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Objectives To test associations between subclinical brain infarcts (SBIs) and functional decline independently of intervening clinical vascular events and other vascular risk factors. Design Longitudinal follow‐up for a mean 7.3 years. Generalized estimating equation models were used to test associations between SBIs, number of perivascular spaces (PVSs), baseline Barthel Index (BI), and change in BI, adjusting for sociodemographic, vascular, and cognitive risk factors and for stroke and myocardial infarction occurring during follow‐up. Setting Population‐based prospective cohort study. Participants Stroke‐free individuals from the racially and ethnically diverse Northern Manhattan Study (N=1,290). Measurements Annual functional assessments using the BI (range 0–100). Results Mean age was 70.6 ± 9.0, 40% of participants were male, 66% were Hispanic, 193 (16%) had SBIs, and 508 (42%) had large PVSs. SBIs were not associated with baseline BI. In a fully adjusted model, there was a change in BI of –0.85 points per year (95% confidence interval (CI)=–1.01 to –0.69); those with SBI had an additional change in BI 0f –0.88 points (95% CI=–1.43 to –0.32). There were no associations between PVS and baseline BI or change in BI. Conclusion In a large population‐based study, we found a strong and independent association between “subclinical” markers of cerebrovascular injury and important clinical, person‐centered functional trajectories. Future research could clarify the evolution of such subclinical markers over time and test strategies to prevent their progression and minimize related disability. J Am Geriatr Soc 66:2144–2150, 2018.

Author(s): Di Tullio, Marco R; Qian, Min; Thompson, John LP; Labovitz, Arthur J; Mann, Douglas L; Sacco, Ralph L; Pullicino, Patrick M; Freudenberger, Ronald S; Teerlink, John R; Graham, Susan; Lip, Gregory YH; Levin, Bruce; Mohr, Jay P; Buchsbaum, Richard; Estol, Conrado J; Lok, Dirk J; Ponikowski, Piotr; Anker, Stefan D; Homma, Shunichi; WARCEF Investigators | Abstract: AimsLeft atrium (LA) dilation is associated with adverse cardiovascular (CV) outcomes. Blood stasis, thrombus formation and atrial fibrillation may occur, especially in heart failure (HF) patients. It is not known whether preventive antithrombotic treatment may decrease the incidence of CV events in HF patients with LA enlargement. We investigated the relationship between LA enlargement and CV outcomes in HF patients and the effect of different antithrombotic treatments.Methods and resultsTwo-dimensional echocardiography with LA volume index (LAVi) measurement was performed in 1148 patients with systolic HF from the Warfarin versus Aspirin in Reduced Ejection Fraction (WARCEF) trial. Patients were randomized to warfarin or aspirin and followed for 3.4 ± 1.7 years. While the primary aim of the trial was a composite of ischaemic stroke, death, and intracerebral haemorrhage, the present report focuses on the individual CV events, whose incidence was compared across different LAVi and treatment subgroups. After adjustment for demographics and clinical covariates, moderate or severe LA enlargement was significantly associated with total death (hazard ratio 1.6 and 2.7, respectively), CV death (HR 1.7 and 3.3), and HF hospitalization (HR 2.3 and 2.6) but not myocardial infarction (HR 1.0 and 1.4) or ischaemic stroke (1.1 and 1.5). The increased risk was observed in both patients treated with warfarin or aspirin. In warfarin-treated patients, a time in therapeutic range g60% was associated with lower event rates, and an interaction between LAVi and time in therapeutic range was observed for death (P = 0.034).ConclusionsIn patients with systolic HF, moderate or severe LA enlargement is associated with death and HF hospitalization despite treatment with antithrombotic medications. The possibility that achieving a more consistent therapeutic level of anticoagulation may decrease the risk of death requires further investigation.

In cohort studies the outcome is often time to a particular event, and subjects are followed at regular intervals. Periodic visits may also monitor a secondary irreversible event influencing the event of primary interest, and a significant proportion of subjects develop the secondary event over the period of follow-up. The status of the secondary event serves as a time-varying covariate, but is recorded only at the times of the scheduled visits, generating incomplete time-varying covariates. While information on a typical time-varying covariate is missing for entire follow-up period except the visiting times, the status of the secondary event are unavailable only between visits where the status has changed, thus interval-censored. One may view interval-censored covariate of the secondary event status as missing time-varying covariates, yet missingness is partial since partial information is provided throughout the follow-up period. Current practice of using the latest observed status produces biased estimators, and the existing missing covariate techniques cannot accommodate the special feature of missingness due to interval censoring. To handle interval-censored covariates in the Cox proportional hazards model, we propose an available-data estimator, a doubly robust-type estimator as well as the maximum likelihood estimator via EM algorithm and present their asymptotic properties. We also present practical approaches that are valid. We demonstrate the proposed methods using our motivating example from the Northern Manhattan Study.

