DOI QR코드

DOI QR Code

Fenofibrate Reduces C-Reactive Protein Levels in Hypertriglyceridemic Patients With High Risks for Cardiovascular Diseases

  • Min, Yun Joo (Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Choi, Young Hwan (Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Hyeon, Cheol Won (Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Cho, Jun Hwan (Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Kim, Kyung Joon (Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Kwon, Jee Eun (Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Kim, Eun Young (Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Lee, Wang-Soo (Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Lee, Kwang Je (Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Kim, Sang-Wook (Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Kim, Tae Ho (Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Kim, Chee Jeong (Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University)
  • Published : 2012.11.30

Abstract

Background and Objectives: The effects of fenofibrate on C-reactive protein (CRP) are under debate. We investigated the effect of fenofibrate on CRP levels and the variables determining changes. Subjects and Methods: This case-control study enrolled 280 hypertriglyceridemic patients who were managed either with 200 mg of fenofibrate (Fenofibrate group, n=140) or with standard treatment (comparison group, n=140). CRP levels were measured before and after management for 2 months. Results: CRP levels decreased in both the fenofibrate (p=0.003) and comparison (p=0.048) groups. Changes in CRP levels were not significantly different between the two groups (p=0.27) and were negatively associated with baseline CRP levels (r=-0.47, p<0.001). In patients with a baseline CRP $level{\geq}1$ mg/L, CRP levels also decreased in both groups (p=0.000 and p=0.001 respectively), however, more in the fenofibrate group than in the comparison group (p=0.025). The reduction of CRP was associated with higher baseline CRP levels (r=-0.29, p=0.001), lower body mass index (BMI, r=0.23, p=0.007), and fenofibrate therapy (r=0.19, p=0.025). CRP levels decreased more in the fenofibrate group than in the comparison group in patients with a BMI ${\leq}$26 kg/m2 with borderline significance ($-1.21{\pm}1.82$ mg/L vs. $-0.89{\pm}1.92$ mg/L, p=0.097). In patients with a high density lipoprotein-cholesterol level <40 mg/dL, CRP levels were reduced only in the fenofibrate group (p=0.006). Conclusion: Fenofibrate reduced CRP levels in hypertriglyceridemic patients with high CRP and/or low high density lipoprotein-cholesterol levels and without severe overweight. This finding suggests that fenofibrate may have an anti-inflammatory effect in selected patients.

