American Journal of Kidney Diseases
Volume 49, Issue 6 , Pages 776-785 , June 2007

A Randomized Trial of the Effect of Statin and Fibrate Therapy on Arterial Function in CKD

  • Gursharan Dogra, MBBCh, FRACP, PhD

      Affiliations

    • School of Medicine and Pharmacology, University of Western Australia and Western Australian Heart Research Institute, Perth, Western Australia
    • Department of Nephrology, Royal Perth Hospital, Perth, Western Australia.
    • Corresponding Author InformationAddress correspondence to Gursharan Dogra, MBBCh, FRACP, PhD, School of Medicine and Pharmacology, Level 4, MRF Bldg, Royal Perth Hospital, Box X2213 GPO Perth, Western Australia 6847.
  • ,
  • Ashley Irish, MBBS, FRACP

      Affiliations

    • Department of Nephrology, Royal Perth Hospital, Perth, Western Australia.
  • ,
  • Dick Chan, PhD

      Affiliations

    • School of Medicine and Pharmacology, University of Western Australia and Western Australian Heart Research Institute, Perth, Western Australia
  • ,
  • Gerald Watts, MD, PhD, FRCP, FRACP

      Affiliations

    • School of Medicine and Pharmacology, University of Western Australia and Western Australian Heart Research Institute, Perth, Western Australia

Received 23 October 2006 ,Accepted 6 March 2007.

