Pioneering studies have revealed the presence of endogenous microRNAs (miRNAs) in the circulation that are not cell-associated. 1 The cellular origin and the biological function of circulating miRNAs, however, are less clear. Editorial, see p 576We have previously quantified circulating miRNAs in a large population-based cohort, the Bruneck study.3,4 Using concepts of network topology, 5 we identified altered miRNA signatures in patients with type 2 diabetes mellitus 3 and with future myocardial infarction. 4 In addition, we subjected healthy volunteers to limb ischemia-reperfusion generated by thigh cuff inflation. 4 Computational analysis identified 6 distinct miRNA clusters. 4 One cluster included all miRNAs associated with risk of myocardial infarction and consisted of miRNAs predominantly expressed in platelets. Microarray screening revealed that miR-126, miR-197, miR-223, miR-24, and miR-21 are among the most highly expressed miRNAs in platelets and platelet microparticles (PMPs), and their circulating levels correlated with PMPs as quantified by flow cytometry.Original received November 14, 2012; revision received December 21, 2012; accepted December 28, 2012. In November 2012, the average time from submission to first decision for all original research papers submitted to Circulation Research was 15.8 days.Brief UltraRapid Communications are designed to be a format for manuscripts that are of outstanding interest to the readership, report definitive observations, but have a relatively narrow scope.

SummaryBackgroundWhether surgery is beneficial for patients with asymptomatic carotid stenosis is controversial. Better methods of identifying patients who are likely to develop stroke would improve the risk–benefit ratio for carotid endarterectomy. We aimed to investigate whether detection of asymptomatic embolic signals by use of transcranial doppler (TCD) could predict stroke risk in patients with asymptomatic carotid stenosis.MethodsThe Asymptomatic Carotid Emboli Study (ACES) was a prospective observational study in patients with asymptomatic carotid stenosis of at least 70% from 26 centres worldwide. To detect the presence of embolic signals, patients had two 1 h TCD recordings from the ipsilateral middle cerebral artery at baseline and one 1 h recording at 6, 12, and 18 months. Patients were followed up for 2 years. The primary endpoint was ipsilateral stroke and transient ischaemic attack. All recordings were analysed centrally by investigators masked to patient identity.Findings482 patients were recruited, of whom 467 had evaluable recordings. Embolic signals were present in 77 of 467 patients at baseline. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack from baseline to 2 years in patients with embolic signals compared with those without was 2·54 (95% CI 1·20–5·36; p=0·015). For ipsilateral stroke alone, the hazard ratio was 5·57 (1·61–19·32; p=0·007). The absolute annual risk of ipsilateral stroke or transient ischaemic attack between baseline and 2 years was 7·13% in patients with embolic signals and 3·04% in those without, and for ipsilateral stroke was 3·62% in patients with embolic signals and 0·70% in those without. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack for patients who had embolic signals on the recording preceding the next 6-month follow-up compared with those who did not was 2·63 (95% CI 1·01–6·88; p=0·049), and for ipsilateral stroke alone the hazard ratio was 6·37 (1·59–25·57; p=0·009). Controlling for antiplatelet therapy, degree of stenosis, and other risk factors did not alter the results.InterpretationDetection of asymptomatic embolisation on TCD can be used to identify patients with asymptomatic carotid stenosis who are at a higher risk of stroke and transient ischaemic attack, and also those with a low absolute stroke risk. Assessment of the presence of embolic signals on TCD might be useful in the selection of patients with asymptomatic carotid stenosis who are likely to benefit from endarterectomy.FundingBritish Heart Foundation.

Background:Multiple myeloma is a plasma cell disorder that is characterised by clonal proliferation of malignant plasma cells in the bone marrow, monoclonal paraprotein in the blood or urine and associated organ dysfunction. It accounts for approximately 1% of cancers and 13% of haematological cancers. Myeloma arises from an asymptomatic proliferation of monoclonal plasma cells termed monoclonal gammopathy of undetermined significance (MGUS).Methods:MicroRNA expression profiling of serum samples was performed on three patient groups as well as normal controls. Validation of the nine microRNAs detected as promising biomarkers was carried out using TaqMan quantitative reverse transcription PCR. MicroRNA levels in serum were normalised using standard curves to determine the numbers of microRNAs per μl of serum.Results:Three serum microRNAs, miR-720, miR-1308 and miR-1246, were found to have potential as diagnostic biomarkers in myeloma. Use of miR-720 and miR-1308 together provides a powerful diagnostic tool for distinguishing normal healthy controls, as well as patients with unrelated illnesses, from pre-cancerous myeloma and myeloma patients. In addition, the combination of miR-1246 and miR-1308 can distinguish MGUS from myeloma patients.Conclusion:We have developed a biomarker signature using microRNAs extracted from serum, which has potential as a diagnostic and prognostic tool for multiple myeloma.

Background and Purpose-Asymptomatic embolic signals (ES) detected using transcranial Doppler have been reported in patients with potential cerebral embolic sources. They may be useful in risk stratification and in assessing therapies. First, it is essential to show whether they predict stroke risk. Methods-A systematic review and meta-analysis was performed to determine the prognostic value of ES in different potential cerebral embolic sources. Studies were identified that used transcranial Doppler to detect ES and included prospective stroke/TIA follow-up. Numbers of ES-positive and ES-negative patients were extracted with stroke/TIA and stroke alone outcomes. Results-ES