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The European Respiratory Journal Mar 2022Obstructive sleep apnoea and the related intermittent hypoxia (IH) are widely recognised as risk factors for incident cardiovascular diseases. Numerous studies support... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obstructive sleep apnoea and the related intermittent hypoxia (IH) are widely recognised as risk factors for incident cardiovascular diseases. Numerous studies support the deleterious vascular impact of IH in rodents but an overall interpretation is challenging owing to heterogeneity in rodent species investigated and the severity and duration of IH exposure. To clarify this major issue, we conducted a systematic review and meta-analysis to quantify the impact of IH on systemic artery structure and function depending on the different IH exposure designs.
METHODS
We searched PubMed, Embase and Web of Science, and included 125 articles in a meta-analysis, among them 112 using wild-type rodents and 13 using apolipoprotein E knockout (ApoE) mice. We used the standardised mean difference (SMD) to compare results between studies.
RESULTS
IH significantly increased mean arterial pressure (+13.90 (95% CI 11.88-15.92) mmHg), and systolic and diastolic blood pressure. Meta-regressions showed that mean arterial pressure change was associated with strain and year of publication. IH altered vasodilation in males but not in females and increased endothelin-1-induced but not phenylephrine-induced vasoconstriction. Intima-media thickness significantly increased upon IH exposure (SMD 1.10 (95% CI 0.58-1.62); absolute values +5.23 (2.81-7.84) µm). This increase was observed in mice but not in rats and was negatively associated with age. Finally, IH increased atherosclerotic plaque size in ApoE mice (SMD 1.08 (95% CI 0.80-1.37)).
CONCLUSIONS
Our meta-analysis established that IH, independently of other confounders, has a strong effect on vascular structure and physiology. Our findings support the interest of identifying and treating sleep apnoea in routine cardiology practice.
Topics: Animals; Blood Pressure; Carotid Intima-Media Thickness; Disease Models, Animal; Female; Humans; Hypoxia; Male; Mice; Rats; Rodentia
PubMed: 34413154
DOI: 10.1183/13993003.00866-2021 -
SAGE Open Medicine 2015Amyloid 1-42 (Aβ42) and tau in cerebrospinal fluid are currently used as markers for diagnosis of Alzheimer's disease. Conflicting reports exist regarding their plasma... (Review)
Review
OBJECTIVE
Amyloid 1-42 (Aβ42) and tau in cerebrospinal fluid are currently used as markers for diagnosis of Alzheimer's disease. Conflicting reports exist regarding their plasma levels in Alzheimer's disease patients. A meta-analysis was performed to statistically validate the use of plasma Aβ42 and tau as biomarkers for Alzheimer's disease.
METHODS
Different databases were searched using the search key: (amyloid OR amyloid1-42 OR Aβ42) AND (tau OR total tau) AND plasma AND (alzheimer's OR alzheimer's disease), and for databases not accepting boolean search, records were retrieved using the search key: plasma + amyloid + tau + alzheimer's. A total of 1880 articles for Aβ42 and 1508 articles for tau were shortlisted. The abstracts were screened, and 69 articles reporting plasma Aβ42 levels and 6 articles reporting plasma tau were identified. After exclusion, 25 studies reporting plasma Aβ42 and 6 studies reporting total tau were analysed in Review Manager version 5.2 using weighted mean difference method, and the bias between studies was assessed using the funnel plot.
RESULTS
Plasma Aβ42 and tau did not vary significantly between Alzheimer's disease patients and controls. The funnel plot showed that there was no bias between studies for Aβ42, while possible bias existed for tau due to availability of limited studies.
CONCLUSION
This analysis pinpoints that plasma Aβ42 and tau could not serve as reliable markers independently for diagnosis of Alzheimer's disease and a cohort study with age, sex and apolipoprotein E correction is warranted for their possible use as Alzheimer's disease markers.
