Supplementary Material for: Adjudication of Transient Ischemic Attack and Stroke in the Multi-Ethnic Study of Atherosclerosis

<b><i>Background:</i></b> To describe adjudication of transient ischemic attack (TIA) and stroke in an observational study. <b><i>Methods:</i></b> We detail the process used to adjudicate TIA and stroke in the Multi-Ethnic Study of Atherosclerosis (MESA), a large longitudinal cohort study. Two of three vascular neurologists adjudicated each event using specific protocols. We examined the initial agreement, effect of imaging on diagnosis of TIA versus ischemic stroke, and effect of strict and less strict criteria on the number of ischemic stroke subtypes classified as undetermined. <b><i>Results:</i></b> Of 573 adjudicated events over 13.5 years of follow-up, 95 (16.5%) had TIA and 269 (47.0%) had stroke: 211 (78.4%) ischemic, 43 (16.0%) hemorrhagic, and 15 (5.6%) other. Disagreements occurred on 16% of initial adjudication of events. Using results from imaging, the number with TIA decreased by 8.6% and with ischemic stroke increased by 4.1%. Using less strict criteria to classify ischemic stroke subtypes reduced the number classified as undetermined, from 137 to 59, and numbers classified as cardioembolic and small vessel doubled. <b><i>Conclusions:</i></b> We hope that this work will motivate and facilitate investigators to use MESA data to investigate issues concerning TIA and stroke and will inform investigators seeking to adjudicate TIA and stroke in other studies

Supplementary Material for: Physical Inactivity Predicts Slow Gait Speed in an Elderly Multi-Ethnic Cohort Study: The Northern Manhattan Study

<p><b><i>Introduction:</i></b> Gait speed is associated with multiple adverse outcomes of aging. We hypothesized that physical inactivity would be prospectively inversely associated with gait speed independently of white matter hyperintensity volume and silent brain infarcts on MRI. <b><i>Methods:</i></b> Participants in the Northern Manhattan Study MRI sub-study had physical activity assessed when they were enrolled into the study. A mean of 5 years after the MRI, participants had gait speed measured via a timed 5-meter walk test. Physical inactivity was defined as reporting no leisure-time physical activity. Multi-variable logistic and quantile regression was performed to examine the associations between physical inactivity and future gait speed adjusted for confounders. <b><i>Results:</i></b> Among 711 participants with MRI and gait speed measures (62% women, 71% Hispanic, mean age 74.1 ± 8.4), the mean gait speed was 1.02 ± 0.26 m/s. Physical inactivity was associated with a greater odds of gait speed in the lowest quartile (<0.85 m/s, adjusted OR 1.90, 95% CI 1.17-3.08), and in quantile regression with 0.06 m/s slower gait speed at the lowest 20 percentile (<i>p</i> = 0.005). <b><i>Conclusions:</i></b> Physical inactivity is associated with slower gait speed independently of osteoarthritis, grip strength, and subclinical ischemic brain injury. Modifying sedentary behavior poses a target for interventions aimed at reducing decline in mobility.</p

Supplementary Material for: Regional Subclinical Cerebrovascular Disease Is Associated with Balance in an Elderly Multi-Ethnic Population

<b><i>Introduction:</i></b> White matter hyperintensity volume (WMHV) and subclinical brain infarcts (SBI) are associated with impaired mobility, but less is known about the association of WMHV in specific brain regions. We hypothesized that anterior WMHV would be associated with lower scores on the Short Physical Performance Battery (SPPB), a well-validated mobility scale. <b><i>Methods:</i></b> The SPPB was measured a median of 5 years after enrollment into the Northern Manhattan MRI sub study. Volumetric distributions for WMHV in 14 brain regions as a proportion of total cranial volume were determined. Multi-variable linear regression was performed to examine the association of SBI and regional log-WMHV with the SPPB score. <b><i>Results:</i></b> Among 668 participants with SPPB measurements (mean 74 ± 9 years, 37% male and 70% Hispanic), the mean SPPB score was 8.2 ± 2.9. Total (beta = –0.3 per SD, <i>p</i> = 0.001), anterior periventricular (beta = –0.4 per SD, <i>p</i> = 0.001), parietal (beta = –0.2 per SD, <i>p</i> = 0.02) and frontal (beta = –0.3 per SD, <i>p</i> = 0.002) WMHVs were associated with SPPB; other WMHV and SBI were not associated with the SPPB. <b><i>Conclusions:</i></b> WMHV, especially in the anterior ­cerebral regions, is associated with a lower SPPB. Prevention of subclinical cerebrovascular disease is a potential target to prevent physical decline in the elderly

