Biological Pathways of Long-Term Visit-to-Visit Blood Pressure Variability in the American Population: Cardiovascular Health Study and Women's Health Initiatives

Studies reported a positive relationship between visit-to-visit blood pressure variability (VVBPV) and cardiovascular morbidity and mortality independently of the mean arterial blood pressure across clinical visits. The literature is scarce on the genes and biological mechanisms that regulate long-term VVBPV. We sought to identify biological pathways that regulate visit-to-visit blood pressure variability. We used phenotypic and genotype data from the Women's Health Initiatives and Cardiovascular Health Studies. We defined VVBPV of systolic and diastolic blood pressure phenotypes as the standard deviation about the participant's regression line with systolic and diastolic blood pressure regressed separately across visits. We imputed missing genotypes and then conducted a genome-wide association analysis to identify genomic variants related to the VVBPV and detect biological pathways. For systolic VVBPV, we identified a neurological pathway, the GABAergic pathway (P values = 1.1E-2), and a vascular pathway, the RAP1 signaling pathway (P values = 5.8E-2). For diastolic VVBPV, the hippo signaling (P values = 4.1E-2), CDO myogenesis (P values = 7.0E-2), and O-glycosylation of TSR domain-containing protein pathways (P values = 9.0E-2) were the significant pathways. Future studies are warranted to validate these results. Further understanding of the roles of the genes regulating the identified pathways will help researchers to improve future pharmacological interventions to treat VVBPV in clinical practice.