Tooth Loss as a Predictor of Long-Term Care Requirements in the Elderly: A Study in Kobe City, Japan.

INTRODUCTION: The Kobe project, which utilizes prospective data from the national health insurance system, focuses on early detection and preventive strategies through the Frail Kenshin health check-up program. Previous research has underscored the correlation between tooth loss and the decline in physical and cognitive functions. In this study, using Kobe project data, we examined the link between remaining teeth and long-term care needs in individuals aged 64-65 years, with primary and secondary objectives involving various health parameters and quality of life. METHODS: We analyzed baseline data from a prospective study conducted alongside the Frail Check program for generally healthy individuals aged 64-65 years to examine the relationship between the number of remaining teeth and various health indicators. This study focused on citizens aged 64-65 years to identify those at risk of needing long-term care by the age of 65 years. RESULTS: Data from 1,530 participants were obtained, excluding eight individuals for specific reasons. At the end of the follow-up period, 41 (2.7%) individuals required support and 15 (1.0%) needed long-term care alone. The data revealed a significant association between the number of remaining teeth and the need for long-term care or support, as demonstrated by the Cochran-Armitage trend test (p<0.001). Although trends were noted for nutrition and total Cognitive Functional Instrument Self scores, they did not reach statistical significance. Additionally, a decrease in the number of remaining teeth was significantly associated with worse European Quality of Life Five Dimensions (EQ-5D-5L) visual analog scale scores, mobility, and regular activities (p<0.001). CONCLUSION: Tooth loss indicates the potential long-term care needs of older adults. Monitoring oral health is crucial for addressing care requirements.

Implication of using cognitive function-related simple questions to stratify the risk of long-term care need: population-based prospective study in Kobe, Japan.

BACKGROUND: This study investigated how cognitive function-related simple questions can be used to identify older individuals who are at risk of needing long-term care. METHODS: This cohort study was conducted in Kobe city, Japan. In 2015, the municipal office distributed the Kihon Checklist by post, a 25-item questionnaire including three cognitive function-related questions (questions 18, 19, 20) to citizens aged ≥ 70 years. Need certification is routinely done by Kobe city as part of the national Long-Term Care Insurance Act. The answers to the 2015 questionnaire were merged with need certification data between the questionnaire delivery and the end of December 2019. RESULTS: Of the 77,877 citizens (age: 72.9 ± 2.7 years) who received the questionnaire, 50,154 responded (response rate: 64.4%). During the study period, the cumulative incidence of the need for long-term care was higher in those who did not respond than in those who did (12.5% vs 8.4%; P < 0.001). Among those who responded, the incidence of the need for long-term care was progressively greater as the number of negative answers to cognitive function-related questions increased (5.0%, 8.4%, 15.7% and 30.2% at 4 years' follow-up, for respondents with, respectively, 0, 1, 2 and 3 negative answers). Similarly, when the need certification for long-term care was confined to that accompanied by dementia, the incidence also rose as the number of negative responses to the cognitive function-related questions increased (3.4%, 6.5%, 13.7% and 27.9% for respondents with, respectively, 0, 1, 2 and 3 negative answers). Using multivariate Cox regression analysis, all three cognitive function-related questions were predictive of the need for long-term care, and question 18 (about memory loss) had the highest hazard ratio for predicting the need for long-term care accompanied by dementia. CONCLUSIONS: Use of cognitive function-related simple questions may help identify older adults at risk for needing long-term care, suggesting their potential value for use in administrative and policy approaches aimed at reducing the societal burden of dementia.

The effect of a multimodal dementia prevention program involving community-dwelling elderly.

BACKGROUND: With the rapid increase in the average age of society, the number of people with dementia has increased in Japan. Thus, the need to prevent dementia is greater, and prevention programs have been implemented throughout Japan. This study aims to evaluate both the short-term and the long-term effects of a dementia prevention program on physical and cognitive function in community-dwelling elderly. METHODS: Cognitive and physical assessments were carried out at baseline for a sample including 57 elderly participants. The participants underwent an intensive training program lasting for 2 h per week for 10 days. After the last period of training, the assessment performed was reapplied. The outcome measures used to establish effectiveness were a Mini-Mental State Examination, Five Cognitive Tests, a Cognitive Function Instrument, a Timed Up & Go Test, a grip strength evaluation, a Geriatric Depression Scale, an EQ-5D and a Physical Activity Scale for the Elderly. Participants were then divided randomly into two groups: a booster group and a non-booster group. The booster group received booster training every 3 months after the intensive training period, whereas the non-booster group did not. Both groups were monitored every 6 months for approximately two and a half years after baseline assessment. RESULTS: The Mini-Mental State Examination, the subtests of the Five Cognitive Tests (attention, memory, language and reasoning) and the Timed Up & Go Test revealed a significant improvement after intensive training. For most of the outcome measures, the booster training showed no additional significant improvements. CONCLUSIONS: In this study, intensive training had a short-term positive effect. Although the effect of the booster training was not clear, the functions of the elderly participants were found to be maintained during a follow-up assessment. The study findings recommend conducting intensive training for the community-dwelling elderly without follow-up training.

Patient safety management systems and activities related to promoting voluntary in-hospital reporting and mandatory national-level reporting for patient safety issues: A cross-sectional study.

Both voluntary in-hospital reporting and mandatory national-level reporting systems for patient safety issues need to work well to develop a patient safety learning system that is effective in preventing the recurrence of adverse events. Some of the hospital systems and activities may increase voluntary in-hospital reporting and mandatory national-level reporting. This study aimed to identify the hospital systems and activities that increase voluntary in-hospital reporting and mandatory national-level reporting for patient safety issues. An anonymous mail survey of hospitals in Japan was conducted in 2017. The hospitals were selected by stratified random sampling according to number of beds. The survey examined the annual number of reported events in the voluntary in-hospital reporting system for patient safety and experience of reporting unexpected patient deaths possibly due to medical interventions to the mandatory national-level reporting system in the last 2 years. The relationship of the answer to the questions with the patient safety management systems and activities at each hospital was analyzed. The response rate was 18.8% (603/3,215). The number of in-hospital reports per bed was positively related to identifying events by referring complaints or questions of patients or family members, using root cause analysis for analyzing reported events, and developing manuals or case studies based on reported events, and negatively related to the unification and standardization of medical devices and equipment. The experience with mandatory national-level reporting of serious adverse events was positively related to identifying problematic cases by a person in charge of patient safety management from the in-hospital reporting system of complications and accidental symptoms. Enhanced feedback for reporters may promote voluntary in-hospital reporting of minor cases with low litigation risks. Developing an in-hospital mechanism that examines all serious complications and accidental symptoms may promote mandatory national-level reporting of serious adverse events with high litigation risks.

Kobe project for the exploration of newer strategies to reduce the social burden of dementia: a study protocol of cohort and intervention studies.

INTRODUCTION: This research project addresses the lack of screening tools for the early detection of high-risk individuals for long-term care, through four individual studies.Study 1 investigates the predictive ability of the 'Kihon Check List', study 2 the 'Cognitive Function instrument' and EuroQol-5 Dimension (EQ-5D) and study 3 the 'Cognitive Function instrument' and EQ-5D as well as the 'Frail Kenshin' health check-up, for incident long-term care certification over a follow-up period of up to 4 years. This is the first large prospective study to evaluate the predictive ability of these tools for the outcome measure long-term care certification. The last subsection of this project study four aims to explore a mixed methods intervention for delaying the need for long-term care. This section is purely exploratory, looking for clues for further studies. METHODS AND ANALYSIS: Baseline data have been collected through local government programs, as well as through postal self-reported questionnaires. The primary outcome variable for all studies is long-term care certification data. Statistical analysis will be carried out using Kaplan-Meier, Multiple Cox regression as well as logistic regression. CONCLUSION: This project hopes to identify tools effective in predicting long-term care need. This will enable identification of citizens that are of higher risk for long-term care in the near future. This subset of high-risk individuals can in the future be addressed for extra support/intervention. ETHICS AND DISSEMINATION: All studies have been approved by respective institutional ethical committees and the WHO ethical committee ERC.0002899. In addition, all studies conform to the provisions of the Declaration of Helsinki and are conducted in accordance with Japan's 'Ethical Guidelines for Medical and Health Research Involving Human Subjects'. All findings will be disseminated at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000023283.

