微粒化非诺贝特对高三酰甘油血症患者血管内皮功能的作用

目的 :探讨微粒化非诺贝特对高三酰甘油血症患者血管内皮功能的作用。方法 :对 30例高三酰甘油血症患者 (口服微粒化非诺贝特 2 0 0mg/d治疗 4周前后 )和 30例正常人采用高分辨超声技术检测血流介导的和硝酸甘油介导的肱动脉舒张功能 ,并测定血浆内皮素 (ET)和血脂。结果 :①高三酰甘油血症组血流介导的肱动脉舒张反应较正常组明显减弱 [(2 .7± 2 .0 ) %∶(15 .0± 8.0 ) % ,P <0 .0 1],而两组对硝酸甘油的血管舒张反应差异无显著性意义 [(15 .0± 5 .0 ) %∶(16 .8± 9.0 ) % ,P >0 .0 5 ]。②高三酰甘油血症患者微粒化非诺贝特治疗后血流介导的肱动脉舒张显著改善 [(11.0± 9.0 ) % ,P <0 .0 1],而硝酸甘油介导的血管舒张较治疗前无明显改变[(16 .2± 6 .0 ) % ,P >0 .0 5 ]。③高三酰甘油血症患者血浆ET水平显著高于正常人 [(10 6 .2± 19.2 ) μg/L∶(72 .4± 14 .1) μg/L ,P <0 .0 1],微粒化非诺贝特治疗后血浆ET水平显著降低 [(82 .7± 15 .5 ) μg/L ,P <0 .0 1],血清三酰甘油明显降低 (P <0 .0 5 )。结论 :微粒化非诺贝特对高三酰甘油血症患者受损的血管内皮依赖性舒张功能有改善作用。改善血管内皮功能亦是微粒化非诺贝特防治冠心病的作用机制之一     

Effects of retinoid therapy on insulin sensitivity, lipid profile and circulating adipocytokines

OBJECTIVE: In vitro and in vivo models indicate that all-trans retinoic acids influence glucose and lipid metabolism. We aimed to evaluate the effects of chronic treatment with acitretin, an all-trans retinoic acid, on glucose metabolism, lipid profile and adiponectin and resistin levels. DESIGN: Ten normoglycemic, normolipemic patients affected with psoriasis vulgaris were studied before and after 1 and 3 months of oral treatment with 35 microg of acitretin. METHODS: Glucose metabolism, lipid profile, and adiponectin and resistin levels were evaluated in basal conditions and after acitretin treatment. Ten healthy subjects matched for age, body mass index (BMI) and insulin sensitivity were studied as controls. RESULTS: One-month acitretin treatment reduced psoriasis activity, insulin sensitivity, evaluated as QUICKI values (0.364 +/- 0.034 versus 0.329 +/- 0.051; P < 0.05) and HOMA-IR index (1.53 +/- 0.73 versus 2.59 +/- 1.41; P < 0.05), and high-density lipoprotein (HDL)-cholesterol levels (45.2 +/- 11.7 versus 39.4 +/- 10.4 mg/dl; P = 0.01). The impairment in glucose and lipid homeostasis was transient and not associated to BMI variations. Adiponectin levels did not change during the treatment, while resistin levels, which were higher in untreated patients than in controls (9.4 +/- 4.4 versus 6.2 +/- 2.1 ng/ml; P = 0.05), fell within the normal range after 1 and 3 months of therapy. The normalization of resistin levels occurred without significant changes in circulating tumor necrosis factor alpha (TNFalpha) levels, which persisted elevated throughout the treatment. CONCLUSIONS: Treatment with a low dose of acitretin induced a mild, transient reduction of insulin sensitivity and HDL-cholesterol levels that was not related to modifications of adiponectin, resistin and TNFalpha levels. Although the role of resistin in humans remains elusive, the levels of this adipocytokine seem to be affected, at least in part, by retinoids.     

Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia

BackgroundOmega-3 fatty acids and fenofibrate are both used to treat patients with hypertriglyceridemia. However, a head-to-head comparison of the lipoprotein and metabolic effects of these two medicines has not been published.MethodsThis was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Fifty patients in each group were given placebo, omega-3 fatty acids 2 g (most commonly used dosage in Korean patients), or fenofibrate 160 mg, respectively daily for 2 months.ResultsOmega-3 fatty acids therapy decreased triglycerides by 21% and triglycerides/HDL cholesterol and improved flow-mediated dilation (P < 0.01), however, did not significantly change insulin, plasma adiponectin levels, and insulin sensitivity (determined by QUICKI) relative to baseline measurements. Fenofibrate therapy decreased total cholesterol, triglycerides by 29%, and triglycerides/HDL-cholesterol (all P < 0.01) and improved flow-mediated dilation when compared with baseline. When compared with placebo and omega-3 fatty acids, fenofibrate therapy decreased non-HDL cholesterol (P < 0.001) and triglycerides/HDL cholesterol (P = 0.016) while increasing HDL cholesterol (P < 0.001) and apolipoprotein AI (P = 0.001). Of note, when compared with omega-3 fatty acids, fenofibrate therapy decreased fasting insulin (P = 0.023) and increased plasma adiponectin (P = 0.002) and insulin sensitivity (P = 0.015).ConclusionsOmega-3 fatty acids and fenofibrate therapy promoted similar changes in triglycerides and endothelium-dependent dilation. However, fenofibrate therapy had substantially better effects on lipoprotein and metabolic profiles in patients with hypertriglyceridemia.     

Effects of short-term fenofibrate treatment on circulating markers of inflammation and hemostasis in patients with impaired glucose tolerance

CONTEXT: Apart from lowering lipid levels, peroxisome proliferator-activated receptor (PPAR) alpha activators (fibrates) produce many other favorable effects that may contribute to their clinical effectiveness in dyslipidemic and diabetic patients. OBJECTIVE: The objective of this study was to compare the impact of a short-term treatment with fenofibrate and the American Heart Association (AHA) step 1 diet on systemic inflammation, hemostasis, and monocyte secretory function in relationship with their metabolic actions. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: This was a prospective, randomized, placebo-controlled trial involving the group of 91 ambulatory patients with impaired glucose tolerance (IGT) (diagnosed on the basis of the American Diabetes Association criteria), randomly divided into three groups, simultaneously treated for 30 d with the AHA step 1 diet (n = 30), micronized fenofibrate (267 mg/d, n = 31), or placebo (n = 30). The control group included 34 age-, sex-, and weight-matched subjects with normal glucose tolerance. Eighty-six (95%) patients and all control subjects completed the study. MAIN OUTCOME MEASURES: Plasma markers of inflammation and hemostasis and monocyte release of proinflammatory cytokines were measured. RESULTS: Compared with subjects with normal glucose tolerance, IGT patients exhibited higher plasma levels/activities of fibrinogen, factor VII, plasminogen activator inhibitor-1, high-sensitivity C-reactive protein, and oxidized low-density lipoproteins. Lipopolysaccharide-activated monocytes from IGT patients released significantly more TNF-alpha, IL-1beta, IL-6, and monocyte chemoattractant protein-1 in comparison with monocytes from control subjects. Thirty-day treatment with fenofibrate but not with the AHA step 1 diet: 1) improved lipid/lipoprotein profile and glucose metabolism, and 2) reversed or alleviated all the above-mentioned abnormalities. The favorable effects of fenofibrate on plasma high-sensitivity C-reactive protein and on monocyte release of TNF-alpha, IL-1beta, IL-6, and monocyte chemoattractant protein-1 did not correlate with its action on plasma lipids but was related to the improvement in insulin sensitivity and weakly to free fatty acid-lowering action. CONCLUSIONS: Our study is the first to show that relatively small disturbances in glucose metabolism are associated with marked and multidirectional abnormalities in plasma markers of inflammation and hemostasis and in monocyte secretory function. Moreover, fenofibrate may exhibit early pleiotropic effects in patients with IGT.     

