Abstract 15339: Impact of Polymorphisms in the Renin-Angiotensin-Aldosterone System on Vascular Alterations in Essential Hypertension
Background: The angiotensinogen M235T and aldosterone synthase (CYP11B2) gene polymorphisms may be associated with vascular function in cardiovascular disease. Hypertension is associated with vascular dysfunction and the renin-angiotensin-aldosterone system has significant impact. Therefore, we investigated whether these variants provide useful information with regards to subclinical atherosclerosis and vascular damage in essential hypertension.
Methods: The study population consisted of 319 newly diagnosed essential hypertensives and 191 healthy individuals. Polymorphisms were determined using polymerase chain reaction (PCR) technique. In all participants, carotid-femoral pulse wave velocity (cf-PWV), flow mediated dilation (FMD), ultrasound measurement of the intima-media thickness of carotid arteries (C-IMT), augmentation index, ankle-brachial index, as well as the incidence and progression of retinopathy were evaluated. Serum cystatin-C levels were measured by the ELISA method.
Results: 235TT homozygotes had significantly lower FMD compared with M allele carriers in controls (p=0.038) whereas PWV was higher in TT homozygotes compared with MM+MT genotypes in hypertensive patients (p=0.025). Regarding the aldosterone synthase polymorphism we have observed higher values of 344TT homozygosity compared to CC-allele carriers in the group of hypertensives (781.6±33.5 vs 712.5±16.2 μ m, p=0.03). Moreover, T-allele carriage was significantly associated with higher prevalence of atherosclerotic plaques in total population (OR: 0.32; p=0.01). Cystatin-C levels were correlated significantly only with PWV values both in total (r=0.27, p=0.03) and in hypertensive populations (r=0.23, p=0.0008). Interestingly, increased levels of cystatin-C (above 75th percentile) were correlated with higher PWV values (p=0.0019).
Conclusions: The present study suggests that angiotensinogen genotypes are associated with vascular function and structure alterations, whereas CYP11B2 promoter variant is a marker of subclinical atherosclerosis in untreated hypertension. Increased levels of cystatin-C may be useful to identify individuals with more pronounced arterial stiffness.
- © 2012 by American Heart Association, Inc.