Deep terminal negative of the P wave in V1 and incidence of ischemic stroke: The atherosclerosis risk in communities (ARIC) study.

BACKGROUND: Deep terminal negative of the P wave in V1 (DTNPV1) is a marker of left atrial remodeling. We aimed to evaluate the association of DTNPV1 with incident ischemic stroke. METHODS: The Atherosclerosis Risk in Communities study is a prospective community-based cohort study. All participants at visit 4 (1996-1998) except those with prevalent stroke, missing covariates, and missing or uninterpretable ECG were included. DTNPV1 was defined as the absolute value of the depth of the terminal negative phase >100 µV in the presence of biphasic P wave in V1. Association between DTNPV1 as a time-dependent exposure variable and incident ischemic stroke was evaluated. The accuracy of the prediction model consisting of DTNPV1 and CHA2DS2-VASc variables in predicting ischemic stroke was analyzed. RESULTS: Among 10,605 participants (63 ± 6 years, 56% women, 20% Black), 803 cases of ischemic stroke occurred over a median follow-up of 20.19 years. After adjusting for demographics, DTNPV1 was associated with an increased risk of stroke (HR 1.96, [95% CI 1.39-2.77]). After further adjusting for stroke risk factors, use of aspirin and anticoagulants, and time-dependent atrial fibrillation, DTNPV1 was associated with a 1.50-fold (95% CI 1.06-2.13) increased risk of stroke. When added to the CHA2DS2-VASc variables, DTNPV1 did not significantly improve stroke prediction as assessed by C-statistic. However, there was improvement in risk classification for participants who did not develop stroke. CONCLUSION: DTNPV1 is significantly associated with higher risk of ischemic stroke. Since DTNPV1 is a simplified electrocardiographic parameter, it may help stroke prediction, a subject for further research.

Percutaneous left atrial appendage occlusion and risk of stroke, hospitalized bleeding and death in Medicare beneficiaries.

PURPOSE: Among patients with atrial fibrillation (AF), a nonpharmacologic option (e.g., percutaneous left atrial appendage occlusion [LAAO]) is needed for patients with oral anticoagulant (OAC) contraindications. Among beneficiaries in the Medicare fee-for-service coverage 20% sample databases (2015-18) who had AF and an elevated CHA2DS2-VASc score, we assessed the association between percutaneous LAAO versus OAC use and risk of stroke, hospitalized bleeding, and death. METHODS: Patients undergoing percutaneous LAAO were matched to up to five OAC users by sex, age, date of enrollment, index date, CHA2DS2-VASc score, and HAS-BLED score. Overall, 17 156 patients with AF (2905 with percutaneous LAAO) were matched (average ± SD 78 ± 6 years, 44% female). Cox proportional hazards model were used. RESULTS: Median follow-up was 10.3 months. After multivariable adjustments, no significant difference for risk of stroke or death was noted when patients with percutaneous LAAO were compared with OAC users (HRs [95% CIs]: 1.14 [0.86-1.52], 0.98 [0.86-1.10]). There was a 2.94-fold (95% CI: 2.50-3.45) increased risk for hospitalized bleeding for percutaneous LAAO compared with OAC use. Among patients 65 to <78 years old, those undergoing percutaneous LAAO had higher risk of stroke compared with OAC users. No association was present in those ≥78 years. CONCLUSION: In this analysis of real-world AF patients, percutaneous LAAO versus OAC use was associated with similar risk of death, nonsignificantly elevated risk of stroke, and an elevated risk of bleeding in the post-procedural period. Overall, these results support results of randomized trials that percutaneous LAAO may be an alternative to OAC use for patients with contraindications.

Obstructive sleep apnea, nocturnal hypoxemia, and retinal microvasculature: The Atherosclerosis Risk in Communities Study.

