Japan Standard Stroke Registry Study Research Articles

Greater Severity of Neurological Defects in Women Admitted With Atrial Fibrillation-Related Stroke

The magnitude of the CHA2DS2-VASc score is associated with not only stroke incidence but also long-term outcomes. The association between sex and initial stroke severity in AF-related cardioembolic stroke patients has not been clarified. The present study aimed to elucidate the risk factors for initial stroke severity among patients with cardioembolic stroke enrolled in a multicenter registry. We selected 12,701 patients (age, 77±10 years; 5,653 women) with AF-related cardioembolic stroke from the Japan Standard Stroke Registry Study between January 2000 and July 2013. Indicators of National Institutes of Health Stroke Scale (NIHSS) scores at admission were identified using a multiple linear regression. Increased NIHSS scores positively correlated with CHA2DS2-VASc score (ρ=0.197; P<0.001). The initial neurological deficits were more severe in women than in men (NIHSS scores, median [interquartile range] 14 [5-22] vs. 8 [3-18]; P<0.001). Multiple regression analysis revealed that higher age (standardized partial regression coefficient [β] 0.162; P<0.001), female sex (β 0.120; P<0.001), diabetes mellitus (β 0.020; P=0.019), dyslipidemia (β -0.076; P<0.001), congestive heart failure (β 0.039; P<0.001), vascular disease (β 0.030; P=0.001), prior stroke/TIA (β 0.085; P<0.001) and prior anticoagulant use (β -0.020; P=0.028) were associated with the NIHSS score at admission. Female sex was independently associated with the initial neurological severity among AF-related cardioembolic stroke patients.

Cardioembolic Stroke Is the Most Serious Problem in the Aging Society: Japan Standard Stroke Registry Study

Japan has the fastest aging society in the world. Older patients have a different stroke risk profile and different stroke features compared with younger patients. The aim of the present study was to examine the stroke subtypes, risk factor profiles, stroke severities, and functional outcomes in the different age groups. A total of 78,096 patients with acute ischemic stroke, including transient ischemic attacks, were included in a multicenter, hospital-based registration study based on a computerized database involving 95 Japanese institutes between 2000 and2012. The frequency of atrial fibrillation increased even after the age of 90years; consequently, the proportion of patients experiencing cardioembolic stroke also increased in the same age group. Furthermore, more severe symptoms on arrival and worse functional outcomes were observed with increasing age. The frequency of hypertension increased with age, peaking in patients in their 70s, and decreasing slightly thereafter. The frequency of diabetes mellitus and hyperlipidemia peaked in patients in their 50s or 60s and gradually decreased thereafter. The findings of the present study suggest that in the currently aging society, cardioembolic stroke is the most important stroke subtype. The roles of hypertension, diabetes mellitus, and hyperlipidemia are greatest in stroke patients in their 50s to 60s. In older patients, the role of atrial fibrillation is more significant.

Abstract T P163: Inpatient Stroke Mortality Has Been Declining in Japan: Japanese Stroke Databank

Background and Purpose: Although thrombolytic therapy, novel oral anticoagulants and neuroendovascular therapy became available in this decade, the stroke victims are facing the increasing risk of death including the comorbidity such as pneumonia due to rapid aging in Japan. As a part of the Japan Standard Stroke Registry Study (JSSRS) which is a multi-center registration study of acute stroke cases in Japan, we analyzed the trends in the inpatient stroke mortality in relation to the demographic data and stroke subtypes. Subjects and Methods: The present study was based on 101,160 acute stroke cases including 59,493 men (58.8%) and 41,667 women (41.2%) who were registered to the JSSRS databank between 1999 and 2012. Among them, 72,774 cases (71.9%) were diagnosed as having cerebral infarction (CI), 17,723 cases (17.5%) as intracerebral hemorrhage (ICH), 5,343 (5.3%) as subarachnoid hemorrhage (SAH), and 5,320 cases (5.3%) as transient ischemic attack (TIA). Results: There were 7,651 deceased cases and the overall mortality rate (MR) was 7.6%. The MR was greater in women (9.2%) than in men (6.4%), and greater in those who were 75 years or older (10.2%) than in younger age categories. The MR was greater for SAH (23.5%) and ICH (15.1%) than for CI (5.1%), and greater for cardiogenic embolism (11.7%) than for atherothrombotic infarction (3.8%) and lacunar infarction (0.6%). Among the deceased cases, 53.7% died in the acute stage whereas 26.0% died in the subacute stage and 20.3% died in the chronic stage. 23% of the in-hospital death was due to SAH in women, whereas that was only 9% in men. The overall MR was 9.2 % and the MR was 6.8% for CI and 15.6% for ICH in 2000, whereas the overall MR was 6.3% and the MR was 3.9% for CI and 13.3% for ICH in 2012. The MR for SAH was 21.4% in 2000 and 21.8% in 2012. Conclusions: The greater stroke MR in women was considered to be due to the greater MR for SAH. Our data revealed the stroke MR decreased significantly in last 12 years. This decline can be partly explained by the improved outcome in cerebral infarction in the acute phase.

