Genetically determined hypoalbuminemia as a risk factor for hypertension: instrumental variable analysis

Hypoalbuminemia is associated with vascular endothelial dysfunction and the development of chronic cardiovascular diseases. However, the relationship between serum albumin concentration and blood pressure changes remains controversial. Community-based longitudinal cohort data collected from Korean Genome and Epidemiology Study were used in this study. Hypoalbuminemia was defined as a serum albumin concentration of <= 4.0 g/dL. A total of 4325 participants were categorized into control (n=3157) and hypoalbuminemia (n=1168) groups. Serum albumin had a non-linear relationship with the risk of hypertension development. A genome-wide association study revealed 71 susceptibility loci associated with hypoalbuminemia. Among susceptibility loci, genetic variations at rs2894536 in LOC107986598 and rs10972486 in ATP8B5P were related to elevated blood pressure. Serum albumin (HR=0.654, 95% CI 0.521-0.820) and polymorphisms of rs2894536 (HR=1.176, 95% CI 1.015-1.361) and rs10972486 (HR=1.152, 95% CI 1.009-1.316) were significant predictors of hypertension development. Increased albumin concentration instrumented by 2 hypoalbuminemia-associated SNPs (rs2894536 and rs10972486) was associated with decreased HRs for hypertension development (HR=0.762, 95% CI 0.659-0.882 and HR=0.759, 95% CI 0.656-0.878). Our study demonstrated that genetically determined hypoalbuminemia is a significant predictor of incipient hypertension.