Hyperhomocysteinemia is an emerging comorbidity in ischemic stroke.
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ABSTRACT:
SUBMITTER: Poddar R
PROVIDER: S-EPMC7856041 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe Charlson comorbidity index (CCI) is commonly used to adjust for patient casemix. We reevaluated the CCI in an ischemic stroke (IS) cohort to determine whether the original seventeen comorbidities and their weights are relevant.MethodsWe identified an IS cohort (N = 6988) from the Ontario Stroke Registry (OSR) who were discharged from acute hospitals (N = 100) between April 1, 2012 and March 31, 2013. We used hospital discharge ICD-10-CA data to identify Charlson comorbidities. We developed a multivariable Cox model to predict one-year mortality retaining statistically significant (P < 0.05) comorbidities with hazard ratios ≥1.2. Hazard ratios were used to generate revised weights (1-6) for the comorbid conditions. The performance of the IS adapted Charlson comorbidity index (ISCCI) mortality model was compared to the original CCI using the c-statistic and continuous Net Reclassification Index (cNRI).ResultsTen of the 17 Charlson comorbid conditions were retained in the ISCCI model and 7 had reassigned weights when compared to the original CCI model . The ISCCI model showed a small but significant increase in the c-statistic compared to the CCI for 30-day mortality (c-statistic 0.746 vs. 0.732, p = 0.009), but no significant increase in c-statistic for in-hospital or one-year mortality. There was also no improvement in the cNRI when the ISCCI model was compared to the CCI.ConclusionsThe ISCCI model had similar performance to the original CCI model. The key advantage of the ISCCI model is it includes seven fewer comorbidities and therefore easier to implement in situations where coded data is unavailable.
| S-EPMC6892203 | biostudies-literature
Project description:Background and Purpose: Hyperhomocysteinemia (Hhcy) is a well-known risk factor for ischemic stroke. However, the role of Hhcy in the clinical outcome of ischemic stroke has not been fully elucidated. In addition, previous studies have found that Hhcy was implicated in the disruption of the blood-brain barrier, which may increase the risk of hemorrhagic transformation (HT) after thrombolysis. Thus, the aim of this study was to investigate the effect of Hhcy on the clinical outcome and HT after thrombolysis in ischemic stroke patients. Methods: Patients who were diagnosed with ischemic stroke and received intravenous thrombolytic therapy between January 2016 and September 2018 were included in this study. Multivariate logistic regression analysis was used to assess the association between Hhcy, clinical outcome, and HT after thrombolysis. Furthermore, the potential interaction between Hhcy and hypertension on the clinical outcome and HT after thrombolysis was also assessed. Results: Of 568 patients, 455 (80.1%) had Hhcy, 66 (11.6%) had HT, and 219 (38.6%) had poor outcome. Patients with Hhcy had a higher incidence of poor outcome than the patients with non-Hhcy (40.9 vs. 29.2%, p = 0.022). However, there was no significant difference in the incidence of HT (11.9 vs. 10.6%, p = 0.711) between patients with Hhcy and non-Hhcy. After adjustment for major covariates, multivariate logistic regression analysis disclosed that Hhcy was independently associated with increased risk of poor outcome (OR = 1.760; 95% CI: 1.069-2.896) but was not associated with the risk of HT (OR = 1.017; 95% CI: 0.495-2.087). In addition, we found no significant interaction between Hhcy and hypertension on the clinical outcome (p = 0.513) or HT (p = 0.170) after thrombolysis. Conclusion: We found that Hhcy was an independent risk factor for poor outcome, but not an independent risk factor for HT after thrombolysis in ischemic stroke patients. In addition, there was no significant interaction of Hhcy and hypertension on the clinical outcome or HT after thrombolysis.
| S-EPMC6584786 | biostudies-literature
Project description:Systemic cancer and ischemic stroke are common conditions and two of the most frequent causes of death among the elderly. The association between cancer and stroke has been reported worldwide. Stroke causes severe disability for cancer patients, while cancer increases the risk of stroke. Moreover, cancer-related stroke is expected to increase due to advances in cancer treatment and an aging population worldwide. Because cancer and stroke share risk factors (such as smoking and obesity) and treatment of cancer can increase the risk of stroke (e.g., accelerated atherosclerosis after radiation therapy), cancer may accelerate conventional stroke mechanisms (i.e., atherosclerosis, small vessel disease, and cardiac thrombus). In addition, active cancer and chemotherapy may enhance thrombin generation causing stroke related to coagulopathy. Patients with stroke due to cancer-related coagulopathy showed the characteristics findings of etiologic work ups, D-dimer levels, and infarct patterns. In this review, we summarized the frequency of cancer-related stroke among patients with ischemic stroke, mechanisms of stroke with in cancer patients, and evaluation and treatment of cancer-related stroke. We discussed the possibility of cancer-related stroke as a stroke subtype, and presented the most recent discoveries in the pathomechanisms and treatment of stroke due to cancer-related coagulopathy.
| S-EPMC7005348 | biostudies-literature
Project description:Cell death is a key feature of neurological diseases, including stroke and neurodegenerative disorders. Studies in a variety of ischemic/hypoxic mouse models demonstrate that poly(ADP-ribose) polymerase 1 (PARP-1)-dependent cell death, also named PARthanatos, plays a pivotal role in ischemic neuronal cell death and disease progress. PARthanatos has its unique triggers, processors, and executors that convey a highly orchestrated and programmed signaling cascade. In addition to its role in gene transcription, DNA damage repair, and energy homeostasis through PARylation of its various targets, PARP-1 activation in neuron and glia attributes to brain damage following ischemia/reperfusion. Pharmacological inhibition or genetic deletion of PARP-1 reduces infarct volume, eliminates inflammation, and improves recovery of neurological functions in stroke. Here, we reviewed the role of PARP-1 and PARthanatos in stroke and their therapeutic potential.
