Incident Ischemic Stroke Cases Research Articles

Plasma uric acid concentrations and risk of ischaemic stroke in women.

Elevated plasma uric acid has been inconsistently associated with an increased risk of total stroke; however, data are sparse amongst women. The association between plasma uric acid concentrations and ischaemic stroke amongst women was examined and the effect modification by key cardiovascular risk factors was evaluated. A nested case-control design with matching by age, race/ethnicity, smoking status, menopausal status, postmenopausal hormone therapy use, date of blood draw and fasting status was utilized amongst female participants of the Nurses' Health Study who provided blood samples between 1989 and 1990. Plasma uric acid was measured on stored blood samples. The National Survey of Stroke criteria were utilized to confirm 460 incident cases of ischaemic stroke by medical records from 1990 to 2006. Multivariable conditional logistic regression models were estimated. In matched analysis, risk of ischaemic stroke increased by 15% for each 1 mg/dl increase in plasma uric acid [95% confidence interval (CI) 3%-28%], but was no longer significant after adjustment for cardiovascular risk factors, particularly history of hypertension. The highest quartile of uric acid was significantly associated with greater risk of ischaemic stroke (relative risk 1.56; 95% CI 1.06-2.29, extreme quartiles) in matched analysis, but estimates were no longer significant after adjustment for cardiovascular risk factors (relative risk 1.43; 95% CI 0.93-2.18). Significant effect modification by key cardiovascular risk factors was not observed. Plasma uric acid levels were not independently associated with increased risk of ischaemic stroke in this cohort of women. Whilst plasma uric acid was associated with stroke risk factors, it was not independently associated with stroke risk.

The Influence of Left Atrial Enlargement on the Relationship between Atrial Fibrillation and Stroke

Left atrial enlargement (LAE) is independently associated with an increased risk of stroke and atrial fibrillation (AF). The combination of both LAE and AF possibly increases the risk of stroke beyond that observed with AF. This analysis included 4572 (43% men, 95% white) participants from the Cardiovascular Health Study. LAE was defined using transthoracic echocardiographic 2-dimensional M-mode measurements of the left atrial diameter using sex-specific cut-points (men: ≥4.1 cm, women: ≥3.9 cm). AF cases were identified during the initial study electrocardiogram or by self-reported history. We examined the association between baseline AF and incident ischemic stroke stratified by the presence of LAE. Incident cases of ischemic stroke were identified by adjudication of medical records, including hospitalization data, through December 31, 2010. At baseline, a total of 253 (5.5%) participants had AF and 1947 (43%) had LAE. Participants with AF (n = 163, 64%) were more likely to have LAE than those without AF (n = 1784, 41%; P < .001). Over a median follow-up of 13 years, 739 (16%) ischemic stroke events were identified. Both AF (hazard ratio [HR] = 2.12, 95% confidence interval [CI] = 1.64-2.74) and left atrial diameter (per 1-cm increase: HR = 1.14, 95% CI = 1.01-1.28) were associated with an increased risk for ischemic stroke. The association between AF and ischemic stroke was not modified by the presence of LAE (LAE: HR = 2.13, 95% CI = 1.42-3.19; no LAE: HR = 1.91, 95% CI = 1.36-2.68; P interaction = .86). Our results suggest that echocardiographic LAE does not modify the stroke risk observed with AF.

Seizures Following Ischemic Stroke: Frequency of Occurrence and Impact on Outcome in a Long-Term Population-Based Study

Seizures are a known complication of ischemic stroke (IS). This study assesses the long-term incidence and characteristics of poststroke seizures in a well-defined population. Using the Rochester Epidemiology Project medical records-linkage system, we identified all incident cases of IS among Rochester, Minnesota, residents from 1990 to 1994 and followed the patients in the comprehensive medical record through March 2014. All patients with poststroke seizures were identified, and data regarding incident IS, seizures, and status at last follow-up were analyzed. We identified 489 patients with first IS. Mean follow-up was 6.5 (standard deviation 6.3) years. New onset seizures occurred in 35 patients (7.2%). Patients with poststroke seizure did not differ from those without in terms of IS etiologic subtype (P = .44) or IS risk factors (P > .05). Early seizures (within 14 days of index stroke) developed in 14 patients (40%), the majority within the first 24 hours (n = 9, 64.3%). The median time of seizure onset for the remaining 21 patients was 13.8 months. Functional outcome, as measured by modified Rankin Scale (mRS), was worse following development of poststroke seizures (mean mRS score 2.9 after IS, 3.3 following index seizure; P = .005), and mortality was higher as well, even after adjusting for IS etiologic subtype (HR 1.52, 95% confidence interval 1.07-2.16, P = .02). Development of poststroke seizures is an infrequent but significant complication of IS, portending a worse short-term functional outcome and a higher long-term mortality rate. Seizure occurrence did not differ based on IS etiologic subtype or stroke risk factors.

