The impact of psoriasis on 10-year Framingham risk

Abstract

To the Editor: Psoriasis is a chronic inflammatory skin disease, and when severe, may be a risk factor for major adverse cardiac events (MACE) including myocardial infarction,1Gelfand J.M. Neimann A.L. Shin D.B. Wang X. Margolis D.J. Troxel A.B. Risk of myocardial infarction in patients with psoriasis.JAMA. 2006; 296: 1735-1741Crossref PubMed Scopus (1466) Google Scholar stroke, and cardiovascular (CV) death. Indeed, recent studies evaluating the risk of MACE with interleukin 12/23 inhibitors in randomized trials emphasize the need for efforts at decreasing the risk of CV disease in patients with psoriasis.2Ryan C. Leonardi C.L. Krueger J.G. Kimball A.B. Strober B.E. Gordon K.B. et al.Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials.JAMA. 2011; 306: 864-871Crossref PubMed Scopus (239) Google Scholar Risk stratification and treatment goals for cholesterol and blood pressure in psoriasis remain understudied, and the Framingham risk score (FRS) for CV risk may underestimate long-term risk of MACE in patients with psoriasis. The Adult Treatment Panel for lipid management recommends that providers consider emerging risk factors when deciding on lipid treatment but does not provide specific guidelines. We described an initial estimate of this excess attributable risk (AR) of severe psoriasis on MACE3Mehta N.N. Yu Y. Pinnelas R. Krishnamoorthy P. Shin D.B. Troxel A.B. et al.Attributable risk estimate of severe psoriasis on major adverse cardiac events.Am J Med. 2011; 124: 775e1-775e6Google Scholar and herein describe how this AR may affect FRS in psoriasis. We consecutively enrolled patients (n = 138), and calculated FRS before and after adding the AR of psoriasis (6.2%),3Mehta N.N. Yu Y. Pinnelas R. Krishnamoorthy P. Shin D.B. Troxel A.B. et al.Attributable risk estimate of severe psoriasis on major adverse cardiac events.Am J Med. 2011; 124: 775e1-775e6Google Scholar and estimated the reclassification rate by examining patients moved from a lower risk category to a higher risk category.Patients with psoriasis were relatively young with higher than expected tobacco use, alcohol use, body mass index, and lipids (Table I). Nonetheless, their risk for MACE by FRS was low (<10%) (male mean FRS 7.4 ± 7.75, female 5.9 ± 5.86), attributable to their young age. After considering the estimated AR (mean FRS 13.36 ± 7.10, male 13.92 ± 7.77, female 12.48 ± 5.86), the majority of patients were reclassified to a higher risk category: 73% (95% confidence interval 61.5%-82.3%) of patients at low risk were reclassified as intermediate risk, and 53% (95% confidence interval 36.4%-64.1%) of those at intermediate risk were reclassified as high risk (Table II). These findings suggest that adding the estimated AR of psoriasis on MACE to the FRS results in clinically important changes in prevention strategies.3Mehta N.N. Yu Y. Pinnelas R. Krishnamoorthy P. Shin D.B. Troxel A.B. et al.Attributable risk estimate of severe psoriasis on major adverse cardiac events.Am J Med. 2011; 124: 775e1-775e6Google ScholarTable IDemographic characteristics of study sampleVariablesTotal, n = 138Men, n = 85Women, n = 53Median (IQR§Except where measurement is indicated as percent in the left column.)Age, y44 (35-55)41 (33-53)50 (40-57)Diabetes (%)13 (9.3)7 (8.1)6 (11.1)Tobacco use (%)55 (39.8)30 (35.2)25 (47.1)Family history of CAD (%)81 (59.1)49 (58.3)32 (60.3)Alcohol use (%)93 (67.3)64 (75.2)29 (54.7)Systolic blood pressure, mm Hg123 (112-136)125 (112-135)122 (112-136)Diastolic blood pressure, mm Hg80 (72-86)80 (75-86)80 (72-86)Total cholesterol, mg/dL184 (157-218)179 (154-206)190 (160-223)LDL cholesterol, mg/dL108 (87-138)108 (90-138)108 (85-132)HDL cholesterol, mg/dL44.5 (38-55)41 (37-49)55 (39-63)Triglycerides, mg/dL107 (79-155)104 (78-155)107 (81-152)Non-HDL cholesterol, mg/dL134 (110.5-172)136 (109-164)134 (113-172)VLDL cholesterol, mg/dL29 (21-40)35 (27-43)23.5 (16-35)Lipoprotein A, mg/dL12.1 (6-27.8)11 (4.6-31)13.4 (8.15-22)Homocysteine, μmol/L10.3 (8-12.9)11.2 (8.5-14.7)9.2 (7.7-10.9)C-reactive protein, mg/L2.4 (0.56-7.9)1.5 (0.3-4.4)4.7 (1.5-12.7)ESR, mm/h8 (3-17)3 (2-10)12 (7-22)Glucose, mg/dL91 (85-104)88 (82-99)96 (87-117)Body mass index28.4 (24.8-33.5)27.3 (24.8-31.2)29.1 (26.5-36.5)Waist circumference, in38.7 (34.3-43)38 (34.5-43)40 (33-43)Waist to hip ratio0.93 (0.87-0.97)0.93 (0.9-1)0.87 (0.84-0.93)Metabolic syndrome (%)51 (39.5)31 (37.8)20 (42.5)Family history of diabetes (%)28 (20.44)19 (22.6)9 (16.9)Myocardial infarction (%)6 (4.3)5 (5.8)1 (1.8)10-y Framingham risk percent event (LDL cholesterol), mean (±SD) Without psoriasis risk added6.8 (±7.10)7.4 (±7.75)5.9 (±5.86) With psoriasis risk added13.36 (±7.10)13.92 (±7.77)12.48 (±5.86)Psoriasis severity∗Available in 80% of population. (body surface area involvement) Low (<2%)26 (24.3%)12 (18.4%)14 (33%) Intermediate (2%-10%)58 (54.2%)38 (58.4%)20 (48%) Severe (>10%)23 (21.5%)15 (23.1%)8 (19%)Psoriasis therapy†Patient could be in >1 group. Topical only21 (15.2%) Ever systemic‡Defined as biologic or oral methotrexate, cyclosporine, acitretin therapy.78 (56.5%) Ever phototherapy86 (62.3%)CAD, Coronary artery disease; ESR, erythrocyte sedimentation rate; HDL, high-density lipoprotein; IQR, interquartile range; LDL, low-density lipoprotein; VLDL, very-low-density lipoprotein.∗ Available in 80% of population.† Patient could be in >1 group.‡ Defined as biologic or oral methotrexate, cyclosporine, acitretin therapy.§ Except where measurement is indicated as percent in the left column. Open table in a new tab Table IICategory of risk before and after adding psoriasis attributable risk with treatment goalsCategoryBaseline riskModified riskTreatment goals∗Adult Treatment Panel III in conjunction with the Joint National Congress for Blood Pressure Management Executive Summary.2Total, n = 138Male, n = 85Female, n = 53Total, n = 138Male, n = 85Female, n = 53LDL, mg/dLBlood pressure, mm HgLow1116645462125<160<140/90Intermediate21156795623<130<130/80High6421385<100<120/80LDL, Low-density lipoprotein.∗ Adult Treatment Panel III in conjunction with the Joint National Congress for Blood Pressure Management Executive Summary.2Ryan C. Leonardi C.L. Krueger J.G. Kimball A.B. Strober B.E. Gordon K.B. et al.Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials.JAMA. 2011; 306: 864-871Crossref PubMed Scopus (239) Google Scholar Open table in a new tab Because of the young age of our population, the majority of patients were in the low risk category, which would not warrant aggressive risk reduction strategies. However, when considering an AR estimate of MACE, the majority of our patients were reclassified into the intermediate risk category, which would warrant change in treatment plans and goals for more than 60% of our patients (Table II), an important finding in this population potentially at higher risk for CV disease with increased subclinical vascular inflammation.4Mehta N.N. Yu Y. Saboury B. Foroughi N. Krishnamoorthy P. Raper A. et al.Systemic and vascular inflammation in patients with moderate to severe psoriasis as measured by [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT): a pilot study.Arch Dermatol. 2011; 147: 1031-1039Crossref PubMed Scopus (169) Google ScholarWe recognize this proof-of-concept study is limited by the generalizability of United Kingdom data to a US population. However, guidelines for identifying CV disease risk factors are similar. Secondly, our AR was derived in severe psoriasis defined by treatment with systemic therapy or phototherapy; similarly, more than 80% of our patients had been exposed to these therapies permitting this estimate to be applicable in this proof-of-concept study.The major implication of these findings is that patients with psoriasis may warrant more aggressive control of established CV risk factors. Measures to decrease CV risk include lifestyle and dietary education through targeted counseling. The percentage of these patients requiring drug interventions such as statins and antihypertensive is unknown but likely to be small. Finally, this illustration provides a quantitative approach for CV risk estimation in psoriasis, an approach gaining acceptance in the care of patients with rheumatoid arthritis.5Peters M.J. Symmons D.P. McCarey D. Dijkmans B.A. Nicola P. Kvien T.K. et al.EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis.Ann Rheum Dis. 2010; 69: 325-331Crossref PubMed Scopus (1063) Google Scholar To the Editor: Psoriasis is a chronic inflammatory skin disease, and when severe, may be a risk factor for major adverse cardiac events (MACE) including myocardial infarction,1Gelfand J.M. Neimann A.L. Shin D.B. Wang X. Margolis D.J. Troxel A.B. Risk of myocardial infarction in patients with psoriasis.JAMA. 2006; 296: 1735-1741Crossref PubMed Scopus (1466) Google Scholar stroke, and cardiovascular (CV) death. Indeed, recent studies evaluating the risk of MACE with interleukin 12/23 inhibitors in randomized trials emphasize the need for efforts at decreasing the risk of CV disease in patients with psoriasis.2Ryan C. Leonardi C.L. Krueger J.G. Kimball A.B. Strober B.E. Gordon K.B. et al.Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials.JAMA. 2011; 306: 864-871Crossref PubMed Scopus (239) Google Scholar Risk stratification and treatment goals for cholesterol and blood pressure in psoriasis remain understudied, and the Framingham risk score (FRS) for CV risk may underestimate long-term risk of MACE in patients with psoriasis. The Adult Treatment Panel for lipid management recommends that providers consider emerging risk factors when deciding on lipid treatment but does not provide specific guidelines. We described an initial estimate of this excess attributable risk (AR) of severe psoriasis on MACE3Mehta N.N. Yu Y. Pinnelas R. Krishnamoorthy P. Shin D.B. Troxel A.B. et al.Attributable risk estimate of severe psoriasis on major adverse cardiac events.Am J Med. 2011; 124: 775e1-775e6Google Scholar and herein describe how this AR may affect FRS in psoriasis. We consecutively enrolled patients (n = 138), and calculated FRS before and after adding the AR of psoriasis (6.2%),3Mehta N.N. Yu Y. Pinnelas R. Krishnamoorthy P. Shin D.B. Troxel A.B. et al.Attributable risk estimate of severe psoriasis on major adverse cardiac events.Am J Med. 2011; 124: 775e1-775e6Google Scholar and estimated the reclassification rate by examining patients moved from a lower risk category to a higher risk category. Patients with psoriasis were relatively young with higher than expected tobacco use, alcohol use, body mass index, and lipids (Table I). Nonetheless, their risk for MACE by FRS was low (<10%) (male mean FRS 7.4 ± 7.75, female 5.9 ± 5.86), attributable to their young age. After considering the estimated AR (mean FRS 13.36 ± 7.10, male 13.92 ± 7.77, female 12.48 ± 5.86), the majority of patients were reclassified to a higher risk category: 73% (95% confidence interval 61.5%-82.3%) of patients at low risk were reclassified as intermediate risk, and 53% (95% confidence interval 36.4%-64.1%) of those at intermediate risk were reclassified as high risk (Table II). These findings suggest that adding the estimated AR of psoriasis on MACE to the FRS results in clinically important changes in prevention strategies.3Mehta N.N. Yu Y. Pinnelas R. Krishnamoorthy P. Shin D.B. Troxel A.B. et al.Attributable risk estimate of severe psoriasis on major adverse cardiac events.Am J Med. 2011; 124: 775e1-775e6Google Scholar CAD, Coronary artery disease; ESR, erythrocyte sedimentation rate; HDL, high-density lipoprotein; IQR, interquartile range; LDL, low-density lipoprotein; VLDL, very-low-density lipoprotein. LDL, Low-density lipoprotein. Because of the young age of our population, the majority of patients were in the low risk category, which would not warrant aggressive risk reduction strategies. However, when considering an AR estimate of MACE, the majority of our patients were reclassified into the intermediate risk category, which would warrant change in treatment plans and goals for more than 60% of our patients (Table II), an important finding in this population potentially at higher risk for CV disease with increased subclinical vascular inflammation.4Mehta N.N. Yu Y. Saboury B. Foroughi N. Krishnamoorthy P. Raper A. et al.Systemic and vascular inflammation in patients with moderate to severe psoriasis as measured by [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT): a pilot study.Arch Dermatol. 2011; 147: 1031-1039Crossref PubMed Scopus (169) Google Scholar We recognize this proof-of-concept study is limited by the generalizability of United Kingdom data to a US population. However, guidelines for identifying CV disease risk factors are similar. Secondly, our AR was derived in severe psoriasis defined by treatment with systemic therapy or phototherapy; similarly, more than 80% of our patients had been exposed to these therapies permitting this estimate to be applicable in this proof-of-concept study. The major implication of these findings is that patients with psoriasis may warrant more aggressive control of established CV risk factors. Measures to decrease CV risk include lifestyle and dietary education through targeted counseling. The percentage of these patients requiring drug interventions such as statins and antihypertensive is unknown but likely to be small. Finally, this illustration provides a quantitative approach for CV risk estimation in psoriasis, an approach gaining acceptance in the care of patients with rheumatoid arthritis.5Peters M.J. Symmons D.P. McCarey D. Dijkmans B.A. Nicola P. Kvien T.K. et al.EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis.Ann Rheum Dis. 2010; 69: 325-331Crossref PubMed Scopus (1063) Google Scholar