Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆.

OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.

Detailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study.

OBJECTIVE: Posterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. METHODS: Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. RESULTS: PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. CONCLUSION: Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.

Brain Perivascular Spaces as Biomarkers of Vascular Risk: Results from the Northern Manhattan Study.

BACKGROUND AND PURPOSE: Dilated perivascular spaces in the brain are associated with greater arterial pulsatility. We hypothesized that perivascular spaces identify individuals at higher risk for systemic and cerebral vascular events. MATERIALS AND METHODS: Stroke-free participants in the population-based Northern Manhattan Study had brain MR imaging performed and were followed for myocardial infarction, any stroke, and death. Imaging analyses distinguished perivascular spaces from lesions presumably ischemic. Perivascular spaces were further subdivided into lesions with diameters of ≤3 mm (small perivascular spaces) and >3 mm (large perivascular spaces). We calculated relative rates of events with Poisson models and hazard ratios with Cox proportional models. RESULTS: The Northern Manhattan Study participants who had MR imaging data available for review (n = 1228; 59% women, 65% Hispanic; mean age, 71 ± 9 years) were followed for an average of 9 ± 2 years. Participants in the highest tertile of the small perivascular space score had a higher relative rate of all deaths (relative rate, 1.38; 95% CI, 1.01-1.91), vascular death (relative rate, 1.87; 95% CI, 1.12-3.14), myocardial infarction (relative rate, 2.08; 95% CI, 1.01-4.31), any stroke (relative rate, 1.79; 95% CI, 1.03-3.11), and any vascular event (relative rate, 1.74; 95% CI, 1.18-2.56). After we adjusted for confounders, there was a higher risk of vascular death (hazard ratio, 1.06; 95% CI, 1.01-1.11), myocardial infarction (hazard ratio, 2.22; 95% CI, 1.12-4.42), and any vascular event (hazard ratio, 1.04; 95% CI, 1.01-1.08) with higher small perivascular space scores. CONCLUSIONS: In this multiethnic, population-based study, participants with a high burden of small perivascular spaces had increased risk of vascular events. By gaining pathophysiologic insight into the mechanism of perivascular space dilation, we may be able to propose novel therapies to better prevent vascular disorders in the population.

Utility of blood pressure genetic risk score in admixed Hispanic samples.

Hypertension is strongly influenced by genetic factors. Although hypertension prevalence in some Hispanic sub-populations is greater than in non-Hispanic whites, genetic studies on hypertension have focused primarily on samples of European descent. A recent meta-analysis of 200 000 individuals of European descent identified 29 common genetic variants that influence blood pressure, and a genetic risk score derived from the 29 variants has been proposed. We sought to evaluate the utility of this genetic risk score in Hispanics. The sample set consists of 1994 Hispanics from 2 cohorts: the Northern Manhattan Study (primarily Dominican/Puerto Rican) and the Miami Cardiovascular Registry (primarily Cuban/South American). Risk scores for systolic and diastolic blood pressure were computed as a weighted sum of the risk alleles, with the regression coefficients reported in the European meta-analysis used as weights. Association of risk score with blood pressure was tested within each cohort, adjusting for age, age2, sex and body mass index. Results were combined using an inverse-variance meta-analysis. The risk score was significantly associated with blood pressure in our combined sample (P=5.65 × 10-4 for systolic and P=1.65 × 10-3 for diastolic) but the magnitude of the effect sizes varied by degree of European, African and Native American admixture. Further studies among other Hispanic sub-populations are needed to elucidate the role of these 29 variants and identify additional genetic and environmental factors contributing to blood pressure variability in Hispanics.

Differences in lipid profiles in two Hispanic ischemic stroke populations.

