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

Chang-Sheng Sheng, Ya Miao, Lili Ding, Yi Cheng, Dan Wang, Yulin Yang, Jingyan Tian, Chang-Sheng Sheng, Ya Miao, Lili Ding, Yi Cheng, Dan Wang, Yulin Yang, Jingyan Tian

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.

Conflict of interest statement

No potential conflicts of interest relevant to this article were reported.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Hazard ratios for risk of outcomes by decile of LDL cholesterol variability indices. All hazard ratios for the primary outcome (B), all-cause death (C) and cardiovascular death (D) were adjusted for the mean lipid during visits, sex, and baseline age, education, body mass index, systolic and diastolic blood pressure, smoking, drinking, and fasting plasma glucose. Hazard ratios and 95% confidence intervals for each decile relative to the first decile in the placebo group and for each 10-percentile point increase in variability were estimated in a single model. The distributions of variability indices are also shown (A). VIM indicates variability independent of the mean (left); ARV, average real variability (middle); and MMD, the difference of maximum minus minimum LDL-C (right).

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