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  • 1
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. Suppl_1 ( 2020-02)
    Abstract: Introduction: With improvements in acute care, more patients are surviving a first-time spontaneous intracerebral hemorrhage (ICH). In the growing survivor population, little is known about effective secondary stroke prevention strategies or long-term causes of illness and death. This study aims to determine the cause of death in first-time ICH survivors. Methods: We performed a longitudinal analysis of prospectively collected claims data. We used data collected on all hospitalizations from California (2005-2011) and New York (2005-2014). State residents admitted with a primary diagnosis of non-traumatic ICH (ICD-9-CM code 431) who survived to discharge were included in the study. Patients were followed for a primary outcome of any readmission event resulting in death. Cause of death was defined as the primary diagnosis assigned at discharge. Kaplan-Meier survival analysis was used to estimate the risk of in-hospital death during follow-up. Cox proportional hazards and multinomial logistic regression were used to determine factors associated with the risk and cause for death. Subgroup analyses stratified by a history of atrial fibrillation (AF) were performed. Results: Of 56,593 identified ICH survivors (mean age 69 [SD 15], 49% female), 6,931 (14%) died during a median follow-up period of 3.6 years (IQR 1.5-5.9). The one-year risk of death was 7% (95% CI 7.0-7.4) and the median time to death was 0.7 years (IQR 0.1-2.3). Patients who died were old er (74 vs. 68, p 〈 0.001) and more likely to have history of AF (24% vs. 16%, p 〈 0.001), congestive heart disease (15% vs. 8%, p 〈 0.001), and diabetes (32% vs. 26%, p 〈 0.001). The leading causes of death were infection (29%), recurrent ICH (12%), cardiac causes (8%), respiratory failure (7%), and ischemic stroke (4%). Patients with AF were at an increased the risk of death from ischemic stroke (OR 2.04, 95% CI 1.56-2.68, p 〈 0.001) and cardiac causes (OR 1.49, 95% CI 1.19-1.87, p=0.002) compared to those without AF. Conclusions: The leading causes of inpatient death in ICH survivors are infection, recurrent ICH, and cardiac causes while survivors with AF are at an elevated risk for death by recurrent stroke. These findings may represent interventional targets in the effort to extend improved outcomes in ICH survivors.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467823-8
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  • 2
    In: JAMA Neurology, American Medical Association (AMA), Vol. 79, No. 9 ( 2022-09-01), p. 911-
    Type of Medium: Online Resource
    ISSN: 2168-6149
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. Suppl_1 ( 2020-02)
    Abstract: Introduction: Animal and observational studies indicate that smoking is a risk factor for aneurysm formation and rupture, leading to subarachnoid hemorrhage (SAH). However, a definitive causal relationship between smoking and SAH has not been established. We leveraged the causal properties of mutation-disease associations to test the hypothesis that smoking is causally linked to SAH. Methods: We conducted a one-sample Mendelian Randomization (MR) study within the UK Biobank, a prospective, population-based observational study. We restricted the analysis to study participants with genetically-confirmed European ancestry. SAH cases were ascertained using previously validated codes. As the instrument, we built a polygenic risk score (PRS) using independent (R2 〈 0.1) genetic variants known to be associated (p 〈 5x10-8) with smoking. For the primary MR analysis, we implemented the ratio method using the estimates obtained from testing the PRS for association with risk of SAH and smoking. In secondary analyses, we implemented the inverse-variance weighted (IVW) and weighted median (WM) methods. Pleiotropy was assessed via the MR-Egger approach. Results: We included a total of 408,622 individuals in this study (mean age 57 [SD 8], female sex 220,944 [54%] ). Of these, 132,568 (32%) ever smoked regularly and 904 (0.22%) had an SAH. Each additional standard deviation of the smoking PRS was associated with a 9% increased risk of SAH (OR 1.09, 95%CI 1.03-1.17; p=0.006) and 21% increased risk of smoking (OR 1.21, 95%CI 1.2-1.21; p=1x10-16). In the primary analysis, genetically-determined smoking was associated with a 63% increase in risk of SAH (OR 1.63, 95%CI 1.15-2.30; p=0.006). Secondary analyses using the IVW method (OR 1.57, 95%CI 1.13-2.17; p=0.007) and the WM method (OR 1.74, 95%CI 1.06-2.86; p=0.028) yielded comparable results. There was no significant pleiotropy (MR-Egger intercept p=0.38). Conclusion: Genetically-determined smoking is strongly associated with the risk of SAH. These findings provide evidence for a causal link between smoking and the occurrence of this often-debilitating condition. Interventions aimed at reducing smoking behavior could offer significant benefits, especially to those at high risk of SAH.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467823-8
