sdLDL cholesterol.     

Lipid and lipoprotein profiles in Ethiopian patients with diabetes mellitus

The association between dyslipidemia and diabetes mellitus is well established. Although various lipoprotein abnormalities have been described in patients with diabetes mellitus elsewhere, there is limited information from African patients. We undertook a cross-sectional study to assess the prevalence of dyslipidemia in Ethiopian patients with types 1 and 2 diabetes. A total of 193 subjects were included in the study (54 patients had type 1 diabetes mellitus, 92 patients had type 2 diabetes mellitus, and 47 were nondiabetic controls). Of these, 93 (48.6%) were men and 103 (51.4%) were women. The mean age+/-SEM for patients with type 1 diabetes mellitus, type 2 diabetes mellitus, and controls were 29.8+/-1.4, 51.2+/-1.1, and 29.0+/-1.7 years, respectively. Hypercholesterolemia and hypertriglyceridemia, defined as cholesterol level of greater than 5.2 mmol/L and triglyceride level of greater than 1.8 mmol/L, were found in 47.3% and 41.8% of patients with diabetes mellitus compared with 27% and 17% in controls (P<.05 for both). The mean total cholesterol level+/-SEM was significantly higher in patients with type 1 or 2 diabetes mellitus than controls (5.76+/-0.27 mmol/L in type 1 diabetes mellitus, 5.25+/-0.2 mmol/L in type 2 diabetes mellitus, and 4.67+/-0.28 mmol/L in healthy controls, P<.02). Triglycerides and low-density lipoprotein levels were also significantly higher in patients with diabetes than in controls, whereas high-density lipoprotein levels were significantly lower in patients with diabetes. In conclusion, our study demonstrates that in Ethiopians with diabetes mellitus, dyslipidemia occurs more frequently than in controls. Thus, we recommend periodic screening for dyslipidemia in all Ethiopian patients with diabetes. Other studies are needed to assess the potential negative effect of dyslipidemia and obesity on morbidity and mortality in Ethiopians with diabetes.