Baseline Cognitive Impairment in Patients With Asymptomatic Carotid Stenosis in the CREST-2 Trial.

BACKGROUND AND PURPOSE: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort. METHODS: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of Z scores less than the anticipated deviate for the population-based cohort for representative percentiles. RESULTS: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall Z score for patients was significantly below expected for higher percentiles (P<0.0001 for 50th, 75th, and 95th percentiles) and marginally below expected for the 25th percentile (P=0.015). Lower performance was attributed largely to Word List Recall (P<0.0001 for all percentiles) and for Word List Learning (50th, 75th, and 95th percentiles below expected, P≤0.01). The scores for left versus right carotid disease were similar. CONCLUSIONS: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02089217.

Inaugural Health Equity and Actionable Disparities in Stroke: Understanding and Problem-Solving Symposium.

Race/ethnic minorities face significant inequities in stroke incidence, prevalence, care, and outcomes. The Health Equity and Actionable Disparities in Stroke: Understanding and Problem-solving symposium, a collaborative initiative of the American Heart Association and National Institute of Neurological Disorders and Stroke, was the first-ever annual multidisciplinary scientific forum focused on race/ethnic inequities in cerebrovascular disease, with the overarching goal of reducing inequities in stroke and accelerating the translation of research findings to improve outcomes for race/ethnic minorities. The symposium featured esteemed invited plenary speakers, lecturing on determinants of race/ethnic inequities in stroke and interventions aimed at redressing the inequities. The Edgar J. Kenton III Award recognized Ralph Sacco, MD, MS, for his lifetime contributions to investigation, management, mentorship, and community service in the field of stroke inequities. Early career investigators were provided with travel awards to attend the symposium; presented their research at moderated poster and Think Tank sessions; received career development advice at the Building Momentum session; and networked with experienced stroke inequities researchers. Future conferences-The Health Equity and Actionable Disparities in Stroke: Understanding and Problem-solving 2021 to 2024-will broaden the focus to include 5 major persistent inequities (race/ethnic, sex, geographic, socioeconomic, and global). Each year will focus on a different theme (community and stakeholder engagement; clinical trials; implementation science; and policy and dissemination). By fostering a community of stroke inequities researchers, we hope to highlight promising work, illuminate research gaps, facilitate networking, inform policy makers, recognize achievement, inspire greater interest among junior investigators to pursue careers in this field, and provide networking opportunities for underrepresented minority scientists.

The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma: IV. Local Treatment Failure and Enucleation in the First 5 Years after Brachytherapy. COMS Report No. 19.

OBJECTIVE: To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I125) brachytherapy in patients with choroidal melanoma treated and followed up in a large randomized clinical trial. DESIGN: Prospective, noncomparative, interventional case series within a randomized, multicenter clinical trial. PARTICIPANTS: Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) trial of enucleation versus brachytherapy between February 1987 and July 1998; tumors measured 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal dimension. METHODS: I125 brachytherapy was administered via episcleral plaque according to a standard protocol. Follow-up ophthalmic evaluations, including ophthalmic ultrasound and fundus photography, were performed according to a standard protocol at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Survival analysis methods were used to estimate the cumulative risk of postirradiation treatment failure and enucleation. Factors associated with treatment failure and enucleation of plaqued eyes were evaluated using Cox proportional hazards analysis. MAIN OUTCOME MEASURES: Reports of enucleation and of local treatment failure, defined as tumor growth, recurrence, or extrascleral extension, derived from clinical reports based on echographic and photographic documentation. RESULTS: As of September 30, 2000, 638 of the 650 patients randomized to brachytherapy and so treated had been followed up for 1 year or longer, and 411 had been followed up for at least 5 years. Sixty-nine eyes were enucleated during the first 5 years after brachytherapy, and treatment failure was reported for 57 eyes. The Kaplan-Meier estimate of proportion of patients undergoing enucleation by 5 years was 12.5% (95% confidence interval [CI], 10.0%-15.6%); the risk of treatment failure was 10.3% (95% CI, 8.0%-13.2%). Treatment failure was the most common reason for enucleation within 3 years of treatment; beyond 3 years, ocular pain was most common. Risk factors for enucleation were greater tumor thickness, closer proximity of the posterior tumor border to the foveal avascular zone, and poorer baseline visual acuity in the affected eye. Risk factors for treatment failure were older age, greater tumor thickness, and proximity of the tumor to the foveal avascular zone. Local treatment failure was associated weakly with reduced survival after controlling for baseline tumor and personal characteristics (adjusted risk ratio, 1.5; P = 0.08). CONCLUSIONS: Local treatment failure and enucleation were relatively infrequent events after I125 brachytherapy within the COMS. Treatment failure typically occurred early and was associated weakly with poorer survival. The COMS randomized trial documented the absence of a clinically or statistically significant difference in survival for patients randomly assigned to enucleation versus brachytherapy. This analysis documents the efficacy of brachytherapy to achieve sustained local tumor control and to conserve the globe.

