IMPORTANCE Hospital cooling improves outcome after cardiac arrest, but prehospital cooling immediately after return of spontaneous circulation may result in better outcomes. OBJECTIVE To determine ...whether prehospital cooling improves outcomes after resuscitation from cardiac arrest in patients with ventricular fibrillation (VF) and without VF. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial that assigned adults with prehospital cardiac arrest to standard care with or without prehospital cooling, accomplished by infusing up to 2 L of 4°C normal saline as soon as possible following return of spontaneous circulation. Adults in King County, Washington, with prehospital cardiac arrest and resuscitated by paramedics were eligible and 1359 patients (583 with VF and 776 without VF) were randomized between December 15, 2007, and December 7, 2012. Patient follow-up was completed by May 1, 2013. Nearly all of the patients resuscitated from VF and admitted to the hospital received hospital cooling regardless of their randomization. MAIN OUTCOMES AND MEASURES The primary outcomes were survival to hospital discharge and neurological status at discharge. RESULTS The intervention decreased mean core temperature by 1.20°C (95% CI, −1.33°C to −1.07°C) in patients with VF and by 1.30°C (95% CI, −1.40°C to −1.20°C) in patients without VF by hospital arrival and reduced the time to achieve a temperature of less than 34°C by about 1 hour compared with the control group. However, survival to hospital discharge was similar among the intervention and control groups among patients with VF (62.7% 95% CI, 57.0%-68.0% vs 64.3% 95% CI, 58.6%-69.5%, respectively; P = .69) and among patients without VF (19.2% 95% CI, 15.6%-23.4% vs 16.3% 95% CI, 12.9%-20.4%, respectively; P = .30). The intervention was also not associated with improved neurological status of full recovery or mild impairment at discharge for either patients with VF (57.5% 95% CI, 51.8%-63.1% of cases had full recovery or mild impairment vs 61.9% 95% CI, 56.2%-67.2% of controls; P = .69) or those without VF (14.4% 95% CI, 11.3%-18.2% of cases vs 13.4% 95% CI,10.4%-17.2% of controls; P = .30). Overall, the intervention group experienced rearrest in the field more than the control group (26% 95% CI, 22%-29% vs 21% 95% CI, 18%-24%, respectively; P = .008), as well as increased diuretic use and pulmonary edema on first chest x-ray, which resolved within 24 hours after admission. CONCLUSION AND RELEVANCE Although use of prehospital cooling reduced core temperature by hospital arrival and reduced the time to reach a temperature of 34°C, it did not improve survival or neurological status among patients resuscitated from prehospital VF or those without VF. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00391469
BACKGROUND AND PURPOSE—Emerging data suggest that left atrial disease may cause ischemic stroke in the absence of atrial fibrillation or flutter (AF). If true, this condition may provide a cause for ...many strokes currently classified as cryptogenic.
METHODS—Among 6741 participants in the Multi-Ethnic Study of Atherosclerosis who were free of clinically apparent cerebrovascular or cardiovascular disease (including AF) at baseline, we examined the association between markers of left atrial abnormality on a standard 12-lead ECG—specifically P-wave area, duration, and terminal force in lead V1—and the subsequent risk of ischemic stroke while accounting for incident AF.
RESULTS—During a median follow-up of 8.5 years, 121 participants (1.8%) had a stroke and 541 participants (8.0%) were diagnosed with AF. In Cox proportional hazards models adjusting for potential baseline confounders, P-wave terminal force in lead V1 was more strongly associated with incident stroke (hazard ratio per 1 SD increase, 1.21; 95% confidence interval, 1.02–1.44) than with incident AF (hazard ratio per 1 SD, 1.11; 95% confidence interval, 1.03–1.21). The association between P-wave terminal force in lead V1 and stroke was robust in numerous sensitivity analyses accounting for AF, including analyses that excluded those with any incident AF or modeled any incident AF as having been present from baseline.
CONCLUSIONS—We found an association between baseline P-wave morphology and incident stroke even after accounting for AF. This association may reflect an atrial cardiopathy that leads to stroke in the absence of AF.