Background/Objectives We previously showed that global brain white matter hyperintensity volume (WMHV) was associated with accelerated long-term functional decline. The objective of the current study was to determine whether WMHV in particular brain regions is more predictive of functional decline. Design Prospective population-based study. Setting Northern Manhattan magnetic resonance imaging (MRI) study. Participants Individuals free of stroke at baseline (N = 1,195; mean age 71 ± 9; n = 460 (39%) male). Measurements Participants had brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences. Volumetric WMHV distribution across 14 brain regions (brainstem; cerebellum; bilateral frontal, occipital, temporal, and parietal lobes; and bilateral anterior and posterior periventricular white matter (PVWM)) was determined using a combination of bimodal image intensity distribution and atlas-based methods. Participants had annual functional assessments using the Barthel Index (BI) (range 0–100) over a mean of 7.3 years and were followed for stroke, myocardial infarction (MI), and mortality. Because there were multiple collinear variables, least absolute shrinkage and selection operator (LASSO) regression–selected regional WMHV variables most associated with outcomes and adjusted generalized estimating equations models were used to estimate associations with baseline BI and change over time. Results Using LASSO regularization, only right anterior PVWM was found to meet criteria for selection, and each standard deviation greater WMHV was associated with accelerated functional decline of 0.95 additional BI points per year (95% confidence interval (CI) = −1.20 to −0.70) in an unadjusted model, −0.92 points per year (95% CI = −1.18 to −0.67) with baseline covariate adjustment, and −0.87 points per year (95% CI = −1.12 to −0.62) after adjusting for incident stroke and MI. Conclusion In this large population-based study with long-term repeated measures of function, periventricular WMHV was particularly associated with accelerated functional decline.

A high pulse pressure (PP) is associated with adverse cardiovascular (CV) outcomes; however, this relationship may be reversed in patients with heart failure with reduced ejection fraction (HFREF).Patients from the WARCEF trial with left ventricular ejection fraction ≤35% were included. PP was divided into tertiles: ≤42, 42-54 and54 mm Hg. Age and ejection fraction adjusted Kaplan-Meier curves were generated to evaluate the relationship between PP and outcomes [mortality, CV mortality, stroke and HF hospitalizations (HFH)]. Cox proportional hazards models were created incorporating PP as a continuous variable. The interaction of PP with New York Heart Association (NYHA) functional class was examined. Linear and restricted cubic splines were used to study nonlinear association between PP and outcomes.We included 2,299 patients with a mean(±SD) follow-up of 3.5 ± 1.8 years. The lowest tertile of PP (≤42 mm Hg) was associated with significantly higher CV mortality and HFH. Cox proportional hazards models showed a reduction in CV death and HFH with higher PP, with adjusted hazard ratios (HR) of 0.91 (P = 0.02) and 0.93 (P = 0.04) per 10 mm Hg increase in PP. This relationship was more pronounced in subjects with NYHA functional class III-IV. Spline analysis showed that the association between PP and CV mortality and HFH was only seen at PP values lower than 40 mm Hg.In patients with advanced HFREF, a low PP (40 mm Hg) portends a worse prognosis, whereas a high PP (50 mm Hg) predicts a relatively favourable prognosis.

When analyzing time-to-event cohort data, two different ways of choosing a time scale have been discussed in the literature: time-on-study or age at onset of disease. One advantage of choosing the latter is interpretability of the hazard ratio as a function of age. To handle the analysis of age at onset in a principled manner, we present an analysis of the Cox Proportional Hazards model with time-varying coefficient for left-truncated and right-censored data. In the analysis of Northern Manhattan Study (NOMAS) with age at onset of stroke as outcome, we demonstrate that well-established risk factors may be important only around a certain age span and less established risk factors can have a strong effect in a certain age span.

