Inefficient arterial hypertension control in patients with metabolic syndrome and its link to renin–angiotensin–aldosterone system polymorphisms

Abstract

There is evidence that uncontrolled arterial hypertension (AHT) in patients with metabolic syndrome (MS) increases cardiovascular risks. The renin-angiotensin-aldosterone system (RAAS) and its polymorphisms apparently confer a genetic risk for uncontrolled AHT. This study aims to investigate the influence of RAAS polymorphisms on AHT control in patients diagnosed with MS. This is a two-stage population-based nested case-control pilot study (n=1514). We differentiated between MS-diagnosed patients and non-MS patients (ATP-III criteria) and selected those individuals diagnosed with AHT from each group (n=161 and n=156, respectively). Those who successfully controlled their AHT (controls) and those who did not were compared. In the MS population, the C/G and G/G genotypes of single-nucleotide polymorphism rs1040288 (NR3C2) and A/G and G/G of rs11099680 (NR3C2) were associated with uncontrolled AHT (odds ratio (OR)=2.94 (1.34-6.47) and OR=2.54 (1.09-5.93), respectively). According to Akaike's information criteria, the best adjusted model included gender and age as confounding variables (adjusted OR (ORa)=2.91 (1.31-6.46) and ORa=2.67 (1.13-6.31), respectively). Regarding rs1040288, an ORa of 4.03 (1.44-11.26) was obtained for the saturated model (adjusted for gender, age, waist-to-hip ratio, body mass index, biochemical profile, renal damage, smoking habit and anti-AHT treatment). Yet, when the same analysis was performed on the non-MS population, no association was found between rs11099680 and the failure to control AHT. The results reveal a possible association between the rs11099680 RAAS polymorphism and uncontrolled AHT in MS-diagnosed patients. rs1040288 appears to be associated with uncontrolled blood pressure regardless of MS profile.