Abstract TMP82: Increased Intracerebral Hemorrhage During Acute and Chronic Hypertension in Alzheimer's Transgenic Mice

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
David H Cribbs ◽  
Giselle Passos ◽  
Vitaly Vasilevko
Keyword(s):  
Risk Factor ◽  
Transgenic Mice ◽  
Intracerebral Hemorrhage ◽  
Amyloid Precursor Protein ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Chronic Hypertension ◽  
Cerebrovascular System ◽  
The Brain ◽  
Tg2576 Mice

Hypertension is a major risk factor for intracerebral hemorrhage (ICH), and the accumulation of amyloid-beta (Aβ) in the cerebrovascular system, cerebral amyloid angiopathy (CAA), is also a significant risk factor for intracerebral hemorrhage ICH. Currently, there are no animal studies demonstrating a direct involvement of hypertension in the accumulation of Alzheimer’s disease-like pathology. To address this issue we have developed several mouse models that combine hypertension protocols with amyloid precursor protein (APP) transgenic mice (Tg2576), which accumulate significant CAA in the large cerebral vessels and the meninges by 18 months of age. The goal of this study was to determine the effect of acute and chronic hypertension on ICH in wildtype and a transgenic mouse model overexpressing a mutant human amyloid precursor protein (Tg2576 mice) associated with early onset AD and CAA. Fifteen-month-old Tg2576 mice and non-transgenic (nTg) littermates were treated with an angiotensin II (AngII) infusion (1000 ng/kg/min) and L-NAME (100 mg/kg/day) in drinking water to produce chronic hypertension. One week later, transient acute hypertension was induced by daily AngII injections (0.5 μg/g, s.c., twice daily) to produce ICH. A similar increase in mean blood pressure was observed in Tg2576 and nTg mice when evaluated 2 weeks after initiation of treatment. However Tg2576 mice had a higher incidence of signs of stroke compared with nTg littermates (P > 0.05). These data suggest that the accumulation of Aβ in the brain has an important role in development of ICH. Moreover, there was robust glial activation and increase in CAA in the gray matter of Tg2576 mice showing that hypertension may affect gray as well as white matter in the brain. Further studies may provide insights into the hypertension-induced changes in the cerebral vascular system that initiated the increase in CAA. The accumulation of Aβ in the cerebrovascular system is a significant risk factor for intracerebral hemorrhage (ICH), and has been linked to endothelial transport failure and blockage of perivascular drainage. While management of hypertension and atherosclerosis can reduce the incidence of ICH, there are currently no approved therapies for attenuating CAA.

scholarly journals Racial/ethnic variation of APOE alleles for lobar intracerebral hemorrhage

Neurology ◽  
2018 ◽  
Vol 91 (5) ◽  
pp. e410-e420 ◽  
Author(s):  
Russell P. Sawyer ◽  
Padmini Sekar ◽  
Jennifer Osborne ◽  
Steven J. Kittner ◽  
Charles J. Moomaw ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Intracerebral Hemorrhage ◽  
Significant Risk ◽  
Geographic Location ◽  
Significant Risk Factor ◽  
Predominately White ◽  
Ethnic Populations ◽  
Lower Effect ◽  
Racial Ethnic

