Inflammation is Related to Coronary Flow Reserve Detected by Positron Emission Tomography in Asymptomatic Male Twins

Objectives This study sought to examine the relationship between inflammation and coronary microvascular function in asymptomatic individuals using positron emission tomography (PET) and assessment of coronary flow reserve (CFR). Background Coronary microvascular dysfunction is an early precursor of coronary artery disease (CAD) thought to result from endothelial cell activation and inflammation, but data are limited. Methods We examined 268 asymptomatic male monozygotic and dizygotic twins. Plasma biomarkers of inflammation and endothelial cell activation included C-reactive protein (CRP), interleukin (IL)-6, white blood cell count (WBC), vascular cell adhesion molecule (VCAM)-1, and intercellular adhesion molecule (ICAM)-1. Blood flow quantitation was obtained with [(13)N] ammonia PET at rest and after adenosine stress. CFR was measured as the ratio of maximum flow to baseline flow at rest; abnormal CFR was defined as a ratio < 2.5. A summed stress score for visible perfusion defects was calculated. Results In within-pair analyses, all biomarkers, except VCAM-1, were higher in twins with lower CFR than their brothers with higher CFR (p < 0.05). This was observed in the entire sample, as well as within pairs discordant for a CFR of < 2.5. Associations persisted after adjusting for summed stress score and CAD risk factors. In contrast no biomarker, except IL-6, was related to the summed stress score of visible defects. Conclusions Even in asymptomatic subjects, a decrease in coronary microvascular function is accompanied by a systemic inflammatory response, independent of CAD risk factors. Our results, using a controlled twin design, highlight the importance of coronary microvascular function in the early phases of CAD. (J Am Coll Cardiol 2011;57:1271-9) (C) 2011 by the American College of Cardiology Foundation