Background Minimally elevated serum cardiac troponin (Tn) reflects myocardial injury and

Background Minimally elevated serum cardiac troponin (Tn) reflects myocardial injury and is associated with increased mortality even absent coronary artery disease (CAD). tomography (PET) were followed (median 2.8 years) for Bazedoxifene acetate major adverse cardiovascular events (MACE) including cardiovascular death nonfatal myocardial infarction or late revascularization. Patients with flow-limiting CAD left ventricular ejection fraction (LVEF) <40% Bazedoxifene acetate and/or revascularization within 60 days of imaging were excluded. CFR was quantified from stress/rest myocardial blood flow using PET. Compared to patients with unfavorable Tn those with at least one positive Tn (n=97) had higher pretest clinical scores more renal dysfunction and lower LVEF and CFR. In adjusted analysis impaired CFR remained independently associated with positive Tn (odds ratio 2.18 95 1.37 P=0.001) and both impaired CFR and positive Tn independently associated with MACE (hazard ratio 2.25; 95%CI 1.31-3.86; P=0.003 and 2.42; 95%CI 1.34-4.40; P=0.004 respectively). Impaired CFR and positive Tn Snr1 identified patients at highest risk of MACE (log-rank P<0.0001) with a significant conversation (P<0.007) seen between CFR and Tn. Conclusions In patients without overt CAD impaired CFR independently associated Bazedoxifene acetate with minimally elevated Tn and MACE. Impaired CFR here reflecting microvascular dysfunction altered the effect of a positive Tn on adverse outcomes. Keywords: coronary artery disease troponin coronary flow reserve microvascular dysfunction Minimally elevated levels of serum cardiac troponin are associated with increased mortality even among subjects without acute coronary syndromes (ACS)1-3 or overt coronary artery disease.4 Increasing evidence from screening of large epidemiologic cohorts primarily using high-sensitivity cardiac troponin assays suggests that subclinical cardiac structural abnormalities may contribute to excess risk 5 6 especially of incident heart failure 7 8 in patients with low but detectable levels of troponin. These cardiac troponin values have been associated with the presence of left ventricular hypertrophy diabetes mellitus and chronic kidney disease.9 10 Bazedoxifene acetate Although impaired hemodynamics endothelial dysfunction and coronary vasomotor stiffness all of which may lead to chronic myocardial ischemia and injury have been invoked as potential mechanisms of mild elevations in cardiac troponin 9 11 the pathophysiology of this process in non-ACS settings remains unclear. Coronary vascular dysfunction as assessed by a reduced coronary flow reserve (CFR calculated as the ratio of hyperemic to rest absolute myocardial blood flow) is highly prevalent among patients with known or suspected coronary artery disease (CAD) and identifies patients at high risk for major adverse cardiac events including cardiac death.12-15 These associations are seen even in the absence of obstructive epicardial CAD16 or defects in relative myocardial perfusion imaging 14 15 and are especially evident across heterogeneous-risk cohorts such as those with diabetes 17 older age 18 19 or chronic kidney disease 20 in whom diffuse atherosclerosis and/or microvascular dysfunction likely contribute to adverse Bazedoxifene acetate outcomes. Because CFR provides a quantitative assessment of the integrated effects of epicardial coronary stenosis diffuse atherosclerosis and microvascular dysfunction 21 its role as a sensitive marker of myocardial tissue perfusion warrants further investigation. We sought to explore the mechanistic relationship between biomarkers of coronary vasomotor function and low-level myocardial injury and their contributions to cardiovascular outcomes in patients without overt CAD. We hypothesized that impaired CFR as quantified noninvasively by positron emission tomography (PET) associates independently with low but positive levels of cardiac troponin and that both impaired CFR and elevated troponin associate independently with adverse cardiovascular outcomes. Methods Study Population Study participants were consecutive patients referred for serial serum cardiac troponin testing within 14 days prior to stress testing with myocardial perfusion PET for evaluation of suspected CAD at Brigham and Women’s Hospital (BWH) between January 1 2006 and July 31 2011 The most common indications for testing included evaluation of chest pain dyspnea or their combination. Patient history medication use and select laboratory values were ascertained at time of PET imaging. From 1975 patients.