Ethnic differences in ambient air pollution and risk of acute ischemic stroke

ObjectivesTo investigate the association between short-term changes in ambient pollution (particulate matter <2.5μm in aerodynamic diameter (PM2.5) and ozone (O3)) and the risk of ischemic stroke among individuals living in a bi-ethnic community and whether this association is modified by ethnicity. MethodsWe identified incident ischemic stroke cases from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project between 2000 and 2012. Associations between PM2.5 (mean 24-h) and O3 (maximal 8-h) levels, measured on the same-day and lags of 1–3 days, and odds of ischemic stroke were assessed using a time-stratified case-crossover design and modeled using conditional logistic regression. We explored race/ethnicity (Mexican American versus non-Hispanic white) as a modifier by including interaction terms in the models. ResultsThere were 2948 ischemic strokes with median age 71 years (IQR: 59-80). We observed no overall associations between the air pollutants and odds of ischemic stroke at any lag. When stratified by ethnicity, higher O3 was consistently associated with greater odds of ischemic stroke for non-Hispanic whites, but not for Mexican Americans. Higher PM2.5 was generally associated with lower odds of ischemic stroke for non-Hispanic whites but modestly greater odds for Mexican Americans. ConclusionEthnic differences in the associations between ischemic stroke and short-term exposures to O3 and PM2.5 were suggested indicating that further study in diverse populations may be warranted.

Dietary isoflavones, urinary isoflavonoids, and risk of ischemic stroke in women

Hormone therapy has been shown to increase risk of ischemic stroke in women. Plant-derived estrogens, particularly soy isoflavones, are known to have some estrogenic effects and have been marketed as natural alternatives to hormone therapy. Concerns have been raised about whether high isoflavone exposure may be related to ischemic stroke risk as well. We examined the dietary intake of isoflavones and the urinary excretion of isoflavonoids in relation to risk of ischemic stroke in women. A prospective cohort study was conducted in 66,832 Chinese women (aged 40-70 y) who had no cardiovascular disease or cancer at baseline. Usual dietary intakes were assessed via in-person interviews with the use of a validated food-frequency questionnaire. Incident strokes were ascertained during follow-up home visits and confirmed by medical records. We also conducted a nested case-control study in postmenopausal women who had never used hormone therapy, including 1422 incident ischemic stroke cases and 1422 controls individually matched by age, date and time of urine sample collection, time since last meal, and use of antibiotics. Urinary isoflavonoids were measured with the use of high-performance liquid chromatography coupled with mass spectrometry. During a mean follow-up of 10 y, 3110 incident ischemic strokes were verified. Dietary isoflavone intake was associated with increased risk of ischemic stroke; multivariable-adjusted HRs from lowest to highest quintiles were 1.00, 1.05, 1.10, 1.11, and 1.24, respectively (95% CI: 1.08, 1.42; P-trend = 0.002). In the case-control study, a similar positive association was observed for dietary isoflavones, but no significant associations were shown for the urinary isoflavonoid concentration [OR: 1.01 (95% CI: 0.77, 1.32) for comparison of extreme quintiles]. A habitually high intake of soy isoflavones may be associated with a modest but significant increase in risk of ischemic stroke in women. However, no association was shown for the urinary excretion of isoflavonoids.

Abstract W P161: Incidence and Characteristics of Post-Stroke Seizures: A Population-Based Study

