Outcomes in the Year After First-Ever Ischemic Stroke in a Bi-Ethnic Population.

OBJECTIVE: To investigate stroke outcomes at 3, 6, and 12 months post-stroke overall and by ethnicity in a population-based, longitudinal study. METHODS: First-ever ischemic strokes (2014-2019, n = 1,332) among Mexican American persons (n = 807) and non-Hispanic white persons (n = 525) were identified from the Brain Attack Surveillance in Corpus Christi Project. Data were collected from patient or proxy interviews (baseline, 3, 6, and 12 months post-stroke) and medical records, including functional (activities of daily living/instrumental activities of daily living score), neurological (National Institutes of Health Stroke Scale), cognitive (Modified Mini-Mental State Examination), and quality of life (QOL) outcomes (12-domain Stroke-specific Quality of Life scale). Outcome trajectories were analyzed using multivariable adjusted linear models, with generalized estimating equations to account for within-subject correlations; interactions between ethnicity and time were included to investigate ethnic differences in outcomes. RESULTS: The median age was 67 years (interquartile range 58,78), 48.5% were women, and 60.6% were Mexican American persons. For all outcomes, significant improvement was seen between 3 and 6 months (p < 0.05 for all), with stability between 6 and 12 months. Mexican American persons had significantly worse outcomes compared with non-Hispanic white persons at all time points (3, 6, and 12 months), with the exception of the National Institutes of Health Stroke Scale, which did not differ by ethnicity at 6 and 12 months, and the average change in outcomes did not vary significantly by ethnicity. INTERPRETATION: Outcomes were at their worst at 3 months post-stroke, and ethnic disparities were already present, suggesting the need for early assessment and strategies to improve outcomes and possibly reduce disparities. ANN NEUROL 2023;93:348-356.

Association of Neighborhood Recreation Centers and Poststroke Outcomes in a Population-Based Cohort.

BACKGROUND: Higher neighborhood socioeconomic status has been favorably associated with stroke outcomes. This may be due to these areas having more beneficial resources such as recreational centers. We aimed to determine if neighborhood density of recreation centers is favorably associated with stroke outcomes. METHODS: We conducted analyses of data from the Brain Attack Surveillance in Corpus Christi project, a cohort of stroke survivors ≥45 years of age residing in Nueces County, TX (2009-2020). We included non-Hispanic White and Mexican American incident stroke survivors, who were not institutionalized prestroke and completed baseline and follow-up assessments (N=1392). We calculated the density of fitness and recreational sports centers within their residential census tract during the year of their stroke. Outcomes included function (self-ratings on activities of daily living and instrumental activities of daily living), cognition (modified mini-mental state exam), depression (Patient Health Questionnaire-8), and quality of life (abbreviated Stroke-Specific Quality of Life Scale). We fit confounder-adjusted gamma-distributed mixed generalized linear models with a log link for each outcome and considered interaction with stroke severity. RESULTS: On average, participants were 65 years old, 53% male, and 63% Mexican American. Median recreational centers were 1.60 per square mile (interquartile range, 0.41-3.06). Among moderate-severe stroke survivors, greater density of recreation centers (75th versus 25th percentile) was associated with more favorable function and possibly quality of life (activities of daily living/instrumental activities of daily living, 4.8% change [95% CI, -0.11% to -9.27%]; Stroke-Specific Quality of Life Scale, 3.7% change [95% CI, -0.7% to 8.2%]). Minimal nonsignificant differences were observed among the overall stroke population and those with mild stroke. CONCLUSIONS: The availability of recreation centers may be beneficial for poststroke function and quality of life among those with moderate-severe stroke. If further research confirms recreation centers to be beneficial, this could inform rehabilitation following stroke.

Methods and early recruitment of the Brain Attack Surveillance in Corpus Christi-Post-acute Care (BASIC-PAC) Project.

