Association of Head Injury With Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Cohort

Background and Objectives:Late-onset epilepsy (LOE; i.e., epilepsy starting in later adulthood) is affects a significant number of individuals. Head injury is also a risk factor for acquired epilepsy, but the degree to which prior head injury may contribute to LOE is less well understood. Our objective was to determine the association between head injury and subsequent development of LOE.Methods:Included were 8,872 participants enrolled in the Atherosclerosis Risk in Communities (ARIC) study with continuous Centers for Medicare Services (CMS) fee-for-service (FFS) coverage (55.1% women, 21.6% black). We identified head injuries through 2018 from linked Medicare FFS claims for inpatient/emergency department care, active surveillance of hospitalizations, and participant self-report. LOE cases through 2018 were identified from linked Medicare FFS claims. We used Cox proportional hazards models to evaluate associations of head injury with LOE, adjusting for demographic, cardiovascular, and lifestyle factors.Results:The adjusted hazard ratio (HR) for developing LOE after a history of head injury was 1.88 (95%CI=1.44-2.43). There was evidence for dose-response associations with greater risk for LOE with increasing number of prior head injuries (HR=1.37, 95%CI=1.01-1.88 for 1 prior head injury and HR=3.55, 95%CI=2.51-5.02 for 2+ prior head injuries, compared to no head injuries) and with more severe head injury (HR=2.53, 95%CI=1.83-3.49 for mild injury and HR=4.90, 95%CI=3.15-7.64 for moderate/severe injury, compared to no head injuries). Associations with LOE were significant for head injuries sustained at older age (age≥67 years: HR=4.01, 95%CI=2.91-5.54), but not for head injuries sustained at younger age (age<67 years: HR=0.98, 95%CI=0.68-1.41).Discussion:Head injury was associated with increased risk of developing LOE, particularly when head injuries were sustained at an older age, and there was evidence for higher risk for LOE after a greater number of prior head injuries and after more severe head injuries.Classification of Evidence:This study provides Class I evidence that an increased risk of late-onset epilepsy is associated with head injury and increases further with multiple and more severe head injuries.

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Mortality in Patients With Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study

Neurology ◽

10.1212/wnl.0000000000012483 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012483

Author(s):

Emily L. Johnson ◽

Gregory L. Krauss ◽

Anna Kucharska-Newton ◽

Alice D. Lam ◽

Rani Sarkis ◽

...

Keyword(s):

Causes Of Death ◽

Excess Mortality ◽

Proportional Hazards ◽

Late Onset ◽

Cox Proportional Hazards ◽

Fee For Service ◽

Atherosclerosis Risk In Communities ◽

Risk Of Death ◽

Increased Risk ◽

Atherosclerosis Risk

ObjectiveTo determine the risk of mortality and causes of death in persons with late-onset epilepsy (LOE) compared to those without epilepsy in a community-based sample, adjusting for demographics and comorbid conditions.MethodsThis is an analysis of the prospective Atherosclerosis Risk in Communities (ARIC) study, initiated in 1987-1989 among 15,792 mostly black and white men and women in 4 U.S. communities. We used Centers for Medicare Services fee-for-service claims codes to identify cases of incident epilepsy starting at or after age 67. We used Cox proportional hazards analysis to identify the hazard of mortality associated with LOE and to adjust for demographics and vascular risk factors. We used death certificate data to identify dates and causes of death.ResultsAnalyses included 9090 participants, of whom 678 developed LOE during median 11.5 years of follow-up after age 67. Participants who developed LOE were at an increased hazard of mortality compared to those who did not, with adjusted hazard ratio 2.39 (95% CI 2.12-2.71). We observed excess mortality due to stroke, dementia, neurologic conditions, and end-stage renal disease in participants with compared to without LOE. Only 4 deaths (1.1%) were directly attributed to seizure-related causes.ConclusionsPersons who develop LOE are at increased risk of death compared to those without epilepsy, even after adjusting for comorbidities. The majority of this excess mortality is due to stroke and dementia.

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Abstract MP75: Glycemia (Hemoglobin A1c) is Not Related to Incident Venous Thromboembolism in the Atherosclerosis Risk in Communities Study

Circulation ◽

10.1161/circ.127.suppl_12.amp75 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Elizabeth J Bell ◽

Pamela L Lutsey ◽

Vijay Nambi ◽

Mary Cushman ◽

Elizabeth Selvin ◽

...

