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With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

The optimal treatment for patients with ischaemic stroke with a high risk of cerebral haemorrhage is unclear. We assessed the efficacy and safety of cilostazol versus aspirin, with and without probucol, in these patients. In this randomised, controlled, 2 × 2 factorial trial, we enrolled patients with ischaemic stroke with a history of or imaging findings of intracerebral haemorrhage or two or more microbleeds from 67 centres in three Asian countries. Patients were randomly assigned (1:1:1:1) to receive oral cilostazol (100 mg twice a day), aspirin (100 mg once a day), cilostazol plus probucol (250 mg twice a day), or aspirin plus probucol with centralised blocks stratified by centre. Cilostazol versus aspirin was investigated double-blinded; probucol treatment was open-label, but the outcome assessor was masked to assignment. The co-primary outcomes were incidence of the composite of stroke, myocardial infarction, or vascular death (efficacy) and incidence of haemorrhagic stroke (safety), which were assessed in intention-to-treat and modified intention-to-treat populations. Efficacy was analysed with a non-inferiority test and a superiority test if non-inferiority was satisfied. Safety was assessed with a superiority test only. This trial is registered with ClinicalTrials.gov, NCT01013532. Between Aug 1, 2009, and Aug 31, 2015, we randomly assigned 1534 patients to one of the four study groups, of whom 1512 were assessed for the co-primary endpoints. During a median follow-up of 1·9 years (IQR 1·0–3·0), the incidence of composite vascular events was 4·27 per 100 person-years in patients who received cilostazol and 5·33 per 100 person-years in patients who received aspirin (HR 0·80, 95% CI 0·57–1·11; non-inferiority p=0·0077; superiority p=0·18). Incidence of cerebral haemorrhage was 0·61 per 100 person-years in patients who received cilostazol and 1·20 per 100 person-years in those who received aspirin (HR 0·51, 97·5% CI 0·20–1·27; superiority p=0·18). The incidence of vascular events was 3·91 per 100 person-years in the probucol group compared with 5·75 per 100 person-years in the non-probucol group (HR 0·69, 95% CI 0·50–0·97; superiority p=0·0316). The incidence of cerebral haemorrhage was 0·72 per 100 person-years in the probucol group and 1·11 per 100 person-years in the non-probucol group (HR 0·65, 97·5% CI 0·27–1·57; p=0·55). Adverse events were similar across the four study groups; the most common events were dizziness, headache, diarrhoea, and constipation. In patients with ischaemic stroke at high risk of cerebral haemorrhage, cilostazol was non-inferior to aspirin for the prevention of cardiovascular events, but did not reduce the risk of haemorrhagic stroke. Addition of probucol to aspirin or cilostazol could be beneficial for reducing the incidence of cardiovascular events. Korea Otsuka Pharmaceutical.

Objective To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians.Design Pooled analyses of 20 prospective cohorts in Asia, including data from 835 082 east Asians and 289 815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability.Setting General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh).Participants 1 124 897 men and women (mean age 53.4 years at baseline).Main outcome measures Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes.Results 49 184 cardiovascular deaths (40 791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12).Conclusions Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.

Significant racial/ethnic differences exist in the incidence of atrial fibrillation (AF). However, less is known about racial/ethnic differences in quality of life (QoL), treatment, and outcomes associated with AF. Using data from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we compared clinical characteristics, QoL, management strategies, and long-term outcomes associated with AF among various racial/ethnic groups. We analyzed 9,542 participants with AF (mean age 74 ± 11 years, 43% women, 91% white, 5% black, 4% Hispanic) from 174 centers. Compared with AF patients identified as white race, patients identified as Hispanic ethnicity and those identified as black race were younger, were more often women, and had more cardiac and noncardiac comorbidities. Black patients were more symptomatic with worse QoL and were less likely to be treated with a rhythm control strategy than other racial/ethnic groups. There were no significant racial/ethnic differences in CHA2DS2-VASc stroke or ATRIA bleeding risk scores and rates of oral anticoagulation use were similar. However, racial and ethnic minority populations treated with warfarin spent a lower median time in therapeutic range of international normalized ratio (59% blacks vs 68% whites vs 62% Hispanics, P < .0001). There was no difference in long-term outcomes associated with AF between the 3 groups at a median follow-up of 2.1 years. Relative to white and Hispanic patients, black patients with AF had more symptoms, were less likely to receive rhythm control interventions, and had lower quality of warfarin management. Despite these differences, clinical events at 2 years were similar by race and ethnicity.

