Marcella A. Wozniak

PREGNANCY AND THE RISK OF STROKE

BACKGROUND It is widely believed that pregnancy increases the risk of stroke, but there are few data available to quantify that risk. METHODS We identified all female patients 15 through 44 years of age in central Maryland and Washington, D.C., who were discharged from any of 46 hospitals in the study area in 1988 or 1991. Two neurologists reviewed each case, using data from the womens medical records. We determined whether the women had been pregnant at the time of the stroke or up to six weeks before it occurred. For purposes of this analysis, the six-week period after pregnancy could begin with an induced or spontaneous abortion or with the delivery of a live or stillborn child. RESULTS Seventeen cerebral infarctions and 14 intracerebral hemorrhages occurred in women who were or had recently been pregnant (pregnancy-related strokes), and there were 175 cerebral infarctions and 48 intracerebral hemorrhages that were not related to pregnancy. For cerebral infarction, the relative risk during pregnancy, adjusted age and race, was 0.7 (95 percent confidence interval, 0.3 to 1.6), but it increased to 8.7 for the postpartum period (after a live birth or stillbirth) (95 percent confidence interval, 4.6 to 16.7). For intracerebral hemorrhage, the adjusted relative risk was 2.5 during pregnancy (95 percent confidence interval, 1.0 to 6.4) but 28.3 for the postpartum period (95 percent confidence interval, 13.0 to 61.4). Overall, for either type of stroke during or within six weeks after pregnancy, the adjusted relative risk was 2.4 (95 percent confidence interval, 1.6 to 3.6), and the attributable, or excess, risk was 8.1 strokes per 100,000 pregnancies (95 percent confidence interval, 6.4 to 9.7). CONCLUSIONS The risks of both cerebral infarction and intracerebral hemorrhage are increased in the six weeks after delivery but not during pregnancy itself.

Probable Migraine With Visual Aura and Risk of Ischemic Stroke: The Stroke Prevention in Young Women Study

Background and Purpose— Migraine with aura is associated with ischemic stroke, but few studies have investigated the clinical and anatomic features of this association. We assessed the association of probable migraine with and without visual aura with ischemic stroke within subgroups defined by stroke subtype, vascular territory, probable migraine characteristics, and other clinical features. Methods— Using data from a population-based, case-control study, we studied 386 women ages 15 to 49 years with first ischemic stroke and 614 age- and ethnicity-matched controls. Based on their responses to a questionnaire on headache symptoms, subjects were classified as having no migraine, probable migraine without visual aura, or probable migraine with visual aura (PMVA). Results— Women with PMVA had 1.5 greater odds of ischemic stroke (95% CI, 1.1 to 2.0); the risk was highest in those with no history of hypertension, diabetes, or myocardial infarction compared to women with no migraine. Women with PMVA who were current cigarette smokers and current users of oral contraceptives had 7.0-fold higher odds of stroke (95% CI, 1.3 to 22.8) than did women with PMVA who were nonsmokers and non–oral contraceptive users. Women with onset of PMVA within the previous year had 6.9-fold higher adjusted odds of stroke (95% CI, 2.3 to 21.2) compared to women with no history of migraine. Conclusions— PMVA was associated with an increased risk of stroke, particularly among women without other medical conditions associated with stroke. Behavioral risk factors, specifically smoking and oral contraceptive use, markedly increased the risk of PMVA, as did recent onset of PMVA.

Cerebral infarction in young adults The Baltimore-Washington Cooperative Young Stroke Study

Background: Few reports on stroke in young adults have included cases from all community and referral hospitals in a defined geographic region. Methods: At 46 hospitals in Baltimore City, 5 central Maryland counties, and Washington, DC, the chart of every patient 15 to 44 years of age with a primary or secondary diagnosis of possible cerebral arterial infarction during 1988 and 1991 was abstracted. Probable and possible etiologies were assigned following written guidelines. Results: Of 428 first strokes, 212 (49.5%) were assigned at least one probable cause, 80 (18.7%) had no probable cause but at least one possible cause, and 136 (31.8%) had no identified probable or possible cause. Of the 212 with at least one probable cause, the distribution of etiologies was cardiac embolism(31.1%), hematologic and other (19.8%), small vessel (lacunar) disease(19.8%), nonatherosclerotic vasculopathy (11.3%), illicit drug use (9.4%), oral contraceptive use (5.2%), large artery atherosclerotic disease (3.8%), and migraine (1.4%). There were an additional 69 recurrent stroke patients. Conclusions: In this hospital-based registry within a region characterized by racial/ethnic diversity, cardiac embolism, hematologic and other causes, and lacunar stroke were the most common etiologies of cerebral infarction in young adults. Nearly a third of both first and recurrent strokes had no identified cause.