Study Objectives: Retinal microvascular pathology (RMP) and obstructive sleep apnea (OSA) are both cardiovascular disease risk factors. Limited data exists on their interrelationship. We tested the hypotheses that OSA and nocturnal hypoxemia would be associated with RMP and vessel calibers. Methods: We conducted a quasi-cross-sectional analysis of 1625 participants in the Atherosclerosis Risk in Communities Sleep Heart Health Study. Participants completed in-home polysomnography monitoring (1996-1998) and were categorized by OSA severity (apnea-hypopnea index: <5, 5-14.9, and ≥15) and proportion of total sleep time with oxygen saturation < 90% (T90). Retinal photography (1993-1995) was used to assess RMP and measure vascular diameters (central retinal arteriolar equivalent [CRAE] and central retinal venular equivalent [CRVE]). Logistic and linear models were adjusted for demographics, behaviors, and BMI. Results: Of the participants, 19% had OSA (AHI > 15) and 4% had RMP. Severe OSA was not associated with RMP [OR (95% CI): 1.08 (0.49 to 2.38)] or CRAE in adjusted models. OSA severity showed a positive linear relationship with CRVE; adjusted mean CRVE for those with OSA was 195.8 µm compared to 193.2 µm for those without OSA (Ptrend = 0.03). T90 was strongly associated with CRVE, but not with RMP or CRAE. Adjusted mean CRVE for T90 ≥ 5% was 199.0 and 192.9 for T90 < 1% (ptrend < 0.0001). Conclusions: OSA and T90 were not associated with RMP or CRAE. However, both OSA and T90 ≥ 5% were associated with wider venules, which may be early and indicative changes of increased inflammation and future risk of stroke and CHD.

Sex-specific racial and ethnic variations in short-term outcomes among patients with first or recurrent ischemic stroke: Paul Coverdell National Acute Stroke Program, 2016-2020.

BACKGROUND AND PURPOSE: To understand the association of sex-specific race and ethnicity on the short-term outcomes of initial and recurrent ischemic stroke events. METHODS: Using the Paul Coverdell National Acute Stroke Program from 2016-2020, we examined 426,062 ischemic stroke admissions from 629 hospitals limited to non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic patients. We performed multivariate logistic regression analyses to assess the combined effects of sex-specific race and ethnicity on short-term outcomes for acute ischemic stroke patients presenting with initial or recurrent stroke events. Outcomes assessed include rates of in-hospital death, discharge to home, and symptomatic intracranial hemorrhage (sICH) after reperfusion treatment. RESULTS: Among studied patients, the likelihood of developing sICH after reperfusion treatment for initial ischemic stroke was not significantly different. The likelihood of experiencing in-hospital death among patients presenting with initial stroke was notably higher among NHW males (AOR 1.59 [95 % CI 1.46, 1.73]), NHW females (AOR 1.34 [95 % CI 1.23, 1.45]), and Hispanic males (AOR 1.57 [95 % CI 1.36, 1.81]) when compared to NHB females. Hispanic females were more likely to be discharged home when compared to NHB females after initial stroke event (AOR 1.32 [95 % CI 1.23, 1.41]). NHB males (AOR 0.90 [95 % CI 0.87, 0.94]) and NHW females (AOR 0.89 [95 % CI 0.86, 0.92]) were less likely to be discharged to home. All groups with recurrent ischemic strokes experienced higher likelihood of in-hospital death when compared to NHB females with the highest likelihood among NHW males (AOR 2.13 [95 % CI 1.87, 2.43]). Hispanic females had a higher likelihood of discharging home when compared to NHB females hospitalized for recurrent ischemic stroke, while NHB males and NHW females with recurrent ischemic stroke hospitalizations were less likely to discharge home. CONCLUSIONS: Sex-specific race and ethnic disparities remain for short-term outcomes in both initial and recurrent ischemic stroke hospitalizations. Further studies are needed to address disparities among recurrent ischemic stroke hospitalizations.

Post-Stroke Brain Health Monitoring and Optimization: A Narrative Review.