Prioritization of patient safety health policies: Delphi survey using patient safety experts in Japan.

Various patient safety interventions have been implemented since the late 1990s, but their evaluation has been lacking. To obtain basic information for prioritizing patient safety interventions, this study aimed to extract high-priority interventions in Japan and to identify the factors that influence the setting of priority. Six perspectives (contribution, dissemination, impact, cost, urgency, and priority) on 42 patient safety interventions classified into 3 levels (system, organizational, and clinical) were evaluated by Japanese experts using the Delphi technique. We examined the relationships of the levels and the perspectives on interventions with the transition of the consensus state in rounds 1 and 3. After extracting the high-priority interventions, a chi-squared test was used to examine the relationship of the levels and the impact/cost ratio with high priority. Regression models were used to examine the influence of each perspective on priority. There was a significant relationship between the level of interventions and the transition of the consensus state (p = 0.033). System-level interventions had a low probability of achieving consensus. "Human resources interventions," "professional education and training," "medication management/reconciliation protocols," "pay-for performance (P4P) schemes and financing for safety," "digital technology solutions to improve safety," and "hand hygiene initiatives" were extracted as high-priority interventions. The level and the impact/cost ratio of interventions had no significant relationships with high priority. In the regression model, dissemination and impact had an influence on priority (ß = -0.628 and 0.941, respectively; adjusted R-squared = 0.646). The influence of impact and dissemination on the priority of interventions suggests that it is important to examine the dissemination degree and impact of interventions in each country for prioritizing interventions.

Relationship of patient safety culture with factors influencing working environment such as working hours, the number of night shifts, and the number of days off among healthcare workers in Japan: a cross-sectional study.

BACKGROUND: Patient safety culture is defined as a product of individual and group values, attitudes, perceptions, competencies, and patterns of behavior that determine the commitment to, and the style and proficiency of, an organization's health and safety management. Factors influencing healthcare workers' working environment such as working hours, the number of night shifts, and the number of days off may be associated with patient safety culture, and the association pattern may differ by profession. This study aimed to examine the relationship between patient safety culture and working environment. METHODS: Questionnaire surveys were conducted in 2015 and 2016. The first survey was conducted in hospitals in Japan to investigate their patient safety management system and activities and intention to participate in the second survey. The second survey was conducted in 40 hospitals; 100 healthcare workers from each hospital answered a questionnaire that was the Japanese version of the Hospital Survey on Patient Safety Culture for measuring patient safety culture. The relationship of patient safety culture with working hours in a week, the number of night shifts in a month, and the number of days off in a month was analyzed. RESULTS: Response rates for the first and second surveys were 22.4% (731/3270) and 94.2% (3768/4000), respectively. Long working hours, numerous night shifts, and few days off were associated with low patient safety culture. Despite adjusting the working hours, the number of event reports increased with an increase in the number of night shifts. Physicians worked longer and had fewer days off than nurses. However, physicians had fewer composites of patient safety culture score related to working hours, the number of night shifts, and the number of days off than nurses. CONCLUSIONS: This study suggested a possibility of improving the patient safety culture by managing the working environment of healthcare workers. High number of night shifts may lead to high number of event reports. Working hours, the number of night shifts, and the number of days off may differently influence patient safety culture in physicians and nurses.

Different Influences of Statin Treatment in Preventing At-Risk Stroke Subtypes: A Post Hoc Analysis of J-STARS.

AIMS: To understand the different influences of statins on the incidence rate of each stroke subtype in association with low-density lipoprotein (LDL) cholesterol levels, we performed a post hoc analysis on the data from the Japan Statin Treatment Against Recurrent Stroke (J-STARS) study. METHODS: Subjects (n=1,578) were divided into three groups according to their mean postrandomized LDL cholesterol level (＜100, 100-120, and ≥ 120 mg/dL) until the last observation before the event or the end of follow-up. A Cox proportional hazard model for time to events was used for calculating adjusted hazard ratios, 95% confidence intervals, and the trend tests. RESULTS: The event rates for atherothrombotic stroke did not decrease in accordance with the postrandomized LDL cholesterol level subgroups of either the control or the pravastatin group (p=0.15 and 0.33 for the trend, respectively). In the control group, however, no atherothrombotic stroke event was observed in the subgroup of the low postrandomized LDL cholesterol level (less than 100 mg/dL). The event rates for atherothrombotic stroke were lower in the middle postrandomized LDL cholesterol level subgroup (100-120 mg/dL) of the pravastatin group than that of the control group. The event rates for lacunar stroke decreased in the lower postrandomized LDL cholesterol level subgroup of the control group but not of the pravastatin group (p=0.004 and 0.06 for the trend, respectively). CONCLUSIONS: Statins showed different influences on the risks of atherothromobotic and lacunar stroke according to postrandomized LDL cholesterol levels.

Effect of Statin on Stroke Recurrence Prevention at Different Infarction Locations: A Post Hoc Analysis of The J-STARS Study.

AIM: Posterior circulation stroke (PCS) has different clinical features and prognosis compared with anterior circulation stroke (ACS), and whether the effect of statin therapy on stroke prevention differs according to infarction location remains unclear. This post hoc analysis of the J-STARS study aimed to compare the usefulness of statin at different infarction locations (i.e., ACS and PCS). METHODS: In the J-STARS study, 1578 patients were randomly assigned to the pravastatin or control group. The subjects were divided into two subgroups (ACS and PCS groups) based on the arteries responsible for the infarction. Cox proportional hazards models were used to investigate whether the all stroke recurrence rate was different between the ACS and PCS groups. RESULTS: The PCS group (n=499) had a significantly higher prevalence of diabetes than the ACS group (n=1022) (30.7% vs. 19.8%, P＜0.001). During the follow-up (4.9±1.4 years), the incidence of all stroke was significantly lower in the pravastatin group than in the control group among patients with PCS (adjusted hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25-0.83, P=0.009); however, the stroke recurrence rates were not significantly different between both groups among patients with ACS (adjusted HR 1.32, 95% CI 0.93-1.88,P=0.123). A significant interaction between the ACS and PCS groups in terms of pravastatin effects was noted (P=0.003 for interaction). CONCLUSIONS: Pravastatin significantly reduced the recurrence rate of all stroke among patients with PCS. Thus, the effect of statin on the recurrence of stroke may differ according to infarction location.

Patient safety management systems, activities and work environments related to hospital-level patient safety culture: A cross-sectional study.

Improvement in patient safety culture requires constant attention. This study aimed to identify hospital-level elements related to patient safety culture, such as patient safety management systems, activities and work environments.Two questionnaire surveys were administered to hospitals in Japan in 2015 and 2016. The first survey aimed to determine which hospitals would allow their staff to respond to a questionnaire survey. The second survey aimed to measure the patient safety culture in those hospitals. Patient safety culture was assessed using the Hospital Survey on Patient Safety Culture (HSOPS). The relationship of hospital-level patient safety culture with the aforementioned elements in each hospital was analyzed.The response rate to the first survey was 22% (721/3270), and 40 eligible hospitals were selected from the respondents. The second survey was administered to healthcare workers in those 40 hospitals, and the response rate was 94% (3768/4000). The proportion of respondents who had 7 or more days off each month was related to the scores of 7 composites and the Patient Safety Grade of HSOPS. Both the presence of a mission statement describing patient safety and the proportion of respondents who participated in in-house patient safety workshops at least twice annually were related to the scores of 5 composites and the Patient Safety Grade of HSOPS.Our study suggests that the number of days off each month, the presence of a hospital patient safety mission statement, and the participation rate in in-house patient safety workshops might be key factors in creating a good patient safety culture within each hospital.

Baseline Carotid Intima-Media Thickness and Stroke Recurrence During Secondary Prevention With Pravastatin.

Background and Purpose- As a prespecified post hoc analysis of the J-STARS (Japan Statin Treatment Against Recurrent Stroke) Echo Study, the 5-year stroke recurrence rate according to the baseline mean carotid intima-media thickness (IMT) with and without pravastatin treatment was investigated. Methods- Patients were randomly assigned to receive pravastatin 10 mg/day (pravastatin group) or control group (nonstatin treatment; 1:1) for 5 years. Baseline mean IMT of the common carotid artery was measured by ultrasonography. Cox proportional hazards models were used to investigate whether the stroke (any ischemic stroke, atherothrombotic brain infarction, or lacunar infarction) recurrence rate was different according to tertiles of baseline mean IMT. Results- A total of 793 patients, including 388 in the pravastatin group and 405 in the control group, were investigated. In the control group, Cox proportional hazards models showed that participants in the highest tertile IMT group (≥0.931 mm) had a higher rate of atherothrombotic brain infarction than those in the lowest tertile IMT group (<0.812 mm; [hazard ratio, 9.08; 95% CI, 1.15-71.43]). Patients in the pravastatin group had a lower risk of atherothrombotic brain infarction than those in the control group only in the highest tertile IMT group by the log-rank test ( P value=0.045). Conclusions- Long-term pravastatin administration may prevent the occurrence of atherothrombotic brain infarction in noncardioembolic infarction patients with the highest tertile IMT. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00361530.

Assessing long-term care risk in older individuals with possible cognitive decline: A large population-based study using the Kihon Checklist.

AIM: The present population-based study investigated the predictive ability of the Kihon Checklist (a self-reported frailty questionnaire) and the cognitive domain therein for incident long-term care need certification. This is the first large population-based study to investigate an association between the Kihon Checklist and the outcome measure, long-term care need certification. METHODS: The study population consisted of community-dwelling citizens aged >65 years who responded to the Kihon Checklist in Kobe City. The Kihon Checklist is a simple 26-item questionnaire to identify frail citizens, including three items (Q18-20) on subjective cognitive function (the cognitive domain). RESULTS: A total of 182 099 citizens were included for statistical analysis. The overall incidence of long-term care need certification was 1.6%, 3.5% and 5.4% at 1, 2 and 3 years. Associations were found between the Kihon Checklist questions and long-term care need certification. Furthermore, each unfavorable answer on the cognitive domain was associated with the risk for long-term care need (HR 1.493 for Q18, 1.285 for Q19, 1.321 for Q20, all P < 0.0001), independent of age, sex and other items on the Kihon Checklist. Also, after 3 years, as the number of unfavorable answers to the cognitive domain increased from 0 to 1, 2 and 3, the incidence of long-term care need certification progressively increased from 3.5% to 6.4%, 12.6% and 29.6%. CONCLUSIONS: The Kihon Checklist, especially the cognitive domain therein, appears to be predictive of long-term care need in community-dwelling citizens, suggesting the potential utility of the questionnaire for early detection of high-risk individuals. Geriatr Gerontol Int 2019; 19: 598-603.

Japanese Surveillance of Neuroendovascular Therapy in JR-NET - Part II. Japanese Registry of NeuroEndovascular Treatment 3. Main Report.

This study, following Japanese Registry of NeuroEndovascular Treatment 1 and 2 (JR-NET 1 & 2), shows an annual trend of cases including adverse events and clinical outcomes at 30 days after NET. JR-NET3 was registered by 749 cumulative total number of physicians, certified by the Japanese Society of Neuroendovascular Therapy in 166 centers, between 2010 and 2014. Medical information about the patients was anonymized and retrospectively registered through a website. A total of 40,177 patients were recruited, 632 patients were excluded because data of preprocedural status were not available. So we analyzed 39,545 patients retrospectively. The proportion of octogenarians is increasing year-by-year and 14.7% in 2014 compared with 10.4% in 2010. Most frequent target disease is intracranial aneurysm. For the proportion of the treatment of intracranial aneurysm, 50.0% in 2010, but that has decreased to 44.8% in 2014. However, number of procedures were increased from 3150 in 2010 to 3419 in 2014. Although before the positive clinical evidence of mechanical thrombectomy for acute ischemic stroke (AIS) was established, the proportion of endovascular treatment for AIS increased 13.8% in 2014 compared with 6.3% in 2010. The number of patients requiring neuroendovascular treatment in Japan is increasing since 2010-2013, but that declined a little in 2014 caused by study operation suspended at the end of 2013. The outcomes of such therapy are clinically acceptable. Details of each type of treatment will be investigated in sub-analyses of the database.

