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Biomedical subjects

M A Sloan

Publications and source records attributed to M A Sloan.

At least 19 recordsLinked to original sources

Alcohol intake, type of beverage, and the risk of cerebral infarction in young women.

BACKGROUND AND PURPOSE: The relationship between alcohol consumption and cerebral infarction remains uncertain, and few studies have investigated whether the relationship varies by alcohol type or is present in young adults. We examined the relationship between alcohol consumption, beverage type, and ischemic stroke in the Stroke Prevention in Young Women Study. METHODS: All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. Case patients (n=224) were aged 15 to 44 years with a first cerebral infarction, and control subjects (n=392), identified by random-digit dialing, were frequency matched by age and region of residence. The interview assessed lifetime alcohol consumption and consumption and beverage type in the previous year, week, and day. ORs were obtained from logistic regression models controlling for age, race, education, and smoking status, with never drinkers as the referent. RESULTS: Alcohol consumption, up to 24 g/d, in the past year was associated with fewer ischemic strokes (<12 g/d: OR 0.57, 95% CI 0. 38 to 0.86; 12 to 24 g/d: OR 0.38, 95% CI 0.17 to 0.86; >24 g/d: OR 0.95, 95% CI 0.43 to 2.10) in comparison to never drinking. Analyses of beverage type (beer, wine, liquor) indicated a protective effect for wine consumption in the previous year (<12 g/wk: OR 0.58, 95% CI 0.35 to 0.97; 12 g/wk to <12 g/d: OR 0.55, 95% CI 0.28 to 1.10; >/=12 g/d: OR 0.92, 95% CI 0.23 to 3.64). CONCLUSIONS: Light to moderate alcohol consumption appears to be associated with a reduced risk of ischemic stroke in young women.

Adolescent↗

Utilization of multiple imperfect assessments of the dependent variable in a logistic regression analysis.

Often, in biomedical research, there are multiple sources of imperfect information regarding a dichotomous variable of interest. For example, in a study we are conducting on the relationship between cocaine use and stroke risk, information on the cocaine use of each study patient is available from three fallible sources: patient interviews; urine toxicology testing, and medical record review. Regression analyses based on a rule for classifying patients from this information can result in biased estimation of associations and variances due to the misclassification of some subjects and to the assumption of certainty. We describe a likelihood-based method that directly incorporates multiple sources of information regarding an outcome variable into a regression analysis and takes into account the uncertainty in the classification. The method can be applied when some sources of information are missing for some subjects. We show how the availability of multiple sources can be exploited to generate estimates of the quality (for example, sensitivity and specificity) of each source and to model the degree to which missing data are informative. A fitting algorithm and issues of identifiability are discussed. We illustrate the method using data from our study.

Adult↗

Lipoprotein (a) and the risk of ischemic stroke in young women.

BACKGROUND AND PURPOSE: lipoprotein (a) (lp (a)) is a lipid-containing particle similar to LDL which has been found in atherosclerotic plaque. The role of lp (a) in ischemic stroke remains controversial, but some studies suggest lp (a) is particularly important as a risk factor for stroke in young adults. We investigated the role of lp (a) as a risk factor for stroke in young women enrolled in the Stroke Prevention in Young Women Study. METHODS: subjects were participants in a population-based, case-control study of risk factors for ischemic stroke in young women. Cases were derived from surveillance of 59 regional hospitals in the central Maryland, Washington DC, Pennsylvania and Delaware area. Lp (a) was measured in 110 cases and 216 age-matched controls. Demographics, risk factors, and stroke subtype were determined by interview and review of medical records. RESULTS: lp (a) values were higher in blacks than whites, but within racial groups, the distribution of lp (a) values was similar between cases and controls. After adjustment for age, race, hypertension, diabetes, cigarette smoking, coronary artery disease, total cholesterol and HDL cholesterol, the odds ratio for an association of lp (a) and stroke was 1.36 (95% CI 0.80-2.29). There was no dose-response relationship between lp (a) quintile and stroke risk. Among stroke subtypes, only lacunar stroke patients had significantly elevated lp (a) values compared to controls. CONCLUSIONS: we found no association of lp (a) with stroke in a population of young women with ischemic stroke. Small numbers of patients limit conclusions regarding risk in ischemic stroke subtypes, but we could not confirm previous suggestions of an association of lp (a) with atherosclerotic stroke in young adults.

