Relation between aldosterone synthase polymorphism and atrial fibrillation in patients with systolic heart failure

Abstract

Background: Activation of the renin-angiotensin system (RAS) has been suggested to have an important role in the pathogenesis of atrial fibrillation (AF). Aldosterone synthase is a key enzyme in aldosterone production, the final product of the RAS. We analyzed the possible association between CYP11B2 T-344C polymorphism in aldosterone synthase, which is associated with increased aldosterone activity, and the prevalence of AF in patients with chronic systolic heart failure (HF). Methods: We studied 178 consecutive patients who had symptomatic systolic HF (LVEF<40%) for at least 3 months prior to recruitment. Subjects were genotyped for the CYP11B2 polymorphism, using the polymerase chain reaction-restriction fragment length polymorphism approach. Results: AF was present in 57 (32%) patients. We found the -344 CC genotype to be a strong independent marker for AF: almost half (45%) patients with this genotype had AF compared to a quarter (27%) with -344 TT and TC genotypes ( Figure, p=0.02). A multivariate stepwise logistic regression model which included age, sex, New York Heart Association (NYHA) class, CYP11B2 -344CC genotype and echocardiographic measurements of LVEF, left atrium size, left ventricular end diastolic diameter and mitral regurgitation severity showed that after age and LA size, the CYP11B2 CC genotype was the most powerful independent predictor of AF (adjusted OR 2.59, 95% CI 1.68 -3.98, p=0.02). AF according to CYP11B2 T-344C genotypeConclusion: in chronic systolic HF patients, the CYP11B2 T-344 C polymorphism predisposes to clinical AF. The possibility of identifying patients at increased risk for AF supports the use of genome based treatment strategies in HF patients. In selected patient subsets, more aggressive pharmacotherapy aimed at modulating the RAS may be preferable to reduce rhythm disturbances in HF. 530Dinstinct pro-inflammatory cytokines regulate matrix metalloproteinase-2 and 9 levels in congestive heart failure

The AGTR1 gene A1166C polymorphism as a risk factor and outcome predictor of primary intracerebral and aneurysmal subarachnoid hemorrhages

“…Although A1166C is not directly associated with stroke risk it correlates with stroke outcome in the aSAH group. Its effect on outcome was also shown in patients after percutaneous coronary interventions and in patients with heart failure and reduced systolic function patient [13,14]. Based on mice models several authors have shown that interaction of AII with activated T leukocytes contributes to T-cell cytokine production and tissue invasion [24][25][26].…”

“…In patients after percutaneous coronary intervention it was associated with long term clinical outcome defined as death, repeat revascularization and myocardial infarction [13]. In heart failure and reduced systolic function it was associated with poor prognostic markers and increased mortality [14].…”