Cumulative Effects of LDL Cholesterol and CRP Levels on Recurrent Stroke and TIA.

AIMS: To investigate the relative contribution of on-treatment low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) to the risk of recurrent stroke and transient ischemic attack (TIA) in patients with history of ischemic stroke. METHODS: A total of 1095 patients with non-cardioembolic ischemic stroke were randomized into two groups: control and patients receiving 10 mg of pravastatin per day. After excluding 18 patients who did not have baseline CRP data, the effects of LDL cholesterol and CRP on recurrent stroke and TIA were prospectively assessed in 1077 patients. RESULTS: During the follow-up of 4.9±1.4 years, there were 131 recurrent stroke or TIA cases. Patients with ontreatment LDL cholesterol ＜120 mg/dL showed 29% reduction in recurrent stroke and TIA than those with LDL cholesterol ≥ 120 mg/dL (event rate 2.20 vs. 3.11 per 100 person-years, hazard ratio [HR] 0.71, 95% confidence interval (CI) 0.50-0.99, p＝0.048). Patients with CRP ＜1 mg/L had 32% reduction compared with that of patients with CRP ≥ 1 mg/L (event rate 2.26 vs. 3.40 per 100 person-years; HR 0.68, 95% CI 0.48-0.96, p＝0.031). Although LDL cholesterol and CRP levels were not correlated in individual patients, those who achieved both LDL cholesterol ＜120 mg/dL and CRP ＜1 mg/L showed 51% reduction compared with that of patients with LDL cholesterol ≥ 120 mg/dL and CRP ≥ 1 mg/L (event rate 2.02 vs. 4.19 per 100 person-years; HR 0.49, 95% CI 0.31-0.79). CONCLUSIONS: The control of both LDL cholesterol and CRP levels appears to be effective for preventing recurrent stroke and TIA in patients with non-cardiogenic ischemic stroke.

One-year Outcome of Shanghai Mild Cognitive Impairment Cohort Study.

BACKGROUND & OBJECTIVE: The purpose of this study is to identify the risk factors associated with the conversion from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD) dementia for the early detection of AD. METHODS: The study comprised a prospective cohort study that included 400 MCI subjects with annual follow-ups for 3 years. RESULTS: During the first 12 months' follow-up, 42 subjects converted to Alzheimer's dementia (21 probable AD and 21 possible AD), two subjects converted to other types of dementia and 56 subjects lost follow. The factors associated with a greater risk of conversion from MCI to AD included gender, whole brain volume, and right hippocampal volume (rt. HV), as well as scores on the Revised Chinese version of the Alzheimer's Disease Assessment Scale-Cognitive subscale 13 (ADAS-Cog-C), Clock Drawing Test (CDT), Symbol Digit Modalities Test (SDMT), and Rey-Osterrieth Complex Figure Test (ROCFT). The risk classification of the combined ADAS-Cog-C and Alzheimer Cognitive Composite (ACC) score with the rt. HV and left Entorhinal Cortex Volume (lt. ECV) showed a conversion difference among the groups. CONCLUSION: Early detection of AD and potential selection for clinical trial design should utilize the rt. HV, as well as neuropsychological test scores, including those of the ADAS-Cog-C and ACC.

Desirable Low-Density Lipoprotein Cholesterol Levels for Preventing Stroke Recurrence: A Post Hoc Analysis of the J-STARS Study (Japan Statin Treatment Against Recurrent Stroke).

