……..Shared inflammatory mechanisms may explain the association
Patients with psoriasis — whether mild or severe — are at increased risk of abdominal aortic aneurysms (AAA), a Danish nationwide cohort study found.
In an analysis adjusted for multiple factors including age, sex, comorbidities, smoking, and medications, the incidence rate ratios for AAA were 1.20 (95% CI 1.03-1.39, P=0.017) for mild psoriasis and 1.67 (95% CI 1.21-2.32, P=0.002) for severe psoriasis compared with the general population, according to Usman Khalid, MD, PhD, of Copenhagen University Gentofte Hospital in Hellerup, and colleagues.
“These findings add importantly to current evidence of psoriasis as a clinically relevant risk factor for cardiovascular disease and may require increased focus on heightened risk of AAA in patients with psoriasis,” the researchers wrote in Atherosclerosis, Thrombosis, and Vascular Biology.
AAA is relatively common and can be asymptomatic, with progressive dilation of the abdominal aorta that can rupture — often with fatal results.
“Emerging evidence suggests that AAA is a focal representation of a systemic disease with a distinct inflammatory component, rather than a mere consequence of atherosclerosis,” Khalid explained.
Earlier case series have linked AAA with other autoimmune diseases such as rheumatoid arthritis, but a possible association with psoriasis has not previously been explored.
Accordingly, Khalid and colleagues conducted a retrospective study of the Danish national registries for the years 1997 to 2011. The team identified 70,989 patients with psoriasis (59,423 mild and 11,566 severe) and a reference population of 5,404,544 individuals.
Mean ages at baseline ranged from 41 to 44, and slightly less than half were men. More patients with severe psoriasis were ever-smokers, but in general, the psoriasis groups and the reference population were similar in their comorbidities and the medications used.
During the study period, AAA was diagnosed in 23,986 patients.
During a mean follow-up of 14.4 years in the reference population, the incidence rate of AAA was 3.72 per 10,000 person-years. In contrast, with a mean follow-up of 5.7 years, the incidence rates were 7.30 per 10,000 for mild psoriasis and 9.87 per 10,000 for severe psoriasis.
In an analysis adjusted only for age, sex, and calendar year, the incidence rate ratios were 1.36 (95% CI 1.19-1.54, P<0.001) for mild psoriasis and 2 (95% CI 1.51-2.64, P<0.001) for severe psoriasis. A supplementary analysis found that the incidence rate ratios of AAA rupture were 1.60 (95% CI 1.21-2.12) for mild and 1.94 (95% CI 1.01-3.36) for severe psoriasis, and the incidence rates for surgical repair were 3.03, 7.73, and 8.09 per 10,000 person-years for the reference population, mild psoriasis, and severe psoriasis groups, respectively. And in an additional analysis that excluded patients who developed atherosclerosis, the incidence rate ratios were 1.36 (95% CI 1.20-1.54, P<0.001) for mild psoriasis and 1.92 (95% CI 1.46-2.52, P<0.001) for severe psoriasis. Patients with atherosclerotic disease at baseline also had been excluded, so these findings suggest that unlike "the traditional view that atherosclerotic disease is the primary driving factor for the development of AAA," the disease today is considered "a multifactorial process that comprises, for example, inflammation, matrix degradation, thrombosis, increased biomechanical aortic wall stress, and a host of associated mediator molecules," the researchers wrote. Systemic inflammatory markers such as C-reactive protein and tumor necrosis factor (TNF)-α also are elevated in patients with AAA and in those with psoriasis. In a murine model of AAA, TNF-α was shown to be involved in matrix remodeling and aortic wall inflammation, while administration of the TNF blocker infliximab inhibited the development of aneurysms. In addition, a systematic review found that TNF inhibition improved endothelial function in patients with psoriasis and psoriatic arthritis. "Taken together, these data support the notion that shared inflammatory mechanisms contribute to the psoriasis severity-dependent increased risk of AAA observed in the current study," the researchers observed. However, the implications for treatment are as yet uncertain, Khalid told MedPage Today. "At present, it is unclear whether treatment with anti-inflammatory agents would reduce the observed risk. "Further studies are clearly required to investigate the mechanisms and consequences of these novel findings." A limitation of the study was the possibility of surveillance bias if patients were followed more closely after being diagnosed with psoriasis. The study was funded by the LEO Foundation, and one co-author was supported by an unrestricted research scholarship from the Novo Nordisk Foundation. The authors also reported financial relationships with Bayer, Pfizer, AstraZeneca, Boehringer Ingelheim, and Bristol-Myers Squibb. Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner