Implications of Total to High-Density Lipoprotein Cholesterol Ratio Discordance With Alternative Lipid Parameters for Coronary Atheroma Progression and Cardiovascular Events

The total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio may quantify atherogenic lipoproteins beyond low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apolipoprotein B (apoB). We analyzed pooled data from 9 trials involving 4,957 patients with coronary artery disease undergoing serial intravascular ultrasonography to assess changes in percent atheroma volume (ΔPAV) and 2-year major adverse cardiovascular event (MACE) rates when TC/HDL-C levels were discordant with LDL-C, non-HDL-C, and apoB. Discordance was investigated when lipid levels were stratified by/≥median levels (TC/HDL-C 3.3 vs LDL-C 80, non-HDL-C 107, and apoB 76 mg/dl) or/≥very low percentile equivalent cutoffs (TC/HDL-C 2.5 vs LDL-C 70, non-HDL-C 89, and apoB 59 mg/dl). When stratified by median levels, TC/HDL-C was commonly observed to be discordant with LDL-C (26%), non-HDL-C (20%), and apoB (27%). In patients with LDL-C, non-HDL-C, or apoBmedian, those with a discordant TC/HDL-C ≥median demonstrated less PAV regression and greater MACE (18.9%, 17.7%, 19.8%, respectively) compared with TC/HDL-Cmedian (14.4%, 14.0%, 12.8%; p = 0.02, 0.14, 0.003, respectively). In patients with LDL-C, non-HDL-C, or apoB ≥median, those with a discordant TC/HDL-Cmedian demonstrated less PAV progression and lower MACE (15.0%, 17.3%, 19.9%, respectively) compared with TC/HDL-C ≥median (24.7%, 24.2%, 26.4%; p0.001, 0.003, 0.03, respectively). In conclusion, the TC/HDL-C ratio reclassifies atheroma progression and MACE rates when discordant with LDL-C, non-HDL-C, and apoB within subjects. Thus, using the ratio, in addition to individual lipid parameters, may identify patients who may benefit from more intensive lipid modification.