Mohammad Tarek Kabbany

Association Between Skin and Aortic Vascular Inflammation in Patients With Psoriasis: A Case-Cohort Study Using Positron Emission Tomography/Computed Tomography

Importance Inflammation is critical in the development of atherosclerosis. Psoriasis is a chronic inflammatory skin disease that is associated with increased vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography in vivo and future cardiovascular events. It provides a human model to understand the effect of treating inflammation in a target organ (eg, the skin) on vascular diseases. Objective To investigate the association between change in skin disease severity and change in vascular inflammation at 1 year and to characterize the impact of 1 year of anti–tumor necrosis factor therapy on vascular inflammation. Design, Setting, and Participants In this prospective cohort study, 220 participants from outpatient practices were recruited at the US National Institutes of Health. A total of 115 consecutively recruited patients with psoriasis were followed up at 1 year. The study was conducted from January 1, 2013, through October 31, 2016, with data analyzed in November 2016. Exposure Skin inflammation measured as Psoriasis Area and Severity Index (PASI) score. Main Outcomes and Measures Vascular inflammation assessed as target-to-background ratio by 18fluorodeoxyglucose positron emission tomography/computed tomography. Results Among the 115 patients, the mean (SD) age at 1-year follow-up was 50.8 (12.8) years and 68 were men (59%). The cohort had a low cardiovascular risk by Framingham risk score and mild-to-moderate psoriasis, with a median PASI score of 5.2 (interquartile range, 3.0-8.9). At follow-up, the total cohort had a median improvement in PASI score of 33%, with use of topical therapy (60%), biological therapy (66%, mostly anti–tumor necrosis factor) and phototherapy (15%) (P < .001). Moreover, improvement in PASI score was associated with improvement in target-to-background ratio of 6%, mainly driven by those with higher responses in PASI score (P < .001). This association persisted beyond traditional risk factors (&bgr; = 0.19; 95% CI, 0.012-0.375; P = .03) and was the strongest in those initiated with anti–tumor necrosis factor therapy (&bgr; = 0.79; 95% CI, 0.269-1.311; P = .03). Conclusions and Relevance Improvement in psoriasis skin disease severity was associated with improvement in aortic vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography, with greater improvement in aortic vascular inflammation observed in those who had higher than 75% reduction in skin disease severity. These findings suggest that controlling remote target organ inflammation (eg, in the skin) may improve vascular diseases; however, randomized clinical trials are needed to confirm these findings.

SMALL DENSE LOW-DENSITY LIPOPROTEIN (LDL) PARTICLE NUMBER PREDICTS VASCULAR INFLAMMATION INDEPENDENT OF TRADITIONAL LIPID CARDIOVASCULAR RISK FACTORS IN PSORIASIS

Small, dense low-density lipoproteins (sLDL-p) by nuclear magnetic resonance (NMR) were recently shown to be a strong predictor of CV events. If this relationship is true in inflammatory states, which modulate lipoprotein structure and function, is unclear. Psoriasis (PSO), a chronic inflammatory

18: IMPROVEMENT IN PSORIASIS SKIN DISEASE SEVERITY IS ASSOCIATED WITH REDUCTION OF CORONARY PLAQUE BURDEN

Purpose of Study Psoriasis (PSO), a chronic inflammatory disease associated with increased cardiovascular (CV) risk, provides a clinical human model to study inflammatory atherogenesis. While PSO severity is associated with both in vivo vascular disease and future CV risk, the longitudinal impact of PSO severity on coronary disease progression is unknown. We hypothesized that an improvement in PSO severity may lead to a reduction in coronary plaque burden by coronary CT angiography (CCTA). Methods Used Consecutively recruited PSO patients (N=50) underwent CCTA (320 detector row, Toshiba) and cardiometabolic profiling at baseline and 1-year follow-up. Total (TB) and non-calcified (NCB) coronary plaque burden were quantified using QAngio (Medis, Netherlands). PSO severity was measured as the psoriasis area severity index (PASI). The longitudinal change in coronary plaque burden was analyzed with unadjusted and adjusted regression. Summary of Results The cohort had a low Framingham Risk Score and mild to moderate PSO. Patients whose PSO severity improved (ΔPASI −27%; p<0.001) (N=33) had significant improvement in TB (β=0.40, p=0.003) and NCB (β=0.49, p<0.001) (table 1), beyond adjustment for traditional CV risk factors, BMI, statin use, & systemic/biologic PSO therapy. Conclusions Improvement in PSO severity was associated with improvement in coronary plaque burden by CCTA. Our study suggests that a reduction in skin inflammation may reduce the progression of early, non-calcified coronary plaque. Larger studies are needed to confirm these findings. Abstract 18 Figure 1 *P-value is calculated by comparing baseline and 1-year follow-up values for variables using paired t-test for continuous variables, and Pearsons chi-squared test for categorical variables. All values are expressed as Mean±SD, unless specified otherwise. PASI: Psoriasis Area Severity Index.