Background &amp; Purpose: Seizures are a recognized complication of stroke. However, available data are conflicting in terms of incidence, risk factors for occurrence, and impact on functional outcome and mortality. The aim of this study was to assess the incidence and characteristics of seizures following ischemic stroke in a well-defined population, and their effect on long-term patient outcome. Methodology: Utilizing the Rochester Epidemiology Project medical record linkage system, we identified all incident cases of ischemic stroke (IS) that occurred between January 1, 1990, and December 31, 1994. We identified all patients who developed seizures following first IS. Detailed data regarding stroke (including TOAST subtype, anatomic location, functional outcome), seizures (date, type, functional outcome, recurrence, presence of status epilepticus, complications, treatment, EEG findings), and patient status at the last follow-up were recorded and analyzed. Results: We identified 490 patients with first IS. Mean follow-up was 6.5 years (range 0.0 - 23.8). Of these, 35 (7.1%) developed seizures. Early seizures (occurring within 14 days of stroke) were present in 13 (37.1%), of which 9 (69.2%) had their seizure within the first 24 hours. Partial seizures were the most common type (23 patients, 65.7%). Status epilepticus occurred in two cases (5.7%). Tongue biting was the most common complication of poststroke seizures (4 patients, 11.4%). Treatment with antiepileptic drugs (AEDs) was initiated in 32 cases (91.4%). Only one drug was necessary for seizure control in all treated patients. The mean modified Rankin Scale score was 2.9 (SD 1.48) after the first IS, and worsened to 3.3 (SD 1.43) after the first seizure. Mortality at the last follow-up was higher in the seizure group compared to the non-seizure group, even after adjusting for TOAST subtype (HR 1.52; 95% CI 1.07 - 2.16; P = 0.02). Conclusion: Seizures are mostly a late complication of IS. They do not bear a high risk of life-threatening complications and are readily controllable by a single AED. However, patients who developed poststroke seizures tended to have a worse functional outcome and an increased mortality.

Abstract T P151: Ethnic Differences in Associations Between Short-Term Exposures to Ambient Air Pollution and the Risk of Acute Ischemic Stroke

Background: Air pollution may contribute to ethnic differences in stroke risk, but little research has been conducted in diverse US populations. We investigated the association between daily changes in ambient pollution (PM2.5 and ozone (O3)) and the risk of ischemic stroke among individuals living in a biethnic community and whether the association differed by ethnicity. Methods: We identified incident ischemic stroke cases from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project between 2000 and 2012. Air pollutant data were obtained from a state website. The association between average daily levels of PM2.5 and O3, measured on the same-day and lags of 1-3 days, and odds of ischemic stroke was assessed using a time-stratified case-crossover study design. We explored race/ethnicity of Mexican American (MA) and non-Hispanic white (NHW) as an interaction of the associations between air pollution and stroke. Results: There were 2,948 ischemic strokes during the study period. Median age was 71 years (interquartile range: 59-80); 51% were women and 56% were MA. In models combining ethnic groups, an association between lag 1 O3 and stroke was found (OR: 1.05, 95% CI: 1.00-1.10); no other significant associations were noted. Ethnic differences in the associations between PM2.5 and O3 with stroke were suggested (Figure). When stratified by ethnicity, increases in O3 were consistently associated with increased odds of stroke for NHWs, but not for MAs. Increases in same-day PM2.5 were marginally associated with increases in the odds of stroke in MAs (OR: 1.12, 95% CI: 0.98-1.27), but not for NHWs. Conclusion: We observed an association between previous-day O3 and ischemic stroke, but found little evidence of an association between PM2.5 and ischemic stroke. Ethnic differences in the associations with both O3 and PM2.5 and stroke were also noted, suggesting that further study of environmental influences on stroke in diverse populations is warranted.

Abstract 153: Synergistic Effects of Air Pollution Exposure and Neighborhood Socioeconomic Disadvantage on Initial Stroke Severity

Background: Stroke risk and severity are patterned by neighborhood socioeconomic disadvantage (ND). Air pollution may also influence stroke severity through biologic mechanisms. We sought to identify potential synergistic effects of ND and air pollution on initial stroke severity in a large population-based stroke study. Methods: We identified incident ischemic stroke cases from the BASIC project from 2000-2012. NIH Stroke Scale (NIHSS) was determined from the medical record or abstracted. Particulate matter (PM2.5) and ozone (O3) data were obtained from a state website. An ND score was created for census tracts (proxy for neighborhood) of residence using 12 Census variables. The association between pollutants, ND, and NIHSS was modeled continuously (NIHSS score) and dichotomously (upper quartile (≥7) vs. lower quartiles (&lt;7)). Generalized estimating equations accounted for clustering within neighborhoods. Models were adjusted for demographics and stroke risk factors and run as single exposure models of pollution and ND, dual exposure models including both pollution and ND, and by adding interactions between pollution and ND. Results: A total of 3,035 ischemic strokes occurred; mean age was 70 (SD=13), 51% female and 53% Mexican American. The difference from the 10th to 90th percentile of the ND score (more disadvantage) was associated with a 24% (95% CI: 0.98 - 1.57) higher odds of severe stroke (Table). Higher previous-day O3 levels were associated with both continuous NIHSS and severe stroke in single and dual exposure models; these associations were not modified by ND. Larger associations between PM2.5 and severe stroke were found for those in higher ND areas than those in lower ND areas (p=0.03). Same-day PM2.5 was not associated with continuous NIHSS nor modified by ND. Conclusion: Synergistic effects of air pollution and ND score on stroke severity existed; increases in PM2.5 were associated with greater odds of severe stroke as ND increased.