本邦の脳動脈瘤治療の現状─当院，脳卒中データバンク，（社）日本脳神経外科学会調査より─

本邦の脳動脈瘤治療の現状─当院，脳卒中データバンク，（社）日本脳神経外科学会調査より─

Subsequent Vascular Events after Ischemic Stroke: The Japan Statin Treatment against Recurrent Stroke—Longitudinal

We undertook a multicenter cohort observational study to investigate the frequency and type of subsequent vascular events after an ischemic stroke and to compare the rates of vascular events between patients with and without hyperlipidemia. This nationwide study was conducted in 19 hospitals participating in the Japan Standard Stroke Registry Study. We enrolled ischemic stroke patients, including those with a transient ischemic attack, who had not experienced any vascular events before enrollment after their ischemic stroke events. Each subject was observed prospectively from September 1, 2003, to October 1, 2005, or until a primary end point or death. Primary end points included subsequent fatal or nonfatal vascular events: stroke, angina pectoris, acute myocardial infarction, aortic aneurysm, or arteriosclerosis obliterans. A total of 449 patients (mean age, 67.6 years; 64.8% men) were enrolled in this study. Of the 41 vascular events observed during follow-up, 40 were stroke. The median observation period was 568 days. We found that patients with hyperlipidemia had a significantly higher rate of vascular events compared with those without hyperlipidemia according to the Kaplan-Meier method and the log-rank test (P = .013). Hyperlipidemia significantly increased the risk of vascular events (hazard ratio, 2.169 [1.125-4.312]; P = .021) according to the Cox proportional hazard model after adjusting for confounding factors (age, sex, days from ischemic stroke until enrollment, smoking habits, and daily drinking habits). This study demonstrated that stroke was the most common subsequent vascular event after ischemic stroke; the study also indicated that hyperlipidemia could be a risk factor for subsequent vascular events after ischemic stroke.

Epidemiology and Registry Studies of Stroke in Japan

Stroke is the most prevalent cardiovascular disease in Japan. This review introduces two epidemiologic studies and four registry studies of stroke in Japan. The Hisayama Study was begun as a population-based prospective cohort study of cerebrovascular and cardiovascular diseases in 1961 in the town of Hisayama. Most of the deceased subjects of the study underwent autopsy examinations from the beginning of the study. Changes in stroke trends in the last 50 years were clarified by comparison of data from different study cohorts registered every 13 to 14 years. The Suita Study was based on a random sampling of Japanese urban residents. Several reports from this study showed the significance of pre-hypertension, as well as hypertension, as a risk factor for stroke by itself and in combination with other underlying characteristics. In addition, the Japan Multicenter Stroke Investigators' Collaboration (J-MUSIC), the Japan Standard Stroke Registry Study, the Fukuoka Stroke Registry, and the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rt-PA Registry are explained as registry studies involving Japanese stroke patients.

Effects of Sex Difference on Clinical Features of Acute Ischemic Stroke in Japan

Sex differences in stroke characteristics and outcomes have been inconsistent. The goal of this study was to determine the influence of sex on underlying patient characteristics, stroke subtypes and conditions, and outcomes after ischemic stroke from a nationwide registration study. A total of 33,953 patients with acute ischemic stroke, including 13,323 women, were registered in a multicenter, hospital-based registration study based on a computerized database from 162 Japanese institutes (the Japan Standard Stroke Registry Study) between January 2000 and November 2007. Women were significantly older than men at stroke onset (75.0 ± 11.7 v 69.3 ± 11.4 years; P < .0001). After age adjustment, women more frequently had cardioembolic events (odds ratio [OR] 1.090; 95% confidence interval [95% CI] 1.036-1.146; P = .0009) and other strokes (OR 1.177; 95% CI 1.079-1.284; P = .0003) and were more hypertensive (OR 1.056; 95% CI 1.006-1.108; P = .0267) and more dyslipidemic (OR 1.301; 95% CI 1.234-1.373; P < .0001) than men. After multivariate adjustment, onset-to-arrival time was longer (β = 0.0554; P = .026), the initial National Institutes of Health Stroke Scale score was higher (β = 0.1565; P < .001), and the duration of hospitalization was longer (β = 0.035; P = .010) in women than in men. At hospital discharge, women less commonly had a modified Rankin Scale (mRS) score of 0 to 1 (OR 0.802; 95% CI 0.741-0.868; P < .0001) and more commonly had a mRS score of 4 to 6 (OR 1.410; 95% CI 1.293-1.537; P < .0001) than men. Women developed more severe strokes than men in Japan. After multivariate adjustment for initial severity and other characteristics, acute care hospital stays were longer and stroke outcomes at discharge were worse in women than in men.

