Objective To understand whether directly-measured psoriasis severity is associated with vascular inflammation assessed by 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG PET/CT). Approach In depth cardiovascular and metabolic phenotyping was performed in adult psoriasis patients (n=60) and controls (n=20). Psoriasis severity was measured using psoriasis area severity index (PASI). Vascular inflammation was measured using average aortic target-to-background ratio using FDG PET/CT. Results Both the psoriasis patients (28 men, 32 women, mean age 47 years) and controls (13 men, 7 women, mean age 41 years) were young with low cardiovascular risk. PASI scores (Median 5.4; IQR 2.8-8.3) were consistent with mild to moderate skin disease severity. Increasing PASI score was associated with an increase in aortic TBR (β=0.41, p=0.001), an association that changed little after adjustment for age, sex and Framingham risk score. We observed evidence of increased neutrophil frequency (mean psoriasis: 3.7±1.2; vs 2.9±1.2; p=0.02) and activation by lower neutrophil surface CD16 and CD62L in blood. Serum levels of S100A8/A9 (745.1±53.3 vs 195.4±157.8 ng/mL; p<0.01) and neutrophil elastase-1 (43.0±2.4 vs 30.8±6.7 ng/mL; p<0.001) were elevated in psoriasis. Finally, S100A8/A9 protein related to both psoriasis skin disease severity (β=0.53; p=0.02) and vascular inflammation (β=0.48; p=0.02). Conclusions Psoriasis severity is associated with vascular inflammation beyond cardiovascular risk factors. Psoriasis increased neutrophil activation and neutrophil markers, and S100A8/A9 related to both skin disease severity and vascular inflammation.

Rationale GlycA, an emerging inflammatory biomarker, predicted cardiovascular events in population-based studies. Psoriasis, an inflammatory disease associated with increased cardiovascular risk, provides a model to study inflammatory biomarkers in cardiovascular disease (CVD). Whether GlycA associates with psoriasis and how it predicts subclinical CVD beyond hsCRP in psoriasis is unknown. Objective To investigate the relationships between GlycA and psoriasis, and between GlycA and subclinical CVD. Methods and Results Psoriasis patients and controls (n=412) participated in a two-stage study. We measured GlycA by NMR spectroscopy. NIH participants underwent 18-FDG PET/CT scans to assess vascular inflammation (VI) and coronary CT angiography to quantify coronary artery disease (CAD) burden. Psoriasis cohorts were young (mean age=47.9), with low cardiovascular risk and moderate skin disease. HsCRP and GlycA were increased in psoriasis compared to controls [GlycA: (PENN: 408.8±75.4 vs. 289.4±60.2, p<0.0001, NIH: 415.8±63.2 vs. 346.2±46, p<0.0001)] and demonstrated a dose-response with psoriasis severity. In stage 2, VI (β=0.36, p<0.001) and CAD (β=0.29, p=0.004) associated with GlycA beyond CV risk factors in psoriasis. In ROC analysis, GlycA added value in predicting VI (p=0.01) and CAD (p<0.01). Finally, initiating anti-TNF therapy (n=16) reduced psoriasis severity (p<0.001), GlycA (463.7±92.5 vs. 370.1±78.5; p<0.001) and VI (1.93±0.36 vs. 1.76±0.19; p<0.001), while GlycA remained associated with VI (β=0.56, p<0.001) post-treatment. Conclusions GlycA associated with psoriasis severity and subclinical CVD beyond traditional CV risk and hsCRP. Moreover, psoriasis treatment reduced GlycA and VI. These findings support the potential utility of GlycA in subclinical CVD risk assessment in psoriasis and potentially other inflammatory diseases.