Keywords

References

  1. Shah A, Rader DJ, Millar JS. The effect of PPAR-alpha agonism on apolipoprotein metabolism in humans. Atherosclerosis 2010;210:35-40. https://doi.org/10.1016/j.atherosclerosis.2009.11.010
  2. Frick MH, Elo O, Haapa K, Heinonen OP, et al. Helsinki Heart Study: primary- prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987;317:1237-45. https://doi.org/10.1056/NEJM198711123172001
  3. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of highdensity lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 341:410-8. https://doi.org/10.1056/NEJM199908053410604
  4. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation 2000;102:21-7. https://doi.org/10.1161/01.CIR.102.1.21
  5. Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005;366:1849-61. https://doi.org/10.1016/S0140-6736(05)67667-2
  6. ACCORD Study Group, Ginsberg HN, Elam MB, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010;362:1563-74. https://doi.org/10.1056/NEJMoa1001282
  7. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340:115-26. https://doi.org/10.1056/NEJM199901143400207
  8. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003;107:363-9. https://doi.org/10.1161/01.CIR.0000053730.47739.3C
  9. Staels B, Koenig W, Habib A, et al. Activation of human aortic smoothmuscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature 1998;393:790-3. https://doi.org/10.1038/31701
  10. Malik J, Melenovsky V, Wichterle D, et al. Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial--FAT). Cardiovasc Res 2001;52:290-8. https://doi.org/10.1016/S0008-6363(01)00382-0
  11. Wu TJ, Ou HY, Chou CW, Hsiao SH, Lin CY, Kao PC. Decrease in inflammatory cardiovascular risk markers in hyperlipidemic diabetic patients treated with fenofibrate. Ann Clin Lab Sci 2007;37:158-66.
  12. Cortellaro M, Cofrancesco E, Boschetti C, et al. Effects of fluvastatin and bezafibrate combination on plasma fibrinogen, t-plasminogen activator inhibitor and C reactive protein levels in coronary artery disease patients with mixed hyperlipidaemia (FACT study). Fluvastatin Alone and in Combination Treatment. Thromb Haemost 2000;83:549-53.
  13. Gomez-Gerique JA, Ros E, Olivan J, et al. Effect of atorvastatin and bezafibrate on plasma levels of C-reactive protein in combined (mixed) hyperlipidemia. Atherosclerosis 2002;162:245-51. https://doi.org/10.1016/S0021-9150(01)00708-0
  14. 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 2003;170:315-23. https://doi.org/10.1016/S0021-9150(03)00296-X
  15. Hogue JC, Lamarche B, Tremblay AJ, Bergeron J, Gagné 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 2008;57:380-6. https://doi.org/10.1016/j.metabol.2007.10.014
  16. Muhlestein JB, May HT, Jensen JR, et al. 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. https://doi.org/10.1016/j.jacc.2006.05.009
  17. Jonkers IJ, Mohrschladt MF, Westendorp RG, van der Laarse A, Smelt AH. Severe hypertriglyceridemia with insulin resistance is associated with systemic inflammation: reversal with bezafibrate therapy in a randomized controlled trial. Am J Med 2002;112:275-80. https://doi.org/10.1016/S0002-9343(01)01123-8
  18. Farnier M, Freeman MW, Macdonell G, et al. Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia. Eur Heart J 2005;26:897-905. https://doi.org/10.1093/eurheartj/ehi231
  19. 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 2010;95:829-36. https://doi.org/10.1210/jc.2009-1487
  20. Ye P, Li JJ, Su G, Zhang C. Effects of fenofibrate on inflammatory cytokines and blood pressure in patients with hypertriglyceridemia. Clin Chim Acta 2005;356:229-32. https://doi.org/10.1016/j.cccn.2005.01.023
  21. Okopien B, Krysiak R, Kowalski J, et al. 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 2005;46:377-86. https://doi.org/10.1097/01.fjc.0000175455.46245.c8
  22. 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 2006;91:1770-8. https://doi.org/10.1210/jc.2005-1615
  23. Kim CJ. Effects of fenofibrate on C-reactive protein levels in hypertriglyceridemic patients. J Cardiovasc Pharmacol 2006;47:758-63. https://doi.org/10.1097/01.fjc.0000211787.30034.0a
  24. Haim M, Benderly M, Tanne D, et al. C-reactive protein, bezafibrate, and recurrent coronary events in patients with chronic coronary heart disease. Am Heart J 2007;154:1095-101. https://doi.org/10.1016/j.ahj.2007.07.026
  25. Hiukka A, Westerbacka J, Leinonen ES, et al. 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;52:2190-7. https://doi.org/10.1016/j.jacc.2008.09.049
  26. Shin HS, Sung KC, Kim BJ, et al. Effect of exercise on serum C-reactive protein. Korean Circ J 2005;35:533-8. https://doi.org/10.4070/kcj.2005.35.7.533
  27. Kim SJ, Lee KE, Lee SH, et al. Effect of fibrate on lipoprotein(a) level in hypertriglyceridemic patients. Korean Circ J 2005;35:30-6. https://doi.org/10.4070/kcj.2005.35.1.30
  28. Ridker PM, Rifai N, Pfeffer MA, et al. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1998;98:839-44. https://doi.org/10.1161/01.CIR.98.9.839
  29. Shen J, Ordovas JM. Impact of genetic and environmental factors on hsCRP concentrations and response to therapeutic agents. Clin Chem 2009;55:256-64.

Cited by

  1. Fibrates in the management of atherogenic dyslipidemia vol.15, pp.12, 2012, https://doi.org/10.1080/14779072.2017.1408410
  2. Benefits and risks of the treatment with fibrates--a comprehensive summary vol.11, pp.11, 2012, https://doi.org/10.1080/17512433.2018.1537780