TY - JOUR
T1 - Visit-to-visit lipid variability, coronary artery calcification, inflammation, and mortality in the Multi-Ethnic Study of Atherosclerosis
AU - Chan, Jeffrey Shi Kai
AU - Satti, Danish Iltaf
AU - Chan, Raymond Ngai Chiu
AU - Chevli, Parag
AU - Mehta, Adhya
AU - Martin, Seth S.
AU - Sharma, Garima
AU - Tse, Gary
AU - Virani, Salim S.
AU - Shapiro, Michael D.
N1 - Publisher Copyright:
© 2025 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site - for further information please contact [email protected].
PY - 2025/9/1
Y1 - 2025/9/1
N2 - 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 0.250.02-0.48)], but not LDL-C, TC, and triglyceride variability. Over a 15.1-year median follow-up, higher HDL-C [Q4vs.Q1: adjusted sub-hazard ratio 2.68(1.61-4.48)] and TC [Q4vs.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 [Q4vs.Q1: adjusted hazard ratio 1.46(1.00-2.11)], but LDL-C, TC, and triglyceride variability were not. HDL-C [Q4vs.Q1: adjusted β: 0.132(0.034-0.230)] and TC [Q4vs.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.
AB - 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 0.250.02-0.48)], but not LDL-C, TC, and triglyceride variability. Over a 15.1-year median follow-up, higher HDL-C [Q4vs.Q1: adjusted sub-hazard ratio 2.68(1.61-4.48)] and TC [Q4vs.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 [Q4vs.Q1: adjusted hazard ratio 1.46(1.00-2.11)], but LDL-C, TC, and triglyceride variability were not. HDL-C [Q4vs.Q1: adjusted β: 0.132(0.034-0.230)] and TC [Q4vs.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.
KW - Atherosclerosis
KW - C-reactive protein
KW - Calcium score
KW - Coronary artery calcium
KW - Inflammation
KW - Lipid
KW - MESA
KW - Mortality
KW - Variability
UR - https://www.scopus.com/pages/publications/105016521148
U2 - 10.1093/eurjpc/zwaf085
DO - 10.1093/eurjpc/zwaf085
M3 - Article
C2 - 39977247
AN - SCOPUS:105016521148
SN - 2047-4873
VL - 32
SP - 1235
EP - 1244
JO - European Journal of Preventive Cardiology
JF - European Journal of Preventive Cardiology
IS - 13
ER -