Adolescent↗

Clinical features of cardioembolic strokes identified by transesophageal echocardiography.

Clinical and CT scan features predictive of a cardiac source of embolism (CSOE) are helpful in planning appropriate investigations in ischaemic strokes. The currently described predictors of CSOE were determined before the availability of trans esophageal echocardiography (TEE). After the advent of TEE, many new CSOE were discovered. The present study was planned to investigate if the previously described predictors of CSOE are also valid for patients with CSOE detectable only with TEE (TEE-detected CSOE). From 1992-1995, 485 consecutive patients of ischemic stroke were enrolled in the Maryland Stroke Data Bank (MSDB). Patients with CSOE identified only by TEE and not by clinical, electrocardiographic or transthoracic echocardiographic (TTE) examination were compared to patients with a CSOE with respect to the features of the history, neurologic examination and CT scan. Of 485 patients with cerebral infarction, 132 (27%) patients had CSOE. In 21/132 (16%), diagnosis of high risk CSOE could be established only by TEE. The most discriminating clinical findings in TEE-detected CSOE patients were visual field deficit (OR 2.9; 95% CI, 1.1-7.4) and neglect (OR 3.4; 95% CI,1.2-9.3). Less strong associations were also found with other clinical features described previously for CSOE. No significant differences were found for features of the initial CT scan. In summary, presence of visual field defect and hemineglect may suggest a higher likelihood of finding a CSOE by TEE, even if the clinical cardiac examination and TTE are normal.

Adult↗

Stroke in patients with acute coronary syndromes: incidence and outcomes in the platelet glycoprotein IIb/IIIa in unstable angina. Receptor suppression using integrilin therapy (PURSUIT) trial. The PURSUIT Investigators.

BACKGROUND: The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates. METHODS AND RESULTS: We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were randomly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial to determine stroke rates, stroke types, clinical outcomes in patients with stroke, and independent baseline clinical predictors for nonhemorrhagic stroke. Stroke occurred in 79 (0.7%) patients, with 66 (0.6%) nonhemorrhagic, 6 intracranial hemorrhages, 3 cerebral infarctions with hemorrhagic conversion, and 4 of uncertain cause. There were no differences in stroke rates between patients who received placebo and those assigned high-dose eptifibatide (odds ratios and 95% confidence intervals 0.82 [0.59, 1.14] and 0.70 [0.49, 0.99], respectively). Of the 79 patients with stroke, 17 (22%) died within 30 days, and another 26 (32%) were disabled by hospital discharge or 30 days, whichever came first. Higher heart rate was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by older age, prior anterior myocardial infarction, prior stroke or transient ischemic attack, and diabetes mellitus. These factors were used to develop a simple scoring nomogram that can predict the risk of nonhemorrhagic stroke. CONCLUSIONS: Stroke was an uncommon event in patients with acute coronary syndromes in the PURSUIT trial. These strokes are, however, associated with substantial morbidity and mortality rates. The majority of strokes were of nonhemorrhagic causes. Eptifibatide was not associated with an increase in intracranial hemorrhage, and no significant effect on nonhemorrhagic stroke was observed. We developed a useful nomogram for assigning baseline nonhemorrhagic stroke risk in this patient population.

Acute Disease↗

Effects of stroke on medical resource use and costs in acute myocardial infarction. GUSTO I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Study.