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Abstract: Introduction: Lung cancer has been linked to increased risk of thromboembolic events, including stroke. However, a causal relationship between lung cancer and ischemic stroke (IS) has yet to be established. Methods: We conducted a two-stage study using observational and genetic data from the UK Biobank, a large cohort study that enrolled over 500,000 Britons aged 40-69. We included participants of European descent. In Stage I, we used logistic regression to test the association between self-reported / ICD-defined lung cancer and risk of IS. In Stage II, we constructed a polygenic risk score (PRS) using 31 independent genetic variants known to associate with lung cancer, fitted logistic regression to assess the relationship between this PRS and risk of IS, and implemented the inverse variance weighted method of Mendelian randomization (MR). We tested for horizontal pleiotropy using the MR-Egger and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) approaches. Results: Out of 409,629 participants of European descent enrolled in the UK Biobank, there were 5,060 IS cases (mean age, 61.6 [standard deviation 6.5]; female sex, 1813 [35.8%] ). The prevalence of lung cancer was 1.9% (n=94) and 0.5% (n=1,961) among persons with and without IS, respectively (unadjusted p 〈 0.001). In multivariable analyses, self-reported / ICD-defined lung cancer was associated with a 54% increase in risk of IS (adjusted OR, 1.54; 95% CI, 1.30-1.81; p 〈 0.001). Genetic analyses supported a causal link between lung cancer and IS. In PRS analysis, each additional standard deviation of the lung cancer-related PRS was associated with a 3% increase in risk of IS (adjusted OR, 1.03; 95% CI, 1.01-1.06; p=0.018). In MR analysis, genetically determined lung cancer was associated with a 5% increase in risk of IS (OR, 1.05; 95% CI, 1.01-1.09; p=0.022). There was no significant horizontal pleiotropy (MR-Egger intercept p=0.663; MR-PRESSO global test p=0.993). Conclusions: Genetically determined lung cancer is associated with increased risk of ischemic stroke. These findings provide evidence for a causal link between lung cancer and ischemic stroke. Further studies are needed to identify the biological pathways that mediate this link.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 5
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Abstract: Introduction: Non-traumatic subarachnoid hemorrhage (SAH) is strongly linked to hypertension, a condition highly influenced by common genetic variants. For complex diseases influenced by genetic and environmental factors, genetic predisposition plays a key role in earlier onset. We tested the hypothesis that persons with a higher polygenic burden of hypertension-related alleles have SAH at younger ages. Methods: We analyzed data from the UK Biobank, a large cohort study that enrolled over 500,000 Britons aged 40-69. We included participants of European descent. We constructed two polygenic risk scores (PRS) using 807 independent genetic variants known to associate with higher systolic and diastolic blood pressure (BP). We fitted linear regression to assess the relationship between these PRS and the age-of-onset of SAH, using product terms to test for interaction with sex. We subsequently implemented Mendelian Randomization analyses using the inverse variance weighted and weighted median methods to evaluate causality. Results: We evaluated a total of 1,178 SAH cases (mean age, 58; female sex, 722 [61.3%]). When evaluating all participants jointly, there was no association between the systolic BP PRS and age-of-onset for SAH (p=0.130). There was a significant interaction between the PRS and sex (p=0.002): each additional standard deviation of the systolic BP PRS was associated with an earlier onset of SAH in females (beta, -1.45; 95% CI, -2.31 to -0.58; p=0.001), but not in males (adjusted beta, 0.83; 95% CI, -0.37 to 2.02; p=0.176). In MR analyses, a 10mmHg increase in genetically determined systolic BP was associated with a 5-year earlier onset of SAH in female participants using both the inverse variance weighted (beta, -4.72; 95% CI, -7.34 to -2.10; p 〈 0.001) and weighted median approaches (beta, -5.05; 95% CI, -9.19 to -0.90; p=0.017). Analyses with the diastolic BP SNPs yielded comparable results (all p 〈 0.05). Conclusions: Genetically determined hypertension is associated with earlier onset of non-traumatic SAH in women. These results indicate that genetic predisposition may play a more important causal role in younger patients and point to genetic information as possible tools for early identification of high-risk individuals.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 5 ( 2021-05), p. 1835-1838
