The Controversial Role of Glucose-6-Phosphate Dehydrogenase Deficiency on Cardiovascular Disease: A Narrative Review

Table 2

Level of evidence for the association of G6PD deficiency with CVD.

Study	Patients ()	Effect and proposed mechanism	Association^#	Evidence	Reference
Long et al. (1967)	1,465	G6PD protective for CVD. OR 0.41 (95% CI 0.24–0.70) “statin-like” effect	Weak	Level 3	[7]
Cocco et al. (1998)	1,756	G6PD protective for ischemic heart disease. SMR 0.28 (0.10–0.62); Impaired NO metabolism	Moderate	Level 3	[8]
Pinna et al. (2007)	1,344	G6PD protective for retinal vein occlusion. OR 0.39 (95% CI 0.24–0.64); “Statin-like” effect	Moderate	Level 3	[98].
Pinna et al. (2008)	420	G6PD protective for nonarteritic anterior ischemic optic neuropathy. OR 0.40 (95% CI 0.17–0.94) “statin-like” effect and impaired NO metabolism	Weak	Level 3	[99]
Meloni et al. (2008)	738	G6PD protective. OR 0.58 (95% CI 0.38–0.89); “Statin-like” effect and reduced ROS production by NADPH oxidase downregulation	Moderate	Level 2	[10]
Seyedian et al. (2016)	1484	G6PD protective for coronary artery disease. OR 0.87 (95% CI 0.56-1.35). “Statin-like effect”	Weak	Level 2	[102]
Thomas et al. (2018)	17,338	G6PD detrimental. OR 1.39 (95% CI 1.04–1.87). Impaired glutathione and NO metabolism	Strong	Level 2	[15]
Pes et al. (2019)	9,604	G6PD detrimental. OR 1.71 (95% CI 1.17–2.49). Multiple mechanisms including impaired inflammation, glutathione, and NO metabolism	Moderate	Level 2	[17]
Ou et al. (2020)	1,251	G6PD detrimental. OR 1.53 (95% CI 1.09–2.17); Impaired vascular redox state	Strong	Level 3	[18]

#The strength of association was reported based on effect size (OR, HR, frequency, value and so on). The level of evidence was ranked according to Hadorn [180] in descending order: (level 1) meta-analyses of randomized studies, (level 2) a single study, (level 3) nonrandomized studies, (level 4) retrospective studies, and (level 5) a series of cases without controls.