Glucose interaction magnifies atherosclerotic risk from cholesterol: Findings from the PDAY Study

Objective: To examine whether the atherosclerotic risk from cholesterol is modified by serum glucose level. Methods: Data from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study of 1530 individuals with complete autopsy data for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and hemoglobin A1c (HbA1c) were examined with any atherosclerotic raised lesions (RL) >0% of surface area on any of three arterial specimens as the outcome. A TC/HDL-C ratio was categorized into quintiles and HbA1c was dichotomized as the upper quartile versus lower three quartiles. Odds ratios (ORs) were estimated from logistic regression models adjusting for sex, race, age, body mass index, smoking and hypertension. Results: An interaction product term of TC/HDL × HbA1c was statistically significant (P=0.006) despite adjustment for the main effects and other covariates. In models stratified by HbA1c, ORs (3.0, 3.9, 1.9, 3.5) for four upper quintiles of TC/HDL-C in the upper HbA1c stratum were substantially higher than those in the lower HbA1c stratum (0.9, 1.3, 1.4 and 1.1). Strata differences were even more striking in the subset of those ≥25 years old. Conclusions: These results suggest a synergistic interaction between glucose and cholesterol that magnifies the atherosclerotic risk associated with TC/HDL-C for those with higher HbA1c levels.