Rates of operative intervention and in-hospital mortality following subarachnoid hemorrhage in patients with COVID-19.

OBJECTIVE: COVID-19 had massive effects on the healthcare system and multifactorial implications for the management of intensive care unit and cerebrovascular patients. This study aimed to assess the effect of COVID-19 on the outcomes of patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: The National Inpatient Sample (NIS) was used to identify patients with nontraumatic SAH (ICD-10 code I60.x). Patients with nonaneurysmal cerebrovascular malformations or traumatic intracranial injuries were excluded. Only patients managed from April to December 2020 were included in the study given the availability of an ICD-10 code for COVID-19. Data on sociodemographic factors, hospital characteristics, comorbidities, NIS SAH Severity Score (NIS-SSS), surgical treatment, and death were acquired. Multivariable analysis was used to assess predictors of both surgical intervention and in-hospital mortality. RESULTS: In total, 6984 patients met the study criteria, 359 (5.1%) of whom had COVID-19. Those with COVID-19 were more likely to be younger and male and had a higher All Patient Refined Diagnosis-Related Groups illness severity subclass, and NIS-SSS. Moreover, patients with COVID-19 were less likely to undergo surgery (10.0% vs 23.6%, OR 0.35, p < 0.0001) and had significantly higher mortality rates (48.2% vs 22.7%, p < 0.0001). When controlling for other variables, COVID-19 was an independent predictor of death (OR 1.67, p = 0.0002). Aneurysm surgery was performed in 1597 patients (317 open and 1280 endovascular procedures). There was no difference between the cohorts positive and negative for COVID-19 in terms of time to surgery or type of surgery. CONCLUSIONS: COVID-19 had significant impacts on patients with nontraumatic SAH. Specifically, patients with COVID-19 were significantly less likely to undergo surgery and had higher in-hospital mortality rates; however, for patients who did undergo procedural intervention, there was no significant difference in the type of intervention. Multiple factors, from medical acuity to healthcare system limitations, may contribute to these findings. Further retrospective research is needed to identify both specific causes of lower intervention rates and other potential nonaneurysmal causes of SAH in patients with COVID-19.

Direct V3 Vertebral Artery Access for Embolization of Partially Thrombosed Fusiform Basilar Trunk Aneurysm: Technical Case Instruction.

BACKGROUND AND IMPORTANCE: Fusiform vertebrobasilar aneurysms carry significant morbidity. Endovascular strategies are preferred; however, unsafe or unfeasible access can call for innovative strategies. CLINICAL PRESENTATION: An octogenarian patient with an enlarging fusiform proximal basilar artery aneurysm causing a sixth nerve palsy was found to have multiple anatomic features that precluded a transradial or transfemoral endovascular approach. She was thus treated with direct microsurgical access of the V3 segment of the vertebral artery for subsequent coil embolization and flow diversion. CONCLUSION: This case introduces a novel combined microsurgical and endovascular strategy for treating a complex partially thrombosed fusiform basilar artery aneurysm. This approach should be reserved only for patients where conventional endovascular access is dangerous or unfeasible.

Differential associations between abnormal cardiac left ventricular geometry types and cerebral white matter disease.

OBJECTIVES: Reduced cardiac outflow due to left ventricular hypertrophy has been suggested as a potential risk factor for development of cerebral white matter disease. Our study aimed to examine the correlation between left ventricular geometry and white matter disease volume to establish a clearer understanding of their relationship, as it is currently not well-established. METHODS: Consecutive patients from 2016 to 2021 who were ≥18 years and underwent echocardiography, cardiac MRI, and brain MRI within one year were included. Four categories of left ventricular geometry were defined based on left ventricular mass index and relative wall thickness on echocardiography. White matter disease volume was quantified using an automated algorithm applied to axial T2 FLAIR images and compared across left ventricular geometry categories. RESULTS: We identified 112 patients of which 34.8 % had normal left ventricular geometry, 20.5 % had eccentric hypertrophy, 21.4 % had concentric remodeling, and 23.2 % had concentric hypertrophy. White matter disease volume was highest in patients with concentric hypertrophy and concentric remodeling, compared to eccentric hypertrophy and normal morphology with a trend-P value of 0.028. Patients with higher relative wall thickness had higher white matter disease volume (10.73 ± 10.29 cc vs 5.89 ± 6.46 cc, P = 0.003), compared to those with normal relative wall thickness. CONCLUSION: Our results showed that abnormal left ventricular geometry is associated with higher white matter disease burden, particularly among those with abnormal relative wall thickness. Future studies are needed to explore causative relationships and potential therapeutic options that may mediate the adverse left ventricular remodeling and its effect in slowing white matter disease progression.

