The Impact of Sustained LDL-C Elevation on Plaque Changes: Primary Coronary plaque progression results from the Keto CTA Study

ABSTRACT Background Carbohydrate-restricted diets are gaining popularity, including among lean individuals. In these populations, a lipid phenotype often emerges comprising elevated LDL cholesterol (LDL-C), alongside elevated HDL-C and low triglycerides, termed the lean mass hyper-responder (LMHR). Objective To evaluate one-year coronary plaque progression in LMHRs and near-LMHRs. Methods This prospective study followed 100 participants who developed the triad of high LDL-C, high HDL-C, and low triglycerides after adopting a ketogenic diet over one year. Coronary plaque changes were assessed using coronary CT angiography and analyzed using the prespecified QAngio ® methodology (Leiden, the Netherlands), with AI-enabled coronary plaque analysis (AI-CPA; HeartFlow ® Inc., Mountain View, CA) used as an independent, blinded confirmatory analysis. Plaque burden and plaque progression predictors were examined using linear regression. Results All 100 participants with elevated LDL-C and a mean BMI of 22.5 ± 2.7 kg/m2 completed the study. At baseline, 57 (57%) had zero CAC. After follow-up, most participants remained with low-risk plaque burden markers: 81% of participants had a CAC score