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R L Sacco

Publications and source records attributed to R L Sacco.

At least 19 recordsLinked to original sources

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.

Aged↗

Projected costs of ischemic stroke in the United States.

BACKGROUND: There are barriers to acute stroke care in minority groups as well as a higher incidence of ischemic stroke when compared with non-Hispanic whites. OBJECTIVE: To estimate the future economic burden of stroke in non-Hispanic whites, Hispanics, and African Americans in the United States from 2005 to 2050. METHODS: We used U.S. Census estimates of the race-ethnic group populations age 45 years and older. We obtained stroke epidemiology and service utilization data from the Northern Manhattan Stroke Study and the Brain Attack Surveillance in Corpus Christi project and other published data. We estimated costs directly from Medicare reimbursement or from studies that used Medicare reimbursement. Direct and indirect costs considered included ambulance services, initial hospitalization, rehabilitation, nursing home costs, outpatient clinic visits, drugs, informal caregiving, and potential lost earnings. RESULTS: The total cost of stroke from 2005 to 2050, in 2005 dollars, is projected to be 1.52 trillion dollars for non-Hispanic whites, 313 billion dollars for Hispanics, and 379 billion dollars for African Americans. The per capita cost of stroke estimates are highest in African Americans (25,782 dollars), followed by Hispanics (17,201 dollars), and non-Hispanic whites (15,597 dollars). Loss of earnings is expected to be the highest cost contributor in each race-ethnic group. CONCLUSIONS: The economic burden of stroke in African Americans and Hispanics will be enormous over the next several decades. Further efforts to improve stroke prevention and treatment in these high stroke risk groups are necessary.

Black or African American↗

Intracerebral hemorrhage in pregnancy: frequency, risk factors, and outcome.

OBJECTIVE: To describe the frequency, risk factors, and outcome of intracerebral hemorrhage (ICH) in pregnancy and the postpartum period using a large database of US inpatient hospitalizations. METHODS: The authors obtained data from an administrative dataset, the Nationwide Inpatient Sample, which includes approximately 20% of all discharges from non-Federal hospitals, for the years 1993 through 2002. Women aged 15 to 44 years with a diagnosis of ICH were selected from the database for analysis, and within this group patients coded as pregnant or postpartum were identified. Using US Census data, estimates were made of the rates of ICH in pregnant/postpartum and non-pregnant women. Rates of various comorbidities in patients with pregnancy-related ICH were compared to the rates found in the general population of delivering patients using multivariate logistic regression to identify independent risk factors for pregnancy-related ICH. RESULTS: The authors identified 423 patients with pregnancy-related ICH, which corresponded to 6.1 pregnancy-related ICH per 100,000 deliveries and 7.1 pregnancy-related ICH per 100,000 at-risk person-years (compared to 5.0 per 100,000 person-years for non-pregnant women in the age range considered). The increased risk of ICH associated with pregnancy was largely attributable to ICH occurring in the postpartum period. The in-hospital mortality rate for pregnancy-related ICH was 20.3%. ICH accounted for 7.1% of all pregnancy-related mortality recorded in this database. Significant independent risk factors for pregnancy-related ICH included advanced maternal age (OR 2.11, 95% CI 1.69 to 2.64), African American race (OR 1.83, 95% CI 1.39 to 2.41), preexisting hypertension (OR 2.61, 95% CI 1.34 to 5.07), gestational hypertension (OR 2.41, 95% CI 1.62 to 3.59), preeclampsia/eclampsia (OR 10.39, 95% CI 8.32 to 12.98), preexisting hypertension with superimposed preeclampsia/eclampsia (OR 9.23, 95% CI 5.26 to 16.19), coagulopathy (OR 20.66, 95% CI 13.67 to 31.23), and tobacco abuse (OR 1.95, 95% CI 1.11 to 3.42). CONCLUSION: Intracerebral hemorrhage (ICH) accounts for a substantial portion of pregnancy-related mortality. The risk of ICH associated with pregnancy is greatest in the postpartum period. Advanced maternal age, African American race, hypertensive diseases, coagulopathy, and tobacco abuse were all independent risk factors for pregnancy-related ICH.

Adolescent↗

Quality improvement in acute stroke: the New York State Stroke Center Designation Project.

