Systemic Atherosclerotic Inflammation Following Acute Myocardial Infarction: Myocardial Infarction Begets Myocardial Infarction

Abstract

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.

Keywords: 18F‐fluorodeoxyglucose positron emission and computed tomography; atherosclerosis; inflammation; vulnerable plaque.

Figure 1

Measurement of radiotracer uptake in the aorta. The aorta was segmented into ascending aorta (A), arch of aorta (B), and descending aorta (C), as shown. Regions of interest were drawn around the aorta on axial slices to provide measures of radiotracer uptake.

Figure 2

Uptake of 18F-FDG by aortic atherosclerosis in patients with stable and unstable coronary heart disease. Aortic mean of the maximum tissue-to-background ratio for 18F-FDG uptake in patients with stable angina, STEMI, and NSTEMI. Mean with 95% CI. 18F-FDG indicates 18F-fluorodeoxyglucose; NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction.

Figure 3

Kaplan–Meier curves demonstrating survival free from early recurrent myocardial infarction at 30 days. Patients were placed in tertiles according to their peak plasma troponin I concentrations (tertile 1, ≤220 ng/L; tertile 2, 230 to 6130 ng/L; tertile 3, ≥6140 ng/L).