High visit-to-visit cholesterol variability predicts heart failure and adverse cardiovascular events: a population-based cohort study

Background: Dyslipidaemia is associated with adverse cardiovascular outcomes. However, the long-term prognostic value of visit-to-visit cholesterol variability for the risks of heart failure (HF) is uncertain. We investigated the associations between cholesterol variability and the risk of HF and adverse cardiovascular events. Methods: This retrospective cohort study included patients attending family medicine clinics in Hong Kong during 2000-2003 with follow-up until 2019. Patients with at least three sets of blood cholesterol (low-density (LDL-C) and high-density (HDL-C) lipoprotein cholesterol) levels available at different visits were included. Patients with prior HF, myocardial infarction (MI), use of HF medications, and pregnancy were excluded. Visit-to-visit variability was calculated using standard deviation and coefficient of variation (CV). The primary outcome was HF. The secondary outcomes were cardiovascular mortality, and myocardial infarction. Results: A total of 5662 patients were included (2152 males; mean age 63.3+/-12.4 years; mean follow-up 15.3+/-4.6 years). Higher variability of HDL-C (hazard ratio (HR) for CV: 13.757 [6.261, 30.226], p<0.0001) predicted new-onset HF. Higher variability of LDL-C (HR for CV: 3.885 [1.942, 7.775], p=0.0001) and HDL-C (HR for CV: 39.118 [13.583, 112.657], p<0.0001) predicted higher risk of MI, but not cardiovascular mortality. These associations remained significant in patients without baseline usage of lipid-lowering medication(s) (N=4068), but were all insignificant in patients with baseline usage of lipid-lowering medication(s) (N=1594). Conclusion: Higher visit-to-visit cholesterol variability was varyingly associated with significantly increased long-term risks of HF and adverse cardiovascular events. Such associations may be negated by using lipid-lowering medication(s).