Dongbeom Song

Association of cerebral microbleeds with mortality in stroke patients having atrial fibrillation

Objectives: We investigated the association of cerebral microbleeds (CMBs) with long-term mortality in patients with nonvalvular atrial fibrillation (NVAF) according to burden and distribution of CMBs. Methods: This was a retrospective, hospital-based, observational study. In total, 504 consecutive ischemic stroke patients with NVAF who underwent brain T2-weighted, gradient-recalled echo MRI were included. Data for the date and causes of death were based on the death certificates from the Korean National Statistical Office. We determined the association of the presence, burden, and distribution of CMBs with mortality from all-cause, ischemic heart disease, ischemic stroke, and hemorrhagic stroke. Results: CMBs were found in 30.7% of patients (155/504). During a median follow-up of 2.5 years, 176 patients (34.9%) died (ischemic stroke, 81; hemorrhagic stroke, 12; ischemic heart disease, 32). Patients with CMBs died more frequently than those without (41.9% vs 31.8%, p = 0.028). After adjusting for age, sex, and other significant variables, the presence of multiple (≥5) CMBs was as an independent predictor for all-cause (hazard ratio [HR]: 1.99) and ischemic stroke (HR: 3.39) mortality. Patients with strictly lobar CMBs had an increased risk of hemorrhagic stroke mortality (HR: 5.91). Conclusions: The presence and burden of CMBs were associated with increased mortality in stroke patients with NVAF. Patients with lobar CMBs were at increased risk of death due to hemorrhagic stroke. The diagnosis of CMBs is of value in predicting long-term prognosis in stroke patients with NVAF.

Interarm blood pressure difference and mortality in patients with acute ischemic stroke

Objective: The objective of this study was to assess the prognostic value of interarm difference of blood pressure (IAD) measured in acute ischemic stroke and to investigate its association with systemic atherosclerosis. Methods: This was a hospital-based retrospective observational study. Survival data and systolic/diastolic IAD were collected in patients with acute ischemic stroke. Systemic atherosclerosis was determined based on coronary CT angiography, transesophageal echocardiography, ankle-brachial index examination, and cerebral angiography covering both intracranial and extracranial cerebral arteries. Results: Of 834 patients, 10.3% had a systolic IAD ≥10 mm Hg, and 6.0% had a diastolic IAD ≥10 mm Hg. During a mean follow-up period of 2.96 ± 0.95 years, 92 patients died (including 68 cardiovascular deaths). In multivariate Cox regression adjusted for cardiovascular risk factors and initial stroke severity, the presence of systolic IAD ≥10 mm Hg was associated with increased risk of all-cause mortality (hazard ratio [HR] 1.97, 95% confidence interval [CI] 1.16–3.35) and cardiovascular mortality (HR 2.49, 95% CI 1.39–4.46). Patients with diastolic IAD ≥10 mm Hg also had increased risk of all-cause mortality (HR 3.43, 95% CI 1.94–6.08) and cardiovascular mortality (HR 3.51, 95% CI 1.83–6.74). The presence of systolic or diastolic IAD ≥10 mm Hg was associated with peripheral artery disease in the lower limbs, but not with atherosclerosis in the cerebral artery, coronary artery, or the aorta. Conclusions: The presence of interarm systolic or diastolic blood pressure difference ≥10 mm Hg is a strong independent prognostic marker in acute ischemic stroke.

Brachial-Ankle Pulse Wave Velocity Is a Strong Predictor for Mortality in Patients With Acute Stroke

Brachial-ankle pulse wave velocity (baPWV) has been proposed as a simple, noninvasive method for estimating arterial stiffness. Although high baPWV was predictive of cardiovascular mortality and morbidity among general population, its predictive value for mortality in patients with acute stroke is unknown. We evaluated the prognostic value of baPWV in 1765 patients who had been admitted for acute ischemic stroke and had completed measurement of baPWV during admission. Primary outcomes were all-cause mortality and vascular mortality (death because of heart diseases, cerebrovascular diseases, or diseases of arteries, arterioles, and capillaries, determined according to the International Classification of Diseases) after stroke. During a mean follow-up period of 3.33±1.57 years, there were 228 all-cause deaths, including 143 vascular deaths. In multivariate Cox hazard regression, patients in the highest tertile of baPWV (>22.63 m/s) were at an increased risk for both all-cause death (adjusted hazard ratio, 1.97; 95% confidence interval, 1.25–3.08) and vascular death (adjusted hazard ratio, 2.39; 95% confidence interval, 1.33–4.29) compared with the lowest tertile (<17.79 m/s). This study suggested that measurement of baPWV during the acute phase of stroke might be useful in identifying patients at a higher risk for mortality.

