Mary J. Sparks

Obesity Increases Risk of Ischemic Stroke in Young Adults

Background and Purpose— Body mass index has been associated with ischemic stroke in older populations, but its association with stroke in younger populations is not known. In light of the current obesity epidemic in the United States, the potential impact of obesity on stroke risk in young adults deserves attention. Methods— A population-based case–control study design with 1201 cases and 1154 controls was used to investigate the relationship of obesity and young onset ischemic stroke. Stroke cases were between the ages of 15 and 49 years. Logistic regression analysis was used to evaluate the association between body mass index and ischemic stroke with and without adjustment for comorbid conditions associated with stroke. Results— In analyses adjusted for age, sex, and ethnicity, obesity (body mass index >30 kg/m2) was associated with an increased stroke risk (odds ratio, 1.57; 95% confidence interval, 1.28–1.94) although this increased risk was highly attenuated and not statistically significant after adjustment for smoking, hypertension, and diabetes mellitus. Conclusions— These results indicate that obesity is a risk factor for young onset ischemic stroke and suggest that this association may be partially mediated through hypertension, diabetes mellitus, or other variables associated with these conditions.

Factor V Leiden and Ischemic Stroke Risk: The Genetics of Early Onset Stroke (GEOS) Study

BACKGROUNDnFactor V Leiden (FVL) has been associated with ischemic stroke in children but not in adults. Although the FVL mutation is associated with increased risk for venous thrombosis, its association with ischemic stroke in young adults remains uncertain. Therefore, we examined the association between FVL and ischemic stroke in participants of the Genetics of Early Onset Stroke (GEOS) study.nnnMETHODSnA population-based case control study identified 354 women and 476 men 15 to 49xa0years of age with first-ever ischemic stroke and 907 controls. Participant-specific data included vascular risk factors, FVL genotype and, for cases, the ischemic stroke subtype by modified Trial of ORG 10172 in Acute Stroke criteria. Logistic regression was used to calculate odds ratios for the entire population and for subgroups stratified by risk factors and ischemic stroke subtype.nnnRESULTSnThe frequency of the FVL mutation was similar between ischemic stroke patients (3.6%; 95% confidence interval [CI] 2.5%-5.1%) and nonstroke controls (3.8%; 95% CI 2.7%-5.2%). This frequency did not change significantly when cases were restricted to patients with stroke of undetermined etiology (4.1%; 95% CI 2.6%-6.4%).nnnCONCLUSIONSnAmong young adults, we found no evidence for an association between FVL and either all ischemic stroke or the subgroup with stroke of undetermined etiology.

Clinician judgment vs formal scales for predicting intracerebral hemorrhage outcomes

Objective: To compare the performance of formal prognostic instruments vs subjective clinical judgment with regards to predicting functional outcome in patients with spontaneous intracerebral hemorrhage (ICH). Methods: This prospective observational study enrolled 121 ICH patients hospitalized at 5 US tertiary care centers. Within 24 hours of each patients admission to the hospital, one physician and one nurse on each patients clinical team were each asked to predict the patients modified Rankin Scale (mRS) score at 3 months and to indicate whether he or she would recommend comfort measures. The admission ICH score and FUNC score, 2 prognostic scales selected for their common use in neurologic practice, were calculated for each patient. Spearman rank correlation coefficients (r) with respect to patients actual 3-month mRS for the physician and nursing predictions were compared against the same correlation coefficients for the ICH score and FUNC score. Results: The absolute value of the correlation coefficient for physician predictions with respect to actual outcome (0.75) was higher than that of either the ICH score (0.62, p = 0.057) or the FUNC score (0.56, p = 0.01). The nursing predictions of outcome (r = 0.72) also trended towards an accuracy advantage over the ICH score (p = 0.09) and FUNC score (p = 0.03). In an analysis that excluded patients for whom comfort care was recommended, the 65 available attending physician predictions retained greater accuracy (r = 0.73) than either the ICH score (r = 0.50, p = 0.02) or the FUNC score (r = 0.42, p = 0.004). Conclusions: Early subjective clinical judgment of physicians correlates more closely with 3-month outcome after ICH than prognostic scales.

Ischemic stroke risk, smoking, and the genetics of inflammation in a biracial population: the stroke prevention in young women study.