非诺贝特对高甘油三酯血症人群胰岛素抵抗和胰岛β细胞分泌功能的影响

目的观察非诺贝特对高甘油三酯(TG)血症人群的胰岛素抵抗和胰岛β细胞分泌功能的影响。方法正常糖耐量、高TG血症(TG≥12．3 mmol/L)患者12例(HTG组),予非诺贝特200 mg/d治疗3个月,于治疗前后应用高葡萄糖钳夹技术评价胰岛素敏感性和胰岛β细胞功能。并与正常糖耐量、正常血脂志愿者12名(NC组)进行比较。结果HTG组胰岛素敏感性指数(ISI)显著低于NC组;第一时相胰岛素分泌(1PH)稍低于NC组;第二时相胰岛素分泌(2PH)和最大胰岛素分泌(INS120-150)均明显高于NC组。HTG组非诺贝特治疗后,ISI较治疗前显著升高(18．35±1．76 vs 9．40±1．76,P＜0．01);1PH变化无统计学意义[(247．7±32．9)mIU/L vs (225．7±36．7)mIU/L,P=0．94];2PH和INS120-150较治疗前降低[分别为(73．2±9．0)mIU/L vs (106．0±11．3)mlU/L,p=0．014;(89．2±8．9)mIU/L vs (141．6±13．8) mIU/L,P=0．005]。结论非诺贝特调脂治疗能显著改善高TG血症人群的胰岛素抵抗及高葡萄糖钳夹试验中的胰岛素分泌。     

Efficacy of fenofibrate in Chinese patients with primary biliary cirrhosis partially responding to ursodeoxycholic acid therapy

OBJECTIVE: To investigate the efficacy of fenofibrate combination therapy in Chinese patients with primary biliary cirrhosis (PBC) who had a partial response to standard dose of ursodeoxycholic acid (UDCA) for at least one year. METHODS: PBC patients were treated with UDCA (13–15 mg/kg/day) for more than one year. The biochemical response to UDCA treatment was evaluated after treatment. Fenofibrate (200 mg/day) was added to 22 patients with partial response to UDCA. RESULTS: In patients with partial response to UDCA, serum alkaline phosphatase (ALP) and γ‐glutamyl transpeptidase levels significantly decreased after 3‐month combination therapy of UDCA and fenofibrate, 68% of these patients even reached normal ALP level. Serum triglyceride (TG) and cholesterol levels were improved, and alanine transaminase (ALT) and aspartate transaminase (AST) were also decreased during the combination therapy. However, fenofibrate had no significant effect on serum bilirubin levels. The improvement of liver biochemical tests was maintained in some patients with long‐term therapy (at least 6 months). No obvious adverse effects were observed in patients taking fenofibrate. CONCLUSIONS: Fenofibrate is effective for improving liver biochemical tests in patients who have partial response to UDCA monotherapy. It is worth exploring the efficacy of fenofibrate on histological changes in PBC patients.     

非诺贝特对高甘油三酯合并低高密度脂蛋白冠心病患者前列环素活性的影响

目的观察冠心病合并高甘油三酯（ＴＧ），低高密度脂蛋白－胆固醇（ＨＤＬ－Ｃ）血症患者应用非诺贝特治疗后，其血清对前列环素（ＰＧＩ２）生物活性的影响。方法选择冠心病组和正常组各２０例，以ＰＧＩ２对二磷酸腺苷（ＡＤＰ）诱导的血小板聚集的抑制率作为ＰＧＩ２生物活性的指标，在冠心病组服用非诺贝特前及一个月后，比较两组患者的血清对ＰＧＩ２生物活性的影响及与血脂的关系。结果实验发现，在应用非诺贝特治疗前，冠心病组血清对ＰＧＩ２生物活性的稳定作用明显低于正常组（Ｐ＜０．０１）。应用非诺贝特治疗１个月后，冠心病组的血ＴＧ水平显著降低（Ｐ＜０．００１），血ＨＤＬ－Ｃ水平显著升高（Ｐ＜０．０１）；同时，冠心病组血清对ＰＧＩ２的稳定作用与正常组相比不再有显著性差异（Ｐ＞０．０５）。结论本实验进一步证实了ＨＤＬ－Ｃ对ＰＧＩ２的保护作用。因低ＨＤＬ－Ｃ血症是冠心病的危险因子，因而其降低ＰＧＩ２生物活性从而增加血小板聚集很可能是其作用机制的一部分。经过调脂治疗后，升高血ＨＤＬ－Ｃ水平，恢复ＨＤＬ－Ｃ对ＰＧＩ２的保护作用对防止粥样斑块破裂和减少急性冠状动脉综合征的发生可能起重要作用。     

