SKIN March 2020 Volume 4 Issue 2 Copyright 2020 The National Society for Cutaneous Medicine 112 IN-DEPTH REVIEWS Review of the Prevalence of Cardiovascular and Metabolic Comorbidities of Psoriasis Jonathan Vebman1, Alexa Choy1, Christopher J. Yao, MPH1,2 1Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 2Unviersity of Rochester School of Medicine and Dentistry, Rochester, NY Psoriasis is a common disease of the skin characterized by erythematous scaling plaques that can be linked to several other diseases that can have severe health consequences for the patient.1 There have been a number of research studies exploring the prevalence of comorbidities-such as myocardial/heart disease, stroke, diabetes, INTRODUCTION Introduction: Psoriasis is a common disease that is linked with several other diseases. Our goals were to analyze and present literature on prevalence of various psoriatic comorbidities, and provide an estimate of what percent of psoriasis patients might have or develop Myocardial/cardiovascular/heart disease, stroke, diabetes, obesity, hypertension, or metabolic syndrome. Methods: To collect the results, we searched PubMed to identify papers that studied the frequency of the most common comorbidities of psoriasis. We used about 20. The search terms used were the particular comorbidity (or synonyms) and psoriasis. Papers were selected where the prevalence data were listed by percentages of the studied population. Prevalence data from each paper were collected and charted, and then compared. We did not use data that concerned Psoriatic Arthritis. We also recorded outliers, where frequencies did not fit with the other data found. Results: Results for prevalence of myocardial/cardiovascular/heart disease were mixed, varying by age and severity of disease. There are few papers on prevalence of stroke, but our review suggests risk of stroke increases with severity of psoriasis. The prevalence of diabetes was largely between 10% and 20%. Obesity’s prevalence was mostly between 15% and 30%, while hypertension hovered around 30%, and metabolic syndrome prevalence was mostly between 27% and 50%. Conclusion: There are many comorbidities of psoriasis. The complex interaction between cutaneous inflammation and heart disease, stroke, diabetes, hypertension and metabolic syndrome raises many questions about cause and effect or simple association. ABSTRACT SKIN March 2020 Volume 4 Issue 2 Copyright 2020 The National Society for Cutaneous Medicine 113 obesity, hypertension, and metabolic syndrome-in various populations of psoriasis patients.1 This paper reviews the literature on the prevalence of specific psoriasis co- morbidities and summarizes published findings on the frequency of each of these conditions in psoriasis patients. These results are discussed below and summarized in Table 1. We aim to review the literature on the prevalence of specific psoriasis co-morbidities and summarizes published findings on the frequency of each of these conditions in psoriasis patients. These results are discussed below and summarized in Table 1. The discussion below demonstrates that psoriasis can range from mild to severe and can be associated with a wide variety of co- morbidities. As we better understand these variables, it becomes clear that the most effective treatment regimens are targeted to the specific disease manifestations, co- morbidities, previous treatments, and impact on patients’ quality of life.2,3 We searched PubMed to identify papers that studied the frequency of the most common co-morbidities of psoriasis. The search terms used were the particular comorbidity (or synonyms) and psoriasis. Papers were selected where the prevalence data were listed by percentages of the studied population. Prevalence data from each paper were collected and charted, and then compared. We did not use data that concerned Psoriatic Arthritis. We also recorded outliers, where frequencies did not fit with the other data found, and they are discussed below. Cardiovascular Disease Cardiovascular disease (or myocardial disease or heart disease) is one of the most commonly reported comorbidities of psoriasis. Studies suggest mixed correlation with psoriasis. Some studies showed, a relationship between increasing psoriasis severity and decreasing prevalence of cardiovascular disease, while others showed increasing risk with increasing severity of psoriasis. Studies also showed that the increase in risk is particularly noteworthy in younger patients, partly because baseline risk of myocardial infarction is greater in older patients. It is also apparent that psoriasis with other cardiovascular risk factors increases the risk of heart disease. Studies have reported very different