BACKGROUND AND PURPOSE: To define desirable target low-density lipoprotein (LDL) cholesterol levels for the prevention of stroke recurrence, a post hoc analysis was performed in the J-STARS study (Japan Statin Treatment Against Recurrent Stroke). METHODS: Subjects (n=1578) were divided into groups based on mean value of postrandomized LDL cholesterol levels until the last observation in 20 mg/dL increments. Adjusted hazard ratios (HRs) and 95% confidence intervals were analyzed for each group, with adjustments for baseline LDL cholesterol, baseline body mass index, hypertension, diabetes mellitus, and statin usage. RESULTS: The postrandomized LDL cholesterol level until the last observation were 104.1±19.3 mg/dL in the pravastatin group and 126.1±20.6 mg/dL in the control group. The adjusted HRs for stroke and transient ischemic attack and all vascular events decreased in the postrandomized LDL cholesterol level of 80 to 100 mg/dL (P=0.23 and 0.25 for the trend, respectively). The adjusted HR for atherothrombotic infarction significantly reduced with the usage of statin after adjusting baseline LDL cholesterol levels (HR, 0.39; 95% confidence intervals, 0.19-0.83). The adjusted HR for atherothrombotic infarction and intracranial hemorrhage were similar among the postrandomized LDL-cholesterol-level subgroups (P=0.50 and 0.37 for the trend, respectively). The adjusted HR for lacunar infarction decreased in the postrandomized LDL cholesterol level of 100 to 120 mg/dL (HR, 0.45; 95% confidence intervals, 0.20-0.99; P=0.41 for the trend). CONCLUSIONS: The composite risk of stroke and transient ischemic attack reduced in the postrandomized LDL cholesterol level of 80 to 100 mg/dL after adjusting for statin usage. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00221104.

Factors Associated with Intima-Media Complex Thickness of the Common Carotid Artery in Japanese Noncardioembolic Stroke Patients with Hyperlipidemia: The J-STARS Echo Study.

AIMS: There may be ethnic differences in carotid atherosclerosis and its contributing factors between Asian and other populations. The purpose of this study was to examine intima-media complex thickness (IMT) of the carotid artery and associated clinical factors in Japanese stroke patients with hyperlipidemia from a cohort of the Japan Statin Treatment Against Recurrent Stroke Echo Study. METHODS: Patients with hyperlipidemia, not on statins, who developed noncardioembolic ischemic stroke were included in this study. Mean IMT and maximum IMT of the distal wall of the common carotid artery were centrally measured using carotid ultrasonography. Significant factors related to mean IMT and maximum IMT were examined using multivariable analysis. RESULTS: In 793 studied patients, mean IMT was 0.89±0.15 mm and maximum IMT was 1.19±0.32 mm.Age (per 10 years, parameter estimate=0.044, p＜0.001), smoking (0.022, p=0.004), category of blood pressure (0.022, p=0.006), HDL cholesterol (per 10 mg/dl, －0.009, p=0.008), and diabetes mellitus (0.033, p=0.010) were independently associated with mean IMT. Age (per 10 years, 0.076, p＜0.001), smoking (0.053, p=0.001), HDL cholesterol (－0.016, p=0.036), and diabetes mellitus (0.084, p=0.002) were independently associated with maximum IMT. CONCLUSION: Baseline mean and maximum values of carotid IMT in Japanese noncardioembolic stroke patients with hyperlipidemia were 0.89±0.15 mm and 1.19±0.32 mm, respectively, which were similar to those previously reported from Western countries. Age, smoking, hypertension, HDL cholesterol, and diabetes mellitus were associated with mean IMT, and those, except for hypertension, were associated with maximum IMT.

Long-Term Effect of Pravastatin on Carotid Intima-Media Complex Thickness: The J-STARS Echo Study (Japan Statin Treatment Against Recurrent Stroke).

BACKGROUND AND PURPOSE: The effect of statins on progression of carotid intima-media complex thickness (IMT) has been shown exclusively in nonstroke Western patients. This study aimed to determine the effect of low-dose pravastatin on carotid IMT in Japanese patients with noncardioembolic ischemic stroke. METHODS: This is a substudy of the J-STARS trial (Japan Statin Treatment Against Recurrent Stroke), a multicenter, randomized, open-label, parallel-group trial to examine whether pravastatin reduces stroke recurrence. Patients were randomized to receive pravastatin (10 mg daily, usual dose in Japan; pravastatin group) or not to receive any statins (control group). The primary outcome was IMT change of the common carotid artery for a 5-year observation period. IMT change was compared using mixed-effects models for repeated measures. RESULTS: Of 864 patients registered in this substudy, 71 without baseline ultrasonography were excluded, and 388 were randomly assigned to the pravastatin group and 405 to the control group. Baseline characteristics were not significantly different, except National Institutes of Health Stroke Scale scores (median, 0 [interquartile range, 0-2] versus 1 [interquartile range, 0-2]; P=0.019) between the 2 groups. Baseline IMT (mean±SD) was 0.887±0.155 mm in the pravastatin group and 0.887±0.152 mm in the control group (P=0.99). The annual change in the IMT at 5-year visit was significantly reduced in the pravastatin group as compared with that in the control group (0.021±0.116 versus 0.040±0.118 mm; P=0.010). CONCLUSIONS: The usual Japanese dose of pravastatin significantly reduced the progression of carotid IMT at 5 years in patients with noncardioembolic stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00361530.