Keyword(s):

Venous Thromboembolism ◽

Smoking Status ◽

Cox Proportional Hazards ◽

Self Report ◽

Diabetes Diagnosis ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Diagnosed Diabetes

Introduction— Diabetes has been inconsistently associated with increased risk of venous thromboembolism (VTE). Glycemia is positively associated with coagulation activation and hypofibrinolysis, resulting in a procoagulant state. However, there is little direct evidence on associations of glycemia with VTE. Hypothesis— Glycemia, as measured by hemoglobin A 1c (A 1c ), is positively associated with incident VTE over a follow-up period of 15 years. Methods— The Atherosclerosis Risk in Communities (ARIC) study is a population-based cohort study of middle-aged adults followed for 15 years after visit 2, when A 1c was measured. Because A 1c is affected by treatment in diagnosed diabetics, separate analyses were conducted for individuals with diagnosed diabetes. Diagnosed diabetes was defined as taking diabetes medication or a history of diabetes (self-report). We assessed the relation between A 1c and incident VTE during follow-up using Cox proportional hazards models, controlling for potential confounders: age, sex, race, smoking status and amount, hormone use, body mass index, and waist-to-hip ratio. Results— The cohort free of VTE and/or anticoagulant use in 1990-1992 included 11,976 participants without a diagnosis of diabetes (317 VTE events) and 1,040 participants with a diagnosis of diabetes (45 VTE events). As shown in the figure, the adjusted hazard ratio estimates, using participants with an A 1c < 5.70 % and without diagnosed diabetes as the referent, were close to 1, regardless of A 1c level and diabetes diagnosis status. Further, there was no relation in analyses conducted by VTE type (provoked and unprovoked) or in participants with diabetes (both diagnosed and undiagnosed) relative to those without diabetes. Conclusions— In conclusion, although a modest association cannot be ruled out, our findings do not support an association between A 1c and VTE.

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Vital exhaustion and sudden cardiac death in the Atherosclerosis Risk in Communities Study

Heart ◽

10.1136/heartjnl-2017-311825 ◽

2017 ◽

Vol 104 (5) ◽

pp. 423-429 ◽

Cited By ~ 2

Author(s):

Brittany M Bogle ◽

Nona Sotoodehnia ◽

Anna M Kucharska-Newton ◽

Wayne D Rosamond

Keyword(s):

Risk Factors ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Disease Risk ◽

Ventricular Tachyarrhythmia ◽

Atherosclerosis Risk In Communities ◽

Vital Exhaustion ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Aric Study

ObjectiveVital exhaustion (VE), a construct defined as lack of energy, increased fatigue and irritability, and feelings of demoralisation, has been associated with cardiovascular events. We sought to examine the relation between VE and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) Study.MethodsThe ARIC Study is a predominately biracial cohort of men and women, aged 45–64 at baseline, initiated in 1987 through random sampling in four US communities. VE was measured using the Maastricht questionnaire between 1990 and 1992 among 13 923 individuals. Cox proportional hazards models were used to examine the hazard of out-of-hospital SCD across tertiles of VE scores.ResultsThrough 2012, 457 SCD cases, defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual, were identified in ARIC by physician record review. Adjusting for age, sex and race/centre, participants in the highest VE tertile had an increased risk of SCD (HR 1.48, 95% CI 1.17 to 1.87), but these findings did not remain significant after adjustment for established cardiovascular disease risk factors (HR 0.94, 95% CI 0.73 to 1.20).ConclusionsAmong participants of the ARIC study, VE was not associated with an increased risk for SCD after adjustment for cardiovascular risk factors.

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Abstract MP48: Social Network, Social Support, and the Risk of Incident Stroke: The Atherosclerosis Risk in Communities Study

Circulation ◽

10.1161/circ.129.suppl_1.mp48 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Mako Nagayoshi ◽

Susan A Everson-Rose ◽

Hiroyasu Iso ◽

Thomas H Mosley ◽

Kathryn M Rose ◽

...

Keyword(s):