OBJECTIVES: Compared with non-Hispanic whites (NHWs), Mexican Americans (MAs) have worse stroke outcomes. We report here the methods, background literature, and initial recruitment of the Brain Attack Surveillance in Corpus Christi-Post Acute Care (BASIC-PAC) Project which aims to explore PAC in MAs and NHWs from multiple perspectives: patients, caregivers, and community. MATERIALS AND METHODS: Rigorous active and passive stroke surveillance captures all strokes in Nueces County, Texas. Stroke patients are followed for 90 days to determine their care transitions and factors influencing their rehabilitation setting. Informal caregivers of the stroke patients are identified and interviewed at 90 days to determine aspects of their caregiving and caregiver outcomes. Available community resources are compared with stated needs among stroke patient and caregivers to determine unmet needs. RESULTS: Between October, 2019 and October, 2021, among the 629 stroke patients eligible, 413 were MA, 227 were NHW. Of the 629, all of the six follow-up calls were completed by 355 of the MAs (87%) and 191 of the NHWs (87%). During this same time period, we attempted to approach 621 potential caregivers. Of these, 458 (73.8%) potential caregivers participated in interviews to determine caregiver eligibility, and 373 (81.4%) of these participating potential caregivers met the eligibility criteria. CONCLUSIONS: BASIC-PAC has strong initial recruitment and is poised to provide valuable data on multiple aspects of PAC and how PAC differs by ethnicity and contributes to worse stroke outcomes in MAs. Based on the study findings, interventions can be developed that will improve stroke health equity.

Estrogen and Progesterone Integration in an in vitro Model of RP3V Kisspeptin Neurons.

Positive feedback on gonadotropin release requires not only estrogen but also progesterone to activate neural circuits. In rodents, ovarian estradiol (E2) stimulates progesterone synthesis in hypothalamic astrocytes (neuroP), needed for the luteinizing hormone (LH) surge. Kisspeptin (kiss) neurons are the principal stimulators of gonadotropin-releasing hormone neurons, and disruption of kiss signaling abrogates the LH surge. Similarly, blocking steroid synthesis in the hypothalamus or deleting classical progesterone receptor (PGR) selectively in kiss neurons prevents the LH surge. These results suggest a synergistic action of E2 and progesterone in kiss neurons to affect gonadotropin release. The mHypoA51, immortalized kiss-expressing neuronal cell line derived from adult female mice, is a tractable model for examining integration of steroid signaling underlying estrogen positive feedback. Here, we report that kiss neurons in vitro integrate E2 and progesterone signaling to increase levels of kiss translation and release. mHypoA51 neurons expressed nonclassical membrane progesterone receptors (mPRα and mPRß) and E2-inducible PGR, required for progesterone-augmentation of E2-induced kiss expression. With astrocyte-conditioned media or in mHypoA51-astrocyte co-culture, neuroP augmented stimulatory effects of E2 on kiss protein. Progesterone activation of classical, membrane-localized PGR led to activation of MAPK and Src kinases. Importantly, progesterone or Src activation induced release of kiss from E2-primed mHypoA51 neurons. Consistent with previous studies, the present results provide compelling evidence that the interaction of E2 and progesterone stimulates kiss expression and release. Further, these results demonstrate a mechanism though which peripheral E2 may prime kiss neurons to respond to neuroP, mediating estrogen positive feedback.

Actions of Steroids: New Neurotransmitters.

Over the past two decades, the classical understanding of steroid action has been updated to include rapid, membrane-initiated, neurotransmitter-like functions. While steroids were known to function on very short time spans to induce physiological and behavioral changes, the mechanisms by which these changes occur are now becoming more clear. In avian systems, rapid estradiol effects can be mediated via local alterations in aromatase activity, which precisely regulates the temporal and spatial availability of estrogens. Acute regulation of brain-derived estrogens has been shown to rapidly affect sensorimotor function and sexual motivation in birds. In rodents, estrogens and progesterone are critical for reproduction, including preovulatory events and female sexual receptivity. Membrane progesterone receptor as well as classical progesterone receptor trafficked to the membrane mediate reproductive-related hypothalamic physiology, via second messenger systems with dopamine-induced cell signals. In addition to these relatively rapid actions, estrogen membrane-initiated signaling elicits changes in morphology. In the arcuate nucleus of the hypothalamus, these changes are needed for lordosis behavior. Recent evidence also demonstrates that membrane glucocorticoid receptor is present in numerous cell types and species, including mammals. Further, membrane glucocorticoid receptor influences glucocorticoid receptor translocation to the nucleus effecting transcriptional activity. The studies presented here underscore the evidence that steroids behave like neurotransmitters to regulate CNS functions. In the future, we hope to fully characterize steroid receptor-specific functions in the brain.