BACKGROUND: Many hospitals lack the infrastructure required to treat patients with acute stroke. The Brain Attack Coalition (BAC) published guidelines for the establishment of primary stroke centers. OBJECTIVE: To determine if stroke center designation and selective triage of acute stroke patients improve quality of care. METHODS: Baseline chart abstraction was performed on all stroke patients admitted to 32 hospitals serving Brooklyn and Queens, NY, from March to May 2002. Hospitals were invited to meet BAC guideline-based criteria. Adherence was verified by on-site visits. After designation, acute stroke patients were selectively triaged. Remeasurement data were collected from August to October 2003. RESULTS: The authors abstracted 1,598 charts at baseline and 1,442 charts at remeasurement. From baseline to remeasurement, median times decreased for door to physician contact (25 vs 15 minutes, p = 0.001), CT performance for potential tissue plasminogen activator (t-PA) candidates (68 vs 32 minutes, p < 0.001), and t-PA administration (109 vs 98 minutes (p = NS). IV t-PA utilization increased from 2.4 to 5.2% (p < 0.005), select t-PA protocol violations decreased from 11.1 to 7.9% (p = NS), and the stroke unit admission rate increased from 16 to 39% (p < 0.001). In stroke centers (n = 14) vs nondesignated hospitals (n = 18), there were shorter median times from door to physician contact (10 vs 25 minutes, p < 0.001), CT performance for potential t-PA candidates (31 vs 40 minutes, p = NS), and t-PA administration (95 vs 115 minutes, p < 0.05). Stroke centers, compared with nondesignated centers, admitted acute stroke patients to stroke units more often (55.9 vs 10.9%, p < 0.001). CONCLUSIONS: Stroke center designation and selective triage of acute stroke patients improved the quality of care, including access to timely thrombolytic therapy and stroke units.

Aged↗

Recurrent stroke and cardiac risks after first ischemic stroke: the Northern Manhattan Study.

BACKGROUND: Few population-based studies with long-term follow-up have compared risk of recurrent stroke and cardiac events after first ischemic stroke. The relative risk of these two outcomes may inform treatment decisions. METHODS: In the population-based Northern Manhattan Study, first ischemic stroke patients age 40 or older were prospectively followed for recurrent stroke, myocardial infarction (MI), and cause-specific mortality. Fatal cardiac events were defined as death secondary to MI, congestive heart failure, sudden death/arrhythmia, and cardiopulmonary arrest. Risk of events (with 95% CIs) was calculated using Kaplan-Meier survival analysis and adjusted for sex and age using Cox proportional hazard models. RESULTS: Mean age (n = 655; median follow-up 4.0 years) was 69.7 +/- 12.7 years. The risk of recurrent stroke was more than twice that of cardiac events (including nonfatal MI) at 30 days and approximately twice cardiac risk at 5 years. The age- and sex-adjusted 5-year risk of fatal or nonfatal recurrent stroke was 18.3% (14.8 to 21.7%), and the 5-year risk of MI or fatal cardiac event was 8.6% (6.0 to 11.2%). The adjusted 5-year risk of nonfatal stroke (14.8%, 11.6 to 17.9%) was approximately twice as high as fatal cardiac events (6.4%, 4.1 to 8.6%) and four times higher than risk of fatal stroke (3.7%, 2.1 to 5.4%). CONCLUSIONS: Cardiac mortality is nearly twice as high as mortality owing to recurrent stroke, but long-term risk of all stroke, fatal or nonfatal, is approximately twice the risk of all cardiac events. The high risk of nonfatal recurrent stroke reinforces the importance of therapies aimed at preventing stroke recurrence in addition to preventing cardiac events.

Adult↗

Subarachnoid hemorrhage incidence among Whites, Blacks and Caribbean Hispanics: the Northern Manhattan Study.

