Short-term effect of fenofibrate on C-reactive protein: A meta-analysis of randomized controlled trials

Diabetology & Metabolic Syndrome

Edmond K Kabagambe¹  Alfred A Bartolucci²  Donna K Arnett¹  James N Kiage¹  Jiatao Ye¹ 

[1] Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA;Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

关键词: short-term;    clinical trials;    randomized;    meta-analysis;    fenofibrate;    CRP;   

Others  :  817549
DOI  :  10.1186/1758-5996-3-24

 received in 2011-05-09, accepted in 2011-09-22,  发布年份 2011

【 摘 要 】

Background

C-reactive protein (CRP) is positively associated with risk for cardiovascular disease and all-cause mortality. Some but not all randomized and non-randomized clinical trials found significant associations between fenofibrate therapy and CRP but the direction and magnitude of the association varied across studies. The duration of treatment, patient populations and sample sizes varied greatly, and most short-term studies (i.e., ≤ 12 weeks) had fewer than 50 patients. In this study we meta-analyzed randomized clinical trials to determine the short-term effect of fenofibrate on CRP.

Methods

Two reviewers independently searched PubMed and other online databases for short-term randomized clinical trials that reported CRP concentrations before and after fenofibrate treatment. Of the 81 studies examined, 14 studies with 540 patients were found eligible. Data for the change in CRP and corresponding measures of dispersion were extracted for use in the meta-analysis.

Results

The weighted mean CRP concentrations before and after fenofibrate therapy were 2.15 mg/L and 1.53 mg/L (-28.8% change), respectively. Inverse-variance weighted random effects meta-analysis revealed that short-term fenofibrate treatment significantly lowers CRP by 0.58 mg/L (95% CI: 0.36-0.80). There was significant heterogeneity between studies (Q statistic = 64.5, P< 0.0001, I² = 79.8%). There was no evidence of publication bias and sensitivity analysis revealed that omitting any of the 14 studies did not lead to a different conclusion from the overall meta-analysis result.

Conclusion

Short-term treatment with fenofibrate significantly lowers CRP concentration. Randomized trials that will recruit patients based with high baseline CRP concentrations and with change in CRP as a primary outcome are needed.

