Abstract 11014: Circulating Endothelin-1 Levels Are Not Elevated in Atherosclerotic Coronary Artery Disease and Coronary Microvascular Dysfunction Defined Using [15O]h2o Pet Perfusion, Invasive Ffr and Coronary Ct Angiography

Introduction:Endothelin-1 (ET-1), the most potent cardiovascular vasoconstrictor in humans, is increasingly being linked to coronary microvascular dysfunction (CMD) and atherosclerosis, thus providing a therapeutically modifiable target. In this study we investigated whether increased ET-1 levels are related to atherosclerosis, high risk plaque (HRP), myocardial perfusion and CMD in chest pain patients.Methods:Serum ET-1 was measured by ELISA in 205 patients (64% men; age 58 ± 9 years) with suspected coronary artery disease. All patients underwent 256-slice coronary CT angiography for (quantitative) plaque analysis and coronary artery calcium (CAC) scoring, [15O]H2O PET perfusion imaging and invasive FFR measurements in all coronary arteries. A total of 585 vessels were stratified upon four categories based on [15O]H2O PET perfusion (hyperemic MBF 2.3 ml/min/g) and invasive pressure measurements (FFR 0.80). 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, ET-1 was not related to the CAC score, total plaque volume (TPV) or perfusion (p=0.33; p=0.55; p=0.75, respectively). Also, patients with HRP did not show higher levels of ET-1 (mean logarithmic ET-1 0.29 vs 0.30; p=0.83). ET-1 levels were equally distributed across the four vessel categories and were not elevated in CMD patients (p=0.31).Conclusions:Our findings indicate that circulating ET-1 levels are not elevated in stable patients with either atherosclerotic coronary artery disease or coronary microvascular dysfunction, suggesting that ET-1 may not be a useful therapeutic target in these disease states.Figure 1. A typical case example of a CMD patient with non-flow limiting coronary arteries (A) and an ischemic perfusion (B). ET-1 depicted for the four vessels categories. (C) The upper and lower whiskers represent the 10th and 90th percentile.