High visit-to-visit cholesterol variability predicts new-onset heart failure and adverse cardiovascular events: a retrospective population-based cohort study
Authors: Chan J S K , Zhou J , Satti D I , Lee T T L , Chou O H I , Wai A K C , Ciobanu A , Liu Y , Liu T , Zhang Q , Tse G 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Hyperlipidaemia is associated with adverse cardiovascular outcomes. However, the long-term prognostic value of visit-to-visit cholesterol variability is less certain, particularly regarding the risks of new-onset heart failure (HF). We investigated the associations between visit-to-visit cholesterol variability and adverse cardiovascular events.

Methods
This was a retrospective cohort study of patients attending family medicine clinics in a Chinese city 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, and total 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 new-onset HF. The secondary outcomes were cardiovascular mortality, and myocardial infarction. Multivariable Cox regression with adjustments for significant baseline predictors of outcomes were used to evaluate the association between cholesterol variability and the outcomes.

Results
A total of 5662 patients were included (2152 males; mean age 63.3 ± 12.4 years). The mean follow-up period was 15.3 ± 4.6 years. Lower mean HDL-C and total cholesterol predicted new-onset HF and MI, while higher mean LDL-C and total cholesterol and lower HDL-C predicted cardiovascular mortality (Table 1). Cholesterol variability was a significant predictor of the outcomes (Table 1). Higher variability of HDL-C (hazard ratio (HR) for CV: 14.202 [6.524, 30.916], p &lt; 0.0001; Figure 1A) and total cholesterol (HR for CV: 10.340 [4.582, 23.336], p &lt; 0.0001; Figure 1B) predicted new-onset HF. These also predicted MI (HR for CV: 40.738 [14.412, 115.150], p &lt; 0.0001, and 34.285 [11.450, 102.660], p &lt; 0.0001, respectively), as did higher variability of LDL-C (HR for CV: 3.798 [1.903, 7.578], p = 0.0002). Lower variability of LDL-C (HR for CV: 0.234 [0.104, 0.526], p &lt; 0.0001) predicted cardiovascular mortality. This was probably driven by the association between cardiovascular mortality and higher mean LDL-C. Variability of HDL-C and total cholesterol did not predict cardiovascular mortality

Conclusion
Higher visit-to-visit cholesterol variability was associated with significantly increased long-term risks of new-onset HF and adverse cardiovascular events. Variability of different types of cholesterol had varying prognostic values, with HDL-C showing particular importance for new-onset HF. Visit-to-visit cholesterol variability may be a clinically relevant and important tool for HF and general cardiovascular risk stratification. Abstract Figure 1 Abstract Table 1