Social Support ◽

Social Network ◽

Short Form ◽

Network Size ◽

Community Dwelling ◽

Men And Women ◽

Atherosclerosis Risk In Communities ◽

Vital Exhaustion ◽

Increased Risk ◽

Atherosclerosis Risk

Background and Purpose: Having a small social network and lack of social support have been associated with incident coronary heart disease, but little is known about their association with incident stroke. Thus, we assessed the association of a small social network and lack of social support with risk of incident stroke and evaluated whether the relation was mediated by vital exhaustion and inflammation. Methods: The Atherosclerosis Risk in Communities (ARIC) Study measured social network and social support in 13,686 men and women (mean, 57 ± 5.7 years, 56% female, 24% black; 76% white) initially free of stroke. The 10-item Lubben Social Network Scale and 16-item Interpersonal Support Evaluation List-Short Form were used to assess social network size and social support, respectively. Results: Over a median follow-up of 18.6-years, 905 incident strokes occurred. Relative to participants with a large social network, those with a small social network had a higher risk of stroke [HR (95% CI): 1.43 (1.03-2.00)] after adjustment for demographic and socioeconomic characteristics and marital status ( Table ). Further adjustment for other potential confounders attenuated the association slightly. Vital exhaustion, but not inflammation, partly mediated the association between a small social network and stroke. Social support was unrelated to incident stroke. Conclusions: In this sample of US community-dwelling men and women, having a small social network was associated with excess risk of incident stroke. As with other cardiovascular conditions, having a small social network appears to be associated with modestly increased risk of incident stroke.

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Abstract 47: Atrial Fibrillation is Associated With Increased Risk of Incident Venous Thromboembolism: The Atherosclerosis Risk in Communities Study

Circulation ◽

10.1161/circ.135.suppl_1.47 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Pamela L Lutsey ◽

Faye L Norby ◽

Alvaro Alonso ◽

Mary Cushman ◽

Lin Y Chen ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Incidence Rate ◽

Case Reports ◽

Time Dependent ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Shared Risk

Background: It is well-established that atrial fibrillation (AF) is associated with thrombus formation in the left atrium, which can lead to ischemic stroke. Case reports, autopsies, and transesophageal echo data have indicated that clot formation also occurs in the right atrium (i.e. right-side intracardiac thrombosis) of AF patients, which could lead to pulmonary embolism (PE). However, it is unclear whether this occurrence is common. Objective: Test the hypotheses that individuals with incident AF are at elevated risk of developing venous thromboembolism (VTE), and that the association will be stronger for those presenting with PE alone versus PE and deep vein thrombosis (DVT) or DVT alone. Methods: A total of 15,205 Atherosclerosis Risk in Communities (ARIC) study participants, aged 45-64 years, were followed from baseline (1987-1989) to 2011 for incidence of AF and VTE (median follow-up 19.8 years). Incident AF and VTE events were identified via active surveillance and defined by relevant hospital discharge ICD codes. VTE events were validated by medical record review. Multivariable-adjusted Cox proportional hazards regression models were used, with AF modeled as a time-dependent covariate. We also evaluated separately risk of PE without evidence of DVT, DVT without PE, and events presenting with both PE and DVT. Results: At baseline participants were on average 54 years old, 55% female and 26% black. In the absence of AF there were 678 VTE events, for an incidence rate of 2.6 per 1000 person-years. After an AF diagnosis there were 77 events, with an incidence rate of 7.1 per 1000 person-years. In multivariable-adjusted models, having AF (versus no AF) was associated with a greater risk of incident VTE; the HR (95% CI) was 2.10 (1.65-2.68) after adjustment for demographics, 1.82 (1.42-2.32) additionally accounting for numerous AF and VTE risk factors, and 1.97 (1.53-2.53) after further adjusting for time-dependent anticoagulant use. When we restricted to PE events without evidence of DVT there were 188 events in total, of which 19 occurred following a diagnosis of AF. The HR for AF (versus no AF) was 1.53 (0.92-2.56) in fully adjusted models. For DVT alone there were 384 events in total, of which 48 occurred after AF diagnosis; the HR for AF was 2.43 (1.77-3.33). Among the 116 events presenting with both DVT and PE, 10 occurred after AF diagnosis, and the HR for AF was 1.36 (0.67-2.75). Conclusions: Diagnosis with AF was associated with a nearly 2-fold increased risk of incident VTE. The association was not stronger when isolated to those with PE without DVT, suggesting that higher risk of VTE among AF patients may be due to either the coagulation abnormalities that accompany AF, or shared risk factors that were not fully accounted for in this analysis.