Significant advancements have been made in recent years in the acute treatment and secondary prevention of stroke. However, a large proportion of stroke survivors will go on to have enduring physical, cognitive, and psychological disabilities from suboptimal post-stroke brain health. Impaired brain health following stroke thus warrants increased attention from clinicians and researchers alike. In this narrative review based on an open timeframe search of the PubMed, Scopus, and Web of Science databases, we define post-stroke brain health and appraise the body of research focused on modifiable vascular, lifestyle, and psychosocial factors for optimizing post-stroke brain health. In addition, we make clinical recommendations for the monitoring and management of post-stroke brain health at major post-stroke transition points centered on four key intertwined domains: cognition, psychosocial health, physical functioning, and global vascular health. Finally, we discuss potential future work in the field of post-stroke brain health, including the use of remote monitoring and interventions, neuromodulation, multi-morbidity interventions, enriched environments, and the need to address inequities in post-stroke brain health. As post-stroke brain health is a relatively new, rapidly evolving, and broad clinical and research field, this narrative review aims to identify and summarize the evidence base to help clinicians and researchers tailor their own approach to integrating post-stroke brain health into their practices.

Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study.

BACKGROUND AND OBJECTIVES: Studies on the association between proton pump inhibitor (PPI) use and dementia report mixed results and do not examine the impact of cumulative PPI use. We evaluated the associations between current and cumulative PPI use and risk of incident dementia in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: These analyses used participants from a community-based cohort (ARIC) from the time of enrollment (1987-1989) through 2017. PPI use was assessed through visual medication inventory at clinic visits 1 (1987-1989) to 5 (2011-2013) and reported annually in study phone calls (2006-2011). This study uses ARIC visit 5 as baseline because this was the first visit in which PPI use was common. PPI use was examined 2 ways: current use at visit 5 and duration of use before visit 5 (from visit 1 to 2011, exposure categories: 0 day, 1 day-2.8 years, 2.8-4.4 years, >4.4 years). The outcome was incident dementia after visit 5. Cox proportional hazard models were used, adjusted for demographics, comorbid conditions, and other medication use. RESULTS: A total of 5,712 dementia-free participants at visit 5 (mean age 75.4 ± 5.1 years; 22% Black race; 58% female) were included in our analysis. The median follow-up was 5.5 years. The minimum cumulative PPI use was 112 days, and the maximum use was 20.3 years. There were 585 cases of incident dementia identified during follow-up. Participants using PPIs at visit 5 were not at a significantly higher risk of developing dementia during subsequent follow-up than those not using PPIs (hazard ratio (HR): 1.1 [95% confidence interval (CI) 0.9-1.3]). Those who used PPIs for >4.4 cumulative years before visit 5 were at 33% higher risk of developing dementia during follow-up (HR: 1.3 [95% CI 1.0-1.8]) than those reporting no use. Associations were not significant for lesser durations of PPI use. DISCUSSION: Future studies are needed to understand possible pathways between cumulative PPI use and the development of dementia. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the use of prescribed PPIs for >4.4 years by individuals aged 45 years and older is associated with a higher incidence of newly diagnosed dementia.

Association Between Ischemic Stroke Subtype and Stroke Severity: The Atherosclerosis Risk in Communities Study.

