Abstract 11071: Increased Circulating Raas Activity is Related to Functionally Significant Coronary Artery Disease as Defined by Ffr and [ 15 O]h2o Pet Perfusion as Well as Vulnerable Plaque Characteristics on CT Angiography

Abstract

Introduction: Renin-angiotensin-aldosterone-system (RAAS) activity has been linked to coronary artery disease (CAD) and coronary microvascular dysfunction (CMD), opening potential frontiers for treatment. In this study we investigated if increased RAAS activation is related to CAD, high risk plaque (HRP), myocardial perfusion, and CMD in chest pain patients. Methods: Renin as a measure for RAAS activation, was quantified by immunoradiometric assay in 205 patients (64% men; age 58 ± 9 years) with suspected CAD. Patients underwent 256-slice coronary CT angiography for (quantitative) plaque analysis and coronary artery calcium (CAC) scoring, [ 15 O]H2O PET perfusion imaging and invasive FFR measurements in all coronary arteries. A total of 585 vessels were stratified upon four categories based on [ 15 O]H2O PET perfusion and invasive pressure measurements. Vessels with a FFR >0.80 but with an ischemic hyperemic MBF below 2.3 ml/min/g were defined as CMD. Results: In univariable analysis, renin associated positively with the CAC score, total plaque volume (TPV) and impaired perfusion (p<0.01 for all). Patients with HRP displayed higher levels of renin (p=0.04). As expected, renin (p<0.01) was elevated in males. After correction for baseline characteristics including sex, renin associated positively with CAC score and TPV (p<0.01 and p=0.03), but not with HRP and perfusion (p=0.14 and p=0.40). Figure 1 shows that vessels with a significant flow limiting stenosis (FFR+, PET+; p=0.04) occur in patient with elevated renin levels, while vessels defined as CMD (FFR-, PET+) do not, except for patient without RAAS inhibition. Conclusion: RAAS activation is associated with CAD defined by FFR and [ 15 O]H2O PET and HRP. Future studies should clarify whether RAAS activation and CAD are causally related and represent modifiable targets. Figure 1. Intergroup p values are depicted for significant p values only. The upper and lower whiskers represent the 10 th and 90 th percentile.