Lower prevalence of silent brain infarcts in the physically active: the Northern Manhattan Study.

OBJECTIVE: To examine the independent association between physical activity and subclinical cerebrovascular disease as measured by silent brain infarcts (SBI) and white matter hyperintensity volume (WMHV). METHODS: The Northern Manhattan Study (NOMAS) is a population-based prospective cohort examining risk factors for incident vascular disease, and a subsample underwent brain MRI. Our primary outcomes were SBI and WMHV. Baseline measures of leisure-time physical activity were collected in person. Physical activity was categorized by quartiles of the metabolic equivalent (MET) score. We used logistic regression models to examine the associations between physical activity and SBI, and linear regression to examine the association with WMHV. RESULTS: There were 1,238 clinically stroke-free participants (mean age 70 ± 9 years) of whom 60% were women, 65% were Hispanic, and 43% reported no physical activity. A total of 197 (16%) participants had SBI. In fully adjusted models, compared to those who did not engage in physical activity, those in the upper quartile of MET scores were almost half as likely to have SBI (adjusted odds ratio 0.6, 95% confidence interval 0.4-0.9). Physical activity was not associated with WMHV. CONCLUSIONS: Increased levels of physical activity were associated with a lower risk of SBI but not WMHV. Engaging in moderate to heavy physical activities may be an important component of prevention strategies aimed at reducing subclinical brain infarcts.

Quality of life declines after first ischemic stroke. The Northern Manhattan Study.

OBJECTIVES: Quality of life (QOL) after stroke is poorly characterized. We sought to determine long-term natural history and predictors of QOL among first ischemic stroke survivors without stroke recurrence or myocardial infarction (MI). METHODS: In the population-based, multiethnic Northern Manhattan Study, QOL was prospectively assessed at 6 months and annually for 5 years using the Spitzer QOL index (QLI), a 10-point scale. Functional status was assessed using the Barthel Index (BI) at regular intervals, and cognition using the Mini-Mental State Examination at 1 year. Generalized estimating equations estimated the association between patient characteristics and repeated QOL measures over 5 years. Follow-up was censored at death, recurrent stroke, or MI. RESULTS: There were 525 incident ischemic stroke patients >/=40 years (mean age 68.6 +/- 12.4 years). QLI declined after stroke (annual change -0.10, 95% confidence interval -0.17 to -0.04), after adjusting for age, sex, race-ethnicity, education, insurance, depressed mood, stroke severity, bladder continence, and stroke laterality. This decline remained when BI >/=95 was added to the model as a time-dependent covariate, and functional status also predicted QLI. Changes in QLI over time differed by insurance status (p for interaction = 0.0017), with a decline for those with Medicaid/no insurance (p < 0.0001) but not Medicare/private insurance (p = 0.98). CONCLUSIONS: In this population-based study, QOL declined annually up to 5 years after stroke among survivors free of recurrence or MI and independently of other risk factors. QLI declined more among Medicaid patients and was associated with age, mood, stroke severity, urinary incontinence, functional status, cognition, and stroke laterality.

The Levels of Inflammatory Markers in the Treatment of Stroke study (LIMITS): inflammatory biomarkers as risk predictors after lacunar stroke.