ObjectiveAPOE ε2 and ε4 alleles have been associated with lobar intracerebral hemorrhage (ICH) in predominately white populations; we sought to evaluate whether this held true among black and Hispanic populations.MethodsThe Ethnic/Racial Variations of Intracerebral Hemorrhage study is a prospective, multicenter case-control study of ICH among white, black, and Hispanic participants. Controls were recruited to match cases based on age, ethnicity/race, sex, and geographic location. APOE genotyping and ICH location was determined blinded to clinical data.ResultsThere were 907 cases of lobar ICH and 2,660 controls with APOE results. Both APOE ε2 (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.1–2.0, p = 0.01) and APOE ε4 (OR 2.0, 95% CI 1.5–2.6, p < 1 × 10−4) were associated with lobar ICH among white participants. Among black participants, neither APOE ε2 (OR 1.0, 95% CI 0.7–1.5, p = 0.97) nor APOE ε4 (OR 1.0, 95% CI 0.7–1.4, p = 0.90) were independent risk factors for lobar ICH. Similarly, among Hispanic participants, neither APOE ε2 (OR 1.0, 95% CI 0.6–1.8, p = 0.89) nor APOE ε4 (OR 1.2, 95% CI 0.8–1.7, p = 0.36) were associated with lobar ICH. Hypertension was a significant risk factor for lobar ICH in all 3 racial/ethnic groups.ConclusionIn contrast to Caucasian patients, in which amyloid risk factors predominate in lobar ICH, we found that hypertension was the predominant risk factor for lobar ICH. While APOE alleles are a risk factor for lobar ICH in white patients, they appear to have a much lower effect in lobar ICH in African American and Hispanic American populations. This suggests APOE ε2 and APOE ε4 do not affect lobar ICH risk homogeneously across ethnic populations. In addition, hypertension has a prominent role in lobar ICH risk, particularly among minorities.

Spontaneous intracerebral hemorrhage due to coagulation disorders

2003 ◽  
Vol 15 (4) ◽  
pp. 1-17 ◽  
Author(s):  
Alfredo Quinones-Hinojosa ◽  
Mittul Gulati ◽  
Vineeta Singh ◽  
Michael T. Lawton
Keyword(s):  
Risk Factor ◽  
Mortality Rate ◽  
Intracerebral Hemorrhage ◽  
Intracranial Hemorrhage ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Bleeding Disorders ◽  
Coagulation Disorders ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Comprehensive Review

Although intracranial hemorrhage accounts for approximately 10 to 15% of all cases of stroke, it is associated with a high mortality rate. Bleeding disorders account for a small but significant risk factor associated with intracranial hemorrhage. In conditions such as hemophilia and acute leukemia associated with thrombocytopenia, massive intracranial hemorrhage is often the cause of death. The authors present a comprehensive review of both the physiology of hemostasis and the pathophysiology underlying spontaneous ICH due to coagulation disorders. These disorders are divided into acquired conditions, including iatrogenic and neoplastic coagulopathies, and congenital problems, including hemophilia and rarer diseases. The authors also discuss clinical features, diagnosis, and management of intracranial hemorrhage resulting from these bleeding disorders.

Physical Illness and Suicide Risk in Rural Residents of Contemporary China

Crisis ◽  
2014 ◽  
Vol 35 (5) ◽  
pp. 330-337 ◽  
Author(s):  
Cun-Xian Jia ◽  
Lin-Lin Wang ◽  
Ai-Qiang Xu ◽  
Ai-Ying Dai ◽  
Ping Qin
Keyword(s):  
Risk Factor ◽  
Family Income ◽  
Rural China ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Health Condition ◽  
Physical Illness ◽  
Rural Residents ◽  
Increased Risk ◽  
Study Population

Background: Physical illness is linked with an increased risk of suicide; however, evidence from China is limited. Aims: To assess the influence of physical illness on risk of suicide among rural residents of China, and to examine the differences in the characteristics of people completing suicide with physical illness from those without physical illness. Method: In all, 200 suicide cases and 200 control subjects, 1:1 pair-matched on sex and age, were included from 25 townships of three randomly selected counties in Shandong Province, China. One informant for each suicide or control subject was interviewed to collect data on the physical health condition and psychological and sociodemographic status. Results: The prevalence of physical illness in suicide cases (63.0%) was significantly higher than that in paired controls (41.0%; χ2 = 19.39, p < .001). Compared with suicide cases without physical illness, people who were physically ill and completed suicide were generally older, less educated, had lower family income, and reported a mental disorder less often. Physical illness denoted a significant risk factor for suicide with an associated odds ratio of 3.23 (95% CI: 1.85–5.62) after adjusted for important covariates. The elevated risk of suicide increased progressively with the number of comorbid illnesses. Cancer, stroke, and a group of illnesses comprising dementia, hemiplegia, and encephalatrophy had a particularly strong effect among the commonly reported diagnoses in this study population. Conclusion: Physical illness is an important risk factor for suicide in rural residents of China. Efforts for suicide prevention are needed and should be integrated with national strategies of health care in rural China.