Synergism of Short-Term Air Pollution Exposures and Neighborhood Disadvantage on Initial Stroke Severity.

BACKGROUND AND PURPOSE: Little is known about the relation between environment and stroke severity. We investigated associations between environmental exposures, including neighborhood socioeconomic disadvantage and short-term exposure to airborne particulate matter <2.5 µm and ozone, and their interactions with initial stroke severity. METHODS: First-ever ischemic stroke cases were identified from the Brain Attack Surveillance in Corpus Christi project (2000-2012). Associations between pollutants, disadvantage, and National Institutes of Health Stroke Scale were modeled using linear and logistic regression with adjustment for demographics and risk factors. Pollutants and disadvantage were modeled individually, jointly, and with interactions. RESULTS: Higher disadvantage scores and previous-day ozone concentrations were associated with higher odds of severe stroke. Higher levels of particulate matter <2.5 µm were associated with higher odds of severe stroke among those in higher disadvantage areas (odds ratio, 1.24; 95% confidence interval, 1.00-1.55) but not in lower disadvantage areas (odds ratio, 0.82; 95% confidence interval, 0.56-1.22; P interaction =0.097). CONCLUSIONS: Air pollution exposures and neighborhood socioeconomic status may be important in understanding stroke severity. Future work should consider the multiple levels of influence on this important stroke outcome.

Short-term exposures to ambient air pollution and risk of recurrent ischemic stroke.

OBJECTIVE: To 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 recurrent ischemic stroke among individuals living in a bi-ethnic community. METHODS: We identified recurrent 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 previous day, and odds of ischemic stroke were assessed using a time-stratified case-crossover design and modeled using conditional logistic regression. RESULTS: There were 317 recurrent ischemic strokes after excluding 41 strokes that occurred on days with missing air pollution data. Mean age was 72 years (SD=12) and median time to stroke recurrence was 1.1 years (IQR: 0.2-2.8 years). Median levels of PM2.5 and O3 over the study period were 7.7µg/m3 (IQR: 5.6-10.7µg/m3) and 35.2 ppb (IQR: 25.0-46.1 ppb), respectively. We observed no associations between previous-day PM2.5 and O3 and odds of recurrent stroke (OR=0.95 per 10µg/m3 of PM2.5, 95% CI: 0.71-1.28 and OR=0.97 per 10ppb of O3, 95% CI: 0.87-1.07) after adjusting for ambient temperature and relative humidity. Co-adjustment of both pollutants did not change the results. CONCLUSION: We found no evidence of associations between previous-day air pollution levels and recurrent ischemic stroke. Research on the influence of air pollutants on risk of stroke recurrence is still in its infancy, and more research is necessary in studies that are adequately powered to understand the relation.

Neighborhood Influences on Emergency Medical Services Use for Acute Stroke: A Population-Based Cross-sectional Study.

