Soto-Mota Adrian, Norwitz Nicholas G, Manubolu Venkat S, Kinninger April, Wood Thomas R, Earls James, Feldman David, Budoff Matthew
Metabolic Diseases Research Unit, National Institute for Medical Sciences and Nutrition Salvador Zubiran, Mexico City, Mexico; Tecnologico de Monterrey, School of Medicine, Mexico City, Mexico.
Harvard Medical School Boston, Massachusetts, USA.
JACC Adv. 2025 Jul;4(7):101686. doi: 10.1016/j.jacadv.2025.101686. Epub 2025 Apr 7.
Changes in low-density lipoprotein cholesterol (LDL-C) among people following a ketogenic diet (KD) are heterogeneous. Prior work has identified an inverse association between body mass index and change in LDL-C. However, the cardiovascular disease risk implications of these lipid changes remain unknown.
The aim of the study was to examine the association between plaque progression and its predicting factors.
A total of 100 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.
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. The median change in NCPV was 18.9 mm (IQR: 9.3-47.0 mm) and the median change in PAV was 0.8% (IQR: 0.3%-1.7%). Neither change in ApoB (median 3 mg/dL, Q1-Q3: -17 to 35 mg/dL), 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.
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 predicts plaque but ApoB does not. (Diet-induced Elevations in LDL-C and Progression of Atherosclerosis [Keto-CTA]; NCT05733325).
采用生酮饮食（KD）的人群中，低密度脂蛋白胆固醇（LDL-C）的变化存在异质性。先前的研究已确定体重指数与LDL-C变化之间存在负相关。然而，这些血脂变化对心血管疾病风险的影响仍不明确。
本研究旨在探讨斑块进展与其预测因素之间的关联。
共有100名个体，其KD诱导的LDL-C≥190mg/dL、高密度脂蛋白胆固醇≥60mg/dL且甘油三酯≤80mg/dL，采用冠状动脉钙化和冠状动脉计算机断层扫描血管造影对其进行了1年的随访。用线性回归和贝叶斯因子评估斑块进展预测因素。进行了饮食依从性和基线心血管疾病风险敏感性分析。
基线时观察到高载脂蛋白B（ApoB）（中位数178mg/dL，四分位数间距：149 - 214mg/dL）和LDL-C（中位数237mg/dL，四分位数间距：202 - 308mg/dL）以及低总斑块评分（TPS）（中位数0，四分位数间距：0 - 2.25）。非钙化斑块体积（NCPV）的中位数变化为18.9mm（四分位距：9.3 - 47.0mm），粥样斑块体积（PAV）的中位数变化为0.8%（四分位距：0.3% - 1.7%）。ApoB的变化（中位数3mg/dL，四分位数间距： - 17至35mg/dL）、基线ApoB以及总LDL-C暴露时间（中位数1302天，四分位数间距：984 - 1754天）均与非钙化斑块体积（NCPV）或TPS的变化无关。贝叶斯推断计算结果支持零假设（ApoB与斑块进展之间无关联）的程度比支持备择假设的程度高6至10倍。所有基线斑块指标（冠状动脉钙化、NCPV、总斑块评分和粥样斑块体积百分比）均与NCPV的变化密切相关。
在采用KD的瘦型代谢健康人群中，ApoB和LDL-C的总暴露量及基线水平变化均与斑块变化无关。相反，基线斑块与斑块进展相关，这支持了在该人群中斑块预测斑块进展但ApoB不具有此作用的观点。（饮食诱导的LDL-C升高与动脉粥样硬化进展[生酮CTA]；NCT05733325）