BACKGROUND: Inflammation is increasingly recognised as playing a central role in atherosclerosis, and peripheral blood markers of inflammation have been associated with incident and recurrent cardiac events. The relationship of these potentially modifiable risk markers to prognosis after ischaemic stroke is less clear. The Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) study will address hypotheses related to the role of inflammatory markers in secondary stroke prevention in an efficient manner using the well-established framework of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (NCT00059306). METHODS: SPS3 is an ongoing Phase III multicentre secondary prevention trial focused on preventing recurrent stroke in patients with small vessel ischaemic stroke, or lacunes. In SPS3, patients are assigned in a factorial design to aspirin vs. aspirin plus clopidogrel, and to usual vs. aggressive blood pressure targets. The purpose of LIMITS is to determine whether serum levels of inflammatory markers - including high-sensitivity C-reactive protein, serum amyloid A, CD40 ligand, and monocyte chemoattractant protein-1 - predict recurrent stroke and other vascular events among lacunar stroke patients. The project will also determine whether these markers predict which people will respond best to dual antiplatelet therapy with clopidogrel and aspirin, as well the relationship to cognitive function. ANALYSIS: plan Multivariable Cox proportional hazard regression modeling will be used to estimate hazard ratios for the effect of marker levels on risk of recurrent stroke and other outcomes after adjusting for additional potential risk factors, including age, gender, ethnicity, treatment arm, and traditional stroke risk factors. Interactions between marker levels and treatment assignment for both arms of the SPS3 study will be assessed. Observations will be censored at the time of last follow-up visit. CONCLUSIONS: LIMITS represents an efficient approach to the identification of novel inflammatory biomarkers for use in risk prediction and treatment selection in patients with small vessel disease.

Physical activity and risk of ischemic stroke in the Northern Manhattan Study.

BACKGROUND: It is controversial whether physical activity is protective against first stroke among older persons. We sought to examine whether physical activity, as measured by intensity of exercise and energy expended, is protective against ischemic stroke. METHODS: The Northern Manhattan Study is a prospective cohort study in older, urban-dwelling, multiethnic, stroke-free individuals. Baseline measures of leisure-time physical activity were collected via in-person questionnaires. Cox proportional hazards models were constructed to examine whether energy expended and intensity of physical activity were associated with the risk of incident ischemic stroke. RESULTS: Physical inactivity was present in 40.5% of the cohort. Over a median follow-up of 9.1 years, there were 238 incident ischemic strokes. Moderate- to heavy-intensity physical activity was associated with a lower risk of ischemic stroke (adjusted hazard ratio [HR] 0.65, 95% confidence interval [0.44-0.98]). Engaging in any physical activity vs none (adjusted HR 1.16, 95% CI 0.88-1.51) and energy expended in kcal/wk (adjusted HR per 500-unit increase 1.01, 95% CI 0.99-1.03) were not associated with ischemic stroke risk. There was an interaction of sex with intensity of physical activity (p = 0.04), such that moderate to heavy activity was protective against ischemic stroke in men (adjusted HR 0.37, 95% CI 0.18-0.78), but not in women (adjusted HR 0.92, 95% CI 0.57-1.50). CONCLUSIONS: Moderate- to heavy-intensity physical activity, but not energy expended, is protective against risk of ischemic stroke independent of other stroke risk factors in men in our cohort. Engaging in moderate to heavy physical activities may be an important component of primary prevention strategies aimed at reducing stroke risk.

High-sensitivity C-reactive protein predicts mortality but not stroke: the Northern Manhattan Study.

OBJECTIVE: To determine whether high-sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) predict stroke, vascular events, and mortality in a prospective cohort study. BACKGROUND: Markers of inflammation have been associated with risk of myocardial infarction (MI). Their association with stroke is controversial. METHODS: The Northern Manhattan Study includes a stroke-free community-based cohort study in participants aged > or =40 years (median follow-up 7.9 years). hsCRP and SAA were measured using nephelometry. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association of markers with risk of ischemic stroke and other outcomes after adjusting for demographics and risk factors. RESULTS: hsCRP measurements were available in 2,240 participants (mean age 68.9 +/- 10.1 years; 64.2% women; 18.8% white, 23.5% black, and 55.1% Hispanic). The median hsCRP was 2.5 mg/L. Compared with those with hsCRP <1 mg/L, those with hsCRP >3 mg/L were at increased risk of ischemic stroke in a model adjusted for demographics (HR = 1.60, 95% CI 1.06-2.41), but the effect was attenuated after adjusting for other risk factors (adjusted HR = 1.20, 95% CI 0.78-1.86). hsCRP >3 mg/L was associated with risk of MI (adjusted HR = 1.70, 95% CI 1.04-2.77) and death (adjusted HR = 1.55, 95% CI 1.23-1.96). SAA was not associated with stroke risk. CONCLUSION: In this multiethnic cohort, high-sensitivity C-reactive protein (hsCRP) was not associated with ischemic stroke, but was modestly associated with myocardial infarction and mortality. The value of hsCRP and serum amyloid A may depend on population characteristics such as age and other risk factors.