BACKGROUND: Stroke occurs concurrently with myocardial infarction (MI) in approximately 30 000 US patients each year. This number is expected to rise with the increasing use of thrombolytic therapy for MI. However, no data exist for the economic effect of stroke in the setting of acute MI (AMI). The purpose of this prospective study was to assess the effect of stroke on medical resource use and costs in AMI patients in the United States. METHODS AND RESULTS: Medical resource use and cost data were prospectively collected for 2566 randomly selected US GUSTO I patients (from 23 105 patients) and for the 321 US GUSTO I patients who developed non-bypass surgery-related stroke during the baseline hospitalization. Follow-up was for 1 year. All costs are expressed in 1993 US dollars. During the baseline hospitalization, stroke was associated with a reduction in cardiac procedure rates and an increase in length of stay, despite a hospital mortality rate of 37%. Together with stroke-related procedural costs of $2220 per patient, the baseline medical costs increased by 44% ($29 242 versus $20 301, P<0.0001). Follow-up medical costs were substantially higher for stroke survivors ($22 400 versus $5282, P<0.0001), dominated by the cost of institutional care. The main determinant for institutional care was discharge disability status. The cumulative 1-year medical costs for stroke patients were $15 092 higher than for no-stroke patients. Hemorrhagic stroke patients had a much higher hospital mortality rate than non-hemorrhagic stroke patients (53% versus 15%, P<0.001), which was associated with approximately $7200 lower mean baseline hospitalization cost. At discharge, hemorrhagic stroke patients were more likely to be disabled (68% versus 46%, P=0.002). CONCLUSIONS: In this first large prospective economic study of stroke in AMI patients, we found that strokes were associated with a 60% ($15 092) increase in cumulative 1-year medical costs. Baseline hospitalization costs were 44% higher because of longer mean lengths of stay. Stroke type was a key determinant of baseline cost. Follow-up costs were more than quadrupled for stroke survivors because of the need for institutional care. Disability level was the main determinant of institutional care and thus of follow-up costs.

Activities of Daily Living↗

Neurosurgical evacuation of intracranial hemorrhage after thrombolytic therapy for acute myocardial infarction: experience from the GUSTO-I trial. Global Utilization of Streptokinase and tissue-plasminogen activator (tPA) for Occluded Coronary Arteries.

BACKGROUND: Intracranial hemorrhage is an uncommon but very dangerous complication in patients receiving thrombolytic therapy for acute myocardial infarction. Neurosurgical evacuation is often an available treatment option. However, the association between neurosurgical evacuation and clinical outcomes in these patients has yet to be determined. METHODS: The GUSTO-I trial randomly assigned 41,021 patients with acute myocardial infarction to 1 of 4 thrombolytic strategies in 1081 hospitals in 15 countries. A total of 268 patients (0.65%) had an intracranial hemorrhage. We assessed differences in clinical characteristics, neuroimaging features, Glasgow coma scale scores, functional status (disabled: moderate or severe deficit; not disabled: no or minor deficit) and 30-day mortality rate between the 46 patients who underwent neurosurgical evacuation and the 222 patients who did not. RESULTS: Mortality rate at 30 days for all patients with intracranial hemorrhage was 60%; an additional 27% were disabled. Evacuation was associated with significantly higher 30-day survival (65% versus 35%, P <.001) and a trend toward improved functional status (nondisabling stroke: 20% versus 12%, P =.15). CONCLUSIONS: Although intracranial hemorrhage is uncommon after thrombolysis for acute myocardial infarction, 87% of patients die or have disabling stroke. Although not definitive, these data indicate that neurosurgical evacuation may be associated with improved clinical outcomes. Physicians treating such patients should consider early neurosurgical consultation and intervention in these patients.

Aged↗

Spinal epidural abscess: contemporary trends in etiology, evaluation, and management.

