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.     

Effects of atorvastatin versus fenofibrate on lipoprotein profiles, low-density lipoprotein subfraction distribution, and hemorheologic parameters in type 2 diabetes mellitus with mixed hyperlipoproteinemia

Diabetic dyslipoproteinemia characterized by hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, and often elevated low-density lipoprotein (LDL) cholesterol with predominance of small, dense LDL is a strong risk factor for atherosclerosis. It is unclear whether fibrate or statin therapy is more effective in these patients. We compared atorvastatin (10 mg/day) with fenofibrate (200 mg/day), each for 6 weeks separated by a 6-week washout period in 13 patients (5 men and 8 women; mean age 60.0+/-6.8 years; body mass index 30.0+/-3.0 kg/m2) with type 2 diabetes mellitus (hemoglobin A1c 7.3+/-1.1%) and mixed hyperlipoproteinemia (LDL cholesterol 164.0+/-37.8 mg/dl, triglycerides 259.7+/-107 mg/dl, HDL cholesterol 48.7+/-11.0 mg/dl) using a randomized, crossover design. Lipid profiles, LDL subfraction distribution, fasting plasma viscosity, red cell aggregation, and fibrinogen concentrations were determined before and after each drug. Atorvastatin decreased all LDL subfractions (LDL cholesterol, -29%; p <0.01) including small, dense LDL. Fenofibrate predominantly decreased triglyceride concentrations (triglycerides, -39%; p <0.005) and induced a shift in LDL subtype distribution from small, dense LDL (-31%) to intermediate-dense LDL (+36%). The concentration of small, dense LDL was comparable during therapy to both drugs (atorvastatin 62.8+/-19.5 mg/dl, fenofibrate 63.0+/-18.1 mg/dl). Both drugs induced an increase in HDL cholesterol (atorvastatin +10%, p <0.05; fenofibrate +11%, p = 0.06). In addition, fenofibrate decreased fibrinogen concentration (-15%, p <0.01) associated with a decrease in plasma viscosity by 3% (p <0.01) and improved red cell aggregation by 15% (p <0.05), whereas atorvastatin did not affect any hemorheologic parameter. We conclude that atorvastatin and fenofibrate can improve lipoprotein metabolism in type 2 diabetes. However, the medications affect different aspects of lipoprotein metabolism.     

Effects of bezafibrate and pravastatin on remnant-like lipoprotein particles and lipoprotein subclasses in type 2 diabetes

The effects of bezafibrate and pravastatin on remnant-like lipoprotein particles (RLPs) and lipoprotein subclasses were compared in type 2 diabetes. Bezafibrate (400 mg/day) and pravastatin (10 mg/day) were given to 27 Japanese diabetics in a randomized crossover design. RLP cholesterol (RLP-C) and RLP triglyceride (RLP-TG) were measured by an immunoseparation technique. LDL and HDL were separated each into three subclasses (large, medium, small) and their cholesterol (C) contents were measured by an HPLC method. RLP-C was reduced more effectively by pravastatin (bezafibrate -16.0% vs. pravastatin -40.6%, P < 0.05), whereas RLP-TG was reduced more effectively by bezafibrate (-55.2% vs. -35.0%, P < 0.05). Further, pravastatin decreased large and small LDL-C levels equally (large; -23.6%; medium; -17.2%, small; -21.0%), while bezafibrate produced a relatively larger reduction in small LDL-C (-12.1; -16.9; -21.5%). Whereas bezafibrate significantly decreased large HDL-C and increased medium and small HDL-C (-49.6; 34.1; 35.8%), pravastatin significantly increased only medium HDL-C (5.2; 9.4; 5.9%). Bezafibrate reduced RLP-C and RLP-TG more effectively in patients with high TG levels, whereas pravastatin's effect was not markedly influenced by the initial TG level. Thus measurements of RLP-C, RLP-TG, and HPLC subclasses revealed that bezafibrate and pravastatin differently influence the lipoprotein status in type 2 diabetes.     

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 statins on circulating oxidized low-density lipoprotein in patients with hypercholesterolemia

Recently, it has been reported that circulating oxidized low-density lipoprotein (Ox-LDL) might be a pivotal indicator for coronary artery disease and the severity of acute coronary syndromes. The purpose of this study was to investigate the effects of statins on Ox-LDL in patients with hypercholesterolemia. Sixteen patients with hypercholesterolemia were randomly assigned to 2 groups, one received 10 mg of pravastatin (n = 8) and the other received 20 mg of fluvastatin (n = 8). The plasma level of Ox-LDL was measured using a newly developed sandwich enzyme-linked immunosorbent assay (ELISA) method. There were no differences between the two groups in Ox-LDL, total cholesterol (TC), or LDL cholesterol (LDL-C) at the baseline. The reduction in Ox-LDL in the fluvastatin group was significantly higher than that in the pravastatin group (47.5% versus 25.2%, P = 0.033). The reductions in TC and LDL-C did not differ between the two groups. CONCLUSION: The present study has shown for the first time that the level of circulating Ox-LDL was significantly decreased by treatment with statins. In addition, the lowering effect of statins on the circulating Ox-LDL was independent of their lipid-lowering effect. Fluvastatin was more effective than pravastatin with regard to decreasing the circulating Ox-LDL.     