Predictors of Intracerebral Hemorrhage Severity and Its Outcome in Japanese Stroke Patients

Objective: The aim of this investigation was to determine the factors influencing acute intracerebral hemorrhage severity on admission and clinical outcomes at discharge. Methods: Sixty acute stroke hospitals throughout Japan participated in the Japan Standard Stroke Registry Study (JSSRS), documenting the in-hospital course of 16,630 consecutive patients with acute stroke from January 2001 to March 2004. We identified 2,840 adult patients from the JSSRS who had intracerebral hemorrhage. Results: Intracerebral hemorrhage severity on admission was strongly related to age, previous stroke history, and hemorrhage size in a monotone fashion [χ²(9) = 374.5, p < 0.0001]. Drinking history was also predictive of intracerebral hemorrhage severity on admission, but the association was not monotone. Interestingly, intracerebral hemorrhage severity on admission was increased in nondrinking and heavy drinking compared to mild drinking (p < 0.05). Unsuccessful outcome (modified Rankin scale score = 3–6) was related to age, previous stroke history, hemorrhage size, and intracerebral hemorrhage severity on admission [χ²(9) = 830.4, p < 0.0001]. Mortality was related to hemorrhage size, intraventricular hemorrhage, intracerebral hemorrhage severity on admission, and surgical operation [χ²(7) = 540.4, p < 0.0001]. Conclusion: We could find four varied factors associated with intracerebral hemorrhage severity and its outcomes. Interestingly, intracerebral hemorrhage severity tended to be greater in nondrinking and heavy drinking than mild drinking. Additionally, surgical operation decreased intracerebral hemorrhage mortality.

Early Recurrence of Ischemic Stroke in Japanese Patients: The Japan Standard Stroke Registry Study

Background: To determine the factors that contribute to early ischemic stroke recurrence in Japanese patients. Methods: A multicenter stroke registration study based on a computerized database from 54 Japanese institutes, involving 8,036 patients with brain infarction who were hospitalized within 48 h after symptom onset between January 2000 and March 2004. Results: Within 30 days after the initial stroke, 395 patients (4.9%) developed a recurrent stroke. Recurrence most frequently occurred in atherothrombotic patients (6.6%), followed by cardioembolic patients (6.2%). Overall, hypertension (OR 1.348, 95% CI 1.071–1.696) and atrial fibrillation (OR 1.503, 95% CI 1.177–1.918), but not diabetes mellitus, were independently predictive of early recurrence. In atherothrombotic patients, diabetes mellitus (OR 1.485, 95% CI 1.058–2.085) and atrial fibrillation (OR 1.998, 95% CI 1.231–3.244) were independently related to early recurrence. At hospital discharge, the modified Rankin Scale score was higher in patients who had an early recurrence (p < 0.0001). Conclusions: This study was based on a large number of Japanese patients and confirmed that hypertension and atrial fibrillation contribute to early ischemic stroke recurrence. In addition, analysis by stroke subtype showed that diabetes mellitus was independently related to early recurrence in atherothrombotic patients.

Efficacy of anti-coagulant treatment with argatroban on cardioembolic stroke

Argatroban, which is a thrombin inhibitor, has an indication as a treatment in the acute phase on atherosclerotic ischemic stroke in Japan. Howeve, in cardioembolic stroke, argatroban is considered to be contraindicated with the side effect of hemorrhage, though there is no clear clinical evidence to show that argatroban increases hemorrhagic compared with heparin. The efficacy of anticoagulant treatment with argatroban on cardioembolic stroke was evaluated retrospectively in this study. We identified 3,113 patients from the Japan Standard Stroke Registry Study who had had a cardioembolic ischemic stroke. We excluded patients with the anti-platelet treatment or the combination therapy of anticoagulation. Our analyses are therefore based on a cohort of 2,529 patients who were treated either with heparin, and argatroban, or with no anti-coagulation treatment. With multivariable regression, hemorrhagic it was shown that hemorrhage was significantly reduced in heparin and argatroban treatments in the patients with mild severity. There was no significant difference in the recurrence of ischemic stroke between the treatments. Both argatroban and heparin showed dramatic improvement compared with the no treatment standard, but only heparin achieved statistical significance for mortality and change in NIHSS score (admission to discharge) in the moderate stroke subgroup [NIHSS 11-22]. Both heparin and argatroban [more so than heparin alone] have a significantly reduced mortality risk. From the present study, it is suggested that argatroban may be useful on cardioembolic stroke, increasing the improvement of recovery of stroke severity without increasing the risk of hemorrhage. Further prospective studies are awaited for evaluating better the efficacy of argatroban on cardioembolic stroke.