BACKGROUND AND OBJECTIVES: Disability after stroke occurs across ischemic stroke subtypes, with a suggestion that embolic strokes are more devastating. Whether this difference is as a result of differences in comorbidities or differences in severity at the time of the stroke event is not known. The primary hypothesis was that participants with embolic stroke would have more severe stroke at the time of admission and a higher risk of mortality, compared with thrombotic stroke participants even with consideration of confounders over time, with a secondary hypothesis that this association would differ by race and sex. METHODS: Atherosclerosis Risk in Communities (ARIC) study participants with incident adjudicated ischemic stroke, stroke severity and mortality data, and complete covariates were included. Multinomial logistic regression models determined the association between stroke subtype (embolic vs thrombotic) and admission NIH Stroke Scale (NIHSS) category (minor [≤5], mild [6-10], moderate [11-15], severe [16-20], and very severe [>20]) adjusted for covariates from visits most proximal to the stroke. Separate ordinal logistic models evaluated for interaction by race and sex. Adjusted Cox proportional hazard models estimated the association between stroke subtype and all-cause mortality (through December 31, 2019). RESULTS: Participants (N = 940) were mean age 71 years (SD = 9) at incident stroke, 51% female, and 38% Black. Using adjusted multinomial logistic regression, the risk of having a more severe stroke (reference NIHSS ≤5) was higher among embolic stroke vs thrombotic stroke patients, with a step-wise increase for embolic stroke patients when moving from mild (odds ratio [OR] 1.95, 95% CI 1.14-3.35) to very severe strokes (OR 4.95, 95% CI 2.34-10.48). After adjusting for atrial fibrillation, there was still a higher risk of having a worse NIHSS among embolic vs thrombotic strokes but with attenuation of effect (very severe stroke OR 3.91, 95% CI 1.76-8.67). Sex modified the association between stroke subtype and severity (embolic vs thrombotic stroke, p interaction = 0.03, per severity category, females OR 2.38, 95% CI 1.55-3.66; males OR 1.75, 95% CI 1.09-2.82). The risk of death (median follow-up 5 years, interquartile range 1-12) was also increased for embolic vs thrombotic stroke patients (hazard ratio 1.66, 95% CI 1.41-1.97). DISCUSSION: Embolic stroke was associated with greater stroke severity at the time of the event and a higher risk of death vs thrombotic stroke, even after careful adjustment for patient-level differences.

The role of population-level preventive care for brain health in ageing.

Over the past several decades, a worldwide demographic transition has led to an increasing number of older adults with chronic neurological conditions. These conditions, which have a profound effect on the cognitive function and physical ability of older adults, also have a long preclinical phase. This feature provides a unique opportunity to implement preventive measures for high-risk groups and the population as a whole, and therefore to reduce the burden of neurological diseases. The concept of brain health has emerged as the overarching theme to define overall brain function independently of underlying pathophysiological processes. We review the concept of brain health from the ageing and preventive care perspectives, discuss the mechanisms underpinning ageing and brain ageing, highlight the interplay of various forces resulting in deviation from brain health towards brain disease, and provide an overview of strategies to promote brain health with a life-course approach.

Procedure-Specific Center Volume and Mortality After Infantile Congenital Heart Surgery.

BACKGROUND: Regionalization of congenital heart surgery (CHS) has been proposed to improve postsurgical outcomes by increasing experience in the care of high-risk patients. We sought to determine whether procedure-specific center volume was associated with mortality after infantile CHS up to 3 years post-procedure. METHODS: We analyzed data from 12,263 infants in the Pediatric Cardiac Care Consortium undergoing CHS between 1982 and 2003 at 46 centers within the United States. We used logistic regression to assess the association between procedure-specific center volume and mortality from discharge to 3 years post-procedure, accounting for clustering at the center level and adjusting for patient age and weight at surgery, chromosomal abnormality, and surgical era. RESULTS: We found decreased odds for in-hospital mortality for Norwood procedures (odds ratio [OR] 0.955, 95% CI 0.935-0.976), arterial switch operations (OR 0.924, 95% CI 0.889-0.961), tetralogy of Fallot repairs (OR 0.975, 95% CI 0.956-0.995), Glenn shunts (OR 0.971, 95% CI 0.943-1.000), and ventricular septal defect closures (OR 0.974, 95% CI 0.964-0.985). The association persisted up to 3 years post-surgery for Norwood procedures (OR 0.971, 95% CI 0.955-0.988), arterial switches (OR 0.929, 95% CI 0.890-0.970), and ventricular septal defect closures (OR 0.986, 95% CI 0.977-0.995); however, after excluding deaths that occurred within the first 90 days of following surgery, we observed no association between center volume and mortality for any of the procedures studied. CONCLUSIONS: These findings suggest that procedure-specific center volume is inversely associated with early postoperative mortality for infantile CHS across the complexity spectrum but has no measurable effect on later mortality.

