Subacute decline in serum lipids precedes the occurrence of primary intracerebral hemorrhage.
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ABSTRACT: Objective
We aimed to describe the temporal variation in circulating lipid levels among patients with intracerebral hemorrhage (ICH) and investigate their association with ICH risk.Methods
This was a single-center, retrospective, longitudinal, case-control analysis using cases drawn from an ongoing cohort study of primary ICH and controls drawn from a hospital-based clinical data registry. Piecewise linear mixed-effect random coefficient models were used to determine the significance of changes in serum lipid trends on ICH risk.Results
Two hundred twelve ICH cases and 301 control individuals were analyzed. Overall trends in serum total cholesterol (TC) and low-density lipoprotein (LDL) levels differed between ICH cases and non-ICH controls (p = 0.00001 and p = 0.0092, respectively). Patients with ICH experience accelerated decline in serum TC and LDL levels during 6 months immediately preceding ICH, compared with levels between 6 and 24 months pre-ICH (TC: -29.25 mg/dL, p = 0.001; LDL: -21.48 mg/dL, p = 0.0038), which was not observed in non-ICH controls. Subgroup analysis confirmed that this phenomenon cannot be attributed to statin or alcohol exposure. Serum triglycerides and high-density lipoprotein trends did not differ between groups.Conclusions
Longitudinal lipid levels differ between ICH cases and non-ICH controls, most notably for a decline in serum TC and LDL levels within 6 months preceding primary ICH, independent of statin or alcohol use. These changes in serum TC and LDL trends suggest a biological pathway that precipitates ICH occurrence. Further studies are needed to replicate these results and characterize rate of change in serum lipids as a potential biomarker of impending acute cerebral injury.
SUBMITTER: Phuah CL
PROVIDER: S-EPMC4891207 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Many clinical trials focus on restricting hematoma expansion following acute intracerebral hemorrhage (ICH), but selecting those patients at highest risk of hematoma expansion is challenging.To develop a prediction score for hematoma expansion in patients with primary ICH.Prospective cohort study at 2 urban academic medical centers among patients having primary ICH with available baseline and follow-up computed tomography for volumetric analysis (817 patients in the development cohort and 195 patients in the independent validation cohort).Hematoma expansion was assessed using semiautomated software and was defined as more than 6 mL or 33% growth. Covariates were tested for association with hematoma expansion using univariate and multivariable logistic regression. A 9-point prediction score was derived based on the regression estimates and was subsequently tested in the independent validation cohort.Hematoma expansion occurred in 156 patients (19.1%). In multivariable analysis, predictors of expansion were as follows: warfarin sodium use, the computed tomography angiography spot sign, and shorter time to computed tomography (? 6 vs >6 hours) (P <?.001 for all), as well as baseline ICH volume (<30 [reference], 30-60 [P =?.03], and >60 [P =?.005] mL). The incidence of hematoma expansion steadily increased with higher scores. In the independent validation cohort (n = 195), our prediction score performed well and showed strong association with hematoma expansion (odds ratio, 4.59; P <?.001 for a high vs low score). The C statistics for the score were 0.72 for the development cohort and 0.77 for the independent validation cohort.A 9-point prediction score for hematoma expansion was developed and independently validated. The results open a path for individualized treatment and trial design in ICH aimed at patients at highest risk of hematoma expansion with maximum potential for therapeutic benefit.
| S-EPMC4131760 | biostudies-literature
Project description:ObjectiveLittle information is available about sex-related differences in intracerebral hemorrhage (ICH). This is a prospective observational study to describe the sex differences in demographics, vascular risk factors, stroke care, and outcomes in primary ICH.MethodsBasicMar is a hospital-based registry of all stroke patients admitted to a single public hospital that covers a population of 330,000. From 2005 to 2015, there were 515 consecutive acute primary ICH patients. Outcome data were obtained at 3 months.ResultsMore men than women had ICH (52.4% vs 47.6%); the women were older and had worse previous functional status than men, who were more likely to drink alcohol and smoke and to have ischemic heart disease and peripheral arterial disease. There were no sex differences in etiology, severity, or hemorrhage volume. ICH score was greater in women than in men (p = 0.018). Women had more lobar ICH than men (odds ratio adjusted by age was 1.75 [95% confidence interval 1.18-2.58], p = 0.005). The quality of stroke care was similar in both sexes. Mortality at 3 months was 44.1% in women and 41.1% in men (p = 0.656), and 3-month poor outcome among survivors (modified Rankin Scale [mRS] score 3-5) 58.4% in women and 45.3% in men (p = 0.027). After adjustment for previous mRS and ICH score, there were no differences in 3-month mortality or poor outcome at 3 months between sexes.ConclusionsPatients with ICH showed sex-related differences in demographic characteristics, ICH location, and vascular risk factors, but not in stroke care, 3-month mortality, or adjusted poor outcome.