AIMS The aim of this study was to determine whether the CHA2 DS2 -VASc score can predict adverse outcomes such as death, ischaemic stroke, and major haemorrhage, in patients with systolic heart failure in sinus rhythm. METHODS AND RESULTS CHA2 DS2 -VASc scores were calculated for 1101 patients randomized to warfarin and 1123 patients randomized to aspirin. Adverse outcomes were defined as death or ischaemic stroke, death alone, ischaemic stroke alone, and major haemorrhage. Using proportional hazards models, we found that each 1-point increase in the CHA2 DS2 -VASc score was associated with increased hazard of death or ischaemic stroke events [hazard ratio (HR) for the warfarin arm = 1.21, 95% confidence interval (CI) 1.13-1.30, P < 0.001; for aspirin, HR = 1.20, 95% CI 1.11-1.29, P < 0.001]. Similar increased hazards for higher CHA2 DS2 -VASc scores were observed for death alone, ischaemic stroke alone, and major haemorrhage. Overall performance of the CHA2 DS2 -VASc score was assessed using c-statistics for full models containing the risk score, treatment assignment, and score-treatment interaction, with the c-statistics for the full models ranging from 0.57 for death to 0.68 for major haemorrhage. CONCLUSIONS The CHA2 DS2 -VASc score predicted adverse outcomes in patients with systolic heart failure in sinus rhythm, with modest prediction accuracy.

Objectives To determine whether infectious burden (IB) is associated with worse performance and decline on a battery of neuropsychological tests. Design Prospective cohort study (Northern Manhattan Study (NOMAS)). Setting Community. Participants A subsample of 588 stroke-free NOMAS participants with IB and cognitive data (mean age 71 ± 8, 62% female, 14% white, 16% black, 70% Hispanic) and 419 with repeat cognitive testing. Measurements Samples used for IB data were collected at baseline. Two waves of neurocognitive assessments occurred during follow-up. Participants underwent a neuropsychological battery and had repeated testing (mean time span 6 ± 2 years). Using factor analysis–derived domain-specific Z scores for language, memory, executive function, and processing speed, associations between a quantitative stroke risk-weighted IB index (IBI), based on five common infections (Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, herpes simplex viruses 1 and 2), and cognitive performance and decline in each domain was examined. Results Adjusting for demographic characteristics, socioeconomic status, crystallized cognitive abilities, and vascular risk factors, the IBI was inversely associated with executive function at baseline (beta = −0.10, P = .01) but not with baseline language, memory, or processing speed performance in adjusted analyses. The IBI was associated with cognitive decline in the memory domain, adjusting for demographic and vascular risk factors (P = .02). Conclusion A quantitative stroke risk-weighted measure of IB explained variability in baseline executive function performance and associated with decline in memory. Past exposure to common infections may contribute to vascular cognitive impairment and warrants further study.

Background and purpose Our objective was to investigate the association between recurrent stroke risk and headache induced by extended-release dipyridamole (ER-DP) when administered alone or with low-dose aspirin (ASA+ER-DP). Methods This was a post hoc analysis of prospectively collected data on recurrent stroke risk and headache as an adverse event or reason for treatment discontinuation from the PRoFESS (N = 20 332) and ESPS2 (N = 6602) trials. Hazard ratios (HRs) for recurrent stroke were calculated using the Cox model. Results In PRoFESS, the 2.5-year recurrent stroke risk in patients receiving ASA+ER-DP was 8.2% in those with headache within 7 days of starting treatment and 9.4% in those without [HR 0.85, 95% confidence interval (CI) 0.73–0.98; P = 0.03]. Recurrent stroke risk was 5.0% in patients who discontinued ASA+ER-DP due to headache by day 90 versus 9.2% in those who did not (HR 0.52, 95% CI 0.35–0.77; P = 0.001). No such difference was observed in clopidogrel-treated patients. In ESPS2, risk of recurrent stroke was 6.2% in patients who discontinued ASA+ER-DP due to headache by day 90 versus 9.8% in patients who did not (HR 0.62, 95% CI 0.31–1.27; P = 0.19) and 7.3% in patients who discontinued ER-DP due to headache by day 90 versus 13.2% in those who did not (HR 0.53, 95% CI 0.27–1.04; P = 0.06). Conclusions Patients taking ASA+ER-DP in PRoFESS who developed headache had significantly reduced stroke recurrence risk versus those without headache. Similar (non-significant) findings for ASA+ER-DP and ER-DP in ESPS2 suggest that dipyridamole-induced headache may reflect better cerebrovascular function.