VISCERAL BUT NOT SUBCUTANEOUS ADIPOSE TISSUE ASSOCIATES WITH VASCULAR INFLAMMATION BY 18-FDG PET/CT IN PSORIASIS

Background: Psoriasis, a chronic inflammatory disease, is associated with vascular inflammation (VI) by FDG PET/CT and increased cardiometabolic dysfunction including adipose tissue dysregulation. Recently, visceral adiposity (VAT) was shown to associate with cardiovascular events in non-psoriasis

IMPROVEMENT IN CHOLESTEROL EFFLUX CAPACITY IS ASSOCIATED WITH IMPROVEMENT IN VASCULAR INFLAMMATION BY 18- FDG PET CT IN PSORIASIS

Background: Psoriasis (PSO), a chronic inflammatory disease associated with increased CV risk, provides a human model to study atherogenesis. While PSO is associated with increased vascular inflammation (VI), and impaired cholesterol efflux (CEC), the longitudinal impact of change in CEC on VI is

AORTIC VASCULAR INFLAMMATION BY 18-FDG PET/MRI IS RELATED TO CORONARY PLAQUE BURDEN BY QUANTITATIVE CORONARY CT ANGIOGRAPHY IN PSORIASIS

Psoriasis (PSO), a chronic inflammatory skin disease, is associated with vascular inflammation (VI) by 18-F FDG PET/MRI and an increased risk of MI. Coronary computed tomography angiography (CCTA) characterizes the composition of plaque in coronary heart disease (CHD). We hypothesized that VI in the

IMPROVEMENT IN PSORIASIS SKIN DISEASE SEVERITY IS ASSOCIATED WITH REDUCTION OF CORONARY PLAQUE BURDEN

18 Figure 1 *P-value is calculated by comparing baseline and 1-year follow-up values for variables using paired t-test for continuous variables, and Pearson’s chi-squared test for categorical variables. All values are expressed as Mean±SD, unless specified otherwise. PASI: Psoriasis Area Severity Index. 814 J Investig Med 2016;64:800–825 Abstracts group.bmj.com on December 16, 2016 Published by http://jim.bmj.com/ Downloaded from

21: DETERMINANTS OF VASCULAR INFLAMMATION BY 18-FLUORODEOXYGLUCOSE PET/MRI: FINDINGS FROM THE PSORIASIS, ATHEROSCLEROSIS AND CARDIOMETABOLIC DISEASE INITIATIVE

Purpose of Study Psoriasis (PSO), a chronic inflammatory disease associated with increased CV risk, provides a clinical human model to study inflammatory atherogenesis. We aimed to assess the major determinants of vascular inflammation (VI) measured by 18FDG PET-MRI in a well-phenotyped PSO cohort. Methods Used 124 consecutive patients with PSO underwent 18FDG PET-MRI scans. We used target-to-background ratio to quantify VI 120 minutes post FDG injection. Homeostatic model assessment of insulin resistance (HOMA-IR) was measured, along with cholesterol efflux capacity (CEC) and HDL particle concentration by NMR (Liposcience) fasting. Summary of Results Our cohort was middle aged (mean 49±13.3 years) with mild to moderate PSO, and low CV risk (median Framingham Risk Score (FRS) 2, IQR 2–6). PSO was associated with increased VI (β=0.27, p<0.005), compared to healthy controls. VI was associated with HOMA-IR (β=0.26, p<0.001), CEC (β=−0.12, p=0.04) and HDL particle concentration (β=−0.19, p=0.003) beyond traditional CV risk factors (age, gender, FRS and BMI). Among these, HOMA-IR provided maximum incremental value in predicting VI beyond traditional risk factors (χ2=39.36, p<0.001). Conclusions VI by FDG PET MRI is associated with traditional CV risk factors and cardiometabolic parameters. Insulin resistance and CEC were most strongly associated with VI by 18FDG PET-MRI beyond traditional CV risk factors and BMI in PSO suggesting that cardiometabolic disease increases CV risk in PSO. Abstract 21 Figure 1

DETERMINANTS OF VASCULAR INFLAMMATION BY 18-FLUORODEOXYGLUCOSE PET/MRI: FINDINGS FROM THE PSORIASIS, ATHEROSCLEROSIS AND CARDIOMETABOLIC DISEASE INITIATIVE

Psoriasis (PSO), a chronic inflammatory disease associated with increased CV risk, provides a clinical human model to study inflammatory atherogenesis. We aimed to assess the major determinants of vascular inflammation (VI) measured by 18FDG PET-MRI in a well-phenotyped PSO cohort. 124 consecutive