The effect of spironolactone on circulating adipocytokines in patients with type 2 diabetes mellitus complicated by diabetic nephropathy

Angiotensin II can influence adipocytokine levels in adipose tissue, but the association between aldosterone, which mediates the effect of angiotensin II, and adipocytokines has yet to be fully elucidated. This study was designed to investigate the effect of spironolactone, a representative aldosterone blocker, on adipocytokines such as adiponectin, visfatin, plasminogen activator inhibitor (PAI)-1 and tumor necrosis factor alpha in patients with type 2 diabetic nephropathy: the study included 33 patients, 22 of whom were randomly assigned to the spironolactone (50 mg/d) group and 11 to the amlodipine (2.5 mg/d) group. Data were collected at baseline and after 3 months of treatment and compared with baseline data for 25 age-matched healthy subjects. A significant decrease in plasminogen activator inhibitor 1 in the spironolactone group was observed (22.6 +/- 13.4 to 19.2 +/- 11.3 ng/mL, P =.0323), but this did not occur in the amlodipine group. Adiponectin and visfatin levels did not change in the spironolactone and amlodipine groups, but significant increases in these adipocytokines were found in a subgroup of patients in the spironolactone group with glycated hemoglobin A(1c) (HbA(1c)) 8.0% or greater (11.8 +/- 6.4 to 13.3 +/- 7.4 microg/mL, P = .0344; and 1.39 +/- 0.92 to 2.26 +/- 0.76 ng/mL, P =.0397, respectively). The tumor necrosis factor alpha level at baseline exceeded the lower detection limit of the assay in only 6 patients in the spironolactone group, and no change occurred in these patients. Moreover, neither spironolactone nor amlodipine therapy caused a change in high-sensitivity C-reactive protein or soluble CD40 ligand, but a significant decrease in the level of brain natriuretic peptide was found in the spironolactone group only. Furthermore, significant increases of HbA(1c), creatinine, potassium, and aldosterone levels and plasma renin activity, and a decrease in urinary albumin excretion were also observed only in the spironolactone group. The number of patients with HbA(1c) 8.0% or greater increased after spironolactone treatment. A significant decrease in systolic but not in diastolic blood pressure was observed in both treatment groups. In conclusion, our data suggest that in patients with type 2 diabetes mellitus complicated by diabetic nephropathy, spironolactone can decrease plasminogen activator inhibitor 1 and brain natriuretic peptide levels in addition to urinary albumin excretion, and systolic blood pressure, and that in patients with poor glycemic control, spironolactone can increase the levels of adiponectin and visfatin. However, the significant elevation of HbA(1c) levels by spironolactone should be emphasized.     

罗格列酮对2型糖尿病患者血清脂肪细胞因子的影响

目的观察罗格列酮（RSG）对2型糖尿病（T2DM）患者血清脂肪细胞因子的影响，探讨血清脂肪细胞因子和胰岛素抵抗（IR）的关系及其在T2DM发病机制中的作用。方法38例新诊断T2DM患者（DM组），以RSG每日4mg口服治疗12周；24例年龄和性别匹配的糖耐量正常者为正常对照（NC）组。检测NC组及DM组患者治疗前后的身高、体重、血压、FPG、2hPG、免疫反应胰岛素（IRI）、真胰岛素（TI）、胰岛素原（PI）、血清脂肪细胞因子瘦素（LEP）、抵抗素（RST）、脂联素（APN）、视黄醇结合蛋白4（RBP-4）、尿白蛋白（UAlb）和血脂谱。计算BMI、胰岛素敏感性指数（QUICKI）、胰岛素抵抗指数（HOMA-IR）和FPI／FTI。结果DM组RSG治疗前PG、IRI、FPI、LEP、RST、RBP-4、HOMA-IR和FPI／FTI均较NC组升高，而APN和QUICK下降（P〈0．05）；DM组RSG治疗后，BMI、UAlb、血脂谱和RBP-4无显著变化，其余指标均向正常转化，APN则升高达2倍多（P〈0．01）。LEP与性别、BMI、FIRI、FTI、FPI、HOMA-IR和QUICKI相关；RST与FPI／FTI和TI相关；APN与年龄、BMI、RBP-4、FPI、2hPI、FTI、HOMA-IR和QuICKI相关；RBP-4与BMI、APN、HOMA-IR相关。多元逐步回归分析提示，LEP和APN与IR独立相关。结论新诊断T2DM患者存在IR和血清LEP、RST、RBP-4升高；APN下降；RSG可能通过改善血清脂肪细胞因子谱而发挥降血糖、改善IR和口细胞功能的疗效。     