Sleep for Stroke Management and Recovery Trial (Sleep SMART): Rationale and methods.

RATIONALE: Obstructive sleep apnea is common among patients with acute ischemic stroke and is associated with reduced functional recovery and an increased risk for recurrent vascular events. AIMS AND/OR HYPOTHESIS: The Sleep for Stroke Management and Recovery Trial (Sleep SMART) aims to determine whether automatically adjusting continuous positive airway pressure (aCPAP) treatment for obstructive sleep apnea improves clinical outcomes after acute ischemic stroke or high-risk transient ischemic attack. SAMPLE SIZE ESTIMATE: A total of 3062 randomized subjects for the prevention of recurrent serious vascular events, and among these, 1362 stroke survivors for the recovery outcome. METHODS AND DESIGN: Sleep SMART is a phase III, multicenter, prospective randomized, open, blinded outcome event assessed controlled trial. Adults with recent acute ischemic stroke/transient ischemic attack and no contraindication to aCPAP are screened for obstructive sleep apnea with a portable sleep apnea test. Subjects with confirmed obstructive sleep apnea but without predominant central sleep apnea proceed to a run-in night of aCPAP. Subjects with use (≥4 h) of aCPAP and without development of significant central apneas are randomized to aCPAP plus usual care or care-as-usual for six months. Telemedicine is used to monitor and facilitate aCPAP adherence remotely. STUDY OUTCOMES: Two separate primary outcomes: (1) the composite of recurrent acute ischemic stroke, acute coronary syndrome, and all-cause mortality (prevention) and (2) the modified Rankin scale scores (recovery) at six- and three-month post-randomization, respectively. DISCUSSION: Sleep SMART represents the first large trial to test whether aCPAP for obstructive sleep apnea after stroke/transient ischemic attack reduces recurrent vascular events or death, and improves functional recovery.

Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions.

Importance: The effect of intensive blood pressure lowering on brain health remains uncertain. Objective: To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes. Design, Setting, and Participants: A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016. Interventions: Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315). Main Outcomes and Measures: The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome. Results: Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, -0.54 cm3 [95% CI, -0.87 to -0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 [95% CI, -32.3 to -28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, -3.7 cm3 [95% CI, -6.3 to -1.1]). Conclusions and Relevance: Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Deferoxamine mesylate in patients with intracerebral haemorrhage (i-DEF): a multicentre, randomised, placebo-controlled, double-blind phase 2 trial.