PubMed: 26770797
DOI: 10.1177/2050312115598250 -
FEBS Open Bio 2015Published data regarding the association between Apolipoprotein E (ApoE) genetic variation and myocardial infarction (MI) risk were not always consistent. Therefore, the...
Published data regarding the association between Apolipoprotein E (ApoE) genetic variation and myocardial infarction (MI) risk were not always consistent. Therefore, the current meta-analysis was conducted to derive a more precise estimation of the association between ApoE polymorphism and MI risk. PubMed and Web of Science were searched to identify relevant studies. Summary odds ratio (ORs) and 95% confidence intervals (CIs) were calculated using random-effect or fixed-effect models based on the heterogeneity of included studies. All the tests were performed using Stata 11.0. A total of 22 eligible studies were identified in this meta-analysis. The results show that ApoE ε2 and ε4 alleles were associated with MI risk. The study suggests that there is close association between ApoE polymorphism and MI risk. It shows that ApoE ε2 allele is a protective factor of MI, while ε4 allele is a risk factor of MI, especially in Caucasian and Asian population. Nevertheless, well-designed, unbiased and larger sample size studies are required to confirm the results.
PubMed: 26636027
DOI: 10.1016/j.fob.2015.10.006 -
Journal of Neurotrauma Apr 2021The mortality of traumatic brain injury (TBI) has been largely static despite advances in monitoring and imaging techniques. Substantial variance exists in outcome, not... (Meta-Analysis)
Meta-Analysis
The mortality of traumatic brain injury (TBI) has been largely static despite advances in monitoring and imaging techniques. Substantial variance exists in outcome, not fully accounted for by baseline characteristics or injury severity, and genetic factors likely play a role in this variance. The aims of this systematic review were to examine the evidence for a link between the apolipoprotein E4 (APOE4) polymorphism and TBI outcomes and where possible, to quantify the effect size via meta-analysis. We searched EMBASE, MEDLINE, CINAHL, and gray literature in December 2017. We included studies of APOE genotype in relation to functional adult TBI outcomes. Methodological quality was assessed using the Quality in Prognostic Studies Risk of Bias Assessment Instrument and the prognostic studies adaptation of the Grading of Recommendations Assessment, Development and Evaluation tool. In addition, we contacted investigators and included an additional 160 patients whose data had not been made available for previous analyses, giving a total sample size of 2593 patients. Meta-analysis demonstrated higher odds of a favorable outcome following TBI in those not possessing an ApoE ɛ4 allele compared with ɛ4 carriers and homozygotes (odds ratio 1.39, 95% confidence interval 1.05 to 1.84; = 0.02). The influence of APOE4 on neuropsychological functioning following TBI remained uncertain, with multiple conflicting studies. We conclude that the ApoE ɛ4 allele confers a small risk of poor outcome following TBI, with analysis by TBI severity not possible based on the currently available published data. Further research into the long-term neuropsychological impact and risk of dementia is warranted.
Topics: Apolipoprotein E4; Brain Injuries, Traumatic; Humans; Polymorphism, Single Nucleotide; Treatment Outcome
PubMed: 30848161
DOI: 10.1089/neu.2018.6052 -
BMC Medical Genetics Jun 2019Gallstone disease (GSD) is a common biliary tract disease worldwide. Previous studies have investigated the association of apolipoprotein E (APOE) E4 with GSD and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gallstone disease (GSD) is a common biliary tract disease worldwide. Previous studies have investigated the association of apolipoprotein E (APOE) E4 with GSD and reported inconsistent results.
METHODS
In this paper, we conducted meta-analyses to examine whether APOE E4 is associated with the risk of GSD. A systematic literature search was performed in PubMed, Cochrane Library, EMBASE, and Google Scholar using the following inclusion criteria: 1) Studies on human subjects; 2) subjects in the control group must undergo ultrasound GSD screening, and presence of GSD in the experiment group can be clearly determined, e.g., diagnosis of GSD through ultrasound screening or a previous history of cholecystectomy or cholelithiasis; 3) the studies reported APOE genotype data (APOE E4+ vs. E4-) for subjects with and without GSD. In all the meta-analyses, we used random-effects models to calculate the odds ratios (ORs) as a measure of association as well as the corresponding confidence intervals (CIs).
RESULTS
Our literature search found 13 publications with 14 studies, including a total of 1632 GSD patients and 5001 controls, that met the eligibility criteria and were included in the meta-analyses. We did not find a significant association between APOE E4 and risk of GSD (OR = 1.23, 95% CI: 0.89-1.68; p = 0.205). No significant associations were observed in subgroup analyses by gender and mean age. We obtained similar insignificant findings if an additive model was used, if subjects who had E2E4 genotype were excluded, or if low-quality studies were excluded.
CONCLUSION
Our meta-analysis found insufficient evidence for the effect of APOE E4 on GSD risk. Future studies with large sample sizes that control for important confounding/risk factors are needed to validate our findings and to explore other genetic loci that might affect GSD risk.
Topics: Apolipoproteins E; Databases, Factual; Gallstones; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Odds Ratio; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 31200656
DOI: 10.1186/s12881-019-0843-6 -
Nutrition Reviews Aug 2023In preclinical Alzheimer's disease (AD), the brain gradually becomes insulin resistant. As a result, brain glucose utilization is compromised, causing a cellular energy... (Meta-Analysis)
Meta-Analysis
CONTEXT
In preclinical Alzheimer's disease (AD), the brain gradually becomes insulin resistant. As a result, brain glucose utilization is compromised, causing a cellular energy deficit that leads to the accumulation of free radicals, which increases inflammation and damages neurons. When glucose utilization is impaired, ketone bodies offer an alternative energy source. Ketone bodies are synthesized from fats, obtained from either the diet or adipose tissue. Dietary medium-chain fatty acids (MCFAs), which are preferentially metabolized into ketone bodies, have the potential to supply the insulin-resistant brain with energy.
OBJECTIVE
This systematic review and meta-analysis aims to review the effect of MCFA supplements on circulating ketone bodies and cognition in individuals with subjective cognitive decline, mild cognitive impairment, and AD.
DATA SOURCES
A comprehensive search of electronic databases was performed on August 12, 2019, to retrieve all publications meeting the inclusion criteria. Alerts were then set to identify any publications after the search date up until January 31, 2021.
DATA EXTRACTION
Data were extracted by 2 authors and assessed by a third. In total, 410 publications were identified, of which 16 (n = 17 studies) met the inclusion criteria.
DATA ANALYSIS
All studies assessing change in levels of blood ketone bodies due to MCFA supplementation (n = 12) reported a significant increase. Cognition outcomes (measured in 13 studies), however, varied, ranging from no improvement (n = 4 studies) to improvement (n = 8 studies) or improvement only in apolipoprotein E allele 4 (APOE ε4) noncarriers (n = 2 studies). One study reported an increase in regional cerebral blood flow in APOE ε4 noncarriers and another reported an increase in energy metabolism in the brain.
CONCLUSION
MCFA supplementation increases circulating ketone body levels, resulting in increased brain energy metabolism. Further research is required to determine whether this MCFA-mediated increase in brain energy metabolism improves cognition.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration number CRD42019146967.