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Abstract 12385: Past Alcohol Consumption and Incident Atrial Fibrillation

Circulation ◽

10.1161/circ.132.suppl_3.12385 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Shalini Dixit ◽

Alvaro Alonso ◽

Elsayed Z Soliman ◽

Lin Y Chen ◽

Gregory M Marcus

Keyword(s):

Atrial Fibrillation ◽

Alcohol Consumption ◽

Alcohol Use ◽

Population Based ◽

Self Report ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Before And After ◽

Dietary Intake Assessment ◽

Aric Study

Introduction: Although current alcohol consumption appears to be a risk factor for incident atrial fibrillation (AF), limitations related to self-reported alcohol use and confounding in observational studies limit the certainty of conclusions regarding causality. Whether cessation of alcohol consumption can protect against incident AF remains unknown. Methods: We examined all participants in the Atherosclerosis Risk in Communities (ARIC) study, a population-based cohort of 15,792 men and women aged 45-65, without prevalent AF. Past alcohol consumption was assessed via self-report during the baseline dietary intake assessment. Cases of incident AF were ascertained via study ECGs, hospital discharge ICD-9 codes, and death certificates. Results: Among 15,262 participants with complete survey data, 2,898 (19.0%) were former drinkers. During an average follow-up of 17.4 years, there were 380 cases of incident AF in former consumers. Both before and after adjustment for potential confounders, a longer duration of alcohol abstinence was associated with a lower risk of developing AF; previously consuming alcohol for a longer duration and consuming a greater quantity of alcohol were each associated with a higher risk of developing AF (Table). Conclusions: Among former drinkers, the number of years of drinking and the amount of alcohol consumed may each confer an increased risk of AF. Given that a longer duration of abstinence was associated with a decreased risk of AF, modification of alcohol use could potentially play a role in AF prevention.

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Abstract 79: Troponin T, NT-proBNP, and Incidence of Stroke: The Atherosclerosis Risk in Communities (ARIC) Study

Stroke ◽

10.1161/str.44.suppl_1.a79 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Aaron R Folsom ◽

Vijay Nambi ◽

Elizabeth J Bell ◽

Oludamilola W Oluleye ◽

Rebecca F Gottesman ◽

...

Keyword(s):

Ischemic Stroke ◽

General Population ◽

Troponin T ◽

High Sensitivity ◽

Hazard Ratio ◽

Cardioembolic Stroke ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Aric Study

Increased levels of plasma troponins and natriuretic peptides in the general population are associated with increased future risk of cardiovascular disease, but only limited information exists on these biomarkers and stroke occurrence. In a prospective epidemiological study, the Atherosclerosis Risk in Communities (ARIC) Study, we tested the hypothesis that high-sensitivity troponin T (TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are associated positively with incidence of stroke. We measured plasma high-sensitivity TnT and NT-proBNP in 10,902 men or women initially free of stroke and followed them for a mean of 11.3 years for stroke occurrence (n=507). Analyses were performed using proportional hazards modeling. Both biomarkers were associated positively with total stroke, nonlacunar ischemic, and especially, cardioembolic stroke, but not with lacunar or hemorrhagic stroke. After adjustment for other stroke risk factors, the hazard ratio (95% CI) per one SD greater increment of natural log-transformed TnT was 1.23 (1.13, 1.35) for total stroke, 1.27 (1.15, 1.40) for total ischemic stroke, and 1.36 (1.14, 1.62) for cardioembolic stroke. Likewise, the hazard ratio per one SD greater natural log-transformed NT-proBNP, was 1.37 (1.26, 1.49) for total stroke, 1.39 (1.27, 1.53) for total ischemic stroke, and 1.95 (1.67, 2.28) for cardioembolic stroke. The hazard ratios for jointly high values of TnT (≥0.013 ug/L) and NT-proBNP (≥155.2 pg/mL), versus neither biomarker high, were 2.70 (1.92, 3.79) for total stroke and 6.26 (3.40, 11.5) for cardioembolic stroke, and somewhat stronger for NT-proBNP than TnT. Strikingly, approximately 58% of cardioembolic strokes occurred in the highest quintile of pre-stroke NT-proBNP (versus 3% occurring in the lowest quintile), and 32% of cardioembolic strokes occurred in participants who had both NT-proBNP in the highest quintile and were known by ARIC to have atrial fibrillation sometime before their cardioembolic stroke occurrence. In conclusion, in the general population, elevated plasma TnT and NT-proBNP concentrations are associated with increased risk of cardioembolic and other nonlacunar ischemic strokes.

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Prophylactic phenytoin in severe head injuries

Journal of Neurosurgery ◽

10.3171/jns.1979.51.4.0507 ◽

1979 ◽

Vol 51 (4) ◽

pp. 507-509 ◽

Cited By ~ 56

Author(s):

Richard N. W. Wohns ◽

Allen R. Wyler

Keyword(s):

Retrospective Study ◽

Head Injury ◽

High Probability ◽

Late Onset ◽

Head Injuries ◽

Content Type ◽

Posttraumatic Epilepsy ◽

Fine Print

✓ We are reporting a retrospective study of 62 patients whose head injury was sufficiently severe to cause a high probability of posttraumatic epilepsy. Of 50 patients treated with phenytoin, 10% developed epilepsy of late onset. Twelve patients not treated with phenytoin but who had head injuries of equal magnitude had a 50% incidence of epilepsy. These data from a highly selected group of patients with severe head injuries confirm the bias that treatment with phenytoin decreases the incidence of posttraumatic epilepsy.