Temporal trends in incidence of myocardial infarction and ischemic stroke by socioeconomic position in Sweden 1987-2010.

BackgroundWe analyzed temporal trends in the incidence of myocardial infarction and ischemic stroke in Sweden by socioeconomic position and investigated whether social inequalities in incidence of these diseases changed over time.Materials and MethodsWe studied a cohort of almost three million Swedish residents born between 1932 and 1960 followed from 1987 until 2010. Incident cases of myocardial infarction and ischemic stroke were identified in the Swedish National Inpatient Register and Cause of Death Register. Socioeconomic position was retrieved from the Population and Housing Censuses. Incidence rates of myocardial infarction and ischemic stroke and incidence rate ratios comparing levels of socioeconomic position were estimated using flexible parametric survival models adjusted for calendar year, attained age, sex, and birth country.ResultsThe overall incidences of myocardial infarction and ischemic stroke decreased over time among men, but were stable over time among women. With regard to ischemic stroke incidence, socioeconomic inequality increased over time in the age group 55 to 59: the incidence rate ratios for low manual compared to high non-manual increased from 1.3 (95% CI: 1.2–1.4) in 1997 to 1.5 (1.4–1.7) in 2010 among men, and from 1.4 (1.3–1.6) in 1997 to 2.1 (1.8–2.5) in 2010 among women. The socioeconomic inequality in incidence of myocardial infarction was stable over time for both men and women.ConclusionThere was a decrease in myocardial infarction and ischemic stroke incidence over time among men but no significant change for women. Our study highlights existing, and in some cases increasing, social inequalities in the incidence of cardiovascular diseases.

Abstract P346: Novel Protein Glycan Derived Marker of Systemic Inflammation is Associated with Incident Coronary Heart Disease and Ischemic Stroke

Background: Enzymatically glycosylated proteins participate in multiple cellular processes, with variations in their concentration implicated in innate immunity and chronic inflammation. In addition, most inflammatory proteins are enzymatically glycosylated. GlycA is a novel nuclear magnetic resonance (NMR) biomarker whose signal originates from the N-acetyl groups of N-acetylglucosmine and N-acetylgalatosamine moieties of protein glycans. We assessed the association of GlycA with both incident CHD and ischemic stroke and performed a comparative analysis with hsCRP. Method: GlycA was quantified by proton NMR spectroscopy (LipoScience, NC) and hsCRP by immunoturbidimetric assay (Denka Seiken) in 27 649 participants of the Women’s Health Study. During a median follow up of 17 years, 1 089 incident cases of CHD and 465 incident cases of ischemic stroke were confirmed. Results: GlycA correlated with LDL cholesterol (r = 0.17), HDL cholesterol (r = -0.27), triglycerides (r = 0.47), BMI (r = 0.41) and hsCRP (r = 0.61), all p&lt;0.0001. Multivariable-adjusted HRs (95% CIs) for top versus bottom quartiles of GlycA were 1.78 (1.44-2.20) with CHD and 1.50 (1.11-2.03) with ischemic stroke respectively (p-trend for both ≤ 0.006); these associations were similar in magnitude to that obtained for hsCRP and were weakened but remained significant after adjustment for lipids. (Table) Further adjustment for hsCRP attenuated the associations which were no longer statistically significant (p-trend ≥0.40 for both CHD and ischemic stroke). Conclusion: A novel protein glycan derived biomarker, GlycA, was associated with a graded increase in the risk of both incident CHD and ischemic stroke in this prospective study of initially healthy women in a manner similar to hsCRP. Adjustment for hsCRP attenuated this association, consistent with a possible role for protein glycans in inflammation.