    Abstract: To determine whether obstructive sleep apnea (OSA) is associated with intracerebral hemorrhage (ICH) risk, we assessed premorbid OSA exposure of patients with nontraumatic ICH and matched controls. Methods: Ethnic/Racial Variations of Intracerebral Hemorrhage is a multicenter, case-control study evaluating risk factors for ICH that recruited 3000 cases with ICH and 3000 controls. OSA status was ascertained using the Berlin Questionnaire as a surrogate for premorbid OSA. We performed logistic regression analyses to evaluate the association between OSA and ICH. Results: Two thousand and sixty-four (71%) cases and 1516 (52%) controls were classified as having OSA by the Berlin Questionnaire. Cases with OSA were significantly more likely to be male and have hypertension, heart disease, hyperlipidemia, and higher body mass index compared with those without OSA. OSA was more common among cases compared with controls (71% versus 52%, odds ratio, 2.28 [95% CI, 2.05–2.55]). In a multivariable logistic regression model, OSA was associated with increased risk for ICH (odds ratio, 1.47 [95% CI, 1.29–1.67] ). Conclusions: OSA is a risk factor for ICH.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 7
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. Suppl_1 ( 2020-02)
    Abstract: Introduction: Obstructive sleep apnea (OSA) is a treatable condition and well-established risk factor for ischemic stroke, but the prevalence in ICH is unknown. We aim to characterize the frequency of OSA in spontaneous intracerebral hemorrhage (ICH). Methods: The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a prospective observational study evaluating risk factors for ICH among whites, blacks, and Hispanics. OSA status was determined using two different strategies: (1) the Berlin Questionnaire, a validated screening tool to identify those with a high likelihood of OSA where “high risk” is defined as 〉 1 point in at least 2 of 3 categories assessing snoring, fatigue, and hypertension, and (2) self-reported history of diagnosed sleep apnea. Results: We evaluated 3000 ICH cases. Within this group, 2896 (96.5%) completed the Berlin questionnaire, with 2064 (71%) patients being high risk for OSA. Compared to patients with low risk of OSA, those at high risk were more likely to be male (61% versus 53%, p 〈 0.001) with hypertension (93% versus 65%, p 〈 0.001), diabetes (32% versus 20%, p 〈 0.001), hyperlipidemia (49% versus 38%, p 〈 0.001), and higher BMI (29.8 +/- 8.1 versus 26.8 +/- 6.5, p 〈 0.001), and less likely to have lobar ICH location (29% versus 35%, p 〈 0.001). Self-reported history of prior sleep apnea diagnosis was present in only 175 (9.5%) of ICH cases. Conclusions: OSA is highly prevalent and underdiagnosed in our cohort of ICH patients. Given the effective treatments available for OSA, which have been shown to improve morbidity and mortality in patients with ischemic stroke, further studies are needed to assess the role of OSA as both a determinant of both risk and outcome in ICH.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467823-8
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  • 8
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Introduction: Chronic kidney disease (CKD) is a well-established risk factor for spontaneous intracerebral hemorrhage (ICH). However, the biological pathway underlying this association remains unclear. We therefore conducted a phenome-wide association study (PheWAS) to assess for mediators of the association between CKD and ICH risk. Methods: We conducted a PheWAS using data from the UK Biobank (UKB), a large cohort study that enrolled over 500,000 Britons aged 40-69. We first developed a polygenic risk score that contained 27 independent (r2 〈 0.1) genetic risk variants known to be associated with CKD at genome-wide significant levels (p 〈 5x10 -8 ). We subsequently tested for associations between this CKD genetic risk score and the 1,840 disease phenotypes available through the UKB baseline assessment. We used a Bonferroni corrected p 〈 2.7x10 -5 as our threshold for significance. For all phenotypes that reached statistical significance in the PheWAS, we obtained summary results from previously published genome-wide association studies and implemented multivariable Mendelian Randomization (MR) to evaluate the proportion of the total effect of CKD on ICH risk mediated through these phenotypes. The indirect effect of CKD on ICH risk via mediators was calculated by subtracting the direct effect of CKD obtained from multivariable MR from the total effect of CKD obtained from univariable MR. Results: Excluding renal-related diseases, hypertension was the only significant phenotype in the PheWAS (p=3.2x10 -21 ). Genetically determined CKD was associated with a total increase in ICH risk of 38% in univariable MR (OR 1.38; 95% CI 1.12-1.71; p=0.002). This association was reduced to a 19% increase in ICH risk after adjusting for hypertension in multivariable MR (OR 1.19; 95% CI 1.03-1.39; p=0.021). The proportion of the total effect of CKD on ICH risk mediated through hypertension was estimated to be 55%. Conclusions: Hypertension accounts for approximately 55% of the total effect of CKD on ICH risk in genetic analyses. This aligns with existing knowledge that CKD worsens hypertension by causing renal retention of sodium and increased sympathetic activity. Further studies are needed to identify other pathways that mediate the remaining effect of CKD on ICH risk.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467823-8