STUDY OBJECTIVE: Delay to hospital arrival limits acute stroke treatment. Use of emergency medical services (EMS) is key in ensuring timely stroke care. We aim to identify neighborhoods with low EMS use and to evaluate whether neighborhood-level factors are associated with EMS use. METHODS: We conducted a secondary analysis of data from the Brain Attack Surveillance in Corpus Christi project, a population-based stroke surveillance study of ischemic stroke and intracerebral hemorrhage cases presenting to emergency departments in Nueces County, TX. The primary outcome was arrival by EMS. The primary exposures were neighborhood resident age, poverty, and violent crime. We estimated the association of neighborhood-level factors with EMS use, using hierarchic logistic regression, controlling for individual factors (stroke severity, ethnicity, and age). RESULTS: During 2000 to 2009 there were 4,004 identified strokes, with EMS use data available for 3,474. Nearly half (49%) of stroke cases arrived by EMS. Adjusted stroke EMS use was lower in neighborhoods with higher family income (odds ratio [OR] 0.86; 95% confidence interval [CI] 0.75 to 0.97) and a larger percentage of older adults (OR 0.70; 95% CI 0.56 to 0.89). Individual factors associated with stroke EMS use included white race (OR 1.41; 95% CI 1.13 to 1.76) and older age (OR 1.36 per 10-year age increment; 95% CI 1.27 to 1.46). The proportion of neighborhood stroke cases arriving by EMS ranged from 17% to 71%. The fully adjusted model explained only 0.3% (95% CI 0% to 1.1%) of neighborhood EMS stroke use variance, indicating that individual factors are more strongly associated with stroke EMS use than neighborhood factors. CONCLUSION: Although some neighborhood-level factors were associated with EMS use, patient-level factors explained nearly all variability in stroke EMS use. In this community, strategies to increase EMS use should target individuals rather than specific neighborhoods.

Factors influencing sex differences in poststroke functional outcome.

BACKGROUND AND PURPOSE: Our objective was to identify factors that contribute to or modify the sex difference in poststroke functional outcome. METHODS: Ischemic strokes (n=439) were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) Project (2008-2011). Data were ascertained from interviews (baseline and 90 days post stroke) and medical records. Functional outcome was measured as an average of 22 activities of daily living (ADL)/instrumental ADL items (range, 1-4; higher scores worse function). Tobit regression was used to estimate sex differences and to identify confounding and modifying factors. RESULTS: Fifty-one percent were women. Median age was 71 (interquartile range, 59-80) years in women and 64 (interquartile range, 56-77) years in men. Median ADL/instrumental ADL score at 90 days was 2.7 (interquartile range, 1.8-3.6) in women and 2.0 (interquartile range, 1.3-3.1) in men (P<0.01); this difference remained after age-adjustment (P<0.001). Factors contributing to higher ADL/instrumental ADL scores in women included prestroke function, marital status, prestroke cognition, nursing home residence, stroke severity, history of stroke/transient ischemic attack, and body mass index; prestroke function was the largest contributor. Stroke severity modified the sex difference in outcome such that differences were apparent for mild to moderate but not severe strokes. After adjustment, women still had significantly worse functional outcome than men. CONCLUSIONS: These findings yield insight into possible strategies and subgroups to target to reduce the sex disparity in stroke outcome; demographics and prestroke and clinical factors explained only 41% of the sex difference in stroke outcome highlighting the need for future research to identify modifiable factors that contribute to sex differences.

Stroke risk after nonstroke emergency department dizziness presentations: a population-based cohort study.

OBJECTIVE: Acute stroke is a serious concern in emergency department (ED) dizziness presentations. Prior studies, however, suggest that stroke is actually an unlikely cause of these presentations. Lacking are data on short- and long-term follow-up from population-based studies to establish stroke risk after presumed nonstroke ED dizziness presentations. METHODS: From May 8, 2011 to May 7, 2012, patients ≥45 years of age presenting to EDs in Nueces County, Texas, with dizziness, vertigo, or imbalance were identified, excluding those with stroke as the initial diagnosis. Stroke events after the ED presentation up to October 2, 2012 were determined using the BASIC (Brain Attack Surveillance in Corpus Christi) study, which uses rigorous surveillance and neurologist validation. Cumulative stroke risk was calculated using Kaplan-Meier estimates. RESULTS: A total of 1,245 patients were followed for a median of 347 days (interquartile range [IQR] = 230-436 days). Median age was 61.9 years (IQR = 53.8-74.0 years). After the ED visit, 15 patients (1.2%) had a stroke. Stroke risk was 0.48% (95% confidence interval [CI] = 0.22-1.07%) at 2 days, 0.48% (95% CI = 0.22-1.07%) at 7 days, 0.56% (95% CI = 0.27-1.18%) at 30 days, 0.56% (95% CI = 0.27-1.18%) at 90 days, and 1.42% (95% CI = 0.85-2.36%) at 12 months. INTERPRETATION: Using rigorous case ascertainment and outcome assessment in a population-based design, we found that the risk of stroke after presumed nonstroke ED dizziness presentations is very low, supporting a nonstroke etiology to the overwhelming majority of original events. High-risk subgroups likely exist, however, because most of the 90-day stroke risk occurred within 2 days. Vascular risk stratification was insufficient to identify these cases.