Carotid plaque, a subclinical precursor of vascular events: the Northern Manhattan Study.

BACKGROUND: Carotid atherosclerosis is a known biomarker associated with future vascular disease. The risk associated with small, nonstenotic carotid plaques is less clear. The objective of this study was to examine the association between maximum carotid plaque thickness and risk of vascular events in an urban multiethnic cohort. METHODS: As part of the population-based Northern Manhattan Study, carotid plaque was analyzed among 2,189 subjects. Maximum carotid plaque thickness was evaluated at the cutoff level of 1.9 mm, a prespecified value of the 75th percentile of the plaque thickness distribution. The primary outcome measure was combined vascular events (ischemic stroke, myocardial infarction, or vascular death). RESULTS: Carotid plaque was present in 1,263 (58%) subjects. After a mean follow-up of 6.9 years, vascular events occurred among 319 subjects; 121 had fatal or nonfatal ischemic stroke, 118 had fatal or nonfatal myocardial infarction, and 166 died of vascular causes. Subjects with maximum carotid plaque thickness greater than 1.9 mm had a 2.8-fold increased risk of combined vascular events in comparison to the subjects without carotid plaque (hazard ratio, 2.80; 95% CI, 2.04-3.84). In fully adjusted models, this association was significant only among Hispanics. Approximately 44% of the low-risk individuals by Framingham risk score had a 10-year vascular risk of 18.3% if having carotid plaque. CONCLUSIONS: Maximum carotid plaque thickness is a simple and noninvasive marker of subclinical atherosclerosis associated with increased risk of vascular outcomes in a multiethnic cohort. Maximum carotid plaque thickness may be a simple and nonexpensive tool to assist with vascular risk stratification in preventive strategies and a surrogate endpoint in clinical trials.

Gender differences in self-report of recovery after stroke: the Northern Manhattan Study.

We compared subjective responses to simple questions after stroke with interviewer-assessed stroke outcome measures. Among those in the highest functional category, women were more likely to report incomplete recovery and greater need for help than men. Among these women, depressed mood was associated with a response of a need for help despite a good functional recovery. Self-reported responses in stroke outcome assessments require further validation by gender and may need to consider the confounding effects of depression.

Relative elevation in baseline leukocyte count predicts first cerebral infarction.

BACKGROUND: Atherosclerosis is an inflammatory disease, and leukocyte levels are associated with future risk of ischemic cardiac disease. OBJECTIVE: To investigate the hypothesis that relative elevations in leukocyte count in a stroke-free population predict future ischemic stroke (IS). METHODS: A population-based prospective cohort study was performed in a multiethnic urban population. Stroke-free community participants were identified by random-digit dialing. Leukocyte levels were measured at enrollment, and participants were followed annually for IS, myocardial infarction (MI), and cause-specific mortality. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs for IS, MI, and vascular death after adjustment for medical, behavioral, and socioeconomic factors. RESULTS: Among 3,103 stroke-free community participants (mean age 69.2 +/- 10.3 years) with baseline leukocyte levels measured, median follow-up was 5.2 years. After adjusting for stroke risk factors, each SD in leukocyte count (1.8 x 10(9) cells/L) was associated with an increased risk of IS (HR 1.22, 95% CI 1.05 to 1.42), and IS, MI, or vascular death (HR 1.13, 95% CI 1.02 to 1.26). Compared with those in the lowest quartile of leukocyte count, those in the highest had an increased risk of IS (adjusted HR 1.75, 95% CI 1.08 to 2.82). The effect on atherosclerotic and cardioembolic stroke was greater than in other stroke subtypes. CONCLUSION: Relative elevations in leukocyte count are independently associated with an increased risk of future ischemic stroke and other cardiovascular events.

