Traditional risk factors may not explain increased incidence of myocardial infarction in MS

ObjectiveTo compare the risk of incident acute myocardial infarction (AMI) in the multiple sclerosis (MS) population and a matched population without MS, controlling for traditional vascular risk factors.MethodsWe conducted a retrospective matched cohort study using population-based administrative (health claims) data in 2 Canadian provinces, British Columbia and Manitoba. We identified incident MS cases using a validated case definition. For each case, we identified up to 5 controls without MS matched on age, sex, and region. We compared the incidence of AMI between cohorts using incidence rate ratios (IRR). We used Cox proportional hazards regression to compare the hazard of AMI between cohorts adjusting for sociodemographic factors, diabetes, hypertension, and hyperlipidemia. We pooled the provincial findings using meta-analysis.ResultsWe identified 14,565 persons with MS and 72,825 matched controls. The crude incidence of AMI per 100,000 population was 146.2 (95% confidence interval [CI] 129.0–163.5) in the MS population and 128.8 (95% CI 121.8–135.8) in the matched population. After age standardization, the incidence of AMI was higher in the MS population than in the matched population (IRR 1.18; 95% CI 1.03–1.36). After adjustment, the hazard of AMI was 60% higher in the MS population than in the matched population (hazard ratio 1.63; 95% CI 1.43–1.87).ConclusionThe risk of AMI is elevated in MS, and this risk may not be accounted for by traditional vascular risk factors.

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Hypertension and Hypercholesterolemia Modify Dementia Risk in Relation to APOE ɛ4 Status

Journal of Alzheimer s Disease ◽

10.3233/jad-201609 ◽

2021 ◽

pp. 1-12

Author(s):

Jagan A. Pillai ◽

Kou Lei ◽

James Bena ◽

Lisa Penn ◽

James B. Leverenz

Keyword(s):

Risk Factors ◽

Lower Risk ◽

Proportional Hazards ◽

Age Groups ◽

Cox Proportional Hazards ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Cox Proportional Hazards Models ◽

Dementia Risk ◽

Dementia Onset

Background: There is significant interest in understanding the role of modifiable vascular risk factors contributing to dementia risk across age groups. Objective: Risk of dementia onset was assessed in relation to vascular risk factors of hypertension and hypercholesterolemia among cognitively normal APOE ɛ4 carriers and non-carriers. Methods: In a sample of prospectively characterized longitudinal cohort from the National Alzheimer’s Coordinating Center database, 9,349 participants met criteria for normal cognition at baseline, had a CDR-Global (CDR-G) score of zero, and had concomitant data on APOE ɛ4 status and medical co-morbidities including histories of hypertension and hypercholesterolemia. Multivariable Cox proportional hazards models adjusted for well-known potential confounders were used to compare dementia onset among APOE ɛ4 carriers and non-carriers by young (≤65 years) and old (> 65 year) age groups. Results: 519 participants converted to dementia within an average follow up of 5.97 years. Among older APOE ɛ4 carriers, hypercholesterolemia was related to lower risk of dementia (HR (95% CI), 0.68 (0.49–0.94), p = 0.02). Among older APOE ɛ4 non-carriers, hypertension was related to higher risk of dementia (HR (95% CI), 1.44 (1.13–1.82), p = 0.003). These results were corroborated among a subset with autopsy data characterizing underlying neuropathology. Among younger participants, vascular risk factors did not impact dementia risk, likely from a lower frequency of vascular and Alzheimer’s as etiologies of dementia among this cohort. Conclusion: A history of hypercholesterolemia related to a lower risk of dementia among older APOE ɛ4 carriers, while hypertension related to a higher risk of dementia among older APOE ɛ4 non-carriers.

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Abstract TP177: Long-term Stroke Risk in Patients Diagnosed with Hypertensive Encephalopathy

Stroke ◽

10.1161/str.48.suppl_1.tp177 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Michael P Lerario ◽

Alexander E Merkler ◽

Gino Gialdini ◽

Neal S Parikh ◽

Gary L Bernardini ◽

...

Keyword(s):

Risk Factors ◽

Proportional Hazards ◽

Hypertensive Encephalopathy ◽

Cox Proportional Hazards ◽

Vascular Risk Factors ◽

Misclassification Error ◽

Rank Test ◽

Vascular Risk ◽

Comorbidity Index

Introduction: The long-term cerebrovascular consequences of hypertensive encephalopathy (HE) are poorly understood. Therefore, we aimed to measure the risk of stroke following HE. Methods: We identified all adult patients discharged from nonfederal acute care hospitals between 2005 and 2013 in New York with a primary ICD-9-CM discharge diagnosis of HE (437.2). Only patients who underwent magnetic resonance imaging were included to reduce the likelihood of misclassification error. Patients with all other forms of hypertension (401-405), without concomitant codes for HE or cerebrovascular disease (430-438), served as controls. The primary outcome was incident stroke (431, 433.x1, 434.x1, or 436 in the absence of hemorrhage, trauma, or rehabilitation codes). Kaplan-Meier survival analysis was used to calculate cumulative rates of incident stroke and Cox proportional hazards analysis was used to determine the association between HE and incident stroke while adjusting for demographics, vascular risk factors, and the Elixhauser comorbidity index. Results: We identified 1,386 patients with HE and 2,869,873 with hypertension. Over a mean follow-up period of 3.3 (+/-1.8) years, we identified 66,594 ischemic and 12,343 hemorrhagic strokes. After 5 years, the cumulative rate of stroke was 7.8% (95% CI, 6.2-9.9%) in patients with HE and 3.2% (95% CI, 3.2-3.2%; P<0.001 for the log-rank test) in patients with any other hypertensive disease. After adjusting for demographics, vascular risk factors, and the Elixhauser comorbidity index, HE was independently associated with incident stroke (hazard ratio, 1.9; 95% CI, 1.5-2.4) as compared to controls. This association was similar when considering ischemic and hemorrhagic stroke separately. Conclusions: Patients discharged after HE face a higher long-term risk of subsequent stroke than patients without prior neurological complications of hypertension.

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Abstract TP165: Associations Between Parkinson Disease and Stroke

Stroke ◽

10.1161/str.48.suppl_1.tp165 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Benjamin R Kummer ◽

Ashley E Aaroe ◽

Hooman Kamel ◽

Costantino Iadecola ◽

Babak B Navi

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Parkinson Disease ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Vascular Risk Factors ◽

Annual Incidence ◽

Vascular Risk ◽

Medicare Beneficiaries ◽

The Relationship

Introduction: Cerebral ischemia and vascular risk factors are associated with the development of Alzheimer disease (AD). While Parkinson disease (PD) is also a common neurodegenerative condition, the relationship between ischemic stroke and PD remains unclear. Some evidence suggests a shared pathogenic pathway between both diseases. Methods: We used inpatient and outpatient claims data from 2008-2014 in a 5% sample of Medicare beneficiaries ≥66 years of age. Our variables of interest were: 1) a hospital-based diagnosis of ischemic stroke and 2) an outpatient or hospital-based diagnosis of idiopathic PD. Previously validated ICD-9-CM code algorithms were used to identify all diagnoses. We used Cox proportional hazards modeling to characterize the relationship between ischemic stroke and PD, while adjusting for demographics and vascular risk factors. We assessed both the association between PD and subsequent stroke, as well as stroke and subsequent PD. In a separate but identically designed set of analyses, we characterized the relationship between ischemic stroke and AD as a point of comparison. Results: Our analysis encompassed nearly 1.6 million patients with a mean age of 73(+/- 8) years, of whom 57% were female. The annual incidence of ischemic stroke was 1.75% (95% confidence interval [CI], 1.67-1.85%) after a diagnosis of PD versus 0.96% (95% CI, 0.96-0.97%) in those without PD (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.19-1.32). In contrast, the annual incidence of ischemic stroke was 1.96% (95% CI, 1.89-2.03%) after a diagnosis of AD versus 0.96% (95% CI, 0.96-0.97%) in those without AD (aHR, 0.98; 95% CI, 0.95-1.02). The annual incidence of PD was 0.97% (95% CI, 0.92-1.03%) after ischemic stroke versus 0.39% (95% CI, 0.38-0.39%) in those without ischemic stroke (aHR, 1.62; 95% CI, 1.53-1.72). In contrast, the annual incidence of AD was 3.66% (95% CI, 3.56-3.78%) after a diagnosis of ischemic stroke versus 1.17% (95% CI, 1.16-1.17%) in those without ischemic stroke (aHR, 1.67; 95% CI, 1.61-1.72). Conclusions: Among Medicare beneficiaries, the relationships between stroke and PD were similar to those between stroke and AD. As in AD, a link may exist between cerebrovascular disease and PD.

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MS risk in immigrants in the McDonald era

Neurology ◽

10.1212/wnl.0000000000008611 ◽

2019 ◽

Vol 93 (24) ◽

pp. e2203-e2215 ◽

Cited By ~ 3

Author(s):

Dalia L. Rotstein ◽

Ruth Ann Marrie ◽

Colleen Maxwell ◽

Sima Gandhi ◽

Susan E. Schultz ◽

...

Keyword(s):

Risk Factors ◽

Middle East ◽

Lower Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Health Claims ◽

Increased Risk ◽

Health Claims Data ◽

Incident Cases

ObjectiveTo determine risk factors for multiple sclerosis (MS) in immigrants and to compare MS risk in immigrants and long-term residents in Ontario, Canada.MethodsWe applied a validated algorithm to linked, population-based immigration and health claims data to identify incident cases of MS in immigrants and long-term residents between 1994 and 2016. We conducted 2 multivariable Cox proportional hazards regression analyses: 1 analysis limited to the immigrant cohort assessing potential risk factors for developing MS, and 1 analysis comparing MS risk between immigrants and matched long-term residents (1:3 match).ResultsWe identified 2,304,302 immigrants for the immigrant-only analysis, of whom 1,526 (0.066%) developed MS. Risk was greatest in those <15 years old at landing (referent <15 years; 16–30 years: hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.63–0.85; 31–45 years: HR 0.55, 95% CI 0.47–0.64). Immigrants from the Middle East (HR 1.22, 95% CI 1.06–1.40) were at greater MS risk than immigrants from Western nations; all other regions had lower risk (p < 0.0001). The matched analysis included 2,207,751 immigrants and 6,362,169 long-term residents. Immigrants were less likely to develop MS than long-term residents (p < 0.0001), although this lower risk was attenuated with longer residence in Canada.ConclusionsMS incidence in immigrants to Ontario, Canada, varied widely by region of origin, with greatest risk seen in those from the Middle East. Longer residence in Canada was associated with increased risk, even with migration in adulthood, suggesting that environmental exposures into adulthood contribute to MS risk.

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Aerobic exercise interventions reduce blood pressure in patients after stroke or transient ischaemic attack: a systematic review and meta-analysis

British Journal of Sports Medicine ◽

10.1136/bjsports-2017-098903 ◽

2018 ◽

Vol 53 (24) ◽

pp. 1515-1525 ◽

Cited By ~ 10

Author(s):

Cheng Wang ◽

Jessica Redgrave ◽

Mohsen Shafizadeh ◽

Arshad Majid ◽

Karen Kilner ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Blood Pressure ◽

Transient Ischaemic Attack ◽

Meta Analysis ◽

Vascular Risk Factors ◽

Cochrane Library ◽

Vascular Risk ◽

Exercise Interventions ◽

Ischaemic Attack

ObjectiveSecondary vascular risk reduction is critical to preventing recurrent stroke. We aimed to evaluate the effect of exercise interventions on vascular risk factors and recurrent ischaemic events after stroke or transient ischaemic attack (TIA).DesignIntervention systematic review and meta-analysis.Data sourcesOVID MEDLINE, PubMed, The Cochrane Library, Web of Science, The National Institute for Health and Care Excellence, TRIP Database, CINAHL, PsycINFO, SCOPUS, UK Clinical Trials Gateway and the China National Knowledge Infrastructure were searched from 1966 to October 2017.Eligibility criteriaRandomised controlled trials evaluating aerobic or resistance exercise interventions on vascular risk factors and recurrent ischaemic events among patients with stroke or TIA, compared with control.ResultsTwenty studies (n=1031) were included. Exercise interventions resulted in significant reductions in systolic blood pressure (SBP) −4.30 mm Hg (95% CI −6.77 to −1.83) and diastolic blood pressure −2.58 mm Hg (95% CI −4.7 to −0.46) compared with control. Reduction in SBP was most pronounced among studies initiating exercise within 6 months of stroke or TIA (−8.46 mm Hg, 95% CI −12.18 to −4.75 vs −2.33 mm Hg, 95% CI −3.94 to −0.72), and in those incorporating an educational component (−7.81 mm Hg, 95% CI −14.34 to −1.28 vs −2.78 mm Hg, 95% CI −4.33 to −1.23). Exercise was also associated with reductions in total cholesterol (−0.27 mmol/L, 95% CI −0.54 to 0.00), but not fasting glucose or body mass index. One trial reported reductions in secondary vascular events with exercise, but was insufficiently powered.SummaryExercise interventions can result in clinically meaningful blood pressure reductions, particularly if initiated early and alongside education.