BACKGROUND AND PURPOSE: The study aims to compare lipid profiles among ischemic stroke patients in a predominantly Caribbean-Hispanic population in Miami and a Mestizo Hispanic population in Mexico City. METHODS: We analyzed ischemic stroke Hispanic patients with complete baseline fasting lipid profile enrolled contemporaneously in the prospective registries of two tertiary care teaching hospitals in Mexico City and Miami. Demographic characteristics, risk factors, medications, ischemic stroke subtype, and first fasting lipid profile were compared. Vascular risk factor definitions were standardized. Multiple linear regression analysis was performed to compare lipid fractions. RESULTS: A total of 324 patients from Mexico and 236 from Miami were analyzed. Mexicans were significantly younger (58 · 1 vs. 67 · 4 years), had a lower frequency of hypertension (53 · 4% vs. 79 · 7%), and lower body mass index (27 vs. 28 · 5). There was a trend toward greater prevalence of diabetes in Mexicans (31 · 5 vs. 24 · 6%, P = 0 · 07). Statin use at the time of ischemic stroke was more common in Miami Hispanics (18 · 6 vs. 9 · 4%). Mexicans had lower total cholesterol levels (169 · 9 ± 46 · 1 vs. 179 · 9 ± 48 · 4 mg/dl), lower low-density lipoprotein (92 · 3 ± 37 · 1 vs. 108 · 2 ± 40 · 8 mg/dl), and higher triglyceride levels (166 · 9 ± 123 · 9 vs. 149 · 2 ± 115 · 2 mg/dl). These differences remained significant after adjusting for age, gender, hypertension, diabetes, body mass index, smoking, ischemic stroke subtype, and statin use. CONCLUSION: We found significant differences in lipid fractions in Hispanic ischemic stroke patients, with lower total cholesterol and low-density lipoprotein, and higher triglyceride levels in Mexicans. These findings highlight the heterogeneity of dyslipidemia among the Hispanic race-ethnic group and may lead to different secondary prevention strategies.

Perivascular spaces are associated with atherosclerosis: an insight from the Northern Manhattan Study.

BACKGROUND AND PURPOSE: Perivascular spaces are potential spaces found between brain blood vessels and surrounding leptomeninges that have been associated with cardiovascular risk factors and dementia, but less is known about their relationship to atherosclerosis. We tested the hypothesis that perivascular spaces are associated with atherosclerosis. MATERIALS AND METHODS: Participants from the Northern Manhattan Study who remained stroke-free were invited to participate in an MR imaging substudy. Parenchymal hypointensities of <3 mm identified on brain axial T1-weighted MR imaging were scored as perivascular spaces. A semiquantitative score was created to express the degree of brain involvement. Generalized linear models were used to assess statistical associations with carotid plaque as a surrogate marker of atherosclerosis. RESULTS: The studied sample included 706 participants (mean age, 72.6 ± 8.0 years; 60% women, 61% Hispanic, 68% with hypertension, 19% with diabetes, and 57% with high cholesterol). The perivascular spaces score ranged from 0 to 19 with 52% of the sample having a perivascular spaces score of ≤4. In unadjusted analysis, perivascular spaces were associated with age (ß = 0.01 per year, P = < .001), non-Hispanic black race-ethnicity (ß = 0.16, P = .02), hypertension (ß = 0.24, P = < .001), and carotid plaque (ß = 0.22, P < .001). In multivariable analysis, only age (ß = 0.01, P = .02), hypertension (ß = 0.17, P = .01), and carotid plaque (ß = 0.22, P = < .001) remained independently associated with perivascular spaces. CONCLUSIONS: Perivascular spaces were more frequently found in older participants, in those with hypertension, and in the presence of carotid plaque. These results suggest that mechanisms leading to atherosclerosis might also lead to an increased number of perivascular spaces. These results need confirmation in prospective studies.

Effect of parathyroidectomy on subclinical cardiovascular disease in mild primary hyperparathyroidism.

