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      Association of Biologic Therapy With Coronary Inflammation in Patients With Psoriasis as Assessed by Perivascular Fat Attenuation Index

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          Abstract

          This cohort study investigates the association of biologic therapy with coronary inflammation in patients with psoriasis as assessed by the perivascular fat attenuation index, an imaging biomarker that assesses coronary inflammation by mapping spatial changes of perivascular fat composition via coronary computed tomography angiography. Is biologic therapy for psoriasis associated with a change in coronary inflammation as assessed by the perivascular fat attenuation index? In this cohort study of 134 consecutive patients with moderate to severe psoriasis, biologic therapy was associated with a significant decrease in coronary inflammation as assessed by perivascular fat attenuation index, a marker of coronary inflammation associated with cardiovascular outcomes. Patients not receiving biologic therapy had no change in perivascular fat attenuation index at 1 year. The findings suggest that biologic therapy for moderate to severe psoriasis is associated with a reduction in coronary inflammation assessed as perivascular fat attenuation index and thus that perivascular fat attenuation index may be used to track response to interventions in the coronary artery. Psoriasis is a chronic inflammatory skin disease associated with increased coronary plaque burden and cardiovascular events. Biologic therapy for psoriasis has been found to be favorably associated with luminal coronary plaque, but it is unclear whether these associations are attributable to direct anti-inflammatory effects on the coronary arteries. To investigate the association of biologic therapy with coronary inflammation in patients with psoriasis using the perivascular fat attenuation index (FAI), a novel imaging biomarker that assesses coronary inflammation by mapping spatial changes of perivascular fat composition via coronary computed tomography angiography (CCTA). This prospective cohort study performed from January 1, 2013, through March 31, 2019, analyzed changes in FAI in patients with moderate to severe psoriasis who underwent CCTA at baseline and at 1 year and were not receiving biologic psoriasis therapy at baseline. Biologic therapy for psoriasis. Perivascular FAI mapping was performed based on an established method by a reader blinded to patient demographics, visit, and treatment status. Of the 134 patients (mean [SD] age, 51.1 [12.1] years; 84 [62.5%] male), most had low cardiovascular risk by traditional risk scores (median 10-year Framingham Risk Score, 3% [interquartile range, 1%-7%]) and moderate to severe skin disease. Of these patients, 82 received biologic psoriasis therapy (anti–tumor necrosis factor α, anti–interleukin [IL] 12/23, or anti–IL-17) for 1 year, and 52 did not receive any biologic therapy and were given topical or light therapy (control group). At baseline, 46 patients (27 in the treated group and 19 in the untreated group) had a focal coronary atherosclerotic plaque. Biologic therapy was associated with a significant decrease in FAI at 1 year (median FAI −71.22 HU [interquartile range (IQR), −75.85 to −68.11 HU] at baseline vs −76.09 HU [IQR, −80.08 to −70.37 HU] at 1 year; P  < .001) concurrent with skin disease improvement (median PASI, 7.7 [IQR, 3.2-12.5] at baseline vs 3.2 [IQR, 1.8-5.7] at 1 year; P  < .001), whereas no change in FAI was noted in those not receiving biologic therapy (median FAI, −71.98 [IQR, −77.36 to −65.64] at baseline vs −72.66 [IQR, −78.21 to −67.44] at 1 year; P  = .39). The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents, including anti–tumor necrosis factor α (median FAI, −71.25 [IQR, −75.86 to −66.89] at baseline vs −75.49 [IQR, −79.12 to −68.58] at 1 year; P  < .001) and anti–IL-12/23 or anti–IL-17 therapy (median FAI, −71.18 [IQR, −75.85 to −68.80] at baseline vs −76.92 [IQR, −81.16 to −71.67] at 1 year; P  < .001). In this study, biologic therapy for moderate to severe psoriasis was associated with reduced coronary inflammation assessed by perivascular FAI. This finding suggests that perivascular FAI measured by CCTA may be used to track response to interventions for coronary artery disease.

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          Most cited references12

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          Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (the CRISP CT study): a post-hoc analysis of prospective outcome data

