Abhishek Chaturvedi

Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study.

Background: Psoriasis, a chronic inflammatory disease associated with an accelerated risk of myocardial infarction, provides an ideal human model to study inflammatory atherogenesis in vivo. We hypothesized that the increased cardiovascular risk observed in psoriasis would be partially attributable to an elevated subclinical coronary artery disease burden composed of noncalcified plaques with high-risk features. However, inadequate efforts have been made to directly measure coronary artery disease in this vulnerable population. As such, we sought to compare total coronary plaque burden and noncalcified coronary plaque burden (NCB) and high-risk plaque (HRP) prevalence between patients with psoriasis (n=105), patients with hyperlipidemia eligible for statin therapy under National Cholesterol Education Program-Adult Treatment Panel III guidelines (n=100) who were ≈10 years older, and healthy volunteers without psoriasis (n=25). Methods: Patients underwent coronary computed-tomography angiography for total coronary plaque burden and NCB quantification and HRP identification, defined as low attenuation (<30 hounsfield units), positive remodeling (>1.10), and spotty calcification. A consecutive sample of the first 50 patients with psoriasis was scanned again 1 year after therapy. Results: Despite being younger and at lower traditional risk than patients with hyperlipidemia, patients with psoriasis had increased NCB (mean±SD: 1.18±0.33 versus 1.11±0.32, P=0.02) and similar HRP prevalence (P=0.58). Furthermore, compared to healthy volunteers, patients with psoriasis had increased total coronary plaque burden (1.22±0.31 versus 1.04±0.22, P=0.001), NCB (1.18±0.33 versus 1.03±0.21, P=0.004), and HRP prevalence beyond traditional risk (odds ratio, 6.0; 95% confidence interval, 1.1–31.7; P=0.03). Last, among patients with psoriasis followed for 1 year, improvement in psoriasis severity was associated with improvement in total coronary plaque burden (&bgr;=0.45, 0.23–0.67; P<0.001) and NCB (&bgr;=0.53, 0.32–0.74; P<0.001) beyond traditional risk factors. Conclusions: Patients with psoriasis had greater NCB and increased HRP prevalence than healthy volunteers. In addition, patients with psoriasis had elevated NCB and equivalent HRP prevalence as older patients with hyperlipidemia. Last, modulation of target organ inflammation (eg, skin) was associated with an improvement in NCB at 1 year, suggesting that control of remote sites of inflammation may translate into reduced coronary artery disease risk.

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.

Identification of proresolving and inflammatory lipid mediators in human psoriasis

BACKGROUND Psoriasis (PSO) is an immune-mediated inflammatory disease associated with metabolic and cardiovascular comorbidities. It is now known that resolution of inflammation is an active process locally controlled by specialized proresolving mediators (SPMs), named resolvins (Rvs), protectins, and maresins. OBJECTIVE It is unknown whether these potent lipid mediators (LMs) are involved in PSO pathophysiology and if the skin and blood have disease-specific SPMs phenotype profiles. METHODS We used liquid chromatography-tandem mass spectrometry-based LM metabololipidomics to obtain skin and peripheral blood LM profiles from PSO compared to healthy subjects. Some LMs were tested in cell culture experiments with corresponding gene expression and protein concentration analyses. RESULTS The levels of several LM were significantly elevated in lesional PSO skin compared to nonlesional and skin from healthy subjects. Particularly, RvD5, protectins Dx, and aspirin-triggered forms of lipoxin were present only in lesional PSO skin, whereas protectin D1 was present in nonlesional PSO skin. To determine specific roles of SPMs on skin-related inflammatory cytokines, RvD1 and RvD5 were incubated with human keratinocytes. RvD1 and RvD5 reduced the expression levels of interleukin 24 and S100A12, whereas only RvD1 significantly abrogated interleukin-24 production by keratinocytes. CONCLUSIONS These findings suggest that an imbalance between locally produced proresolution and proinflammatory LMs identified in PSO skin and blood compartments might play a role in PSO pathophysiology. Moreover, some of the PSO-related cytokines can be modified by specific SPMs and involved mechanisms support investigation of targeting novel proresolving lipid mediators as a therapy for PSO.

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

Vascular Inflammation Imaging in Psoriasis

Purpose of ReviewPsoriasis is a common, chronic inflammatory skin disease driven by immune dysregulation involving helper T cell 17 pathways. Psoriasis is associated with systemic inflammation, which increases the risk of joint disease (psoriatic arthritis), subclinical cardiovascular disease, and major adverse cardiovascular events, especially in young patients with severe skin disease. Furthermore, vascular inflammation by 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) provides a valuable tool with utility in predicting future cardiovascular events. As such, psoriasis provides a clinical human model to characterize the vascular disease by non-invasive imaging techniques such as vascular inflammation by FDG PET/CT.Recent FindingsFDG PET/CT has garnered considerable interest in multiple completed and ongoing cardiovascular and psoriasis trials. Indeed, recent studies have shown that psoriasis is associated with increased vascular inflammation. Furthermore, a dose-response was demonstrated between severity of skin disease and severity of vascular inflammation in psoriasis. Additionally, observational studies have reported that treatment of psoriasis decreases vascular inflammation with several randomized trials still ongoing. Emerging data from a single report demonstrated that use of FDG PET/MRI may provide soft tissue localization of the FDG tracer in the aorta and the carotids but larger studies are underway.SummaryThis review outlines the initial use, development, and current utility of FDG PET/CT in psoriasis covering cross-sectional and longitudinal studies that examined the relationship between psoriasis, severity of skin disease, presence of joint disease, treatment of skin disease, and emerging techniques to identify vascular inflammation as a marker of cardiovascular risk in psoriasis.