Psoriasis Severity Tied to Vascular Inflammation

Diana Swift

October 09, 2015

Psoriasis severity is independently associated with vascular inflammation beyond traditional cardiovascular risk factors, according to a small case-control study published online October 8 in Arteriosclerosis, Thrombosis, and Vascular Biology.

"These data suggest that psoriasis plaques are biologically active in promoting inflammation at remote sites," dermatologist Haley B. Naik, MD, from the National Heart, Lung, and Blood Institute and the National Cancer Institute in Bethesda, Maryland, and colleagues write.

The researchers found that psoriasis upregulated activation of neutrophils, the earliest immune cells present in psoriatic plaques, and neutrophil markers. In addition, increased levels of S100A8/A9, a proinflammatory protein that helps increase circulating neutrophils, were related to both skin disease severity and vascular inflammation, as measured by 18F-fluorodeoxyglucose positron emission tomography–computed tomography.

These findings suggest that neutrophils, primary cellular sources of the proinflammatory cytokine interleukin 17 in psoriatic skin disease, play a potentially important role in related cardiovascular disease, according to the authors.

In other findings, the Psoriasis Area and Severity Index score added incremental value beyond the Framingham Risk Score for cardiovascular disease (Χ2 = 8.66; P < .01) and high-sensitivity C-reactive protein (Χ2 = 6.48; P = .01) when added to nested models.

Study Details

The study analyzed 60 patients with psoriasis (median age, 47.5 years; 28 men) and 20 healthy age- and sex-matched control participants (median age, 41.0 years; 13 men) during 2013 to 2015. Both groups were overweight but had low cardiovascular risk by Framingham Risk Score; about half of the participants in both groups had a past history of dyslipidemia. In patients with psoriasis, Psoriasis Area and Severity Index scores (median, 5.4) were consistent with mild-to-moderate skin disease severity, and about half were receiving systemic biologic or other therapies.

The mean neutrophil-to-lymphocyte ratio was elevated in the psoriasis cohort compared with controls (2.1 vs 1.4; P < .001), and there was a nonsignificant trend for increased mean high-sensitivity C-reactive protein levels (2.0 vs 1.4 mg/L; P = .18), suggesting subclinical systemic inflammation in patients with psoriasis compared with control patients. Other indicators of increased innate immune activation, including interleukin 6 and tumor necrosis factor alpha, were noted in the psoriasis group.

The researchers also found that S100A8/A9 protein levels were related to both psoriasis severity (P = 02) and vascular inflammation (P = .02).

"S100A8/A9 protein may serve as a mediator or by-product in one of the potential pathways linking psoriasis severity and arterial inflammation," the authors write.

No sex- or racial/ethnic-based differences emerged in either the psoriasis or control cohort with regard to vascular inflammation.

Increasing Psoriasis Area and Severity Index scores in patients with psoriasis were associated with a rise in aortic target-to-background ratio (β = 0.41; P = .001), an association that remained significant after adjustment for age, sex, and Framingham Risk Score. The researchers also report increased neutrophil frequency (mean, 3.7 in the psoriasis group vs 2.9 in the controls; P = .02) and activation by lower neutrophil surface CD16 and CD62L in blood.

The association between psoriasis severity and atherosclerotic vascular disease outcomes is now well established by population-based cohort studies and several clinical studies, said Vinod Chandran, MD, PhD, a professor of rheumatology at the University of Toronto, Ontario, Canada, commenting on the study for Medscape Medical News.

"The translational research work in this investigation provides strong evidence based on imaging vascular inflammation and clinical evaluation of psoriasis severity, traditional risk factors, and select biomarkers, that psoriasis severity is indeed associated with increased vascular inflammation beyond risk factors for vascular disease," he said.

Although the exact mechanisms remain unknown, there is evidence that similar mechanisms operate at sites of vascular inflammation and psoriatic plaques, Dr Chandran said, "Previous studies interrogating the skin transcriptome and serum markers have demonstrated potential linkage between altered gene transcription in the skin and changes in serum markers for comorbidities commonly seen in patients with moderate-to-severe psoriasis."

Calling their study the first attempt at systematic characterization of psoriasis severity and aortic vascular inflammation, the authors concede that the study's cross-sectional design precludes establishing causality and cite the need for more understanding of how skin severity relates to vascular inflammation and how this relationship changes with biological therapy. National clinical trials of treatment effect outcomes are underway to elucidate these relationships.

In the meantime, Dr Chandran said, the management of cardiovascular disease risk in patients with psoriasis should include early optimal management of both inflammatory skin disease and traditional cardiovascular disease risk factors.

"Prospective studies will need to demonstrate that treatment of severe psoriasis leads to reduction in vascular inflammation, as observed by imaging, as well as reduce [cardiovascular disease] events," he said.

This study was supported by the National Heart, Lung and Blood Institute Intramural Research Program and a National Psoriasis Foundation Discovery Grant. The authors have disclosed no relevant financial relationships. Dr. Chandran has declared no competing interests.

Arterioscler Thromb Vasc Biol. Published online October 8, 2015. Abstract

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