Trends in intravenous thrombolysis utilization for acute ischemic stroke based on hospital size: Paul Coverdell National Acute Stroke Program, 2010-2019.

INTRODUCTION: The rate of intravenous thrombolysis (IVT) utilization in acute ischemic stroke (AIS) has been increasing, and this has coincided with improved door-to-needle times (DNTs). Smaller hospitals have been observed to utilize IVT less frequently or even not at all. Using a multistate stroke registry, we sought to determine the impact of hospital size on trends in IVT utilization for AIS. METHODS: Utilizing data from the Paul Coverdell National Acute Stroke Program (PCNASP), we studied trends in IVT for AIS patients between 2010 and 2019 based on hospital size. Hospitals were grouped into quartiles based on size. We studied the impact of hospital size on DNTs and overall IVT utilization. RESULTS: During the study period, there were 530,828 AIS patients (mean age 70.3 ± 0.02 years, 50.4% men) from 540 participating hospitals. We did not identify a significant trend in IVT utilization among hospitals within the first quartile (p = 0.1005), but there were significantly increased trends within the hospitals belonging to the second, third, and fourth quartiles (p < 0.001 for all). All quartiles were observed to have significantly increased trends in DNTs ≤60 min (p < 0.0001), but only hospitals within the second, third, and fourth quartiles experienced significantly increased trends in DNTs ≤45 min (p < 0.0001). CONCLUSION: In our registry-based analysis, we observed an increased trend in IVT utilization for AIS among larger hospitals. There was an overall improvement in rates of DNTs ≤60 min, but only larger hospitals were observed to have improved DNTs ≤45 min.

OSA and Subsequent Risk of Hospitalization With Pneumonia, Respiratory Infection, and Total Infection: The Atherosclerosis Risk in Communities Study.

BACKGROUND: OSA has been linked to microaspiration, systemic inflammation, and suboptimal immune function. RESEARCH QUESTION: Is OSA prospectively associated with risk of hospitalization for pneumonia, respiratory, and total infections? STUDY DESIGN AND METHODS: Prospective cohort. Participants in the Atherosclerosis Risk in Communities (ARIC) study (N = 1,586) underwent polysomnography in 1996-1998 and were followed up through 2018 for infection-related hospitalizations. The apnea-hypopnea index (AHI; events/h) was used to categorize participants as having severe OSA (≥ 30), moderate OSA (15-29), mild OSA (5-14), or a normal breathing pattern (< 5). Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. RESULTS: ARIC participants were on average 62.7 (SD = 5.5) years of age, and 52.8% were female. Severe OSA was present in 6.0%, moderate OSA in 12.7%, mild OSA in 30.0%, and normal breathing in 51.3%. A total of 253 hospitalizations with pneumonia occurred over a median 20.4 (max, 22.9) years' follow-up. Participants with severe OSA were at 1.87 times (95% CI, 1.19-2.95) higher risk of hospitalization with pneumonia compared with those with a normal breathing pattern after adjustment for demographics and lifestyle behaviors. Results were attenuated modestly after adjustment for BMI (1.62 [0.99-2.63]), and prevalent asthma and COPD (1.62 [0.99-2.63]). A similar pattern existed for hospitalization with respiratory infection and composite infection (demographic and behavior-adjusted HRs: 1.47 [0.96-2.25] and 1.48 [1.07-2.04], respectively). INTERPRETATION: Severe OSA was associated with increased risk of hospitalizations with pneumonia in this community-based cohort. OSA patients may benefit from more aggressive efforts to prevent pneumonia and other infectious conditions.

Changes in physical activity and risk of ischemic stroke: The ARIC study.

