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

BackgroundCarbohydrate-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). ObjectiveTo evaluate one-year coronary plaque progression in LMHRs and near-LMHRs. MethodsThis 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(R) methodology (Leiden, the Netherlands), with AI-enabled coronary plaque analysis (AI-CPA; HeartFlow(R) Inc., Mountain View, CA) used as an independent, blinded confirmatory analysis. Plaque burden and plaque progression predictors were examined using linear regression. ResultsAll 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 <100, and 54% had a CAC of 0. The median increase in non-calcified plaque volume was 5.6 mm3 (37% relative increase). Notably, 15% of participants exhibited plaque regression despite sustaining elevated LDL-C (mean 242 mg/dL) and ApoB (mean 180 mg/dL). Additionally, 78% had percent atheroma volume (PAV) below the high-risk threshold of 2.6%, and 93% had total plaque volume (TPV) below the high-risk threshold of 254 mm3. Baseline plaque metrics were consistently predictive of plaque progression. By contrast, neither ApoB levels nor cumulative LDL-C exposure predicted plaque progression in this population of LMHR and near-LMHR individuals. ConclusionThese findings suggest that over one year, progression was modest and heterogeneous in this population, with baseline coronary plaque emerging as the strongest predictor of subsequent plaque progression in LMHRs, whereas traditional lipid markers such as ApoB and LDL are not.