BACKGROUND: Iron from haemolysed blood is implicated in secondary injury after intracerebral haemorrhage. We aimed to assess the safety of the iron chelator deferoxamine mesylate in patients with intracerebral haemorrhage and to establish whether the drug merits investigation in a phase 3 trial. METHODS: We did a multicentre, futility-design, randomised, placebo-controlled, double-blind, phase 2 trial at 40 hospitals in Canada and the USA. Adults aged 18-80 years with primary, spontaneous, supratentorial intracerebral haemorrhage were randomly assigned (1:1) to receive deferoxamine mesylate (32 mg/kg per day) or placebo (saline) infusions for 3 consecutive days within 24 h of haemorrhage onset. Randomisation was done via a web-based trial-management system centrally in real time, and treatment allocation was concealed from both participants and investigators. The primary outcome was good clinical outcome, which was defined as a modified Rankin Scale score of 0-2 at day 90. We did a futility analysis: if the 90% upper confidence bound of the absolute risk difference between the two groups in the proportion of participants with a good clinical outcome was less than 12% in favour of deferoxamine mesylate, then to move to a phase 3 efficacy trial would be futile. Primary outcome and safety data were analysed in the modified intention-to-treat population, comprising only participants in whom the study infusions were initiated. This trial is registered with ClinicalTrials.gov, number NCT02175225, and is completed. FINDINGS: We recruited 294 participants between Nov 23, 2014, and Nov 10, 2017. The modified intention-to-treat population consisted of 144 patients assigned to the deferoxamine mesylate group and 147 assigned to the placebo group. At day 90, among patients with available data for the primary outcome, 48 (34%) of 140 participants in the deferoxamine mesylate group, and 47 (33%) of 143 patients in the placebo group, had modified Rankin Scale scores of 0-2 (adjusted absolute risk difference 0·6% [90% upper confidence bound 6·8%]). By day 90, 70 serious adverse events were reported in 39 (27%) of 144 patients in the deferoxamine mesylate group, and 78 serious adverse events were reported in 49 (33%) of 147 patients in the placebo group. Ten (7%) participants in the deferoxamine mesylate and 11 (7%) in the placebo group died. None of the deaths were judged to be treatment related. INTERPRETATION: Deferoxamine mesylate was safe. However, the primary result showed that further study of the efficacy of deferoxamine mesylate with anticipation that the drug would significantly improve the chance of good clinical outcome (ie, mRS score of 0-2) at day 90 would be futile. FUNDING: US National Institutes of Health and US National Institute of Neurological Disorders and Stroke.

Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial.

Importance: There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia. Objective: To evaluate the effect of intensive blood pressure control on risk of dementia. Design, Setting, and Participants: Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018. Interventions: Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures: The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia. Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97). Conclusions and Relevance: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods.

RATIONALE: Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion of cryptogenic strokes. AIMS: The aim of the ARCADIA trial is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy. SAMPLE SIZE ESTIMATE: 1100 participants. METHODS AND DESIGN: Biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial conducted at 120 U.S. centers participating in NIH StrokeNet. POPULATION STUDIED: Patients ≥ 45 years of age with embolic stroke of undetermined source and evidence of atrial cardiopathy, defined as ≥ 1 of the following markers: P-wave terminal force >5000 µV × ms in ECG lead V1, serum NT-proBNP > 250 pg/mL, and left atrial diameter index ≥ 3 cm/m2 on echocardiogram. Exclusion criteria include any atrial fibrillation, a definite indication or contraindication to antiplatelet or anticoagulant therapy, or a clinically significant bleeding diathesis. Intervention: Apixaban 5 mg twice daily versus aspirin 81 mg once daily. Analysis: Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation. STUDY OUTCOMES: The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage. DISCUSSION: ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation.

Sex and Race Differences in the Association of Incident Ischemic Stroke With Risk Factors.

Importance: Race-specific and sex-specific stroke risk varies across the lifespan, yet few reports describe sex differences in stroke risk separately in black individuals and white individuals. Objective: To examine incidence and risk factors for ischemic stroke by sex for black and white individuals. Design, Setting, and Participants: This prospective cohort study included participants 45 years and older who were stroke-free from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, enrolled from the continental United States 2003 through 2007 with follow-up through October 2016. Data were analyzed from March 2018 to September 2018. Exposures: Sex and race. Main Outcomes and Measures: Physician-adjudicated incident ischemic stroke, self-reported race/ethnicity, and measured and self-reported risk factors. Results: A total of 25 789 participants (14 170 women [54.9%]; 10 301 black individuals [39.9%]) were included. Over 222 120 person-years of follow-up, 939 ischemic strokes occurred: 159 (16.9%) in black men, 326 in white men (34.7%), 217 in black women (23.1%), and 237 in white women (25.2%). Between 45 and 64 years of age, white women had 32% lower stroke risk than white men (incidence rate ratio [IRR], 0.68 [95% CI, 0.49-0.94]), and black women had a 28% lower risk than black men (IRR, 0.72 [95% CI, 0.52-0.99]). Lower stroke risk in women than men persisted at age 65 through 74 years in white individuals (IRR, 0.71 [95% CI, 0.55-0.94]) but not in black individuals (IRR, 0.94 [95% CI, 0.68-1.30]); however, the race-sex interaction was not significant. At 75 years and older, there was no sex difference in stroke risk for either race. For white individuals, associations of systolic blood pressure (women: hazard ratio [HR], 1.13 [95% CI, 1.05-1.22]; men: 1.04 [95% CI, 0.97-1.11]; P = .099), diabetes (women: HR, 1.84 [95% CI, 1.35-2.52]; men: 1.13 [95% CI, 0.86-1.49]; P = .02), and heart disease (women: HR, 1.76 [95% CI, 1.30-2.39]; men, 1.26 [95% CI, 0.99-1.60]; P = .09) with stroke risk were larger for women than men, while antihypertensive medication use had a smaller association in women than men (women: HR, 1.17 [95% CI, 0.89-1.54]; men: 1.61 [95% CI, 1.29-2.03]; P = .08). In black individuals, there was no evidence of a sex difference for any risk factors. Conclusions and Relevance: For both races, at age 45 through 64 years, women were at lower stroke risk than men, and there was no sex difference at 75 years or older; however, the sex difference pattern may differ by race from age 65 through 74 years. The association of risk factors on stroke risk differed by race-sex groups. While the need for primordial prevention, optimal management, and control of risk factors is universal across all age, racial/ethnic, and sex groups, some demographic subgroups may require earlier and more aggressive strategies.

Association of Clinical and Social Factors With Excess Hypertension Risk in Black Compared With White US Adults.

Importance: The high prevalence of hypertension among the US black population is a major contributor to disparities in life expectancy; however, the causes for higher incidence of hypertension among black adults are unknown. Objective: To evaluate potential factors associated with higher risk of incident hypertension among black adults. Design, Setting, and Participants: Prospective cohort study of black and white adults selected from a longitudinal cohort study of 30 239 participants as not having hypertension at baseline (2003-2007) and participating in a follow-up visit 9.4 years (median) later. Exposures: There were 12 clinical and social factors, including score for the Southern diet (range, -4.5 to 8.2; higher values reflect higher level of adherence to the dietary pattern), including higher fried and related food intake. Main Outcomes and Measures: Incident hypertension (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or use of antihypertensive medications) at the follow-up visit. Results: Of 6897 participants (mean [SD] age, 62 [8] years; 26% were black adults; and 55% were women), 46% of black participants and 33% of white participants developed hypertension. Black men had an adjusted mean Southern diet score of 0.81 (95% CI, 0.72 to 0.90); white men, -0.26 (95% CI, -0.31 to -0.21); black women, 0.27 (95% CI, 0.20 to 0.33); and white women, -0.57 (95% CI, -0.61 to -0.54). The Southern diet score was significantly associated with incident hypertension for men (odds ratio [OR], 1.16 per 1 SD [95% CI, 1.06 to 1.27]; incidence of 32.4% at the 25th percentile and 36.1% at the 75th percentile; difference, 3.7% [95% CI, 1.4% to 6.2%]) and women (OR, 1.17 per 1 SD [95% CI, 1.08 to 1.28]; incidence of 31.0% at the 25th percentile and 34.8% at the 75th percentile; difference, 3.8% [95% CI, 1.5% to 5.8%]). The Southern dietary pattern was the largest mediating factor for differences in the incidence of hypertension, accounting for 51.6% (95% CI, 18.8% to 84.4%) of the excess risk among black men and 29.2% (95% CI, 13.4% to 44.9%) of the excess risk among black women. Among black men, a higher dietary ratio of sodium to potassium and an education level of high school graduate or less each mediated 12.3% of the excess risk of incident hypertension. Among black women, higher body mass index mediated 18.3% of the excess risk; a larger waist, 15.2%; less adherence to the Dietary Approaches to Stop Hypertension diet, 11.2%; income level of $35 000 or less, 9.3%; higher dietary ratio of sodium to potassium, 6.8%; and an education level of high school graduate or less, 4.1%. Conclusions and Relevance: In a mediation analysis comparing incident hypertension among black adults vs white adults in the United States, key factors statistically mediating the racial difference for both men and women included Southern diet score, dietary ratio of sodium to potassium, and education level. Among women, waist circumference and body mass index also were key factors.

Blood Pressure-Attained Analysis of ATACH 2 Trial.

BACKGROUND AND PURPOSE: We compared the rates of death or disability, defined by modified Rankin Scale score of 4 to 6, at 3 months in patients with intracerebral hemorrhage according to post-treatment systolic blood pressure (SBP)-attained status. METHODS: We divided 1000 subjects with SBP ≥180 mm Hg who were randomized within 4.5 hours of symptom onset as follows: SBP <140 mm Hg achieved or not achieved within 2 hours; subjects in whom SBP <140 mm Hg was achieved within 2 hours were further divided: SBP <140 mm Hg for 21 to 22 hours (reduced and maintained) or SBP was ≥140 mm Hg for at least 2 hours during the period between 2 and 24 hours (reduced but not maintained). RESULTS: Compared with subjects without reduction of SBP <140 mm Hg within 2 hours, subjects with reduction and maintenance of SBP <140 mm Hg within 2 hours had a similar rate of death or disability (relative risk of 0.98; 95% confidence interval, 0.74-1.29). The rates of neurological deterioration within 24 hours were significantly higher in reduced and maintained group (10.4%; relative risk, 1.98; 95% confidence interval, 1.08-3.62) and in reduced but not maintained group (11.5%; relative risk, 2.08; 95% confidence interval, 1.15-3.75) compared with reference group. The rates of cardiac-related adverse events within 7 days were higher among subjects with reduction and maintenance of SBP <140 mmHg compared to subjects without reduction (11.2% versus 6.4%). CONCLUSIONS: No decline in death or disability but higher rates of neurological deterioration and cardiac-related adverse events were observed among intracerebral hemorrhage subjects with reduction with and without maintenance of intensive SBP goals. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01176565.

Estimated 24-Hour Urinary Sodium and Potassium Excretion in US Adults.

Importance: In 2010, the Institute of Medicine (now the National Academy of Medicine) recommended collecting 24-hour urine to estimate US sodium intake because previous studies indicated 90% of sodium consumed was excreted in urine. Objective: To estimate mean population sodium intake and describe urinary potassium excretion among US adults. Design, Setting, and Participants: In a nationally representative cross-sectional survey of the US noninstitutionalized population, 827 of 1103 (75%) randomly selected, nonpregnant participants aged 20 to 69 years in the examination component of the National Health and Nutrition Examination Survey (NHANES) collected at least one 24-hour urine specimen in 2014. The overall survey response rate for the 24-hour urine collection was approximately 50% (75% [24-hour urine component response rate] × 66% [examination component response rate]). Exposures: 24-hour collection of urine. Main Outcomes and Measures: Mean 24-hour urinary sodium and potassium excretion. Weighted national estimates of demographic and health characteristics and mean electrolyte excretion accounting for the complex survey design, selection probabilities, and nonresponse. Results: The study sample (n = 827) represented a population of whom 48.8% were men; 63.7% were non-Hispanic white, 15.8% Hispanic, 11.9% non-Hispanic black, and 5.6% non-Hispanic Asian; 43.5% had hypertension (according to 2017 hypertension guidelines); and 10.0% reported a diagnosis of diabetes. Overall mean 24-hour urinary sodium excretion was 3608 mg (95% CI, 3414-3803). The overall median was 3320 mg (interquartile range, 2308-4524). In secondary analyses by sex, mean sodium excretion was 4205 mg (95% CI, 3959-4452) in men (n = 421) and 3039 mg (95% CI, 2844-3234) in women (n = 406). By age group, mean sodium excretion was 3699 mg (95% CI, 3449-3949) in adults aged 20 to 44 years (n = 432) and 3507 mg (95% CI, 3266-3748) in adults aged 45 to 69 years (n = 395). Overall mean 24-hour urinary potassium excretion was 2155 mg (95% CI, 2030-2280); by sex, 2399 mg (95% CI, 2253-2545) in men and 1922 mg (95% CI, 1757-2086) in women; and by age, 1986 mg (95% CI, 1878-2094) in adults aged 20 to 44 years and 2343 mg (95% CI, 2151-2534) in adults aged 45 to 69 years. Conclusions and Relevance: In cross-sectional data from a 2014 sample of US adults, estimated mean sodium intake was 3608 mg per day. The findings provide a benchmark for future studies.

Alcohol Consumption and Incident Stroke Among Older Adults.

Objectives: This study examines the relationship between alcohol consumption and incident stroke among older adults and tests whether alcohol consumption contributes to observed race and sex differences in stroke. Method: Data are from a U.S. national cohort of black and white adults aged 45 and older, the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Current and past drinking levels were reported at baseline (2003-2007). Participants who had never had a stroke were followed for adjudicated stroke events through September 2015 (n = 27,265). We calculated Cox proportional hazard models for stroke, adjusting for demographic, socioeconomic, behavioral, and health characteristics. Results: Participants, mean age 64.7 years, consumed on average 2.2 drinks/week and experienced 1,140 first-time stroke events over median 9.1 years follow-up. Nondrinkers had a 12% higher risk of stroke than current drinkers; the risk of stroke among nondrinkers largely reflected high risks among past drinkers; these differences were explained by socioeconomic characteristics. Among current drinkers, light drinkers had significantly lower stroke risks than moderate drinkers after accounting for demographic, socioeconomic, behavioral, and health characteristics. Implications of alcohol did not differ between blacks and whites but did differ by sex: Especially among women, nondrinkers, and specifically past drinkers, had higher risks; these differences were largely explained by health characteristics and behaviors. Alcohol did not explain race and sex differences in stroke incidence. Discussion: Among older adults, those who used to, but no longer, drink had higher risks of stroke, especially among women; current light drinkers had the lowest risk of stroke.

Alzheimer's Disease-Related Dementias Summit 2016: National research priorities.

Goal 1 of the National Plan to Address Alzheimer's Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease-related dementias by 2025. To help inform the research agenda toward achieving this goal, the NIH hosts periodic summits that set and refine relevant research priorities for the subsequent 5 to 10 years. This proceedings article summarizes the 2016 Alzheimer's Disease-Related Dementias Summit, including discussion of scientific progress, challenges, and opportunities in major areas of dementia research, including mixed-etiology dementias, Lewy body dementia, frontotemporal degeneration, vascular contributions to cognitive impairment and dementia, dementia disparities, and dementia nomenclature.

Functional impairments for outcomes in a randomized trial of unruptured brain AVMs.

OBJECTIVE: To investigate the effects of medical vs interventional management on functional outcome in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA). METHODS: We used the initial results of a nonblinded, randomized, controlled, parallel-group trial involving adults ≥18 years of age with an unruptured brain arteriovenous malformation (AVM) to compare the effects of medical management (MM) with or without interventional therapy (IT) on functional impairment, defined by a primary outcome of death or symptomatic stroke causing modified Rankin Scale (mRS) score ≥2. ARUBA closed recruitment on April 15, 2013. RESULTS: After a median of 33.3 months of follow-up (interquartile range 16.3-49.8 months), of the 223 enrolled in the trial, those in the MM arm were less likely to experience primary outcomes with an mRS score ≥2 than those who underwent IT. The results applied for both those as randomized (MM n = 109 vs IT n = 114) (hazard ratio [HR] 0.25, 95% confidence interval [CI] 0.11-0.57, p = 0.001) and as treated (MM n = 125 vs IT n = 98) (HR 0.10, 95% CI 0.04-0.28, p < 0.001). Functional impairment for the outcomes showed no significant difference by Spetzler-Martin grade for MM but was more frequent with increasing grades for IT (p < 0.001). CONCLUSION: Death or stroke with functional impairment in ARUBA after a median follow-up of 33 months was significantly lower for those in the MM arm both as randomized and as treated compared with those with IT. Functional severity of outcomes was lower in the MM arm, regardless of Spetzler-Martin grades. CLINICALTRIALSGOV IDENTIFIER: NCT00389181. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for adults with unruptured brain AVMs, interventional management compared to MM increases the risk of disability and death over ≈3 years.

Carotid revascularization and medical management for asymptomatic carotid stenosis: Protocol of the CREST-2 clinical trials.

Rationale Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeons reduced stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in medical prevention of stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization. Aim Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test whether carotid endarterectomy or carotid stenting plus contemporary intensive medical therapy is superior to intensive medical therapy alone in the primary prevention of stroke in patients with high-grade asymptomatic carotid stenosis. Methods and design CREST-2 is two multicenter randomized trials of revascularization plus intensive medical therapy versus intensive medical therapy alone. One trial randomizes patients to carotid endarterectomy plus intensive medical therapy versus intensive medical therapy alone; the other, to carotid stenting plus intensive medical therapy versus intensive medical therapy alone. The risk factor targets of centrally directed intensive medical therapy are LDL cholesterol <70 mg/dl and systolic blood pressure <140 mmHg. Study outcomes The primary outcome is the composite of stroke and death within 44 days following randomization and stroke ipsilateral to the target vessel thereafter, up to four years. Change in cognition and differences in major and minor stroke are secondary outcomes. Sample size Enrollment of 1240 patients in each trial provides 85% power to detect a treatment difference if the event rate in the intensive medical therapy alone arm is 4.8% higher or 2.8% lower than an anticipated 3.6% rate in the revascularization arm. Discussion Management of asymptomatic carotid stenosis requires contemporary randomized trials to address whether carotid endarterectomy or carotid stenting plus intensive medical therapy is superior in preventing stroke beyond intensive medical therapy alone. Whether carotid endarterectomy or carotid stenting has favorable effects on cognition will also be tested. Trial registration United States National Institutes of Health Clinicaltrials.gov NCT02089217.

Self-Reported Stroke Risk Stratification: Reasons for Geographic and Racial Differences in Stroke Study.

BACKGROUND AND PURPOSE: The standard for stroke risk stratification is the Framingham Stroke Risk Function (FSRF), an equation requiring an examination for blood pressure assessment, venipuncture for glucose assessment, and ECG to determine atrial fibrillation and heart disease. We assess a self-reported stroke risk function (SRSRF) to stratify stroke risk in comparison to the FSRF. METHODS: Participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) were evaluated at baseline and followed for incident stroke. The FSRF was calculated using directly assessed stroke risk factors. The SRSRF was calculated from 13 self-reported questions to exclude those with prevalent stroke and assess stroke risk. Proportional hazards analysis was used to assess incident stroke risk using the FSRF and SRSRF. RESULTS: Over an average 8.2-year follow-up, 939 of 23 983 participants had a stroke. The FSRF and SRSRF produced highly correlated risk scores (rSpearman=0.852; 95% confidence interval, 0.849-0.856); however, the SRSRF had higher discrimination of stroke risk than the FSRF (cSRSRF=0.7266; 95% confidence interval, 0.7076-0.7457; cFSRF=0.7075; 95% confidence interval, 0.6877-0.7273; P=0.0038). The 10-year stroke risk in the highest decile of predicted risk was 11.1% for the FSRF and 13.4% for the SRSRF. CONCLUSIONS: A simple self-reported questionnaire can be used to identify those at high risk for stroke better than the gold standard FSRF. This instrument can be used clinically to easily identify individuals at high risk for stroke and also scientifically to identify a subpopulation enriched for stroke risk.