Cardiovascular disease in psoriasis may be due to a cardiosplenic axis

LONDON - The spleen may have a role in driving the higher rate of cardiovascular disease seen in psoriasis patients through a spleen–atherosclerotic axis, suggests research presented at the Psoriasis: From Gene to Clinic International Congress in London on December 2.

It is well know that psoriasis is associated with an increased risk for cardiovascular disease and it has been suggested that this could be a consequence of systemic inflammation prompting cardiovascular comorbidities, such as premature atherosclerotic disease.

Studies of soluble biomarkers of systemic inflammation have shown evidence of mild systemic inflammation in patients with psoriasis compared with healthy controls. However, unlike with other inflammatory diseases, such as rheumatoid arthritis, evidence of systemic inflammation in psoriasis has been contradictory and a relatively recent review showed only a weak association between psoriasis and system inflammation, Dr. Kasper Hjuler of Aarhus University Hospital in Denmark reported at the meeting.

Previous studies have also shown increased levels of arterial inflammation in psoriasis, but Dr. Hjuler pointed out that “these studies are generally showing an increased level of vascular wall inflammation and not specifically systemic inflammation.”

Researchers have now moved their attention to an organ involved in the regulation of immune responses and systemic inflammation – the spleen – as research has shown that the spleen plays a role in disease mechanisms in other Th17 regulated diseases, such as muscular sclerosis.

A central role for the spleen in the progression of atherosclerotic disease has been proposed through a mechanism conceptualized as the ‘cardiosplenic axis.’ Positron emission tomography (PET) computed tomography (CT) has shown that splenic inflammation, assessed by 18F-fluorodeoxyglucose (FDG), is increased in patients with autoimmune and inflammatory diseases, and that the splenic FDG uptake correlates with measures of systemic inflammation.

Dr Hjuler presented data from an observational study which assessed splenic FDG uptake as a measure of systemic inflammation in 12 untreated patients with moderate-to-severe psoriasis compared with 23 retrospectively matched controls. The psoriasis patients had a mean PASI of 14.5 and there were no other significant differences between the two groups. Aortic inflammation was also assessed.

The CT results showed that splenic volume was greater in psoriasis patients than controls (269.5cc3 versus  224.5cc3) which suggested there may be inflammation, he said. Splenic inflammation measured using the background corrected spleen liver ratio (SLR) based on mean standardized uptake values, showed that psoriasis patients had higher levels of splenic inflammation and a higher SLR compared with controls (mean SLR 0.94   0.11 vs. 0.82 ¬ 0.08, P=0.001). This remained significant after adjusting for age, gender and BMI.

The results also showed that an association between splenic inflammation and aortic wall inflammation in both the psoriasis group and the population overall, and a weaker correlation between splenic inflammation and subcutaneous adipose tissue inflammation.

Dr Hjuler said: “Our data confirm the existence of systemic inflammation in patients with psoriasis beyond that ascertained in previous biomarker studies, and provide the rationale for a mechanistic link between psoriasis driven inflammation and cardiovascular comorbidity through a spleen–atherosclerotic axis. The cardiosplenic axis may mechanistically, at least in part, explain the epidemiological observation that patients with psoriasis have an increased risk of heart disease.”

REFERENCE

Systemic inflammation and evidence of a cardiosplenic axis in patients with psoriasis. K.F. Hjuler, L.C. Gormsen, M.H. Vendelbo, A. Egeberg, J. Nielsen, L. Iversen. FC28. Psoriasis: From Gene to Clinic International Congress, London , 2nd December 2017, 10.05.  http://psoriasisg2c.com/wp-content/uploads/2017/11/Online-Psoriasis-G2C-Programme-2017.pdf (page 68).