BACKGROUND: Limited data exist regarding the impact of changes in physical activity (PA) over time on ischemic stroke risk. Exploring this understudied area could help improve stroke prevention strategies and promote PA during the lifespan. METHODS: We evaluated 11,089 Atherosclerosis Risk in Communities (ARIC) participants recruited in 1987-1989 who completed Visit 3 (1993-1995). We classified PA as meeting recommendations, not meeting recommendations, or no PA. Categories of increased, decreased, stable high, and stable low PA and a continuous PA variable were also evaluated. Crude and adjusted Cox regression models were used to characterize the association of 6-year changes in PA and ischemic stroke risk. RESULTS: Participants had a mean age of 60 years. During a median of 21 years, 762 ischemic stroke events occurred. Compared to the participants with recommended PA at both visits, those with no PA had 46% higher hazards of ischemic stroke (hazard ratio (HR) = 1.46 (95% confidence interval (CI) = 1.17, 1.82)), and those with recommended PA at Visit 1 and no PA at Visit 3 also had 37% higher hazards (HR = 1.37 (95% CI = 1.02, 1.83)). Participants who increased their PA from Visit 1 to Visit 3 had 23% lower hazard than those with stable low PA at both visits (HR = 0.77 (95% CI = 0.63, 0.94)), while those who decreased their PA had 25% higher hazards compared to those with stable high PA at both visits (HR = 1.25 (95% CI = 1.01, 1.54)). CONCLUSION: Physical inactivity during midlife increases ischemic stroke risk, while meeting PA recommendations reduces it.

Mobile health technology for hypertension management with Hmong and Latino adults: mixed-methods community-based participatory research.

OBJECTIVE: To identify Hmong and Latino adults' perspectives about a mHealth-based care model for hypertension (HTN) management involving blood pressure (BP) self-monitoring, electronic transmission of BP readings, and responsive HTN medication adjustment by a provider team. DESIGN: We conducted a mixed-methods formative study with 25 Hmong and 25 Latino participants with HTN at an urban federally-qualified health center. We used a tool to assess HTN knowledge and conducted open-ended interviews to identify perspectives about mHealth-based care model. RESULTS: While most participants agreed that lowering high blood pressure decreased the risk of strokes, heart attacks, and kidney failure, there were gaps in medical knowledge. Three major themes emerged about the mHealth-based care model: (1) Using mHealth technology could be useful, especially if assistance was available to patients with technological challenges; (2) Knowing blood pressures could be helpful, especially to patients who agreed with doctors' medical diagnosis and prescribed treatment; (3) Transmitting blood pressures to the clinic and their responsive actions could feel empowering, and the sense of increased surveillance could feel entrapping. Some people may feel empowered since it could increase patient-provider communication without burden of clinic visits and could increase involvement in BP control for those who agree with the medical model of HTN. However, some people may feel entrapped as it could breach patient privacy, interfere with patients' lifestyle choices, and curtail patient autonomy. CONCLUSIONS: In general, Hmong and Latino adults responded positively to the empowering aspects of the mHealth-based care model, but expressed caution for those who had limited technological knowledge, who did not agree with the medical model and who may feel entrapped. In a shared decision-making approach with patients and possibly their family members, health care systems and clinicians should explore barriers and potential issues of empowerment and entrapment when offering a mHealth care model in practice.

High Incidence and Unique Features of Cerebral Venous Sinus Thrombosis in Hospitalized Patients With COVID-19 Infection.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) secondary to vaccine-induced thrombotic thrombocytopenia is an extremely rare side effect of adenovirus-based COVID-19 vaccines. CVST incidence associated with COVID-19 itself has not been widely reported. We report the incidence of CVST in patients hospitalized with COVID-19 during the first year of the pandemic. METHODS: We analyzed de-identified electronic medical records of a retrospective cohort of patients admitted with COVID-19 to >200 hospitals between March 2020 and March 2021. We used International Classification of Diseases, Tenth Revision codes and natural language processing extracts to identify patients with a new CVST diagnosis during COVID-19 hospitalization. The primary outcome was CVST incidence in hospitalized, COVID-19-positive patients. Secondary outcomes included CVST incidence and mortality. Incidence rates were calculated using the DerSimonian-Laird estimator method. RESULTS: Ninety-one thousand seven hundred twenty-seven patients were evaluated; 22 had new CVST diagnoses by electronic medical record review. CVST incidence in the hospitalized COVID-19 cohort was 231 per 1 000 000 person-years (95% CI, 152.1-350.8). Females<50 had the highest incidence overall (males <50: 378.4 [142-1008.2]; females<50: 796.5 [428.6-1480.4]). In patients ≥50 years old, males had a higher estimated CVST incidence (males≥50: 130.5 [54.3-313.6]; females≥50: 88.8 [28.6-275.2]). Older patients (45.5% of patients ≥50 versus 0% of <50 years of age, P=0.012) and males (44.4% of males versus 7.7% of females, P=0.023) were more likely to die in hospital. CONCLUSIONS: CVST incidence in COVID-19-positive hospitalized patients is high. Advanced age and male gender were associated with likelihood of death in hospital; further studies are required to confirm these findings.