OBJECTIVE: We recently demonstrated that mild primary hyperparathyroidism (PHPT) is associated with increased carotid intima-media thickness (IMT) and stiffness, and increased aortic valve calcification. It is unclear whether parathyroidectomy (PTX) improves these abnormalities. The purpose of this study was to determine whether cardiovascular abnormalities in PHPT improve with PTX. DESIGN: Forty-four patients with PHPT were studied using carotid ultrasound and transthoracic echocardiography before and after PTX. Carotid IMT, carotid plaque and stiffness, left ventricular mass index (LVMI), myocardial and valvular calcification, and diastolic function were measured before, 1- and 2-year post-PTX. RESULTS: Two years after PTX, increased carotid stiffness tended to decline to the normal range (17%, P=0.056) while elevated carotid IMT did not improve. Carotid plaque number and thickness, LVMI and cardiac calcifications did not change after PTX, while some measures of diastolic function (isovolumic relaxation time (IVRT) and tissue Doppler peak early diastolic velocity) worsened within the normal range. Indices did improve in patients with cardiovascular abnormalities at baseline. Increased carotid stiffness improved by 28% (P=0.004), a decline likely to be of clinical significance. More limited improvements also occurred in elevated IMT (3%, P=0.017) and abnormal IVRT (13%, P<0.05), a measure of diastolic dysfunction. CONCLUSIONS: In mild PHPT, PTX led to modest changes in some cardiovascular indices. Improvements were mainly evident in those with preexisting cardiovascular abnormalities, particularly elevated carotid stiffness. These findings are reassuring with regard to current international guidelines that do not include cardiovascular disease as a criterion for PTX.

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.

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.

Primary end-point times, functional outcome and adverse event profile after acute ischaemic stroke.

BACKGROUND: Poststroke complications such as pulmonary embolism, deep vein thrombosis and pneumonia can impact outcome by causing deterioration in general health, delaying or preventing rehabilitation. While stroke carries a direct risk of complications, some events may be unrelated to index stroke severity and could confound outcome. We examined whether the presence of complications 'unrelated' to index stroke at later time-points could confound outcome, and if this could be minimised through altering study end-points. METHODS: We analysed 531 placebo-treated patients from the Virtual International Stroke Trials Archive who had experienced an acute ischaemic stroke and at least one poststroke complication during the 90-day follow-up period. We categorised complications into those deemed 'related' or 'unrelated' to index stroke severity. We examined modified Rankin Scale at 30 and 90 days, stratified by type of complication and assessed the impact of eliminating 'unrelated' complications on functional outcome (modified Rankin Scale) at 30 and 90 days using logistic regression (accounting for age and baseline National Institutes of Health Stroke Scale). RESULTS: The majority of complications in the early acute period after index stroke were 'stroke related' (30.2%). Patients did not have a better modified Rankin Scale profile at 30 days when compared with 90 days, regardless of the type of complications experienced. The absence of 'stroke unrelated' complications was associated with a worse outcome at 30 days [P=0.04, adjusted odds ratio for good functional outcome=0.54, 95% confidence interval (0.3, 0.96)], and had no significant effect on outcome at 90 days. CONCLUSIONS: We identified complications, which we deemed not to have occurred as a direct consequence of index stroke, but found that the absence of these events did not beneficially alter outcome at either short-term (30 days) or long-term (90 days) follow-up periods. Our analyses did not support the shortening of trial follow-up periods with the aim of minimising the risk of stroke-unrelated complications.

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.

Natural history of complications after intracerebral haemorrhage.

BACKGROUND AND PURPOSE: Numerous trials of haemostatic and neuroprotective agents for intracerebral haemorrhage (ICH) have failed. We characterized the risk of complications after ICH in a trial-eligible patient population, to inform safety in future trials. METHODS: We used the Virtual International Stroke Trials Archive database to identify placebo-treated patients with spontaneous ICH, who were not comatose at admission, where randomization took place within 4 h of symptom onset, and where serious complication and outcome data were available. We described the complications encountered and assessed whether the absence of common complications influenced attainment of good functional outcome (mRS < or =4) at 90 days using logistic regression. RESULTS: Of 201 patients examined, 70.2% experienced at least one serious complication. Neurological complications occurred in 21%, infections amongst 11%, and thromboembolic complications in 2%. Extension of the haemorrhage occurred most frequently: its absence was a significant predictor of good functional outcome (P < 0.0001, adjusted OR for good functional outcome = 21.9, 95% CI: [5.5, 88.3]). Neither infection, nor cardiac, nor thromboembolic complications influenced functional outcome at 90 days. CONCLUSIONS: Three month outcome in ICH patients depends on initial stroke severity and on enlargement of the haemorrhage. Our results should inform safety in future clinical trials of putative ICH therapies.

Oral anticoagulation in patients with cardiomyopathy or heart failure in sinus rhythm.