BACKGROUND: Despite advances in neuroimaging and neurosurgical treatment, spinal epidural abscess remains a challenging problem; early diagnosis is often difficult and treatment is delayed. Optimal management is unclear, and morbidity and mortality are significant. To define contemporary trends in etiology and management, and establish diagnostic and therapeutic guidelines, we reviewed our 10-year experience with spinal epidural abscess. METHODS: We examined medical records, laboratory data, radiological (CT and MRI) studies, and operative reports from 75 cases of spinal epidural abscess between 1983 and 1992. Demographic characteristics, frequency, clinical features, pathogens, risk factors, surgical and medical treatment, and outcome were analyzed. RESULTS: We found a significant increase in the frequency of spinal epidural abscess over the 10-year period (p-value = 0.0195). Intravenous drug abuse was present in 28 patients (33%), diabetes mellitus in 22 patients (27%), and prior spinal surgery in 11 patients (17%). Back pain, progressive neurologic deficit, and low grade fever remained the distinguishing diagnostic features. Erythrocyte sedimentation rate was elevated in 48 of 50 patients (95%); peripheral leukocyte count was elevated in 45 patients (60%). MRI was the most effective technique for diagnosing spinal epidural abscess, revealing or suggesting the diagnosis in all 59 patients (100%) studied. Sites of spinal epidural abscess were equally distributed along the spinal axis. Staphylococcus aureus was the predominant organism (67% of patients, with 15% having a methicillin-resistant strain); 8% of patients had Streptococcal species. Most patients had open surgical drainage followed by prolonged antibiotic treatment; 22 patients were managed with antibiotics alone; 50 patients (66%) had a good clinical outcome after treatment. Multiple medical problems, prior spinal surgery, and methicillin-resistant Staphylococci were correlated with a significantly worse outcome. CONCLUSIONS: The frequency of diagnosis of spinal epidural abscess is increasing. To prevent serious morbidity and mortality, early diagnosis is essential. Patients with localized back pain who are at risk for developing such abscesses or who have an increased erythrocyte sedimentation rate and/or neurologic deficit should have an immediate MRI scan with contrast enhancement. Surgical drainage and prolonged antibiotic use are the cornerstones of treatment, although selected patients may be treated conservatively.

Abscess↗

Distribution and correlates of elevated total homocyst(e)ine: the Stroke Prevention in Young Women Study.

PURPOSE: To determine the distribution and correlates of elevated total homocyst(e)ine (tHcy) concentration in a population of premenopausal black and white women. METHODS: Data from the Stroke Prevention in Young Women Study (N = 304), a population-based study of risk factors for stroke in women aged 15-44 years of age, were used to determine the distribution and correlates of elevated tHcy in black (N = 103) and white women (N = 201). RESULTS: The mean tHcy level for the population was 6.58 micromol/L (range 2.89-26.5 micromol/L). Mean tHcy levels increased with age, cholesterol level, alcohol intake, and number of cigarettes smoked (all: p < 0.05). There were no race differences (mean tHcy 6.72 micromol/L among blacks and 6.51 micromol/L among whites; p = 0.4346). Regular use of multivitamins and increasing education was associated with significant reductions in tHcy concentration. Approximately 13% of the sample had elevated tHcy levels, defined as a tHcy concentration > or = 10.0 micromol/L. Multivariate-adjusted correlates of elevated tHcy included education > 12 vs. < or = 12 (odds ratio [OR] = 0.4, 95% confidence interval [CI] = 0.2-0.8); smoking > or = 20 cigarettes/day vs. nonsmokers (OR = 2.8, 95% CI = 1.1-7.3); and the regular use of multivitamins (OR = 0.4, 95% CI = 0.2-0.9). CONCLUSIONS: These results suggest that a substantial proportion of healthy young premenopausal women have tHcy levels that increase their risk for vascular disease. A number of potentially modifiable behavioral and environmental factors appear to be significantly related to elevated tHcy levels in young women.