Objectives: To examine the association between successful aging without subsequent cognitive decline (SA-ND) and the Northern Manhattan Study (NOMAS) global vascular risk score (GVRS), which is predictive of stroke, myocardial infarction, and vascular death. Design: Prospective cohort study. Setting: A stroke-free sample of Hispanic, black, and white participants living in the same community enrolled in a magnetic resonance imaging (MRI) substudy of NOMAS, a population-based prospective cohort study. Participants: One thousand two hundred ninety individuals in whom a cognitive screen was administered at baseline and at enrollment in the MRI substudy. Measurements: SA-ND was based on disease, disability, and cognitive function. The GVRS includes age, sex, race and ethnicity, waist circumference, alcohol intake, smoking, physical activity, blood pressure, antihypertensive medication use, fasting blood sugar, lipid levels, and peripheral vascular disease. Results: Data at baseline and follow-up were available for 1,162 participants (mean age 70 ± 9; 61% women; 13% white, 16% black, 69% Hispanic; mean GVRS 8.6 ± 0.9). Logistic regression, adjusted for education, socioeconomic status, and follow-up time, showed that the odds of SA-ND were 38% greater for each additional 1-point decrease on the GVRS (odds ratio = 1.38, 95% confidence interval = 1.17�1.61; P < .001). An inverse dose-response was observed between quartiles of GVRS and SA-ND. Greater diastolic blood pressure in participants taking antihypertensive medication and a history of claudication (P = .003) or peripheral arterial disease (P < .001) were inversely associated with SA-ND in the fully adjusted model. Conclusion: Potentially modifiable vascular risk factors were independently associated with SA-ND in a multiethnic community-based sample. Improvements in GVRSs could help promote healthy longevity in the aging population.

BACKGROUND AND PURPOSE Dolichoectasia (DE) is a vasculopathy that consists of abnormal elongation and dilatation of arteries. The objective of this study is to evaluate the frequency of DE in an unselected population and assess different diagnostic methods. METHODS The Northern Manhattan Study is a multiethnic population based cohort of stroke-free participants. The definition proposed for DE was total cranial volume (TCV)-adjusted arterial diameter ≥2 SD. Other methods studied included visual assessment, unadjusted arterial diameters cutoff, Smoker's criteria and basilar artery (BA) volume. RESULTS A total of 718 subjects were included in the analysis (mean age 71.6 ± 8.0 years, 40% men, 61% Hispanic). Using the TCV-adjusted DE definition, 19% of the sample had at least one dolichoectatic artery. In 7% of the subjects, two or more arteries were affected. The BA was the most common dolichoectatic artery. Reproducibility for arterial diameter measurements was good to excellent (.70–.95), while for visual assessment ranged from fair to good (.49–.79). CONCLUSIONS A TCV-adjusted intracranial arterial diameter ≥2 SD is proposed as a useful DE definition. The variability in the prevalence of DE depending on the methods used underscores the need to agree on a reliable, universal definition of DE.

Incomplete covariates often obscure analysis results from a Cox regression. In an analysis of the Northern Manhattan Study (NOMAS) to determine the influence of insulin resistance on the incidence of stroke in non-diabetic individuals, insulin level is unknown for 34.1% of the subjects. The available data suggest that the missingness mechanism depends on outcome variables, which may generate biases in estimating the parameters of interest if only using the complete observations. This article aimed to introduce practical strategies to analyze the NOMAS data and present sensitivity analyses by using the reweighting method in standard statistical packages. When the data set structure is in counting process style, the reweighting estimates can be obtained by built-in procedures with variance estimated by the jackknife method. Simulation results indicate that the jackknife variance estimate provides reasonable coverage probability in moderate sample sizes. We subsequently conducted sensitivity analyses for the NOMAS data, showing that the risk estimates are robust to a variety of missingness mechanisms. At the end of this article, we present the core SAS and R programs used in the analysis.

