Lipid variability as an independent predictor of major adverse cardiovascular events: a systematic review and meta-analysis
O Rueda Ochoa, S A Serrano Henandez, L N Calderon Martinez, J D Rico RodriguezAbstract
Introduction
Adverse cardiovascular events persist even in patients who achieve lipid therapeutic targets, highlighting a residual cardiovascular risk. This indicates that static lipid parameters may be insufficient for a comprehensive risk assessment. In this context, longitudinal lipid variability has emerged as a possible additional determinant of cardiovascular risk, the characterisation of which could provide complementary information to traditional stratification approaches.
Purpose
To evaluate the association between longitudinal variability in lipids (total cholesterol, LDL, and triglycerides) and the risk of major adverse cardiovascular events (MACE) and mortality, analysing the predictive value of the coefficient of variation as an independent risk marker.
Methods
A systematic review and meta-analysis was conducted across PubMed, Scopus, LILACS, and Google Scholar using MeSH terms for lipid variability and major adverse cardiovascular events; of 16,273 identified records, 4,904 duplicates were removed, 40 full-texts were assessed, and 7 studies were included following independent screening by three investigators. Random-effects models were utilised in Stata 19 to estimate pooled risk ratios (RR) for the coefficient of variation of total cholesterol and triglycerides, with heterogeneity evaluated via the I² statistic.
Results
Pooled analyses were conducted using random-effects models to evaluate the impact of lipid variability on clinical outcomes. Regarding triglyceride variability, the random-effects model identified a significant association with an increased risk of major adverse cardiovascular events (RR 1.21, 95% CI 1.10–1.33; I² = 0%, indicating no heterogeneity) (Figure 1) and myocardial infarction (RR 1.17, 95% CI 1.05–1.30; I² = 5%, low heterogeneity) (Figure 2), whereas no significant association was observed for stroke (RR 1.01, 95% CI 0.92–1.12; I² = 0%). For total cholesterol variability, random-effects models demonstrated a significant correlation across all studied endpoints, with substantial between-study heterogeneity: all-cause mortality (RR 1.60, 95% CI 1.58–1.62; I² = 97.4%), major adverse cardiovascular events (RR 1.95, 95% CI 1.73–2.21; I² = 87.6%), myocardial infarction (RR 1.40, 95% CI 1.37–1.43; I² = 91.0%), and stroke (RR 1.46, 95% CI 1.43–1.49; I² = 76.3%).
Conclusions
Elevated variability in both triglycerides and total cholesterol is independently associated with a significantly increased risk of mortality and adverse cardiovascular events. While triglyceride-related associations demonstrated low between-study heterogeneity, total cholesterol analyses showed substantial heterogeneity across clinical outcomes. These findings suggest that maintaining lipid stability, beyond absolute target levels, represents a critical therapeutic objective for optimizing cardiovascular protection.Triglyceride and Variability and MACETriglyceride and Myocardial Infarction