Time-Dependent Thrombus Resolution After Tissue-Type Plasminogen Activator in Patients With Stroke and Mice

Background and Purpose— We investigated the relationship between the degree of thrombus resolution and the time from stroke onset or thrombus formation to intravenous tissue-type plasminogen activator (tPA) treatment. Methods— In patients with stroke, we measured thrombus volume on thin-section noncontrast brain computed tomographic scans taken at baseline and 1 hour after tPA administration. We determined the association between the time from symptom onset to tPA treatment and the degree of thrombus resolution. In a C57/BL6 mouse model of FeCl3-induced carotid artery thrombosis, we investigated the effect of tPA administered at different time intervals after thrombus formation, using Doppler-based blood flow measurement. Results— Of 249 patients enrolled, 171 showed thrombus on baseline computed tomography. Thrombus was resolved by ≥50% in 43 patients (25.1%, good volume reduction) and by <50% in 94 patients (55.0%, moderate volume reduction) 1 hour after tPA treatment. In 34 patients (19.9%, nonvolume reduction; either no change or thrombus volume increased), overall thrombus volume increased. The probability of thrombus resolution decreased as the time interval from symptom onset to treatment increased. On multivariate analysis, good volume reduction was independently related with shorter time intervals from symptom onset to tPA treatment (odds ratio, 0.986 per minute saved; 95% confidence interval, 0.974–0.999). In the mouse model, as the interval between thrombus formation and tPA treatment increased, the initiation of recanalization was delayed (P=0.006) and the frequency of final recanalization decreased (P for trends=0.006). Conclusions— Early administration of tPA after stroke onset is associated with better thrombus resolution.

Brachial-Ankle Pulse Wave Velocity for Predicting Functional Outcome in Acute Stroke

Background and Purpose— We investigated whether the brachial-ankle pulse wave velocity (baPWV) has prognostic value for predicting functional outcome after acute cerebral infarction and whether the prognostic value differs between stroke subtypes. Methods— We included 1091 consecutive patients with first-ever acute cerebral infarction who underwent baPWV measurements. Stroke subtypes were classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Poor functional outcomes were defined as modified Rankin Scale score >2 at 3 months after stroke onset. Results— We noted that 181 (16.59%) patients had a poor functional outcome. In multivariate logistic regression, patients in the highest tertile of baPWV (>22.25 m/s) were found to be at increased risk for poor functional outcome (adjusted odds ratio, 1.88; 95% confidence interval, 1.06–3.40) compared with those in the lowest tertile (<17.55 m/s). No significant interaction between baPWV and stroke subtype was noted. Receiver operating characteristic curve analysis indicated that the addition of baPWV to the prediction model significantly improved the discrimination ability for poor functional outcome. Conclusions— baPWV has an independent prognostic value for predicting functional outcome after acute cerebral infarction. The prognostic value did not differ according to the stroke subtype.

Repeated thrombolytic therapy in patients with recurrent acute ischemic stroke.

Background and Purpose Widespread use of thrombolytic treatments, along with improved chances of survival after an initial ischemic stroke, increases the possibility of repeated thrombolysis. There are few reports, however, regarding repeated thrombolysis in patients who have suffered acute ischemic stroke. We explored the number and outcome of patients with repeated thrombolytic therapy in the era of multimodal thrombolytic treatments. Methods We investigated patients with acute ischemic stroke who had received thrombolytic treatments for a period of 10 years. Number of thrombolysis was determined in each patient. Recanalization was defined as Thrombolysis in Cerebral Infarction grading ≥2a. Symptomatic hemorrhagic transformation was defined as any increase in the National Institutes of Health Stroke Scale score that could be attributed to intracerebral hemorrhage. A good outcome was defined as a modified Rankin scale score ≤2. Results Of the 437 patients who received thrombolytic treatments, only 7 underwent repeated thrombolysis (1.6%). The median age at the time of repeated thrombolytic therapy was 71 years old; 4 of the patients were female. All patients had 1 or more potential sources of cardiac embolism. Recanalization was achieved in all patients, in both the first and the second thrombolysis. No symptomatic intracranial hemorrhage occurred after repeated thrombolytic treatments. Five patients (71.4%) showed good outcomes at 3 months. Conclusions Repeated thrombolysis for recurrent acute ischemic stroke appears to be safe and feasible. Among patients who experience recurrent acute ischemic stroke, thrombolytic therapy could be considered even if the patient has had previous thrombolytic treatments.