prevalences of cardiovascular disease in psoriasis patients, ranging from 1.8% to 17.7%. According to a 2018 study published by Hajiebrahimi et al, myocardial infarction had a prevalence of 2.5%, 2.3%, and 1.8%, when Psoriasis was mild, moderate, and severe, respectively.4 It also suggested that younger patients were at higher risk of myocardial infarction. That range of results is supported by a 2015 study, which found that 2.59% of psoriasis patients had a major cardiovascular event as compared to 2.3% of controls.5 This study concluded that psoriasis was not-independent of other risk factors-associated with an increased risk of cardiovascular events.5 According to Gelfand et al., the prevalence of myocardial infarction in mild and severe psoriasis was 1.8% (mild) and 2.9% (severe).6 It also indicated that the risk of myocardial infarction was increased in younger psoriasis patients as opposed to older patients. Differing only slightly were the METHODS RESULTS SKIN March 2020 Volume 4 Issue 2 Copyright 2020 The National Society for Cutaneous Medicine 114 results of a ten-year review of Malaysian psoriasis patients, which reported the prevalence of ischemic heart disease at 5.45% and the prevalence of cerebrovascular disease at 1.6%.7 A 2017 study of Czech registry patients found the prevalence of coronary heart disease to be 4.9%.8 In contrast, Schaarschmidt et al found that the prevalence of cardiovascular disease was 15%.9 Even larger was the prevalence of cardiovascular disease reported by BMC Health Service Research, at 17.7%.10 However, by far the highest prevalence was from Assessment of Possible Drug Interactions in Patients with Psoriasis and Associated Comorbid Medical Conditions: An Observational Study, which reported the prevalence of cardiovascular comorbidities at a staggering 77.3%.11 Nevertheless, this paper noted that this unusually high percentage might be attributable to the fact that the study was focused in India, where cardiovascular comorbidities are more common. Type 2 Diabetes Mellitus Type 2 diabetes mellitus (DMII) is another common comorbidity of psoriasis. DMII‘s prevalence in psoriasis patients mostly hovers between 10% and 20%, higher than in control groups, with the prevalence increasing with the severity of psoriasis. According to a 2018 study on patients in Swedish health registries, the prevalence of DMII is 7.6% (mild psoriasis), 8.0% (moderate-severe psoriasis), and 10.7% (severe psoriasis).4 French and Czech studies found the prevalence of DMII in psoriatic patients to be 11%12 and 11.4%8 respectively. The Czech study also refers to other European registries showing a prevalence of DMII in psoriasis patients of 9.9-12%. Similarly, 2017 and 2018 studies found the prevalence of DMII in psoriasis patients to be 10%13 and 12%,14 respectively. Another 2015 paper by Schaarschmidt et al. reported the prevalence of DMII to be 14.5%9 while a review from the Malaysian Psoriasis Registry, spanning 2007-2016, and a study of over 2,700 patients in the Bringham psoriasis and psoriatic arthritis registries both found the prevalence of DMII in their cohorts to be at or near 17%.7,15 All other results were close to the results mentioned, and can be found in Table 1 below, except for one unusual finding. Far and away the largest percentage found of DMII in psoriasis patients was the 49.3% found in an observational study of psoriasis patients taking two or more drugs.11 Stroke Stroke is another serious comorbidity of psoriasis, but only a few studies assess the correlation between the two conditions. One study, however, demonstrated a 2.4% prevalence of stroke in individuals with mild psoriasis, 2.2% in individuals with moderate to severe psoriasis, and 1.1% in individuals with severe psoriasis.4 Obesity Obesity is a risk factor for cardiovascular and other diseases, and is also a common comorbidity of psoriasis, with reports of prevalence ranging from 15.2% (in a study of the Czech national registry of psoriatic patients treated with biologics, and a comparison with other European registries)8 to 32.6% (a study of prevalence of metabolic disease and its various components comparing 95 psoriatic patients to 95 controls).16 A French study of 2,210 patients reports the prevalence to be 24%,12 while a large study over 48,000, and another of over 15,000 patients, report 20.36%5 and 24.3%7 respectively. Trattner et al. report 27% in a study of plantar pustulosis.17 SKIN March 2020 Volume 4 Issue 2 Copyright 2020 The National Society for Cutaneous Medicine 115 Hypertension Hypertension can potentially cause many other diseases including cardiovascular disease and stroke. Salunke et al. reports a prevalence rate of hypertension at 18.9%, but found