【 授权许可】

   
2011 Ye et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Kabagambe EK, Judd SE, Howard VJ, Zakai NA, Jenny NS, Hsieh M, Warnock DG, Cushman M: Inflammation biomarkers and risk of all-cause mortality in the reasons for geographic and racial differences in stroke cohort. American Journal of Epidemiology 2011, 174:284-292.
• [2]Koenig W, Sund M, Frohlich M, Fischer HG, Lowel H, Doring A, Hutchinson WL, Pepys MB: C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999, 99:237-242.
• [3]Marsik C, Kazemi-Shirazi L, Schickbauer T, Winkler S, Joukhadar C, Wagner OF, Endler G: C-reactive protein and all-cause mortality in a large hospital-based cohort. Clin Chem. United States 2008, 54:343-349.
• [4]Kones R: Rosuvastatin, inflammation, C-reactive protein, JUPITER, and primary prevention of cardiovascular disease--a perspective. Drug Des Devel Ther 2010, 4:383-413.
• [5]Jenny NS, Yanez ND, Psaty BM, Kuller LH, Hirsch CH, Tracy RP: Inflammation biomarkers and near-term death in older men. Am J Epidemiol 2007, 165:684-695.
• [6]Kincl V, Panovsky R, Meluzin J, Semenka J, Groch L, Tomcikova D, Jarkovsky J, Dusek L: Association between laboratory markers and presence of coronary artery disease. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2010, 154:227-233.
• [7]Shi B, Ni Z, Cai H, Zhang M, Mou S, Wang Q, Cao L, Yu Z, Yan Y, Qian J: High-sensitivity C-reactive protein: an independent risk factor for left ventricular hypertrophy in patients with lupus nephritis. J Biomed Biotechnol 2010, 2010:373-426.
• [8]Brull DJ, Serrano N, Zito F, Jones L, Montgomery HE, Rumley A, Sharma P, Lowe GD, World MJ, Humphries SE, Hingorani AD: Human CRP gene polymorphism influences CRP levels: implications for the prediction and pathogenesis of coronary heart disease. Arterioscler Thromb Vasc Biol. United States 2003, 23:2063-2069.
• [9]Ruckerl R, Greven S, Ljungman P, Aalto P, Antoniades C, Bellander T, Berglind N, Chrysohoou C, Forastiere F, Jacquemin B, et al.: Air pollution and inflammation (interleukin-6, C-reactive protein, fibrinogen) in myocardial infarction survivors. Environ Health Perspect 2007, 115:1072-1080.
• [10]Dutheil F, Lesourd B, Courteix D, Chapier R, Dore E, Lac G: Blood lipids and adipokines concentrations during a 6-month nutritional and physical activity intervention for metabolic syndrome treatment. Lipids Health Dis. England 2010, 9:148. BioMed Central Full Text
• [11]Hermsdorff HH, Zulet MA, Puchau B, Martinez JA: Fruit and vegetable consumption and proinflammatory gene expression from peripheral blood mononuclear cells in young adults: a translational study. Nutr Metab (Lond). England 2010, 7:42. BioMed Central Full Text
• [12]Ridker PM, Rifai N, Lowenthal SP: Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation 2001, 103:1191-1193.
• [13]Muhlestein JB, May HT, Jensen JR, Horne BD, Lanman RB, Lavasani F, Wolfert RL, Pearson RR, Yannicelli HD, Anderson JL: The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study. J Am Coll Cardiol 2006, 48:396-401.
• [14]Okopien B, Krysiak R, Kowalski J, Madej A, Belowski D, Zielinski M, Herman ZS: Monocyte release of tumor necrosis factor-alpha and interleukin-1beta in primary type IIa and IIb dyslipidemic patients treated with statins or fibrates. J Cardiovasc Pharmacol. United States 2005, 46:377-386.
• [15]Wi J, Kim JY, Park S, Kang SM, Jang Y, Chung N, Shim WH, Cho SY, Lee SH: Optimal pharmacologic approach to patients with hypertriglyceridemia and low high-density lipoprotein-cholesterol: randomized comparison of fenofibrate 160 mg and niacin 1500 mg. Atherosclerosis 2010, 213:235-240.
• [16]Hiukka A, Westerbacka J, Leinonen ES, Watanabe H, Wiklund O, Hulten LM, Salonen JT, Tuomainen TP, Yki-Jarvinen H, Keech AC, Taskinen MR: Long-term effects of fenofibrate on carotid intima-media thickness and augmentation index in subjects with type 2 diabetes mellitus. J Am Coll Cardiol 2008, 52:2190-2197.
• [17]Fegan PG, Shore AC, Mawson D, Tooke JE, MacLeod KM: Microvascular endothelial function in subjects with Type 2 diabetes and the effect of lipid-lowering therapy. Diabet Med. England 2005, 22:1670-1676.
• [18]Hogue JC, Lamarche B, Tremblay AJ, Bergeron J, Gagne C, Couture P: 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. Metabolism. United States 2008, 57:380-386.
• [19]Higgins JPT, Green S: Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. [http://www.cochrane-handbook.org] webcite 2011.
• [20]Bax L, Yu L-M, Ikeda N, Tsuruta H, Moons K: Development and validation of MIX: comprehensive free software for meta-analysis of causal research data. BMC Medical Research Methodology 2006, 6:50. BioMed Central Full Text
• [21]Bax L: MIX 1.7: Comprehensive free soft ware for metaanalysis of causal research data. [http://www.meta-analysis-made-easy.com/] webcite (Last accessed: August 16, 2011)
• [22]Orwin RG: A fail-safe N for effect size in meta-analysis. Journal of Educational Statistics 1983, 8:157-159.