Adolescent↗

Elevated tissue plasminogen activator antigen and stroke risk: The Stroke Prevention In Young Women Study.

BACKGROUND AND PURPOSE: Abnormalities in endogenous fibrinolysis are associated with an increased risk for stroke in men and older adults. We tested the hypothesis that elevated plasma tissue plasminogen activator (tPA) antigen, a marker for impaired endogenous fibrinolysis, is an independent risk factor for stroke in young women. METHODS: Subjects were 59 nondiabetic females ages 15 to 44 years with cerebral infarction from the Baltimore-Washington area and 97 control subjects frequency-matched for age who were recruited by random-digit dialing from the same geographic area. A history of cerebrovascular disease risk factors was obtained by face-to-face interview. Plasma tPA antigen was measured by enzyme-linked immunosorbent assay. RESULTS: Mean plasma tPA antigen levels were significantly higher in stroke patients than control subjects (4. 80+/-4.18 versus 3.23+/-3.67 ng/mL; P=0.015). After adjustment for age, hypertension, cigarette smoking, body mass index, and ischemic heart disease, there was a dose-response association between tPA antigen and stroke with a 3.9-fold odds ratio of stroke (95% CI, 1.2 to 12.4; P=0.03) for the upper quartile (>4.9 ng/mL) of tPA antigen compared with the lowest quartile. The dose-response relationship between tPA antigen and stroke was equally present in white and nonwhite women, and further adjustment for total and HDL cholesterol levels only modestly attenuated this association. CONCLUSIONS: This population-based case-control study shows that elevated plasma tPA antigen level is independently associated with an increased risk for ischemic stroke in nondiabetic females 15 to 44 years of age. These findings support the hypothesis that impaired endogenous fibrinolysis is an important risk factor for stroke in young women.

Adolescent↗

Stroke location is not associated with return to work after first ischemic stroke.

BACKGROUND AND PURPOSE: In prior studies, age, race, job category, disability, and cortical functions such as praxis, language, and memory have been associated with vocational outcome, but the influence of stroke location on return to work has never been critically examined. METHODS: We examined the influence of stroke location on vocational outcome in patients with clinically confirmed acute ischemic stroke from the National Institute of Neurological Disorders and Stroke Stroke Data Bank. RESULTS: Of 143 patients working full time at the time of first ischemic stroke, 23 patients were dead and 120 were alive at 1 year. Employment status was known in 109 (mean age, 55 years; 51 [47%] were white, and 82 [75%] were male). Fifty-eight (53%) had returned to work; most (85%) worked full time. Younger age was positively associated with return to work (P<0.05). In an age-adjusted analysis, stroke severity as measured by the Barthel Index 7 to 10 days after stroke was negatively associated with return to work (P<0.001). Higher household income and absence of cortical neurological dysfunction 7 to 10 days after stroke were positively but less strongly associated with return to work (P<0.08). Stroke location, sex, and depression at time of stroke were not associated with vocational outcome. CONCLUSIONS: Our data suggest that stroke location may be less important than other more easily measured factors in predicting vocational outcome.

Age Factors↗

Homocyst(e)ine and risk of cerebral infarction in a biracial population : the stroke prevention in young women study.

BACKGROUND AND PURPOSE: Genetic enzyme variation and vitamin intake are important determinants of blood homocyst(e)ine levels. The prevalence of common genetic polymorphisms influencing homocyst(e)ine levels varies by race, and vitamin intake varies by socioeconomic status. Therefore, we examined the effect of vitamin intake, race, and socioeconomic status on the association of homocyst(e)ine with stroke risk. METHODS: All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. One hundred sixty-seven cases of first ischemic stroke among women aged 15 to 44 years were compared with 328 controls identified by random-digit dialing from the same region. Risk factor data were collected by standardized interview and nonfasting phlebotomy. Plasma homocyst(e)ine was measured by high-performance liquid chromatography and electrochemical detection. RESULTS: Blacks and whites did not differ in median homocyst(e)ine levels, nor did race modify the association between homocyst(e)ine and stroke. After adjustment for cigarettes per day, poverty status, and regular vitamin use, a plasma homocyst(e)ine level of >/=7.3 micromol/L was associated with an odds ratio for stroke of 1.6 (95% CI, 1.1 to 2.5). CONCLUSIONS: The association between elevated homocyst(e)ine and stroke was independent not only of traditional vascular risk factors but also of vitamin use and poverty status. The degree of homocyst(e)ine elevation associated with an increased stroke risk in young women is lower than that previously reported for middle-aged men and the elderly and was highly prevalent, being present in one third of the control group.