Importance of truncal-type occlusion in stentriever-based thrombectomy for acute stroke

Objective: To investigate whether angiographically defined occlusion type could predict of the etiology of acute intracranial large artery occlusion and the stentriever response. Methods: We reviewed consecutive patients with acute intracranial large artery occlusion who underwent endovascular treatment and examined their workups for embolic sources. Patient demographics, laboratory findings, hyperdense artery sign, and angiographic occlusion type (truncal-type or branching-site occlusion) were compared between embolic sources (+) and (−) groups. These variables were also compared between stentriever failure and success groups. Details of endovascular procedures were also compared according to occlusion type. Results: A total of 259 patients (mean age 70.3 years; M:F = 132:127) were finally included. Of these patients, 216 (83.4%) were assigned to the embolic sources (+) group after thorough evaluation. Young age, no coronary artery disease, and truncal-type occlusion (odds ratio [OR] 9.07; 95% confidence interval [CI] 3.74–22.0) were independently associated with the embolic source (−) group. Of the overall group, 224 patients (86.5%) underwent stentriever-based endovascular treatment. Hypertension, diabetes, high C-reactive protein level, and truncal-type occlusion (OR 32.2; 95% CI 7.78–133.0) were independent predictors of stentriever failure. Truncal-type occlusion was associated with more reocclusion (77.3% vs 5.0%), resulting in recanalization failure by the stentriever (81.8% vs 20.3%), a longer puncture-to-recanalization time (118.0 vs 49.5 minutes), and more rescue treatment for final successful recanalization (78.9% vs 7.0%). Conclusions: Angiographic occlusion type is an independent predictor of stentriever refractoriness and of the underlying stroke mechanism.

Serum Alkaline Phosphatase and Phosphate in Cerebral Atherosclerosis and Functional Outcomes After Cerebral Infarction

Background and Purpose— Higher serum alkaline phosphatase (ALP) and phosphate levels are associated with atherosclerotic disease and an increased risk of cardiovascular events. However, the association of ALP/phosphate with cerebral atherosclerosis and prognosis in patients with acute stroke is not well known. Methods— In 1034 patients with first-ever acute cerebral infarction, levels of ALP and phosphate were compared with (1) cerebral atherosclerosis and (2) poor long-term functional outcomes as defined by the modified Rankin Scale >2 at 3 months after stroke onset. Results— ALP levels were not associated with cerebral atherosclerosis. However, higher levels of ALP were associated with a poor functional outcome (adjusted odds ratio per 1 SD, 1.25; 95% confidence interval, 1.04–1.50). Phosphate was associated with neither cerebral atherosclerosis nor functional outcome. Conclusions— A higher level of ALP was not associated with cerebral atherosclerosis but was an independent prognostic factor for long-term functional outcome after acute cerebral infarction.

Effect and Safety of Rosuvastatin in Acute Ischemic Stroke

Background and Purpose The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. Methods This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naïve stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. Results This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53–1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2±1.0 mm3 vs. placebo: 0.3±1.3 mm3; P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. Conclusions The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation.

Total Cerebral Small-Vessel Disease Score is Associated with Mortality during Follow-Up after Acute Ischemic Stroke

Background and Purpose The recently developed total cerebral small-vessel disease (CSVD) score might appropriately reflect the total burden or severity of CSVD. We investigated whether the total CSVD score is associated with long-term outcomes during follow-up in patients with acute ischemic stroke. Methods In total, 1,096 consecutive patients with acute ischemic stroke who underwent brain magnetic resonance imaging were enrolled. We calculated the total CSVD score for each patient after determining the burden of cerebral microbleeds (CMBs), high-grade white-matter hyperintensities (HWHs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs). We recorded the date and cause of death for all of the patients using data from the Korean National Statistical Office. We compared the long-term mortality rate with the total CSVD score using Cox proportional-hazards models. Results CMBs were found in 26.8% of the subjects (294/1,096), HWHs in 16.4% (180/1,096), HPVSs in 19.3% (211/1,096), and ALIs in 38.0% (416/1,096). After adjusting for age, sex, and variables that were significant at p<0.1 in the univariate analysis, the total CSVD score was independently associated with long-term death from all causes [hazard ratio (HR)=1.18 per point, 95% confidence interval (CI)=1.07–1.30], ischemic stroke (HR=1.20 per point, 95% CI=1.01–1.42), and hemorrhagic stroke (HR=2.05 per point, 95% CI=1.30–3.22), but not with fatal cardiovascular events (HR=1.17 per point, 95% CI=0.82–1.67). Conclusions The total CSVD score is a potential imaging biomarker for predicting mortality during follow-up in patients with acute ischemic stroke.