Educational Attainment and Dementia: Mediation by Mid-Life Vascular Risk Factors.

INTRODUCTION: Lower education is associated with higher burden of vascular risk factors in mid-life and higher risk of dementia in late life. We aim to understand the causal mechanism through which vascular risk factors potentially mediate the relationship between education and dementia. METHODS: In a cohort of 13,368 Black and White older adults in the Atherosclerosis Risk in Communities Study, we assessed the relationship between education (grade school, high school without graduation, high school graduate or equivalent, college, graduate/professional school) and dementia among all participants and among those with incident stroke. Cox models were adjusted for age, race-center (a variable stratified by race and field center), sex, apolipoprotein E (APOE) ε4 genotype, and family history of cardiovascular disease. Causal mediation models assessed mediation by mid-life systolic blood pressure, fasting blood glucose, body mass index, and smoking. RESULTS: More education was associated with 8 to 44% lower risk of dementia compared to grade school-level education in a dose-response pattern, while the relationship between education and post-stroke dementia was not statistically significant. Up to 25% of the association between education and dementia was mediated through mid-life vascular risk factors, with a smaller percentage mediated for lower levels of education. INTERPRETATION: A substantial proportion of the relationship between education and dementia was mediated through mid-life vascular risk factors. However, risk factor modification is unlikely to fully address the large educational disparities in dementia risk. Prevention efforts must also address disparities in socioeconomic resources leading to divergent early-life education and other structural determinants of mid-life vascular risk factors. ANN NEUROL 2023;94:13-26.

Temporal trends and rural-urban disparities in cerebrovascular risk factors, in-hospital management and outcomes in ischaemic strokes in China from 2005 to 2015: a nationwide serial cross-sectional survey.

BACKGROUND: Stroke is the leading cause of mortality in China, with limited evidence of in-hospital burden obtained from nationwide surveys. We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors, management and outcomes from 2005 to 2015. METHODS: We used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005, 2010 and 2015. We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach. We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015. RESULTS: We analysed 28 277 ischaemic stroke admissions from 189 participating hospitals. From 2005 to 2015, the estimated national hospital admission rate for ischaemic stroke per 100 000 people increased (from 75.9 to 402.7, Ptrend<0.001), and the prevalence of risk factors, including hypertension, diabetes, dyslipidaemia and current smoking, increased. The composite score of diagnostic tests for stroke aetiology assessment (from 0.22 to 0.36, Ptrend<0.001) and secondary prevention treatments (from 0.46 to 0.70, Ptrend<0.001) were improved. A temporal decrease was found in discharge against medical advice (DAMA) (from 15.2% (95% CI 13.7% to 16.7%) to 8.6% (8.1% to 9.0%); adjusted Ptrend=0.046), and decreases in in-hospital mortality (0.7% in 2015 vs 1.8% in 2005; adjusted OR (aOR) 0.52; 95% CI 0.32 to 0.85) and the composite outcome of in-hospital mortality or DAMA (8.4% in 2015 vs 13.9% in 2005; aOR 0.65; 95% CI 0.47 to 0.89) were observed. Disparities between rural and urban hospitals narrowed; however, disparities persisted in in-hospital management (brain MRI: rural-urban difference from -14.4% to -11.2%; cerebrovascular assessment: from -20.3% to -16.7%; clopidogrel: from -2.1% to -10.3%; anticoagulant for atrial fibrillation: from -10.9% to -8.2%) and in-hospital outcomes (DAMA: from 2.7% to 5.0%; composite outcome of in-hospital mortality or DAMA: from 2.4% to 4.6%). CONCLUSIONS: From 2005 to 2015, improvements in hospital admission and in-hospital management for ischaemic stroke in China were found. A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed. Disparities between rural and urban hospitals generally narrowed but persisted.

Pre-stroke dementia and in-hospital outcomes in the Chinese Stroke Center Alliance.

Background: Little is known about the impact of prevalent dementia on in-hospital outcomes of patients with incident stroke in China. Using data from the Chinese Stroke Center Alliance (CSCA), we aim to quantify the prevalence of pre-stroke dementia and whether this group is at higher risk of adverse in-hospital outcomes compared to those without pre-stroke dementia. Methods: We used multivariable logistic regression models to assess the associations between pre-stroke dementia and ambulation by day 2, in-hospital mortality, in-hospital complications, and being discharged home. Covariates included age, sex, comorbidities [dyslipidemia, atrial fibrillation, peripheral vascular disease (PVD), smoking, and alcohol use], medication history (antiplatelet drugs or lipid-lowering drugs), stroke severity [measured by the National Institute of Health Stroke Scale (NIHSS)], administration of intravenous tissue plasminogen activator (IV tPA) within 4.5 hours of stroke onset, and receipt of deep vein thrombosis (DVT) prophylaxis if indicated. Results: In the final analytic sample of 559,070 ischemic stroke patients with no prior stroke history enrolled across 1,476 hospitals, those with pre-stroke dementia (n=1,511; 0.3%) were older and more likely to be female. Despite having received similar treatment, patients with pre-stroke dementia had lower odds of ambulating by day 2 [odds ratio (OR) =0.69; 95% confidence interval (CI): 0.62-0.78], higher odds of in-hospital mortality (OR =2.01; 95% CI: 1.35-2.99) or complications (OR =2.17; 95% CI: 1.93-2.44), and lower odds of being discharged home compared to those without pre-stroke dementia (OR =0.71; 95% CI: 0.62-0.83). Conclusions: Worse in-hospital outcomes among patients with pre-stroke dementia may be explained by pre-existing cognitive impairment that limited their ability to advocate for care needs. Further research is needed to determine whether a different care pathway or additional attention from clinicians is necessary for patients with pre-stroke dementia.