Total homocysteine and cognition in a tri-ethnic cohort: the Northern Manhattan Study.

OBJECTIVE: Several studies implicate elevated homocysteine as a risk factor for dementia and cognitive decline, but most studies have involved subjects older than 55 years from homogeneous populations. The authors examined homocysteine and cognition in a tri-ethnic community sample 40 years and older. METHOD: The Northern Manhattan Study includes 3,298 stroke-free subjects. Of these 2,871 had baseline fasting total homocysteine (tHcy) levels and Mini-Mental State Examination (MMSE) scores available. The authors used multiple linear regression to examine the cross-sectional association between baseline tHcy levels and mean MMSE scores adjusting for sociodemographic and vascular risk factors. RESULTS: Homocysteine levels were related to age, renal function, and B12 deficiency. Those with B12 deficiency had tHcy levels five points higher (9.4 vs 14.4 nmol/L). Mean MMSE scores differed by age, sex, and race-ethnic group. Those with hypertension, diabetes, cardiac disease, and B12 deficiency had lower MMSE scores. In multivariate analyses, elevated tHcy was associated with lower mean MMSE scores for those older than 65 but not for those 40 to 64. Adjusting for B12 deficiency and sociodemographic factors the mean MMSE was 2.2 points lower for each unit increase in the log tHcy level (95% CI -3.6, -0.9). Adding vascular risk factors to the model did not attenuate this effect (mean MMSE -2.2 points; 95% CI -3.5, -0.9). CONCLUSIONS: Elevated homocysteine was independently associated with decreased cognition in subjects older than 65 in this tri-ethnic cohort, adjusting for sociodemographic and vascular risk factors.

Mortality and causes of death after first ischemic stroke: the Northern Manhattan Stroke Study.

OBJECTIVE: To analyze the early and long-term causes of death after first ischemic stroke in the multiethnic northern Manhattan community. METHODS: In the prospective, population-based Northern Manhattan Stroke Study, 980 patients with first ischemic stroke (mean age 70 years; 56% women; 49% Caribbean Hispanic, 31% black, 20% white) were followed for a mean of 3 years. Causes of death were classified as vascular (incident stroke, recurrent stroke, cardiac) or nonvascular. Life table analyses were used to assess mortality risks among different race-ethnic groups. Early (< or =1 month) vs long-term (> 1 month to 5 years) causes of death were compared. RESULTS: Among the 980 patients followed, 278 (28%) died; 47 (5%) died during the first month. Cumulative mortality risk was 5% at 1 month, 16% after 1 year, 29% after 3 years, and 41% after 5 years. The proportion of vascular deaths among all deaths was 75% at 1 month and 43% thereafter (p = 0.001). Stroke, either incident (53%) or recurrent (4%), caused early deaths in 57% and long-term deaths in 14% (p = 0.001). Overall mortality risks did not differ significantly among race-ethnic groups. However, the proportion of incident stroke-related early deaths was 85% in Caribbean Hispanic patients, 33% in white patients, and 25% in black patients (p = 0.002). CONCLUSIONS: Among patients with first ischemic stroke, incident stroke is the leading cause of early deaths. A large proportion of long-term deaths are nonvascular in origin. Despite similar overall mortality rates in race-ethnic groups, our data suggest a higher incident stroke-related early mortality among Caribbean Hispanics.

Race-ethnic disparities in the impact of stroke risk factors: the northern Manhattan stroke study.

