Coronary Artery Disease in Patients With Psoriasis Referred for Coronary Angiography

Transcription

1 Coronary Artery Disease in Patients With Psoriasis Referred for Coronary Angiography April W. Armstrong, MD, MPH a, *, Caitlin T. Harskamp, BA a, Lynda Ledo, BS a, Jason H. Rogers, MD b, and Ehrin J. Armstrong, MD, MSc b Patients with psoriasis may have an increased risk of cardiovascular disease and myocardial infarction. The aim of this study was to investigate whether psoriasis is associated with an increased prevalence of coronary artery disease (CAD) independent of established cardiovascular risk factors in patients undergoing coronary angiography. A retrospective cohort analysis was performed by linking records of all patients undergoing coronary angiography from 2004 through 2009 with dermatology medical records. From an overall cohort of 9,473 patients, we identified 204 patients (2.2%) with psoriasis before coronary angiography. Patients with psoriasis had higher body mass index ( vs kg/m 2,p<0.001) but the prevalence of other risk factors was similar. Median duration of psoriasis before cardiac catheterization was 8 years (interquartile range 2 to 24). Patients with psoriasis were more likely to have CAD (84.3% vs 75.7%, p 0.005) at coronary angiography. After adjusting for established cardiovascular risk factors, psoriasis was independently associated with presence of angiographically confirmed CAD (adjusted odds ratio 1.8, 95% confidence interval 1.2 to 2.8, p 0.006). In patients with psoriasis, duration of psoriasis >8 years was also independently associated with angiographically confirmed CAD after adjusting for established cardiovascular risk factors (adjusted odds ratio 3.5, 95% confidence interval 1.3 to 9.6, p 0.02). In conclusion, patients with psoriasis and especially those with psoriasis for >8 years have a higher prevalence of CAD than patients without psoriasis undergoing coronary angiography Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109: ) No study to date has systematically examined the presence of coronary artery disease (CAD) in patients with psoriasis undergoing coronary angiography. In this study we linked cardiac catheterization data with clinical data on patients with psoriasis. By creating this unique database, we were able to examine whether psoriasis is independently associated with angiographically confirmed CAD in patients undergoing coronary angiography. Methods We identified all patients who underwent cardiac catheterization at the University of California, Davis from 2004 through This database contains prospective data entered at the time of cardiac catheterization including patient risk factors, medical history, and quantitative results of coronary angiography. Patients were included if they were 18 years of age and had undergone coronary angiography from 2004 through This study was approved by the University of California, Davis, institutional review board. a Department of Dermatology and b Division of Cardiovascular Medicine, University of California Davis, Sacramento, California. Manuscript received October 17, 2011; revised manuscript received and accepted November 11, This work was supported by the Dermatology Foundation, Evanston, Illinois. Dr. Rogers is a consultant for Volcano, Medtronic, Cordis and Boston Scientific. Dr. A.W. Armstrong is an investigator and consultant for Abbott and Centocor. *Corresponding author: Tel: ; fax: address: aprilarmstrong@post.harvard.edu (A.W. Armstrong). To identify psoriatic patients within the catheterization database, we first obtained a list of patients from the University of California, Davis, Medical Center electronic health records with a diagnostic code of psoriasis before This list was then cross-referenced with the cardiac catheterization database list to identify those patients with possible psoriasis who underwent cardiac catheterization. To confirm the presence of