OBJECTIVETo examine the hypothesis that atrial fibrosis and associated atrial cardiopathy may be in the causal pathway of cardioembolic stroke independently of atrial fibrillation (AF) by comparing ...atrial fibrosis burden between patients with embolic stroke of undetermined source (ESUS), patients with AF, and healthy controls.
METHODSWe used late-gadolinium-enhancement MRI to compare atrial fibrosis in 10 patients with ESUS against 10 controls (no stroke, no AF) and 10 patients with AF. Fibrosis was compared between groups, controlling for stroke risk factors.
RESULTSMean age was 51 ± 15 years, and 43% of participants were female. Patients with ESUS had more atrial fibrosis than controls (16.8 ± 5.7% vs 10.6 ± 5.7%, p = 0.019) and similar fibrosis compared to patients with AF (17.8 ± 4.8%, p = 0.65). Odds ratios of ESUS per quartile of fibrosis were 3.22 (95% CI CI 1.11–9.32, p = 0.031, unadjusted) and 3.17 (95% CI 1.05–9.52, p = 0.041, CHA2DVASc score adjusted). Patients with >12% fibrosis had a higher percentage of ESUS (77.8% vs 27.3%, p = 0.02), and patients with >20% fibrosis had the highest proportion of ESUS (4 of 5).
CONCLUSIONSPatients with ESUS exhibit similar atrial fibrosis compared to patients with AF and more fibrosis than healthy controls. Fibrosis is associated with ESUS after controlling for stroke risk factors, supporting the hypothesis that fibrosis is in the causal pathway of cardioembolic stroke independently of AF. Prospective studies are needed to assess the role of anticoagulation in primary and secondary stroke prevention in patients with high atrial fibrosis.
Trends in cardiovascular disparities are poorly understood, even as diversity increases in the United States.
To examine U.S. trends in racial/ethnic and nativity disparities in cardiovascular ...health.
Repeated cross-sectional study.
NHANES (National Health and Nutrition Examination Survey), 1988 to 2014.
Adults aged 25 years or older who did not report cardiovascular disease.
Racial/ethnic, nativity, and period differences in Life's Simple 7 (LS7) health factors and behaviors (blood pressure, cholesterol, hemoglobin A1c, body mass index, physical activity, diet, and smoking) and optimal composite scores for cardiovascular health (LS7 score ≥10).
Rates of optimal cardiovascular health remain below 40% among whites, 25% among Mexican Americans, and 15% among African Americans. Disparities in optimal cardiovascular health between whites and African Americans persisted but decreased over time. In 1988 to 1994, the percentage of African Americans with optimal LS7 scores was 22.8 percentage points (95% CI, 19.3 to 26.4 percentage points) lower than that of whites in persons aged 25 to 44 years and 8.0 percentage points (CI, 6.4 to 9.7 percentage points) lower in those aged 65 years or older. By 2011 to 2014, differences decreased to 10.6 percentage points (CI, 7.4 to 13.9 percentage points) and 3.8 percentage points (CI, 2.5 to 5.0 percentage points), respectively. Disparities in optimal LS7 scores between whites and Mexican Americans were smaller but also decreased. These decreases were due to reductions in optimal cardiovascular health among whites over all age groups and periods: Between 1988 to 1994 and 2011 to 2014, the percentage of whites with optimal cardiovascular health decreased 15.3 percentage points (CI, 11.1 to 19.4 percentage points) for those aged 25 to 44 years and 4.6 percentage points (CI, 2.7 to 6.5 percentage points) for those aged 65 years or older.
Only whites, African Americans, and Mexican Americans were studied.
Cardiovascular health has declined in the United States, racial/ethnic and nativity disparities persist, and decreased disparities seem to be due to worsening cardiovascular health among whites rather than gains among African Americans and Mexican Americans. Multifaceted interventions are needed to address declining population health and persistent health disparities.
National Institute of Neurological Disorders and Stroke and National Center for Advancing Translational Sciences of the National Institutes of Health.
Rationale
Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion of cryptogenic ...strokes.
Aims
The aim of the ARCADIA trial is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy.
Sample size estimate
1100 participants.
Methods and design
Biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial conducted at 120 U.S. centers participating in NIH StrokeNet.