          Summary Background Coronary artery inflammation inhibits adipogenesis in adjacent perivascular fat. A novel imaging biomarker—the perivascular fat attenuation index (FAI)—captures coronary inflammation by mapping spatial changes of perivascular fat attenuation on coronary computed tomography angiography (CTA). However, the ability of the perivascular FAI to predict clinical outcomes is unknown. Methods In the Cardiovascular RISk Prediction using Computed Tomography (CRISP-CT) study, we did a post-hoc analysis of outcome data gathered prospectively from two independent cohorts of consecutive patients undergoing coronary CTA in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort). Perivascular fat attenuation mapping was done around the three major coronary arteries—the proximal right coronary artery, the left anterior descending artery, and the left circumflex artery. We assessed the prognostic value of perivascular fat attenuation mapping for all-cause and cardiac mortality in Cox regression models, adjusted for age, sex, cardiovascular risk factors, tube voltage, modified Duke coronary artery disease index, and number of coronary CTA-derived high-risk plaque features. Findings Between 2005 and 2009, 1872 participants in the derivation cohort underwent coronary CTA (median age 62 years [range 17–89]). Between 2008 and 2016, 2040 patients in the validation cohort had coronary CTA (median age 53 years [range 19–87]). Median follow-up was 72 months (range 51–109) in the derivation cohort and 54 months (range 4–105) in the validation cohort. In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other. Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR] 2·15, 95% CI 1·33–3·48; p=0·0017 in the derivation cohort, and 2·06, 1·50–2·83; p<0·0001 in the validation cohort). The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as −70·1 Hounsfield units (HU) or higher in the derivation cohort (HR 9·04, 95% CI 3·35–24·40; p<0·0001 for cardiac mortality; 2·55, 1·65–3·92; p<0·0001 for all-cause mortality). This cutoff was confirmed in the validation cohort (HR 5·62, 95% CI 2·90–10·88; p<0·0001 for cardiac mortality; 3·69, 2·26–6·02; p<0·0001 for all-cause mortality). Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality. Interpretation The perivascular FAI enhances cardiac risk prediction and restratification over and above current state-of-the-art assessment in coronary CTA by providing a quantitative measure of coronary inflammation. High perivascular FAI values (cutoff ≥–70·1 HU) are an indicator of increased cardiac mortality and, therefore, could guide early targeted primary prevention and intensive secondary prevention in patients. Funding British Heart Foundation, and the National Institute of Health Research Oxford Biomedical Research Centre.
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            Detecting human coronary inflammation by imaging perivascular fat.

            Early detection of vascular inflammation would allow deployment of targeted strategies for the prevention or treatment of multiple disease states. Because vascular inflammation is not detectable with commonly used imaging modalities, we hypothesized that phenotypic changes in perivascular adipose tissue (PVAT) induced by vascular inflammation could be quantified using a new computerized tomography (CT) angiography methodology. We show that inflamed human vessels release cytokines that prevent lipid accumulation in PVAT-derived preadipocytes in vitro, ex vivo, and in vivo. We developed a three-dimensional PVAT analysis method and studied CT images of human adipose tissue explants from 453 patients undergoing cardiac surgery, relating the ex vivo images with in vivo CT scan information on the biology of the explants. We developed an imaging metric, the CT fat attenuation index (FAI), that describes adipocyte lipid content and size. The FAI has excellent sensitivity and specificity for detecting tissue inflammation as assessed by tissue uptake of 18F-fluorodeoxyglucose in positron emission tomography. In a validation cohort of 273 subjects, the FAI gradient around human coronary arteries identified early subclinical coronary artery disease in vivo, as well as detected dynamic changes of PVAT in response to variations of vascular inflammation, and inflamed, vulnerable atherosclerotic plaques during acute coronary syndromes. Our study revealed that human vessels exert paracrine effects on the surrounding PVAT, affecting local intracellular lipid accumulation in preadipocytes, which can be monitored using a CT imaging approach. This methodology can be implemented in clinical practice to noninvasively detect plaque instability in the human coronary vasculature.
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              SCCT guidelines for the performance and acquisition of coronary computed tomographic angiography: A report of the society of Cardiovascular Computed Tomography Guidelines Committee: Endorsed by the North American Society for Cardiovascular Imaging (NASCI).

              In response to recent technological advancements in acquisition techniques as well as a growing body of evidence regarding the optimal performance of coronary computed tomography angiography (coronary CTA), the Society of Cardiovascular Computed Tomography Guidelines Committee has produced this update to its previously established 2009 "Guidelines for the Performance of Coronary CTA" (1). The purpose of this document is to provide standards meant to ensure reliable practice methods and quality outcomes based on the best available data in order to improve the diagnostic care of patients. Society of Cardiovascular Computed Tomography Guidelines for the Interpretation is published separately (2). The Society of Cardiovascular Computed Tomography Guidelines Committee ensures compliance with all existing standards for the declaration of conflict of interest by all authors and reviewers for the purpose ofclarity and transparency.
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                Author and article information

                Journal
                JAMA Cardiology
                JAMA Cardiol
                American Medical Association (AMA)
                2380-6583
                July 31 2019
                Affiliations
                [1 ]National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
                [2 ]Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
                [3 ]DermAssociates, Silver Spring, Maryland
                [4 ]Division of Cardiology, The George Washington University School of Medicine, Washington, District of Columbia
                [5 ]Department of Dermatology, University of Pennsylvania, Philadelphia
                [6 ]Department of Radiology, University of Wisconsin, Madison
                [7 ]Caristo Diagnostics, Oxford, United Kingdom
                Article
                10.1001/jamacardio.2019.2589
                6669789
                31365032
                177d05bc-c748-4eed-9473-4864b67512f2
                © 2019
                History

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