To assess the independent and combined effects of diabetes and hypertension on left ventricular (LV) diastolic function in a community-based cohort at high cardiovascular risk.Two-dimensional echocardiography was performed in 708 subjects from the Cardiac Abnormalities and Brain Lesions (CABL) study. Peak diastolic early (E) and late (A) transmitral flow, and tissue Doppler-derived early mitral annulus velocity (E') were recorded, and E/A and E/E' ratios were calculated. The population was divided into four groups: those without hypertension or diabetes (HT-/DM-), those with only hypertension (HT), only diabetes (DM), and with hypertension plus diabetes (HT + DM). In multivariate analysis, hypertension and diabetes were independent predictors of worse diastolic function. The coexistence of hypertension and diabetes was associated with greater impairment of diastolic function (higher E/E' ratio than HT-/DM-, HT, or DM, all P0.05), independent of covariates. The negative, synergistic effect of hypertension and diabetes on LV diastolic function was present both in lean participants and in overweight/obese ones. An E/E' ratio15, suggestive of increased LV filling pressure, was found in 2.2% of HT-/DM-, 8.9% of HT, 5.9% of DM, and 14.7% of HT + DM (P0.01).Hypertension and diabetes are independently associated with impaired LV diastolic function, independent of the effect of overweight/obesity and other covariates. Their coexistence results in a negative synergistic effect on LV diastolic mechanics and is associated with higher LV filling pressures than either condition alone.

Over the last decade we have made significant strides in reducing the stroke burden in the US demonstrated by decreased age-adjusted rates in stroke incidence and mortality.1,2 Recurrent stroke also appears to be decreasing.3 Accordingly, the disability-adjusted life-year (DALY) rank for stroke in the US decreased from 5th in 1990 to 7th in 2010.4 Improvement in vascular risk factor control1,5 and greater access to evidence-based preventive and acute stroke treatments6 has certainly contributed to these favorable trends. Future predictions for stroke in the US, however, demonstrate a consistent rise in prevalence due to the aging of our population.7 Moreover, the race and ethnic composition of the US population is dramatically and rapidly changing and could lead to further alterations in the US stroke profile. Racial and ethnic minorities now account for 37% of the population, including 16.9% Hispanics and 13.1% African Americans;8 it is anticipated that by mid-century Hispanics will account for 28% of the US population.9 There is strong evidence of greater stroke incidence and mortality in blacks,10 and relatively few studies have addressed stroke in Hispanics. The Brain Attack Surveillance in Corpus Christi (BASIC), which evaluated Mexican Americans (MA), and the Northern Manhattan Stroke Study (NOMAS), which included primarily Caribbean Hispanics, described a greater age adjusted incidence of ischemic stroke in Hispanics compared to whites.11–13 Over the next 4 decades, forecasts estimate that there will be 1.3 million strokes each year in the US, with the greatest growth coming from Hispanics.14 Furthermore, the accumulated cost of stroke from 2005 to 2050 is expected to balloon to 1.52 trillion with almost half attributed to minorities.15 Given these alarming forecasts, it is of great importance to elucidate and address these stroke disparities in the Hispanic population. Morgenstern and colleagues16 contribute to the emerging picture of stroke in Hispanics by reporting on ischemic stroke incidence trends over a long period of time in the BASIC study. Corpus Christi, Texas, is a bi-ethnic non-immigrant community where Mexican-Americans (MA) account for two thirds of the population. Over the 11 years of surveillance, a total of 4,646 ischemic strokes were recorded. Active hospital surveillance methods, supplemented by passive review of stroke discharge codes and county coroner records, and event validation by trained physicians, provide a robust methodological basis for detecting and ascertaining most strokes. From January 2000 to December 2010, the rate of ischemic stroke significantly declined by 35.9% and this was similar for both MA and non-Hispanic whites (NHW). However, the disparity in stroke incidence persisted for those under age 75. The age and sex-adjusted rate ratio for a first ischemic stroke was 1.34 for MA compared to NHW, but the disparities were greater at younger ages: 1.94 for those 45–59 years of age, 1.50 for those 60–74, and 1.0 for those 75 and older. Similar trends were detected for first and recurrent stroke. Therefore, despite similar reductions in stroke incidence in both ethnic groups, disparities in stroke incidence have persisted and are more prominent in younger age groups. The greater disparity in stroke incidence in the young has also been reported among African Americans. The biracial Greater Cincinnati/Northern Kentucky Stroke Study has reported stroke incidence trends between 1993 and 2005: ischemic stroke incidence decreased in whites but remained stable for blacks.17 Moreover, a significant increase in ischemic stroke was noted for those aged 20–54 in both races, but the incidence in this younger group was 2.7 times greater in blacks compared to whites.18 Observational epidemiological surveillance studies are critical for establishing temporal trend data that is often difficult to document. However, such studies sometimes are not set up to provide definite explanations for the disparities. Matching trend data on the prevalence of known stroke risk factors are helpful, but still only provide speculative evidence. Various explanations have been suggested to explain the ischemic stroke incidence disparities in Hispanics. The impact of known vascular risk factors, such as diabetes, obesity, physical inactivity and the metabolic syndrome, is greater in Hispanics compared to whites19,20 the prevalence of ideal cardiovascular health is less among Hispanics,21 and control of risk factors, particularly diabetes and hypercholesterolemia, has not improved for MA.22 The relative contribution of genetic polymorphisms is an area of interest23,24 but biological determinants of health need to be approached cautiously given the significant disparity in socioeconomic factors in Hispanics, including decreased access to health care resources, lower income and less insurance.25,26 Given the anticipated increase in stroke prevalence, the expected growth in the Hispanic population, and the persistent disparities in stroke, it is imperative to address these gaps in a comprehensive and effective manner. One of the CDC Healthy People 2020 goals is to “achieve health equity, eliminate disparities, and improve the health of all groups”.27 This is no easy task, given the complex causes of health disparities, and will call for innovative solutions. To close the gap, various interventions are required, including increasing awareness among health care providers, the general public, and key stakeholders, including payers and policy makers, smart deployment of targeted resources, educating those most at risk and increasing research on interventions to reduce stroke disparities. Community awareness, education, and provider and institutional cultural competence, are required to effectively address these issues. Identification and quantification of disparities through research reports such as the Morgenstern et al publication are the first steps in recognition of the problem, and need to be followed by design, testing, and implementation of solutions. The NIH/NINDS has recognized the importance of addressing stroke disparities by awarding the Stroke Prevention/Intervention Research Program (SPIRP) to 4 centers in the US.28 These programs will further define the causes of stroke disparities and institute innovative strategies to prevent stroke among Blacks and Hispanics. We are hopeful that these projects will develop effective interventions that can be implemented in wider segments of the population to eliminate the persistent stroke disparities that continue to greatly impact the health of Americans.

