Abstract

Background: Patients with systemic lupus erythematosus (SLE) have higher risk of coronary artery disease (CAD) and stroke than the general population 1-2. Because these comorbidities influence on patients’ vital prognosis and quality of life, it is essential for rheumatologists to manage them appropriately. Considering differences in life style and ethnicity, it is of great interest and needed to investigate risk of these comorbidities in Asia. However, to date, such evidence is scarce. Objectives: To estimate incidence rate (IR) and identify risk factors of CAD and stroke in patients with SLE using a Japanese health insurance database. Methods: This retrospective longitudinal population-based study was conducted using claims data provided by Medical Data Vision Co., Ltd (Tokyo, Japan). We defined individuals as SLE cases if they met all of the following: 1) had at least one ICD10 code (M321 or M329); 2) had at least one prescription of oral corticosteroids (CS), methylprednisolone (mPSL) pulse therapy, immunosuppressive drugs (IS) (azathioprine, mizoribine, tacrolimus, mycophenolate mofetil, cyclophosphamide, methotrexate), biologics (belimumab, rituximab) or hydroxychloroquine between April 2008 and July 2017; 3) were 16 years old or over. The start of observation was defined by the first month in which cases met all of the above criteria. Patients were followed until the earliest of date of first CAD event or stroke, date of loss of follow-up, or the end of follow-up (June 2018). CAD and stroke were defined as follows: for CAD, at least one ICD10 code (I20.x or I21.x or I23-24.x) and either percutaneous coronary intervention, coronary artery bypass procedure, or thrombolytic agents during hospitalization: for stroke, at least one ICD10 code (I60-62.x or I63-64.x) and either cerebrovascular procedures, thrombolytic agents, or antiplatelet drugs during hospitalization. Patients were excluded if they had a previous diagnosis of CAD or stroke and were prescribed antiplatelet drugs or anticoagulants during the first 3 months. We defined baseline characteristics using the data from the first 3 months, and calculated IR and adjusted hazard ratio (HR) of risk factors for CAD or stroke after adjusting for baseline characteristics using a Cox proportional hazard model. Results: In this study, 19,138 cases were included. The median age was 53 years and 81.3% were female. Median observation period was 3.1 years. IR [95% CI]/1,000 patient-years (PY) of CAD or stroke was 1.41 [1.11-1.77] and 4.10 [3.56-4.70], respectively. IR of any CAD or stroke was increased age-dependently (2.06 [1.47-2.80] for 16-39 years-old, 5.07 [4.36-5.86] for 40-69, 13.0 [10.9-15.5] for 70-). Adjusted HR [95% CI] was 1.37 [95% CI, 1.27-1.47] for age by decade, 3.34 [1.78-6.28] for CS use, 1.46 [1.16-1.84] for presence of hypertension (HT), 1.38 [1.04-1.85] for diabetes mellitus (DM), 1.73 [1.25-2.38] for chronic kidney disease (CKD), and 1.95 [1.15-3.32] for atrial fibrillation (AF). Conclusion: This is the first study investigating the risk of CAD or stroke in Japanese patients with SLE using a large health insurance database. Older age, use of CS, and presence of HT, DM, CKD, and AF were identified as significant risk factors of these comorbidities.

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