Abstract
IntroductionCardiovascular 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.MethodsA 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.ResultsFollow 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.ConclusionsIn 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.
Highlights
Cardiovascular disease (CVD) is a major cause of premature mortality among Systemic lupus erythematosus (SLE) patients
In healthy individuals high circulating levels of vWf predicted cardiovascular events (CVE) in several studies [23,24], but in contrast to this study, significance did not remain after adjustment for other coronary artery disease (CAD) risk factors [24,25]
The present study extends these findings as we can report that high levels of sVCAM-1 predict future CVE, independently of aPLs
Summary
Cardiovascular disease (CVD) is a major cause of premature mortality among Systemic lupus erythematosus (SLE) patients. Systemic lupus erythematosus (SLE) is a heterogeneous chronic systemic autoimmune disease, which mainly affects women (90%). As treatment for lupus itself has gradually improved, mortality rates have declined and cardiovascular comorbidity has become a growing clinical problem. Circulatory diseases are today a leading cause of mortality among SLE patients [1,2]. At follow-up (2004-2007) living patients were reinvestigated in person when possible. If not, they were interviewed by telephone. Medical charts were reviewed for all patients and death certificates were collected from all deceased patients.
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