Persistent Inequities in Intravenous Thrombolysis for Acute Ischemic Stroke in the United States: Results From the Nationwide Inpatient Sample.

BACKGROUND: Despite its approval for acute ischemic stroke >25 years ago, intravenous thrombolysis (IVT) remains underused, with inequities by age, sex, race, ethnicity, and geography. Little is known about IVT rates by insurance status. METHODS AND RESULTS: We assessed temporal trends from 2002 to 2015 in IVT for acute ischemic stroke in the Nationwide Inpatient Sample using adjusted, survey-weighted logistic regression. We calculated odds ratios for IVT for each category in 2002 to 2008 (period 1) and 2009 to 2015 (period 2). IVT use for acute ischemic stroke increased from 1.0% in 2002 to 6.8% in 2015 (adjusted annual relative ratio, 1.15). Individuals aged ≥85 years had the most pronounced increase during 2002 to 2015 (adjusted annual relative ratio, 1.18) but were less likely to receive IVT compared with 18- to 44-year-olds in period 1 (adjusted odds ratio [aOR], 0.23) and period 2 (aOR, 0.36). Women were less likely than men to receive IVT, but the disparity narrowed over time (period 1: aOR, 0.81; period 2: aOR, 0.94). Inequities in IVT resolved for Hispanic individuals in period 2 (aOR, 0.96) but not for Black individuals (period 2: aOR, 0.81). The disparity in IVT for Medicare patients, compared with privately insured patients, lessened over time (period 1: aOR, 0.59; period 2: aOR, 0.75). Patients treated in rural hospitals remained less likely to receive IVT than in urban hospitals; a more dramatic increase in urbanity widened the inequity (period 2, urban nonteaching versus rural: aOR, 2.58, period 2, urban teaching versus rural: aOR, 3.90). CONCLUSIONS: IVT for acute ischemic stroke increased among adults. Despite some encouraging trends, the remaining disparities highlight the need for intensified efforts at addressing inequities.

Geriatric Emergency Medication Safety Recommendations (GEMS-Rx): Modified Delphi Development of a High-Risk Prescription List for Older Emergency Department Patients.

STUDY OBJECTIVE: Half of emergency department (ED) patients aged 65 years and older are discharged with new prescriptions. Potentially inappropriate prescriptions contribute to adverse drug events. Our objective was to develop an evidence- and consensus-based list of high-risk prescriptions to avoid among older ED patients. METHODS: We performed a modified, 3-round Delphi process that included 10 ED physician experts in geriatrics or quality measurement and 1 pharmacist. Consensus members reviewed all 35 medication categories from the 2019 American Geriatrics Society Beers Criteria and ranked each on a 5-point Likert scale (5=highest) for overall priority for avoidance (Round 1), risk of short-term adverse events and avoidability (Round 2), and reasonable medical indications for high-risk medication use (Round 3). RESULTS: For each round, questionnaire response rates were 91%, 82%, and 64%, respectively. After Round 1, benzodiazepines (mean, 4.60 [SD, 0.70]), skeletal muscle relaxants (4.60 [0.70]), barbiturates (4.30 [1.06]), first-generation antipsychotics (4.20 [0.63]) and first-generation antihistamines (3.70 [1.49]) were prioritized for avoidance. In Rounds 2 and 3, hypnotic "Z" drugs (4.29 [1.11]), metoclopramide (3.89 [0.93]), and sulfonylureas (4.14 [1.07]) were prioritized for avoidability, despite lower concern for short-term adverse events. All 8 medication classes were included in the final list. Reasonable indications for prescribing high-risk medications included seizure disorders, benzodiazepine/ethanol withdrawal, end of life, severe generalized anxiety, allergic reactions, gastroparesis, and prescription refill. CONCLUSION: We present the first expert consensus-based list of high-risk prescriptions for older ED patients (GEMS-Rx) to improve safety among older ED patients.

