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Objective: To systematically review temporal changes in perioperative safety of carotid endarterectomy (CEA) in asymptomatic individuals in trial and registry studies. Methods:The MEDLINE and EMBASE databases were searched using the terms "carotid" and "endarterectomy" and "asymptomatic" from 1947 to August 23, 2014. Articles dealing with 50%-99% stenosis in asymptomatic individuals were included and low-volume studies were excluded. The primary endpoint was 30-day stroke or death and the secondary endpoint was 30-day all-cause mortality. Statistical analysis was performed using random-effects metaregression for registry data and for trial data graphical interpretation alone was used.Results: Six trials (n 5 4,431 procedures) and 47 community registries (n 5 204,622 procedures) reported data between 1983 and 2013. Registry data showed a significant decrease in postoperative stroke or death incidence over the period 1991-2010, equivalent to a 6% average proportional annual reduction (95% credible interval [CrI] 4%-7%; p , 0.001). Considering postoperative all-cause mortality, registry data showed a significant 5% average proportional annual reduction (95% CrI 3%-9%; p , 0.001). Trial data showed a similar visual trend.Conclusions: CEA is safer than ever before and high-volume registry results closely mirror the results of trials. New benchmarks for CEA are a stroke or death risk of 1.2% and a mortality risk of 0.4%. This information will prove useful for quality improvement programs, for health care funders, and for those re-examining the long-term benefits of asymptomatic revascularization in future trials. Carotid endarterectomy (CEA) in asymptomatic individuals was introduced in the 1970s for long-term prevention of ipsilateral stroke 1 and now comprises the bulk of those undergoing endarterectomy in the United States.2 However, the 10-year absolute risk reduction in stroke or death risk in the largest and most recent trial, the Asymptomatic Carotid Surgery Trial 1 (ACST-1), was only 4.6%, demonstrating small absolute benefit of CEA. 3,4On modern medical therapy, ipsilateral ischemic stroke rates have fallen, 5 with 3 recent cohort studies demonstrating annual ipsilateral ischemic stroke risks in patients with 50%-99% asymptomatic stenosis of 0.3%-0.8%, 6-8 less than the 0.96% risk in ACST. 4 If CEA is to prove effective in the future, one of the prerequisites is that perioperative outcomes must become safer not only in trials, but in wider clinical practice.The aim of this systematic review was to examine temporal trends in perioperative safety of CEA in asymptomatic individuals with 50%-99% internal carotid artery stenosis. When compared with symptomatic patients, 9 the benefits of asymptomatic revascularization are less pronounced, and without marked improvements in operative safety, asymptomatic revascularization faces becoming a historical footnote. This analysis will provide valuable information for From the Academic Section of Vascular Surgery (A.B.M., M.I.Q., A.T.,

The application of metabonomic science to interrogate stroke permits the study of metabolite entities, small enough to cross the blood-brain barrier, that provide insight into neuronal dysfunction, and may serve as reservoirs of biomarker discovery. This systematic review examines the applicability of metabolic profiling in ischemic stroke research. Six human studies utilizing metabolic profiling to analyze biofluids from ischemic stroke patients have been included, employing H-NMR and/or mass spectrometry to analyze plasma, serum, and/or urine in a targeted or untargeted fashion. Three are diagnostic studies, and one investigates prognostic biomarkers of stroke recurrence following transient ischemic attack. Two studies focus on metabolic distinguishers of depression or cognitive impairment following stroke. Identified biomarkers from blood and urine predominantly relate to homocysteine and folate, branched chain amino acid, and lipid metabolism. Statistical models are well fitted and reproducible, with excellent validation outcomes, demonstrating the feasibility of metabolic profiling to study a complex disorder with multicausal pathology, such as stroke.