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.     

Association between small dense low-density lipoprotein and postprandial accumulation of triglyceride-rich remnant-like particles in normotriglyceridemic patients with myocardial infarction.

BACKGROUND: Although the small dense low-density lipoprotein (sd-LDL) is associated with hypertriglyceridemia, more than 60% of myocardial infarction (MI) patients are normotriglyceridemic in the fasting state. This study was aimed to investigate the relationship between the low-density lipoprotein (LDL) phenotype and postprandial hyperlipemia (PPL) in MI patients. METHODS AND RESULTS: Oral fat tolerance tests were performed in 71 patients with acute MI and fasting triglyceride concentrations below 200 mg/dl. Postprandial changes in the LDL particle diameter (LDL-PD) and lipids over a 6-h period after a meal were compared among 4 groups of patients classified according to fasting triglyceride levels (A, B as <150, and C, D as > or =150) and postprandial triglyceride levels (A, C as <230 and B, D as > or =230). Although fasting concentrations of triglyceride and remnant-like particle (RLP)-triglyceride were significantly higher in group C than in group B, the areas under the curves of the RLPs were significantly higher in group B. The triglyceride-to-cholesterol ratio in the RLPs was significantly higher in the PPL group than in the nonPPL group postprandially. The prevalence of sd-LDL (LDL-PD < or =25.5 nm) was significantly higher in group D but similar between groups B and C (23%, 42%, 50% and 83% in groups A, B, C and D, respectively). CONCLUSION: These results suggest that postprandial accumulation of triglyceride-rich lipoproteins is strongly associated with sd-LDL in MI patients without hypertriglyceridemia.     

Clinical significance of high-density lipoprotein cholesterol in patients with low low-density lipoprotein cholesterol.

OBJECTIVES: We sought to evaluate the significance of high-density lipoprotein cholesterol (HDL-C) in the context of low low-density lipoprotein cholesterol (LDL-C). BACKGROUND: Earlier studies support an inverse correlation between circulating HDL-C and coronary risk in patients with normal or elevated LDL-C. METHODS: This study involved 4,188 patients attending the Palo Alto Veterans Administration Medical Center or affiliated clinics with LDL-C levels below 60 mg/dl. Outcomes were examined 1 year after the index LDL-C date. The combined primary end point was myocardial injury or hospitalization from ischemic heart disease. The secondary end point was all-cause mortality. RESULTS: Mean HDL-C levels (mg/dl) by quartile (Q) were: Q1 28 mg/dl, Q2 36 mg/dl, Q3 43 mg/dl, and Q4 63 mg/dl. The rate of myocardial injury or hospitalization for ischemic heart disease showed an inverse relationship to HDL-C (adjusted odds ratios: Q1 1.59 [95% confidence interval (CI) 1.16 to 2.19], Q2 1.39 [95% CI 1.01 to 1.92], Q3 1.33 [95% CI 0.96 to 1.84], and Q4 reference) that persisted regardless of statin use or recent myocardial injury. Analyzing HDL-C as a continuous variable revealed a 10% [95% CI 3% to 17%] increase in the combined end point of myocardial injury or hospitalization for ischemic heart disease for every 10-mg/dl decrease in HDL-C. The unadjusted and adjusted incidence of all-cause mortality demonstrated a U-shaped relationship to HDL-C (adjusted odds ratios: Q1 1.13 [95% CI 0.79 to 1.62], Q2 0.97 [95% CI 0.67 to 1.40], Q3 0.74 [95% CI 0.50 to 1.09], and Q4 reference). CONCLUSIONS: The inverse relationship between HDL-C and coronary risk persists even among patients with LDL-C below 60 mg/dl, although a U-shaped relationship is observed between HDL-C and all-cause mortality.     

