Prognostic significance of visit-to-visit variability, and maximum and minimum LDL cholesterol in diabetes mellitus

Lipids Health Dis. 2022 Feb 10;21(1):19. doi: 10.1186/s12944-022-01628-8.

Abstract

Background: 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.

Methods: The 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).

Results: Compared 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.

Conclusions: Visit-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: NCT00000620.

Keywords: ACCORD trial; Diabetes mellitus; LDL cholesterol; Variability.

MeSH terms

  • Cholesterol / blood
  • Cholesterol, LDL / blood*
  • Coronary Disease / diagnosis
  • Coronary Disease / mortality
  • Coronary Disease / prevention & control
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / mortality
  • Dyslipidemias / drug therapy
  • Female
  • Fenofibrate / therapeutic use
  • Humans
  • Hypolipidemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Time Factors
  • Triglycerides / blood

Substances

  • Cholesterol, LDL
  • Hypolipidemic Agents
  • Triglycerides
  • Cholesterol
  • Fenofibrate

Associated data

  • ClinicalTrials.gov/NCT00000620