Prediction of Cumulative Exposure to Atherogenic Lipids During Early Adulthood

BACKGROUND The ability of a 1-time measurement of non–high-density lipoprotein cholesterol (non–HDL-C) or
low-density lipoprotein cholesterol (LDL-C) to predict the cumulative exposure to these lipids during early adulthood
(age 18-40 years) and the associated atherosclerotic cardiovascular disease (ASCVD) risk after age 40 years is not clear.
OBJECTIVES The objectives of this study were to evaluate whether a 1-time measurement of non-HDL-C or LDL-C in a
young adult can predict cumulative exposure to these lipids during early adulthood, and to quantify the association
between cumulative exposure to non-HDL-C or LDL-C during early adulthood and the risk of ASCVD after age 40 years.
METHODS We included CARDIA (Coronary Artery Risk Development in Young Adults Study) participants who were free
of cardiovascular disease before age 40 years, were not taking lipid-lowering medications, and had $3 measurements of
LDL-C and non–HDL-C before age 40 years. First, we assessed the ability of a 1-time measurement of LDL-C or non–
HDL-C obtained between age 18 and 30 years to predict the quartile of cumulative lipid exposure from ages 18 to 40
years. Second, we assessed the associations between quartiles of cumulative lipid exposure from ages 18 to 40 years with
ASCVD events (fatal and nonfatal myocardial infarction and stroke) after age 40 years.
RESULTS Of 4,104 CARDIA participants who had multiple lipid measurements before and after age 30 years, 3,995
participants met our inclusion criteria and were in the final analysis set. A 1-time measure of non–HDL-C and LDL-C
had excellent discrimination for predicting membership in the top or bottom quartiles of cumulative exposure (AUC:
0.93 for the 4 models). The absolute values of non–HDL-C and LDL-C that predicted membership in the top quartiles with
the highest simultaneous sensitivity and specificity (highest Youden’s Index) were >135 mg/dL for non–HDL-C
and >118 mg/dL for LDL-C; the values that predicted membership in the bottom quartiles were <107 mg/dL for
non–HDL-C and <96 mg/dL for LDL-C. Individuals in the top quartile of non–HDL-C and LDL-C exposure had
demographic-adjusted HRs of 4.6 (95% CI: 2.84-7.29) and 4.0 (95% CI: 2.50-6.33) for ASCVD events after age 40 years,
respectively, when compared with each bottom quartile.
CONCLUSIONS Single measures of non–HDL-C and LDL-C obtained between ages 18 and 30 years are highly predictive
of cumulative exposure before age 40 years, which in turn strongly predicts later-life ASCVD events.
(JACC. 2024;84:961–973) © 2024 Published by Elsevier on behalf of the American College of Cardiology Foundation