Visit-to-visit lipid variability, coronary artery calcification, inflammation, and mortality in the Multi-Ethnic Study of Atherosclerosis

Abstract 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.