Purpose
Systemic sclerosis (SSc) is characterized by calcification, vasculopathy, and endothelial wall damage, all of which can increase the risk for atherosclerosis and cardiovascular disease. Our objective was to perform a systematic review and meta-analysis to determine if atherosclerosis is increased in patients with SSc compared to healthy individuals.
Methods
We performed a systematic search of studies published in PubMed and the Cochrane database up to May 2010, and reviewed recently-published abstracts. Two reviewers independently screened articles to identify studies comparing rates of atherosclerosis in SSc patients vs. healthy controls using one of the following modalities: angiography, doppler ultrasound to assess plaque and carotid intima-medial thickness (CIMT), computer tomography, magnetic resonance imaging, flow mediated dilation (FMD), ankle-brachial index, or autopsy findings. For CIMT and FMD, we computed a pooled estimate of the summary mean difference (MD) and explored predictors of CIMT using random-effects meta-regression.
Results
Of 3,156 articles initially identified, 33 were selected for the systematic review. Meta-analysis included 14 CIMT and 7 FMD studies. Compared to healthy controls, SSc patients had higher prevalence of coronary atherosclerosis, peripheral vascular disease, and cerebrovascular calcification. Meta-analysis showed SSc subjects had increased CIMT [MD 0.11mm (95% CI 0.05, 0.17), P=0.0006] and lower FMD [MD -3.07% (95%CI -5.44, -0.69), P=0.01]. There was marked heterogeneity between the studies, namely from variations in disease duration and difference in mean/median age between SSc and control groups.
Conclusion
Patients with SSc have increased atherosclerosis compared to healthy controls. Further studies should elucidate the mechanism of this increased risk.
Background and Purpose-Platelets bearing complement C4d were recently reported to be 99% specific for a diagnosis of systemic lupus erythematosus (SLE) and associated with neuropsychiatric lupus. We compared the prevalence of platelet C4d and investigated the clinical associations of platelet C4d in patients with acute ischemic stroke. Methods-We recruited 80 patients hospitalized for acute ischemic stroke. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIH-SS). Infarct volume was determined by MRI. Platelet C4d was measured by flow cytometry. Results-Mean age was 57.9 years (range: 24.6 to 86.8 years), 58% were male, and 91% were white. Eight patients (10%) with acute ischemic stroke were platelet C4d-positive, which was significantly higher in prevalence compared to healthy controls (0%, PϽ0.0001) and non-SLE patients with immune/inflammatory disease (2%, Pϭ0.004). The median NIH-SS score and infarct volume for acute stroke patients were 6 (interquartile range [IQR]: 2 to 13) and 3.4 cc (IQR: 1.1 to 16.6), respectively. Platelet C4d-positive patients were more likely to have a severe stroke compared to those with negative platelet C4d (NIH-SS median: 17.5 versus 5, Pϭ0.003). Positive platelet C4d was independently associated with stroke severity (Pϭ0.03) after controlling for age, anticardiolipin antibody (aCL) status, and total anterior circulation of stroke involvement, and also with infarct volume (Pϭ0.005) after controlling for age, aCL status, and old stroke by MRI.
Conclusions-Platelet
Patients with SSc have a higher prevalence of carotid plaque than matched controls, and patients with SSc-plaque vs patients without plaque have elevated serum proteins implicated in both vasculopathy and fibrosis. Further studies are needed to evaluate the role of these proteins in SSc compared with healthy controls.
Objective. To evaluate changes in vascular and musculoskeletal involvement in subjects in the Scleroderma Lung Study, a multicenter, double-blind, randomized, controlled trial comparing placebo treatment with oral cyclophosphamide (CYC) for 1 year in systemic sclerosis patients with interstitial lung disease. Subjects were then followed off the study agent for an additional 12 months. Methods. The following parameters were noted at baseline and every 6 months for each patient: digital tip ulcers, other dermal ulcers, joint swelling, joint tenderness, large joint contractures, muscle tenderness, muscle weakness, oral aperture, hand extension, and fist closure. Results. A total of 158 patients were enrolled from 13 centers in the US; 79 were randomized to the CYC group and 79 to the placebo group. There were no differences in dermal ulcer and musculoskeletal measures between the CYC and placebo groups at baseline and 12 and 24 months. Improvement in percent predicted forced vital capacity was associated with improvement in the Rodnan skin thickness score (P < 0.05) at 12 and 24 months, and with increased mean oral aperture at 24 months (P ؍ 0.005). Conclusion. These data document the frequency and course of these vascular and musculoskeletal features over time, therefore providing essential information for sample size calculations and magnitude of effect in future clinical trials. There was no treatment effect of CYC on the vascular and musculoskeletal features described.
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