Topics: Humans; Alzheimer Disease; Apolipoprotein E4; Fatty Acids; Ketone Bodies; Insulin; Glucose
PubMed: 36633304
DOI: 10.1093/nutrit/nuac104 -
Journal of Cellular Physiology Jun 2019Aberrant blood vessel functioning and systemic circulation are key causes for vascular disorders; cardiovascular, cerebrovascular, renal artery stenosis, and peripheral... (Meta-Analysis)
Meta-Analysis Review
Aberrant blood vessel functioning and systemic circulation are key causes for vascular disorders; cardiovascular, cerebrovascular, renal artery stenosis, and peripheral artery diseases. Epidemiological and basic science evidence supported genetic reasons, compounded by obesity, hypercholesterolemia, hypertension, diabetes, and smoking as risk factors. This is an umbrella review of risk factors and therapies in vascular disorders, exploring systematic reviews and meta-analyses studies in PubMed, Cochrane, Embase, and Central published in January 2000-May 2018. We made qualitative eligibility gradation of the articles based on inclusion criteria, and independently extracted descriptive and methodologic data to compile their outcomes. We considered 95% confidence interval and the between-study heterogeneity, designated by I . Overall, we extracted 217 studies of impressive quality and at low risk of bias, including 124, 30, 23, 32, and 8, respectively, for the search terms "cardiovascular," "renal," "cerebral," and "limb ischemia" each in combination with "risk factors" and "therapeutics." Our search on genome-wide analyses revealed genes associated with HDL-cholesterol, matrix metalloproteases, angiogenesis, notch3, renin-angiotensin, apolipoprotein E, insulin, and cytokine levels as critical participants in the pathogenesis of vascular diseases. Hypertension and endothelial growth factor-linked polymorphisms were found to contribute to vascular damage. The studies reinforced that lifestyle and dietary patterns influenced susceptibility of circulatory system diseases. Additionally, endovascular medicines, surgical vascularization, angioplasty, and renal artery stenting appeared as major therapeutic approaches in vascular patients. Altogether, our review offers up-to-date information on pathophysiology of vascular diseases and provides insight into existing research, clinical management and clinical gaps in the field.
Topics: Cardiovascular Diseases; Diabetes Complications; Endothelial Growth Factors; Genome-Wide Association Study; Humans; Hypercholesterolemia; Hypertension; Life Style; Obesity; Risk Factors
PubMed: 30317627
DOI: 10.1002/jcp.27633 -
Disease Markers 2022Rising studies indicate that the apolipoprotein E (APOE) gene is related to the susceptibility of ischemic stroke (IS). However, certain consensus is limited by the lack... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Rising studies indicate that the apolipoprotein E (APOE) gene is related to the susceptibility of ischemic stroke (IS). However, certain consensus is limited by the lack of a large sample size of researches. This meta-analysis was performed to explore the potential association between the APOE gene and IS.
METHODS
To identify relevant case control studies in English publications by October 2020, we searched PubMed, Embase, Web of Science, and the Cochrane Library. Pooled odds ratios (ORs) with fixed- or random-effect models and corresponding 95% confidence intervals (CIs) were calculated to analyze potential associations.
RESULTS
A total of 55 researches from 32 countries containing 12207 IS cases and 27742 controls were included. The association between APOE gene 4 mutation and IS was confirmed (4 vs. 3 allele: pooled OR = 1.374, 95% CI, 1.214-1.556; 2/4 vs. 3/3: pooled OR = 1.233, 95% CI, 1.056-1.440; 3/4 vs. 3/3: pooled OR = 1.340, 95% CI, 1.165-1.542; 4/4 vs. 3/3: pooled OR = 1.833, 95% CI, 1.542-2.179; and APOE 4 carriers vs. non-4 carriers: pooled OR = 1.377; 95% CI, 1.203-1.576). Interestingly, APOE 4 mutation showed a dose-response correlation with IS risk (4/4 vs. 2/4: pooled OR = 1.625; 95% CI, 1.281-2.060; 4/4 vs. 3/4: pooled OR = 1.301; 95% CI, 1.077-1.571). Similar conclusions were drawn in the small artery disease (SAD) subtype, but not in large artery atherosclerosis (LAA) or in cardioaortic embolism (CE), by subgroup analysis.
CONCLUSIONS
These observations reveal that specific APOE 4 mutation was significantly associated with the risk of IS in a dose-dependent manner, while APOE 4 mutation was related to SAD subtype onset without a cumulative effect.