American blacks and Hispanics may have a greater incidence of subarachnoid hemorrhage (SAH) than whites, but incidence data are scant. We used an active hospital and community surveillance program and autopsy reports to identify incident SAH cases among white, black and Hispanic adults living in Northern Manhattan between July 1993 and June 1997. The annual incidence adjusted for age and sex to the 1990 US Census was 9.7 per 100,000 (95% CI 7.5-12.0). Compared with whites (9 cases, age- and sex-adjusted annual incidence 8.2 per 100,000), the rate ratio of SAH was 1.3 (95% CI 0.7-2.4) for Hispanics (34 cases, incidence 10.9), and 1.6 (95% CI 0.8-2.8) for blacks (9 cases, incidence 12.8). The 30-day case fatality rate was 26%. Risk of death increased significantly with age and severity at onset but was not influenced by gender or race-ethnicity.

Adult↗

The incidence of deep and lobar intracerebral hemorrhage in whites, blacks, and Hispanics.

BACKGROUND: Black and Hispanic Americans have a greater risk of primary intracerebral hemorrhage (ICH) than whites. Deep ICH is most often associated with hypertension, while lobar ICH is associated with cerebral amyloid angiopathy. The authors conducted a population-based incidence study to directly compare the incidence of deep vs lobar ICH in all three race-ethnic groups. METHODS: The authors used an active hospital and community surveillance program and autopsy reports to identify incident ICH cases among white, black, and Caribbean Hispanic adults in Northern Manhattan between July 1993 and June 1997. Incidence rates were adjusted for age and sex to the 1990 US Census. CIs for risk ratios (RR) were calculated with Byar's chi2 approximation of the Poisson distribution. RESULTS: The authors identified 155 cases of ICH for an annual incidence of 30.9/100,000 (26.7 to 35.0). Men had a higher risk of ICH than women (RR 1.5, 95% CI 1.2 to 1.8), driven entirely by the incidence of deep ICH (RR 1.8) rather than lobar ICH (RR 1.0). Compared with whites, RR for blacks was all ICH 3.8 (2.2 to 8.9), deep 4.8 (2.3 to 21.1), lobar 2.8 (1.2 to 14.4); RR for Hispanics was all 2.6 (1.4 to 6.1), deep 3.7 (1.7 to 16.5), lobar 1.4 (0.4 to 7.4). CONCLUSIONS: ICH is a heterogeneous disease with deep and lobar subtypes distinguishable on an epidemiologic basis. The different patterns of these two subtypes in our race-ethnically diverse population lend credence to the notion that ICH should no longer be treated as a single entity.

Adult↗

Heritabilities of the metabolic syndrome and its components in the Northern Manhattan Family Study.

AIMS/HYPOTHESIS: Growing evidence suggests that the traits comprising the metabolic syndrome have a genetic basis. However, studies of genetic contributions to the syndrome are sparse. Against this background, we sought to estimate the heritability of the metabolic syndrome and its component traits. MATERIALS AND METHODS: We investigated 803 subjects from 89 Caribbean-Hispanic families who have enrolled to date in the current Northern Manhattan Family Study and for whom metabolic syndrome information was available. Metabolic syndrome was defined in accordance with the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII) criteria. Variance component methods were used to estimate age and sex-adjusted heritability of the metabolic syndrome and its components. To obtain the structures underlying the metabolic syndrome, we performed principal component factor analyses using six quantitative phenotypes included in the ATPIII definition. RESULTS: The heritability for the metabolic syndrome was 24% (p=0.009), and ranged from 16 to 60% for its five components. Factor analysis yielded two independent factors (factor 1: lipids/glucose/obesity; factor 2: blood pressure). Heritability analysis revealed significant genetic effects on both factors (44% for lipids/glucose/obesity, and 20% for blood pressure). CONCLUSIONS/INTERPRETATION: In the Caribbean-Hispanic families investigated, we demonstrated moderate and significant heritabilities for the metabolic syndrome itself, as well as for individual components and independent factors of the syndrome. These results provide evidence that could support future tasks of mapping susceptibility loci for this syndrome.

Adolescent↗

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.

Aged↗

Social isolation and outcomes post stroke.