Population studied
Patients ≥ 45 years of age with embolic stroke of undetermined source and evidence of atrial cardiopathy, defined as ≥ 1 of the following markers: P-wave terminal force >5000 µV × ms in ECG lead V1, serum NT-proBNP > 250 pg/mL, and left atrial diameter index ≥ 3 cm/m2 on echocardiogram. Exclusion criteria include any atrial fibrillation, a definite indication or contraindication to antiplatelet or anticoagulant therapy, or a clinically significant bleeding diathesis. Intervention: Apixaban 5 mg twice daily versus aspirin 81 mg once daily. Analysis: Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation.
Study outcomes
The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage.
Discussion
ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation.
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A multicenter trial evaluated patients with previous anterior-wall myocardial infarction who were not candidates for an implantable cardioverter–defibrillator. Patients were randomly assigned either ...to have an automated external defibrillator (AED) at home for management of cardiac arrest or to receive standard treatment. At a median follow-up of 3 years, there was no significant difference between the two groups in mortality from any cause.
Patients with previous anterior-wall myocardial infarction were randomly assigned either to have an automated external defibrillator (AED) at home for management of cardiac arrest or to receive standard treatment. At a median follow-up of 3 years, there was no significant difference between the two groups in mortality from any cause.
Sudden cardiac arrest remains an unsolved public health problem, with approximately 166,200 out-of-hospital cardiac arrests occurring annually in the United States.
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The use of automated external defibrillators (AEDs) by trained lay responders in community-based public-access defibrillation programs has been shown to increase survival after sudden cardiac arrest. However, what effect the use of the device has on overall mortality for the community at risk is unknown.
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Particularly impressive results have been reported when sudden cardiac arrest is witnessed and an AED is immediately available, as on airplanes and in casinos and airports.
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However, the effect of such programs . . .
Research based on administrative data has advantages, including large numbers, consistent data, and low cost. This study was designed to compare different methods of stroke classification using ...administrative data.
Administrative hospital discharge data and medical record review of 206 patients were used to evaluate 3 algorithms for classifying stroke patients. These algorithms were based on all (algorithm 1), the first 2 (algorithm 2), or the primary (algorithm 3) administrative discharge diagnosis code(s). The diagnoses after review of medical record data were considered the gold standard. Then, using a large administrative data set, we compared patients with a primary discharge diagnosis of stroke with patients with their stroke discharge diagnosis code in a nonprimary position.
Compared with the gold standard, algorithm 1 had the highest kappa for classifying ischemic stroke, with a sensitivity of 86%, specificity of 95%, positive predictive value of 90%, and kappa=0.82. Algorithm 3 had the highest kappa values for intracerebral hemorrhage and subarachnoid hemorrhage. For intracerebral hemorrhage, the sensitivity was 85%, specificity was 96%, positive predictive value was 89%, and kappa=0.82. For subarachnoid hemorrhage, those values were 90%, 97%, 94%, and 0.88, respectively. Nonprimary position ischemic stroke patients had significantly greater comorbidity and 30-day mortality (odds ratio, 3.2) than primary position ischemic stroke patients.
Stroke classification in these administrative data were optimal using all discharge diagnoses for ischemic stroke and primary discharge diagnosis only for intracerebral and subarachnoid hemorrhage. Selecting ischemic stroke patients on the basis of primary discharge diagnosis may bias administrative samples toward more benign, unrepresentative outcomes and should be avoided.
BACKGROUND—Although guidelines suggest that older adults engage in regular physical activity (PA) to reduce cardiovascular disease (CVD), surprisingly few studies have evaluated this relationship, ...especially in those >75 years. In addition, with advancing age the ability to perform some types of PA might decrease, making light-moderate exercise such as walking especially important to meet recommendations.