Pandemic phase-related racial and ethnic disparities in COVID-19 positivity and outcomes among patients presenting to emergency departments during the first two pandemic waves in the USA.

BACKGROUND: In many countries including the USA, the UK and Canada, the impact of COVID-19 on people of colour has been disproportionately high but examination of disparities in patients presenting to ED has been limited. We assessed racial and ethnic differences in COVID-19 positivity and outcomes in patients presenting to EDs in the USA, and the effect of the phase of the pandemic on these outcomes. METHODS: This is a retrospective cohort study of adult patients tested for COVID-19 during, or 14 days prior to, the index ED visit in 2020. Data were obtained from the National Registry of Suspected COVID-19 in Emergency Care network which has data from 155 EDs across 27 US states. Hierarchical models were used to account for clustering by hospital. The outcomes included COVID-19 diagnosis, hospitalisation at index visit, subsequent hospitalisation within 30 days and 30-day mortality. We further stratified the analysis by time period (early phase: March-June 2020; late phase: July-September 2020). RESULTS: Of the 26 111 adult patients, 38% were non-Hispanic White (NHW), 29% Black, 20% Hispanic/Latino, 3% Asian and 10% all others; half were female. The median age was 56 years (IQR 40-69), and 53% were diagnosed with COVID-19; of those, 59% were hospitalised at index visit. Of those discharged from ED, 47% had a subsequent hospitalisation in 30 days. Hispanic/Latino patients had twice (adjusted OR (aOR) 2.3; 95% CI 1.8 to 3.0) the odds of COVID-19 diagnosis than NHW patients, after adjusting for age, sex and comorbidities. Black, Asian and other minority groups also had higher odds of being diagnosed (compared with NHW patients). On stratification, this association was observed in both phases for Hispanic/Latino patients. Hispanic/Latino patients had lower odds of hospitalisation at index visit, but when stratified, this effect was only observed in early phase. Subsequent hospitalisation was more likely in Asian patients (aOR 3.1; 95% CI 1.1 to 8.7) in comparison with NHW patients. Subsequent ED visit was more likely in Blacks and Hispanic/Latino patients in late phase. CONCLUSION: We found significant differences in ED outcomes that are not explained by comorbidity burden. The gap decreased but persisted during the later phase in 2020.

Asymptomatic Females Are at Higher Risk for Perioperative TIA/Stroke and Males Are at Higher Risk for Long-Term Mortality after Carotid Artery Stenting: A Vascular Quality Initiative Analysis.

The study aims to review the sex differences with respect to transient ischemic attack (TIA)/stroke and death in the perioperative period and on long-term follow-up among asymptomatic patients treated with carotid stenting (CAS) in the vascular quality initiative (VQI). All cases reported to VQI of asymptomatic CAS (ACAS) patients were reviewed. The primary end point was risk of TIA/stroke and death in the in-hospital perioperative period and in the long-term follow-up. The secondary end point was to evaluate predictors of in-hospital perioperative TIA/stroke and mortality on long-term follow-up after CAS. There were 22,079 CAS procedures captured from January 2005 to April 2019. There were 5,785 (62.7%) patients in the ACAS group. The rate of in-hospital TIA/stroke was higher in female patients (2.7 vs. 1.87%, p = 0.005) and the rate of death was not significant (0.03 vs. 0.07%, p = 0.66). On multivariable logistic regression analysis, prior/current smoking history (odds ratio = 0.58 [95% confidence interval or CI = 0.39-0.87]; p = 0.008) is a predictor of in-hospital TIA/stroke in females. The long-term all-cause mortality is significantly higher in male patients (26.9 vs. 15.7%, p < 0.001). On multivariable Cox-regression analysis, prior/current smoking history (hazard ratio or HR = 1.17 [95% CI = 1.01-1.34]; p = 0.03), coronary artery disease or CAD (HR = 1.15 [95% CI = 1.03-1.28]; p = 0.009), chronic obstructive pulmonary disease or COPD (HR = 1.73 [95% CI = 1.55-1.93]; p < 0.001), threat to life American Society of Anesthesiologists (ASA) class (HR = 2.3 [95% CI = 1.43-3.70]; p = 0.0006), moribund ASA class (HR = 5.66 [95% CI = 2.24-14.29]; p = 0.0003), and low hemoglobin levels (HR = 0.84 [95% CI = 0.82-0.86]; p < 0.001) are the predictors of long-term mortality. In asymptomatic carotid disease patients, women had higher rates of in-hospital perioperative TIA/stroke and a predictor of TIA/stroke is a prior/current history of smoking. Meanwhile, long-term all-cause mortality is higher for male patients compared with their female counterparts. Predictors of long-term mortality are prior/current smoking history, CAD, COPD, higher ASA classification of physical status, and low hemoglobin level. These data should be considered prior to offering CAS to asymptomatic female and male patients and careful risks versus benefits discussion should be offered to each individual patient.