氧化型低密度脂蛋白和同型半胱氨酸与冠状动脉病变的相关性研究

目的 通过研究冠状动脉粥样硬化性心脏病（冠心病）患者血浆氧化型低密度脂蛋白（oxidized low-densitylipoprotein cholesterol,OX-LDL-C）和同型半胱氨酸（homoeysteine,HCY）浓度与Gensini评分的相关性,探讨其对冠状动脉病变严重程度的预测价值.方法 选择疑似冠心病患者86例,据冠状动脉造影结果分为冠心病组（67例）及对照组（19例）,冠心病组根据Gensini评分分为轻度亚组（23例）、中度亚组（22例）和重度亚组（22例）.分析各组血浆OX-LDL-C和HCY浓度与Gensini评分的相关性.结果 （1）冠心病组与对照组血浆OX-LDL-C、HCY浓度比较,冠心病组较高,差异有统计学意义（P＜0.05）.（2） Gensini评分三个亚组间血浆OX-LDL-C和HCY浓度比较,差异有统计学意义（P＜0.05）;随着冠状动脉狭窄程度加重,血浆OX-LDL-C、HCY浓度有增高趋势,差异有统计学意义（P＜0.05）.（3） Gensini评分与血浆OX-LDL-C（r=0.805,P＜0.01）、HCY （r=0.700,P＜0.01）浓度呈正相关,且OX-LDL-C与Gensini评分相关性较HCY高;血浆OX-LDL-C与HCY浓度呈正相关（r=0.698,P＜0.01）.结论 血浆OX-LDL-C和HCY浓度与Gensini评分有关,血浆OX-LDL-C与HCY具有相关一致性,联合检测血浆OX-LDL-C和HCY浓度可更好地了解病情、指导治疗及判断预后.     

Effects of atorvastatin on triglyceride-rich lipoproteins, low-density lipoprotein subclass, and C-reactive protein in hemodialysis patients

Dyslipidemia is an important risk factor for cardiovascular disease in patients with chronic renal failure (CRF). We evaluated the safety and efficacy of atorvastatin in patients with dyslipidemia associated with CRF who were undergoing hemodialysis (HD). Thirty-five patients who were receiving HD were given atorvastatin (10 mg/d) for 3 months. Chylomicron (CM), light and dense very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and light and dense low-density lipoprotein (LDL) were separated by ultracentrifugation. Apolipoprotein (apo) B was measured by electroimmunoassay. Mean LDL particle diameter was measured by gradient gel electrophoresis. Atorvastatin therapy reduced LDL-cholesterol (C) by 36% and remnant-like particle (RLP)-C by 58%. Atorvastatin significantly reduced apo B, apo CIII, and apo E in VLDL by 40% to 46% and IDL-apo B by 66%. Atorvastatin also significantly reduced cholesterol in CM, light VLDL, and dense VLDL without consistently affecting triglyceride (TG) in these lipoproteins. Atorvastatin similarly reduced both light and dense LDL-apo B by 38%. LDL particle size in the HD patients significantly increased during atorvastatin treatment from 25.7 +/- 0.4 to 26.2 +/- 0.6 nm. High sensitive C-reactive protein (HS-CRP) was halved by atorvastatin decreasing from 0.08 +/- 0.05 to 0.04 +/- 0.03 mg/dL. Atorvastatin treatment did not affect the creatinine kinase level, and no classical adverse effects were observed during the study. These results suggest that atorvastatin is safe and effective for the management of dyslipidemia in patients with CFR who are receiving HD, which may help to suppress the development of atherosclerosis.     

血脂康对高脂血症患者低密度脂蛋白颗粒和氧化型低密度脂蛋白的影响

目的探讨血脂康对高脂血症患者低密度脂蛋白(LDL)颗粒和氧化型低密度脂蛋白(ox-LDL)的影响。方法连续入选未服用降脂药物治疗的受试人群40例(其中高脂血症患者20例,健康受试者20例),分为血脂康组(n=20例)和对照组(n=20例)。Lipoprint脂蛋白分类检测仪对LDL颗粒进行分类。治疗8周后比较两组治疗前后LDL颗粒和ox-LDL的变化。结果与治疗前相比,治疗后血脂康组的血清低密度脂蛋白胆固醇(LDLC)、总胆固醇(TC)、甘油三酯(TG)和载脂蛋白B的浓度显著降低(P0. 05),小颗粒LDLC的浓度和小颗粒LDL的百分比均降低(P0. 05)。经血脂康治疗后,ox-LDL的浓度显著降低(P0. 05)。结论血脂康治疗8周可显著改善高脂血症患者的血脂谱,并降低致动脉粥样硬化性小颗粒LDLC浓度和百分比,同时减少氧化应激反应。     

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.     

Effects of atorvastatin and pravastatin on malondialdehyde-modified LDL in hypercholesterolemic patients.

