Abstract

BackgroundCurrent guidelines for dyslipidemia management recommend that the LDL-C goal be lower than 70 mg/dL. The present study investigated the prognostic significance of visit-to-visit variability in LDL-C, and minimum and maximum LDL-C during follow-up in diabetes mellitus.MethodsThe risk of outcomes in relation to visit-to-visit LDL-C variability was investigated in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial. LDL-C variability indices were coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV). Multivariable Cox proportional hazards models were employed to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI).ResultsCompared with the placebo group (n=2667), the fenofibrate therapy group (n=2673) had a significantly (P<0.01) lower mean plasma triglyceride (152.5 vs. 178.6 mg/dL), and total cholesterol (158.3 vs.162.9 mg/dL) but a similar mean LDL-C during follow-up (88.2 vs. 88.6 mg/dL, P>0.05). All three variability indices were associated with primary outcome, total mortality and cardiovascular mortality both in the total population and in the fenofibrate therapy group but only with primary outcome in the placebo group. The minimum LDL-C but not the maximum during follow-up was significantly associated with various outcomes in the total population, fenofibrate therapy and placebo group. The minimum LDL-C during follow-up ≥70 mg/dL was associated with an increased risk for various outcomes.ConclusionsVisit-to-visit variability in LDL-C was a strong predictor of outcomes, independent of mean LDL-C. Patients with LDL-C controlled to less than 70 mg/dL during follow-up might have a benign prognosis.ClinicalTrials.gov number: NCT 00000620.

Highlights

  • Current guidelines for dyslipidemia management recommend that the low-density lipoprotein cholesterol (LDL-C) goal be lower than 70 mg/dL

  • Visit-to-visit variability in LDL-C was a strong predictor of outcomes, independent of mean LDL-C

  • For LDL-C variability indices, the fenofibrate group showed no difference in mean LDL-C level and LDL-C variability independent of the mean (VIM) but lower standard deviation (SD) and average real variability (ARV)

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Summary

Introduction

Current guidelines for dyslipidemia management recommend that the LDL-C goal be lower than 70 mg/dL. The present study investigated the prognostic significance of visit-to-visit variability in LDL-C, and minimum and maximum LDL-C during follow-up in diabetes mellitus. The role of monitoring the level of LDL-C using a target-oriental method in patients on lipid-lowering therapy remains controversial [4]. Previous observational studies in diabetes have raised concerns on visit-to-visit lipid variability in relation to longterm major adverse cardiac events. The post-hoc analysis of the Treating to New Targets (TNT) trial showed that visitto-visit LDL-C variability was an independent predictor of cardiovascular events in patients 35 to 75 years of age who had known coronary artery disease [7]. No studies have concerned the prognostic value of visit-to-visit LDL-C variability and persistence of LDL-C control in type 2 diabetes at high cardiovascular risk

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