The Clinical Emergency Data Registry: Structure, Use, and Limitations for Research.

The Clinical Emergency Data Registry (CEDR) is a qualified clinical data registry that collects data from participating emergency departments (EDs) in the United States for quality measurement, improvement, and reporting purposes. This article aims to provide an overview of the data collection and validation process, describe the existing data structure and elements, and explain the potential opportunities and limitations for ongoing and future research use. CEDR data are primarily collected for quality reporting purposes and are obtained from diverse sources, including electronic health records and billing data that are de-identified and stored in a secure, centralized database. The CEDR data structure is organized around clinical episodes, which contain multiple data elements that are standardized using common data elements and are mapped to established terminologies to enable interoperability and data sharing. The data elements include patient demographics, clinical characteristics, diagnostic and treatment procedures, and outcomes. Key limitations include the limited generalizability due to the selective nature of participating EDs and the limited validation and completeness of data elements not currently used for quality reporting purposes, including demographic data. Nonetheless, CEDR holds great potential for ongoing and future research in emergency medicine due to its large-volume, longitudinal, near real-time, clinical data. In 2021, the American College of Emergency Physicians authorized the transition from CEDR to the Emergency Medicine Data Institute, which will catalyze investments in improved data quality and completeness for research to advance emergency care.

Extracranial-Intracranial Bypass for Moyamoya Disease: The Influence of Racial and Socioeconomic Disparities on Outcomes - A National Inpatient Sample Analysis.

BACKGROUND: Extracranial-intracranial (EC-IC) bypass is an established therapeutic option for Moyamoya disease (MMD). However, little is known about the effects of racial and ethnic disparities on outcomes. This study assessed trends in EC-IC bypass outcomes among MMD patients stratified by race and ethnicity. METHODS: Utilizing the US National Inpatient Sample, we identified MMD patients undergoing EC-IC bypass between 2002 and 2020. Demographic and hospital-level data were collected. Multivariable analysis was conducted to identify independent factors associated with outcomes. Trend analysis was performed using piecewise joinpoint regression. RESULTS: Out of 14,062 patients with MMD, 1771 underwent EC-IC bypass. Of these, 60.59% were White, 17.56% were Black, 12.36% were Asians, 8.47% were Hispanic, and 1.02% were Native Americans. Nonhome discharge was noted in 21.7% of cases, with a 6.7% death and 3.8% postoperative neurologic complications rates. EC-IC bypass was more commonly performed in Native Americans (23.38%) and Asians (17.76%). Hispanics had the longest mean length of stay (8.4 days) and lower odds of nonhome discharge compared to Whites (odds ratio: 0.64; 95% confidence interval: 0.40-1.03; P = 0.04). Patients with Medicaid, private insurance, self-payers, and insurance paid by other governments had lower odds of nonhome discharge than those with Medicare. CONCLUSION: This study highlights racial and socioeconomic disparities in EC-IC bypass for patients with MMD. Despite these disparities, we did not find any significant difference in the quality of care. Addressing these disparities is essential for optimizing MMD outcomes.

Beyond the Four Walls: The American College of Emergency Physicians 2022 New Practice Models Task Force Report.