Carotid Intima-Media Thickness and Amyloid-ß Deposition: The ARIC-PET Study.

We assessed whether carotid intima-media thickness (cIMT) is prospectively associated with amyloid-ß (Aß). 332 nondemented Atherosclerosis Risk in Communities Study participants with carotid ultrasounds (1990-1992) and PET scans (2012-2014) were studied. Participants in the highest (versus lowest) cIMT tertile had 2.17 times the odds of elevated Aß (95% CI: 1.15-4.11), after demographic and APOE ɛ4 adjustments. An interaction with APOE ɛ4 was observed (p = 0.02). Greater cIMT was associated with elevated Aß independent of vascular risk factors among those with ≥1 APOE ɛ4 allele, but not in noncarriers. In this cohort, higher cIMT was associated with Aß deposition 22 years later, particularly among APOE ɛ4 carriers.

Association of Carotid Intima-Media Thickness with Brain MRI Markers in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

OBJECTIVE: Elevated carotid intima-media thickness (cIMT) and carotid plaque are markers of arterial injury and may be linked to structural brain injury. We hypothesized cIMT or presence of carotid plaque at midlife are associated with presence of infarcts and cerebral microbleeds, greater white matter hyperintensity (WMH) volume, and smaller regional brain volumes in late-life. METHODS: We included 1,795 Atherosclerosis Risk in Communities (ARIC) Study participants (aged 57±6 years, 57% female, 23% Black) with carotid ultrasounds in 1990-1992 and brain MRI scans in 2011-2013. Weighted linear regression was used for brain volume outcomes, while logistic regression was used for infarcts and cerebral microbleeds. RESULTS: After multivariable adjustments, the highest cIMT quintile was associated with smaller deep gray matter (ß [95% CI]: -0.11 [-0.22, -0.01]) and cortical volume in a temporal-parietal meta region of interest (ROI) (ß [95% CI]: -0.10 [-0.20, -0.01]) in late-life. Similarly, those with carotid plaque had smaller regional brain volumes than those without (ßs [95% CIs]: -0.05 [-0.12, 0.03] and -0.06 [-0.13, 0.01] for deep gray matter and temporal-parietal meta ROI). No significant relations were observed with WMH volume, infarcts, or cerebral microbleeds. CONCLUSION: Over a median follow-up of 21 years, greater midlife cIMT and presence of carotid plaque were associated with smaller deep gray matter volume and cortical volume in a meta ROI involving temporal and parietal lobe regions typically involved in neurodegeneration, including Alzheimer's disease, in later life. Contrary to our hypothesis, associations between measures of arterial injury and markers of vascular brain injury were null.

Association of Ischemic Stroke Incidence, Severity, and Recurrence With Dementia in the Atherosclerosis Risk in Communities Cohort Study.