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

OBJECTIVES: To investigate the association between short-term changes in ambient pollution (particulate matter <2.5 µm 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. METHODS: We 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. RESULTS: There 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. CONCLUSION: Ethnic 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.

Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature.

Estrogen withdrawal in menopausal women leads to hot flushes, a syndrome characterized by the episodic activation of heat dissipation effectors. Despite the extraordinary number of individuals affected, the etiology of flushes remains an enigma. Because menopause is accompanied by marked alterations in hypothalamic kisspeptin/neurokinin B/dynorphin (KNDy) neurons, we hypothesized that these neurons could contribute to the generation of flushes. To determine if KNDy neurons participate in the regulation of body temperature, we evaluated the thermoregulatory effects of ablating KNDy neurons by injecting a selective toxin for neurokinin-3 expressing neurons [NK(3)-saporin (SAP)] into the rat arcuate nucleus. Remarkably, KNDy neuron ablation consistently reduced tail-skin temperature (T(SKIN)), indicating that KNDy neurons facilitate cutaneous vasodilatation, an important heat dissipation effector. Moreover, KNDy ablation blocked the reduction of T(SKIN) by 17ß-estradiol (E(2)), which occurred in the environmental chamber during the light phase, but did not affect the E(2) suppression of T(SKIN) during the dark phase. At the high ambient temperature of 33 °C, the average core temperature (T(CORE)) of ovariectomized (OVX) control rats was significantly elevated, and this value was reduced by E(2) replacement. In contrast, the average T(CORE) of OVX, KNDy-ablated rats was lower than OVX control rats at 33 °C, and not altered by E(2) replacement. These data provide unique evidence that KNDy neurons promote cutaneous vasodilatation and participate in the E(2) modulation of body temperature. Because cutaneous vasodilatation is a cardinal sign of a hot flush, these results support the hypothesis that KNDy neurons could play a role in the generation of flushes.

Residential ethnic segregation and stroke risk in Mexican Americans: the Brain Attack Surveillance in Corpus Christi project.

OBJECTIVE: Residential ethnic segregation may operate through multiple mechanisms to increase stroke risk. The current study evaluated if residential ethnic segregation was associated with stroke risk in a bi-ethnic population. DESIGN: Incident strokes were identified in Nueces County, Texas from 2000 to 2010. Residential ethnic segregation (range: 0-1) was derived for each census tract in the county (n=64) using 2000 US Census data, and categorized into: predominantly non-Hispanic White (NHW, <.3); ethnically mixed (.3-.7); predominantly Mexican American (MA, >.7). Multilevel Poisson regression models were fitted separately for NHWs and MAs to assess the association between residential ethnic segregation (predominantly NHW referent) and relative risk for stroke, adjusted for age category, sex and census tract-level median per capita income. Effect modification by age was also examined. RESULTS: In adjusted models, residential ethnic segregation was not associated with stroke risk in either ethnic group. Effect modification by age was significant in both groups. Young MAs and NHWs living in predominantly MA census tracts were at greater relative risk for stroke than those living in predominantly NHW census tracts, but this association was only significant for MAs (MAs: RR = 2.38 [95% CI: 1.31-4.31]; NHWs: RR = 1.53 [95% CI: .92-2.52]). CONCLUSION: Our findings demonstrate that residential ethnic segregation may influence downstream stroke risk in young MAs. Pathways between residential ethnic segregation and stroke in young MAs should be explored.

Ischemic stroke subtype and presence of sleep-disordered breathing: the BASIC sleep apnea study.