Abstract P073: Urinary Isoflavonoids And Risk Of Ischemic Stroke In Postmenopausal Women

Background: Postmenopausal hormone therapy has been shown to increase stroke risk. It is unclear whether high exposure to pytoestrogens, such as soy isoflavones, may confer the same risk of stroke. Objective: To examine associations of urinary isoflavonoids, which reflect isoflavones intake, absorption, and metabolism, with risk of ischemic stroke in postmenopausal Chinese women. Design: A nested case-control study. Method: We identified 1438 incident cases of ischemic stroke druing 1997-2010 and individually matched them to 1438 controls on age, date and time of sample collection, time since last meal, and recent use of antibiotics. All subjects were postmenopausal women who had never used hormone therapy and had no history of CVD or cancer at baseline. Seven isoflavonoids were measured by LC-MS and standardized by urinary creatinine. Results: We found no significant difference between case-control pairs in mean levels of total or individual urinary isoflavonoids, including 3 parent compounds (daidzein, genistein, and glycitein) and 4 metabolites derived from intestinal bacteria (dihydrogenistein, dihydrodaidzein, O-desmethylangolensin, and equol). Multivariate analyses revealed that women in the highest quintile of equol concentration had a lower risk of ischemic stroke (OR=0.77, 95%CI=0.60-0.98). Analyses stratified by equol producing status showed a significant inverse association between isoflavone bacterial metabolites and stroke risk in equol producers (31.8% of the study population, OR=0.40 across extreme quartiles, 95%CI=0.18-0.87, Ptrend=0.002), but no association in equol non-producers. Conclusion: Overall, this large prospective study suggests that urinary isoflavonoids are not associated with risk of ischemic stroke in postmenopausal Chinese women. High level of bacteria-derived metabolites of isoflavones, however, was associated with a reduced risk in equol producers, suggesting a possible interaction between gut microbiome and soy foods in the pathogenesis of ischemic stroke.

Abstract 64: The Use of Oral Anticoagulation After Ischemic Stroke Increases, Users Have Fewer Recurrences, and Are Increasingly Likely to Survive. A Nationwide Study From Finland

Background and Purpose: Oral anticoagulation (OAC) is an effective secondary preventive therapy after atrial fibrillation related cardioembolic ischemic stroke. We explored the use of OAC after ischemic stroke in Finland, the country with the most rapidly aging population in Europe. Methods: Data from 1999 to 2010 were extracted from the PERFECT Stroke registry, a nationwide database of all incident stroke patients hospitalized in Finland. Purchase of warfarin, the only OAC available during the study period in Finland, was registered in all pharmacies in a national database. Recurrence was defined as re-hospitalization with new acute stroke diagnosis through an emergency department. Survival was tracked from the national death registry with 100% follow-up. Results: Among the 99,677 incident ischemic stroke cases over the study period, there were 24,327 cases surviving their initial hospitalization and using OAC for secondary prevention. This represented 24.4% of all ischemic stroke patients, increasing from 20.3% in 1999 to 26.7% in 2010. In these OAC users, 1-year recurrence rate of ischemic stroke decreased from 20.1% in 1999 to 12.5% in 2010, while 1-year hemorrhagic stroke rate remained unchanged at 0.4%. Increases in the secondary preventive use of blood pressure medications (from 83.5% to 92.7%), statins (from 32.8% to 73.5%), and a combination of these (from 28.2% to 69.0%) were observed from 1999 to 2010. One-year case-fatality of patients surviving to go home was 4.2% when no recurrences occurred. When secondary prevention failed, patients who experienced a new ischemic stroke had 11.3% likelihood of dying within a year, increasing to 42.0% after a hemorrhagic stroke. After adjusting for age, sex, and comorbidities with a logistic regression model, the odds of 1-year case-fatality decreased over time (OR 0.97; 95% CI 0.95-0.99 per year). Conclusion: As the population ages, the proportion of ischemic stroke patients that require oral anticoagulation increases, in our data from 20% to 27% over a period of 12 years. Secondary prevention of stroke in OAC users improved, which could be due to increased use of antihypertensives and statins, and reflected on survival. The risk of hemorrhagic stroke due to anticoagulation for ischemic stroke remains small.

Outdoor air pollution, subtypes and severity of ischemic stroke--a small-area level ecological study.

