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Cardiovascular Disease and Psoriasis.

The epidemiologic association of psoriasis with cardiovascular (CV) risk is well known. (1) Recent studies have illuminated the pathophysiology underlying this association. Additionally, biologic agents approved by the US Food and Drug Administration for psoriasis therapy have the potential to reduce the risk of CV events in patients with psoriasis.

Cardiovascular disease (CVD), obesity, and psoriasis are all systemic inflammatory disorders. Psoriasis is associated with an elevated risk for obesity (2) and myocardial infarction (MI), (1) as well as with multiple CV risk factors. (2) Severe psoriasis is associated with an increased risk of CV death independent of CV risk factors. (3,4)

Imaging has revealed significantly more vascular inflammation in patients with severe psoriasis (n=4; body surface area >10%) compared with age- and sex-matched controls (n=4). A nested case-control study used [[sup.18]F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) to detect and compare systemic inflammation in the study participants. FDG-PET/CT revealed increased inflammation in multiple aorta segments, including the coronary, hepatic, renal, and femoral arteries compared with controls. The difference remained significant after adjustment for CV risk factors (P<0.001). (5,6)

Chronic inflammation may explain why the Framingham Risk Score underestimated the 10-year incidence of CVD events in patients with psoriatic arthritis. Actual 10-year cumulative incidence of CVD events in a population-based cohort of 126 patients with psoriatic arthritis and no history of CV events was 17% (95% CI, 10-24), nearly twice as high as that predicted by the Framingham Risk Score. (7)

The coronary artery calcium score offers another way to quantify subclinical CV risk. A study measured coronary artery calcium scores in patients with moderate-to-severe psoriasis (n=129) compared with individuals with type 2 diabetes (n=129) and healthy controls (n=100). The prevalence of moderate-to-severe coronary calcification was similar for patients with psoriasis and patients with type 2 diabetes and roughly three times greater than that of controls. (8)

Do Psoriasis Therapies Reduce Risk of CVD?

Because inflammation is central to the pathophysiology of both psoriasis and CVD, investigators have evaluated whether anti-inflammatory psoriasis therapies affect the risk of CVD. Multiple observational studies report a benefit.

Analysis of nationwide databases in Denmark revealed that treatment with biologic agents (80% received tumor necrosis factor-alpha [TNF-[alpha]] inhibitors) or methotrexate was associated with lower CVD event rates over a mean follow-up of 18 months compared with patients given other antipsoriatic therapies. Adjusted hazard ratios (HRs) for the composite endpoint of death, MI, and stroke were 0.28 (95% CI, 0.12-0.64) with biologic therapies and 0.65 (95% CI, 0.42-1.00) with methotrexate. (9)

Retrospective cohort studies using claims databases have demonstrated that in patients with psoriasis, TNF-[alpha] inhibitor use was associated with:

* Significantly lower risk of MI compared with topical therapy (10)

* Significantly lower risk of major CV events (hospitalization for MI, stroke, transient ischemic attack, unstable angina) compared with methotrexate. Every additional 6 months of TNF-[alpha] inhibitor therapy was associated with an 11% reduced risk of a major CV event (P=0.02) (11)

* Significantly lower risk of major CV events compared with phototherapy (adjusted HR, 0.77; P<0.05). As in the study comparing TNF-[alpha] inhibitor therapy with methotrexate, longer use of TNF-[alpha] inhibitors was associated with increased risk reduction (12)

Crude incidence rates of atrial fibrillation and major adverse cardiovascular events (MACE) were similar with ustekinumab and TNF-[alpha] inhibitor use in patients with psoriasis or psoriatic arthritis, according to a retrospective claims data analysis. (13) However, studies examining the relationship between CV events and ustekinumab are mixed. According to a retrospective analysis of clinical trials, the rate of MACE observed with the anti-IL-12/IL-23 agents (ustekinumab and briakinumab) did not differ from that seen with placebo (P=0.12 for risk difference between anti-IL-12/23 agents and placebo). The rate of MACE observed with TNF-[alpha] inhibitors also did not differ from that reported with placebo (P=0.94 for the risk difference between anti-TNF-[alpha] agents and placebo). MACE was defined as a composite of MI, cerebrovascular accident, or CV death during the placebo-controlled phase of treatment. (14)

