Joint effect of visit-to-visit variability in LDL-cholesterol, HDL-cholesterol and HbA1c on cardiovascular and total mortality in patients with diabetes

BACKGROUND: We aimed to investigate the joint effect of visit-to-visit variability (VVV) in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides and glycosylated hemoglobin (HbA1c) on cardiovascular mortality and total mortality in patients with diabetes. METHODS: Among 5194 participants with type 2 diabetes enrolled in the ACCORD lipid trial, VVVs of LDL-C, triglycerides, HDL-C, and HbA1c were assessed from baseline to 2 years of follow-up and expressed as coefficient of variation (CV). The study outcomes included cardiovascular mortality and all-cause mortality. RESULTS: Over a median follow-up of 3.0 years from the end of variability measurements at years 2, there were 305 (5.9%) cases of all-cause mortality, of which, 144 were cardiovascular causes. The positive relations between LDL-C CV and cardiovascular mortality were significantly stronger among participants with higher HDL-C CV (P for interaction = 0.023), and higher HbA1c CV (P for interaction = 0.015). However, there were no significant interactions between LDL-C CV and triglycerides CV (P for interaction = 0.591). Similar trends were found for all-cause mortality. Consistently, there were graded trends in the risk of mortality with the increasing numbers of higher CV of the three variables: LDL-C, HbA1c, and HDL-C (P for trend = 0.008 for cardiovascular mortality, and P for trend < 0.001 for all-cause mortality). CONCLUSION: VVVs in LDL-C, HDL-C, and HbA1c may jointly affect the risks of cardiovascular and all-cause mortality in diabetes patients. Those with higher CVs of all three variables had the highest risks of cardiovascular and all-cause mortality.