title: Predictors of the first cardiovascular event in patients with systemic lupus erythematosus - a prospective cohort study.
abstract: BACKGROUND
  Cardiovascular disease (CVD) is a major cause of premature mortality among Systemic lupus erythematosus (SLE) patients. Many studies have measured and evaluated risk factors for premature subclinical atherosclerosis, but few studies are prospective and few have evaluated risk factors for hard endpoints, i.e. clinically important cardiovascular events (CVE). We investigated the impact of traditional and lupus associated risk factors for the first ever CVE in a longitudinal cohort of SLE patients.
  
  
  METHODS
  A total of 182 SLE patients (mean age 43.9 years) selected to be free of CVE were included. Cardiovascular and autoimmune biomarkers were measured on samples collected after overnight fasting at baseline. Clinical information was collected at baseline and at follow up. End point was the first ever CVE (ischemic heart, cerebrovascular or peripheral vascular disease or death due to CVD). Impact of baseline characteristics/biomarkers on the risk of having a first CVE was evaluated with Cox regression.
  
  
  RESULTS
  Follow up was 99.5% after a mean time of 8.3 years. Twenty-four patients (13%) had a first CVE. In age-adjusted Cox regression, any positive antiphospholipid antibody (aPL), elevated markers of endothelial activation (von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1)) and fibrinogen predicted CVEs. Of SLE manifestations, arthritis, pleuritis and previous venous occlusion were positively associated with future CVEs while thrombocytopenia was negatively associated. Among traditional risk factors only age and smoking were significant predictors. In a multivariable Cox regression model age, any positive aPL, vWf and absence of thrombocytopenia were all predictors of the first CVE.
  
  
  CONCLUSIONS
  In addition to age, positive aPL, biomarkers indicating increased endothelial cell activity/damage, and absence of thrombocytopenia were independent predictors of CVEs in this prospective study. Our results indicate that activation of the endothelium and the coagulation system are important features in SLE related CVD. Furthermore, we observed that the risk of CVEs seems to differ between subgroups of SLE patients.
authors.affiliation: Rheumatology Unit, Department of Medicine Karolinska University Hospital, Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden. johanna.gustafsson@karolinska.se
authors.forename: Johanna
authors.initials: J
authors.lastname: Gustafsson
authors.forename: Iva
authors.initials: I
authors.lastname: Gunnarsson
authors.forename: Ola
authors.initials: O
authors.lastname: Börjesson
authors.forename: Susanne
authors.initials: S
authors.lastname: Pettersson
authors.forename: Sonia
authors.initials: S
authors.lastname: Möller
authors.forename: Guo-Zhong
authors.initials: GZ
authors.lastname: Fei
authors.forename: Kerstin
authors.initials: K
authors.lastname: Elvin
authors.forename: Julia F
authors.initials: JF
authors.lastname: Simard
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Hansson
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Lundberg
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Elisabet
authors.initials: E
authors.lastname: Svenungsson
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D017152:Antibodies, Antiphospholipid / Q000097:blood; D015415:Biomarkers / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D015331:Cohort Studies; D042783:Endothelial Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013921:Thrombocytopenia / Q000453:epidemiology
chemical_list: D017152:Antibodies, Antiphospholipid; D015415:Biomarkers