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Fibrates and future PPARalpha agonists in the treatment of cardiovascular disease.
Nat Clin Pract Cardiovasc Med 2008; 5(9):542-53NC

Abstract

Statins lower cardiovascular risk in patients with diabetes; however, as these patients are at higher risk than other cardiovascular patients, statins merely decrease coronary event rates to the level seen in untreated nondiabetic individuals at risk for cardiovascular disease, indicating the existence of substantial residual risk. One reasonable explanation resides in the fact that statins have only limited effectiveness on hypertriglyceridemia and low HDL cholesterol, and they do not normalize the LDL size-distribution pattern. Peroxisome proliferator-activated receptor (PPAR)alpha agonists, which include fibrates, normalize this atherogenic lipid profile, as well as several cardiovascular risk markers associated with the metabolic syndrome and type 2 diabetes. In particular, hypertriglyceridemia and the ratio of small dense:large buoyant LDL particles are significantly improved. Outcome trials of PPARalpha agonists have demonstrated reductions in cardiovascular morbidity in patients with diabetes and in those with the metabolic syndrome; plaque progression is diminished, diabetic nephropathy and retinopathy are counteracted and amputation-risk decreased. The combination of fibrates with statins improves overall lipoprotein profile further. PPARalpha agonists seem particularly indicated in patients with diabetes who have residual dyslipidemia (high triglyceride and/or low HDL) despite receiving statin therapy, and patients who are nondiabetic, overweight, insulin-resistant and who have hypertriglyceridemia and/or low HDL cholesterol and chronic inflammation.

Authors+Show Affiliations

Department of Atherosclerosis, Institut Pasteur de Lille, UMR545 Inserm, University of Lille 2, Lille, France. bart.staels@pasteur-lille.frNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

18628776

Citation

Staels, Bart, et al. "Fibrates and Future PPARalpha Agonists in the Treatment of Cardiovascular Disease." Nature Clinical Practice. Cardiovascular Medicine, vol. 5, no. 9, 2008, pp. 542-53.
Staels B, Maes M, Zambon A. Fibrates and future PPARalpha agonists in the treatment of cardiovascular disease. Nat Clin Pract Cardiovasc Med. 2008;5(9):542-53.
Staels, B., Maes, M., & Zambon, A. (2008). Fibrates and future PPARalpha agonists in the treatment of cardiovascular disease. Nature Clinical Practice. Cardiovascular Medicine, 5(9), pp. 542-53. doi:10.1038/ncpcardio1278.
Staels B, Maes M, Zambon A. Fibrates and Future PPARalpha Agonists in the Treatment of Cardiovascular Disease. Nat Clin Pract Cardiovasc Med. 2008;5(9):542-53. PubMed PMID: 18628776.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibrates and future PPARalpha agonists in the treatment of cardiovascular disease. AU - Staels,Bart, AU - Maes,Michel, AU - Zambon,Alberto, Y1 - 2008/07/15/ PY - 2007/12/05/received PY - 2008/04/29/accepted PY - 2008/7/17/pubmed PY - 2008/10/24/medline PY - 2008/7/17/entrez SP - 542 EP - 53 JF - Nature clinical practice. Cardiovascular medicine JO - Nat Clin Pract Cardiovasc Med VL - 5 IS - 9 N2 - Statins lower cardiovascular risk in patients with diabetes; however, as these patients are at higher risk than other cardiovascular patients, statins merely decrease coronary event rates to the level seen in untreated nondiabetic individuals at risk for cardiovascular disease, indicating the existence of substantial residual risk. One reasonable explanation resides in the fact that statins have only limited effectiveness on hypertriglyceridemia and low HDL cholesterol, and they do not normalize the LDL size-distribution pattern. Peroxisome proliferator-activated receptor (PPAR)alpha agonists, which include fibrates, normalize this atherogenic lipid profile, as well as several cardiovascular risk markers associated with the metabolic syndrome and type 2 diabetes. In particular, hypertriglyceridemia and the ratio of small dense:large buoyant LDL particles are significantly improved. Outcome trials of PPARalpha agonists have demonstrated reductions in cardiovascular morbidity in patients with diabetes and in those with the metabolic syndrome; plaque progression is diminished, diabetic nephropathy and retinopathy are counteracted and amputation-risk decreased. The combination of fibrates with statins improves overall lipoprotein profile further. PPARalpha agonists seem particularly indicated in patients with diabetes who have residual dyslipidemia (high triglyceride and/or low HDL) despite receiving statin therapy, and patients who are nondiabetic, overweight, insulin-resistant and who have hypertriglyceridemia and/or low HDL cholesterol and chronic inflammation. SN - 1743-4300 UR - https://www.unboundmedicine.com/medline/citation/18628776/Fibrates_and_future_PPARalpha_agonists_in_the_treatment_of_cardiovascular_disease_ L2 - http://dx.doi.org/10.1038/ncpcardio1278 DB - PRIME DP - Unbound Medicine ER -