The perceived risk of serious bleeding is an obstacle to the use of oral anticoagulation in East Asia. The efficacy and safety of apixaban in East Asian patients with atrial fibrillation are unknown. ARISTOTLE included 18,201 patients with nonvalvular atrial fibrillation randomized to apixaban 5mg twice daily or warfarin. The efficacy and safety of apixaban and warfarin among patients recruited from East Asia (n = 1,993) were compared with those recruited from outside East Asia (n = 16,208). Compared with warfarin, apixaban resulted in a consistent reduction in stroke or systemic embolism in East Asian (hazard ratio [HR] 0.74, 95% CI 0.50-1.10) and non–East Asian (HR 0.81, 95% CI 0.66-0.99) patients (interaction P = .70). Consistent benefits of apixaban over warfarin were also seen for major bleeding in East Asian (HR 0.53, 95% CI 0.35-0.80) and non–East Asian (HR 0.72, 95% CI 0.62-0.83) patients (interaction P = .17). There was a greater reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin in East Asian (HR 0.49, 95% CI 0.35-0.67) than in non–East Asian (HR 0.71, 95% CI 0.63-0.79) patients (interaction P = .03). Numerically higher rates of intracranial bleeding were seen in East Asian patients with warfarin but not with apixaban. Apixaban resulted in similar reductions in stroke or systemic embolism and major bleeding and greater reductions in major or clinically relevant nonmajor bleeding in patients from East Asia. Warfarin is associated with more intracranial bleeding, particularly in patients from East Asia.

BackgroundA number of studies have demonstrated a J-shaped curve between blood pressure (BP) and all-cause mortality, but few studies have used longitudinal change in BP to study mortality in the Chinese population.MethodsWe performed a 30-year follow-up study to examine the association between BP (at baseline and longitudinal change) and risk of mortality in the Linxian General Population Trial Cohort. At baseline, a total of 29 584 healthy adults were enrolled in the Linxian General Population Trial in 1985 and followed through to the end of 2014. The final analysis was restricted to 29 439 participants (55% women) after exclusion of outliers. We also examined the potential effects of BP trajectory patterns during the period of 1985–1999 on sequent risk of mortality. Adjusted Cox proportional hazards models were used to estimate HRs and 95% CIs.ResultsCompared with participants with normal BP, patients with prehypertension, stage 1, stage 2 or stage 3 hypertension had an increased risk of all-cause mortality, with HRs of 1.09 (95% CI 1.05 to 1.14), 1.34 (95% CI 1.28 to 1.40), 1.69 (95% CI 1.60 to 1.79) and 2.14 (95% CI 2.01 to 2.28), respectively. Relative to stable BP of normotension, having a rise in BP from normotension to hypertension or from prehypertension to hypertension both conferred an increased risk of total and cardiovascular disease and stroke mortality (total: HRs 1.22 (95% CI 1.12 to 1.34) and 1.36 (95% CI 1.23 to 1.51); cardiovascular disease: HRs 1.42 (95% CI 1.17 to 1.73) and 1.55 (95% CI 1.24 to 1.93); stroke: HRs 2.29 (95% CI 1.88 to 2.80) and 2.61 (95% CI 2.11 to 3.24), respectively).ConclusionsThese findings emphasise that development of incident hypertension in middle age could increase the risk of total, cardiovascular disease and stroke mortality, and suggest that current BP targets could be revised.Trial registration number NCT00342654;Post-results.

To investigate the impact of low socioeconomic status (SES), indicated by low level of education, occupation and income, on 3 months functional outcome after ischemic stroke. We analyzed data from the China National Stroke Registry (CNSR), a multicenter and prospective registry of consecutive patients with acute cerebrovascular events occurred between September 2007 and August 2008. 11226 patients with ischemic stroke had SES and clinical characteristics data collected at baseline and mRS measured as indicator of functional outcome in 3 months follow up. Multinomial and ordinal logistic regression models were performed to examine associations between SES and the functional outcome. At 3 months after stroke, 5.3% of total patients had mRS scored at 5, 11.3% at score 4, 11.1% at score 3, 14.4% at score 2, 34.2% at score 1 and 23.7% at score 0. Compared to patients with educational level of ≥ 6 years and non-manual laboring, those < 6 years and manual laboring tended to have higher mRS score (P<0.001). Multinomial adjusted odds ratios (ORs) of outcome in manual workers were significantly increased (ORs from1.38 to 1.87), but OR in patients with less income was not significant. There were similar patterns of association The impact may be stronger in patients aged <65 years (P = 0.003, P<0.001 respectively) and being male (P = 0.001, P<0.001 respectively). Our study provides evidence that people who are relatively more deprived in socioeconomic status suffer poorer outcome after ischemic stroke. The influence of low educational level and manual laboring can be more intensive than low income level on 3-month outcome. Health policy and service should target the deprived populations to reduce the public health burden in the society.