| S-EPMC4955279 | biostudies-literature
Project description:ObjectiveWhether diabetes mellitus (DM) is a risk factor for spontaneous intracerebral hemorrhage (ICH) and influences outcome after ICH remains unclear.MethodsOne reviewer searched Ovid MEDLINE and Embase 1980-2014 inclusive for studies investigating the associations between DM and ICH occurrence or DM and ICH case fatality. Two reviewers independently confirmed each study's eligibility, assessed risk of bias, and extracted data. One reviewer combined studies using random effects meta-analysis.ResultsNineteen case-control studies involving 3,397 people with ICH and 5,747 people without ICH found an association between DM and ICH occurrence (unadjusted odds ratio [OR] 1.23, 95% confidence interval [CI] 1.04-1.45; I(2) = 22%), which did not differ between 17 hospital-based and 2 population-based studies (pdiff = 0.70), and was similar in the 16 studies that controlled for age and sex (unadjusted OR 1.15, 95% CI 0.95-1.40; I(2) = 14%). This association was not identified in 3 population-based cohort studies in which ICH occurred in 38 (0.66%) of 5,724 people with DM and 448 (0.57%) of 78,702 people without DM (unadjusted risk ratio [RR] 1.27, 95% CI 0.68-2.36; I(2) = 69%). DM was associated with a higher case fatality by 30 days or hospital discharge in 18 cohort studies involving 813 people with DM and 3,714 people without DM (unadjusted RR 1.52, 95% CI 1.28-1.81; I(2) = 49%).ConclusionsThe findings suggest that there may be modest associations between DM and ICH occurrence and outcome, but further information from large, population-based studies that account for confounding is required before the association can be confirmed.
| S-EPMC5035156 | biostudies-literature
Project description:BackgroundCognitive impairment and depressive symptoms are highly prevalent after Intracerebral Hemorrhage (ICH). We leveraged Latent Profile Analysis (LPA) to identify profiles for cognitive decline and depression onset after ICH. We also investigated differences in clinical, genetic and neuroimaging characteristics across patients' profiles.MethodsWe analyzed data from the ICH study conducted at Massachusetts General Hospital between January 1998 and December 2019. We collected information from electronical health records, follow-up interviews, CT and MRI imaging, and APOE genotype. We conducted LPA and multinomial logistic regression analyses to: 1) identify distinct profiles for cognitive decline and depression onset after ICH; 2) identify clinical, neuroimaging and genetic factors predicting individuals' likelihood to express a specific profile.ResultsWe followed 784 ICH survivors for a median of 45.8 months. We identified four distinct profiles in cognitive and depressive symptoms after ICH: low depression and dementia risk, early-onset depression and dementia, late-onset depression and dementia, high depression with low dementia risk. Cerebral small vessel disease severity and APOE genotype were specifically associated with the late-onset profile (both p < 0.05). Acute hematoma characteristics (size, intraventricular extension) and functional disability were specifically associated with the early-onset profile (all p < 0.05).ConclusionWe identified four distinct profiles for cognitive and depressive symptoms after ICH, each displaying specific associations with individual patients' clinical, genetic and neuroimaging data. These associations reflect separate biological mechanisms influencing dementia and depression risk after ICH. Our findings support employing LPA in future ICH studies, and is likely applicable to stroke survivors at large.