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Midlife Vascular Risk Factors and the Risk of Alzheimer's Disease: A Systematic Review and Meta-Analysis

Journal of Alzheimer s Disease ◽

10.3233/jad-140954 ◽

2014 ◽

Vol 42 (4) ◽

pp. 1295-1310 ◽

Cited By ~ 80

Author(s):

Xiang-Fei Meng ◽

Jin-Tai Yu ◽

Hui-Fu Wang ◽

Meng-Shan Tan ◽

Chong Wang ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Meta Analysis ◽

Vascular Risk Factors ◽

Vascular Risk

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Abstract 140: Association Between Epilepsy and the Risk of Ischemic Stroke or Myocardial Infarction

Stroke ◽

10.1161/str.48.suppl_1.140 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Matthew A Mercuri ◽

Alexander E Merkler ◽

Neal S Parikh ◽

Michael E Reznik ◽

Hooman Kamel

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Ischemic Stroke ◽

Elderly Patients ◽

Proportional Hazards ◽

Predictor Variable ◽

Cox Proportional Hazards ◽

Vascular Events ◽

Increased Risk ◽

Acute Mi

Background: Vascular brain injury can result in epilepsy. It is posited that seizures in elderly patients might reflect subclinical vascular disease and thus herald future clinical vascular events. Hypothesis: Seizures in elderly patients are associated with an increased risk of ischemic stroke or myocardial infarction (MI). Methods: We obtained inpatient and outpatient claims data from 2008-2014 on a 5% sample of Medicare beneficiaries ≥66 years of age. The predictor variable was epilepsy, defined as two or more inpatient or outpatient claims with a diagnosis of seizure. The primary outcome was a composite of ischemic stroke or acute MI. The predictors and outcomes were all ascertained with previously validated ICD-9-CM code algorithms. Survival statistics and Cox proportional hazards models were used to assess the relationship between epilepsy and incident ischemic stroke or MI while adjusting for demographic characteristics and vascular risk factors. Patients were censored at the first occurrence of a stroke or MI, at the time of death, or on December 31, 2014. Results: Among 1,548,556 beneficiaries with a mean follow-up of 4.4 (±1.8) years, 15,055 (1.0%) developed epilepsy and 121,866 (7.9%) experienced an ischemic stroke or acute MI. Patients with seizures were older (76.1 versus 73.7 years) and had a significantly higher burden of vascular comorbidities than the remainder of the cohort. The annual incidence of stroke or acute MI was 3.28% (95% confidence interval [CI], 3.10-3.47%) in those with seizures versus 1.79% (95% CI, 1.78-1.80%) in those without (unadjusted hazard ratio [HR], 1.89; 95% CI, 1.78-2.00). After adjustment for demographics and risk factors, epilepsy had a weak association with the composite outcome (adjusted HR, 1.36; 95% CI, 1.29-1.44), a stronger association with ischemic stroke (adjusted HR, 1.77; 95% CI, 1.65-1.90), and no association with acute MI (adjusted HR, 0.95; 95% CI, 0.86-1.04). Conclusions: We found an association between epilepsy in elderly patients and future ischemic stroke but not acute MI. Therefore, seizures might signify occult cerebrovascular disease but not necessarily occult disease in other vascular beds.

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Abstract WP479: Associations Between Vascular Risk, Amyloid Burden and Incident Dementia: The ARIC-PET Study

Stroke ◽

10.1161/str.51.suppl_1.wp479 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Rebecca F Gottesman ◽

Aozhou Wu ◽

Josef Coresh ◽

Clifford R Jack ◽

David S Knopman ◽

...