BackgroundAlthough cigarette smoking is a well-established risk factor for vascular disease, the genetic mechanisms that link cigarette smoking to an increased incidence of stroke are not well understood. Genetic variations within the genes of the inflammatory pathways are thought to partially mediate this risk. Here we evaluate the association of several inflammatory gene single nucleotide polymorphisms (SNPs) with ischemic stroke risk among young women, further stratified by current cigarette smoking status.MethodsA population-based case-control study of stroke among women aged 15–49 identified 224 cases of first ischemic stroke (47.3% African-American) and 211 age-comparable control subjects (43.1% African-American). Several inflammatory candidate gene SNPs chosen through literature review were genotyped in the study population and assessed for association with stroke and interaction with smoking status.ResultsOf the 8 SNPs (across 6 genes) analyzed, only IL6 SNP rs2069832 (allele C, African-American frequency = 92%, Caucasian frequency = 55%) was found to be significantly associated with stroke using an additive model, and this was only among African-Americans (age-adjusted: OR = 2.2, 95% CI = 1.0–5.0, p = 0.049; risk factor adjusted: OR = 2.5, 95% CI = 1.0–6.5, p = 0.05). When stratified by smoking status, two SNPs demonstrated statistically significant gene-environment interactions. First, the T allele (frequency = 5%) of IL6 SNP rs2069830 was found to be protective among non-smokers (OR = 0.30, 95% CI = 0.11–.082, p = 0.02), but not among smokers (OR = 1.63, 95% CI = 0.48–5.58, p = 0.43); genotype by smoking interaction (p = 0.036). Second, the C allele (frequency = 39%) of CD14 SNP rs2569190 was found to increase risk among smokers (OR = 2.05, 95% CI = 1.09–3.86, p = 0.03), but not among non-smokers (OR = 0.93, 95% CI = 0.62–1.39, p = 0.72); genotype by smoking interaction (p = 0.039).ConclusionThis study demonstrates that inflammatory gene SNPs are associated with early-onset ischemic stroke among African-American women (IL6) and that cigarette smoking may modulate stroke risk through a gene-environment interaction (IL6 and CD14). Our finding replicates a prior study showing an interaction with smoking and the C allele of CD14 SNP rs2569190.

Genome-wide association analysis of ischemic stroke in young adults.

Ischemic stroke (IS) is among the leading causes of death in Western countries. There is a significant genetic component to IS susceptibility, especially among young adults. To date, research to identify genetic loci predisposing to stroke has met only with limited success. We performed a genome-wide association (GWA) analysis of early-onset IS to identify potential stroke susceptibility loci. The GWA analysis was conducted by genotyping 1 million SNPs in a biracial population of 889 IS cases and 927 controls, ages 15–49 years. Genotypes were imputed using the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic regression models adjusting for age, recruitment stages, and population structure were used to determine the association of IS with individual SNPs. Although no single SNP reached genome-wide significance (P < 5 × 10−8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P = 1.2 × 10−7) and rs1986743 (in ARL6IP6; P = 2.7 × 10−7), strongly associated with early-onset stroke. These data suggest that a novel locus on human chromosome 2q23.3 may be associated with IS susceptibility among young adults.

Prothrombin G20210A mutation is associated with young-onset stroke: the genetics of early-onset stroke study and meta-analysis.

Background and Purpose— Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a white case–control population and additionally performed a meta-analysis. Methods— From the population-based Genetics of Early Onset Stroke (GEOS) study, we identified 397 individuals of European ancestry aged 15 to 49 years with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios (ORs) in the entire population and for subgroups stratified by sex, age, oral contraceptive use, migraine, and smoking status. A meta-analysis of 17 case–control studies (n=2305 cases <55 years) was also performed with and without GEOS data. Results— Within GEOS, the association of the prothrombin G20210A mutation with ischemic stroke did not achieve statistical significance (OR=2.5; 95% confidence interval [CI]=0.9–6.5; P=0.07). However, among adults aged 15 to 42 years (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9; 95% CI=1.2–28.1; P=0.03), whereas adults aged 42 to 49 years were not (OR=1.4; 95% CI=0.4–5.1; P=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults ⩽55 years (OR=1.4; 95% CI=1.1–1.9; P=0.02), with significance increasing with addition of the GEOS results (OR=1.5; 95% CI=1.1–2.0; P=0.005). Conclusions— The prothrombin G20210A mutation is associated with ischemic stroke in young adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger young adult population requires replication.