OBJECTIVE: To assess the relationship between social isolation and stroke outcomes in a multiethnic cohort. METHODS: As part of the Northern Manhattan Stroke Study, the authors prospectively followed a cohort of patients with stroke for 5 years. Baseline data including social isolation were collected. At follow-up, the authors documented outcome events as defined by the first occurrence of myocardial infarction (MI), stroke recurrence, or death. Cox hazard models were used to calculate the hazard ratio (HR, 95% CI) for prestroke predictors of post stroke outcomes. RESULTS: The authors followed 655 ischemic stroke cases for a mean of 5 years. The cohort was 55% women; 17% white, 27% African American, 54% Hispanic; mean age 69 +/- 12 years. There were 265 first outcome events. In univariate analysis, coronary artery disease (OR 1.3, 1.0 to 1.7), age > 70 years (OR 1.9, 1.5 to 2.5), atrial fibrillation (AF) (OR 1.8, 1.3 to 2.5), race-ethnicity (white vs Hispanic) (OR 1.7, 1.1 to 2.9), physical inactivity (OR 1.3, 1.1 to 2.6), help at home (OR 1.8, 1.4 to 2.4), and social isolation (OR 1.4, 1.2 to 1.6) were associated with increased risk of an outcome event. No association was seen for hypertension, diabetes, education, sex, insurance, occupation, marital status, or primary care physician. In the multivariable model controlling for age, AF (OR 1.9, 1.5 to 2.5), help at home (OR 1.5, 1.1 to 2.0), and social isolation (OR 1.4, 1.1 to 1.8) predicted outcome events. CONCLUSION: Prestroke social isolation is a predictor of outcome events post stroke. Lack of social support may contribute to poorer outcomes due to poor compliance, depression, and stress.

Age Factors↗

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.

Adult↗

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.

Aged↗

A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke.

BACKGROUND: Despite the use of antiplatelet agents, usually aspirin, in patients who have had an ischemic stroke, there is still a substantial rate of recurrence. Therefore, we investigated whether warfarin, which is effective and superior to aspirin in the prevention of cardiogenic embolism, would also prove superior in the prevention of recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke. METHODS: In a multicenter, double-blind, randomized trial, we compared the effect of warfarin (at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combined primary end point of recurrent ischemic stroke or death from any cause within two years. RESULTS: The two randomized study groups were similar with respect to base-line risk factors. In the intention-to-treat analysis, no significant differences were found between the treatment groups in any of the outcomes measured. The primary end point of death or recurrent ischemic stroke was reached by 196 of 1103 patients assigned to warfarin (17.8 percent) and 176 of 1103 assigned to aspirin (16.0 percent; P=0.25; hazard ratio comparing warfarin with aspirin, 1.13; 95 percent confidence interval, 0.92 to 1.38). The rates of major hemorrhage were low (2.22 per 100 patient-years in the warfarin group and 1.49 per 100 patient-years in the aspirin group). Also, there were no significant treatment-related differences in the frequency of or time to the primary end point or major hemorrhage according to the cause of the initial stroke (1237 patients had had previous small-vessel or lacunar infarcts, 576 had had cryptogenic infarcts, and 259 had had infarcts designated as due to severe stenosis or occlusion of a large artery). CONCLUSIONS: Over two years, we found no difference between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Consequently, we regard both warfarin and aspirin as reasonable therapeutic alternatives.

Adult↗

Epidemiology and natural history of arteriovenous malformations.

The epidemiology and natural history of cerebral arteriovenous malformations (AVMs) remains incompletely elucidated. Several factors are responsible. With regard to the incidence and prevalence of AVMs, the results of prior studies have suffered because of the retrospective design, the use of nonspecific ICD-9 codes, and a focus on small genetically isolated populations. Recent data from the New York Islands AVM Hemorrhage Study, an ongoing, prospective, population-based survey determining the incidence of AVM-related hemorrhage and the associated rates of morbidity and mortality in a zip code-defined population of 10 million people, suggests that the AVM detection rate is 1.21/100,000 person-years (95% confidence interval [CI] 1.02-1.42) and the incidence of AVM-hemorrhage is 0.42/100,000 person-years (95% CI 0.32-0.55). Contemporaneous data from the Northern Manhattan Stroke Study, a prospective, longitudinal population-based study of nearly 150,000 patients in which the focus is to define the incidence of stroke, suggest the crude incidence for first-ever AVM-related hemorrhage to be 0.55/100,000 person-years (95% CI 0.11-1.61). Efforts are ongoing to study the natural history of both ruptured and unruptured AVMs in these datasets to examine the relevance of prior studies of patients selected for conservative follow up in Finland. In addition, data are being gathered to determine whether risk factors for future hemorrhage, which have previously been established in small case series, are valid when applied to whole populations. Together, these data should help inform therapeutic decisionmaking.

