https://www.jacc.org/doi/10.1016/j.jacadv.2025.101686
Plaque Begets Plaque, ApoB Does Not: Longitudinal Data From the KETO-CTA Trial
Methods
One hundred individuals exhibiting KD-induced LDL-C ≥190 mg/dL, high-density lipoprotein cholesterol ≥60 mg/dL, and triglycerides ≤80 mg/dL were followed for 1 year using coronary artery calcium and coronary computed tomography angiography. Plaque progression predictors were assessed with linear regression and Bayes factors. Diet adherence and baseline cardiovascular disease risk sensitivity analyses were performed.
Results
High apolipoprotein B (ApoB) (median 178 mg/dL, Q1-Q3: 149-214 mg/dL) and LDL-C (median 237 mg/dL, Q1-Q3: 202-308 mg/dL) with low total plaque score (TPS) (median 0, Q1-Q3: 0-2.25) were observed at baseline. Neither change in ApoB (median 3 mg/dL, Q1-Q3: −17 to 35), baseline ApoB, nor total LDL-C exposure (median 1,302 days, Q1-Q3: 984-1,754 days) were associated with the change in noncalcified plaque volume (NCPV) or TPS. Bayesian inference calculations were between 6 and 10 times more supportive of the null hypothesis (no association between ApoB and plaque progression) than of the alternative hypothesis. All baseline plaque metrics (coronary artery calcium, NCPV, total plaque score, and percent atheroma volume) were strongly associated with the change in NCPV.
Conclusions
In lean metabolically healthy people on KD, neither total exposure nor changes in baseline levels of ApoB and LDL-C were associated with changes in plaque. Conversely, baseline plaque was associated with plaque progression, supporting the notion that, in this population, plaque begets plaque but ApoB does not. (Diet-induced Elevations in LDL-C and Progression of Atherosclerosis [Keto-CTA]; NCT05733325)
Characteristics of the sample population are as follows:
The inclusion criteria were
• Being on a KD for ≥24 months
• LDL-C ≤160 mg/dL from the last lipid panel drawn prior to adopting a KD
• LDL-C ≥190 mg/dL on the most recent laboratory on a KD
• An increase of ≥50% in LDL-C after adopting a KD
• HDL-C ≥60 mg/dL
• Triglycerides ≤80 mg/dL
• Glycated hemoglobin <6.0%
• Fasting glucose <110 mg/dL
• High-sensitivity C-reactive protein <2 mg/L
Exclusion criteria were
• Elevated blood pressure (systolic >130 mm Hg, diastolic >80 mm Hg)
• Type 2 diabetes or any lifetime use of antidiabetic medication
• Untreated hypothyroidism (thyroid stimulating hormone >10 mIU/mL)
• Renal insufficiency (calculated creatinine clearance of <50 mL/min with the MDRD [Modification of Diet in Renal Disease Study] equation)
• Liver enzymes >2 times the upper limit of normal at screening visit or total bilirubin >1.5
• Use of medications that elevate LDL-C (anabolic steroids, isotretinoin, immunosuppressant, amiodarone, thiazide diuretics, glucocorticoids, or thiazolidinediones)
• Use of lipid-lowering supplements or medications (statins, red yeast rice, garlic, ezetimibe, berberine, PCSK9 inhibitors)
• Genetically defined familial hypercholesterolemia