BACKGROUND AND PURPOSE: Stroke risk factors have been determined in large part through epidemiological studies in white cohorts; as a result, race-ethnic disparities in stroke incidence and mortality rates remained unexplained. The aim in the present study was to compare the prevalence, OR, and etiological fraction (EF) of stroke risk factors among white, blacks, and Caribbean Hispanics living in the same urban community of northern Manhattan. METHODS: In this population-based incident case-control study, cases (n=688) of first ischemic stroke were prospectively matched 1:2 by age, sex, and race-ethnicity with community controls (n=1156). Risk factors were determined through in-person assessment. Conditional logistic regression was used to calculate adjusted ORs in each race-ethnic group. Prevalence and multivariate EFs were determined in each race-ethnic group. RESULTS: Hypertension was an independent risk factor for whites (OR 1.8, EF 25%), blacks (OR 2.0, EF 37%), and Caribbean Hispanics (OR 2.1, EF 32%), but greater prevalence led to elevated EFs among blacks and Caribbean Hispanics. Greater prevalence rates of diabetes increased stroke risk in blacks (OR 1.8, EF 14%) and Caribbean Hispanics (OR 2.1 P<0.05, EF 10%) compared with whites (OR 1.0, EF 0%), whereas atrial fibrillation had a greater prevalence and EF for whites (OR 4.4, EF 20%) compared with blacks (OR 1.7, EF 3%) and Caribbean Hispanics (OR 3.0, EF 2%). Coronary artery disease was most important for whites (OR 1.3, EF 16%), followed by Caribbean Hispanics (OR 1.5, EF 6%) and then blacks (OR 1.1, EF 2%). Prevalence of physical inactivity was greater in Caribbean Hispanics, but an elevated EF was found in all groups. CONCLUSIONS: The prevalence, OR, and EF for stroke risk factors vary by race-ethnicity. These differences are crucial to the etiology of stroke, as well as to the design and implementation of stroke prevention programs.

High-density lipoprotein cholesterol and ischemic stroke in the elderly: the Northern Manhattan Stroke Study.

CONTEXT: Elevated high-density lipoprotein cholesterol (HDL-C) levels have been shown to be protective against cardiovascular disease. However, the association of specific lipoprotein classes and ischemic stroke has not been well defined, particularly in higher-risk minority populations. OBJECTIVE: To evaluate the association between HDL-C and ischemic stroke in an elderly, racially or ethnically diverse population. DESIGN: Population-based, incident case-control study conducted July 1993 through June 1997. SETTING: A multiethnic community in northern Manhattan, New York, NY. PARTICIPANTS: Cases (n = 539) of first ischemic stroke (67% aged >/=65 years; 55% women; 53% Hispanic, 28% black, and 19% white) were enrolled and matched by age, sex, and race or ethnicity to stroke-free community residents (controls; n = 905). MAIN OUTCOME MEASURE: Independent association of fasting HDL-C levels, determined at enrollment, with ischemic stroke, including atherosclerotic and nonatherosclerotic ischemic stroke subtypes. RESULTS: After risk factor adjustment, a protective effect was observed for HDL-C levels of at least 35 mg/dL (0.91 mmol/L) (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.39-0.72). A dose-response relationship was observed (OR, 0.65; 95% CI, 0.47-0.90 and OR, 0.31; 95% CI, 0.21-0.46) for HDL-C levels of 35 to 49 mg/dL (0.91-1.28 mmol/L) and at least 50 mg/dL (1.29 mmol/L), respectively. The protective effect of a higher HDL-C level was significant among participants aged 75 years or older (OR, 0.51; 95% CI, 0.27-0.94), was more potent for the atherosclerotic stroke subtype (OR, 0.20; 95% CI, 0.08-0.50), and was present in all 3 racial or ethnic groups studied. CONCLUSIONS: Increased HDL-C levels are associated with reduced risk of ischemic stroke in the elderly and among different racial or ethnic groups. These data add to the evidence relating lipids to stroke and support HDL-C as an important modifiable stroke risk factor.

Elevated white blood cell count and carotid plaque thickness : the northern manhattan stroke study.

