Glucose-6-phosphate dehydrogenase deficiency and risk of cardiovascular disease: A propensity score-matched study

Background and aims: Cardiovascular disease (CVD) is associated with high morbidity and mortality. Studies in animal models and humans suggested that glucose‒6‒phosphate dehydrogenase (G6PD) deficiency, a genetically inherited condition causing haemolytic anemia, may be a risk factor for CVD. This hypothesis was tested in a large cohort from Northern Sardinia, where the population prevalence of G6PD deficiency is the highest in the Mediterranean area. Methods: A retrospective observational case‒control study was performed using clinical records of 9604 patients undergoing digestive endoscopy between 2002 and 2017, with a known G6PD status and a complete clinical history including CVD and leading CVD risk factors. To circumvent covariates imbalance between cases and controls, a 1:2 propensity score‒matched analysis was performed. Results: Major predictors of CVD, as expected, were age (OR 1.07; 95%CI 1.06–1.08), male sex (1.63; 95%CI 1.29–2.06), high blood pressure (OR 1.46; 95%CI 1.16–1.84), smoking (OR 3.03; 95%CI 2.42–3.79), diabetes (OR 1.65; 95%CI 1.23–2.21) and hypercholesterolemia (OR 2.20; 95%CI 1.71–2.84). The propensity score matching procedure resulted in 1123 G6PD deficient patients and 2246 patients with normal enzyme activity. When G6PD status was regressed on the CVD, including propensity score as a continuous covariate, an OR of 1.71 (95%CI 1.17–2.49; p = 0.006) was obtained. Conclusions: G6PD deficiency is significantly associated with increased risk of CVD, although the underlying mechanisms are still poorly understood. The loss of important protective pathways against oxidative stress, especially in the early stages of atherogenesis, might play a crucial role.