Erratum: Update on the Global Burden of Ischemic and Hemorrhagic Stroke in 1990-2013: The GBD 2013 Study

<b><i>Background:</i></b> Global stroke epidemiology is changing rapidly. Although age-standardized rates of stroke mortality have decreased worldwide in the past 2 decades, the absolute numbers of people who have a stroke every year, and live with the consequences of stroke or die from their stroke, are increasing. Regular updates on the current level of stroke burden are important for advancing our knowledge on stroke epidemiology and facilitate organization and planning of evidence-based stroke care. <b><i>Objectives:</i></b> This study aims to estimate incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke (IS) and hemorrhagic stroke (HS) for 188 countries from 1990 to 2013. <b><i>Methodology:</i></b> Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated using all available data on mortality and stroke incidence, prevalence and excess mortality. Statistical models and country-level covariate data were employed, and all rates were age-standardized to a global population. All estimates were produced with 95% uncertainty intervals (UIs). <b><i>Results:</i></b> In 2013, there were globally almost 25.7 million stroke survivors (71% with IS), 6.5 million deaths from stroke (51% died from IS), 113 million DALYs due to stroke (58% due to IS) and 10.3 million new strokes (67% IS). Over the 1990-2013 period, there was a significant increase in the absolute number of DALYs due to IS, and of deaths from IS and HS, survivors and incident events for both IS and HS. The preponderance of the burden of stroke continued to reside in developing countries, comprising 75.2% of deaths from stroke and 81.0% of stroke-related DALYs. Globally, the proportional contribution of stroke-related DALYs and deaths due to stroke compared to all diseases increased from 1990 (3.54% (95% UI 3.11-4.00) and 9.66% (95% UI 8.47-10.70), respectively) to 2013 (4.62% (95% UI 4.01-5.30) and 11.75% (95% UI 10.45-13.31), respectively), but there was a diverging trend in developed and developing countries with a significant increase in DALYs and deaths in developing countries, and no measurable change in the proportional contribution of DALYs and deaths from stroke in developed countries. <b><i>Conclusion:</i></b> Global stroke burden continues to increase globally. More efficient stroke prevention and management strategies are urgently needed to halt and eventually reverse the stroke pandemic, while universal access to organized stroke services should be a priority

Supplementary Material for: Recurrent Stroke in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

<b><i>Background and Purpose:</i></b> WARCEF randomized 2,305 patients in sinus rhythm with ejection fraction (EF) ≤35% to warfarin (INR 2.0-3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. In this study, we explore IIS rates in WARCEF patients with and without baseline stroke to look for risk factors for IIS and determine if a subgroup with an IIS rate high enough to give a clinically relevant stroke risk reduction can be identified. <b><i>Methods:</i></b> We compared potential stroke risk factors between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS, by comparing IIS rates between different risk factors. For EF we tried cut-off points of 10, 15 and 20%. The cut-off point 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. IIS rates per hundred patient years (/100PY) were calculated in patient groups with significant risk factors. Missing values were assigned the modal value. <b><i>Results:</i></b> Twenty of 248 (8.1%) patients with baseline stroke and 64 of 2,048 (3.1%) without had IIS. IIS rate in patients with baseline stroke (2.37/100PY) was greater than patients without (0.89/100PY) (rate ratio 2.68, p < 0.001). Fourteen of 219 (6.4%) patients with ejection fraction (EF) <15% and 70 of 2,079 (3.4%) with EF ≥15% had IIS. In the multiple regression analysis stroke at baseline (p < 0.001) and EF <15% vs. ≥15% (p = 0.005) remained significant predictors of IIS. IIS rate was 2.04/100PY in patients with EF <15% and 0.95/100PY in patients with EF ≥15% (p = 0.009). IIS rate in patients with baseline stroke and reduced EF was 5.88/100PY with EF <15% decreasing to 2.62/100PY with EF <30%. <b><i>Conclusions:</i></b> In a WARCEF exploratory analysis, prior stroke and EF <15% were risk factors for IIS. Further research is needed to determine if a clinically relevant stroke risk reduction is obtainable with warfarin in HF patients with prior stroke and reduced EF