References 

  1. Baigent C, Burbury K, Wheeler D. Premature cardiovascular disease in chronic renal failure. Lancet. 2000;356:147–152
  2. Lowrie EG, Lew NL. Death risk in hemodialysis patients: The predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis. 1990;15:458–482
  3. Liu Y, Coresh J, Eustace JA, et al. Association between cholesterol level and mortality in dialysis patients: Role of inflammation and malnutrition. JAMA. 2004;291:451–459
  4. Tonelli M, Isles C, Curhan GC, et al. Effect of pravastatin on cardiovascular events in people with chronic kidney disease. Circulation. 2004;110:1557–1563
  5. Tonelli M, Collins D, Robins S, et al. Effect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease. Am J Kidney Dis. 2004;44:832–839
  6. Wanner C, Krane V, Marz W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353:238–248
  7. Isbel NM, Haluska B, Johnson DW, et al. Increased targeting of cardiovascular risk factors in patients with chronic kidney disease does not improve atheroma burden or cardiovascular function. Am Heart J. 2006;151:745–753
  8. Rakhit DJ, Marwick TH, Armstrong KA, et al. Effect of aggressive risk factor modification on cardiac events and myocardial ischaemia in patients with chronic kidney disease. Heart. 2006;92:1402–1408
  9. Blacher J, Guerin AP, Pannier B, et al. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension. 2001;38:938–942
  10. Yeun JY, Kaysen GA. C-Reactive protein, oxidative stress, homocysteine, and troponin as inflammatory and metabolic predictors of atherosclerosis in ESRD. Curr Opin Nephrol Hypertens. 2000;9:621–630
  11. Irish AB, Green FR. Factor VII coagulant activity (VIIc) and hypercoagulability in chronic renal disease and dialysis: Relationship with dyslipidaemia, inflammation, and factor VII genotype. Nephrol Dial Transplant. 1998;13:679–684
  12. Treasure CB, Klein JL, Weintraub WS, et al. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med. 1995;332:481–487
  13. Dogra GK, Watts GF, Chan DC, et al. Statin therapy improves brachial artery vasodilator function in patients with type 1 diabetes and microalbuminuria. Diabet Med. 2005;22:239–242
  14. Vaughan CJ, Gotto AM, Basson CT. The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol. 2000;35:1–10
  15. Irish AB, Thompson CH. The effects of gemfibrozil upon the hypercoagulable state in dyslipidaemic patients with chronic renal failure. Nephrol Dial Transplant. 1996;11:2223–2228
  16. Watts GF, Dimmitt SB. Fibrates, dyslipoproteinaemia and cardiovascular disease. Curr Opin Lipidol. 1999;10:561–574
  17. Rubanyi GM. The role of endothelium in cardiovascular homeostasis and diseases. J Cardiovasc Pharmacol. 1993;22(suppl 4):S1–S14
  18. Suwaidi JA, Hamasaki S, Higano ST, et al. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000;101:948–954
  19. Neunteufl T, Heher S, Katzenschlager R, et al. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol. 2000;86:207–210
  20. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation. 2000;101:1899–1906
  21. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111–1115
  22. Woodman RJ, Watts GF. Measurement and application of arterial stiffness in clinical research: Focus on new methodologies and diabetes mellitus. Med Sci Monit. 2003;9:RA81–RA89
  23. Grey E, Bratteli C, Glasser SP, et al. Reduced small artery but not large artery elasticity is an independent risk marker for cardiovascular events. Am J Hypertens. 2003;16:265–269
  24. London GM, Guerin AP, Marchais SJ, et al. Cardiac and arterial interactions in end-stage renal disease. Kidney Int. 1996;50:600–608
  25. London GM. Arterial function in renal failure. Nephrol Dial Transplant. 1998;13(suppl 4):S12–S15
  26. Blacher J, Safar ME, Guerin AP, et al. Aortic pulse wave velocity index and mortality in end-stage renal disease. Kidney Int. 2003;63:1852–1860
  27. London GM, Blacher J, Pannier B, et al. Arterial wave reflections and survival in end-stage renal failure. Hypertension. 2001;38:434–438
  28. Tsunekawa T, Hayashi T, Kano H, et al. Cerivastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, improves endothelial function in elderly diabetic patients within 3 days. Circulation. 2001;104:376–379
  29. McVeigh GE, Brennan GM, Cohn JN, et al. Fish oil improves arterial compliance in non-insulin-dependent diabetes mellitus. Arterioscler Thromb. 1994;14:1425–1429
  30. Nestel PJ, Pomeroy SE, Sasahara T, et al. Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidizability. Arterioscler Thromb Vasc Biol. 1997;17:1163–1170
  31. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis Model Assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–419
  32. Woodman RJ, Playford DA, Watts GF, et al. Improved analysis of brachial artery ultrasound using a novel edge-detection software system. J Appl Physiol. 2001;91:929–937
  33. Dogra G, Irish A, Chan D, et al. Insulin resistance, inflammation, and blood pressure determine vascular dysfunction in CKD. Am J Kidney Dis. 2006;48:926–934
  34. Fathi R, Isbel N, Short L, et al. The effect of long-term aggressive lipid lowering on ischemic and atherosclerotic burden in patients with chronic kidney disease. Am J Kidney Dis. 2004;43:45–52
  35. Ichihara A, Hayashi M, Ryuzaki M, et al. Fluvastatin prevents development of arterial stiffness in haemodialysis patients with type 2 diabetes mellitus. Nephrol Dial Transplant. 2002;17:1513–1517
  36. Holdaas H, Fellstrom B, Jardine AG, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: A multicentre, randomised, placebo-controlled trial. Lancet. 2003;361:2024–2031
  37. Baigent C, Landry M. Study of Heart and Renal Protection (SHARP). Kidney Int Suppl. 2003;84:S207–S210
  38. Seliger SL, Weiss NS, Gillen DL, et al. HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients. Kidney Int. 2002;61:297–304
  39. Mason NA, Bailie GR, Satayathum S, et al. HMG-coenzyme A reductase inhibitor use is associated with mortality reduction in hemodialysis patients. Am J Kidney Dis. 2005;45:119–126
  40. Jardine AG, Holdaas H, Fellstrom B, et al. Fluvastatin prevents cardiac death and myocardial infarction in renal transplant recipients: Post-hoc subgroup analyses of the ALERT Study. Am J Transplant. 2004;4:988–995
  41. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet. 2002;360:7–22
  42. Shinohara K, Shoji T, Emoto M, et al. Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease. J Am Soc Nephrol. 2002;13:1894–1900
  43. London GM, Guerin AP, Marchais SJ, et al. Arterial media calcification in end-stage renal disease: Impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003;18:1731–1740
  44. Alaupovic P, Attman PO, Knight-Gibson C, et al. Effect of fluvastatin on apolipoprotein-defined lipoprotein subclasses in patients with chronic renal insufficiency. Kidney Int. 2006;69:1865–1871

 Support: This study was supported by Medical Research Grants from Pfizer Cardiovascular Lipid (CVL) grants, the Faculty of Medicine and Dentistry at the University of Western Australia, and the Royal Perth Hospital Medical Research Foundation. Potential conflicts of interest: None.

 Trial registration: www.cochrane-renal.org; study number: CRG080500011.

 Originally published online as doi:10.1053/j.ajkd.2007.03.003 on April 25, 2007.

PII: S0272-6386(07)00560-4

doi: 10.1053/j.ajkd.2007.03.003

American Journal of Kidney Diseases
Volume 49, Issue 6 , Pages 776-785 , June 2007