BACKGROUND: Little is known about the prevalence of sleep-disordered breathing (SDB) across ischemic stroke subtypes. Given the important implications for SDB screening, we tested the association between SDB and ischemic stroke subtype in a population-based study. METHODS: Within the Brain Attack Surveillance in Corpus Christi Project, ischemic stroke patients were offered SDB screening with the ApneaLink Plus (n = 355). A neurologist assigned Trial of the ORG 10172 in Acute Stroke Treatment subtype (with an additional category for nonlacunar infarctions of unknown etiology) using hospital records. Unadjusted and adjusted (demographics, body mass index, National Institutes of Health Stroke Scale, diabetes, history of stroke/transient ischemic attack) logistic and linear regression models were used to test the association between subtype and SDB or apnea-hypopnea index (AHI). RESULTS: Median age was 65%, and 55% were men; 59% were Mexican American. Median time from stroke onset to SDB screen was 13 days (interquartile range [IQR] 6, 21). Overall, 215 (61%) had SDB (AHI ≥ 10). Median AHI was 13 (IQR 6, 27). Prevalence of SDB by subtype was cardioembolism, 66%; large-artery atherosclerosis, 57%; small-vessel occlusion, 68%; other determined, 50%; undetermined etiology, 58%; and nonlacunar stroke of unknown etiology, 63%. Ischemic stroke subtype was not associated with SDB in unadjusted (P = .72) or adjusted models (P = .91) models. Ischemic stroke subtype was not associated with AHI in unadjusted (P = .41) or adjusted models (P = .62). CONCLUSIONS: In this population-based stroke surveillance study, ischemic stroke subtype was not associated with the presence or severity of SDB. Sleep-disordered breathing is likely to be present after ischemic stroke, and the subtype should not influence decisions about SDB screening.

Neurological, functional, and cognitive stroke outcomes in Mexican Americans.

BACKGROUND AND PURPOSE: Our objective was to compare neurological, functional, and cognitive stroke outcomes in Mexican Americans (MAs) and non-Hispanic whites using data from a population-based study. METHODS: Ischemic strokes (2008-2012) were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) Project. Data were collected from patient or proxy interviews (conducted at baseline and 90 days poststroke) and medical records. Ethnic differences in neurological (National Institutes of Health Stroke Scale: range, 0-44; higher scores worse), functional (activities of daily living/instrumental activities of daily living score: range, 1-4; higher scores worse), and cognitive (Modified Mini-Mental State Examination: range, 0-100; lower scores worse) outcomes were assessed with Tobit or linear regression adjusted for demographics and clinical factors. RESULTS: A total of 513, 510, and 415 subjects had complete data for neurological, functional, and cognitive outcomes and covariates, respectively. Median age was 66 (interquartile range, 57-78); 64% were MAs. In MAs, median National Institutes of Health Stroke Scale, activities of daily living/instrumental activities of daily living, and Modified Mini-Mental State Examination score were 3 (interquartile range, 1-6), 2.5 (interquartile range, 1.6-3.5), and 88 (interquartile range, 76-94), respectively. MAs scored 48% worse (95% CI, 23%-78%) on National Institutes of Health Stroke Scale, 0.36 points worse (95% CI, 0.16-0.57) on activities of daily living/instrumental activities of daily living score, and 3.39 points worse (95% CI, 0.35-6.43) on Modified Mini-Mental State Examination than non-Hispanic whites after multivariable adjustment. CONCLUSIONS: MAs scored worse than non-Hispanic whites on all outcomes after adjustment for confounding factors; differences were only partially explained by ethnic differences in survival. These findings in combination with the increased stroke risk in MAs suggest that the public health burden of stroke in this growing population is substantial.

Loss of the Mexican American survival advantage after ischemic stroke.