Emergency physicians are highly trained to deliver acute unscheduled care. The emergency physician core skillset gained during emergency medicine residency can be applied to many other roles that benefit patients and extend and diversify emergency physician careers. In 2022, the American College of Emergency Physicians (ACEP) convened the New Practice Models Task Force to describe new care models and emergency physician opportunities outside the 4 walls of the emergency department. The Task Force consisted of 21 emergency physicians with broad experience and 2 ACEP staff. Fifty-nine emergency physician roles were identified (21 established clinical roles, 16 emerging clinical roles, 9 established nonclinical roles, and 13 emerging nonclinical roles). A strength-weakness-opportunity-threat (SWOT) analysis was performed for each role. Using the analysis, the Task Force made recommendations for guiding ACEP internal actions, advocacy, education, and research opportunities. Emphasis was placed on urgent care, rural medicine, telehealth/virtual care, mobile integrated health care, home-based services, emergency psychiatry, pain medicine, addiction medicine, and palliative care as roles with high or rising demand that draw on the emergency physician skillset. Advocacy recommendations focused on removing state and federal regulatory and legislative barriers to the expansion of new and emerging roles. Educational recommendations focused on aggregating available resources, developing a centralized resource for career guidance, and new educational content for emerging roles. The Task Force also recommended promoting research on potential advantages (eg, improved outcomes, lower cost) of emergency physicians in certain roles and new care models (eg, emergency physician remote supervision in rural settings).

Effect of cerebral arteriovenous malformation location on outcomes of repeat, single-fraction stereotactic radiosurgery: a matched-cohort analysis.

OBJECTIVE: Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes. METHODS: This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose. RESULTS: After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047). CONCLUSIONS: AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

Erratum: Development of a gene edited next-generation hematopoietic cell transplant to enable acute myeloid leukemia treatment by solving off-tumor toxicity.

[This corrects the article DOI: 10.1016/j.omtm.2023.101135.].

Effects of Everolimus in Modulating the Host Immune Responses against Mycobacterium tuberculosis Infection.

The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (P13K/AKT/mTOR) pathway plays a key role in tuberculosis (TB) pathogenesis and infection. While the activity levels of this pathway during active infection are still debated, manipulating this pathway shows potential benefit for host-directed therapies. Some studies indicate that pathway inhibitors may have potential for TB treatment through upregulation of autophagy, while other studies do not encourage the use of these inhibitors due to possible host tissue destruction by Mycobacterium tuberculosis (M. tb) and increased infection risk. Investigating further clinical trials and their use of pathway inhibitors is necessary in order to ascertain their potential for TB treatment. This paper is particularly focused on the drug everolimus, an mTOR inhibitor. One of the first clinical trials sponsored by the Aurum Institute showed potential benefit in using everolimus as an adjunctive therapy for tuberculosis. Infection with tuberculosis is associated with a metabolic shift from oxidative phosphorylation towards glycolysis. The everolimus arm in the clinical trial showed further reduction than the control for both maximal and peak glycolytic activity. Compared with control, those receiving everolimus demonstrated increased lung function through forced expiratory volume in 1 s (FEV1) measurements, suggesting that everolimus may mitigate inflammation contributing to lung damage.

Development of a gene edited next-generation hematopoietic cell transplant to enable acute myeloid leukemia treatment by solving off-tumor toxicity.

Immunotherapy of acute myeloid leukemia (AML) has been challenging because the lack of tumor-specific antigens results in "on-target, off-tumor" toxicity. To unlock the full potential of AML therapies, we used CRISPR-Cas9 to genetically ablate the myeloid protein CD33 from healthy donor hematopoietic stem and progenitor cells (HSPCs), creating tremtelectogene empogeditemcel (trem-cel). Trem-cel is a HSPC transplant product designed to provide a reconstituted hematopoietic compartment that is resistant to anti-CD33 drug cytotoxicity. Here, we describe preclinical studies and process development of clinical-scale manufacturing of trem-cel. Preclinical data showed proof-of-concept with loss of CD33 surface protein and no impact on myeloid cell differentiation or function. At clinical scale, trem-cel could be manufactured reproducibly, routinely achieving >70% CD33 editing with no effect on cell viability, differentiation, and function. Trem-cel pharmacology studies using mouse xenograft models showed long-term engraftment, multilineage differentiation, and persistence of gene editing. Toxicology assessment revealed no adverse findings, and no significant or reproducible off-target editing events. Importantly, CD33-knockout myeloid cells were resistant to the CD33-targeted agent gemtuzumab ozogamicin in vitro and in vivo. These studies supported the initiation of the first-in-human, multicenter clinical trial evaluating the safety and efficacy of trem-cel in patients with AML (NCT04849910).