| S-EPMC8662844 | biostudies-literature
Project description:Background and Purpose- Cirrhosis-clinically overt, advanced liver disease-is associated with an increased risk of hemorrhagic stroke and poor stroke outcomes. We sought to investigate whether subclinical liver disease, specifically liver fibrosis, is associated with clinical and radiological outcomes in patients with primary intracerebral hemorrhage. Methods- We performed a retrospective cohort study using data from the Virtual International Stroke Trials Archive-Intracerebral Hemorrhage. We included adult patients with primary intracerebral hemorrhage presenting within 6 hours of symptom onset. We calculated 3 validated fibrosis indices-Aspartate Aminotransferase-Platelet Ratio Index, Fibrosis-4 score, and Nonalcoholic Fatty Liver Disease Fibrosis Score-and modeled them as continuous exposure variables. Primary outcomes were admission hematoma volume and hematoma expansion. Secondary outcomes were mortality, and the composite of major disability or death, at 90 days. We used linear and logistic regression models adjusted for previously established risk factors. Results- Among 432 patients with intracerebral hemorrhage, the mean Aspartate Aminotransferase-Platelet Ratio Index, Fibrosis-4, and Nonalcoholic Fatty Liver Disease Fibrosis Score values on admission reflected intermediate probabilities of fibrosis, whereas standard hepatic assays and coagulation parameters were largely normal. After adjusting for potential confounders, Aspartate Aminotransferase-Platelet Ratio Index was associated with hematoma volume (?, 0.20 [95% CI, 0.04-0.36]), hematoma expansion (odds ratio, 1.6 [95% CI, 1.1-2.3]), and mortality (odds ratio, 1.8 [95% CI, 1.1-2.7]). Fibrosis-4 was also associated with hematoma volume (?, 0.27 [95% CI, 0.07-0.47]), hematoma expansion (odds ratio, 1.9 [95% CI, 1.2-3.0]), and mortality (odds ratio, 2.0 [95% CI, 1.1-3.6]). Nonalcoholic Fatty Liver Disease Fibrosis Score was not associated with any outcome. Indices were not associated with the composite of major disability or death. Conclusions- In patients with largely normal liver chemistries, 2 liver fibrosis indices were associated with admission hematoma volume, hematoma expansion, and mortality after intracerebral hemorrhage.
| S-EPMC7048169 | biostudies-literature
Project description:Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. Understanding the molecular mechanisms underlying ICH and its severe form is crucial for developing effective therapeutic strategies. This study investigates transcriptomic alterations in rodent models of ICH and severe intracerebral hemorrhage to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to intracerebral hemorrhage and severe intracerebral hemorrhage rats. We further employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the different molecular pathways involved. Using comprehensive RNA sequencing and bioinformatics analyses, we identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, intracerebral hemorrhage, and severe intracerebral hemorrhage groups in the upregulated genes group, and 1196 common genes in the downregulated genes. A volcano plot comparing the groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.
2024-06-11 | GSE264394 | GEO
Project description:BACKGROUND:Hematoma expansion (HE) after intracerebral hemorrhage (ICH) is associated with worse outcome. Lobar ICHs are known to have better outcomes compared to deep ICH; however, it is unclear whether there are HE differences between these locations. We sought to investigate the hypothesis that lobar ICH has less HE compared to deep ICH. METHODS:Primary ICH patients admitted between 2009 and 2016 were included in a prospective single-center ICH cohort study. Patients with preceding anticoagulant use, coagulopathy on admission labs, or presenting after 24?h from symptom onset were excluded. Lobar and deep ICH patients with baseline and follow-up computed tomography (CT) (within 24?h of admission CT) were evaluated. HE was defined primarily as relative growth >?33% given expected baseline hematoma volume differences between locations. Other commonly utilized definitions of HE: >?6 mL, and >?33% or >?6 mL, were additionally assessed. Multivariable logistic regression was used to assess the association of ICH location with HE while adjusting for previously identified covariates of HE. RESULTS:There were 59 lobar and 143 deep ICH patients analyzed. Lobar ICH patients had significantly larger baseline hematoma volumes, lower admission systolic blood pressure, and longer times to admission CT compared to deep ICH. Multivariable logistic regression revealed an association of lobar ICH with lower odds of HE (>?33%) [odds ratio (OR) 0.32; 95% confidence interval (CI) 0.11-0.93; p?=?0.04] compared to deep ICH after adjusting for baseline ICH volume, blood pressure, and time to CT. Secondary analysis did not identify an association of lobar ICH with HE defined as >?6 mL (adjusted OR 1.44; 95% CI 0.59-3.50; p?=?0.41) or >?33% or >?6 mL (adjusted OR 0.71; 95% CI 0.29-1.70; p?=?0.44). CONCLUSION:We identified less HE in lobar compared to deep ICH. The use of absolute growth thresholds in defining HE may be limited when assessing groups with largely different baseline hematoma sizes. Further study is required to replicate our findings and investigate mechanisms for HE differences between lobar and deep ICH locations.