BACKGROUND AND PURPOSE: Elevated leukocyte count has been associated with cardiovascular and cerebrovascular disease in several epidemiological studies. We sought to determine whether white blood cell count (WBC) is associated with carotid plaque thickness in a stroke-free, multiethnic cohort. METHODS: For this cross-sectional analysis, WBC was measured in stroke-free community subjects undergoing carotid duplex Doppler ultrasound. Maximal internal carotid plaque thickness (MICPT) was measured for each subject. Demographic and potential medical confounding factors were analyzed with linear and logistic regression to calculate the effect of quartile of WBC on MICPT. Odds ratios (ORs) and 95% confidence intervals (CIs) for the effect of quartile of WBC on MICPT >/=75th percentile were calculated. All analyses were stratified by race-ethnicity. RESULTS: The mean age of the 1422 subjects was 68.6+/-10.2 years; 40.0% were men; 24.4% were white, 46.9% Hispanic, and 26.7% black. Among Hispanics, compared with the lowest quartile of WBC, those in the highest quartile had significantly increased MICPT (mean difference=0.30 mm, P:=0.0086) after adjustment for age, sex, and other atherosclerotic risk factors. There was no significant increase for blacks or whites. The OR for MICPT >/=75th percentile (1.9 mm) was significantly increased for Hispanics (OR, 2.8; 95% CI, 1.4 to 5.6), marginally elevated for black non-Hispanics (OR, 1.6; 95% CI, 0.8 to 3.2), and not increased for white non-Hispanics (OR, 0.5; 95% CI, 0.2 to 1.1). CONCLUSIONS: Relative elevation in WBC is associated with carotid atherosclerosis, but this relationship differs by race-ethnicity. The association is strongest in Hispanics, intermediate in black non-Hispanics, and not present in white non-Hispanics in this population. Chronic subclinical infection or inflammation may account for this association.

Matched case-control data analysis with selection bias.

Case-control studies offer a rapid and efficient way to evaluate hypotheses. On the other hand, proper selection of the controls is challenging, and the potential for selection bias is a major weakness. Valid inferences about parameters of interest cannot be drawn if selection bias exists. Furthermore, the selection bias is difficult to evaluate. Even in situations where selection bias can be estimated, few methods are available. In the matched case-control Northern Manhattan Stroke Study (NOMASS), stroke-free controls are sampled in two stages. First, a telephone survey ascertains demographic and exposure status from a large random sample. Then, in an in-person interview, detailed information is collected for the selected controls to be used in a matched case-control study. The telephone survey data provides information about the selection probability and the potential selection bias. In this article, we propose bias-corrected estimators in a case-control study using a joint estimating equation approach. The proposed bias-corrected estimate and its standard error can be easily obtained by standard statistical software.

Bivariate binary data analysis with nonignorably missing outcomes.

One of the objectives in the Northern Manhattan Stroke Study is to investigate the impact of stroke subtype on the functional status 2 years after the first ischemic stroke. A challenge in this analysis is that the functional status at 2 years after stroke is not completely observed. In this paper, we propose a method to handle nonignorably missing binary functional status when the baseline value and the covariates are completely observed. The proposed method consists of fitting four separate binary regression models: for the baseline outcome, the outcome 2 years after the stroke, the product of the previous two, and finally, the missingness indicator. We then conduct a sensitivity analysis by varying the assumptions about the third and the fourth binary regression models. Our method belongs to an imputation paradigm and can be an alternative to the weighting method of Rotnitzky and Robins (1997, Statistics in Medicine 16, 81-102). A jackknife variance estimate is proposed for the variance of the resulting estimate. The proposed analysis can be implemented using statistical software such as SAS.

Predictors of resource use after acute hospitalization: the Northern Manhattan Stroke Study.

