Abstract 5510: Inflammation is Related to Coronary Flow Reserve Detected by Positron Emission Tomography in Healthy Twins

Abstract

Introduction. Coronary microvascular dysfunction is an early precursor of CAD and is thought to result from endothelial cell activation and inflammation. Coronary flow reserve (CFR) is an index of microvascular dysfunction, but limited and conflicting data exist on the relationship between CFR and inflammation. Methods. We examined 292 healthy male twins selected from the Vietnam Era Twin Registry. Plasma biomarkers of inflammation and endothelial cell activation were assessed and included C-reactive protein (CRP), interleukin-6 (IL-6), total white blood cell count (WBC), sVCAM-1 and sICAM-1. We performed myocardial perfusion imaging and blood flow quantitation with [13N] ammonia positron emission tomography at rest and after adenosine stress. CFR was measured as the ratio of maximum flow to baseline flow at rest averaged across 20 myocardial regions; abnormal CFR was defined as <2.5. A summed stress score for visible perfusion defects was also calculated. Traditional CAD risk factors were also measured. Mixed-effect and GEE models were used to conduct matched-pair analyses. Results. The twins had a mean age of 54 and 57% were monozygotic. In the overall sample, all biomarkers except sVCAM-1 were significantly correlated with CFR. In contrast, only IL-6 was correlated with the summed stress score of visible defects. Of 146 twin pairs, 138 were discordant for CFR (using no cutpoint) and 56 pairs were discordant for CFR <2.5. Values of all biomarkers were higher in twins with lower CFR than their brothers with higher CFR (Table ). The associations persisted after adjusting for summed stress score and CAD risk factors; after stratifying by zygosity results were similar. Conclusions. Systemic inflammation and endothelial cell activation are associated with coronary microvascular dysfunction, independent of CAD risk factors. Our results using a highly controlled twin design highlight the importance of inflammatory processes in the early phases of CAD. Percent Higher Biomarker Level in Twin with Lower CFR Compared to Brother with Higher CFR This research has received full or partial funding support from the American Heart Association, National Center.