Topics: Apolipoprotein E4; Humans; Ischemic Stroke; Polymorphism, Genetic; Risk Factors
PubMed: 35154509
DOI: 10.1155/2022/1407183 -
Journal of Clinical Neuroscience :... Oct 2017Cervical spondylotic myelopathy (CSM) is a degenerative disorder of the neck. Recent studies have reported the roles of single nucleotide polymorphisms and abnormal gene... (Review)
Review
BACKGROUND
Cervical spondylotic myelopathy (CSM) is a degenerative disorder of the neck. Recent studies have reported the roles of single nucleotide polymorphisms and abnormal gene expression in the etiology and development of CSM. However, a systemic review of these findings is currently unavailable.
METHODS
A systemic review of genetic factors of CSM was conducted through searching PubMed and EMbase databases. A total of 9 studies were included in this study, which included 8 genes: brain derived neurotrophic factor (BDNF), osteopontin (OPN), bone morphogenic protein (BMP) 4, collagen IX, vitamin D receptor (VDR), apolipoprotein E (ApoE), hypoxia-inducible factor α (HIF-1α), and cyclooxygenase 2 (COX-2).
RESULTS
The polymorphisms of 6 genes (OPN, BMP-4, collagen IX, VDR, HIF-1α) showed significant association with the susceptibility to or risk of CSM. The polymorphisms of 3 genes (BMP-4, ApoE4, HIF-1α) were significantly associated with the postoperative outcome. The polymorphism of BDNF, VDR, and expression of COX-2 were associated with the severity of disease.
CONCLUSION
This review demonstrates that 8 genes were associated with CSM although there is no repeated study. This review also suggests that large scale and high quality studies are needed to provide more reliable evidence for future evaluation.
Topics: Humans; Apolipoprotein E4; Brain-Derived Neurotrophic Factor; Cyclooxygenase 2; Genetic Predisposition to Disease; Neurosurgical Procedures; Osteopontin; Polymorphism, Single Nucleotide; Postoperative Complications; Receptors, Calcitriol; Spondylosis
PubMed: 28734792
DOI: 10.1016/j.jocn.2017.06.043 -
Current Medical Science Feb 2019Intracerebral hemorrhage (ICH) is a serious clinical disease with high morbidity, whose pathogenesis might be related to apolipoprotein E (APOE) gene polymorphisms. To... (Meta-Analysis)
Meta-Analysis
Intracerebral hemorrhage (ICH) is a serious clinical disease with high morbidity, whose pathogenesis might be related to apolipoprotein E (APOE) gene polymorphisms. To comprehensively evaluate the risk factors for ICH occurrence, we performed a meta-analysis. We searched online databases to identify eligible studies based on the relationship between APOE genetic polymorphisms and ICH occurrence risk. Specific and pooled odds ratios (ORs) were calculated and by assessing small study bias, we drew the relationship between APOE polymorphisms and ICH risk. We included 15 eligible studies in our study containing a total of 1642 ICH samples and 5545 normal controls. The comparison of ɛ4 and ɛ3 APOE genotypes revealed that specific and pooled ORs showed a significantly increased odds ratio in ICH patients with the ɛ4 genotype, indicating that ɛ4 gene is a risk factor for ICH occurrence, and the heterogeneity is acceptable. Similarly, it was found that the ɛ2 genotype also contributed to the incidence rate of ICH. However, after the subgroup analysis by ethnicity, this APOE genetic polymorphism acted as a harmful factor only in white populations, but did not show an effect in Asian populations. It was suggested that both ε2 and ε4 APOE alleles were risk factors for ICH in general. They were risk factors in white populations only, neither had a detectable effect in Asian populations after subgroup analysing by ethnicity.
Topics: Alleles; Apolipoproteins E; Asian People; Cerebral Hemorrhage; Genetic Predisposition to Disease; Genotype; Humans; Incidence; Odds Ratio; Polymorphism, Genetic; Research Design; Risk Factors; White People
PubMed: 30868499
DOI: 10.1007/s11596-019-2007-5