OBJECTIVE: To determine demographic and clinical predictors of discharge destinations following acute care hospitalization for stroke in the community of northern Manhattan. METHODS: A group of 893 patients (mean age, 70 +/- 12 years; 56% women; 51% Hispanic, 30% African-American, 19% white) who survived acute care hospitalization for a first ischemic stroke were followed prospectively. Stroke severity was assessed by the NIH Stroke Scale and categorized as mild (< or = 5), moderate (6 to 13), and severe (> or = 14). Polytomous logistic regression was used to determine predictors for rehabilitation and nursing home placement versus returning home. RESULTS: Among the survivors of acute stroke care hospitalization, 611 (68%) patients were discharged to their homes, 168 (19%) to rehabilitation, and 114 (13%) to nursing homes. Patients with moderate and severe neurologic deficits had more than a threefold increased risk of being sent to a nursing home and more than an eightfold increased risk of being sent to rehabilitation. Age over 65 and cognitive impairment were associated with placement to a nursing home (age over 65: OR, 2.4; 95% CI, 1.0 to 5.6; cognitive impairment: OR, 2.9; 95%, CI 1.4 to 5.7), and rehabilitation (age over 65: OR, 1.8; 95% CI, 1.1 to 2.9; cognitive impairment: OR, 2.9; 95% CI, 1.4 to 5.7). CONCLUSION: Our results demonstrated that one-third of patients with acute stroke from the community of northern Manhattan required placement in a temporary or a long-term disability care institution following acute care hospitalization. Severity of stroke is an important factor that influences discharge planning following acute care hospitalization and its reduction can improve health care resource usage.

Frequency and clinical determinants of dementia after ischemic stroke.

OBJECTIVE: To investigate the frequency and clinical determinants of dementia after ischemic stroke. METHODS: The authors administered neurologic, neuropsychological, and functional assessments to 453 patients (age 72.0 +/- 8.3 years) 3 months after ischemic stroke. They diagnosed dementia using modified Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised criteria requiring deficits in memory and two or more additional cognitive domains as well as functional impairment. RESULTS: The authors diagnosed dementia in 119 of the 453 patients (26.3%). Regarding dementia subtypes, 68 of the 119 patients (57.1%) were diagnosed with vascular dementia, 46 patients (38.7%) were diagnosed with AD with concomitant stroke, and 5 patients (4.2%) had dementia for other reasons. Logistic regression suggested that dementia was associated with a major hemispheral stroke syndrome (OR 3.0), left hemisphere (OR 2.1) and right hemisphere (OR 1.8) infarct locations versus brainstem/cerebellar locations, infarcts in the pooled anterior and posterior cerebral artery territories versus infarcts in other vascular territories (OR 1.7), diabetes mellitus (OR 1.8), prior stroke (OR 1.7), age 80 years or older (OR 12.7) and 70 to 79 years (OR 3.9) versus 60 to 69 years, 8 or fewer years of education (OR 4.1) and 9 to 12 years of education (OR 3.0) versus 13 or more years of education, black race (OR 2.6) and Hispanic ethnicity (OR 3.1) versus white race, and northern Manhattan residence (OR 1.6). CONCLUSIONS: Dementia is frequent after ischemic stroke, occurring in one-fourth of the elderly patients in the authors' cohort. The clinical determinants of dementia include the location and severity of the presenting stroke, vascular risk factors such as diabetes mellitus and prior stroke, and host characteristics such as older age, fewer years of education, and nonwhite race/ethnicity. The results also suggest that concomitant AD plays an etiologic role in approximately one-third of cases of dementia after stroke.

Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage : a randomized controlled trial.

BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) is reduced after subarachnoid hemorrhage (SAH), and symptomatic vasospasm is a major cause of morbidity and mortality. Volume expansion has been reported to increase CBF after SAH, but CBF values in hypervolemic (HV) and normovolemic (NV) subjects have never been directly compared. METHODS: On the day after aneurysm clipping, we randomly assigned 82 patients to receive HV or NV fluid management until SAH day 14. In addition to 80 mL/h of isotonic crystalloid, 250 mL of 5% albumin solution was given every 2 hours to maintain normal (NV group, n=41) or elevated (HV group, n=41) cardiac filling pressures. CBF ((133)xenon clearance) was measured before randomization and approximately every 3 days thereafter (mean, 4.5 studies per patient). RESULTS: HV patients received significantly more fluid and had higher pulmonary artery diastolic and central venous pressures than NV patients, but there was no effect on net fluid balance or on blood volume measured on the third postoperative day. There was no difference in mean global CBF during the treatment period between HV and NV patients (P=0.55, random-effects model). Symptomatic vasospasm occurred in 20% of patients in each group and was associated with reduced minimum regional CBF values (P=0.04). However, there was also no difference in minimum regional CBF between the 2 treatment groups. CONCLUSIONS: HV therapy resulted in increased cardiac filling pressures and fluid intake but did not increase CBF or blood volume compared with NV therapy. Although careful fluid management to avoid hypovolemia may reduce the risk of delayed cerebral ischemia after SAH, prophylactic HV therapy is unlikely to confer an additional benefit.

Using missing data techniques to explore the lack of survival effect: illustration with the CABG patch trial.

The Multicenter Automatic Defibrillator Implantation Trial (MADIT) showed a conclusive 54 per cent reduction in mortality in patients with inducible sustained monomorphic ventricular tachycardia (VT) and impaired left ventricular function who received an implantable defibrillator compared with those who did not. The Coronary Artery Bypass Graft (CABG) Patch Trial, which studied a patient population with a similar extent of left ventricular dysfunction and overall cardiovascular risk, demonstrated no mortality benefit from placement of an implantable defibrillator. All patients in the MADIT trial were 'VT inducible', while this criterion was neither required nor evaluated for entry into the CABG Patch Trial. A statistical approach to estimating with good accuracy the fraction of CABG Patch patients who were inducible at the time of their randomization from the prevalence of VT inducibility in the surviving CABG Patch Trial control population during follow-up is presented. This more generally applicable approach estimates the mixing percentage using missing data techniques. We present the mathematical and physiological basis of the assumptions underpinning the mixture model and its estimation procedure. The mixture model forms the basis for the electrophysiological substudy to the CABG Patch Trial, which directly tests the hypothesis that the difference in the frequency of inducible VT between the MADIT and CABG Patch patients populations is sufficient to account for the difference in effect on mortality.

Treatment for the secondary prevention of stroke in older patients: the influence of dementia status.

OBJECTIVE: To investigate the influence of dementia status on treatment for the secondary prevention of stroke in older patients. DESIGN: Based on patient examinations and medical record review, we investigated the frequency of aspirin and/or warfarin use at hospital discharge for the prevention of recurrent stroke in older patients hospitalized with acute ischemic stroke. SETTING: A large academic medical center. PARTICIPANTS: A cohort of 272 patients, mean age 72.1 +/- 8.5 years. MEASUREMENTS: We performed neurologic examinations and reviewed medical records to investigate the effects of a clinical diagnosis of dementia and other potentially relevant factors on treatment with aspirin or warfarin at hospital discharge. RESULTS: Thirty-one patients (11.4%) were not prescribed aspirin or warfarin at hospital discharge. Logistic regression determined that dementia (odds ratio (OR) = 2.57, 95% confidence interval (CI), 1.04-6.30) was a significant independent determinant of nontreatment with aspirin or warfarin, adjusting for abnormal gait (OR = 2.01, CI, .88-4.59); discharge to a nursing home or other institutional residence (OR = 2.55, CI, .83-7.81); cardiac disease (OR = .39, CI, .16-.95); cortical infarct location (OR = .45, CI, .18-1.10); male sex (OR = .47, CI, .20-1.15); age 80+ (OR = 1.14, CI, .46-2.82) and age 70-79 (OR = .96, CI, .32-2.88) versus age 60-69. CONCLUSIONS: Our results suggest that dementia is a significant independent determinant of nontreatment with aspirin or warfarin when otherwise indicated for the prevention of recurrent stroke. The underutilization of aspirin and warfarin in older stroke patients with dementia may be a modifiable basis for their increased risk of recurrence and death.