The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool designed to measure the neurological deficits most often seen with acute stroke. It assesses level of consciousness, gaze, visual fields, facial weakness, motor performance of the extremities, sensory deficit, coordination (ataxia), language (aphasia), speech (dysarthria), and hemi-inattention (neglect). For all parameters, a value of 0 is normal; so, the higher the score, the worse the neurological deficit (the highest possible score is 42). The scale was designed to be done quickly and easily at the bedside to provide a rapid and standardized assessment of neurological function in the early periods after a stroke. It has been validated and has been shown to be reliable, even when performed by non-neurologists and non-physicians. Keywords: stroke scales; neurological deficit scales; NIHSS ; clinimetrics

In a prospective study of 1,805 hospitalized patients in the Stroke Data Bank of the National Institute of Neurological and Communicative Disorders and Stroke, the 1,273 with infarction were classified into diagnostic subtypes. Diagnosis was based on the clinical history, examination, and laboratory tests including computed tomography, noninvasive vascular imaging, and where safe and relevant, angiography. Five hundred and eight cases (fully 40%) were labeled as infarcts of undetermined cause (IUC), of which 138 (27%) were evaluated with both computed tomography and angiography. The clinical syndrome and computed tomographic and angiographic findings in 91 (65.9%) of these 138 IUC cases were clearly not attributable to large-artery thrombosis and could permit reclassification of the infarct as due to some form of embolism. Failure to define a source of embolus kept them in the category of IUC. Thirty-one cases (22.5%) could be reclassified as due to stenosis or thrombosis of a large artery, and 16 (11.6%) as lacunar infarction. To determine if those selected for angiography among the IUC patients differed from those with other final diagnoses, a stepwise multiple logistic model was used. The most important characteristics were young age, presence of a superficial infarct, prior transient ischemic attack, low weakness score, and presentation with a nonlacunar syndrome. The results of the model suggest that angiography use was determined by clinical characteristics uniformly across centers and not by final diagnosis. Continued use of the category IUC may help clarify risk factors and stroke subtypes, allow new mechanisms of ischemic stroke to be uncovered, and prevent classification categories of stroke used in clinical trials from becoming too broad.