physician-diagnosed psoriasis in these patients and to further identify other patients with psoriasis who may have received care elsewhere, all patients who underwent cardiac catheterization during the study period were then contacted by telephone and asked to complete a brief survey on their psoriasis status. Based on the medical record reviews and telephone surveys, 204 patients had been diagnosed with psoriasis before cardiac catheterization. Risk factors for CAD, age, self-reported ethnicity, and insurance status were prospectively entered at the time of cardiac catheterization. At the time or coronary angiography, a cardiologist determined the severity of CAD for the left main, left anterior descending, left circumflex, and right coronary arteries. If there were multiple lesions present in a single coronary artery territory, the most severe stenosis was recorded. Any CAD was defined as any stenosis scored visually at the time of coronary angiography. Obstructive CAD was defined as stenosis 50% in the left main coronary artery or 70% in other coronary territories to reflect the presence of more severe lesions for which percutaneous coronary intervention or coronary artery bypass grafting is usually considered /12/$ see front matter 2012 Elsevier Inc. All rights reserved. doi: /j.amjcard

2 Coronary Artery Disease/Psoriasis and Coronary Artery Disease 977 Table 1 Cardiovascular risk factors and presentation of patients with psoriasis undergoing cardiac catheterization Variable Psoriasis p Value Table 2 Prevalence of coronary artery disease in patients with psoriasis undergoing cardiac catheterization Variable Psoriasis p Value Yes (n 204) No (n 9,265) Yes (n 204) No (n 9,265) Age (years) Men 120 (59%) 5,499 (60%) 0.7 Body mass index (kg/m 2 ) Race/ethnicity White 164 (80%) 6,227 (67%) Hispanic 11 (5.4%) 823 (8.9%) African-American 16 (7.8%) 1,141 (12%) Asian 10 (4.9%) 708 (7.7%) Other 3 (1.5%) 351 (3.8%) Previous myocardial 37 (18%) 1,991 (22%) 0.2 infarction Hypertension 158 (78%) 6,811 (75%) 0.3 Current or previous smoker 118 (62%) 4,962 (58%) 0.3 Diabetes mellitus 61 (31%) 2,826 (32%) 0.7 Stroke 27 (13%) 1,022 (11%) 0.4 Renal failure 7 (11%) 680 (20%) 0.2 Peripheral vascular disease 19 (9.5%) 781 (8.7%) 0.7 Hypercholesterolemia* 145 (72%) 5,942 (66%) 0.06 Heart failure 38 (19%) 1,818 (20%) 0.6 Family history of coronary 39 (19%) 1,478 (16%) 0.3 artery disease Previous coronary bypass 22 (11%) 1,140 (13%) 0.5 Presentation symptoms 0.8 Stable angina pectoris 105 (55%) 4,760 (55%) Acute coronary syndrome 87 (45%) 3,820 (45%) * Defined as any history of medical treatment for increased cholesterol levels. Defined as presentation with unstable angina or myocardial infarction. Psoriasis disease severity was considered mild if a patient had a history of using only topical medications for treatment of psoriasis and moderate-to-severe if a patient had received phototherapy or systemic medications (including oral and biologic medications). These categories were chosen because they reflect clinically meaningful differences in psoriasis disease severity. Mean SD was used to describe continuous variables and numerical counts (percentages) were used for categorical variables. Univariate analysis using t test or chi-square test was used to identify differences between subjects with or without psoriasis at the time of coronary angiography. A p value 0.05 was considered statistically significant for all analyses. First, univariate logistic regression was used to determine the unadjusted relation (odds ratio [OR]) between predictor variables and angiographically confirmed CAD. A multivariate logistic regression model was then constructed using angiographically confirmed CAD as the outcome. Known risk factors for CAD (including age, diabetes, BMI, hypertension, hypercholesterolemia, peripheral vascular disease, family history of CAD) were automatically included. Second, a list of possible confounders was generated using a directed acyclic graph. 