Paquette Martine, Trinder Mark, Guay Simon-Pierre, Brunham Liam R, Baass Alexis
Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal, QC H2W 1R7, Canada.
Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, BC V6Z 1Y6, Canada.
J Clin Endocrinol Metab. 2025 May 19;110(6):e1959-e1965. doi: 10.1210/clinem/dgae618.
Dysbetalipoproteinemia (DBL) is a disorder of remnant cholesterol metabolism associated with a severe risk of atherosclerotic cardiovascular disease (ASCVD).
The objective of this study was to investigate the univariate and multivariate predictors of ASCVD in individuals with DBL.
Data from 2699 individuals with ɛ2/ɛ2 genotypes from the UK Biobank were included in this study. DBL was defined as having an ɛ2ɛ2 genotype with evidence of dyslipidemia, defined as total cholesterol ≥ 200 mg/dL (5.2 mmol/L) and triglyceride ≥ 175 mg/dL (2.0 mmol/L) or lipid-lowering therapy use (n = 964).
Age, hypertension, waist circumference, and a polygenic risk score for coronary artery disease (PRSCAD) were independent predictors of ASCVD among individuals with DBL. Cumulative ASCVD-free survival was lower in the ɛ2/ɛ2 DBL group (84%) compared to the ɛ2/ɛ2 non-DBL group (94%) (P < .0001) and for DBL individuals with a PRSCAD ≥ median (79%) compared to those with a PRSCAD < median (89%) (P = .001).
We show in a large prospective cohort that a PRSCAD predicts the ASCVD risk among individuals with DBL. The findings of the present study highlight the need for better risk stratification in ɛ2/ɛ2 carriers to identify high-risk individuals who would need aggressive cardiovascular management despite their low apolipoprotein B value.
异常β脂蛋白血症（DBL）是一种残余胆固醇代谢紊乱疾病，与动脉粥样硬化性心血管疾病（ASCVD）的严重风险相关。
本研究的目的是调查DBL个体中ASCVD的单变量和多变量预测因素。
本研究纳入了英国生物银行中2699名携带ɛ2/ɛ2基因型个体的数据。DBL定义为具有ɛ2ɛ2基因型且有血脂异常证据，血脂异常定义为总胆固醇≥200mg/dL（5.2mmol/L）和甘油三酯≥175mg/dL（2.0mmol/L）或使用降脂治疗（n = 964）。
年龄、高血压、腰围和冠状动脉疾病多基因风险评分（PRSCAD）是DBL个体中ASCVD的独立预测因素。ɛ2/ɛ2 DBL组的累积无ASCVD生存率（84%）低于ɛ2/ɛ2非DBL组（94%）（P <.0001），PRSCAD≥中位数的DBL个体的累积无ASCVD生存率（79%）低于PRSCAD<中位数的个体（89%）（P =.001）。
我们在一个大型前瞻性队列中表明，PRSCAD可预测DBL个体的ASCVD风险。本研究结果强调了对ɛ2/ɛ2携带者进行更好的风险分层的必要性，以识别尽管载脂蛋白B值较低但仍需要积极心血管管理的高危个体。
