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IMPORTANCE: Claims data with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes are routinely used in clinical research. However, the use of ICD-10 codes to define incident stroke has not been validated against expert-adjudicated outcomes in the US population. OBJECTIVE: To develop and validate the accuracy of an ICD-10 code list to detect incident stroke events using Medicare inpatient fee-for-service claims data. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 2 prospective population-based cohort studies, the Atherosclerosis Risk in Communities (ARIC) study and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, and included participants aged 65 years or older without prior stroke who had linked Medicare claims data. Stroke events in the ARIC and REGARDS studies were identified via active surveillance and adjudicated by expert review. Medicare-linked ARIC data (2016-2018) were used to develop a list of ICD-10 codes for incident stroke detection. The list was validated using Medicare-linked REGARDS data (2016-2019). Data were analyzed from September 1, 2022, through September 30, 2023. EXPOSURES: Stroke events detected in Medicare claims vs expert-adjudicated stroke events in the ARIC and REGARDS studies. MAIN OUTCOMES AND MEASURES: The main outcomes were sensitivity and specificity of incident stroke detection using ICD-10 codes. RESULTS: In the ARIC study, there were 110 adjudicated incident stroke events among 5194 participants (mean [SD] age, 80.1 [5.3] years) over a median follow-up of 3.0 (range, 0.003-3.0) years. Most ARIC participants were women (3160 [60.8%]); 993 (19.1%) were Black and 4180 (80.5%) were White. Using the primary diagnosis code on a Medicare billing claim, the ICD-10 code list had a sensitivity of 81.8% (95% CI, 73.3%-88.5%) and a specificity of 99.1% (95% CI, 98.8%-99.3%) to detect incident stroke. Using any diagnosis code on a Medicare billing claim, the sensitivity was 94.5% (95% CI, 88.5%-98.0%) and the specificity was 98.4% (95% CI, 98.0%-98.8%). In the REGARDS study, there were 140 adjudicated incident strokes among 6359 participants (mean [SD] age, 75.8 [7.0] years) over a median follow-up of 4.0 (range, 0-4.0) years. More than half of the REGARDS participants were women (3351 [52.7%]); 1774 (27.9%) were Black and 4585 (72.1%) were White. For the primary diagnosis code, the ICD-10 code list had a sensitivity of 70.7% (95% CI, 63.2%-78.3%) and a specificity of 99.1% (95% CI, 98.9%-99.4%). For any diagnosis code, the ICD-10 code list had a sensitivity of 77.9% (95% CI, 71.0%-84.7%) and a specificity of 98.9% (95% CI, 98.6%-99.2%). CONCLUSIONS AND RELEVANCE: These findings suggest that ICD-10 codes could be used to identify incident stroke events in Medicare claims with moderate sensitivity and high specificity.

Multiple challenges confront procedural trials, including slow enrollment, lack of equipoise among patients and physicians, and failure to achieve adequate masking. Nonetheless, randomized clinical trials provide the best evidence of efficacy. The evolution of technology, techniques, and standards of care during the conduct of procedural trials challenges external validity. In this study, we review how a multicenter trial of revascularization of asymptomatic carotid arteries for stroke prevention has managed changes in treating carotid stenosis and medical management of atherothrombotic disease.

The recently published SPACE-2 trial (Stent-Supported Percutaneous Angioplasty of the Carotid Artery Versus Endarterectomy-2) compared 3 treatments to prevent stroke in patients with asymptomatic carotid stenosis ≥70%: (1) carotid endarterectomy plus best medical treatment (BMT), (2) transfemoral carotid artery stenting plus BMT, or (3) BMT alone. Because of low enrollment, the findings of similar safety and efficacy for carotid endarterectomy, carotid artery stenting, or BMT alone were inconclusive. Publication of the CREST (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial)-2 results should provide level A evidence that has been lacking for 2 to 3 decades, to guide treatment of asymptomatic patients with severe carotid stenosis. For symptomatic patients with ≥70% stenosis, no trials are underway to update the degree of benefit reported for carotid endarterectomy by NASCET (North American Carotid Endarterectomy Trial) and ECST (European Carotid Surgery Trial), published in 1991. Subsequently, the use of cigarettes has plummeted, and major improvements in medical treatments and in carotid revascularization have emerged. These advances have coincided with abrupt decline in the clinical end points necessary for treatment comparisons in procedural trials. One of the advances in the invasive management of carotid disease has been transcarotid artery revascularization, already with limited approval by the US Food and Drug Administration. Establishing safety and efficacy of transcarotid artery revascularization compared with carotid endarterectomy, carotid artery stenting, or BMT alone may be challenging because of enrollment, regulatory, and funding barriers to design and complete an adequately powered randomized trial.