scholarly journals Higher premature atrial complex burden from the Holter examination predicts poor cardiovascular outcome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ting-Chun Huang ◽  
Po-Tseng Lee ◽  
Mu-Shiang Huang ◽  
Pei-Fang Su ◽  
Ping-Yen Liu
Keyword(s):  
Risk Factor ◽  
Dose Response ◽  
Cox Model ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Cardiovascular Death ◽  
Specific Model ◽  
Distribution Model ◽  
All Cause Mortality ◽  
Quartile Group

AbstractPremature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose–response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend < 0.001), and both genders shared similar PACs distribution. In Cox model, ln PAC remained an independent risk factor for all-cause mortality (hazard ratio (HR) = 1.09 per ln PAC increase, 95% CI = 1.06‒1.12, p < 0.001). PACs were a significant risk factor in cause-specific model (HR = 1.13, 95% CI = 1.05‒1.22, p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death.

Comorbidity and severity-of-illness risk adjustment for hospital-onset Clostridioides difficile infection using data from the electronic medical record

2020 ◽  
pp. 1-7
Author(s):  
Stephanie M. Cabral ◽  
Katherine E. Goodman ◽  
Natalia Blanco ◽  
Surbhi Leekha ◽  
Larry S. Magder ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Risk Adjustment ◽  
Community Hospital ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Bivariate Analysis ◽  
Patient Admissions ◽  
Clostridioides Difficile ◽  
Risk Adjustment Model

Abstract Objective: To determine whether electronically available comorbidities and laboratory values on admission are risk factors for hospital-onset Clostridioides difficile infection (HO-CDI) across multiple institutions and whether they could be used to improve risk adjustment. Patients: All patients at least 18 years of age admitted to 3 hospitals in Maryland between January 1, 2016, and January 1, 2018. Methods: Comorbid conditions were assigned using the Elixhauser comorbidity index. Multivariable log-binomial regression was conducted for each hospital using significant covariates (P < .10) in a bivariate analysis. Standardized infection ratios (SIRs) were computed using current Centers for Disease Control and Prevention (CDC) risk adjustment methodology and with the addition of Elixhauser score and individual comorbidities. Results: At hospital 1, 314 of 48,057 patient admissions (0.65%) had a HO-CDI; 41 of 8,791 patient admissions (0.47%) at community hospital 2 had a HO-CDI; and 75 of 29,211 patient admissions (0.26%) at community hospital 3 had a HO-CDI. In multivariable regression, Elixhauser score was a significant risk factor for HO-CDI at all hospitals when controlling for age, antibiotic use, and antacid use. Abnormal leukocyte level at hospital admission was a significant risk factor at hospital 1 and hospital 2. When Elixhauser score was included in the risk adjustment model, it was statistically significant (P < .01). Compared with the current CDC SIR methodology, the SIR of hospital 1 decreased by 2%, whereas the SIRs of hospitals 2 and 3 increased by 2% and 6%, respectively, but the rankings did not change. Conclusions: Electronically available patient comorbidities are important risk factors for HO-CDI and may improve risk-adjustment methodology.

scholarly journals Type-2 Diabetes as a Risk Factor for Severe COVID-19 Infection

2021 ◽  
Vol 9 (6) ◽  
pp. 1211
Author(s):  
Mahnaz Norouzi ◽  
Shaghayegh Norouzi ◽  
Alistaire Ruggiero ◽  
Mohammad S. Khan ◽  
Stephen Myers ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Factor ◽  
Inflammatory Responses ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Diabetic Patients ◽  
Angiotensin Converting Enzyme 2 ◽  
Immune System Dysfunction ◽  
Current Outbreak