BACKGROUND AND PURPOSE: Mexican Americans (MAs) were previously found to have lower mortality after ischemic stroke than non-Hispanic whites. We studied mortality trends in a population-based design. METHODS: Active and passive surveillance were used to find all ischemic stroke cases from January 2000 to December 2011 in Nueces County, TX. Deaths were ascertained from the Texas Department of Health through December 31, 2012. Cumulative 30-day and 1-year mortality adjusted for covariates was estimated using log-binomial models with a linear term for year of stroke onset used to model time trends. Models used data from the entire study period to estimate adjusted mortality among stroke cases in 2000 and 2011 and to calculate projected ethnic differences. RESULTS: There were 1974 ischemic strokes among non-Hispanic whites and 2439 among MAs. Between 2000 and 2011, model estimated mortality declined among non-Hispanic whites at 30 days (7.6% to 5.6%; P=0.24) and 1 year (20.8% to 15.5%; P=0.02). Among MAs, 30-day model estimated mortality remained stagnant at 5.1% to 5.2% (P=0.92), and a slight decline from 17.4% to 15.3% was observed for 1-year mortality (P=0.26). Although ethnic differences in 30-day (P=0.01) and 1-year (P=0.06) mortality were apparent in 2000, they were not so in 2011 (30-day mortality, P=0.63; 1-year mortality, P=0.92). CONCLUSIONS: Overall, mortality after ischemic stroke has declined in the past decade, although significant declines were only observed for non-Hispanic whites and not MAs at 1 year. The survival advantage previously documented among MAs vanished by 2011. Renewed stroke prevention and treatment efforts for MAs are needed.

Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes.

Despite affecting millions of individuals, the etiology of hot flushes remains unknown. Here we review the physiology of hot flushes, CNS pathways regulating heat-dissipation effectors, and effects of estrogen on thermoregulation in animal models. Based on the marked changes in hypothalamic kisspeptin, neurokinin B and dynorphin (KNDy) neurons in postmenopausal women, we hypothesize that KNDy neurons play a role in the mechanism of flushes. In the rat, KNDy neurons project to preoptic thermoregulatory areas that express the neurokinin 3 receptor (NK3R), the primary receptor for NKB. Furthermore, activation of NK3R in the median preoptic nucleus, part of the heat-defense pathway, reduces body temperature. Finally, ablation of KNDy neurons reduces cutaneous vasodilatation and partially blocks the effects of estrogen on thermoregulation. These data suggest that arcuate KNDy neurons relay estrogen signals to preoptic structures regulating heat-dissipation effectors, supporting the hypothesis that KNDy neurons participate in the generation of flushes.

Persistent ischemic stroke disparities despite declining incidence in Mexican Americans.

OBJECTIVE: To determine trends in ischemic stroke incidence among Mexican Americans and non-Hispanic whites. METHODS: We performed population-based stroke surveillance from January 1, 2000 to December 31, 2010 in Corpus Christi, Texas. Ischemic stroke patients 45 years and older were ascertained from potential sources, and charts were abstracted. Neurologists validated cases based on source documentation blinded to ethnicity and age. Crude and age-, sex-, and ethnicity-adjusted annual incidence was calculated for first ever completed ischemic stroke. Poisson regression models were used to calculate adjusted ischemic stroke rates, rate ratios, and trends. RESULTS: There were 2,604 ischemic strokes in Mexican Americans and 2,042 in non-Hispanic whites. The rate ratios (Mexican American:non-Hispanic white) were 1.94 (95% confidence interval [CI] = 1.67-2.25), 1.50 (95% CI = 1.35-1.67), and 1.00 (95% CI = 0.90-1.11) among those aged 45 to 59, 60 to 74, and 75 years and older, respectively, and 1.34 (95% CI = 1.23-1.46) when adjusted for age. Ischemic stroke incidence declined during the study period by 35.9% (95% CI = 25.9-44.5). The decline was limited to those aged ≥60 years, and happened in both ethnic groups similarly (p > 0.10), implying that the disparities seen in the 45- to 74-year age group persist unabated. INTERPRETATION: Ischemic stroke incidence rates have declined dramatically in the past decade in both ethnic groups for those aged ≥60 years. However, the disparity between Mexican American and non-Hispanic white stroke rates persists in those <75 years of age. Although the decline in stroke is encouraging, additional prevention efforts targeting young Mexican Americans are warranted.

Differences in initial stroke severity between Mexican Americans and non-Hispanic whites vary by age: the Brain Attack Surveillance in Corpus Christi (BASIC) project.

