PracticeUpdate Cardiology June 2019

EDITOR’S PICKS 12

Vascular Inflammation in Subclinical Atherosclerosis Detected by Hybrid PET/MRI Journal of the American College of Cardiology Take-home message • Patients with known subclinical atherosclerosis detected by vascular ultrasound and/or coronary calcification underwent hybrid 18 F-FDG PET/MRI of the carotid, aortic, and iliofemoral arteries to characterize arterial inflammation. Arterial inflammation was detected in 48.2% of the 755 participants; 90.1% had arterial plaques. Uptake of 18 F-FDG and the presence of plaques were both significantly associated with cardiovascular risk factors. Most 18 F-FDG uptake was seen in plaque-free arterial segments. Plaque burden was associated with arterial inflammation. • Almost half of all patients with subclinical atherosclerosis have arterial inflammation. Most 18 F-FDG uptake occurs in arterial segments without plaque. Atherosclerosis may present initially as arterial inflammation.

COMMENT By Paul M. Ridker MD T he recent CANTOS trial has provided proof of principle that targeted anti-inflammatory therapy can substantially reduce atherothrombotic event rates, with the greatest benefit accruing among patients with the most robust anti-inflammatory response. How, though, to identify in advance of treatment which patients these may be? In an elegant cross-sectional study of 755 patients with known atherosclerosis participating in the PESA-CNIC study, Fernández-Friera and colleagues used hybrid 18 F-FDG-PET/MRI to separate patients with arterial inflammation (defined as those with increased 18 F-FDG- PET uptake) from those with plaque inflammation (defined as coincident

18 F-FDG-PET uptake in MRI-detected plaques). Major findings include the identification of arterial inflammation in almost half of the individuals with subclinical atherosclerosis, typically correlating with traditional cardiovascular risk factors and with elevated levels of hsCRP. Yet, arterial inflammation was present in only 11% of established plaques, with most uptake occurring in plaque- free arterial walls. This is an important observation as it suggests that vascular inflammation may well precede plaque development, a crucial issue for the future targeting of anti-inflammatory therapies. Although testing this hypothesis will ultimately require prospective rather than cross-sectional data, Fernández-Friera

and colleagues have additionally shown that hybrid 18 F-FDG-PET/MRI can be done reproducibly in large-scale settings. By demonstrating that arterial inflammation is highly prevalent in middle-aged individuals with known subclinical atherosclerosis, this paper opens the door toward a possible future where anti-inflammatory therapies are targeted in a personalized manner to those in whom “residual inflammatory risk” is detected by direct visual evidence of arterial inflammation. Dr. Ridker is Director of the Center for Cardiovascular Disease Prevention and Eugene Braunwald Professor of Medicine at Brigham and Women’s Hospital in Boston, Massachusetts.

Abstract BACKGROUND Atherosclerosis is a chronic inflammatory disease, but data on arterial inflammation at early stages is limited. OBJECTIVES The purpose of this study was to characterize vascular inflam- mation by hybrid 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI). METHODS Carotid, aortic, and ilio-femoral 18 F-FDG PET/MRI was performed in 755 individuals (age 40 to 54 years; 83.7% men) with known plaques detected by 2-/3-dimensional vascular ultrasound and/or coronary cal- cification in the PESA (Progression of Early Subclinical Atherosclerosis) study. The authors evaluated the presence, distribution, and number of arterial inflammatory foci (increased 18 F-FDG uptake) and plaques with or without inflammation (coincident 18 F-FDG uptake). RESULTS Arterial inflammation was present in 48.2% of individuals (24.4% femorals, 19.3% aorta, 15.8% carotids, and 9.3% iliacs) and plaques in 90.1% (73.9% femorals, 55.8% iliacs, and 53.1% carotids). 18 F-FDG arterial uptakes and plaques significantly increased with cardiovascular risk factors (p < 0.01). Coincident 18 F-FDG uptakes were present in 287 of 2,605 (11%) plaques, and most uptakes were detected in plaque-free arterial segments (459 of 746; 61.5%). Plaque burden, defined by plaque presence, number, and volume, was significantly higher in individuals with arterial inflamma- tion than in those without (p < 0.01). The number of plaques and 18 F-FDG uptakes showed a positive albeit weak correlation (r = 0.25; p < 0.001). CONCLUSIONS Arterial inflammation is highly prevalent in middle-aged indi- viduals with known subclinical atherosclerosis. Large-scale multiterritorial

PET/MRI allows characterization of atherosclerosis-related arterial inflam- mation and demonstrates 18 F-FDG uptake in plaque-free arterial segments and, less frequently, within plaques. These findings suggest an arterial inflammatory state at early stages of atherosclerosis. Vascular Inflammation in Subclinical Atherosclerosis Detected by Hybrid PET/MRI. J Am Coll Cardiol 2019 Apr 02;73(12)1371-1382, L Fernández- Friera, V Fuster, B López-Melgar, et al. www.practiceupdate.com/c/81650

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