BackgroundEvidence linking outdoor air pollution and incidence of ischemic stroke subtypes and severity is limited. We examined associations between outdoor PM10 and NO2 concentrations modeled at a fine spatial resolution and etiological and clinical ischemic stroke subtypes and severity of ischemic stroke.MethodsWe used a small-area level ecological study design and a stroke register set up to capture all incident cases of first ever stroke (1995–2007) occurring in a defined geographical area in South London (948 census output areas; population of 267839). Modeled PM10 and NO2 concentrations were available at a very fine spatial scale (20 meter by 20 meter grid point resolution) and were aggregated to output area level using postcode population weighted averages. Ischemic stroke was classified using the Oxford clinical classification, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) etiological classification, National Institutes of Health Stroke Scale (NIHSS) score and a pragmatic clinical severity classification based on Glasgow coma score, ability to swallow, urinary continence and death <2 days of stroke onset.ResultsMean (SD) concentrations were 25.1 (1.2) ug/m3 (range 23.3-36.4) for PM10 and 41.4 (3.0) ug/m3 (range 35.4-68.0) for NO2. There were 2492 incident cases of ischemic stroke. We found no evidence of association between these pollutants and the incidence of ischemic stroke subtypes classified using the Oxford and TOAST classifications. We found no significant association with stroke severity using NIHSS severity categories. However, we found that outdoor concentrations of both PM10 and NO2 appeared to be associated with increased incidence of mild but not severe ischemic stroke, classified using the pragmatic clinical severity classification. For mild ischemic stroke, the rate ratio in the highest PM10 category by tertile was 1.20 (1.05-1.38) relative to the lowest category. The rate ratio in the highest NO2 category was 1.22 (1.06-1.40) relative to the lowest category.ConclusionsWe found no evidence of association between outdoor PM10 and NO2 concentrations and ischemic stroke subtypes but there was a suggestion that living in areas with elevated outdoor PM10 and NO2 concentrations might be associated with increased incidence of mild, but not severe, ischemic stroke.

Circulating Fetuin-A and Risk of Ischemic Stroke in Women

Fetuin-A, a protein secreted primarily by the liver, has been associated with nonalcoholic fatty liver disease and insulin resistance. In a recent study, higher circulating fetuin-A was associated with cardiovascular events, particularly ischemic stroke. However, these data have not been replicated. A nested case control design was used to examine the relationship between fetuin-A and ischemic stroke among female participants of the Nurses' Health Study. Fetuin-A was measured in blood samples collected and stored between 1989 and 1990. A total of 459 incident cases of ischemic stroke were identified and confirmed by medical records according to the National Survey of Stroke criteria between 1990 and 2006 and matched to 459 controls by age, race/ethnicity, date of sample collection, menopausal status, postmenopausal hormone use, and smoking status. The association between fetuin-A and ischemic stroke was modeled using conditional logistic regression. Circulating fetuin-A was higher in women (P < 0.01) who reported increased body mass index (BMI) of ≥25 kg/m(2), total cholesterol ≥200 mg/dL, high-sensitivity C-reactive protein ≥3 mg/L, and current hormone use at baseline. Significant partial Spearman correlations (P < 0.001), adjusted for matching factors, were found between measured concentrations of fetuin-A and triglycerides (r = 0.20), C-reactive protein (r = 0.14), and BMI (r = 0.15). Fetuin-A quartiles were not significantly associated with increased risk of incident ischemic stroke when adjusted for matching factors (relative risk, 1.03; 95% CI, 0.69-1.54, extreme quartiles); additional adjustment for lifestyle factors or cardiovascular disease risk factors and biomarkers did not alter results. In this sample of women, fetuin-A was not significantly associated with risk of ischemic stroke. Further research is needed to explore this association.

Adiponectin and Risk of Stroke

The favorable cardiovascular effects attributed to adiponectin may lower risk of stroke. We investigated this in a prospective study and meta-analysis. A case-cohort study nested within the Potsdam cohort of the European Prospective Investigation into Cancer was performed, with 170 incident cases of ischemic stroke and a randomly selected subcohort of 2155 participants without major cardiovascular disease at baseline. A random-effects dose-response meta-analysis was performed on prospective studies reporting on adiponectin and incident stroke in healthy populations up to April 2013, identified through MEDLINE and EMBASE. In European Prospective Investigation into Cancer-Potsdam, after adjustment for cardiovascular risk factors, the hazard ratio of ischemic stroke per 5-µg/mL higher total-adiponectin was 1.10 (95% confidence interval, 0.89-1.37). Participants with higher total-adiponectin had higher high-density lipoprotein-cholesterol and lower high-sensitivity C-reactive protein and triglyceride levels, and had less often diabetes mellitus. Additional adjustment for these putative mediators yielded a hazard ratio of 1.31 (95% confidence interval, 1.04-1.64). Nine studies (19,259 participants, 2960 cases), including European Prospective Investigation into Cancer-Potsdam, were meta-analyzed. Pooling relative risks adjusted for cardiovascular risk factors not including putative mediators indicated moderate between-study heterogeneity (I2=52.2%). This was explained by the smallest study, and the pooled relative risk (95% confidence interval) before and after its exclusion was 1.03 (0.98-1.08) and 0.99 (0.96-1.01) per 5 µg/mL, respectively. The pooled relative risk (95% confidence interval) additionally adjusted for potential mediators was 1.08 (1.01-1.15) and 1.05 (1.00-1.11) before and after excluding the same study, respectively. Adiponectin is not associated with risk of stroke. If anything, adiponectin relates directly to stroke risk after controlling for risk factors that favorably correlate with adiponectin.