BACKGROUND: A wide variety of racial and ethnic disparities in stroke epidemiology and treatment have been reported. Race-ethnic differences in initial stroke severity may be one important determinant of differences in the outcome after stroke. The overall goal of this study was to move beyond ethnic comparisons in the mean or median severity, and instead investigate ethnic differences in the entire distribution of initial stroke severity. Additionally, we investigated whether age modifies the relationship between ethnicity and initial stroke severity as this may be an important determinant of racial differences in the outcome after stroke. METHODS: Ischemic stroke cases were identified from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project. National Institutes of Health Stroke Scale (NIHSS) was determined from the medical record or abstracted from the chart. Ethnicity was reported as Mexican American (MA) or non-Hispanic white (NHW). Quantile regression was used to model the distribution of NIHSS score by age category (45-59, 60-74, 75+) to test whether ethnic differences exist over different quantiles of NIHSS (5 percentile increments). Crude models examined the interaction between age category and ethnicity; models were then adjusted for history of stroke/transient ischemic attack, hypertension, atrial fibrillation, coronary artery disease, and diabetes. RESULTS were adjusted for multiple comparisons. RESULTS: There were 4,366 ischemic strokes, with median age 72 (IQR: 61-81), 55% MA, and median NIHSS of 4 (IQR: 2-8). MAs were younger, more likely to have a history of hypertension and diabetes, but less likely to have atrial fibrillation compared to NHWs. In the crude model, the ethnicity-age interaction was not statistically significant. After adjustment, the ethnicity-age interaction became significant at the 85th and 95th percentiles of NIHSS distribution. MAs in the younger age category (45-59) were significantly less severe by 3 and 6 points on the initial NIHSS than NHWs, at the 85th and 95th percentiles, respectively. However, in the older age category (75+), there was a reversal of this pattern; MAs had more severe strokes than NHWs by about 2 points, though not reaching statistical significance. CONCLUSIONS: There was no overall ethnic difference in stroke severity by age in our crude model. However, several potentially important ethnic differences among individuals with the most severe strokes were seen in younger and older stroke patients that were not explained by traditional risk factors. Age should be considered in future studies when looking at the complex distributional relationship between ethnicity and stroke severity.

Neighborhood Resources and Health Outcomes Among Stroke Survivors in a Population-Based Cohort.

BACKGROUND: Stroke survivors believe neighborhood resources such as community centers are beneficial; however, little is known about the influence of these resources on stroke outcomes. We evaluated whether residing in neighborhoods with greater resource density is associated with favorable post-stroke outcomes. METHODS AND RESULTS: We included Mexican American and non-Hispanic White stroke survivors from the Brain Attack Surveillance in Corpus Christi project (2009-2019). The exposure was density of neighborhood resources (eg, community centers, restaurants, stores) within a residential census tract at stroke onset. Outcomes included time to death and recurrence, and at 3 months following stroke: disability (activities of daily living/instrumental activities of daily living), cognition (Modified Mini-Mental State Exam), depression (Patient Health Questionnaire-8), and quality of life (abbreviated Stroke-Specific Quality of Life scale). We fit multivariable Cox regression and mixed linear models. We considered interactions with stroke severity, ethnicity, and sex. Among 1786 stroke survivors, median age was 64 years (interquartile range, 56-73), 55% men, and 62% Mexican American. Resource density was not associated with death, recurrence, or depression. Greater resource density (75th versus 25th percentile) was associated with more favorable cognition (Modified Mini-Mental State Exam mean difference=0.838, 95% CI=0.092, 1.584) and among moderate-severe stroke survivors, with more favorable functioning (activities of daily living/instrumental activities of daily living=-0.156 [95% CI, -0.284 to 0.027]) and quality of life (abbreviated Stroke-Specific Quality of Life scale=0.194 [95% CI, 0.029-0.359]). CONCLUSIONS: We observed associations between greater resource density and cognition overall and with functioning and quality of life among moderate-severe stroke survivors. Further research is needed to confirm these findings and determine if neighborhood resources may be a tool for recovery.