Lipid Variability and Risk of Cardiovascular Diseases and All-Cause Mortality: A Systematic Review and Meta-Analysis of Cohort Studies

No consensus has yet been reached on the associations of lipid variability (LV) with cardiovascular diseases (CVDs) and all-cause mortality. We aimed to quantify the associations of different types and metrics of LV with CVDs and all-cause mortality. PubMed, Medline, and Embase databases were searched for eligible cohort studies published until 14 December 2021. Lipids included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Metrics of variability included standard deviation (SD), coefficient of variation (CV), and variation independent of the mean (VIM). The primary outcomes were CVDs and all-cause mortality. Random-effects meta-analysis was used to generate a summary of the relative risks (SRRs). Sources of heterogeneity were explored by subgroup analysis and meta-regression. A total of 11 articles based on seven cohorts were included. Participants in the top quartile of TC variability had an increased risk of CVDs (vs. bottom quartile: TC-CV: SRR 1.29, 95% CI 1.15-1.45; TC-SD: 1.28, 1.15-1.43; TC-VIM: 1.26, 1.13-1.41, respectively) and all-cause mortality (vs. bottom quartile: TC-CV: 1.28, 1.15-1.42; TC-SD: 1.32, 1.22-1.44; TC-VIM: 1.32, 1.25-1.40, respectively). Participants in the top quartile of HDL-C variability had an increased risk of CVDs (vs. bottom quartile: HDL-C-CV: 1.11, 1.07-1.15; HDL-C-SD: 1.18, 1.02-1.38; HDL-C-VIM: 1.18, 1.09-1.27, respectively) and all-cause mortality (vs. bottom quartile: HDL-C-CV: 1.29, 1.27-1.31; HDL-C-SD: 1.24, 1.09-1.41; HDL-C-VIM: 1.25, 1.22-1.27, respectively). LDL-C variability was also associated with an increased risk of CVDs (for top vs. bottom quartile; LDL-C-SD: 1.09, 1.02-1.17; LDL-C-VIM: 1.16, 1.02-1.32, respectively) and all-cause mortality (for top vs. bottom quartile; LDL-C-CV: 1.19, 1.04-1.36; LDL-C-SD: 1.17, 1.09-1.26, respectively). The relationships of TG variability with the risk of CVDs and all-cause mortality were inconclusive across different metrics. The effects of SRR became stronger when analyses were restricted to studies that adjusted for lipid-lowering medication and unadjusted for mean lipid levels. These findings indicate that the measurement and surveillance of lipid variability might have important clinical implications for risk assessment of CVDs and all-cause mortality.

Automated summary

No consensus has been reached on the associations of lipid variability with cardiovascular diseases and all-cause mortality. This study found that variability in total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol is associated with an increased risk of cardiovascular diseases and all-cause mortality. The relationship between triglyceride variability and risk is inconclusive. These findings suggest that measuring and monitoring lipid variability could have important clinical implications for risk assessment of cardiovascular diseases and all-cause mortality.