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).