Adolescent↗

Aging affects the ocular circadian pacemaker of Aplysia californica.

The eye of Aplysia has been used to explore various aspects of circadian rhythms. The authors discovered that age has profound effects on the circadian rhythm of nerve impulses from the eye. With age, there was a significant decrease in the amplitude of the rhythm. The decrease appeared to be continuous over the life span of the animal and was observed both in vitro and in vivo. The free-running period and phase angle of the rhythm steadily increased with age, indicating that the pacemaker itself was affected by age. Rates of transcription and translation were significantly increased with age, suggesting that age-associated alterations of the pacemaker may occur through changes in macromolecular synthesis. Interestingly, eyes from some older (> or = 10 months) animals had "cloudy" lenses (cataracts). Highly damped or arrhythmic rhythms always were seen in eyes with cloudy lenses. Morphology of eyes with cloudy lenses indicated severe retinal degeneration. No such degeneration was observed in eyes with clear lenses that were used in the analysis of the rhythm with age.

Action Potentials↗

Risk for intracranial hemorrhage after tissue plasminogen activator treatment for acute myocardial infarction. Participants in the National Registry of Myocardial Infarction 2.

BACKGROUND: The efficacy of thrombolytic therapy in reducing mortality from acute myocardial infarction has been unequivocally shown. However, thrombolysis is related to bleeding complications, including intracranial hemorrhage. OBJECTIVE: To determine the frequency of and risk factors for intracranial hemorrhage after recombinant tissue-type plasminogen activator (tPA) given for acute myocardial infarction in patients receiving usual care. DESIGN: Large national registry of patients who have had acute myocardial infarction. SETTING: 1484 U.S. hospitals. PATIENTS: 71073 patients who had had acute myocardial infarction from 1 June 1994 to 30 September 1996, received tPA as the initial reperfusion strategy, and did not receive a second dose of any thrombolytic agent. MEASUREMENT: Intracranial hemorrhage confirmed by computed tomography or magnetic resonance imaging. RESULTS: 673 patients (0.95%) were reported to have had intracranial hemorrhage during hospitalization for acute myocardial infarction; 625 patients (0.88%) had the event confirmed by computed tomography or magnetic resonance imaging. Of the 625 patients with confirmed intracranial hemorrhage, 331 (53%) died during hospitalization. An additional 158 patients (25.3%) who survived to hospital discharge had residual neurologic deficit. In multivariable models for the main effects of candidate risk factors, older age, female sex, black ethnicity, systolic blood pressure of 140 mm Hg or more, diastolic blood pressure of 100 mm Hg or more, history of stroke, tPA dose more than 1.5 mg/kg, and lower body weight were significantly associated with intracranial hemorrhage. CONCLUSIONS: Intracranial hemorrhage is a rare but serious complication of tPA in patients with acute myocardial infarction. Appropriate drug dosing may reduce the risk for this complication. Other therapies, such as primary coronary angioplasty, may be preferable in patients with acute myocardial infarction who have a history of stroke.

Age Factors↗

Prediction of 30-day mortality among patients with thrombolysis-related intracranial hemorrhage.