Background and Purpose: Blacks have a higher burden of post-stroke disability. Factors associated with racial differences in long-term post-stroke disability are not well-understood. Our aim was to assess the long-term racial differences in risk factors associated with stroke recovery.Methods: We examined Health and Retire­ment Study (HRS) longitudinal interview data collected from adults living with stroke who were aged >50 years during 2000- 2014. Analysis of 1,002 first-time, non- Hispanic, Black (210) or White (792) stroke survivors with data on activities of daily liv­ing (ADL), fine motor skills (FMS) and gross motor skills (GMS) was conducted. Ordinal regression analysis was used to assess the impact of sex, race, household residents, household income, comorbidities, and the time since having a stroke on functional outcomes.Results: Black stroke survivors were young­er compared with Whites (69 ± 10.4 vs 75 ± 11.9). The majority (~65%) of Black stroke survivors were female compared with about 54% White female stroke survivors (P=.007). Black stroke survivors had more household residents (P<.001) and comor­bidities (P<.001). Aging, being female, being Black and a longer time since stroke were associated with a higher odds of hav­ing increased difficulty in ADL, FMS and/or GMS. Comorbidities were associated with increased difficulty with GMS. Black race increased the impact of comorbidities on ADL and FMS in comparison with Whites.Conclusion: Our data suggest that the effects of aging, sex and unique factors associated with race should be taken into consideration for future studies of post-stroke recovery and therapy.Ethn Dis. 2020;30(2):339-348; doi:10.18865/ ed.30.2.339

Background Post-stroke disability is common, costly, and projected to increase. Acute stroke treatments can substantially reduce post-stroke disability, but few patients take advantage of these cost-effective treatments. Practical, cost-efficient, and sustainable interventions to address underutilized acute stroke treatments are currently lacking. In this context, we present the Stroke Ready project, a stepped wedge design, multi-level intervention that combines implementation science and community-based participatory research approaches to increase acute stroke treatments in the predominately African American community of Flint, Michigan, USA. Methods Guided by the Tailored Implementation of Chronic Disease (TICD) framework, we begin with optimization of acute stroke care in emergency departments, with particular attention given to our safety-net hospital partners. Then, we move to a community-wide, multi-faceted, stroke preparedness intervention, with workshops led by peer educators, over 2 years. Measures of engagement of the safety-net hospital and the feasibility and sustainability of the implementation strategy as well as community intervention reach, dose delivered, and satisfaction will be collected. The primary outcome is acute stroke treatment rates, which includes both intravenous tissue plasminogen activator, and endovascular treatment. The co-secondary outcomes are intravenous tissue plasminogen activator treatment rates and the proportion of stroke patients who arrive by ambulance. Discussion If successful, Stroke Ready will increase acute stroke treatment rates through emergency department and community level interventions. The stepped wedge design and process evaluation will provide insight into how Stroke Ready works and where it might work best. By exploring the relative effectiveness of the emergency department optimization and the community intervention, we will inform hospitals and communities as they determine how best to use their resources to optimize acute stroke care. Trial registration ClinicalTrials.gov Trial Identifier NCT03645590 .

Atherothrombosis is a common condition affecting individuals worldwide. Its impact on different ethnic groups receiving evidence-based therapy is unclear. We aimed to determine if ethnicity is an independent predictor for cardiovascular events and bleeding complications in a contemporary clinical trial on antiplatelet therapy. This was a prospective observational study of 15,603 patients enrolled in the CHARISMA trial followed up every 6 months for a median of 28 months. The primary efficacy end point was the first occurrence of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was bleeding. The cohort comprised 12,502 (80.1%) white, 486 (3.1%) black, 775 (5.0%) Asian, and 1,613 (10.3%) Hispanic patients. There was no difference in the occurrence of the primary composite end point among the 4 ethnic groups. Compared with Asians, cardiovascular and all-cause mortality occurred more frequently among black (adjusted hazard 2.19 and 2.04) and Hispanic (adjusted hazard, 1.83 and 1.69) patients. Although the occurrence of severe bleeding was similarly low among the 4 ethnic groups, Asian (adjusted hazard, 2.21) and black (adjusted hazard, 3.06) patients were more likely to have moderate bleeding complications than Hispanic patients. In this trial of individuals at risk of vascular events, ethnicity was not a significant, independent predictor of the primary composite cardiovascular event. However, ethnicity was a significant, independent predictor of the secondary outcomes, cardiovascular and all-cause mortality (blacks and Hispanics), and moderate bleeding complications (blacks and Asians).