The current outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19), has generated a notable challenge for diabetic patients. Overall, people with diabetes have a higher risk of developing different infectious diseases and demonstrate increased mortality. Type 2 diabetes mellitus (T2DM) is a significant risk factor for COVID-19 progression and its severity, poor prognosis, and increased mortality. How diabetes contributes to COVID-19 severity is unclear; however, it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Using the envelope spike glycoprotein SARS-CoV-2, COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) receptors, a key protein expressed in metabolic organs and tissues such as pancreatic islets. Therefore, it has been suggested that diabetic patients are more susceptible to severe SARS-CoV-2 infections, as glucose metabolism impairments complicate the pathophysiology of COVID-19 disease in these patients. In this review, we provide insight into the COVID-19 disease complications relevant to diabetes and try to focus on the present data and growing concepts surrounding SARS-CoV-2 infections in T2DM patients.

scholarly journals Impact of aging on obstetric outcomes: defining advanced maternal age in Barcelona

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Marta Claramonte Nieto ◽  
Eva Meler Barrabes ◽  
Sandra Garcia Martínez ◽  
Mireia Gutiérrez Prat ◽  
Bernat Serra Zantop
Keyword(s):  
Risk Factor ◽  
Gestational Diabetes ◽  
Maternal Age ◽  
Placenta Previa ◽  
Significant Risk ◽  
Advanced Maternal Age ◽  
Obstetric Outcomes ◽  
Chronic Hypertension ◽  
Mediterranean Population ◽  
Confounding Factors

Abstract Background Women of advanced maternal age (AMA) are a growing population, with higher obstetric risks. The Mediterranean population has specific characteristics different from other areas. Thus, the objective of this study was to establish a cut-off to define AMA in a selected mediterranean population coming from a tertiary referral private/mutual health hospital in Barcelona. Methods Retrospective cohort of euploid singleton pregnancies delivered from January 2007 to June 2017. Main maternal outcomes were: gestational diabetes, preeclampsia, placenta previa, c-section and prolonged hospitalization (≥ 7 days). Main adverse perinatal outcomes were: stillbirth, prematurity, preterm prelabor rupture of membranes, low birth weight, need of admission at a neonatal intensive care unit and perinatal mortality. Adjustment for confounding factors (smoking, previous comorbilities, parity, assisted reproductive techniques (ART) and obesity) was performed. Results A total of 25054 pregnancies were included. Mean maternal age was 34.7 ± 4.2 years, with 2807 patients in the group of age between 40 and 44 years (11.2%) and 280 patients ≥45 years (1.1%). Women at AMA had higher incidence of previous comorbilities (compared to the reference group of women < 30 years): prior c-section, chronic hypertension and obesity. In addition, they were more likely to use ART. After adjusting for confounding factors, maternal age was an independent and statistically significant risk factor for gestational diabetes (OR 1.66/2.80/3.14) for ages 30–39, 40–44 and ≥ 45 years respectively, c-section (OR 1.28/2.41/7.27) and placenta previa (OR 2.56/4.83) for ages 40–44 and ≥ 45 years respectively, but not for preeclampsia (neither early-onset nor late-onset). Risk of emergency c-section was only increased in women ≥45 years (OR, 2.03 (95% CI, 1.50–2.74). In the other groups of age, the increase in c-section rate was because of elective indications. Age ≥ 45 years was associated with iatrogenic prematurity < 37 weeks (OR 2.62, 95% CI 1.30–5.27). No other relevant associations between AMA and maternal or neonatal outcomes were found. Conclusions Maternal age is an independent risk factor for adverse obstetric outcomes. Age ≥ 40 years was associated to relevant increased risks and reveals to be an adequate cut-off to define AMA in our population.

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