IMPORTANCE: Ischemic stroke is associated with increased risk of dementia, but the association of stroke severity and recurrence with risk of impaired cognition is not well known. OBJECTIVE: To examine the risk of dementia after incident ischemic stroke and assess how it differed by stroke severity and recurrence. DESIGN, SETTING, AND PARTICIPANTS: The Atherosclerosis Risk in Communities (ARIC) study is an ongoing prospective cohort of 15 792 community-dwelling individuals from 4 US states (Mississippi, Maryland, Minnesota, and North Carolina). Among them, 15 379 participants free of stroke and dementia at baseline (1987 to 1989) were monitored through 2019. Data were analyzed from April to October 2021. Associations between dementia and time-varying ischemic stroke incidence, frequency, and severity were studied across an average of 4.4 visits over a median follow-up of 25.5 years with Cox proportional hazards models adjusted for sociodemographic characteristics, apolipoprotein E, and vascular risk factors. EXPOSURES: Incident and recurrent ischemic strokes were classified by expert review of hospital records, with severity defined by the National Institutes of Health Stroke Scale (NIHSS; minor, ≤5; mild, 6-10; moderate, 11-15; and severe, ≥16). MAIN OUTCOMES AND MEASURES: Dementia cases adjudicated through expert review of in-person evaluations, informant interviews, telephone assessments, hospitalization codes, and death certificates. In participants with stroke, dementia events in the first year after stroke were not counted. RESULTS: At baseline, the mean (SD) age of participants was 54.1 (5.8) years, and 8485 of 15 379 participants (55.2%) were women. A total of 4110 participants (26.7%) were Black and 11 269 (73.3%) were White. A total of 1378 ischemic strokes (1155 incident) and 2860 dementia cases were diagnosed 1 year or more after incident stroke in participants with stroke, or at any point after baseline in participants without stroke, were identified through December 31, 2019. NIHSS scores were available for 1184 of 1378 ischemic strokes (85.9%). Risk of dementia increased with both the number and severity of strokes. Compared with no stroke, risk of dementia by adjusted hazard ratio was 1.76 (95% CI, 1.49-2.00) for 1 minor to mild stroke, 3.47 (95% CI, 2.23-5.40) for 1 moderate to severe stroke, 3.48 (95% CI, 2.54-4.76) for 2 or more minor to mild strokes, and 6.68 (95% CI, 3.77-11.83) for 2 or more moderate to severe strokes. CONCLUSIONS AND RELEVANCE: In this study, risk of dementia significantly increased after ischemic stroke, independent of vascular risk factors. Results suggest a dose-response association of stroke severity and recurrence with risk of dementia.

Body mass index prediction rule for mid-upper arm circumference: the atherosclerosis risk in communities study.

OBJECTIVES: Electronic health records (EHR) are a convenient data source for clinical trial recruitment and allow for inexpensive participant screening. However, EHR may lack pertinent screening variables. One strategy is to identify surrogate EHR variables which can predict the screening variable of interest. In this article, we use BMI to develop a prediction rule for arm circumference using data from the Atherosclerosis Risk in Communities (ARIC) Study. This work applies to EHR patient screening for clinical trials of hypertension. METHODS: We included 11 585 participants aged 52-75 years with BMI and arm circumference measured at ARIC follow-up visit 4 (1996-1998). We selected the following arm circumference cutpoints based on the American Heart Association recommendations for blood pressure (BP) cuffs: small adult (≤26 cm), adult (≤34 cm) and large adult (≤44 cm). We calculated the sensitivity and specificity of BMI values for predicting arm circumference using receiver operating characteristic curves. We report the BMI threshold that maximized Youden's Index for each arm circumference upper limit of a BP cuff. RESULTS: Participants' mean BMI and arm circumference were 28.8 ± 5.6 kg/m2 and 33.4 ± 4.3 cm, respectively. The BMI-arm circumference Pearson's correlation coefficient was 0.86. The BMI threshold for arm circumference≤26 cm was 23.0 kg/m2, arm circumference≤34 cm was 29.2 kg/m2 and arm circumference≤44 cm was 37.4 kg/m2. Only the BMI threshold for arm circumference≤34 cm varied significantly by sex. CONCLUSIONS: BMI predicts arm circumference with high sensitivity and specificity and can be an accurate surrogate variable for arm circumference. These findings are useful for participant screening for hypertension trials. Providers can use this information to counsel patients on appropriate cuff size for BP self-monitoring.