BACKGROUND: Limited information exists on risk factors for mortality after thrombolysis-related intracranial hemorrhage. We wished to determine the characteristics associated with 30-day mortality after thrombolysis-related intracranial hemorrhage. METHODS AND RESULTS: We performed an observational analysis within a randomized trial of 4 thrombolytic therapies, conducted in 1081 hospitals in 15 countries. Patients presented with ST-segment elevation within 6 hours of symptom onset. Our population was composed of the 268 patients who had primary intracranial hemorrhage after thrombolysis. With univariable and multivariable analyses, we identified clinical and brain imaging characteristics that would predict 30-day mortality among these patients. CT or MRI were available for 240 patients (90%). The 30-day mortality rate was 59.7%. Glasgow Coma Scale score, age, time from thrombolysis to symptoms of intracranial hemorrhage, hydrocephalus, herniation, mass effect, intraventricular extension, and volume and location of intracranial hemorrhage were significant univariable predictors. Multivariable analysis of 170 patients with complete data, 98 of whom died, identified the following independent, significant predictors: Glasgow Coma Scale score (chi2, 19.3; P<0. 001), time from thrombolysis to intracranial hemorrhage (chi2, 15.8; P<0.001), volume of intracranial hemorrhage (chi2, 11.6; P<0.001), and baseline clinical predictors of mortality in the overall GUSTO-I trial (chi2, 10.3; P=0.001). The final model had a C-index of 0.931. CONCLUSIONS: This model provides excellent discrimination between patients who are likely to live and those who are likely to die after thrombolytic-related intracranial hemorrhage; this may aid in making decisions about the appropriate level of care for such patients.

Aged↗

Risk factors for in-hospital nonhemorrhagic stroke in patients with acute myocardial infarction treated with thrombolysis: results from GUSTO-I.

BACKGROUND: Nonhemorrhagic stroke occurs in 0.1% to 1.3% of patients with acute myocardial infarction who are treated with thrombolysis, with substantial associated mortality and morbidity. Little is known about the risk factors for its occurrence. METHODS AND RESULTS: We studied the 247 patients with nonhemorrhagic stroke who were randomly assigned to one of four thrombolytic regimens within 6 hours of symptom onset in the GUSTO-I trial. We assessed the univariable and multivariable baseline risk factors for nonhemorrhagic stroke and created a scoring nomogram from the baseline multivariable modeling. We used time-dependent Cox modeling to determine multivariable in-hospital predictors of nonhemorrhagic stroke. Baseline and in-hospital predictors were then combined to determine the overall predictors of nonhemorrhagic stroke. Of the 247 patients, 42 (17%) died and another 98 (40%) were disabled by 30-day follow-up. Older age was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by higher heart rate, history of stroke or transient ischemic attack, diabetes, previous angina, and history of hypertension. These factors remained statistically significant predictors in the combined model, along with worse Killip class, coronary angiography, bypass surgery, and atrial fibrillation/flutter. CONCLUSIONS: Nonhemorrhagic stroke is a serious event in patients with acute myocardial infarction who are treated with thrombolytic, antithrombin, and antiplatelet therapy. We developed a simple nomogram that can predict the risk of nonhemorrhagic stroke on the basis of baseline clinical characteristics. Prophylactic anticoagulation may be an important treatment strategy for patients with high probability for nonhemorrhagic stroke, but further study is needed.