Sex differences in vascular risk factors, in-hospital management, and outcomes of patients with acute ischemic stroke in China.

BACKGROUND: Previous assessments of sex differences for patients with acute ischemic stroke were limited in a specific region or population, narrow scope, or small sample size. METHODS: Patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals were analyzed. Absolute standardized differences (ASDs) were used to assess sex differences in vascular risk factors, guideline-recommended in-hospital management measures and outcomes, including stroke severity (National Institutes of Health Stroke Scale≥16), death/discharge against medical advice, major adverse cardiovascular events, pneumonia, and disability (modified Rankin Scale≥3). RESULTS: Of 838,229 patients analyzed, 524351 (62.6%) were men and 313,878 (37.4%) were women. Compared with men, women were older (68.6 vs. 64.7 years), had higher prevalence of hypertension (67.7% vs. 62.4%), diabetes (24.7% vs. 19.5%), and atrial fibrillation (7.1% vs. 4.3%), but lower prevalence of smoking (4.5% vs. 56.6%) and drinking (2.6% vs 35.8%) (ASDs >10%). No sex differences were seen in guideline-directed management measures, indicated by risk-adjusted individual measures and the all-or-null summary measure (34.5% vs 34.9%, ASD = 1.0%). Compared to men, women tended to have strokes that were more severe at presentation (6.5% vs. 4.5%, ASD = 8.8%) and more disabilities at discharge (34.9% vs 30.5%, ASD =9.4%). However, all sex-related differences in outcomes were attenuated to null after risk adjustments (ASDs<2%). CONCLUSIONS: Compared to male patients, female patients had more vascular risk factors and received similar in-hospital care. They had strokes that were more severe at presentation and more disabilities at discharge, both of which may be explained by worse vascular risk profiles.

Guideline-directed low-density lipoprotein management in high-risk ischemic stroke or transient ischemic attack admissions in China from 2015 to 2019.

BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) is crucial for secondary stroke prevention in stroke patients with preexisting cardiovascular diseases (CVD) or cerebrovascular diseases (CeVD). However, data on attainment of guideline-recommended LDL-C levels are lacking. METHODS: We analyzed data from the Chinese Stroke Center Alliance (CSCA) program for patients with ischemic stroke and transient ischemic attack (TIA) hospitalized between August 2015 and July 2019. Participants were classified into different disease groups according to preexisting CeVD (stroke/TIA) or CVD [coronary heart disease (CHD) or myocardial infarction (MI)]. RESULTS: Of 858,509 patients presenting with an acute stroke/TIA, 251,176 (29.3%) had a preexisting CeVD, 44,158 (5.1%) had preexisting CVD, 33,070 (3.9%) had concomitant preexisting CeVD and CVD, and 530,105 (61.7%) had no documented history of CeVD/CVD. Overall, only 397,596 (46.3%) met the target for LDL-C <2.6 mmol/L, 128,177 (14.9%) for LDL-C <1.8 mmol/L and 55,275 (6.4%) for LDL-C <1.4 mmol/L, and patients with concomitant CeVD and CVD had higher attainment rates than other disease groups (P<0.001). Despite improvements over time in the proportion of patients who attain LDL-C targets (P for trend <0.05), it remains suboptimal. Younger age, women, having a history of hypertension or dyslipidemia, current smoking or drinking, and being admitted to hospitals located in eastern China were associated with lower odds of meeting the LDL-C goals. CONCLUSIONS: Overall attainment of guideline LDL-C targets in a population of stroke/TIA patients is low and indicates the need for better management of dyslipidemia, particularly for high-risk stroke patients with pre-existing CeVD or CVD.

Change in Life's Simple 7 Measure of Cardiovascular Health After Incident Stroke: The REGARDS Study.

BACKGROUND AND PURPOSE: Life's Simple 7 (LS7) is a metric for cardiovascular health based on the 7 domains of smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose. Because they may be targeted for secondary prevention purposes, we hypothesized that stroke survivors would experience improvement in LS7 score over time compared with people who did not experience a stroke. We addressed this hypothesis in the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) cohort of Black and White adults enrolled between 2003 and 2007. METHODS: Participants who had LS7 data at baseline, were stroke-free at baseline, had a 10-year follow-up visit, and either did not have a stroke or had an ischemic stroke >1 year before follow-up were included (N=7569). Among these participants, 149 (2.0%) had an adjudicated ischemic stroke between the LS7 assessments. LS7 scores were classified as 0 to 2 points for each domain for a maximum score of 14, with higher scores representing better health. Multivariable linear regression was used to test the association of ischemic stroke with change in LS7 score. Covariates included baseline LS7 score, age, race, sex, education, and geographic region. RESULTS: The 149 stroke survivors had an average of 4.9 years (SD=2.5) of follow-up from the stroke event to the second LS7 assessment. After adjusting for covariates, participants who experienced an ischemic stroke showed 0.28 points more decline in total LS7 score (P=0.03) than those who did not experience a stroke. CONCLUSIONS: Stroke survivors did not experience improvements in cardiovascular health due to secondary prevention after ischemic stroke. On the contrary, they experienced significantly greater decline, indicating the need for greater efforts in secondary prevention after a stroke.