• [23]Ikewaki K, Tohyama J, Nakata Y, Wakikawa T, Kido T, Mochizuki S: Fenofibrate effectively reduces remnants, and small dense LDL, and increases HDL particle number in hypertriglyceridemic men-a nuclear magnetic resonance study. J Atheroscler Thromb. Japan 2004, 11:278-285.
• [24]Pruski M, Krysiak R, Okopien B: Pleiotropic action of short-term metformin and fenofibrate treatment, combined with lifestyle intervention, in type 2 diabetic patients with mixed dyslipidemia. Diabetes Care. United States 2009, 32:1421-1424.
• [25]Koh KK, Han SH, Quon MJ, Yeal Ahn J, Shin EK: Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia. Diabetes Care. United States 2005, 28:1419-1424.
• [26]Coban E, Ozdogan M, Yazicioglu G, Sari R: The effect of fenofibrate on the levels of high sensitivity C-reactive protein in dyslipidaemic hypertensive patients. Int J Clin Pract. England 2005, 59:415-418.
• [27]Phuntuwate W, Suthisisang C, Koanantakul B, Chaloeiphap P, Mackness B, Mackness M: Effect of fenofibrate therapy on paraoxonase1 status in patients with low HDL-C levels. Atherosclerosis. Ireland 2008, 196:122-128.
• [28]Zhu S, Su G, Meng QH: Inhibitory effects of micronized fenofibrate on carotid atherosclerosis in patients with essential hypertension. Clin Chem. United States 2006, 52:2036-2042.
• [29]Goto M: A comparative study of anti-inflammatory and antidyslipidemic effects of fenofibrate and statins on rheumatoid arthritis. Mod Rheumatol 2010, 20:238-243.
• [30]Ansquer JC, Bekaert I, Guy M, Hanefeld M, Simon A: Efficacy and safety of coadministration of fenofibrate and ezetimibe compared with each as monotherapy in patients with type IIb dyslipidemia and features of the metabolic syndrome: a prospective, randomized, double-blind, three-parallel arm, multicenter, comparative study. Am J Cardiovasc Drugs. New Zealand 2009, 9:91-101.
• [31]Derosa G, Maffioli P, Salvadeo SA, Ferrari I, Gravina A, Mereu R, Palumbo I, D'Angelo A, Cicero AF: Fenofibrate, simvastatin and their combination in the management of dyslipidaemia in type 2 diabetic patients. Curr Med Res Opin 2009, 25:1973-1983.
• [32]Okopien B, Krysiak R, Herman ZS: Effects of short-term fenofibrate treatment on circulating markers of inflammation and hemostasis in patients with impaired glucose tolerance. J Clin Endocrinol Metab. United States 2006, 91:1770-1778.
• [33]Broncel M, Cieslak D, Koter-Michalak M, Duchnowicz P, Mackiewicz K, Chojnowska-Jezierska J: [The anti-inflammatory and antioxidants effects of micronized fenofibrate in patients with visceral obesity and dyslipidemia]. Pol Merkur Lekarski 2006, 20:547-550.
• [34]Keech AC, Mitchell P, Summanen PA, O'Day J, Davis TM, Moffitt MS, Taskinen MR, Simes RJ, Tse D, Williamson E, et al.: Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet. England 2007, 370:1687-1697.
• [35]Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, Macfadyen JG, et al.: Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 2009, 373:1175-1182.
• [36]Meier N, Nedeltchev K, Brekenfeld C, Galimanis A, Fischer U, Findling O, Remonda L, Schroth G, Mattle HP, Arnold M: Prior statin use, intracranial hemorrhage, and outcome after intra-arterial thrombolysis for acute ischemic stroke. Stroke. United States 2009, 40:1729-1737.
• [37]Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J: Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis 2006, 189:19-30.
• [38]Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, et al.: Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010, 375:735-742.
• [39]Buse JB, Bigger JT, Byington RP, Cooper LS, Cushman WC, Friedewald WT, Genuth S, Gerstein HC, Ginsberg HN, Goff DC Jr, et al.: Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol 2007, 99:21i-33i.
• [40]Kim CJ: Effects of fenofibrate on C-reactive protein levels in hypertriglyceridemic patients. J Cardiovasc Pharmacol. United States 2006, 47:758-763.
• [41]Undas A, Celinska-Lowenhoff M, Domagala TB, Iwaniec T, Dropinski J, Lowenhoff T, Szczeklik A: Early antithrombotic and anti-inflammatory effects of simvastatin versus fenofibrate in patients with hypercholesterolemia. Thromb Haemost. Germany 2005, 94:193-199.
• [42]Sebestjen M, Keber I, Zegura B, Simcic S, Bozic M, Fressart MM, Stegnar M: Statin and fibrate treatment of combined hyperlipidemia: the effects on some novel risk factors. Thromb Haemost. Germany 2004, 92:1129-1135.
• [43]Wang TD, Chen WJ, Lin JW, Cheng CC, Chen MF, Lee YT: Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles. Atherosclerosis. Ireland 2003, 170:315-323.
• [44]Krysiak R, Gdula-Dymek A, Bachowski R, Okopien B: Pleiotropic effects of atorvastatin and fenofibrate in metabolic syndrome and different types of pre-diabetes. Diabetes Care. United States 2010, 33:2266-2270.
• [45]Rosenson RS: Effect of fenofibrate on adiponectin and inflammatory biomarkers in metabolic syndrome patients. Obesity (Silver Spring). United States 2009, 17:504-509.
• [46]Belfort R, Berria R, Cornell J, Cusi K: Fenofibrate reduces systemic inflammation markers independent of its effects on lipid and glucose metabolism in patients with the metabolic syndrome. J Clin Endocrinol Metab. United States 2010, 95:829-836.