METHODS AND RESULTS—Prospective cohort analysis among 4207 US men and women of a mean age of 73 years (standard deviation=6) who were free of CVD at baseline in the Cardiovascular Health Study were followed from 1989 to 1999. PA was assessed and cumulatively updated over time to minimize misclassification and assess the long-term effects of habitual activity. Walking (pace, blocks, combined walking score) was updated annually from baseline through 1999. Leisure-time activity and exercise intensity were updated at baseline, 1992, and 1996. Incident CVD (fatal or nonfatal myocardial infarction, coronary death, or stroke) was adjudicated using medical records. During 41 995 person-years of follow-up, 1182 CVD events occurred. After multivariable adjustment, greater PA was inversely associated with coronary heart disease, stroke (especially ischemic stroke), and total CVD, even in those ≥75 years. Walking pace, distance, and overall walking score, leisure-time activity, and exercise intensity were each associated with lower risk. For example, in comparison with a walking pace <2 mph, those that habitually walked at a pace >3 mph had a lower risk of coronary heart disease (0.50; confidence interval, 0.38–0.67), stroke (0.47; confidence interval, 033–0.66), and CVD (0.50; confidence interval, 0.40–0.62).
CONCLUSIONS—These data provide empirical evidence supporting PA recommendations, in particular, walking, to reduce the incidence of CVD among older adults.
BACKGROUND AND PURPOSE—The associations of individual long-chain n-3 polyunsaturated fatty acids with incident ischemic stroke and its main subtypes are not well established. We aimed to investigate ...prospectively the relationship of circulating eicosapentaenoic acid, docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with risk of total ischemic, atherothrombotic, and cardioembolic stroke.
METHODS—We measured circulating phospholipid fatty acids at baseline in 3 separate US cohortsCHS (Cardiovascular Health Study), NHS (Nurses’ Health Study), and HPFS (Health Professionals Follow-Up Study). Ischemic strokes were prospectively adjudicated and classified into atherothrombotic (large- and small-vessel infarctions) or cardioembolic by imaging studies and medical records. Risk according to fatty acid levels was assessed using Cox proportional hazards (CHS) or conditional logistic regression (NHS, HPFS) according to study design. Cohort findings were pooled using fixed-effects meta-analysis.
RESULTS—A total of 953 incident ischemic strokes were identified (408 atherothrombotic, 256 cardioembolic, and 289 undetermined subtypes) during median follow-up of 11.2 years (CHS) and 8.3 years (pooled, NHS and HPFS). After multivariable adjustment, lower risk of total ischemic stroke was seen with higher DPA (highest versus lowest quartiles; pooled hazard ratio HR, 0.74; 95% confidence interval CI, 0.58–0.92) and DHA (HR, 0.80; 95% CI, 0.64–1.00) but not eicosapentaenoic acid (HR, 0.94; 95% CI, 0.77–1.19). DHA was associated with lower risk of atherothrombotic stroke (HR, 0.53; 95% CI, 0.34–0.83) and DPA with lower risk of cardioembolic stroke (HR, 0.58; 95% CI, 0.37–0.92). Findings in each individual cohort were consistent with pooled results.
CONCLUSIONS—In 3 large US cohorts, higher circulating levels of DHA were inversely associated with incident atherothrombotic stroke and DPA with cardioembolic stroke. These novel findings suggest differential pathways of benefit for DHA, DPA, and eicosapentaenoic acid.
Background
The apolipoprotein E (APOE) ε4 allele confers higher risk of neurodegeneration and Alzheimer's disease (AD), but differs by race/ethnicity. We examined this association in American ...Indians.
Methods
The Strong Heart Study is a population‐based cohort of American Indians who were 64 to 95 years of age in 2010 to 2013. APOE ε4 status, brain imaging, and neuropsychological testing was collected in N = 811 individuals. Summary statistics, graphics, and generalized linear regressions—adjusted for sociodemographics, clinical features, and intracranial volume with bootstrap variance estimator—compared APOE ε4 carriers with non‐carriers.
Results
APOE ε4 carriers comprised 22% of the population (0.7% homozygotes). Participants were mean 73 years, 67% female, and 54% had some college education. The majority were obese (>50%), hypertensive (>80%), and diabetic (>50%). Neither imaging findings nor multidomain cognitive testing showed any substantive differences between APOE ε4 carriers and non‐carriers.
Conclusion
We found no evidence of neurodegenerative risk from APOE ε4 in American Indians. Additional studies are needed to examine potential protective features.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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