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Interaction between smoking and functional polymorphism in the TGFB1 gene is associated with ischaemic heart disease and myocardial infarction in patients with rheumatoid arthritis: a cross-sectional study
Authors:Ying Chen  Peter T Dawes  Jon C Packham  Derek L Mattey
Institution:1. Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, SE-171 76, Stockholm, Sweden
2. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, SE-171 76, Stockholm, Sweden
3. Unit of Clinical Immunology, Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, SE-171 76, Stockholm, Sweden
4. Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, SE-171 76, Stockholm, Sweden
5. Department of Clinical Chemistry and Pharmacology, Akademiska Hospital, SE-751 85, Uppsala, Sweden
Abstract:

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on cardiovascular morbidity are abundant, whereas mortality studies focusing on cardiovascular outcomes are scarce. The aim of this study was to investigate causes of death and baseline predictors of overall (OM), non-vascular (N-VM), and specifically cardiovascular (CVM) mortality in SLE, and to evaluate systematic coronary risk evaluation (SCORE).

Methods

208 SLE patients were included 1995-1999 and followed up after 12 years. Clinical evaluation, CVD risk factors, and biomarkers were recorded at inclusion. Death certificates and autopsy protocols were collected. Causes of death were divided into CVM (ischemic vascular and general atherosclerotic diseases), N-VM and death due to pulmonary hypertension. Predictors of mortality were investigated using multivariable Cox regression. SCORE and standardized mortality ratio (SMR) were calculated.

Results

During follow-up 42 patients died at mean age of 62 years. SMR 2.4 (CI 1.7-3.0). 48% of deaths were caused by CVM. SCORE underestimated CVM but not to a significant level. Age, high cystatin C levels and established arterial disease were the strongest predictors for all- cause mortality. After adjusting for these in multivariable analyses, only smoking among traditional risk factors, and high soluble vascular cell adhesion molecule-1 (sVCAM-1), high sensitivity C-reactive protein (hsCRP), anti-beta2 glycoprotein-1 (abeta2GP1) and any antiphospholipid antibody (aPL) among biomarkers, remained predictive of CVM.

Conclusion

With the exception of smoking, traditional risk factors do not capture the main underlying risk factors for CVM in SLE. Rather, cystatin C levels, inflammatory and endothelial markers, and antiphospholipid antibodies (aPL) differentiate patients with favorable versus severe cardiovascular prognosis. Our results suggest that these new biomarkers are useful in evaluating the future risk of cardiovascular mortality in SLE patients.
Keywords:
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