You May Delay, but Time Will Not!

See related article, p 801.In this issue of Stroke , Marnane et al1 reports that 12/44 patients (27%) with 50% to 99% stenoses had recurrent, ipsilateral strokes within 28 days of symptom onset, with 17% occurring <48 hours, 33% <7 days, and 58% <14 days of the index event. A 27% stroke risk at 28 days contrasts markedly with the 21% risk of ipsilateral stroke at 5 years reported in a meta-analysis of medically treated patients with 50% to 99% stenoses in the European Carotid Surgery Trial (ECST), the North American Symptomatic Carotid Endarterectomy Trial (NASCET), and the Veteran’s Affairs (VA) Study.2In the study of Marnane et al,1 recurrent stroke was associated with histological features of plaque instability. After multivariate analysis; the only independent predictor was heavy macrophage inflammation, and this is consistent with evidence that inflammation diminishes after symptom onset after plaque stabilization,3 and that heavy macrophage infiltration is associated with higher rates of spontaneous embolization.4 Marnane et al1 concluded that their findings might influence imaging technologies for identifying patients at highest risk of early, recurrent stroke and for monitoring the effectiveness of medical treatments.Studies like Marnane’s invariably attract differing interpretations. The realist will argue that although the results seem to support investment in technologies for imaging macrophage inflammation (eg, positron emission tomography-computed tomography), history suggests that small, hypothesis-generating studies frequently publish highly positive associations (exemplified by their high hazard ratios and wide confidence intervals), but then rarely complete the dual hurdles of external validation and translation into clinical practice. Therefore, realists will acknowledge the advance in …