ABO blood group is a cardiovascular risk factor in patients with familial hypercholesterolemia

Background: The ABO blood group has been associated with cardiovascular disease (CVD) in observational studies. However, the effect of ABO blood group has never been studied in subjects affected by familial hypercholesterolemia (FH), a severe monogenic disease characterized by accelerated atherosclerotic plaque development.

Objective: Our aim is to investigate the effect of the ABO blood group on CVD risk in FH patients.

Methods: A total of 668 adult subjects with a heterozygous FH-causing mutation in the low density lipoprotein receptor (LDLR) gene were included in the present study. ABO blood group was determined using 2 functional single-nucleotide polymorphisms in the ABO gene (rs8176719 and rs8176746).

Results: Total cholesterol was significantly higher in non-O subjects compared to carriers of the O group (9.48 vs 9.14 mmol/L, P = .02). We observed a greater proportion of subjects carrying the non-O groups (73.4%) in patients with CVD compared to subjects without CVD (63.3%). In a regression model corrected for cardiovascular risk factors, the non-O group was significantly associated with an increased prevalence of CVD (odds ratio = 2.14, 95% confidence interval = 1.25-3.65, P = .005). In average, patients in the non-O blood group experienced more CVD events (0.88 per individual) than those in the O group (0.60 per individual), P = .008.

Conclusion: Carrying a non-O blood group is associated with an independent twofold increased risk of CVD in FH patients. The ABO blood group represents a novel CVD risk factor in FH subjects that is often known by the patient and could be used to further stratify CVD risk in this population of patients.