The Psoriasis and Comorbidity Series: An Approach to Cardiovascular Risk

For most of us, reading that psoriasis is linked to cardiovascular disease is not new information.  Data is continuously emerging to support this notion, and research is in motion to help us understand the how and why of this important cause of morbidity and mortality. It is known that those with psoriasis have a higher incidence of risk factors for both cardiovascular disease and myocardial infarction, and it is highest for those with more severe disease.¹ What is new for us dermatologists is how we adapt our treatment approach when treating this population. As dermatologists, we are on the front lines of treating psoriasis, and we need to learn how to treat the whole patient beyond just their skin. Our days of just using topical corticosteroids to treat moderate to severe disease is coming to an end as we discover that we have an opportunity to not only improve quality of life, but to potentially decrease negative outcomes associated with these linked comorbidities.

A review looking at the shared pathogenic mechanisms between psoriasis and atherosclerosis, the hallmark of cardiovascular disease, found that inflammation is the common element. More specifically, T-helper 1 (Th1) cell mediated immune dysregulation is hallmark to both conditions.  The Th1 type cytokines IFNγ, IL-2 and TNFα are prominent in both disease states, and these, along with many other shared cytokines, chemokines and growth factors, are known to contribute to plaque development in both skin and in arteries.²   

It would then be reasonable to postulate that medications targeting this shared pathway should improve both conditions, and many published studies suggest this. Aggressive lipid lowering is the cornerstone of treating atherosclerosis, second to lifestyle modifications, and studies have found that statins can decrease cutaneous lesions of psoriasis while correcting lipid metabolism.³  Furthermore, data has emerged that suggest that targeted biologic therapies for psoriasis are also lowering cardiovascular disease risk and improving outcomes.^4,5

As the specialty of physicians who are primarily diagnosing and treating psoriasis, it is our responsibility to recognize this risk and act as a resource to our patients. Several studies have suggested that psoriasis patients are inadequately screened and under treated for cardiovascular risk factors,⁶ and this is likely a result of a lack of education and communication to our patients. While confronting these risks can often be difficult, it can serve as an opportunity to build a life-long relationship as we partner with them to attack the multiple facets of this disease. A good starting point would be to encourage our patients to see their primary care physician’s (PCPs) regularly, and we should follow up with the PCP to educate them on the patient’s inherent risks and the importance in partnering to decrease their morbidity and mortality. This may be a good opportunity to mention the studies that suggest the benefits of statins in psoriasis and hyperlipidemia.³ 

As suggested earlier, it is now likely warranted to shift our mindset from just targeting the skin to focusing on treating systemic inflammation. Instead of sending a patient home with just a topical treatment, our goal should be to treat the whole patient. We can do this by discussing the importance of diet and lifestyle modification, and by referring them to the National Psoriasis Foundation for more information on both their disease and how they can take control. With the emerging data from observational studies that suggest that methotrexate and TNF inhibitors may lower the risk of CV events in patients with psoriasis, it might be warranted to begin this discussion early, regardless of disease severity.^4,5,7   It is important to note that there are limitations to these studies, and randomized controlled trials (RTCs) are needed to further explore the subject. However, one study did find that TNF inhibitors may reduce vascular inflammation,⁸ and more studies are currently in process to evaluate this in psoriasis patients treated with ultraviolet B phototherapy (ClinicalTrials.gov identifier NCT01553058), TNF inhibition (NCT01553058, 01866592), IL-12/23 inhibition (NCT02187172), and IL-17 inhibition (NCT02690701).⁴ 

As more research continues to uncover the severity of cardiovascular risk in this patient population and how it can be mitigated, more guidelines will be developed. Until then, all we can do is take a multidisciplinary approach to treatment by partnering with our patients and other relevant specialties in an attempt at giving our patients the best possible care and outcome.

References

1. Kaye JA, Li L, Jick SS. Incidence of risk factors for myocardial infarction and other vascular diseases in patients with psoriasis. Brit J Dermatol. 2008;159(4):895-902. doi:10.1111/j.1365-2133.2008.08707.x

2. Ghazizadeh R, Shimizu H, Tosa M, Ghazizadeh M. Pathogenic mechanisms shared between psoriasis and cardiovascular disease. Int J Med Sci. 2010;7(5):284-289. doi:10.7150/ijms.7.284

3. Shirinsky IV, Shirinsky VS. Efficacy of simvastatin in plaque psoriasis: A pilot study. J Am Acad Dermatol. 2007;57(3):529-531. doi:10.1016/j.jaad.2007.05.040

4. Wu JJ, Poon KYT, Channual JC, et al. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Arch Dermatol. 2012;148():1244-1250. doi:10.1001/archdermatol.2012.2502

5. 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. doi:10.1111/j.1365-2796.2012.02593.x

6. Takeshita J, Grewal S, et al. Psoriasis and comorbid diseases: Implications for management. J Am Acad Dermatol. 2017;76(3):393-403. doi:10.1016/j.jaad.2016.07.065

7. Prodanovich S, Ma F, Taylor JR, et al. Methotrexate reduces incidence of vascular diseases in veterans with psoriasis or rheumatoid arthritis. J Am Acad Dermatol. 2005;52(2):262-267. doi:10.1016/j.jaad.2004.06.017

8. Bissonnette R, Tardif JC, Harel F, et al. Effects of the tumor necrosis factor-alpha antagonist adalimumab on arterial inflammation assessed by positron emission tomography in patients with psoriasis: results of a randomized controlled trial. Circ Cardiovasc Imaging. 2013;6:83-90. doi:10.1161/CIRCIMAGING.112.975730