Keyword(s):

Risk Factors ◽

Proportional Hazards ◽

Brain Mri ◽

Amyloid Β ◽

Standardized Uptake Value ◽

Cox Proportional Hazards ◽

Vascular Risk ◽

Brain Volumes ◽

Dementia Risk ◽

Incident Dementia

Background: Midlife vascular risk factors (MVRF) are associated with incident dementia. Similarly, amyloid β(Aβ) and neurodegeneration (e.g.brain volumes), as parts of the Alzheimer’s Disease (AD) ATN framework, are associated with cognition. Whether vascular and AD-associated factors contribute to dementia independently or interact synergistically to reduce cognitive ability is not well understood. Methods: Recruited from 3 U.S. communities, ARIC-PET participants were followed from 1987-89 (45-64 yo) through 2016-17 (74-94 yo). Cognition was evaluated in 2011-13 (ages 69-88), and twice more, every 2-3 years. In 2011-13, nondemented ARIC-PET participants had a brain MRI, with measurement of white matter hyperintensities (WMH) and brain volumes, with florbetapir (Aβ) PET scans in 2012-14; global cortical standardized uptake value ratio (SUVR) was log-transformed and standardized. Dementia was classified by expert review, as well as phone and medical record surveillance. The relative contributions of vascular risk (MVRF, WMH volume) and AD pathology (elevated Aβ SUVR, smaller AD signature region volumes) to incident dementia were evaluated with Cox proportional hazards regression. Results: In 298 individuals, 36 developed dementia. In models with key MVRF, demographics, and Aβ SUVR, hypertension and Aβ each independently predicted dementia risk (per SD of Aβ SUVR: HR 2.57, 95% CI 1.72-3.84; hypertension: HR 2.57, 95% CI 1.16-5.67), but didn’t interact on dementia risk. WMH (per SD: HR 1.51, 95% CI 1.03-2.20) and Aβ SUVR (per SD: HR 2.52, 95% CI 1.83-3.47) each contributed to incident dementia but WMH lost significance when MVRF were added to the model. Smaller AD signature regions were associated with incident dementia, independent of Aβ SUVR, and remained significant after adjustment for MVRF (HR per SD 2.18, 95% CI 1.18-4.01). Conclusions: Midlife hypertension and late-life Aβ independently contribute to dementia risk, but don’t synergize on a multiplicative scale. Neurodegeneration (e.g.smaller AD signature region volume) is also associated with incident dementia, independent of Aβ and MVRF. Multiple pathways leading to dementia should be considered when evaluating risk factors and interventions to reduce the burden of dementia.

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Abstract 7: Association Between Incidence, Severity and Recurrence of Ischemic Stroke and Risk of Dementia: The Atherosclerosis Risk in Communities Study

Stroke ◽

10.1161/str.52.suppl_1.7 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Silvia Koton ◽

James R Pike ◽

Michelle C Johansen ◽

David Knopman ◽

Kamakshi Lakshminarayan ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Cox Proportional Hazards ◽

Vascular Risk Factors ◽

Stroke Severity ◽

Vascular Risk ◽

Atherosclerosis Risk In Communities ◽

Expert Review ◽

Increased Risk ◽

Atherosclerosis Risk

Background: Ischemic Stroke (IS) is associated with an increased risk of dementia, but the relative contribution of IS severity or recurrence to cognition is not known. We aimed to determine the risk of dementia after incident IS and how it varies by stroke severity and recurrence in the Atherosclerosis Risk in Communities (ARIC) study. Methods: 15,405 ARIC participants free of stroke and dementia at baseline (1987-9) were followed for IS and dementia through 2019. Incident and recurrent IS were classified by expert review of hospital records, with stroke severity by the National Institutes of Health Stroke Scale (NIHSS) classified as NIHSS≤5, 6-10, 11-15, ≥16. Dementia cases were adjudicated through expert review of in-person evaluations, informant interviews, phone assessments, hospitalization code or death certificates. Poisson regression models with robust error variance were used to estimate dementia incidence in participants with and without IS, and associations between time-dependent IS incidence (excluding dementia in the first year after stroke), frequency and severity, and dementia were studied with Cox proportional hazards models, adjusting for demographics, APOE ε4 and vascular risk factors . Results: 1151 IS (970 incident) and 2807 dementia cases were identified. NIHSS was available for 877 IS (76%). Adjusted incidence rates (95% CI) of dementia per 100 person-years were 0.45 (0.42-0.49) in participants without IS vs. 1.33 (1.15-1.55) in those with IS. Compared to no IS, risk of dementia (adjusted HR, 95% CI) increased with IS number and severity from 1.71 (1.47-1.99) for participants with one IS to 6.68 (3.58-12.46) for those with ≥3 events, and from 1.64 (1.36-1.98) for NIHSS≤5 to 4.43 (1.84-10.68) for NIHSS≥16 ( Table ). Conclusion: Risk of dementia is significantly increased after stroke, independent of vascular risk factors. These data suggest a dose-response relationship between number of stroke events and stroke severity, and risk of dementia.

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