非诺贝特辅助治疗原发性胆汁性肝硬化效果的Meta分析

目的对非诺贝特辅助治疗原发性胆汁性肝硬化(PBC)患者的有效性进行系统评估。方法检索中国知网、万方、中国生物医学文献数据库、Pubmed、Embase及Cochrane library数据库中自建库至2014年12月31日间发表的相关随机对照试验(RCT),对纳入的文献进行资料提取和质量评价,采用Stata10.1软件对数据进行统计分析。若具有同质性则选择固定效应模型分析,有异质性则选择随机效应模型分析。结果共纳入6篇RCT进行分析。结果显示:辅助使用非诺贝特治疗后,PBC患者的GGT、ALT、ALP水平较治疗前明显下降(标准化均数差分别为-1.595、-0.447、-2.124,P值均0.05);而AST、TBil水平在干预前后差异无统计学意义(P值均0.05)。在改善免疫球蛋白M方面,非诺贝特辅助治疗前后差异无统计学意义(P0.05)。结论基于当前证据,非诺贝特辅助治疗PBC可以有效改善患者肝功能,但是并不能有效改善患者的免疫功能。本文样本量较少,尚需要更多大样本、多中心、高质量的RCT进行验证。     

Effect of fenofibrate therapy on paraoxonase1 status in patients with low HDL-C levels

ObjectivesWe evaluated the effect of micro-coated fenofibrate on lipid parameters, high sensitivity C-reactive protein and paraoxonase1 levels in dyslipidemic patients with low high-density lipoproteins levels. In addition, the effects of the paraoxonase1 polymorphisms on lipid and paraoxonase1 responses to fenofibrate therapy were examined.MethodsA total of 61 dyslipidemic patients with low high-density lipoproteins levels were recruited into this study to receive micro-coated fenofibrate (160 mg/day) for 12 weeks. Lipid parameters, C-reactive protein, paraoxonase1 concentration and activity were measured at baseline and after 6 and 12 weeks of fenofibrate treatment. Four polymorphisms in both the coding (L55M and Q192R) and regulatory regions (T-108C and G-909C) of human paraoxonase1 were also quantified.ResultsMicro-coated fenofibrate significantly decreased total cholesterol, triglycerides, non-high-density lipoprotein cholesterol, oxidized low-density lipoprotein and apolipoprotein-B levels after 6 and 12 weeks (all p < 0.001). While high-density lipoprotein and apolipoprotein AI levels were significantly increased by 14.7% and 6.9%, respectively, after 6 weeks and by 17.3% and 7.2%, respectively, after 12 weeks (all p < 0.01). There were no significant differences in the mean of low-density lipoprotein and C-reactive protein after fenofibrate treatment. There were significant increases in paraoxonase1 concentration and activity by 7.7% and 5.7% after 6 weeks and by 14.6% and 10.1% after 12 weeks, respectively (all p < 0.01). After micro-coated fenofibrate therapy, a significantly positive correlation between the change in high-density lipoprotein and the changes in paraoxonase1 concentration and activity was observed (p = 0.001). On the other hand, the changes in paraoxonase1 activity were significantly and negatively correlated with the changes in triglycerides (p = 0.007). The therapeutic response of lipid parameters to micro-coated fenofibrate was independent of paraoxonase1 polymorphisms. However, paraoxonase1 Q192R and T-108C polymorphisms significantly affected the increase in paraoxonase1 activity (the highest increase in 192QQ and ?108TT) and paraoxonase1 concentration (the highest increase in ?108TT).ConclusionLipid-modifying therapy with micro-coated fenofibrate in patients with low high-density lipoprotein levels not only reduced atherogenic lipids (total cholesterol, triglycerides, oxidized low-density lipoprotein and apolipoprotein-B) and increased atheroprotective lipids but also increased paraoxonase1 concentration and activity. Increasing paraoxonase1 levels by fenofibrate may play an important role in decreasing low-density lipoprotein oxidation.     