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  • 9
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. Suppl_1 ( 2020-02)
    Abstract: Background: Stroke in middle-aged persons is emerging as a distinct entity from previously described "stroke in the young.” Risk factors for recurrence of vascular events in middle-aged stroke survivors have not been well described in a large, racially diverse US-based population. Methods: We performed a retrospective longitudinal analysis of claims data from all hospitalizations in California (2005-2011), Florida (2005-2014), and New York (2005-2014). We included survivors of first-ever ischemic stroke (IS) and non-traumatic intracerebral hemorrhage (ICH). We used validated ICD-9 codes to identify recurrent vascular events, defined as a readmission with a primary diagnosis of IS, ICH, or myocardial infarction (MI). We used survival analysis and Cox proportional hazards regression to determine factors associated with recurrence risk in middle-aged (40-60 years) versus older ( 〉 60 years) adults. Results: We identified 123,212 non-fatal hospitalizations for first-ever IS or ICH in middle-aged adults. There were 14,721 readmissions for recurrent vascular events (11.9%) over a mean follow-up of 4.0 years (standard deviation [SD] 2.8 years). The 1-year and 10-year recurrence rates were 5.5% (95% confidence interval [CI] , 5.3%-5.6%) and 19.4% (95% CI, 19.0%-19.8%) respectively. In multivariable analysis, black (hazard ratio [HR] 1.44; 95% CI, 1.39-1.50; p 〈 0.001) and Hispanic race (HR 1.10; 95% CI, 1.05-1.16; p 〈 0.001), diabetes (HR 1.76; 95% CI, 1.70-1.82; p 〈 0.001), smoking (HR 1.22; 95% CI, 1.18-1.27; p 〈 0.001), hyperlipidemia (HR 1.08; 95% CI, 1.04-1.12; p 〈 0.001), and hypertension (HR 1.06; 95% CI, 1.03-1.10; p 〈 0.001) were associated with increased risk. The associations of black race and diabetes were modified by age category (both multivariable interactions p 〈 0.001). Black race and diabetes were associated with greater increases in risk in middle-aged versus older adults (in older adults: black race HR 1.28; 95% CI, 1.25-1.31; p 〈 0.001; diabetes HR 1.27; 95% CI, 1.25-1.30; p 〈 0.001). Conclusions: Black race and diabetes were the strongest risk factors for recurrence of vascular events in a middle-aged population. Further study of interventions to reduce recurrence and resulting disability in this younger, higher risk population is needed.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467823-8
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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 5 ( 2021-05), p. 1733-1740
    Abstract: IL-6 (interleukin 6) is a proinflammatory cytokine and an established biomarker in acute brain injury. We sought to determine whether admission IL-6 levels are associated with severity and functional outcome after spontaneous intracerebral hemorrhage (ICH). Methods: We performed an exploratory analysis of the recombinant activated FAST trial (Factor VII for Acute ICH). Patients with admission serum IL-6 levels were included. Regression analyses were used to assess the associations between IL-6 and 90-day modified Rankin Scale. In secondary analyses, we used linear regression to evaluate the association between IL-6 and baseline ICH and perihematomal edema volumes. Results: Of 841 enrolled patients, we included 552 (66%) with available admission IL-6 levels (mean age 64 [SD 13], female sex 203 [37%] ). IL-6 was associated with poor outcome (modified Rankin Scale, 4–6; per additional 1 ng/L, odds ratio, 1.30 [95% CI, 1.04–1.63]; P =0.02) after adjustment for known predictors of outcome after ICH and treatment group. IL-6 was associated with ICH volume after adjustment for age, sex, and ICH location, and this association was modified by location (multivariable interaction, P =0.002), with a stronger association seen in lobar (β, 12.51 [95% CI, 6.47–18.55], P 〈 0.001) versus nonlobar (β 5.32 [95% CI, 3.36–7.28], P 〈 0.001) location. IL-6 was associated with perihematomal edema volume after adjustment for age, sex, ICH volume, and ICH location (β 1.22 [95% CI, 0.15–2.29], P =0.03). Treatment group was not associated with IL-6 levels or outcome. Conclusions: In the FAST trial population, higher admission IL-6 levels were associated with worse 90-day functional outcome and larger ICH and perihematomal edema volumes.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
    Location Call Number Limitation Availability
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