| S-EPMC9010225 | biostudies-literature
Project description:PurposeComorbidities and polypharmacy are risk factors for worse outcome in stroke. However, comorbidities and polypharmacy are mostly studied separately with various approaches to assess them. We aimed to analyze the impact of comorbidity burden and polypharmacy on functional outcome in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT).MethodsAcute ischemic stroke patients with large vessel occlusion (LVO) treated with MT from a prospective observational study were analyzed. Relevant comorbidity burden was defined as a Charlson Comorbidity Index (CCI) score ≥ 2, polypharmacy as the intake of ≥ 5 medications at time of stroke onset. Favorable outcome was a score of 0-2 on the modified Rankin scale at 90 days after stroke. The effect of comorbidity burden and polypharmacy on favorable outcome was studied via multivariable regression analysis.ResultsOf 903 patients enrolled, 703 AIS patients (mean age 73.4 years, 54.9% female) with anterior circulation LVO were included. A CCI ≥ 2 was present in 226 (32.1%) patients, polypharmacy in 315 (44.8%) patients. Favorable outcome was less frequently achieved in patients with a CCI ≥ 2 (47, 20.8% vs. 172, 36.1%, p < 0.001), and in patients with polypharmacy (69, 21.9% vs. 150, 38.7%, p < 0.001). In multivariable regression analysis including clinical covariates, a CCI ≥ 2 was associated with lower odds of favorable outcome (odds ratio, OR 0.52, 95% confidence interval, 95% CI 0.33-0.82, p = 0.005), while polypharmacy was not (OR 0.81, 95% CI 0.52-1.27, p = 0.362).ConclusionRelevant comorbidity burden and polypharmacy are common in AIS patients with LVO, with comorbidity burden being a risk factor for poor outcome.
| S-EPMC10014774 | biostudies-literature
Project description:PurposeComorbidity in stroke is common, but comprehensive reports are sparse. We describe prevalence of comorbidity and the prognostic impact on mortality and functional outcome in a large national ischemic stroke cohort.MethodsWe used outcome data from a long-term follow-up survey conducted in 2016 by the Swedish Stroke Register (Riksstroke). Those included in the study were 11 775 pre-stroke functionally independent patients with first-ever ischemic stroke followed up at three months and 12?months (all patients), and three years (2013 cohort) or five years (2011 cohort). Pre-stroke comorbidity data for 16 chronic conditions were obtained from the Swedish National Patient Register, the Swedish Prescribed Drugs Register and the Riksstroke register. Individuals were grouped according to number of conditions: none (0), low (1), moderate (2-3) or high (?4). Co-occurrence was analysed using hierarchical clustering, and multivariable analyses were used to estimate the prognostic significance of individual conditions.ResultsThe proportion of patients without comorbidity was 24.8%; 31.8% had low comorbidity; 33.5% had moderate comorbidity and 9.9% had high comorbidity. At 12?months, the proportion of poor outcome (dead or dependent: mRS ?3) was 24.8% (no comorbidity), 34.7% (low), 45.2% (moderate) and 59.4% (high). At five years, these proportions were 37.7%, 50.3%, 64.3%, and 81.7%, respectively. There was clustering of cardiovascular conditions and substantial negative effects of dementia, kidney, and heart failure.ConclusionComorbidity is common and has a strong impact on mortality and functional outcome. Our results highlight the need for health systems to shift focus to a comprehensive approach in stroke care that includes multimorbidity as a key component.
| S-EPMC7092731 | biostudies-literature
Project description:Using a hitherto uncharacterized knockout mouse model of Notch 3, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover a striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype. Microarray Studies. Biotinylated cRNA samples from freshly sorted brain SMCs (four Notch 3 +/- mice and five Notch 3 -/- mice) were fragmented before hybridization (15 ug each) onto mouse 430 2.0 Affymetrix chips. The chips were washed, stained by using strepavidin-phycoerytrin, and scanned the next day as described in ref. 24. For data normalization, all probe sets were scaled to a target intensity of 150. Microarray data analysis was performed by using Rosetta Resolver. All cells were from 10- to 12-week-old male mice. Gene Ontology Analyses. PANTHER software was used to define over- and underrepresented functions in the list of signature genes found by microarray analysis (25). P values were calculated by using binomial statistics.
2014-06-11 | E-GEOD-58368 | biostudies-arrayexpress
Project description:This study determined the influence of myeloid cell Trim59 deficiency on experimental stroke outcomes and the cerebral proteomic profile using myeloid cell Trim59 conditional knockout (Trim59-cKO) mice, the middle cerebral artery occlusion/reperfusion ischemic model, and a label-free quantitative proteomic profiling technique.
2024-08-02 | PXD049258 | Pride
Project description:We performed a genome-wide methylation study in whole-blood DNA from 404 ischemic stroke patient cohort, distributed across 3 ischemic stroke subtypes: Large-artery atherosclerosis (n=132), Small-artery disease (n=141) and Cardio embolic (n=127) . Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites. We performed a genome-wide methylation study in whole-blood DNA from 185 ischemic stroke patient cohort. Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites.
2015-08-19 | GSE69138 | GEO
Project description:Using a hitherto uncharacterized knockout mouse model of Notch 3, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover a striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype.
2014-06-11 | GSE58368 | GEO