Systemic Atherosclerotic Inflammation Following Acute Myocardial Infarction: Myocardial Infarction Begets Myocardial Infarction Nikhil V. Joshi, MD; Iqbal Toor, MD; Anoop S. V. Shah, MD; Kathryn Carruthers, MPhil; Alex T. Vesey, MD; Shirjel R. Alam, MD; Andrew Sills, MD; Teng Y. Hoo; Adam J. Melville, MD; Sarah P. Langlands, MD; William S. A. Jenkins, MD; Neal G. Uren, MD; Nicholas L. Mills, PhD; Alison M. Fletcher, PhD; Edwin J. R. van Beek, PhD; James H. F. Rudd, PhD; Keith A. A. Fox, MD; Marc R. Dweck, PhD;* David E. Newby, DSc;* Background-—Preclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans. Methods and Results-—Overall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.150.30 versus 1.840.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.240.32 versus 2.020.21, P=0.03) than those with non–ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI. Conclusions-—The presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI. Clinical Trial Registration-—URL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254. ( J Am Heart Assoc. 2015;4: e001956 doi: 10.1161/JAHA.115.001956) Key Words: 18F-fluorodeoxyglucose positron emission and computed tomography • atherosclerosis • inflammation • vulnerable plaque D espite recent advances, prognosis following acute myocardial infarction (MI) remains poor 1–3 because of a considerable risk of recurrent infarction 4 and ischemia. 5 Such recurrent events are as likely to occur at the site of nonculprit plaques as at the site of the original culprit lesion. 6 In postmortem studies of patients dying after acute MI, there is evidence of multiple plaque-related thrombotic events: on average, 2.4 per patient. 7 Moreover, there is an increased From the Centre for Cardiovascular Science (N.V.J., I.T., A.S.V.S., K.C., A.T.V., S.R.A., A.S., T.Y.H., A.J.M., S.P.L., W.S.A.J., N.G.U., N.L.M., K.A.A.F., M.R.D., D.E.N.) and Clinical Research Imaging Centre (N.V.J., I.T., A.S.V.S., K.C., A.T.V., S.R.A., W.S.A.J., N.G.U., N.L.M., A.M.F., E.J.R.B., K.A.A.F., M.R.D., D.E.N.), University of Edinburgh, United Kingdom; Edinburgh Heart Centre, Royal Infirmary of Edinburgh, United Kingdom (N.V.J., I.T., A.S.V.S., K.C., A.T.V., S.R.A., W.S.A.J., N.G.U., N.L.M., K.A.A.F., M.R.D., D.E.N.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.). An accompanying Table S1 is available at http://jaha.ahajournals.org/content/4/9/e001956/suppl/DC1 *Dr Dweck and Dr Newby contributed equally as joint senior authors. Correspondence to: Nikhil V. Joshi, MD, University/BHF Centre for Cardiovascular Science, SU 305, Chancellors Building, Little France Crescent, Edinburgh, United Kingdom. E-mail: nikhil.joshi@ed.ac.uk Received April 22, 2015; accepted May 20, 2015. ª 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. DOI: 10.1161/JAHA.115.001956 Journal of the American Heart Association 1 ORIGINAL RESEARCH