A comparison of the effects of low- and high-dose atorvastatin on lipoprotein metabolism and inflammatory cytokines in type 2 diabetes: Results from the Protection Against Nephropathy in Diabetes with Atorvastatin (PANDA) randomized trial

J Clin Lipidol. 2018 Jan-Feb;12(1):44-55. doi: 10.1016/j.jacl.2017.10.011. Epub 2017 Nov 13.

Abstract

Background: Statin therapy is recommended in type 2 diabetes (T2DM) although views on treatment intensity and therapeutic targets remain divided.

Objectives: Our objectives were to compare the effects of high-intensity and moderate-intensity atorvastatin treatment on lipoprotein metabolism and inflammatory markers and how frequently treatment goals are met in high-risk T2DM patients.

Methods: Patients with T2DM and albuminuria (urinary albumin:creatinine ratio >5 mg/mmol, total cholesterol <7 mmol/L, proteinuria <2 g/d, creatinine <200 μmol/L) were randomized to receive atorvastatin 10 mg (n = 59) or 80 mg (n = 60) daily. Baseline and 1-year follow-up data are reported.

Results: Patients were at high cardiovascular disease risk (observed combined mortality and nonfatal cardiovascular disease annual event rate 4.8%). The non-high-density lipoprotein cholesterol (HDL-C) goal of <2.6 mmol/L was achieved in 72% of participants receiving high-dose atorvastatin, but only in 40% on low-dose atorvastatin (P < .005). The proportion achieving apolipoprotein B (apoB) <0.8 g/L on high-dose and low-dose atorvastatin was 82% and 70%, respectively (NS). Total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, non-HDL-C, oxidized LDL, apoB, glyc-apoB, apolipoprotein E, and lipoprotein-associated phospholipase A2 decreased significantly, more so in participants on high-dose atorvastatin. Adiponectin increased and serum amyloid A decreased without dose dependency. Neither dose produced significant changes in HDL-C, cholesterol efflux, high-sensitivity C-reactive protein, glycated hemoglobin, serum paraoxonase-1, lecithin:cholesterol acyltransferase, or cholesteryl ester transfer protein.

Conclusions: High-dose atorvastatin is more effective in achieving non-HDL-C therapeutic goals and in modifying LDL-related parameters. Recommended apoB treatment targets may require revision. Despite the increase in adiponectin and the decrease in serum amyloid A, HDL showed no change in functionality.

Keywords: Apolipoprotein B; Atorvastatin; Glycated apolipoprotein B; High-density lipoprotein; Inflammatory cytokines; Low-density lipoprotein; Therapeutic targets; Type 2 diabetes mellitus; Very-low-density lipoprotein.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria / diagnosis
  • Anticholesteremic Agents / therapeutic use*
  • Apolipoproteins B / blood
  • Atorvastatin / therapeutic use*
  • Cholesterol, LDL / blood
  • Cytokines / metabolism*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Down-Regulation
  • Drug Administration Schedule
  • Female
  • Humans
  • Lipoproteins, LDL / blood
  • Male
  • Middle Aged
  • Serum Amyloid A Protein / analysis
  • Treatment Outcome
  • Triglycerides / blood

Substances

  • Anticholesteremic Agents
  • Apolipoproteins B
  • Cholesterol, LDL
  • Cytokines
  • Lipoproteins, LDL
  • Serum Amyloid A Protein
  • Triglycerides
  • oxidized low density lipoprotein
  • Atorvastatin

Associated data

  • ISRCTN/ISRCTN58196433