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Background: Patients with vasculitis (VS) have complex organ- and life-threatening disease manifestations due to autoimmune-mediated inflammatory vascular damage and an increased risk of cardiovascular disease (CVD). Accurate biomarkers do not exist for VS. Cells release extracellular vesicles (EVs) in the setting of activation, injury, or death. In patients with diabetes mellitus and CVD, the effects of the inflammatory cascade, platelets and endothelium, positively correlate with levels of EVs bearing receptors for CD3, CD41, or CD105, and negatively correlate with levels of circulating endothelial progenitor cells (CPCs). Because VS is characterized by systemic inflammation, platelet activation and endothelial damage, this group of diseases may have unique effects on EVs and CPCs. This study evaluated a high dimensional flow cytometry approach to profiling EVs and CPCs in plasma to discern a biomarker pattern in VS. Methods: Levels of CPCs and EVs were measured with a panel of cell surface markers in 10 VS patients and 5 age-similar healthy controls (HC). Data were acquired on a modified Becton Dickinson FACSCanto. Results: Although no significant increase in CPCs in VS compared with HC was detected, the standard deviation of CPC levels in VS was more than double that in HC (SD=574 vs. 165, p=0.081), suggesting heterogeneity in the VS group. EV subsets with lower concentrations in VS, compared with HC, included: Annexin + CD3 + double-positive T Lymphocyte (p=0.026) and CD105 + CD64 + double-positive activated Macrophage (p=0.030). CD144 + CD105 + double-positive endothelial EVs were only detected in a subset of VS and not in HC. CD31 + CD41a + double-positive platelet EVs were increased in VS compared with HC (894 (580) vs. 416 (128), p=0.004). Conclusion: This proof of concept study discovered a distinct EV pattern that correlates with a diagnosis of VS, suggesting that cell- and vesicle-based assays could be useful biomarkers in evaluating VS. This pattern is different from that found in patients with diabetes mellitus and CVD. Larger studies could seek to elucidate correlations between CPCs and disease activity and identify a unique EV signature for VS with increased risk for CVD.

Background Acute decompensated heart failure (ADHF) requiring hospitalization is associated with high postdischarge mortality and readmission rates. Purpose To examine the association between achieving predischarge natriuretic peptide (NP) thresholds and mortality and readmission rates in adults hospitalized for ADHF. Data sources Multiple databases from 1947 to October 2016 (English-language studies only). Study selection Trials and observational studies that compared mortality and readmission outcomes between patients with ADHF achieving a specific predischarge NP goal and those not achieving the goal. Data extraction Two investigators independently extracted study characteristics and assessed study risk of bias. One author graded the overall strength of evidence, with review by a second author. Data synthesis One randomized trial, 3 quasi-experimental studies, and 40 observational studies were identified. The most commonly used thresholds were a brain-type NP (BNP) level of 250 pg/mL or less or an amino-terminal pro-brain-type NP (NT-proBNP) decrease of at least 30%. Achievement of absolute BNP thresholds reduced postdischarge all-cause mortality (7 of 8 studies) and the composite outcome of mortality and readmission (12 of 14 studies). Achievement of percentage-change BNP thresholds reduced the composite outcome (5 of 6 studies), and achievement of percentage-change NT-proBNP thresholds reduced all-cause and cardiovascular mortality (2 of 4 studies) and the composite outcome (9 of 9 studies). All findings were low-strength. The randomized trial, assessed as having high risk of bias, suggested that a predischarge decrease in NT-proBNP level was associated with lower risk for the composite outcome. Two quasi-experimental studies and 5 observational studies had low risk of bias. Low-risk-of-bias studies had outcome estimates similar in magnitude and direction to estimates from high-risk-of-bias studies. Limitation Most studies failed to adjust for critical confounders and had inadequate definition or assessment of exposures and outcomes. Conclusion Low-strength evidence suggests an association between achieving NP predischarge thresholds and reduced ADHF mortality and readmission. Primary funding source None.