Key result
Higher visit-to-visit HDL variability is linked to ~168% higher cardiovascular mortality risk.
Why the study?
The relationships between visit-to-visit lipid variability, coronary artery calcification, inflammation, and long-term mortality, which may be prognostically relevant, remained to be explored.
Does higher visit-to-visit lipid variability increase coronary artery calcification, inflammation, and mortality in participants of the Multi-Ethnic Study of Atherosclerosis?
Cohort (n=1,515)
Yes
Does higher visit-to-visit lipid variability increase coronary artery calcification, inflammation, and mortality in participants of the Multi-Ethnic Study of Atherosclerosis?
Hazard Ratio: 2.68 (95% CI 1.61–4.48)
Elevated HDL-C variability is a prognostic marker associated with greater coronary artery calcification burden and increased long-term risk of cardiovascular and all-cause mortality.
May aid CV risk stratification beyond mean HDL-C; leaves open causality and whether targeting variability improves outcomes.
AIMS: This study aimed to explore relationships between visit-to-visit lipid variability, coronary artery calcification (CAC), inflammation, and long-term mortality, which may be prognostically relevant. METHODS AND RESULTS: This prospective cohort study included participants from the Multi-Ethnic Study of Atherosclerosis with available plasma LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), total cholesterol (TC), and triglycerides from all three initial exams who underwent computed tomography CAC quantification at the third (index) exam. Visit-to-visit variability (coefficient of variation) was calculated from all three initial exams. Outcomes included the index Agatston score, cardiovascular mortality, all-cause mortality, and high-sensitivity C-reactive protein. Altogether, 1515 participants were analysed. Higher HDL-C variability was associated with higher index Agatston score [Quartile 4 (Q4; vs. Q1) adjusted marginal effects 0.25 0.02-0.48)], but not LDL-C, TC, and triglyceride variability. Over a 15.1-year median follow-up, higher HDL-C [Q4 vs. Q1: adjusted sub-hazard ratio 2.68 (1.61-4.48)] and TC [Q4 vs. Q1: adjusted sub-hazard ratio 2.13 (1.17-3.89)] variability, but not LDL-C and triglyceride variability, was associated with higher risk of cardiovascular mortality, which remained significant after adjusting for the index Agatston score. Additionally, higher HDL-C variability was associated with higher risk of all-cause mortality [Q4 vs. Q1: adjusted hazard ratio 1.46 (1.00-2.11)], but LDL-C, TC, and triglyceride variability were not. HDL-C [Q4 vs. Q1: adjusted β: 0.132 (0.034-0.230)] and TC [Q4 vs. Q1: adjusted β: 0.210 (0.064-0.357)] variability, but not LDL-C and triglyceride variability, may be correlated with high-sensitivity C-reactive protein. CONCLUSION: Elevated HDL-C variability was associated with greater CAC burden and long-term risks of cardiovascular and all-cause mortality. These mortality-related associations were probably not completely explainable by atherosclerosis. REGISTRATION: ClinicalTrials.gov: NCT00005487.
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Chan et al. (2025) conducted a cohort in Atherosclerosis (n=1,515). Visit-to-visit HDL cholesterol variability vs. Lowest quartile (Q1) of variability was evaluated on Cardiovascular mortality (sHR 2.68, 95% CI 1.61-4.48). Higher visit-to-visit HDL cholesterol variability was associated with a significantly increased risk of cardiovascular mortality (sHR 2.68; 95% CI 1.61-4.48) over a 15.1-year median follow-up.
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