Age Factors↗

Thrombolysis-related intracranial hemorrhage: a radiographic analysis of 244 cases from the GUSTO-1 trial with clinical correlation. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is a serious complication of thrombolytic therapy. We systematically reviewed the radiographic features of 244 cases of symptomatic ICH complicating thrombolysis for acute myocardial infarction in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial, correlated these observations with clinical data, and speculated on hemorrhage pathogenesis. METHODS: CT scans from 244 patients suffering symptomatic ICH were systematically reviewed for selected radiographic features, including ICH type, location, hematoma characteristics, mass effect features, hydrocephalus, and preexisting lesions. Hematoma volume was estimated by computer-assisted volumetric analysis. Data from this analysis were correlated with clinical data including hypertension, anticoagulation, age, thrombolytic regimen, and ICH timing. RESULTS: Most hemorrhages were large (median [25th, 75th percentile] volume, 72 mL [39, 118]), solitary (66%), lobar (77%), confluent (80%), and intraparenchymal (82%) with a blood/fluid level (82%) and little edema (median [25th, 75th percentile] volume, 9 mL [5, 16]). Hydrocephalus (P<.001), any one mass effect feature (P<.001), intraventricular hemorrhage (P=.022), mottled hematoma appearance (P=.050), and hematoma blood/fluid level (P<.001) were associated with higher hemorrhage volume in the radiographic analysis, as were older age (P=.005), treatment with combined streptokinase and tissue plasminogen activator (P=.034), and hemorrhage onset 8 to 13 hours after treatment (P=.008) in the clinical analysis. Subdural hemorrhage was a high-volume subgroup whose risk increased with antecedent trauma (P=.026) or syncope (P=.006). Deep intraparenchymal hemorrhage was associated with hypertension (P=.016), and multifocal ICH occurred significantly earlier after treatment (P=.002). CONCLUSIONS: Although the majority of postthrombolytic ICH are large, solitary, and supratentorial, the spectrum is diverse. Features of mass effect reflected the large volumes, and hematoma characteristics of mottling and blood/fluid levels were frequent. Thrombolysis-related coagulopathy and age appear to be the most important identifiable factors in the genesis of postthrombolytic ICH, but the hemorrhage subtype seen may reflect an interaction with other factors such as hypertension, ICH timing, antecedent head trauma, and syncope.

Cerebral Hemorrhage↗

Platelet glycoprotein receptor IIIa polymorphism P1A2 and ischemic stroke risk: the Stroke Prevention in Young Women Study.

BACKGROUND AND PURPOSE: Platelet glycoprotein IIb/IIa (GpIIb-IIIa), a membrane receptor for fibrinogen and von Willebrand factor, has been implicated in the pathogenesis of acute coronary syndromes but has not been previously investigated in relation to stroke in young adults. METHODS: We used a population-based case-control design to examine the association of the GpIIIa polymorphism P1A2 with stroke in young women. Subjects were 65 cerebral infarction cases (18 patients with and 47 without an identified probable etiology) 15 to 44 years of age from the Baltimore-Washington region and 122 controls frequency matched by age from the same geographic area. A face-to-face interview for vascular disease risk factors and a blood sample for the P1A2 allele and serum cholesterol were obtained from each participant. Logistic regression was used to estimate the odds ratio for one or more P1A2 alleles after adjustment for other risk factors. RESULTS: Among cases and controls, the prevalence rates of one or more P1A2 alleles were 21% and 22% among blacks and 36% and 28% among whites, respectively. This genotype was significantly associated with hypertension only in black control subjects but otherwise not with any of the established vascular risk factors. The adjusted odds ratio for cerebral infarction of one or more P1A2 alleles was 1.1 (confidence interval [CI], 0.6 to 2.3) overall, 0.5 (CI, 0.1 to 7.1) among blacks, and 1.4 (CI, 0.5 to 3.7) among whites. For the cases with an identified probable etiology, the corresponding odds ratios were 3.0 (CI, 0.9 to 10.4) overall, 0.7 (CI, 0.1 to 7.1) among blacks, and 12.8 (CI, 1.2 to 135.0) among whites. CONCLUSIONS: No association was found between the P1A2 polymorphism of GpIIIa and young women with stroke. However, subgroup analyses showed that the P1A2 polymorphism of GpIIIa appeared to be associated with stroke risk among white women, particularly those with a clinically identified probable etiology for their stroke. Further work with an emphasis on stroke subtypes and with multiracial populations is warranted.

Adolescent↗