Severity of Psoriasis Associates With Aortic Vascular Inflammation Detected by FDG PET/CT and Neutrophil Activation in a Prospective Observational Study

Abstract

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.

Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

“…Atherosclerosis and psoriasis are chronic inflammatory diseases accompanied by changes in blood cell composition and cytokine levels. Our group has shown in the past that psoriasis has increased neutrophil cell counts, which show a direct positive association with psoriasis severity (25). The role of monocytes and their subsets in human psoriasis was highlighted in a recent publication (8), which is in accordance to our mouse data presented in this study.…”

“…In patients with psoriasis, vascular inflammation is observed using 18-fludeoxyglucose PET/CT (FDG-PET/CT) signal in large vessels, namely the aorta -the signals of which have a dose-response relationship to psoriasis severity (25). The FDG-PET/CT signal is believed to be derived from infiltrative macrophages residing within the vessel wall (26).…”

Psoríase e Doença Cardiovascular: Impacto da Terapêutica com Inibidores do TNF-alfa

“…Os doentes com psoríase apresentaram um aumento significativo de inflamação em múltiplos segmentos da aorta, mesmo após ajuste para os fatores de risco cardiovascular tradicionais. Um outro estudo conduzido por Naik et al 40 avaliou a relação entre a inflamação vascular, medida por FDG-PET/ CT, através da média da razão target-to-background (TBR) aórtica, e a gravidade da psoríase, através do índice da área e gravidade da psoríase. Nesse estudo verificou-se que a gravidade da doença estava associada ao aumento da TBR, mesmo efetuando ajuste para a idade, sexo e score de risco de Framingham.…”

Invasive or non-invasive imaging for detecting high-risk coronary lesions?

“…Vascular 18 F-FDG signals have also been shown to be significantly correlated with presence of traditional cardiovascular risk factors (e.g. older age, smoking, hypertension, diabetes mellitus, and hyperlipidemia) and are elevated in patients with systemic inflammatory conditions conferring increased cardiovascular risk, such as rheumatoid arthritis and psoriasis [119][120][121]. Data from the prospective Dublin Carotid Atherosclerosis Stroke Study showed that increased carotid artery 18 F-FDG uptake can identify patients with increased risk of early stroke recurrence, independent of age and stenosis severity (Figure 4a,b) [122].…”