Serum Fatty Acids and Incidence of Ischemic Stroke Among Postmenopausal Women

Although studies have linked types of fatty acids with coronary heart disease, data on individual fatty acids and risk of ischemic stroke are limited. We aimed to examine the associations between serum fatty acid concentrations and incidence of ischemic stroke and its subtypes. We conducted a prospective case-control study nested in the Women's Health Initiative Observational Study cohort of postmenopausal US women aged 50 to 79 years. Between 1993 and 2003, incident cases of ischemic stroke were matched 1:1 to controls on age, race, and length of follow-up (964 matched pairs). Conditional logistic regression was used to estimate odds ratios and 99.9% confidence intervals (CI) for ischemic stroke and its subtypes. The multivariable-adjusted odds ratios and 99.9% CI of ischemic stroke associated with a 1-SD increment in serum fatty acid concentration were 1.38 (99.9% CI, 1.05-1.83) for linoelaidic acid (18:2tt, SD=0.04%), 1.27 (99.9% CI, 1.06-1.51) for palmitic acid (16:0, SD=2.74%), 1.20 (99.9% CI, 1.01-1.43) for oleic acid (18:1n9, SD=2.32%), 0.72 (99.9% CI, 0.59-0.87) for docosapentaenoic acid (22:5n3, SD=0.18%), 0.72 (99.9% CI, 0.59-0.87) for docosahexaenoic acid (22:6n3, SD=0.91%), and 0.81 (99.9% CI, 0.67-0.98) for arachidonic acid (20:4n6, SD=2.02%). These associations were generally consistent for atherothrombotic and lacunar stroke but not cardioembolic stroke. These findings suggest that individual serum trans, saturated, and monounsaturated fatty acids are positively associated with particular ischemic stroke subtypes, whereas individual n3 and n6 polyunsaturated fatty acids are inversely associated.

Non-high-density lipoprotein cholesterol vs low-density lipoprotein cholesterol as a risk factor for ischemic stroke: a result from the Kailuan study

Objectives: To compare the predictive value of serum low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol levels for ischemic stroke in the Chinese population.Methods: We performed a four-year cohort study of 95 778 men and women, aged 18–98 years, selected from the Kailuan study (2006–2007). Baseline LDL cholesterol levels were estimated using direct test method. Total cholesterol levels were estimated using endpoint test method. The predictive values of LDL cholesterol and non-HDL cholesterol for ischemic stroke were compared.Results: During the follow-up period, there were 1153 incident cases of ischemic stroke. The hazard ratio (HR) for ischemic stroke in the top quintile of LDL cholesterol was the highest among five quintiles (HR: 1·25; 95% confidence interval (CI), 1·01–1·53). The HR in the top quintile of non-HDL cholesterol for ischemic stroke was also the highest among five quintiles (HR: 1·53; 95% CI, 1·24–1·88). Analysis of trends showed a significant positive relationship between ischemic stroke incidence and serum LDL cholesterol level, and non-HDL cholesterol level, respectively (both P < 0·05). The area under the curve of LDL cholesterol and non-HDL cholesterol for ischemic stroke was 0·51 and 0·56, respectively (P < 0·05 for the difference).Conclusions: Serum Non-HDL cholesterol level is a stronger predictor for the risk of ischemic stroke than serum LDL cholesterol level in the Chinese population.

