ApoB/LDL-C discordance as a predictor of atherosclerotic cardiovascular disease in genetically confirmed heterozygous familial hypercholesterolemia: A hypothesis-generating cohort study.

• ApoB/LDL-C discordance associates with ASCVD risk in HeFH. • High ApoB/LDL-C ratios correlate with increased event rates. • rdance captures residual risk missed by LDL-C alone. • Findings support ApoB use for HeFH risk stratification. In heterozygous familial hypercholesterolemia (HeFH), low-densi...

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Publicado en:Journal of Clinical Lipidology Vol. 20; no. 3; pp. 490 - 504
Autores principales: Genedy, Nader, Zouwail, Soha
Formato: research Journal Article
Publicado: Elsevier B.V. Mar2026
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Mar2026
      vid: 20
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      pub: Elsevier B.V.
      place: New York, New York
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        10.1016/j.jacl.2025.11.008
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        atl: ApoB/LDL-C discordance as a predictor of atherosclerotic cardiovascular disease in genetically confirmed heterozygous familial hypercholesterolemia: A hypothesis-generating cohort study.
      aug:
        au:
          Genedy, Nader
          Zouwail, Soha
        affil: Department of Metabolic Medicine, University Hospital of Wales, Cardiff, Wales, UK
      sug:
        subj:
          Lipoproteins, LDL Blood
          Apolipoproteins Blood
          Coronary Arteriosclerosis Risk Factors
          Hypercholesterolemia, Familial Complications
          Hypercholesterolemia, Familial Familial and Genetic
          Risk Assessment
          Cardiovascular Risk Factors
          Human
          Retrospective Design
          Record Review
          Middle Age
          Male
          Female
          Cox Proportional Hazards Model
          Myocardial Infarction Risk Factors
          Stroke Risk Factors
          Myocardial Revascularization
          Prospective Studies
          Descriptive Statistics
          Exploratory Research
          Data Analysis Software
          Middle Aged: 45-64 years
          Male
          Female
      ab: • ApoB/LDL-C discordance associates with ASCVD risk in HeFH. • High ApoB/LDL-C ratios correlate with increased event rates. • rdance captures residual risk missed by LDL-C alone. • Findings support ApoB use for HeFH risk stratification. In heterozygous familial hypercholesterolemia (HeFH), low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target, yet emerging evidence suggests apolipoprotein B (ApoB) may offer superior cardiovascular risk stratification. ApoB/LDL-C discordance occurs when ApoB and LDL-C provide conflicting risk information, potentially identifying patients at heightened atherosclerotic cardiovascular disease (ASCVD) risk despite apparently controlled LDL-C levels. However, evidence in genetically confirmed HeFH cohorts is sparse. To examine whether ApoB/LDL-C discordance associates with ASCVD events in a genetically confirmed HeFH cohort and to generate hypotheses for future validation studies. This retrospective cohort study included 424 genetically confirmed HeFH patients (median age 51 years, 54.5% female) followed for a median of 9.1 years. Patients were classified as concordant (both ApoB and LDL-C above or below sex-specific thresholds) or discordant. Cox proportional hazards models evaluated associations with ASCVD events (myocardial infarction, stroke, coronary revascularization), adjusting for age, sex, diabetes, hypertension, smoking, statin therapy, and baseline lipid parameters. Among 424 patients, 61 ASCVD events occurred (41 prevalent, 20 incident). ApoB/LDL-C ratio ≥0.31 g/mmol associated with higher event rates (27.6% vs 11.8%, P =.0022). Adjusted hazard ratio was 38.55 (95% CI 3.72-399.36), though marked by extreme instability from sparse data stratification and small event counts. Additional exploratory analyses using R software revealed linear correlation patterns and threshold-based associations supporting the discordance hypothesis. These preliminary findings suggest ApoB/LDL-C discordance may identify residual ASCVD risk in HeFH patients, warranting prospective validation in larger, independent cohorts before clinical application.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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