Abstract 199: Renin-angiotensin-aldosterone System Polymorphisms-based Risk Score In Resistant Arterial Hypertension And Adverse Cardiovascular Events: The Genhart-rio SubStudy

Introduction: Renin-angiotensin-aldosterone system (RAAS) determines arterial pressure fluctuation. Resistant arterial hypertension (RAH) has increased risk for end organ damage. The aim of this study was to prospectively investigate, in subjects with RAH in a South American city: 1) Adverse cardiovascular events defined as fatal and non-fatal stroke or acute myocardial infarction (AMI); and 2) the association between RAAS polymorphisms and adverse cardiovascular events. Methods: Two hundred and twelve subjects under investigation for RAH were admitted. All subjects received standard drug therapy aiming at achieving <140/90mmHg, and were re-evaluated four weeks later, including 24h ambulatory arterial pressure monitoring. Subjects with secondary causes of RAH were excluded. Eighty eight subjects (age 57±10 y.o, 58 women) underwent genotyping to RAAS polymorphisms: renin (G1051A), angiotensinogen (M235T), angiotensin II type 1 receptor (A1166C) and aldosterone synthase (C344T). In this group, 65% were found RAH and 35% pseudo-RAH. Subjects were actively followed at scheduled clinical visits and phone contact. During follow-up, a composite of fatal and nonfatal stroke and/or AMI was assessed. A genetic score (GEN) based on allele risk was composed for each polymorphism (zero [low risk homozygosis], 1 [heterozygosis] to 2 [high risk homozygosis]), and summed up. Cox proportional-hazard model assessed both RAH and RAAS polymorphisms hazards for adverse events. (α<0.05) Results: During a median follow-up of 26 years, 40 subjects reached composite endpoint (median 22 years of follow-up). Hardy-Weinberg equilibrium was observed in all polymorphism. Optimal cutoff for GEN was >3 (AUC=0.66; p=0.006). In Cox proportional-hazard model, RAH and GEN>3 were independently associated with composite endpoint (RAH Hazard ratio [HR] 2.3; 95%CI [1.1-5.0]; p=0.027; and GEN>3 HR 3.4; 95%CI [1.2-9.6]; p=0.020). No significant differences according to age, gender, hypertension time were found. Conclusion: RAH determines an increased risk for a composite of stroke and AMI. A RAAS stratified genetic score identifies hypertensive subjects at increased risk for adverse cardiovascular events. ( NCT01173029 )