Abstract WP201: Racial Disparities among Incident Ischemic Stroke Cases in the District of Columbia: the ASPIRE Study

Background: Racial disparities in ischemic stroke incidence have been found in previous studies with blacks having higher rates compared to whites. Recent data has suggested a decrease in stroke incidence but not necessarily a decrease in race differentials. We sought to document incidence of ischemic stroke and explore race-ethnic differentials in the urban, Washington, DC metro area. METHODS: ASPIRE is a multi-dimensional intervention with a three-pronged approach (community, hospital, EMS) to acute stroke preparedness targeted to increase IV tPA utilization in underserved black communities in DC. Using a comprehensive active and passive surveillance strategy including stroke admission alerts, stroke champions, admission/discharge data and chart review, the ASPIRE research team prospectively identified all hospitalized incident ischemic strokes between January 2008 and July 2012. Direct age-adjusted rates were estimated using age specific proportions from the 2010 census of the DC population for each sex, gender and race subgroup. RESULTS: Over 4.5 years, we captured 691 incident ischemic strokes: mean age 67 yrs +/- 15 yrs; 79% were blacks; and 55% females. Over 45% of the incident ischemic strokes occurred in black-females. Risk factors including hypertension (79%), diabetes (39%), and current smoking (28%) were significantly greater for blacks than whites. The age-adjusted average annual incidence rate per 100,000 was 226 overall: 171 for blacks, 45 for whites; 65 for black-males; 19 for white-males; 106 for black-females; and 26 for white-females CONCLUSION: We report significant racial disparities in the incidence of hospitalized ischemic in the DC metro area despite potential undercounting of non-hospitalized stroke cases, and potential competing mortalities in black men (ie. ICH, homicide, AIDS). This continued excess burden of ischemic stroke, particularly in black females, highlights the ongoing importance of projects such as ASPIRE to continue education and preparedness among those with increased risk.

Microsomal triglyceride transfer protein -164 T &gt; C gene polymorphism and risk of cardiovascular disease: results from the EPIC-Potsdam case-cohort study

BackgroundThe microsomal triglyceride transfer protein (MTTP) is encoded by the MTTP gene that is regulated by cholesterol in humans. Previous studies investigating the effect of MTTP on ischemic heart disease have produced inconsistent results. Therefore, we have tested the hypothesis that the rare allele of the -164T > C polymorphism in MTTP alters the risk of cardiovascular disease (CVD), depending on the cholesterol levels.MethodsThe -164T > C polymorphism was genotyped in a case-cohort study (193 incident myocardial infarction (MI) and 131 incident ischemic stroke (IS) cases and 1 978 non-cases) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam study, comprising 27 548 middle-aged subjects. The Heinz Nixdorf Recall study (30 CVD cases and 1 188 controls) was used to replicate our findings.ResultsGenotype frequencies were not different between CVD and CVD free subjects (P = 0.79). We observed an interaction between the -164T > C polymorphism and total cholesterol levels in relation to future CVD. Corresponding stratified analyses showed a significant increased risk of CVD (HRadditve = 1.38, 95% CI: 1.07 to 1.78) for individuals with cholesterol levels <200 mg/dL in the EPIC-Potsdam study. HRadditive was 1.06, 95% CI: 0.33 to 3.40 for individuals in the Heinz Nixdorf Recall study. A borderline significant decrease in CVD risk was observed in subjects with cholesterol levels ≥200 mg/dL (HRadditve = 0.77, 95% CI: 0.58 to 1.03) in the EPIC-Potsdam study. A similar trend was observed in the independent cohort (HRadditve = 0.60, 95% CI: 0.29 to 1.25).ConclusionsOur study suggests an interaction between MTTP -164T > C functional polymorphism with total cholesterol levels. Thereby risk allele carriers with low cholesterol levels may be predisposed to an increased risk of developing CVD, which seems to be abolished among risk allele carriers with high cholesterol levels.

Community Level Disadvantage and the Likelihood of First Ischemic Stroke

Background and Purpose. Residing in “disadvantaged” communities may increase morbidity and mortality independent of individual social resources and biological factors. This study evaluates the impact of population-level disadvantage on incident ischemic stroke likelihood in a multiethnic urban population. Methods. A population based case-control study was conducted in an ethnically diverse community of New York. First ischemic stroke cases and community controls were enrolled and a stroke risk assessment performed. Data regarding population level economic indicators for each census tract was assembled using geocoding. Census variables were also grouped together to define a broader measure of collective disadvantage. We evaluated the likelihood of stroke for population-level variables controlling for individual social (education, social isolation, and insurance) and vascular risk factors. Results. We age-, sex-, and race-ethnicity-matched 687 incident ischemic stroke cases to 1153 community controls. The mean age was 69 years: 60% women; 22% white, 28% black, and 50% Hispanic. After adjustment, the index of community level disadvantage (OR 2.0, 95% CI 1.7–2.1) was associated with increased stroke likelihood overall and among all three race-ethnic groups. Conclusion. Social inequalities measured by census tract data including indices of community disadvantage confer a significant likelihood of ischemic stroke independent of conventional risk factors.