Statin-Induced Increase in HDL-C and Renal Function in Coronary Heart Disease Patients§

Abstract

Background:Little is known about the potential of statin-induced high-density lipoprotein cholesterol (HDL-C) increase to improve renal function in coronary heart disease (CHD) patients. Methods and Results:In this post hoc analysis of the GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study we investigated the effect of HDL-C increase after statin treatment on renal function. From a total of 1,600 patients, 880 were on various statins (mainly atorvastatin) and 720 were not. Other secondary prevention therapies were similar in the 2 groups. After a 3 year follow up, the lipid profile was unchanged in the statin untreated group and estimated glomerular filtration rate (eGFR) was reduced by 5.1% compared with baseline (P<0.0001). In contrast, in the statin treated group non-HDL-C was reduced by 43%, HDL-C was increased by 7% and there was a significant increase in eGFR compared with baseline by 9.8% (P<0.0001). In multiple regression analysis, the mean 7% increase in HDL-C in the treated arm during the entire study was associated with a 5.6% increase in eGFR recorded after the 6 th week of treatment. The odds ratio of eGFR increase with every 5% statin-induced rise in HDL-C was 1.78 (95% confidence interval 1.19-3.34; P=0.001).Conclusions: Statin treatment significantly improved renal function. Statin-induced HDL-C increase significantly and independently contributed to this improvement. This finding supports the concept that improving lipid variables other than low density lipoprotein cholesterol is also beneficial to preserving renal function.

Effects of Pitavastatin (LIVALO Tablet) on the Estimated Glomerular Filtration Rate (eGFR) in Hypercholesterolemic Patients with Chronic Kidney Disease

“…Also, the amount change of HDL-C was identified as a significant factor influencing changes in the eGFR during pitavastatin treatment; therefore, the increase of HDL-C might be attributed to the increase of the eGFR. In fact, the results of sub-analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study suggested a relation between increased serum HDL-C and increased eGFR following atorvastatin treatment 21) . The antioxidant effects of HDL-C were considered to possibly underlie this correlation 22) ; however, further analysis is needed to clarify the mechanism underlying the increase of the eGFR induced by pitavastatin.…”

Statins in Type 2 Diabetes

“…The IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) [42,43] and TNT (Treating to New Targets) trials [44,45] demonstrate that both low (10 mg/day) and high (80 mg/day) doses of atorvastatin reduced the risk of non-fatal myocardial infarction by 17-22% (p < 0.02). [42][43][44][45] Sub-studies of the GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation) [45][46][47][48], TNT (Treating to New Targets) [43,[49][50][51] and PROVE-IT (PRavastatin Or atorVastatin Evaluation and Infection Therapy) [52][53][54] trials showed similar results of atorvastatin reduced cardiac events but not only patients without diabetes but also in those with diabetes. Those studies included 15-25% of patients with diabetes.…”

“…In the GREACE sub-study, which compared to physicians'standard care [47], atorvastatin significantly reduced the relative risk of total mortality and cardiac moratility and morbidity (coronary mortality, coronary morbidity, and stroke). Furthermore, atorvastatin improved renal function [47] and liver function [46]. Of interest, patients with non-alcoholic fatty liver disease, statins (atorvastatin 24 mg/day) improved liver function, although liver injury was worsen in others without statin treatment for dyslipidemia.…”

“…In addition, there were no differences in effects on renal function between high-dose versus low-dose. This comparison was performed in the 24 placebo-controlled trials including IDEAL [57], TNT [47], CARDS [69,70], ASPEN (The Atorvastatin Study for Prevention of coronary heart disease Endopoints in Non-diabeties mellitus) [58], SPARCL (The Stroke Prevention by Aggressive Reduction in Cholesterol Levels) [43,71], and other large study using placebo with 10,345 patients with atorvastatin and 8945 patients with placebo. [43] The TNT trial in 10,001 CHD patients with and without pre-existing chronic kidney diseases demonstrated efficacy of atorvastatin (80 mg/day) on reduction of CHD risk as well as improving renal function in both with and without pre-existing renal injury patients.…”

Place of pitavastatin in the statin armamentarium: promising evidence for a role in diabetes mellitus

“…In the GREACE study, various statin treatments (mainly atorvastatin) over 3 years significantly increased eGFR by 9.8% ( P < 0.0001, n = 880). Multiple regression analysis showed that every 5% statin-induced HDL cholesterol increase significantly and independently contributed to eGFR improvement 59. Furthermore, in patients with early diabetic nephropathy, pitavastatin 1 mg/day (n = 10) significantly reduced urinary albumin excretion and urinary liver-type fatty acid-binding protein (L-FABP), which reflected the extent of tubulointerstitial damage 60…”