Pravastatin Reduces the Risk of Atherothrombotic Stroke when Administered within Six Months of an Initial Stroke Event.

AIMS: The J-STARS study examined whether pravastatin (10 mg/day) reduces recurrence of stroke in non-cardioembolic ischemic stroke patients who were enrolled within 1 month to 3 years after initial stroke events (ClinicalTrials.gov, NCT00221104). The main results showed that the frequency of atherothrombotic stroke was low in pravastatin-treated patients, although no effect of pravastatin was found for the other stroke subtypes. We evaluated differences of early (within 6 months) or late (after 6 months) pravastatin treatment benefits on the incidence of stroke or transient ischemic attack (TIA), as well as atherothrombotic stroke and the other subtypes. METHODS: Subjects in the J-STARS study were classified into two cohorts, depending on whether they enrolled early (1 to 6 months) or late (6 months to 3 years) following initial stroke events. RESULTS: A total of 1578 patients (491 female, 66.2±8.5 years) were randomly assigned to either the pravastatin group (n=793; n=426 in the early cohort, n=367 in the late cohort) or the control group (n=785; n=417 in the early cohort, n=368 in the late cohort). During the follow-up of 4.9± 1.4 years, the rate of atherothrombotic stroke was lower in the pravastatin group compared to controls in the early cohort (0.24 vs. 0.88%/year, p=0.01) but not in the late cohort (0.17 vs. 0.39%/year, p=0.29). However, this difference of pravastatin effect on atherothrombotic stroke was not significantly interacted by the early or late cohort (p=0.59). The incidence rates of other stroke subtype were not different in between pravastatin and control groups despite the timing of entry. CONCLUSIONS: Pravastatin is likely to reduce atherothrombotic stroke in patients enrolled within 6 months after stroke onset. However, the clinical efficacy for prevention of recurrent stroke was not conclusive with earlier statin treatment.

Ten-year standardization of lipids and high-sensitivity C-reactive protein in a randomized controlled trial to assess the effects of statins on secondary stroke prevention: Japan Statin Treatment Against Recurrent Stroke.

Background The Japan Statin Treatment Against Recurrent Stroke (J-STARS) is a clinical trial that administered pravastatin for secondary stroke prevention. Lipid concentrations are a well-established risk factor for cerebrovascular diseases. Elevated high-sensitivity C-reactive protein (hs-CRP) indicates a high risk of inflammatory reactions. In clinical trials, internationally approved standardization is essential for obtaining study results that are comparable with those from overseas. Therefore, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and hs-CRP were standardized throughout a 10-year study period. Methods J-STARS specified a single clinical laboratory for blood analyses. Four lipids were evaluated by calculating the total error: accuracy (absolute mean %bias vs. reference value) + precision (1.96 among-run coefficient of variation [CV, %]). Accuracy for hs-CRP was ensured using a calibrator traceable to the international plasma protein reference material and precision was evaluated by CV. Results Average total errors (standard deviation, %) throughout the study period were as follows: TC 1.35% (0.290%), HDL-C 2.45% (1.087%), LDL-C 2.65% (0.956%) and TG 3.70% (0.559%). Four lipids met the performance criteria of the US Centers for Disease Control and Prevention (CDC). The precision of hs-CRP was 3.28% (0.627%), which met the performance criterion established by the American Heart Association/CDC. Conclusions Based on standardization, the results of J-STARS appear to be comparable with those of similar intervention-based clinical studies on statins overseas. These study results will contribute to the establishment of preventive measures against recurrent stroke in Japanese patients. J-STARS is registered in ClinicalTrials.gov under NCT00221104.