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Abstract 158: Progression of Microvascular Brain Disease and Stroke Incidence in the Atherosclerosis Risk in Communities Study

Stroke ◽

10.1161/str.51.suppl_1.158 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Silvia Koton ◽

Andrea L Schneider ◽

B. Gwen Windham ◽

Thomas H Mosley ◽

Rebecca F Gottesman ◽

...

Keyword(s):

Rating Scale ◽

Brain Mri ◽

Brain Disease ◽

Cardiovascular Health Study ◽

Stroke Incidence ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Unit Increase

Background and Purpose: Data on the significance of combined white matter hyperintensities (WMH)/lacunar brain infarcts measures progression for the incidence of clinical stroke are scarce. We aimed to study associations between the progression in measures of microvascular brain disease over time and risk of stroke in the Atherosclerosis Risk in Communities (ARIC) Study. Methods: We analyzed data on 907 ARIC participants who underwent a brain MRI in 1993-95, a second brain MRI in 2004-6, and were subsequently followed for incident stroke through December 31 st , 2017 (median [IQR] follow-up of 12.6 [8.9-13.4] years from the second brain MRI in 2004-6). At each MRI, WMH was categorized according to the Cardiovascular Health Study 0-9 rating scale and scans were centrally reviewed for lacunar infarcts. A combined measure of microvascular brain disease was defined, and progression from the first to the second brain MRI, manifesting as new WMHs and lacunes at the second brain MRI, was categorized as: no progression; increase of ≥1 unit in WMH grade or incident lacune; increase of ≥1 unit in WMH grade and incident lacune. All fatal and non-fatal strokes occurring in the participants during the study period, and adjudicated as definite/probable ischemic or hemorrhagic incident stroke, were included in this analysis. Associations between progression of microvascular brain disease and incidence of stroke were studied with Cox proportional hazard models, adjusting for age, gender, race, education level, BMI, smoking, hypertension, diabetes and coronary heart disease. Results: At the second brain MRI (mean age 72y), no progression in the combined measure of microvascular disease was found in 38% of participants, while 57% showed ≥1 unit increase in WMH grade or new lacune, and 5% showed increased WMH grade and new lacune. Sixty-four incident strokes occurred during follow-up. Compared to no change in the combined measure, progression of microvascular brain disease expressed as ≥1 unit increase in WMH grade and incident lacune was significantly associated with higher risk of stroke (adjusted HR 3.01, 95% CI 1.30-6.95). Conclusion: Progression of combined measures of microvascular brain disease over a decade is associated with a significant increased risk of stroke.

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Incidence of head injury and traumatic brain injury among people with Alzheimer’s disease

Journal of Epidemiology & Community Health ◽

10.1136/jech-2018-211960 ◽

2019 ◽

Vol 73 (5) ◽

pp. 451-454 ◽

Cited By ~ 4

Author(s):

Sarianna Ilmaniemi ◽

Heidi Taipale ◽

Antti Tanskanen ◽

Jari Tiihonen ◽

Sirpa Hartikainen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Head Injury ◽

Head Injuries ◽

Community Dwelling ◽

University Hospital ◽

Health Concern ◽

Increased Risk

BackgroundInjuries caused by falling are a major health concern among older population. For older people, falls are the leading cause of head injuries; especially, persons with cognitive disorders have an increased risk of falling.ObjectiveTo compare the incidence of head injury and traumatic brain injury (TBI) among persons with Alzheimer’s disease (AD) with persons without AD.MethodsThis register-based study was conducted on a nationwide cohort, which includes all community-dwelling persons diagnosed with AD in Finland in 2005–2011. Persons with previous head injuries were excluded, leaving 67 172 persons with AD. For each person with AD, a matching person without AD and previous head injury were identified with respect to age, sex and university hospital district. The Cox proportional hazard model and competing risk analyses were used to estimate HR for head injury and TBI.ResultsPersons with AD had 1.34-fold (95% CI 1.29 to 1.40) risk of head injuries and 1.49-fold (95% CI 1.40 to 1.59) risk of TBIs after accounting for competing risks of death and full adjustment by socioeconomic status, drug use and comorbidities.ConclusionPersons with AD are more likely to have a head injury or TBI incident than persons without AD.

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