Surgery for spontaneous intracerebral hemorrhage has greater remedial value than conservative therapy

Background The aim of this study was to compare the efficacy of surgery for spontaneous intracerebral hemorrhage with that of medical treatment, based on data from the Japan Stroke Registry Study. Methods From 1999 to 2001, 1010 patients with spontaneous intracerebral hemorrhage were registered in the Japan Standard Stroke Registry Study from 45 stroke center hospitals in Japan. The National Institutes of Health Stroke Scale (NIHSS), Japan Stroke Scale (JSS), and modified Rankin Scale scores were used to compare severity and improvement in patients given surgical and medical treatment. Conclusions Surgically treated patients, especially those with cerebellar hemorrhage, had significantly greater improvement in NIHSS or JSS score compared with medically treated patients. Our findings indicated that the patients who underwent surgery appeared to have better outcomes. But, because the study was not randomized, this observation cannot be interpreted as indicating that surgery is advantageous.

Clinical Characteristics of First-Ever Atherothrombotic Infarction or Lacunar Infarction with Hyperlipidemia (J-STARS-C): An Analysis of Data from the Stroke Data Bank of Japan

The clinical trial, Japan Statin Treatment Against Recurrent Stroke (J-STARS), is being carried out to investigate the efficacy of statin treatment against recurrent stroke. To participate in J-STARS, patients must have a past history of ischemic stroke excluding cardioembolic events, and must be clinically diagnosed with hyperlipidemia (HL). Before starting J-STARS, we needed to be aware of the clinical characteristics of the patients who were eligible to participate in this study. Between 1999 and 2002, 7,149 patients with ischemic stroke were enrolled in a stroke data bank developed by the Japan Standard Stroke Registry Study Group. From this, we acquired the data on 1,487 patients with first-ever atherothrombotic infarction (ATI) or lacunar infarction (LI) with a satisfactory functional outcome on discharge. Patients with HL were significantly younger (65.3+/-11.0 vs 68.4+/-10.9, p<0.0001) and showed a higher frequency of concomitant hypertension (70.9% vs 61.0%, p=0.0002), diabetes mellitus (42.2% vs 25.7%, p<0.0001) or both (31.7% vs 16.4%, p<0.0001) compared to those without HL. The ratio of ATI to LI and the frequency of prior ischemic heart disease (IHD) did not differ between the 2 groups. Among 467 patients with HL, 52.7% did not receive treatment on admission. ATI or LI patients with HL had an earlier age of onset and higher frequency of other lifestyle-related diseases, and this probably includes many with metabolic syndrome, whereas the frequency of IHD was not different between these 2 groups.

スタチンによる脳梗塞再発予防研究―Ｊ‐ＳＴＡＲＳ―

The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Study is a prospective, randomised, open, blinded endpoint study designed to evaluate the effects of pravastatin 10 mg/day in patients who preveously experienced an ischemic stroke other than cardioembolic infarction, but who do not have any CHD requiring statin treatment. We planed to enroll a total of 3, 000 patients. aged 45-80 years who have serum cholesterol level of 180-240 mg/dl. The primary endpoint is fatal and non-fatal stroke recurrence during the follow-up period of 5 year and the data collection phase of the study is expected to be completed by April 2010. Effects of statin on hs-CRP and carotid intima-media thickness will also be investigated as substudies of J-STARS. Further, we planned a longitudinal follow-up study called J-STARS-L (J-STARS-Longitudinal), where we aquired a follow-up data from the stroke data bank developed by the Japan Standard Stroke Registry Study (JSSRS) Group, and attempted to confirm the proposed cardiovascular event rate in the ischemic stroke patients who should be enrolled in J-STARS. The present status of J-STARS-L and J-STARS have been presented in this symposium.

全国脳卒中データバンク構築に向けて

There is only a few evidence for stroke management has been reported from Japan. It is necessary to make a data bank of acute stroke patients as infrastructure to make evidence for standardization of stroke management. We made Japan standard stroke registry study (JSSRS) supported by ministry of health and welfare from 1999 to 2002. We completed computerized registry system and accumulated about 8, 000 acute stroke cases from 45 stroke center hospitals. This system is also functioning as a stroke database for each hospital. From the analysis of the distribution of stroke subtype, the incidence of atherothrombotic infarction and cardiogenic embolism was similar to lacunar infarction as shown in Figure 1. Furthermore, the 38% of ischemic stroke patients admitted within 3 hours. Thrombolytic therapy was performed in 15% of the patients who admitted within 3 hours and their initial severity were NIHSS 6-29. The outcome of the patients treated with thrombolytic therapy was significantly better than those without it. These data indicate that the stroke data bank should be useful tool to make verification of the guideline and planning a clinical trial for EBM in near future.