Cocaine Use and Risk of Ischemic Stroke in Young Adults

Background and Purpose— Although case reports have long identified a temporal association between cocaine use and ischemic stroke (IS), few epidemiological studies have examined the association of cocaine use with IS in young adults, by timing, route, and frequency of use. Methods— A population-based case–control study design with 1090 cases and 1154 controls was used to investigate the relationship of cocaine use and young-onset IS. Stroke cases were between the ages of 15 and 49 years. Logistic regression analysis was used to evaluate the association between cocaine use and IS with and without adjustment for potential confounders. Results— Ever use of cocaine was not associated with stroke with 28% of cases and 26% of controls reporting ever use. In contrast, acute cocaine use in the previous 24 hours was strongly associated with increased risk of stroke (age–sex–race adjusted odds ratio, 6.4; 95% confidence interval, 2.2–18.6). Among acute users, the smoking route had an adjusted odds ratio of 7.9 (95% confidence interval, 1.8–35.0), whereas the inhalation route had an adjusted odds ratio of 3.5 (95% confidence interval, 0.7–16.9). After additional adjustment for current alcohol, smoking use, and hypertension, the odds ratio for acute cocaine use by any route was 5.7 (95% confidence interval, 1.7–19.7). Of the 26 patients with cocaine use within 24 hours of their stroke, 14 reported use within 6 hours of their event. Conclusions— Our data are consistent with a causal association between acute cocaine use and risk of early-onset IS.

Prevention Opportunities for Oral Contraceptive–Associated Ischemic Stroke

Background and Purpose— Literature suggests a small increased risk of ischemic stroke with oral contraception (OC) use. We evaluated the association of stroke and OC use in women on the basis of whether they recalled being advised by a physician not to use OC or to discontinue OC use because of the presence of stroke risk modifiers, and whether such advice resulted in behavioral change. Methods— A total of 572 women (224 strokes and 348 controls) aged 15 to 49 years were interviewed about OC use and risk modifiers, including cigarette smoking and headaches, among others. Results— The adjusted odds ratio for OC use and stroke was 2.00 (95% confidence interval, 1.29–3.09). The association of OC use with stroke was stronger in women that reported receiving doctor’s advice against OC use because of the presence of other stroke risk modifiers (odds ratio, 3.12; 95% confidence interval, 1.62–6.00) than in women who did not recall receiving such advice (odds ratio, 1.31; 95%confidence interval, 0.71–2.43). Of 256 women who recalled being advised by their doctor not to start OC or to discontinue OC use because of the presence of other stroke risk modifiers, 24% were still on OC at the time of stroke or interview. Conclusions— We confirm that certain medical conditions increase the risk of stroke during OC use and demonstrate the importance of physician counseling in those using OC in the setting of concurrent high-risk conditions and the need for improved patient compliance with such counseling.

Factors Considered by Clinicians when Prognosticating Intracerebral Hemorrhage Outcomes

BackgroundThe early subjective clinical judgment of clinicians outperforms formal prognostic scales for accurate determination of outcome after intracerebral hemorrhage (ICH), with the judgment of physicians and nurses having equivalent accuracy. This study assessed specific decisional factors that physicians and nurses incorporate into early predictions of functional outcome.MethodsThis prospective observational study enrolled 121 ICH patients at five US centers. Within 24xa0h of each patient’s admission, one physician and one nurse on the clinical team were each surveyed to predict the patient’s modified Rankin Scale (mRS) at 3xa0months and to list up to 10 subjective factors used in prognostication. Factors were coded and compared between (1) physician and nurse and (2) accurate and inaccurate surveys, with accuracy defined as an exact prediction of mRS.ResultsAside from factors that are components of the ICH or FUNC scores, surveys reported pre-existing comorbidities (40.0%), other clinical or radiographic factors not in clinical scales (43.0%), and non-clinical/radiographic factors (21.9%) as important. Compared to physicians, nurses more frequently listed neurologic examination components (Glasgow Coma Scale motor, 27.3 vs. 5.8%, pxa0<xa00.0001; GCS verbal, 12.4 vs. 0.0%, pxa0<xa00.0001) and non-clinical/radiographic factors (31.4 vs. 12.4%, pxa0=xa00.0005). Physicians more frequently listed neuroimaging factors (ICH location, 33.9 vs. 7.4%, pxa0<xa00.0001; intraventricular hemorrhage, 13.2 vs. 2.5%, pxa0=xa00.003). There was no difference in listed factors between accurate versus inaccurate surveys.ConclusionsClinicians frequently utilize factors outside of the components of clinical scales for prognostication, with physician and nurses focusing on different factors despite having similar accuracy.