Work

Glucose-6-Phosphate Dehydrogenase Deficiency and Cardiovascular Risk in Familial Hypercholesterolemia: A Retrospective Cohort Study

Year: 2025

Type: article

Abstract: Background: Familial hypercholesterolemia (FH) is a monogenic disorder causing markedly elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerosis. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in antioxidant defense via NADPH production. G6PD deficiency, an X-linked disorder impairing redox homeostasis, may contribute to cardiovascular disease (CVD) risk. This study examined whether G6PD deficiency increases CVD risk in FH patients. Methods: We retrospectively analyzed 217 FH patients. Clinical data included demographics, lipid profiles, G6PD status, and atherosclerotic CVD outcomes (coronary, cerebrovascular, or peripheral arterial disease). In a subset, FH was confirmed by LDLR gene sequencing, and G6PD Mediterranean and Seattle variants were genotyped. Cumulative CVD prevalence was compared between G6PD-deficient and G6PD-normal FH patients. Multivariable logistic regression was adjusted for age, sex, body mass index, high blood pressure, and smoking. Results: Participants (mean age 47 years, 60% female) had markedly elevated LDL-C (mean 292 mg/dL at diagnosis). Atherosclerotic CVD was present in 119 (55%) patients. G6PD-deficient FH patients had a significantly higher CVD prevalence than those with normal G6PD activity (77.4% vs. 39.8%, p < 0.0001). LDL-C levels were higher in the G6PD-deficient group than in the non-deficient group, and this difference reached statistical significance in the univariate analysis. In the multivariable analysis, G6PD deficiency remained an independent CVD predictor (adjusted OR 3.57, 95% CI 1.30–9.83) after controlling for conventional risk factors. Conclusions: In FH, hereditary G6PD deficiency is associated with a markedly increased risk of atherosclerotic CVD. A pro-oxidative state in G6PD-deficient FH patients may play a role in premature atherogenesis. G6PD status may represent a cardiovascular risk modifier in FH, warranting further research into underlying mechanisms and targeted management.

Source: Lipidology

DOI: 10.3390/lipidology2040022

Authors: Alessandra Errigo, Maria Pina Dore, Elettra Merola, Giovanni Mario Pes

Institutions: University of Sassari, Baylor College of Medicine

Language: English

Topic: Lipoproteins and Cardiovascular Health

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,207