小剂量氟伐他汀联合非诺贝特治疗老年混合型高脂血症的临床研究

目的观察小剂量氟伐他汀联合非诺贝特治疗老年混合型高脂血症的疗效及安全性。方法将入选的70例老年混合型高脂血症患者，随机分为氟伐他汀单药治疗组（12=35，20mg／d），氟伐他汀（20mg／d）、非诺贝特（200mg，隔日1次）联合治疗组（12=35），疗程均为12周。结果联合治疗组血脂参数变化最显著，降低低密度脂蛋白胆固醇、三酰甘油和升高高密度脂蛋白胆固醇的能力明显优于单药组（P〈0．01或P〈0．05），且未发现明显不良反应。结论小荆量氟伐他汀与非诺贝特联合治疗可以更有效地改善老年混合型高脂血症患者的血脂异常，具有良好的安全性和耐受性。     

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.     

Effects of fenofibrate on lipids, lipoproteins, and apolipoproteins in 33 subjects with primary hypercholesterolemia

The effects of fenofibrate on lipids, lipoproteins, and apolipoproteins in 33 subjects with primary hypercholesterolemia were assessed in a 6-month parallel group study, placebo (n = 15) versus fenofibrate 300 mg/day (n = 18), followed by an open label 6-month treatment period. After stabilization on an isocaloric low fat (less than 35% total calories) diet with less than 250 mg cholesterol/day and a P/S ratio of 1, and maintenance of LDL-cholesterol (LDL-C) levels greater than or equal to 175 mg/dl, subjects received placebo for 6 weeks and were then randomized into placebo or fenofibrate groups for 6 months, followed by open label treatment for 6 months. During the 6-month double-blind period, compared to the placebo group, the treatment group had significant reductions in total cholesterol, LDL-C, total apo B, and triglyceride, and increments in HDL-cholesterol, apolipoprotein A-I and apolipoprotein A-II (P less than 0.01 for all comparisons). Compared to placebo baseline, therapy with fenofibrate resulted in a reduction of LDL-C, apo B, and the LDL-C/HDL-C ratio of 15%, 13%, and 18% respectively; HDL-C, apo A-I, and apo A-II increased respectively 12%, 13% and 30% (P less than 0.01 for all comparisons). Mean adherence during the double blind phase of the trial was 95% in the drug group and 96% in the placebo group. An additional 6 months of open label fenofibrate therapy maintained the reduced total and LDL-C as well as the elevated HDL-C, apo A-I and apo A-II in the drug-drug group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of fenofibrate and simvastatin on HDL-related biomarkers in low-HDL patients

The objective of the present study was to compare the effects of fenofibrate versus simvastatin on various HDL-related biomarkers in dyslipidemic patients with low HDL-C, in whom it is as yet unclear whether a statin or a fibrate is the most appropriate treatment. Fifty-two patients received either fenofibrate (160 mg/day) or simvastatin (40 mg/day) for 8 weeks in a randomized, double-blind, parallel group trial. Simvastatin effectively lowered plasma LDL-C and apoB levels, but did not change plasma HDL levels and HDL-related biomarkers, except for a small, significant increase in the capacity of plasma to promote SR-BI mediated cholesterol efflux. Fenofibrate did not affect plasma LDL-C levels but lowered triglycerides, and exerted a remarkable HDL-C raising activity (+22%), with patients in the lowest range of HDL-C getting the maximal benefit. The HDL-C raise was associated with a shift of HDL from large to small particles, and from LpA-I to LpA-I:A-II, which might explain the observed increase in the plasma capacity to promote ABCA1 mediated efflux with no changes in SR-BI efflux. The distinct and complementary effects of fenofibrate and simvastatin on lipid parameters and HDL-related biomarkers suggest that a combination therapy with the two drugs in dyslipidemic patients with low HDL would be fully justified.