that the rates increased with the duration of psoriasis.16 The Malaysian study reports prevalence rate of 25.6%.7 Many studies show results in a consistent range. Hajiebrahimi et al. found the prevalence of hypertension in psoriasis patients at 29.9% (moderate psoriasis), 32.6% (moderate-severe psoriasis), and 36.5% (severe psoriasis).4 The French study mentioned above found the prevalence to be 26%.12 An Australas Journal of Dermatology paper reports the rate of hypertension in psoriasis patients to be 30%,14 as does a Brazilian study.18 The study of the Czech registries reports the prevalence at 35.2%,8 and similarly, Schaarschmidt et al. listed the prevalence of hypertension at 31.5%.9 Similar to the Czech study, a study of over 48,000 psoriasis patients and over 200,000 controls, spanning the years 1994-2009 showed a baseline of 15.39% prevalence of hypertension (compared to nearly 15% in the controls). By the end of the followup period (median of just over 5 years), the hypertension prevalence rose to 24.72% (mild psoriasis) and 31.62% (severe psoriasis), and 31.6% among controls.5 Other studies found outcomes in similar prevalence ranges of 30%,18 32.8%,19 32%,17 34.3%,10 and 35%,13 respectively. In the Brigham study the prevalence was reports at 45%.15 Metabolic Syndrome Metabolic syndrome is a conglomerate of other diseases, defined generally to include several conditions that might include obesity, hypertension, and glucose intolerance.20 Choudhary et al. surveyed 63 studies and found the occurrence of metabolic syndrome in psoriasis patients to be as high as 50% as compared to 15-25% among the general population.20 Another study found the rate to be 30%.14 According to Hajiebrahimi et al., metabolic syndrome has a prevalence of 50% in psoriasis patients.4 Argote et al. also found a high 50% prevalence.13 A similarly high finding in a study of 97 patients, reports 49.4% prevalence.21 In the study by Choudhary et al., a rigorous analysis of 63 papers, sorted by age, gender, and continent, studied 119,923 participants, of which 15,939 were psoriasis patients. Metabolic syndrome was reported among 30.29% of psoriasis patients, compared with 21.70% in the control group.20 Among these patients, 50% of South American patients were reported to have metabolic syndrome, compared to 27.14 in the control group, and 27.12 of Asian patients, compared with 16.95% of the control patients.20 In a case-control study from Western Maharashtra, the reported prevalence rate was 38.9%.16 Similarly, Curco et al., in a 2018 paper, report a prevalence of 30%.14 The second-lowest score came from a plantar pustulosis study in which a cross-sectional analysis in 102 patients claimed a prevalence of 26%.17 However, the lowest prevalence rate, was a low 20.8%.22 There are many comorbidities of psoriasis. While the prevalence of each comorbidity varies according to publication as does the association with severity of psoriasis, it is clear that psoriasis is more than just a skin disease. The complex interaction between CONCLUSION SKIN March 2020 Volume 4 Issue 2 Copyright 2020 The National Society for Cutaneous Medicine 116 cutaneous inflammation and heart disease, stroke, type 2 diabetes mellitus, hypertension and metabolic syndrome raises many questions about cause and effect or simple association. Table 1. Summary of Prevalence of Psoriasis’ Comorbidities with PMID Citations PMID Myocardial/Cardi ovascular/Heart Disease Stroke Diabetes Mellitus Obesity Hypertension Metabolic Syndrome 29950900 Hajiebrahimi 2.5% (mild PS), 2.3% (moderate- severe PS), 1.8% (severe PS) 2.4% (mild PS), 2.2% (moderate- severe PS), 1.1% (severe PS) 7.6% (mild PS), 8.0% (moderate- severe PS), 10.7% (severe PS) 29.9% (mild PS), 32.6% (moderate- severe PS), 36.5% (severe PS) 50.0% 26969480 Phan 11% 24% 26% 28181669 Kojanova 4.9% coronary heart disease 11.4% (9.9-12% various registries 15.2% 35.2% (21%-33.8% various registries) 26633680 Schaarschmidt 15% 14.5% 31.5% 28969252 Salunke 32.6% 18.9% 38.9% 25742120 Parisi 2.59% CV event (v. 2.3% in controls) 5.64% (initial PS) ≥ 9.02% (severe) 20.36% 15.39% (initial PS) ≥ 24.72% (mild); 31.62% (severe) 29849578 Mohd Affandi ischemic heart disease 5.45; cerebrovascular disease 1.6% 17.2% 24.3% 25.6% 28814312 Schneeweiss 17% 45% 28240341 Curcó 12% 67% (obese or overweight) 30% 30% 28099594 Duarte 30% 26402388 Feldman 15.8% 32.8% 26829958 Sherin 77.3% 49.3% 31595859 Choudhary 27.12%- 50% 28482887 Feldman 17.7% (17.45% moderate-severe, 17.8% mild PS) 14.2% (15.92% moderate- severe, 13.7% mild PS) 4.88% (5.18% moderate- severe, 4.79% mild PS) 34.3% (34.86% moderate- severe, 34.16% mild PS) SKIN March 2020 Volume 4 Issue 2 Copyright 2020 The National Society for Cutaneous Medicine 117 PMID Myocardial/Cardi ovascular/Heart Disease Stroke Diabetes Mellitus Obesity Hypertension Metabolic Syndrome 28662815 Argote 10% 35% 50% 30133617 Ferdinando 49.4% 26316538 Lai 20.8% 17032986 Gelfand MI: 1.8% (mild PS) and 2.9% (severe) 28252813 Trattner 27% 32% 26% Conflict of Interest Disclosures: None Funding: None Corresponding Author: Jonathan IIai Vebman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY Email: yivebman@gmail.com References: 1. Mayo. Psoriasis. https://www.mayoclinic.org/diseases- conditions/psoriasis/symptoms-causes/syc- 20355840?utm_source=Google&utm_medium=a bstract&utm_content=Psoriasis&utm_campaign= Knowledge-panel. Accessed. 2. Kaushik SB, Lebwohl MG. Psoriasis: Which therapy for which patient: Focus on special populations and chronic infections. J Am Acad Dermatol. 2019;80(1):43-53. 3. Kaushik SB, Lebwohl MG. Psoriasis: Which therapy for which patient: Psoriasis comorbidities and preferred systemic agents. J Am Acad Dermatol. 2019;80(1):27-40. 4. Hajiebrahimi M, Linder M, Hagg D, et al. Young patients with risk factors prevalent in the elderly - differences in comorbidity depending on severity of psoriasis: a nationwide cross-sectional study in Swedish health registers. Clin Epidemiol. 2018;10:705-715. 5. Parisi R, Rutter MK, Lunt M, et al. Psoriasis and the Risk of Major Cardiovascular Events: Cohort Study Using the Clinical Practice Research Datalink. J Invest Dermatol. 2015;135(9):2189- 2197. 6. 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. 7. Mohd Affandi A, Khan I, Ngah Saaya N. Epidemiology and Clinical Features of Adult Patients with Psoriasis in Malaysia: 10-Year Review from the Malaysian Psoriasis Registry (2007-2016). Dermatol Res Pract. 2018;2018:4371471. 8. Kojanova M, Fialova J, Cetkovska P, et al. Characteristics and risk profile of psoriasis patients included in the Czech national registry BIOREP and a comparison with other registries. Int J Dermatol. 2017;56(4):428-434. 9. Schaarschmidt ML, Kromer C, Herr R, et al. Patient Preferences for Biologicals in Psoriasis: Top Priority of Safety for Cardiovascular Patients. PLoS One. 2015;10(12):e0144335. 10. Feldman SR, Tian H, Gilloteau I, Mollon P, Shu M. Economic burden of comorbidities in psoriasis patients in the United States: results from a retrospective U.S. database. BMC Health Serv Res. 2017;17(1):337. 11. Sherin R, Udaykumar P. Assessment of Possible Drug Interactions in Patients with Psoriasis and Associated Comorbid Medical Conditions: An Observational Study. Rev Recent Clin Trials. 2016;11(2):128-134. 12. Phan C, Sigal ML, Lhafa M, et al. Metabolic comorbidities and hypertension in psoriasis patients in France. Comparisons with French national databases. Ann Dermatol Venereol. 2016;143(4):264-274. mailto:yivebman@gmail.com about:blank about:blank about:blank about:blank about:blank SKIN March 2020 Volume 4 Issue 2 Copyright 2020 The National Society for Cutaneous Medicine 118 13. Argote A, Mora-Hernandez O, Milena Aponte L, et al. Cardiovascular Risk Factors and Carotid Intima-Media Thickness in a Colombian Population With Psoriasis. Actas Dermosifiliogr. 2017;108(8):738-745. 14. Curco N, Barriendos N, Barahona MJ, et al. Factors influencing cardiometabolic risk profile in patients with psoriasis. Australas J Dermatol. 2018;59(2):e93-e98. 15. Schneeweiss M, Merola JF, Karlson EW, Solomon DH. Rationale and Design of the Brigham Cohort for psoriasis and psoriatic arthritis registry (COPPAR). BMC Dermatol. 2017;17(1):11. 16. Salunke AS, Nagargoje MV, Belgaumkar VA, Tolat SN, Chavan RB. Association of Metabolic Syndrome in Chronic Plaque Psoriasis Patients and their Correlation with Disease Severity, Duration and Age: A Case Control Study from Western Maharashtra. J Clin Diagn Res. 2017;11(8):Wc06-wc10. 17. Duarte GV, Oliveira MF, Follador I, Silva TS, Carvalho EMF. Diagnosis and underdiagnosis of comorbidities in psoriasis patients - need for a multidisciplinary approach. An Bras Dermatol. 2016;91(6):743-747. 18. Feldman SR, Zhao Y, Shi L, Tran MH. Economic and Comorbidity Burden Among Patients with Moderate-to-Severe Psoriasis. J Manag Care Spec Pharm. 2015;21(10):874-888. 19. Choudhary S, Pradhan D, Pandey A, et al. The association of metabolic syndrome and psoriasis: A systematic review and meta-analysis of observational study. Endocr Metab Immune Disord Drug Targets. 2019. 20. Ferdinando LB, Fukumoto PK, Sanches S, Fabricio LHZ, Skare TL. Metabolic syndrome and psoriasis: a study in 97 patients. Rev Assoc Med Bras (1992). 2018;64(4):368-373. 21. Lai YC, Yew YW. Psoriasis as an Independent Risk Factor for Cardiovascular Disease: An Epidemiologic Analysis Using a National Database. J Cutan Med Surg. 2016;20(4):327- 333.