| S-EPMC6609462 | biostudies-literature
Project description:Background and purposeRecent studies of intracerebral hemorrhage (ICH) treatments have highlighted the need to identify reliable predictors of hematoma expansion. The goal of this study was to determine whether contrast extravasation on multisection CT angiography (CTA) and/or contrast-enhanced CT (CECT) of the brain is associated with hematoma expansion and increased mortality in patients with primary ICH.Materials and methodsAll patients with primary ICH who underwent CTA and CECT, as well as follow-up noncontrast CT (NCCT) before discharge/death from January 1, 2003, to September 30, 2005, were retrospectively identified. One neuroradiologist reviewed admission and follow-up NCCT for hematoma size and growth. A second neuroradiologist independently reviewed CTA and CECT for active contrast extravasation. Univariate and multivariate logistic regression analyses were performed to evaluate the significance of clinical and radiologic variables in predicting 30-day mortality, designated as the primary outcome. Hematoma growth was considered as a secondary outcome.ResultsOf 56 patients, contrast extravasation was seen in 17.9% of patients on initial CTA and in 23.2% of patients on initial CECT following CTA. Univariate analysis showed that the presence of extravasation on CT, large initial hematoma size (>30 mL), the presence of "swirl sign" on NCCT, the Glasgow Coma Scale and ICH scores, and international normalized ratio were associated with increased mortality. On multivariate analysis, only contrast extravasation on CT (P = .017) independently predicted mortality. Contrast extravasation on CT (P < .001) was also an independent predictor of hematoma growth on multivariate analysis.ConclusionActive contrast extravasation on CT in patients with primary ICH independently predicts mortality and hematoma growth.
| S-EPMC8118895 | biostudies-literature
Project description:BackgroundMagnesium (Mg) has potential hemostatic properties. We sought to investigate the potential association of serum Mg levels (at baseline and at 48 hours) with outcomes in patients with acute spontaneous intracerebral hemorrhage (ICH).Methods and resultsWe reviewed data on all patients with spontaneous ICH with available Mg levels at baseline, over a 5-year period. Clinical and radiological outcome measures included initial hematoma volume, admission National Institutes of Health Stroke Scale and ICH scores, in-hospital mortality, favorable functional outcome (modified Rankin Scale scores, 0-1), and functional independence (modified Rankin Scale scores, 0-2) at discharge. Our study population consisted of 299 patients with ICH (mean age, 61±13 years; mean admission serum Mg, 1.8±0.3 mg/dL). Increasing admission Mg levels strongly correlated with lower admission National Institutes of Health Stroke Scale score (Spearman's r, -0.141; P=0.015), lower ICH score (Spearman's r, -0.153; P=0.009), and lower initial hematoma volume (Spearman's r, -0.153; P=0.012). Higher admission Mg levels were documented in patients with favorable functional outcome (1.9±0.3 versus 1.8±0.3 mg/dL; P=0.025) and functional independence (1.9±0.3 versus 1.8±0.3 mg/dL; P=0.022) at discharge. No association between serum Mg levels at 48 hours and any of the outcome variables was detected. In multiple linear regression analyses, a 0.1-mg/dL increase in admission serum Mg was independently and negatively associated with the cubed root of hematoma volume at admission (regression coefficient, -0.020; 95% confidence interval, -0.040 to -0.000; P=0.049) and admission ICH score (regression coefficient, -0.053; 95% confidence interval, -0.102 to -0.005; P=0.032).ConclusionsHigher admission Mg levels were independently related to lower admission hematoma volume and lower admission ICH score in patients with acute spontaneous ICH.
| S-EPMC6015418 | biostudies-literature
Project description:Background and purposePerihematomal edema (PHE) contributes to secondary brain damage and aggravates patient outcomes after intracerebral hemorrhage (ICH). MicroRNAs (miRNAs) are stable in circulation, and their unique expression profiles have fundamental roles in modulating vascular disease. The objective of this study was to test the hypothesis that altered miRNA levels are associated with PHE in ICH patients.MethodsHematoma and PHE volumes of ICH patients were measured on admission and in follow-up computed tomography scans. Whole-genome miRNA profiles of ICH patients and healthy controls were determined using the Exiqon miRCURY LNA Array, and validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Bioinformatics analysis investigated dysregulated miRNA target genes and the signaling pathways involved.ResultsWe identified 55 miRNAs that were differentially expressed in ICH patients compared with normal controls, of which 54 were down-regulated and one was up-regulated. qRT-PCR confirmation showed decreases in miR-126 (0.63-fold), miR-146a (0.64-fold), miR-let-7a (0.50-fold), and miR-26a (0.54-fold) in ICH patients relative to controls. Serum miR-126, but not miR-146a, miR-let-7a or miR-26a, levels were significantly correlated with relative PHE volume on days 3-4 (r = -0.714; P<0.001) in patients with ICH.ConclusionsICH patients appear to have a specific miRNA expression profile. Low expression of miR-126 was positively correlated with the extent of PHE, suggesting it may have a pathogenic role in the development of PHE after ICH.
| S-EPMC4514469 | biostudies-literature