BACKGROUND: Despite many prospective randomized studies defining the benefits of anticoagulation in atrial fibrillation (AF), there have been no adequate studies in cardiomyopathy (CM) in sinus rhythm. METHODS: We review the current knowledge of the risk of stroke in CM, left ventricular systolic dysfunction and heart failure as well as the indications for antithrombotic agents and compare this with AF. RESULTS: The current knowledge of risk factors for stroke and indications for antithrombotic agents in CM is similar to that of AF prior to the treatment studies of the 1980s-1990s. CONCLUSION: Prospective randomized trial data are urgently needed to determine the role of antithrombotic drugs in CM.

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.

Prevalence and determinants of subclinical brain infarction: the Northern Manhattan Study.

OBJECTIVE: Risk factors for subclinical brain infarcts (SBI) have not been well studied, especially in Hispanic and black populations who may be at higher risk for vascular disease. We examined the prevalence and determinants of SBI in a multiethnic community cohort. METHODS: The Northern Manhattan Study (NOMAS) includes 892 stroke-free participants who underwent brain MRI. Baseline demographic and vascular risk factor data were collected. The presence of SBI was determined from the size, location, and imaging characteristics of the lesion based on fluid attenuated inversion recovery (FLAIR) T1 and T2, and proton density MRI sequences. We calculated the prevalence of SBI and cross-sectional associations with sociodemographic and vascular risk factors, using logistic regression to adjust for relevant covariates. RESULTS: Among 892 subjects (mean age 71.3 years), 158 (17.7%) had SBI (13.5% had 1 lesion, 4.3% had >1 lesion). Of the total 216 infarcts, most were small (<1 cm, 82.4%) and subcortical (82.9%). SBI prevalence increased with age (<65: 9.7%; 65 to 75: 16.4%; >75: 26.1%), was increased among men (21.3% vs 15.2% in women), and was increased among blacks (24.0% vs 18.1% in whites and 15.8% in Hispanics). The presence of SBI was independently associated with older age (per year: OR 1.06, 95% CI 1.04 to 1.09), male sex (OR 1.79, 95% CI 1.22 to 2.61), and hypertension (OR 2.08, 95% CI 1.35 to 3.22) adjusting for age, sex, race-ethnicity, and vascular risk factors. A significant interaction (p = 0.002) between race and age was observed such that younger black subjects had greater odds of having SBI. CONCLUSIONS: SBI were detected in nearly 18% of subjects in a multiethnic community-based cohort. Age, male sex, and hypertension were independently associated with SBI. Subclinical cerebral infarcts are more prevalent than symptomatic infarcts and may increase the true public health burden of stroke.

Impact of valvular thickness on stroke recurrence in medically treated patients with stroke.

BACKGROUND: It remains controversial whether left-sided valvular thickening (VaT) is a risk factor for ischemic stroke. Little is known about the relationship between VaT and the recurrent adverse event rate in medically treated patients with stroke. METHODS: We examined the outcomes of 627 noncardioembolic stroke patients who were double-blindly assigned to either warfarin or aspirin therapy and assessed VaT using transesophageal echocardiography. Endpoints were recurrent ischemic stroke or death from any cause. The Cox proportional hazards model was used to adjust for covariates. RESULTS: VaT was present in 57.3% of the patients (359/627), 34.6% (271/627) involving the aortic valve and 46.4% (291/627) involving the mitral valve. There was no difference in the time to primary endpoints between those with and without VaT of the aortic valve (p = 0.49; hazard ratio, HR: 1.17; 95% CI: 0.74-1.85; 2-year event rates: 18.9 vs. 13.2%) or mitral valve (p = 0.66; HR: 0.91; 95% CI: 0.60-1.38; 2-year event rates: 16.9 vs. 14.7%). Among the patients with VaT, there was no significant difference in the time to primary endpoints between those treated with warfarin and those with aspirin (p = 0.13, HR: 0.65, 95% CI: 0.37-1.14, 2-year event rates: 15.2 vs. 22.7% for the aortic valve; p = 0.22, HR: 0.70, 95% CI: 0.40-1.23, 2-year event rates: 14.2 vs. 19.6% for the mitral valve). CONCLUSIONS: VaT does not appear to increase recurrent adverse event rates in medically treated patients with ischemic stroke, regardless of warfarin or aspirin therapy.

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.

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.