The association between arterial stiffness and the angiotensin II type 1 receptor (A1166C) polymorphism is influenced by the use of cardiovascular medication

OBJECTIVE: To examine in a population with a high prevalence of hypertension, the association between six cardiovascular polymorphisms, arterial stiffness and medication use. METHODS: In this cross-sectional study (Hypertension: Interaction and Prevalence of POlymorphisms related to Cardiovascular Risk and the Association to Treatment Efficacy Study project), arterial stiffness was assessed by measuring pulse wave velocity (PWV) in 575 patients in one primary care practice. Patients were genotyped for the angiotensin II type 1 receptor [AGTR1 (A1166C)], angiotensinogen (M235T), angiotensin-converting enzyme (4656rpt), endothelial nitric oxide synthase (E298D), G-protein beta3 (C825T), and alpha-adducin (G460W) polymorphisms. Linear regression analyses were performed to assess the association between polymorphisms and PWV. RESULTS: Thirty percent of the patients (273 men, 302 women) had a carotid-femoral pulse wave velocity above 12 m/s and more than 60% of the patients had a carotid-femoral/carotid-radial PWV (CF/CR ratio) above 1. The CF/CR ratio was significantly associated with age, sex, dislipidemia, cardiovascular medication use and pulse pressure. After correction for these covariates, multivariate linear regression analyses showed that the C allele of AGTR1 was associated with a lower CF/CR ratio. This association was significantly influenced by cardiovascular medication use (P = 0.011), and showed a dose-allele effect, the CF/CR ratio decreasing with the number of C alleles (P = 0.04). CONCLUSION: In a primary care population, this study showed an independent protective dose-allele effect for the presence of C alleles of the AGTR1 polymorphism on PWV. This association, which was influenced by the use of cardiovascular medication, needs further investigations to identify the underlying mechanisms.