Stroke in children and sickle-cell disease Baltimore-Washington Cooperative Young Stroke Study

Background/Purpose: The Baltimore-Washington Cooperative Young Stroke Study is the largest biracial urban-suburban population-based study to examine the etiology of strokes in children. Methods: We identified all children aged 1 to 14 years discharged from all 46 hospitals in central Maryland and Washington, DC with a diagnosis of ischemic stroke and intracerebral hemorrhage in the years 1988 and 1991. Each medical record was reviewed by two neurologists for appropriateness of the diagnosis of stroke and for information on the patients history, clinical presentation, pertinent investigations, hospital stay, and outcome at time of discharge. Results: Eighteen children with ischemic infarction and 17 with intracerebral hemorrhage were identified. The most common cause of ischemic stroke was sickle-cell disease (39%), followed by vasculopathic (33%) and indeterminate(28%) causes. Causes of intracerebral hemorrhages were arteriovenous malformation (29%), hematologic (23%), vasculopathy (18%), surgical complication (12%), coagulopathy (6%), and indeterminate (12%). The overall incidence for childhood stroke was 1.29 per 100,000 per year, with ischemic stroke occurring at a rate of 0.58 per 100,000 and intracerebral hemorrhage occurring at a rate of 0.71 per 100,000. The incidence of stroke among children with sickle-cell disease was estimated to be 0.28% or 285 per 100,000 per year. Conclusion: Sickle-cell disease plays a disproportionately high role in childhood stroke when a biracial population is surveyed.

Antiphospholipid antibodies and stroke in young women.

Background and Purpose— Antiphospholipid antibodies have been associated with ischemic stroke in some but not all studies. Methods— We performed a population-based case-control study examining antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulants) using stored frozen sera and plasma in 160 cases and 340 controls enrolled in the Stroke Prevention in Young Women study. We evaluated for the presence of anticardiolipin antibody (IgG, IgM, and IgA isotypes) by an enzyme-linked immunosorbent assay and for the lupus anticoagulant using several phospholipid-dependent coagulation tests (activated partial thromboplastin time, dilute Russell’s viper venom time) with mixing studies. If mixing studies were prolonged, confirmatory tests were performed. Results— A positive anticardiolipin antibody level of any isotype was seen in 43 cases (26.9%) and 62 controls (18.2%) (P =0.03), lupus anticoagulant in 29 cases (20.9%) and 38 controls (12.8%) (P =0.03), and either anticardiolipin antibody or lupus anticoagulant in 61 cases (42.1%) and 86 controls (27.9%) (P =0.003). After adjustment for age, current cigarette smoking, hypertension, diabetes, angina, ethnicity, body mass index, and high-density lipoprotein levels, the relative odds of stroke for women with anticardiolipin antibody immunoreactivity of any isotype or a lupus anticoagulant was 1.87 (95% confidence interval, 1.24 to 2.83;P =0.0027). Conclusions— The results from this study support the importance of antiphospholipid antibodies as an independent risk factor for stroke in young women.

Acquired Immunodeficiency Syndrome and the Risk of Stroke

Background and Purpose— Although acquired immunodeficiency syndrome (AIDS) is thought to increase the risk of stroke, few data exist to quantify this risk. This is the first population-based study to quantify the AIDS-associated risk of stroke. Methods— We identified all incident ischemic stroke (IS) and intracerebral hemorrhage (ICH) cases among young adults 15 to 44 years of age in central Maryland and Washington, DC, who were discharged from any of the 46 hospitals in the study area in 1988 and 1991. Using data from the medical records, 2 neurologists reviewed each case to confirm the diagnosis. Cases of AIDS among these patients with stroke were defined using Centers for Disease Control and Prevention criteria (1987). The number of cases of AIDS in the central Maryland and Washington population during 1988 and 1991 was determined from regional health departments working with the Centers for Disease Control and Prevention. Poisson regression was used to estimate the age-, race-, and sex-adjusted relative risk of stroke associated with AIDS. Results— There were 385 IS cases (6 with AIDS) and 171 ICH cases (6 with AIDS). The incidences of IS and ICH among persons with AIDS were both 0.2% per year. AIDS conferred an adjusted relative risk of 13.7 (95% confidence interval [CI], 6.1 to 30.8) for IS and 25.5 (95% CI, 11.2 to 58.0) for ICH. After exclusion of 5 cases of stroke in AIDS patients in whom other potential causes were identified, AIDS patients continued to have an increased risk of stroke with an adjusted relative risk of 9.1 (95% CI, 3.4 to 24.6) for IS and 12.7 (95% CI, 4.0 to 40.0) for ICH. Conclusions— This population-based study found that AIDS is strongly associated with both IS and ICH.