1 Confounders from this second group were retained if they were found to be associated with the outcome using a p value 0.1 as a cutoff for Any coronary artery disease 172 (84%) 7,020 (76%) Any coronary artery disease 107 (53%) 4,735 (51%) % Vessel with any coronary artery disease* Left main coronary artery 54 (27%) 2,453 (27%) 1.0 Left anterior descending 158 (78%) 6,227 (67%) coronary artery Left circumflex coronary 123 (60%) 5,240 (57%) 0.3 artery Right coronary artery 123 (60%) 5,672 (61%) 0.8 Percutaneous coronary intervention performed 77 (39%) 3,306 (37%) 0.7 * Columns add up to 100% because a patient could have stenoses in multiple vessels. inclusion. A manual stepwise elimination algorithm was then used. Covariates in the final model included age, ethnicity, gender, body mass index, history of diabetes, cerebrovascular disease, peripheral vascular disease, hypertension, smoking status, previous myocardial infarction, hypercholesterolemia, previous coronary bypass, and family history of CAD. A secondary analysis was also performed in patients with psoriasis to examine the association between moderate-to-severe psoriasis and history of myocardial infarction. Hosmer Lemeshow goodness-of-fit testing was used to confirm model discrimination for all models. All statistical analysis was performed using STATA 11 (STATA Corp., College Station, Texas). Results From a total population of 9,473 patients who underwent coronary angiography, we identified 204 patients (2.2% of overall population) who had psoriasis before coronary angiography (Table 1). Compared to the overall population, patients with psoriasis had a higher body mass index ( vs kg/m 2,p 0.001) and were more likely to have a history of hypercholesterolemia (72% vs 66%, p 0.06). Eighteen percent of patients with psoriasis had previous myocardial infarction and 45% of patients with psoriasis presented with an acute coronary syndrome. Patients with psoriasis were more likely to have any CAD on coronary angiogram (OR 1.7, p 0.005; Table 2), with a larger percentage of patients having left anterior descending coronary artery disease (78% vs 67%, p 0.002). After adjusting for established cardiovascular risk factors, psoriasis remained independently associated with presence of any CAD on coronary angiogram (adjusted OR [AOR] 1.8, 95% confidence interval [CI] 1.2 to 2.8, p 0.006; Table 3). The independent association of psoriasis with presence of any CAD remained significant when analysis was limited only to patients presenting with stable angina pectoris (AOR 1.9, 95% CI 1.2 to 3.1, p 0.005) or

3 978 The American Journal of Cardiology ( Table 3 Univariate and multivariate associations of Coronary Artery Disease at Time of coronary angiography Predictors Unadjusted OR (95% CI) p Value AOR (95% CI) p Value Psoriasis 1.72 ( ) ( ) Age (years) 1.06 ( ) ( ) Male gender 2.04 ( ) ( ) Caucasian race 1.18 ( ) ( ) Body mass index 0.98 ( ) ( ) Diabetes mellitus 2.01 ( ) ( ) Cerebrovascular disease 1.76 ( ) ( ) Hypertension 2.77 ( ) ( ) Peripheral vascular disease 3.48 ( ) ( ) Current or former smoker 1.58 ( ) ( ) Previous myocardial infarction 3.91 ( ) ( ) History of hypercholesterolemia 3.17 ( ) ( ) Previous coronary bypass 5.19 ( ) ( ) Family history of coronary artery disease 1.20 ( ) ( ) Figure 1. Patients with a diagnosis of psoriasis before coronary angiography were divided into quartiles based on duration of their psoriasis. Patients with psoriasis for a longer duration had a higher prevalence of coronary artery disease at coronary angiography (p for trend 0.009). to patients without previous myocardial infarction (AOR 1.8, 95% CI 1.1 to 2.8, p 0.013). Median duration of psoriasis before cardiac catheterization was 8 years (interquartile range 2 to 24). When patients were divided into quartiles based on duration of psoriasis before cardiac catheterization (Figure 