Adult↗

Prevalence and predictors of early seizure and status epilepticus after first stroke.

BACKGROUND: Early seizure (ES) has been reported in 2% to 6% of strokes and is a predictor of recurrent seizures. Acute stroke has been reported to cause 22% of all cases of status epilepticus in adults. The determinants of ES and status epilepticus (SE) after stroke, however, are not well understood. METHODS: An incidence study was conducted to identify all cases of first stroke in adult residents of northern Manhattan. Cases of ES and SE within 7 days of stroke were identified through medical record review. Statistical analyses were performed using univariate and multivariate logistic regression models. RESULTS: The cohort consisted of 904 patients; ES occurred in 37 (4.1%). The frequency of ES by stroke subtype and location was deep infarct 0.6% (2/356), lobar infarct 5.9% (20/341), deep intracerebral hemorrhage (ICH) 4.0% (4/101), lobar ICH 14.3% (7/49), and subarachnoid hemorrhage 8.0% (4/50). SE occurred in 10 patients (1.1%), representing 27.0% of patients with ES. Diabetes, hypertension, current smoking, alcohol use, age, gender, and race/ethnicity were not significant determinants of ES. In a subgroup of patients who had an NIH stroke scale (NIHSS) score recorded, NIHSS score was not an independent predictor of ES in multivariate analysis. After accounting for stroke severity, ES was not a predictor of 30-day case fatality. CONCLUSIONS: Lesion location and stroke subtype are strong determinants of ES risk, even after adjusting for stroke severity. ES does not predict 30-day mortality. SE occurs in more than one-quarter of patients with ES.

Adult↗

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.

Aged↗

Glycine antagonist in neuroprotection for patients with acute stroke: GAIN Americas: a randomized controlled trial.

CONTEXT: Elucidation of the ischemic cascade has helped stimulate development of neuroprotective drugs aimed at limiting brain injury in the hours following an ischemic stroke. To date, none of these drugs has shown clinical efficacy. OBJECTIVE: To examine the efficacy of gavestinel (GV150526), an antagonist of the glycine site of the N-methyl-D-aspartate receptor, as a neuroprotective therapy for acute ischemic stroke when administered within 6 hours of symptom onset. DESIGN: The Glycine Antagonist in Neuroprotection (GAIN) Americas trial, a randomized, double-blind placebo-controlled trial with enrollment from April 1998 to October 1999. SETTING: One hundred thirty-two hospital centers across the United States and Canada. PATIENTS: The primary efficacy population consisted of 1367 ischemic stroke patients with a predefined level of limb weakness and functional independence prior to stroke, stratified at randomization by age (</=75 vs >75 years) and initial stroke severity (National Institutes of Health [NIH] Stroke Scale scores of 2-5, 6-13, or >/=14). INTERVENTION: Patients were randomly assigned to receive an intravenous loading dose (800 mg) plus 5 maintenance doses (200 mg every 12 hours) of gavestinel (n = 701) or placebo (n = 666) for 3 days. MAIN OUTCOME MEASURE: Functional capability at 3 months, measured by the Barthel Index (BI), with scores trichotomized as dead/0-55, 60-90, and 95-100, compared between the gavestinel and placebo groups. RESULTS: Treatment groups were well matched for baseline characteristics. For each group, median NIH Stroke Scale was 12, median age was 72 years, and median time to treatment was 5.2 hours. No statistically significant improvement on the 3-month BI trichotomy was demonstrated for gavestinel (P =.79). The proportion who were functionally independent (BI score = 95-100) was 39% in the gavestinel group and 37% in the placebo group. No statistically significant difference in 3-month survival was observed using Kaplan-Meier curves (P =.11). No other secondary end point suggested an advantage for gavestinel. Among the 333 patients (24%) who received recombinant tissue-type plasminogen activator, there was also no benefit for gavestinel (P =.53). There were no serious safety issues. CONCLUSION: In this study, gavestinel administered up to 6 hours after an acute ischemic stroke did not improve functional outcome at 3 months.

Aged↗