ObjectivesWork schedule demands contribute to circadian disruption and may influence health via an inflammatory response. We examined the impact of shiftwork and long work hours on inflammation in a national US sample.MethodsParticipants included 12 487 employed black and white men and women aged ≥45 years enrolled in the REasons for Geographic and Racial Differences in Stroke Study who completed an occupational questionnaire (2011–2013) and clinical examination (2013–2016). Cross-sectional associations between shiftwork and work hours with log-transformed high-sensitivity C reactive protein (CRP) and white blood cell (WBC) count were examined by multiple linear regression analysis, overall and by race–sex subgroups.ResultsOverall, rotating shift workers had higher log-CRP concentration compared with day workers (β=0.09, 95% CI:0.02 to 0.16) and findings for WBC were null. Black women had the highest geometric mean CRP (2.82 mg/L), while white men had the highest WBC (6.35×109/L). White men who worked afternoons had higher log-CRP compared with those who worked days (β=0.20, 95% CI: 0.08 to 0.33). Black men engaged in shiftwork <10 years working ≥55 hours/week had higher log-CRP and log-WBC compared with those working days <55 hours/week (β=0.33, 95% CI: 0.02 to 0.64 and β=0.10, 95% CI: 0.003 to 0.19). Among shift workers, non-retired white women working forward and backward shift rotations had higher log-CRP compared with those working forward only (β=0.49, 95% CI: 0.02 to 0.96).ConclusionsShift workers had higher inflammatory markers compared with day workers and race–sex disparities should be examined further. These findings highlight a potential biological pathway linking work schedule demands and chronic disease.

OBJECTIVE--T0 investigate temporal improvements in blood pressure (BP) control in subjects with diabetes and policy changes regarding generic antihypertensives. RESEARCH DESIGN AND METHODS--In a cross-sectional study we used logistic regression [...]

OBJECTIVE--Stroke symptoms among individuals reporting no physician diagnosis of stroke are associated with an increased risk of future stroke. Few studies have assessed whether individuals with diabetes or prediabetes, but [...]

OBJECTIVE--Despite widespread dissemination of target values, achieving a blood pressure of < 130/80 mmHg is challenging for many individuals with diabetes. The purpose of the present study was to examine [...]

BackgroundThe joint associations of total and intensity-specific physical activity with obesity in relation to all-cause mortality risk are unclear.MethodsWe included 34 492 adults (72% women, median age 62.1 years, 2034 deaths during follow-up) in a harmonised meta-analysis of eight population-based prospective cohort studies with mean follow-up ranging from 6.0 to 14.5 years. Standard body mass index categories were cross-classified with sample tertiles of device-measured total, light-to-vigorous and moderate-to-vigorous physical activity and sedentary time. In five cohorts with waist circumference available, high and low waist circumference was combined with tertiles of moderate-to-vigorous physical activity.ResultsThere was an inverse dose–response relationship between higher levels of total and intensity-specific physical activity and mortality risk in those who were normal weight and overweight. In individuals with obesity, the inverse dose–response relationship was only observed for total physical activity. Similarly, lower levels of sedentary time were associated with lower mortality risk in normal weight and overweight individuals but there was no association between sedentary time and risk of mortality in those who were obese. Compared with the obese-low total physical activity reference, the HRs were 0.59 (95% CI 0.44 to 0.79) for normal weight-high total activity and 0.67 (95% CI 0.48 to 0.94) for obese-high total activity. In contrast, normal weight-low total physical activity was associated with a higher risk of mortality compared with the obese-low total physical activity reference (1.28; 95% CI 0.99 to 1.67).ConclusionsHigher levels of physical activity were associated with lower risk of mortality irrespective of weight status. Compared with obesity-low physical activity, there was no survival benefit of being normal weight if physical activity levels were low.

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Disparities are differences in health outcomes among groups that originate from sources including historically experienced social injustice and broadly defined environmental exposures. Large health disparities exist, defined by many factors including race/ethnicity, sex, age, geography, and socioeconomic status. Studying disparities relies on measures of disease burden. Traditional measures, such as mortality, may be less applicable to neurological disorders, which often lead to substantial morbidity and lower quality of life, without necessarily causing death. Measures such as disability-adjusted life-years or healthy life expectancy may be more appropriate for assessing neurological disease and permit comparisons across diseases and communities. There are many approaches that can be used to study disparities. Analyses of population-based observational studies, patient registries, and administrative data all contribute to the understanding of disparities in humans. Animal and other experimental designs, including clinical trials, may be used to identify mechanisms and strategies to reduce disparities. All of these approaches have strengths and weaknesses. Ultimately, understanding and mitigating disparities will require use of all of these methods. Crucially, a focus on not only improving outcomes among all individuals in society but minimizing or eliminating differences between those with better outcomes and those who have historically been disadvantaged should drive the ongoing investigations into disparities. This review is focused on epidemiological approaches to examining the depth and determinants of racial-ethnic disparities in the United States related to stroke, stroke care, and stroke outcomes.

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IMPORTANCE: Intracerebral hemorrhage and arterial ischemic disease share risk factors, to our knowledge, but the association between the 2 conditions remains unknown. OBJECTIVE: To evaluate whether intracerebral hemorrhage was associated with an increased risk of incident ischemic stroke and myocardial infarction. DESIGN, SETTING, AND PARTICIPANTS: An analysis was conducted of pooled longitudinal participant-level data from 4 population-based cohort studies in the United States: the Atherosclerosis Risk in Communities (ARIC) study, the Cardiovascular Health Study (CHS), the Northern Manhattan Study (NOMAS), and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Patients were enrolled from 1987 to 2007, and the last available follow-up was December 31, 2018. Data were analyzed from September 1, 2019, to March 31, 2020. EXPOSURE: Intracerebral hemorrhage, as assessed by an adjudication committee based on predefined clinical and radiologic criteria. MAIN OUTCOMES AND MEASURES: The primary outcome was an arterial ischemic event, defined as a composite of ischemic stroke or myocardial infarction, centrally adjudicated within each study. Secondary outcomes were ischemic stroke and myocardial infarction. Participants with prevalent intracerebral hemorrhage, ischemic stroke, or myocardial infarction at their baseline study visit were excluded. Cox proportional hazards regression was used to examine the association between intracerebral hemorrhage and subsequent arterial ischemic events after adjustment for baseline age, sex, race/ethnicity, vascular comorbidities, and antithrombotic medications. RESULTS: Of 55 131 participants, 47 866 (27 639 women [57.7%]; mean [SD] age, 62.2 [10.2] years) were eligible for analysis. During a median follow-up of 12.7 years (interquartile range, 7.7-19.5 years), there were 318 intracerebral hemorrhages and 7648 arterial ischemic events. The incidence of an arterial ischemic event was 3.6 events per 100 person-years (95% CI, 2.7-5.0 events per 100 person-years) after intracerebral hemorrhage vs 1.1 events per 100 person-years (95% CI, 1.1-1.2 events per 100 person-years) among those without intracerebral hemorrhage. In adjusted models, intracerebral hemorrhage was associated with arterial ischemic events (hazard ratio [HR], 2.3; 95% CI, 1.7-3.1), ischemic stroke (HR, 3.1; 95% CI, 2.1-4.5), and myocardial infarction (HR, 1.9; 95% CI, 1.2-2.9). In sensitivity analyses, intracerebral hemorrhage was associated with arterial ischemic events when updating covariates in a time-varying manner (HR, 2.2; 95% CI, 1.6-3.0); when using incidence density matching (odds ratio, 2.3; 95% CI, 1.3-4.2); when including participants with prevalent intracerebral hemorrhage, ischemic stroke, or myocardial infarction (HR, 2.2; 95% CI, 1.6-2.9); and when using death as a competing risk (subdistribution HR, 1.6; 95% CI, 1.1-2.1). CONCLUSIONS AND RELEVANCE: This study found that intracerebral hemorrhage was associated with an increased risk of ischemic stroke and myocardial infarction. These findings suggest that intracerebral hemorrhage may be a novel risk marker for arterial ischemic events.

IMPORTANCE: The underenrollment of women in randomized clinical trials represents a threat to the validity of the evidence supporting clinical guidelines and potential disparities in access to novel treatments. OBJECTIVE: To determine whether women were underenrolled in contemporary randomized clinical trials of acute stroke therapies published in 9 major journals after accounting for their representation in underlying stroke populations. DATA SOURCES: MEDLINE was searched for acute stroke therapeutic trials published between January 1, 2010, and June 11, 2020. STUDY SELECTION: Eligible articles reported the results of a phase 2 or 3 randomized clinical trial that enrolled patients with stroke and/or transient ischemic attack and examined a therapeutic intervention initiated within 1 month of onset. DATA EXTRACTION: Data extraction was performed by 2 independent authors in duplicate. Individual trials were matched to estimates of the proportion of women in underlying stroke populations using the Global Burden of Disease database. MAIN OUTCOMES AND MEASURES: The primary outcome was the enrollment disparity difference (EDD), the absolute difference between the proportion of trial participants who were women and the proportion of strokes in the underlying disease populations that occurred in women. Random-effects meta-analyses of the EDD were performed, and multivariable metaregression was used to explore the associations of trial eligibility criteria with disparity estimates. RESULTS: The search returned 1529 results, and 115 trials (7.5%) met inclusion criteria. Of 121 105 randomized patients for whom sex was reported, 52 522 (43.4%) were women. The random-effects summary EDD was −0.053 (95% CI, −0.065 to −0.040), indicating that women were underenrolled by 5.3 percentage points. This disparity persisted across virtually all geographic regions, intervention types, and stroke types, apart from subarachnoid hemorrhage (0.117 [95% CI, 0.084 to 0.150]). When subarachnoid hemorrhage trials were excluded, the summary EDD was −0.067 (95% CI, −0.078 to −0.057). In the multivariable metaregression analysis, an upper age limit of 80 years as an eligibility criterion was associated with a 6–percentage point decrease in the enrollment of women. CONCLUSIONS AND RELEVANCE: Further research is needed to understand the causes of the underenrollment of women in acute stroke trials. However, to maximize representation, investigators should avoid imposing age limits on enrollment.

Objective: Dietary modification of insulin resistance may be a strategy for reducing chronic disease. For this study, we tested the hypothesis that higher fasting insulin, a marker for insulin resistance, would be related to diet patterns with a high proportion of carbohydrates, those with a high glycemic index, and those characterized by added sugar and processed starches. Study design: Data were analyzed on 13,528 nondiabetic participants of the REasons for Geographic and Ethnic Differences in Stroke (REGARDS), an observational study of adults aged ≥45 years residing in 1855 counties across the continental USA. Information on habitual diet was collected using the Block 98 Food Frequency Questionnaire. Percent energy from carbohydrate, glycemic index, and glycemic load were determined for each participant, as well as adherence to five established diet patterns. Logistic regression was used to examine associations of baseline diet characteristics with odds for high fasting insulin [quartiles 3 and 4 (median = 98.9 pmol/L) vs. quartile 1], after adjusting for covariates. Result: Greater percent carbohydrate, glycemic index, and glycemic load, and adherence to sweets/fat and southern diet patterns, was associated with greater odds for high insulin (Pfor trend &lt;0.05 to &lt;0.0001), whereas adherence to the plant-based and alcohol/salad patterns was associated with lower odds for high insulin (Pfor linear trend &lt;0.0001). Conclusion: In conclusion, diet pattern is associated with fasting insulin. Future studies are needed to determine if diet interventions designed to lower insulin, perhaps based on the patterns identified in this study, can improve risk for chronic disease.

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ObjectiveTo examine the joint associations of daily time spent in different intensities of physical activity, sedentary behaviour and sleep with all-cause mortality.MethodsFederated pooled analysis of six prospective cohorts with device-measured time spent in different intensities of physical activity, sedentary behaviour and sleep following a standardised compositional Cox regression analysis.Participants130 239 people from general population samples of adults (average age 54 years) from the UK, USA and Sweden.Main outcomeAll-cause mortality (follow-up 4.3–14.5 years).ResultsStudies using wrist and hip accelerometer provided statistically different results (I2=92.2%, Q-test p<0.001). There was no association between duration of sleep and all-cause mortality, HR=0.96 (95% CI 0.67 to 1.12). The proportion of time spent in moderate to vigorous physical activity was significantly associated with lower risk of all-cause mortality (HR=0.63 (95% CI 0.55 to 0.71) wrist; HR=0.93 (95% CI 0.87 to 0.98) hip). A significant association for the ratio of time spent in light physical activity and sedentary time was only found in hip accelerometer-based studies (HR=0.5, 95% CI 0.42 to 0.62). In studies based on hip accelerometer, the association between moderate to vigorous physical activity and mortality was modified by the balance of time spent in light physical activity and sedentary time.ConclusionThis federated analysis shows a joint dose–response association between the daily balance of time spent in physical activity of different intensities and sedentary behaviour with all-cause mortality, while sleep duration does not appear to be significant. The strongest association is with time spent in moderate to vigorous physical activity, but it is modified by the balance of time spent in light physical activity relative to sedentary behaviour.

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Background and aim: Providing care to an older adult with a disability has been associated with increased risk to the caregiver’s health, but most previous studies of caregiving and health compare persons who are already caregivers with poorly matched non-caregiving controls and are often based on convenience samples. In this report, we describe the enrollment of persons who transitioned into a family caregiving role while participating in a national epidemiological study. Methods: Participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were asked on two occasions 9–14 years apart if they were providing care on an ongoing basis to a family member with a chronic illness or disability. Those who answered “no” and “yes”, respectively, to this caregiving question and reported sufficient caregiving responsibilities after their transitions were enrolled in the present study as incident caregivers (N= 251). Participants matched on multiple demographic and health history variables and who reported no history of caregiving were enrolled as non-caregiving controls (N= 251). Results: Among eligible participants, 84% agreed to participate, and 47% of caregivers reported caring for a person with dementia. Descriptive analyses confirmed the success of the matching procedures for balancing the groups on multiple demographic and pre-caregiving health variables. Depressive symptoms and perceived stress increased significantly after the transition to caregiving. Conclusion: Comparable, population-based samples of incident caregivers and matched non-caregivers have been enrolled. Future analyses will examine within-person changes in health and circulating biomarkers as a function of the transition to caregiving.

Short and long sleep duration are associated with poor health outcomes and are most prevalent among racial/ethnic minorities. Few studies have investigated the intersection of other sociodemographic characteristics with race/ethnicity on sleep duration prevalence.

IMPORTANCE: Sedentary behavior is associated with several health outcomes, including diabetes, cardiovascular disease, and all-cause mortality. Less is known about the association between objectively measured sedentary behavior and cancer mortality, as well as the association with physical activity. OBJECTIVE: To examine the association between accelerometer-measured sedentary behavior (total volume and accrual in prolonged, uninterrupted bouts) and cancer mortality. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study conducted in the contiguous US included 8002 black and white adults aged 45 years or older enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. The present analysis was performed from April 18, 2019, to April 21, 2020. EXPOSURES: Sedentary time, light-intensity physical activity (LIPA), and moderate- to vigorous-intensity physical activity (MVPA) were measured using a hip-mounted accelerometer worn for 7 consecutive days. MAIN OUTCOMES AND MEASURES: Cancer mortality. RESULTS: Of the 8002 study participants, 3668 were men (45.8%); mean (SD) age was 69.8 (8.5) years. Over a mean (SD) follow-up of 5.3 (1.5) years, 268 participants (3.3%) died of cancer. In multivariable-adjusted models, including MVPA, greater total sedentary time was associated with a greater risk of cancer mortality (tertile 2 vs tertile 1: hazard ratio [HR], 1.45; 95% CI, 1.00-2.11; tertile 3 vs tertile 1: HR, 1.52; 95% CI, 1.01-2.27). Longer sedentary bout duration was not significantly associated with greater cancer mortality risk: after adjustment for MVPA (tertile 2 vs tertile 1: HR, 1.26; 95% CI, 0.90-1.78; tertile 3 vs tertile 1: HR, 1.36; 95% CI, 0.96-1.93). Replacing 30 minutes of sedentary time with LIPA was significantly associated with an 8% (per 30 minutes: HR, 0.92; 95% CI, 0.86-0.97) lower risk of cancer mortality; MVPA was significantly associated with a 31% (per 30 minutes: HR, 0.69; 95% CI, 0.48-0.97) lower risk of cancer mortality. CONCLUSIONS AND RELEVANCE: In this cohort study, greater sedentary time, as measured with accelerometry, appeared to be independently associated with cancer mortality risk. Replacing sedentary time with either LIPA or MVPA may be associated with a lower risk of cancer mortality. These findings suggest that the total volume of sedentary behavior is a potential cancer mortality risk factor and support the public health message that adults should sit less and move more to promote longevity.

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IMPORTANCE: Stroke incidence is higher among black than white individuals in the United States. It is unclear whether black individuals have a higher risk of stroke recurrence after a minor ischemic stroke or transient ischemic attack (TIA), a high-risk setting in which focused preventive efforts can be effective. OBJECTIVE: To examine the association between black race and early ischemic stroke recurrence. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data from the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial conducted at 269 sites from May 28, 2010, to December 19, 2017. The trial enrolled 4881 adults within 12 hours of onset of a minor ischemic stroke (National Institutes of Health Stroke Scale score, 0-3) or high-risk TIA (ABCD2 score, ≥4). For this analysis, we excluded 598 patients enrolled outside the United States and 239 US patients with missing race/ethnicity data. MAIN OUTCOMES AND MEASURES: The primary outcome for this analysis was ischemic stroke within 90 days after randomization. Covariates included age, sex, Hispanic ethnicity, study assignment to take clopidogrel vs placebo, index stroke vs TIA, vascular risk factors, statin use, study drug adherence, and index event etiological subtype. RESULTS: Among 4044 patients included in the analysis, 918 (22.7%) were black. In an adjusted Cox model, black race was associated with a higher risk of recurrence compared with white race (hazard ratio, 1.6; 95% CI, 1.1-2.3). Findings were similar in subgroup analyses and in analyses limited to sites that enrolled black patients. CONCLUSIONS AND RELEVANCE: Among US participants in the POINT trial, black individuals faced a higher risk of early stroke recurrence after a minor ischemic stroke or TIA. Our findings support research into black-white racial differences in the underlying mechanisms of recurrent stroke. In the meantime, extra effort should be made to ensure that black patients have access to proven secondary prevention measures. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00991029

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The release of the American Heart Association’s 2030 Impact Goal and associated metrics for success underscores the importance of cardiovascular health and cardiovascular disease surveillance systems for the acquisition of information sufficient to support implementation and evaluation. The aim of this policy statement is to review and comment on existing recommendations for and current approaches to cardiovascular surveillance, identify gaps, and formulate policy implications and pragmatic recommendations for transforming surveillance of cardiovascular disease and cardiovascular health in the United States. The development of community platforms coupled with widespread use of digital technologies, electronic health records, and mobile health has created new opportunities that could greatly modernize surveillance if coordinated in a pragmatic matter. However, technology and public health and scientific mandates must be merged into action. We describe the action and components necessary to create the cardiovascular health and cardiovascular disease surveillance system of the future, steps in development, and challenges that federal, state, and local governments will need to address. Development of robust policies and commitment to collaboration among professional organizations, community partners, and policy makers are critical to ultimately reduce the burden of cardiovascular disease and improve cardiovascular health and to evaluate whether national health goals are achieved.

ObjectivesTo examine the joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality.MethodsWe conducted a harmonised meta-analysis including nine prospective cohort studies from four countries. 44 370 men and women were followed for 4.0 to 14.5 years during which 3451 participants died (7.8% mortality rate). Associations between different combinations of moderate-to-vigorous intensity physical activity (MVPA) and sedentary time were analysed at study level using Cox proportional hazards regression analysis and summarised using random effects meta-analysis.ResultsAcross cohorts, the average time spent sedentary ranged from 8.5 hours/day to 10.5 hours/day and 8 min/day to 35 min/day for MVPA. Compared with the referent group (highest physical activity/lowest sedentary time), the risk of death increased with lower levels of MVPA and greater amounts of sedentary time. Among those in the highest third of MVPA, the risk of death was not statistically different from the referent for those in the middle (16%; 95% CI 0.87% to 1.54%) and highest (40%; 95% CI 0.87% to 2.26%) thirds of sedentary time. Those in the lowest third of MVPA had a greater risk of death in all combinations with sedentary time; 65% (95% CI 1.25% to 2.19%), 65% (95% CI 1.24% to 2.21%) and 263% (95% CI 1.93% to 3.57%), respectively.ConclusionHigher sedentary time is associated with higher mortality in less active individuals when measured by accelerometry. About 30–40 min of MVPA per day attenuate the association between sedentary time and risk of death, which is lower than previous estimates from self-reported data.

Low educational attainment is associated with excess cancer mortality. However, the mechanisms driving this association remain unknown.

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.

IMPORTANCE: Get With The Guidelines–Stroke (GWTG-Stroke) is an American Heart Association/American Stroke Association stroke-care quality-improvement program; however, to our knowledge, there has not been a direct comparison of the quality of care between patients hospitalized at participating hospitals and those at nonparticipating hospitals. OBJECTIVE: To contrast quality of stroke care measures for patients admitted to hospitals participating and not participating in GWTG-Stroke. DESIGN, SETTING, AND PARTICIPANTS: Subpopulation of 546 participants with ischemic stroke occurring during a 9-year follow-up of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, a population-based cohort study of 30 239 randomly selected black and white participants 45 years and older recruited between 2003 and 2007. Of those with stroke, 207 (36%) were treated in a hospital participating in GWTG-Stroke and 339 in a nonparticipating hospital. Data were analyzed between July 29, 2017, and April 17, 2018. MAIN OUTCOMES AND MEASURES: Quality of care measures including use of tissue plasminogen activator, performance of swallowing evaluation, antithrombotic use in first 48 hours, lipid profile assessment, discharge receiving antithrombotic therapy, discharge receiving a statin, neurologist evaluation, providing weight loss and exercise counseling, education on stroke risk factors and warning signs, and assessment for rehabilitation. RESULTS: Participants treated at participating hospitals had a mean (SD) age of 74 (8) years and 100 of 207 were men (48%), while those seen at nonparticipating hospitals had a mean (SD) age of 73 (9) years, and 161 of 339 were men (48%). Those seen in participating hospitals were more likely to receive 5 of 10 evidence-based interventions recommended for patients hospitalized with ischemic stroke, including receiving tissue plasminogen activator (RR, 3.74; 95% CI, 1.65-8.50), education on risk factors (RR, 1.54; 95% CI, 1.16-2.05), having an evaluation for swallowing (RR, 1.25; 95% CI, 1.04-1.50), a lipid evaluation (RR, 1.18; 95% CI, 1.05-1.32), and an evaluation by a neurologist (RR, 1.12; 95% CI, 1.05-1.20). Those seen in participating hospitals received a mean of 5.4 (95% CI, 5.2-5.6) interventions compared with 4.8 (95% CI, 4.6-5.0) in nonparticipating hospitals (P &lt; .001). CONCLUSIONS AND RELEVANCE: These data collected independently of the GWTG-Stroke program document improved stroke care for patients with ischemic stroke hospitalized at participating hospitals.

To examine the association between estimated cardiorespiratory fitness (eCRF) and incident stroke by black and white race.

IMPORTANCE: Higher circulating fibroblast growth factor 23 (FGF23) concentrations are associated with cardiovascular disease events linked to heart failure, but associations of FGF23 with coronary heart disease (CHD) have been less consistent. OBJECTIVE: To determine the association of plasma FGF23 concentrations with incident CHD and whether this association differs by race, sex, or chronic kidney disease status. DESIGN, SETTING, AND PARTICIPANTS: We examined the association of FGF23 concentrations with incident CHD risk within the Reasons for Geographic and Racial Differences in Stroke study, a prospective cohort of black and white adults 45 years and older enrolled between January 2003 and October 2007 with follow-up through December 31, 2011. Using a case-cohort design, we measured FGF23 concentrations in 829 participants who developed incident CHD and in 812 participants randomly selected from the Reasons for Geographic and Racial Differences in Stroke study cohort (cohort random sample). To account for the stratified sampling design, the cohort random sample was weighted back to the original cohort overall (n = 22 127). Cox proportional hazards models were used to examine the association of FGF23 concentration with incident CHD, adjusting for CHD risk factors and kidney function. In prespecified analyses, we examined whether race, sex, or chronic kidney disease modified the association of FGF23 concentration with incident CHD. EXPOSURES: Plasma C-terminal FGF23 concentrations. MAIN OUTCOMES AND MEASURES: Investigator-adjudicated incident CHD events. RESULTS: Of the 22 127 participants in the weighted cohort random sample, 13 059 (58.9%) were female and 9435 (42.6%) were black, and the mean age was 64.3 (95% CI, 63.7-64.9) years. Greater age, lower estimated glomerular filtration rate, higher urine albumin to creatinine ratio, and female sex were associated with higher FGF23 concentration at baseline. In multivariable models adjusted for established CHD risk factors and kidney function, higher FGF23 concentrations were associated with greater risk of CHD (hazard ratio [HR] comparing fourth with first quartile, 2.15; 95% CI, 1.35-3.42). The magnitude and strength of these associations differed by sex. However, these differences were no longer observed when adjusting for hormone therapy in women (men: HR comparing fourth with first quartile, 2.40; 95% CI, 1.30-4.42; women: HR comparing fourth with first quartile, 2.34; 95% CI, 1.04-5.27) or when using sex-specific FGF23 quartiles (men: HR comparing fourth with first quartile, 2.65; 95% CI, 1.43-4.90; women: HR comparing fourth with first quartile, 2.26; 95% CI, 1.02-5.03). CONCLUSIONS AND RELEVANCE: Higher FGF23 concentrations were associated with greater risk of CHD. Heterogeneity in the association by sex may be caused by differences in the distribution of plasma FGF23 concentrations or the use of hormone therapy in men vs women.

IMPORTANCE: Recent studies have suggested that the natriuretic peptide system may be endogenously suppressed in black individuals who are free of prevalent cardiovascular disease. Whether natriuretic peptide levels contribute to racial disparities in clinical outcomes is unknown. OBJECTIVE: To examine racial differences in N-terminal pro–B-type natriuretic peptide (NTproBNP) levels and their association with all-cause mortality and cause-specific mortality in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. DESIGN, SETTING, AND PARTICIPANTS: Baseline NTproBNP levels were measured in a randomly selected sample of 4415 REGARDS study participants. Those with prevalent cardiovascular disease and renal dysfunction were excluded. From July 1, 2003, to September 12, 2007, among the remaining 1998 individuals, racial differences in NTproBNP levels were estimated, and the percentage difference in NTproBNP levels by race was meta-analyzed and compared with published results on participants free of prevalent cardiovascular disease from the Dallas Heart Study and Atherosclerosis Risk in Communities study, using random effects modeling. The association of NTproBNP levels, race, all-cause mortality, and cause-specific mortality in the REGARDS study was studied using appropriate modeling techniques. Data analysis was conducted from July 1, 2003, to March 31, 2016. MAIN OUTCOMES AND MEASURES: Racial differences in NTproBNP levels and association with all-cause mortality and cause-specific mortality. RESULTS: Among the 1998 participants studied (972 women and 1026 men; median age, 63 years [interquartile range, 54-72 years]), median NTproBNP levels in black individuals were significantly lower than those in white individuals (46 pg/mL [interquartile range, 23-91] vs 60 pg/mL [interquartile range, 33-106]; P &lt; .001). With multivariable adjustment, NTproBNP levels were up to 27% lower in black individuals as compared with white individuals (β, –0.32; 95% CI, –0.40 to –0.24; P &lt; .001) in the REGARDS study. In meta-analysis of the 3 cohorts, NTproBNP levels were 35% lower in black individuals than white individuals. Among the REGARDS study participants, for every 1-SD higher log NTproBNP, there was a 31% increased risk of death in the multivariable-adjusted model (hazard ratio, 1.31; 95% CI, 1.11-1.54). This increase was driven primarily by association of NTproBNP with cardiovascular mortality (hazard ratio, 1.69; 95% CI, 1.19-2.41). No interaction between race and NTproBNP levels was observed with all-cause mortality and cause-specific mortality. CONCLUSIONS AND RELEVANCE: Plasma NTproBNP levels are significantly lower in black individuals as compared with white individuals in the REGARDS study and in pooled results from the REGARDS study, Dallas Heart Study, and Atherosclerosis Risk in Communities study. Higher NTproBNP levels were associated with higher incidence of all-cause mortality and cardiovascular mortality in healthy black and white individuals, and this association did not differ by race.

Benefit from carotid revascularization is supposed to be lower in women due to increased periprocedural risks. The aim of this study was to investigate the risk of stroke/death after carotid intervention in women treated within 15 days from last neurological event.

In this issue of Neurology®, using a national sample from the Veterans Health Administration, Tarko et al.1provide 30-day and longer mortality estimates for non-Hispanic White, non-Hispanic Black, and Hispanic patients hospitalized with incident stroke and examine the association of race and ethnicity with stroke mortality.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.