In a recent observational study, biologic therapy in a small number of patients with moderate-to-severe psoriasis improved coronary plaque indices. Patients with psoriasis initiating biologic therapy (n=89) and patients who elected not to receive biologic therapy (n=32) were followed prospectively, with total coronary plaque burden and plaque subcomponents measured at baseline and 1 year. Biologic therapy was associated with a small, ie, 6%, reduction in the noncalcified plaque burden (P=0.005 vs baseline), as well as decreases in fibro-fatty burden (P=0.004) and necrotic burden (P=0.03). Fibro-fatty burden increased significantly in the nonbiologic therapy group (P=0.004), but no other significant changes were noted in those patients. (15)

Conclusion

A growing body of evidence shows that moderate-to-severe psoriasis is a significant CV risk factor. The mechanisms underlying this relationship are not well defined, but shared inflammatory pathways between psoriasis and atherosclerosis are likely involved. (16) Multiple studies,(10-12,15) although not all, (14) demonstrate that biologic therapy for psoriasis reduces the risk of CV events. Long-term studies, ie, up to 5 years, will be required with a larger number of patients to definitely show that biologic agents can reduce the incidence of CVD in patients with moderate-to-severe psoriasis. New anti-inflammatory agents are currently being developed as treatments for CVD. (17,18)

References

(1.) Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14): 1735-1741.

(2.) Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB, Gelfand JM. Prevalence of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol. 2006;55(5):829-835.

(3.) Mehta NN, Azfar RS, Shin DB, Neimann AL, Troxel AB, Gelfand JM. Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database. Eur Heart J. 2010;31(8): 1000-1006.

(4.) Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80(4): 1073-1113.

(5.) Mehta NN, Yu Y, Saboury B, et al. Systemic and vascular inflammation in patients with moderate to severe psoriasis as measured by [[sup.18]F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT): a pilot study. Arch Dermatol 2011; 147(9): 1031-1039.

(6.) Kivelevitch D, Schussler JM, Menter A, et al. Coronary plaque characterization in psoriasis. Circulation. 2017; 136(3):277-280.

(7.) Ernste FC, Sanchez-Menendez M, Wilton KM, Crowson CS, Matteson EL, Maradit Kremers H. Cardiovascular risk profile at the onset of psoriatic arthritis: a population-based cohort study. Arthritis Care Res (Hoboken). 2015;67(7): 1015-1021.

(8.) Mansouri B, Kivelevitch D, Natarajan B, et al. Comparison of coronary artery calcium scores between patients with psoriasis and type 2 diabetes. JAMA Dermatol. 2016; 152(11): 1244-1253.

(9.) Ahlehoff O, Skov L, Gislason G, et al. Cardiovascular disease event rates in patients with severe psoriasis treated with systemic anti-inflammatory drugs: a Danish real-world cohort study. J Intern Med. 2013;273(2): 197-204.

(10.) Wu JJ, Poon KT, Channual JC, Shen A. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Arch Dermatol. 2012;148(11): 1244-1250.

(11.) Wu JJ, Guerin A, Sundaram M, Dea K, Cloutier M, Mulani P. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-alpha inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76(1):81-90.

(12.) Wu JJ, Sundaram M, Cloutier M, et al. The risk of cardiovascular events in psoriasis patients treated with tumor necrosis factor-alpha inhibitors versus phototherapy: an observational cohort study. J Am Acad Dermatol. 2018;79(1):60-68.

(13.) Lee MP, Desai RJ, Jin Y, Brill G, Ogdie A, Kim SC. Association of ustekinumab vs TNF inhibitor therapy with risk of atrial fibrillation and cardiovascular events in patients with psoriasis or psoriatic arthritis. JAMA Dermatol. 2019 Mar 27 [Epub ahead of print].

(14.) Ryan C, Leonardi CL, Krueger JG, et al. Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials. JAMA. 2011;306(8):864-871.

(15.) Elnabawi YA, Dey AK, Goyal A, et al. Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study. Cardiovasc Res. 2019;115(4):721-728.

(16.) Frieder J, Ryan C. Psoriasis and cardiovascular disorders. G Ital Dermatol Venereoi. 2016; 151(6): 678-693.

(17.) Ridker PM, Everett BM, Thuren T, et al, for the CANTOS Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119-1131.

(18.) Zhao TX, Mallat Z. Targeting the immune system in atherosclerosis: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73(13): 1691-1706.
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Author:Menter, Alan
Publication:Dermatology News
Date:Aug 1, 2019
Words:1478
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