1), there was a positive association between duration of disease and prevalence of any CAD at coronary angiography (p for trend 0.009). Patients with psoriasis for 8 years were more likely to have CAD compared to patients who had psoriasis for 8 years (OR 2.7, 95% CI 1.2 to 5.9, p 0.02). Duration of psoriasis 8 years remained independently associated with any angiographically confirmed CAD after adjusting for age and other established cardiovascular risk factors (AOR 3.4, 95% CI 1.2 to 9.1, p 0.02). Of the 204 patients with psoriasis before cardiac catheterization, 51 (25%) had previous moderate-to-severe psoriasis (Table 4). Compared to patients with mild psoriasis, patients with moderate-to-severe psoriasis were younger ( vs years, p 0.05), were less likely to be white (71% vs 84%, p 0.05), and were significantly more likely to have previous myocardial infarction (32% vs 14%, p 0.004). Prevalence of hypertension, obesity, hypercholesterolemia, and smoking was similar regardless of psoriasis disease severity. Patients with moderate-to-severe psoriasis had similar rates of any CAD at time of coronary angiography compared to the group with mild psoriasis. On multivariable analysis, moderate-to-severe psoriasis was independently associated with a history of myocardial infarction even after adjusting for established cardiovascular risk factors (AOR 6.7, 95% CI 2.3 to 19.6). Discussion This analysis represents the first systematic study of the prevalence of angiographically confirmed CAD in psoriasis patients referred for coronary angiography. Three important findings emerge from this study. First, patients with psori-

4 Coronary Artery Disease/Psoriasis and Coronary Artery Disease 979 Table 4 Cardiovascular risk factors and severity of psoriasis Variable Psoriasis Severity p Mild (n 153) Moderate/Severe (n 51) Value Age (years) Men 89 (58%) 31 (61%) 0.7 Body mass index (kg/m 2 ) Race/ethnicity White 128 (84%) 36 (71%) 0.06 Hispanic 8 (5%) 3 (6%) African-American 8 (5%) 8 (16%) Asian 6 (4%) 4 (8%) Other 3 (2%) 0 (0%) Previous myocardial infarction 21 (14%) 16 (32%) Hypertension 118 (78%) 40 (78%) 0.9 Current or previous smoker 84 (60%) 34 (68%) 0.3 Diabetes mellitus 51 (34%) 10 (21%) 0.09 Stroke 23 (15%) 4 (8%) 0.2 Renal failure 5 (12%) 2 (10%) 0.8 Peripheral vascular disease 13 (9%) 6 (12%) 0.5 Hypercholesterolemia 109 (72%) 36 (71%) 0.8 Heart failure 25 (17%) 13 (26%) 0.1 Family history of coronary 29 (19%) 10 (20%) 0.9 artery disease Previous coronary bypass 14 (9%) 8 (16%) 0.2 Presentation symptoms 0.9 Stable angina pectoris 78 (55%) 27 (54%) Acute coronary syndrome 64 (45%) 23 (46%) asis have an increased prevalence of cardiovascular risk factors even compared to an otherwise high-risk cohort. Second, patients with psoriasis are more likely to have CAD as visualized on coronary angiogram even after adjusting for established cardiovascular risk factors. Third, an increased duration of psoriasis significantly increases the odds of having any CAD diagnosed at coronary angiography. Our cohort represents a selected group of patients with psoriasis because most previous epidemiologic studies have used large outpatient databases to describe the prevalence of cardiovascular risk factors. 2 7 As a result the subjects in this study had a much higher baseline prevalence of typical cardiovascular risk factors than the general outpatient population. It is therefore striking that, even in this high-risk population, patients with psoriasis had a higher body mass index and trends toward higher rates of hypertension and hypercholesterolemia than the overall cohort. These findings are consistent with other epidemiologic studies that have shown that patients with psoriasis are more likely to be obese, to have dyslipidemia, and to have more severe hypertension Presence of psoriasis was associated with increased odds of having any CAD at time of coronary angiography, with absolute rates of angiographically confirmed CAD 8% higher than in the cohort of patients without psoriasis who were referred for coronary angiography. The increased prevalence of any CAD remained significant even after adjusting for established cardiovascular risk factors, suggesting that psoriasis may contribute to coronary atherosclerosis independent of other risk factors. Recent evidence has suggested that psoriasis is associated with systemic inflammation and an increased risk for developing cardiovascular disease. 