Effects of atorvastatin on inflammatory and fibrinolytic parameters in patients with chronic kidney disease.
Although substantial evidence suggests that treatment of dyslipidemia with statins reduces mortality and morbidity that are associated with cardiovascular disease, only a few studies have examined the efficacy of statins on inflammatory and fibrinolytic status in patients with chronic kidney disease (CKD). A 6-mo, prospective, randomized study was designed to assess the efficacy of atorvastatin in reducing circulating inflammatory and fibrinolytic parameters in patients with CKD. Sixty-six patients with CKD (stages 2, 3, and 4) and LDL cholesterol levels > or =100 mg/dl were randomly assigned (2:1) to receive 20 mg/d atorvastatin (n = 44) or nonatorvastatin therapy (n = 22). Lipid profile, renal function, fibrinolytic balance (tissue plasminogen activator [t-PA] and plasminogen activator inhibitor-1), and inflammatory markers (C-reactive protein [CRP], IL-1 beta, IL-6, and TNF-alpha) were measured before and 6 mo after atorvastatin was added to the treatment. Twenty-five age-matched individuals with normal renal function (estimated GFR >90 ml/min) were used as healthy control subjects. Patients with CKD had higher CRP, IL-1 beta, TNF-alpha, and IL-6 levels than age-matched population with normal renal function. t-PA concentration was higher in patients with CKD (P = 0.000). Plasminogen activator inhibitor-1 values were comparable in all patients. Total cholesterol and LDL cholesterol were significantly reduced only in patients who received atorvastatin. In addition to the hypolipidemic effect, atorvastatin treatment significantly reduced inflammatory parameters: CRP (median 4.1 to 2.9; P = 0.015), TNF-alpha (6.0 +/- 2.7 to 4.7 +/- 2.4; P = 0.046), and IL-1 beta levels (1.9 +/- 0.7 to 1.2 +/- 0.7; P = 0.001). These parameters remained unchanged in patients who were not treated with atorvastatin. Fibrinolytic parameters were not modified by atorvastatin treatment. Patients with CKD showed higher levels of inflammatory parameters and t-PA levels than age-matched healthy control subjects. Atorvastatin treatment, in addition to its beneficial effect on cholesterol levels, improved the inflammatory state of these patients without modifying fibrinolytic balance.
Goicoechea
Marian
M
Department of Nephrology, Hospital General Universitario Gregorio Marañon, C/Dr. Esquerdo 47, 28007 Madrid, Spain. albvia@terra.es
de Vinuesa
Soledad García
SG
Lahera
Vicente
V
Cachofeiro
Victoria
V
Gómez-Campderá
Francisco
F
Vega
Almudena
A
Abad
Soraya
S
Luño
José
J
D000368:Aged; D000369:Aged, 80 and over; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011446:Prospective Studies; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000097:blood
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D011758:Pyrroles; D005340:Fibrinogen; D002097:C-Reactive Protein; D000069059:Atorvastatin; D010959:Tissue Plasminogen Activator