A multilocus genetic risk score is associated with arterial stiffness in hypertensive patients: The CARE NORTH study

Introduction: Arterial stiffness is recognized as an intermediate phenotype and predictor of cardiovascular disease. Arterial stiffness is complex in origin with contributions from lifestyle and genetic factors. However, the association between single nucleotide polymorphisms (SNPs) and arterial stiffness remains unclear. Objective: The aim is to assess whether a multilocus genetic risk score (GRS), composed of selected SNPs linked to cardiovascular traits and outcomes, is associated with arterial stiffness in patients with hypertension. Design and methods: This study included 730 participants derived from the CARE NORTH study. The arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cfPWV). An adjusted linear regression was used to evaluate the association between cfPWV and each individual SNP using multiple genetic models. The association between a constructed GRS and cfPWV was tested in an unadjusted and adjusted model. Results: We selected 13 SNPs found to be associated with cfPWV (P<.05): 6 SNPs in additive, 4 SNPs in recessive and 3 SNPs in dominant mode of inheritance. The GRS based on these SNPs was positively associated with cfPWV both in unadjusted and adjusted models (β = 0.2m/s, 95% CI 0.11-0.29, P - 7.6 × 10^-6 and β = 0.22 m/s, 95% CI 0.15-0.28, P=1.4 × 10^-10, respectively). The GRS explained an additional 3.6% cfPWV variance above clinical covariates. Conclusion: We demonstrate that the GRS composed of 13 SNPs related to cardiovascular phenotypes is associated with an increased arterial stiffness in hypertensive patients. Our findings may help to clarify genetic basis of arterial stiffening and provide insight into mechanisms underlying this phenotype.