11,12 Psoriasis and atherosclerosis share many underlying etiologic mechanisms, including increased T-helper type 1 mediated inflammation and dysregulation of angiogenesis. 12,13 This has led to the concept that systemic inflammation from psoriasis may predispose to atherosclerotic initiation and progression. 14 Consistent with these common underpinnings, patients with psoriasis have increased carotid intima media thickness and may have insulin resistance and endothelial dysfunction, which are crucial steps in the initiation of atherosclerotic plaque. 15,16 Preliminary studies have also suggested that systemic therapies for treatment of severe psoriasis may correct endothelial dysfunction and decrease the risk of cardiovascular events. 17,18 Future research should focus on novel inflammatory mechanisms linking psoriasis to the initiation of atherosclerosis. In further support of the link between psoriasis and CAD, we found that patients with a longer duration of psoriasis (defined as 8 years) were also more likely to have CAD on coronary angiogram even after adjusting for age and other established cardiovascular risk factors. Median time from psoriasis diagnosis to coronary angiography was 8 years, suggesting that psoriasis may modify the risk of progressive atherosclerosis over time. Psoriasis has a bimodal distribution of incidence, with a first peak in patients between 20 to 30 years old and a second peak in patients 50 to 60 years of age. Because this second peak coincides with the age range that patients are also more likely to develop overt CAD, recognizing the increased risk of CAD in older patients with incident psoriasis may have important implications for preventing future cardiovascular events. Screening for psoriasis by cardiologists may increase awareness that a given patient is at higher risk of cardiovascular disease. 19,20 Given the epidemiologic links between psoriasis and cardiovascular disease found in this and other studies, patients with psoriasis may benefit from more aggressive risk stratification and cardiovascular risk factor modification. 21 This study should be interpreted in the context of several potential limitations. First, this study shows an association between psoriasis and angiographic CAD but cannot prove causation. Our findings are consistent with biological mechanisms and the association between psoriasis and CAD remained even after limiting our analysis to patients with stable angina and to those without previous myocardial infarction. Second, this was a single-center cohort study. Third, coronary angiographic scoring was based on visual estimation at the time of cardiac catheterization. Compared to quantitative angiography, visual estimation may overestimate the severity of intermediate (50% to 70%) lesions. 22,23 Although this method may bias the prevalence of obstructive CAD reported in our cohort, it is unlikely that physician bias led to scoring CAD as more severe in patients with psoriasis compared to patients without psoriasis. Fourth, coronary angiography only estimates the intraluminal caliber of coronary artery stenoses. Therefore total coronary atherosclerotic burden may not accurately reflect total coronary plaque burden. Future studies could use intravascular ultrasound or other novel imaging techniques to determine whether the association of psoriasis with CAD is related to total coronary atherosclerotic plaque burden.

5 980 The American Journal of Cardiology ( 1. Weng HY, Hsueh YH, Messam LL, Hertz-Picciotto I. Methods of covariate selection: directed acyclic graphs and the change-in-estimate procedure. Am J Epidemiol 2009;169: Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA 2006;296: 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: Patel RV, Shelling ML, Prodanovich S, Federman DG, Kirsner RS. Psoriasis and vascular disease-risk factors and outcomes: a systematic review of the literature. J Gen Intern Med 2011;26: 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: Kimball AB, Robinson D Jr, Wu Y, Guzzo C, Yeilding N, Paramore C, Fraeman K, Bala M. Cardiovascular disease and risk factors among psoriasis patients in two US healthcare databases, Dermatology 2008;217: Kimball AB, Guerin A, Latremouille-Viau D, Yu AP, Gupta S, Bao Y, Mulani P. Coronary heart disease and stroke risk in patients with psoriasis: retrospective analysis. Am J Med 2010;123: Love TJ, Qureshi AA, Karlson EW, Gelfand JM, Choi HK. Prevalence of the metabolic syndrome in psoriasis: results from the National Health and Nutrition Examination Survey, Arch Dermatol 2011;147: Coimbra S, Oliveira H, Reis F, Belo L, Rocha S, Quintanilha A, Figueiredo A, Teixeira F, Castro E, Rocha-Pereira P, Santos-Silva A. Circulating levels of adiponectin, oxidized LDL and C-reactive protein in Portuguese patients with psoriasis vulgaris, according to body mass index, severity and duration of the disease. J Dermatol Sci 2009;55: Armstrong AW, Lin SW, Chambers CJ, Sockolov ME, Chin DL. Psoriasis and hypertension severity: results from a case-control study. PLoS ONE 2011;6:e Ludwig RJ, Herzog C, Rostock A, Ochsendorf FR, Zollner TM, Thaci D, Kaufmann R, Vogl TJ, Boehncke WH. Psoriasis: a possible risk factor for development of coronary artery calcification. Br J Dermatol 2007;156: Armstrong AW, Voyles SV, Armstrong EJ, Fuller EN, Rutledge JC. Angiogenesis and oxidative stress: common mechanisms linking psoriasis with atherosclerosis. J Dermatol Sci 2011;63: Methe H, Brunner S, Wiegand D, Nabauer M, Koglin J, Edelman ER. Enhanced T-helper-1 lymphocyte activation patterns in acute coronary syndromes. J Am Coll Cardiol 2005;45: Boehncke WH, Boehncke S, Tobin AM, Kirby B. The psoriatic march : a concept of how severe psoriasis may drive cardiovascular comorbidity. Exp Dermatol 2011;20: Balci DD, Balci A, Karazincir S, Ucar E, Iyigun U, Yalcin F, Seyfeli E, Inandi T, Egilmez E. Increased carotid artery intima-media thickness and impaired endothelial function in psoriasis. J Eur Acad Dermatol Venereol 2009;23: Späh F. Inflammation in atherosclerosis and psoriasis: common pathogenic mechanisms and the potential for an integrated treatment approach. Br J Dermatol 2008;159(suppl 2): Boehncke S, Fichtlscherer S, Salgo R, Garbaraviciene J, Beschmann H, Diehl S, Hardt K, Thaci D, Boehncke WH. Systemic therapy of plaque-type psoriasis ameliorates endothelial cell function: results of a prospective longitudinal pilot trial. Arch Dermatol Res 2010;303: Prodanovich S, Ma F, Taylor JR, Pezon C, Fasihi T, Kirsner RS. Methotrexate reduces incidence of vascular diseases in veterans with psoriasis or rheumatoid arthritis. J Am Acad Dermatol 2005;52: Friedewald VE, Cather JC, Gelfand JM, Gordon KB, Gibbons GH, Grundy SM, Jarratt MT, Krueger JG, Ridker PM, Stone N, Roberts WC. AJC editor s consensus: psoriasis and coronary artery disease. Am J Cardiol 2008;102: Gisondi P, Farina S, Giordano MV, Girolomoni G. Usefulness of the Framingham risk score in patients with chronic psoriasis. Am J Cardiol 2010;106: Kimball AB, Gladman D, Gelfand JM, Gordon K, Horn EJ, Korman NJ, Korver G, Krueger GG, Strober BE, Lebwohl MG; National Psoriasis Foundation. National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening. JAm Acad Dermatol 2008;58: Schweiger MJ, Stanek E, Iwakoshi K, Hafer JG, Jacob A, Tullner W, Gianelly RE. Comparison of visual estimate with digital caliper measurement of coronary artery stenosis. Cathet Cardiovasc Diagn 1987; 13: Fleming RM, Kirkeeide RL, Smalling RW, Gould KL. Patterns in visual interpretation of coronary arteriograms as detected by quantitative coronary arteriography. J Am Coll Cardiol 1991;18: