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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.

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.