The aim of the present study was to compare the effects of atorvastatin and pravastatin on lipid parameters and the concentration of malondialdehyde-modified low-density lipoprotein (MDA-LDL) in hypercholesterolemic patients. A total of 17 patients (10 men, 7 women; mean age, 68+/-9 years) who were indicated for drug therapy based on the National Cholesterol Education Program II underwent an 8-week regimen of atorvastatin (10 mg/day) or pravastatin (10 mg/day) with a 4-week washout period between drugs. After an overnight fast, lipid parameters and MDA-LDL concentration were measured before and after the 8-week treatment with each drug. Both atorvastatin and pravastatin produced significant reductions in low-density lipoprotein (LDL) cholesterol and MDA-LDL concentrations, with a significant increase in high-density lipoprotein cholesterol concentration. The percent reductions in LDL cholesterol and MDA-LDL concentration were significantly greater with atorvastatin than pravastatin (46 +/-6% vs 24+/-10%, p<0.0001, and 44+/-10% vs 14+/-13%, p<0.0001, respectively). The ratios of percent reductions in MDA-LDL concentrations and percent reductions in LDL cholesterol concentrations were significantly greater for atorvastatin than pravastatin (0.96+/-0.19 vs 0.59+/-0.55, p<0.0001). In conclusion, atorvastatin reduced serum concentrations of LDL cholesterol and MDA-LDL to a greater degree than pravastatin, indicating that atorvastatin not only has stronger lipid-lowering effects, but also stronger antioxidative effects than pravastatin.     

依折麦布联合瑞舒伐他汀对低密度脂蛋白胆固醇未达标的急性冠脉综合征患者胆固醇代谢的影响

目的探析依折麦布联合瑞舒伐他汀(可定)对低密度脂蛋白胆固醇未达标的急性冠脉综合征患者胆固醇代谢的影响。方法采用随机数字表法将2016-02~2017-02收治的210例低密度脂蛋白胆固醇未达标的急性冠脉综合征患者分为对照组(瑞舒伐他汀治疗)及观察组(依折麦布联合瑞舒伐他汀治疗)各105例持续治疗12周,对两组胆固醇代谢影响效果进行比较。结果观察组不良反应总发生率为6.67%,与对照组4.76%比较,差异无统计学意义(P0.05)。治疗前两组胆固醇代谢指标无明显差异,治疗后观察组各指标数值优于对照组,差异有统计学意义(P0.05)。结论在低密度脂蛋白胆固醇未达标的急性冠脉综合征患者治疗中依折麦布联合瑞舒伐他汀改善胆固醇代谢效果更佳,可作为优选方案推广使用。     

Effects of fenofibrate and ezetimibe, both as monotherapy and in coadministration, on cholesterol mass within lipoprotein subfractions and low-density lipoprotein peak particle size in patients with mixed hyperlipidemia

Coadministration of fenofibrate and ezetimibe (FENO + EZE) produced complementary and favorable effects on the major lipids and lipoproteins, low-density lipoprotein cholesterol (LDL-C), triglycerides, high-density lipoprotein cholesterol (HDL-C), and non-HDL-C levels, and was well tolerated in patients with mixed hyperlipidemia. The current analysis evaluates the effects of FENO and EZE, as monotherapies and in coadministration, on lipoprotein subfractions and LDL particle size distributions in these patients. In a 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients with mixed hyperlipidemia were randomized in a 1:3:3:3 ratio to one of 4 treatment groups: placebo, FENO 160 mg/day, EZE 10 mg/day, or FENO 160 mg/day + EZE 10 mg/day. At baseline and study end point, the Vertical Auto Profile II method was used to measure the cholesterol associated with 2 very low-density lipoprotein (VLDL) subfractions (VLDL-C1 + 2 and VLDL-C3), intermediate-density lipoproteins (IDL-C), and 4 LDL subfractions (LDL-C1 through LDL-C4, from most buoyant to most dense), lipoprotein (Lp) (a), and 2 HDL-C subfractions (HDL-C2 and HDL-C3). The LDL particle size was determined using segmented gradient gel electrophoresis. Fenofibrate reduced cholesterol mass within VLDL, IDL, and dense LDL (primarily LDL-C4) subfractions, and increased cholesterol mass within the more buoyant LDL-C2 subfraction, consistent with a shift to a more buoyant LDL peak particle size. Ezetimibe reduced cholesterol mass within all of the apolipoprotein B-containing particles (eg, VLDL-C, IDL-C, and LDL-C) but did not lead to a shift in the LDL particle size distribution profile. Coadministration of FENO and EZE promoted more pronounced reductions in VLDL-C, IDL-C, and LDL-C, and a preferential decrease in dense LDL subfractions. Fenofibrate and FENO + EZE promoted similar increases in HDL-C2 and HDL-C3. Coadministration of FENO + EZE produced complementary and favorable changes in lipoprotein fractions and subfractions, as assessed by the Vertical Auto Profile II method, in patients with mixed hyperlipidemia. These changes reflected the combined effects of FENO in reducing triglycerides-rich lipoproteins and promoting a shift in the LDL particle distribution profile toward larger, more buoyant particles and of EZE in promoting reductions in cholesterol mass across the apolipoprotein B particle spectrum.