Persistent Inequities in Intravenous Thrombolysis for Acute Ischemic Stroke in the United States: Results from the Nationwide Inpatient Sample.

Background: Despite its approval for use in acute ischemic stroke (AIS) >25 years ago, intravenous thrombolysis (IVT) remains underutilized, with inequities by age, sex, race/ethnicity, and geography. Little is known about IVT rates by insurance status. We aimed to assess temporal trends in the inequities in IVT use. Methods: We assessed trends from 2002 to 2015 in IVT for AIS in the Nationwide Inpatient Sample by sex, age, race/ethnicity, hospital location/teaching status, and insurance, using survey-weighted logistic regression, adjusting for sociodemographics, comorbidities, and hospital characteristics. We calculated odds ratios for IVT for each category in 2002-2008 (Period 1) and 2009-2015 (Period 2). Results: Among AIS patients (weighted N=6,694,081), IVT increased from 1.0% in 2002 to 6.8% in 2015 (adjusted annual relative ratio (AARR) 1.15, 95% CI 1.14-1.16). Individuals ≥85 years had the most pronounced increase from 2002 to 2015 (AARR 1.18, 1.17-1.19), but were less likely to receive IVT compared to those aged 18-44 years in both Period 1 (adjusted odds ratio (aOR) 0.23, 0.21-0.26) and Period 2 (aOR 0.36, 0.34-0.38). Women were less likely than men to receive IVT, but the disparity narrowed over time (Period 1 aOR 0.81, 0.78-0.84, Period 2 aOR 0.94, 0.92-0.97). Inequities in IVT by race/ethnicity resolved for Hispanic individuals in Period 2 but not for Black individuals (Period 2 aOR 0.81, 0.78-0.85). The disparity in IVT for Medicare patients, compared to privately insured patients, lessened over time (Period 1 aOR 0.59, 0.56-0.52, Period 2 aOR 0.75, 0.72-0.77). Patients treated in rural hospitals were less likely to receive IVT than those treated in urban hospitals; a more dramatic increase in urban areas widened the inequity (Period 2 urban non-teaching vs. rural aOR 2.58, 2.33-2.85, urban teaching vs. rural aOR 3.90, 3.55-4.28). Conclusion: From 2002 through 2015, IVT for AIS increased among adults. Despite encouraging trends, only 1 in 15 AIS patients received IVT and persistent inequities remained for Black individuals, women, government-insured, and those treated in rural areas, highlighting the need for intensified efforts at addressing inequities.

Association between within-visit blood pressure variability, stroke, coronary heart disease, and cardiovascular mortality.

INTRODUCTION: Long-term variability in systolic blood pressure (SBP) is associated with a higher risk of cardiovascular events. Little is known about any association between within-visit SBP variability, stroke, coronary heart disease (CHD), and cardiovascular (CV) death. MATERIAL AND METHODS: Participants included adults ≥ 18 years who participated in the US National Health and Nutrition Examination Surveys from 1999 to 2012 linked to the national death index in 2012. Stroke was self-reported. SBP was obtained up to four times by a physician, using a manual sphygmomanometer according to standard procedures. Within-visit SBP variability was defined as the standard deviation of the BP measurements, stratified into quartiles. We evaluated the relationship between within-visit SBP variability and the odds of stroke or CHD using multivariable logistic regression, and with CV mortality, using multivariable Cox regression. RESULTS: Of the 27,987 adults, 16.4% were aged ≥ 65 years, 51.3% were female, 71.2% were white, and 10.7% were black. Factors associated with higher mean SBP variability included older age, hypertension, chronic kidney disease, peripheral artery disease, and smoking (all p < 0.05). The prevalence of stroke significantly increased across SBP variability quartiles, from 2.1% for quartile 1 to 3.7% for quartile 4 (p < 0.001). High SBP variability was associated with higher odds of stroke [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.4-2.2], coronary heart disease (OR 2.0, 95% CI 1.6-2.4), and increased risk of CV mortality [hazard ratio (HR) 2.7, 95% CI 2.3-3.1]. The relationships were not observed after adjusting for covariables. CONCLUSIONS: Within-visit variability in SBP is associated with increased risks of stroke, coronary heart disease, and cardiovascular mortality, but the relationship is confounded by age and covariates.