Preeclampsia and the Risk of Ischemic Stroke Among Young Women Results From the Stroke Prevention in Young Women Study

Background and Purpose— Preeclampsia is a pregnancy-specific systemic syndrome of unknown cause that affects 3% to 8% of pregnancies in the United States. Although preeclampsia is known to be an important risk factor for pregnancy-associated stroke, few data exist with regard to its association with stroke not occurring during pregnancy or the postpartum period. Methods— Using data from the Stroke Prevention in Young Women Study (SPYW), a population-based case-control study of risk factors for ischemic stroke in women aged 15 to 44 years (recruitment period: 1992 to 1996, SPYW-1; 2001 to 2003, SPYW-2), we examined the independent association between a history of preeclampsia and the likelihood of ischemic stroke. Odds ratios (ORs) and 95% CIs were estimated using logistic regression. Cases (n=261) were women with stroke in the greater Baltimore-Washington area, and controls (n=421) were women free of a history of stroke identified by random digit dialing. Women who were pregnant at the time of stroke, those whose stroke occurred within 42 days postpartum, and nulligravida women were excluded from the analysis. Results— The prevalence of preeclampsia among cases and controls was 15% (SPYW-1: 16%; SPYW-2: 15%) and 10% (SPYW-1: 10%; SPYW-2: 11%), respectively. Preeclampsia was associated with an increased likelihood of ischemic stroke (crude OR: 1.59; 95% CI: 1.00 to 2.52). After multivariable adjustment for age, race, education, and number of pregnancies, women with a history of preeclampsia were 60% more likely to have a nonpregnancy-related ischemic stroke than those without a history of preeclampsia (OR: 1.63; 95% CI: 1.02 to 2.62). Similar patterns were observed for women who reported symptoms of preeclampsia (elevated blood pressure and proteinuria). Conclusion— These results suggest an association between a history of preeclampsia and ischemic stroke remote from pregnancy. If these results are confirmed in other studies, evaluation of the importance of targeting women with preeclampsia for close risk factor monitoring and control beyond the postpartum period may be warranted.

Transcranial Doppler detection of vertebrobasilar vasospasm following subarachnoid hemorrhage.

Transcranial Doppler sonography is of established value in the detection and monitoring of middle cerebral artery vasospasm. Little information exists on the utility of transcranial Doppler for detection of posterior circulation vasospasm. Methods Cerebral angiography and conventional handheld transcranial Doppler sonography were compared to determine sensitivity and specificity of transcranial Doppler for detection of vertebral and basilar artery vasospasm. Results Of 59 consecutive subarachnoid hemorrhage patients with transcranial Doppler angiogram correlations, 42 underwent posterior circulation angiography to evaluate 64 vertebral arteries and 42 basilar arteries during the period of risk for vasospasm and had technically adequate transcranial Doppler examinations within 24 hours of the angiogram. A mean flow velocity of 60 cm/s and above was indicative of both vertebral and basilar artery vasospasm. For the vertebral artery, there were 7 true-positive test results, 42 true-negatives, 6 false-positives (unknown cause in 3, increased collateral flow in 1, adjacent vessel vasospasm in 1, hyperperfusion in 1), and 9 false-negatives (anatomic in 7, operator error in 2). Sensitivity was 44% and specificity was 87.5%. For the basilar artery, there were 10 true-positives, 23 true-negatives, 6 falsepositives (unknown cause in 4, hyperemia/hyperperfusion in 1, increased collateral flow in 1), and 3 false-negatives (operator error in 2, tortuous vessel course in 1). Sensitivity was 76.9% and specificity was 79.3%. When the diagnostic criterion was changed to ≥80 cm/s (vertebral artery) and ≥95 cm/s (basilar artery), all false-positive results were eliminated (specificity and positive predictive value, 100%). Conclusions Our data suggest that transcranial Doppler has good specificity for the detection of vertebral artery vasospasm and good sensitivity and specificity for the detection of basilar artery vasospasm. Transcranial Doppler is highly specific (100%) for vertebra] and basilar artery vasospasm when flow velocities are ≥80 and ≥95 cm/s, respectively.

Dose-Response Relationship Between Cigarette Smoking and Risk of Ischemic Stroke in Young Women

Background and Purpose— Although cigarette smoking is known to be a risk factor for ischemic stroke, there are few data on the dose-response relationship between smoking and stroke risk in a young ethnically diverse population. Methods— We used data from the Stroke Prevention in Young Women Study, a population-based case-control study of risk factors for ischemic stroke in women aged 15 to 49 years to examine the relationship between cigarette smoking and ischemic stroke. Historical data, including smoking history, was obtained through standardized interviews. Odds ratios (OR) were estimated using logistic regression. Cases (n=466) were women with stroke in the greater Baltimore-Washington area, and controls (n=604) were women free of a stroke history identified by random digit dialing. Results— After multivariable adjustment, the OR comparing current smokers to never smokers was 2.6 (P<0.0001); no difference in stroke risk was observed between former smokers and never smokers. Adjusted OR increased with increasing number of cigarettes smoked per day (OR=2.2 for 1 to 10 cigs/d; 2.5 for 11 to 20 cigs/d; 4.3 for 21 to 39 cigs/d; 9.1 for 40 or more cigs/d). Conclusion— These results suggest a strong dose-response relationship between cigarette smoking and ischemic stroke risk in young women and reinforce the need for aggressive smoking cessation efforts in young adults.

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.