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Relationship Between Glycated Hemoglobin and Stroke Risk: A Systematic Review and Meta-Analysis.

ABSTRACT: BACKGROUND:Diabetes mellitus is a major risk factor for ischemic stroke. Rising hemoglobin A1c (HbA1c) levels are associated with microvascular diabetes mellitus complication development; however, this relationship has not been established for stroke risk, a macrovascular complication. METHODS AND RESULTS:We conducted a systematic review and meta-analysis of observational cohort and nested case-control cohort studies assessing the association between rising HbA1c levels and stroke risk in adults (?18 years old) with and without type 1 or type 2 diabetes mellitus. Random-effects model meta-analyses were used to calculate pooled adjusted hazard ratios (HRs) and their precision. The systematic review yielded 36 articles, of which 29 articles (comprising n=532 779 participants) were included in our meta-analysis. Compared to non-diabetes mellitus range HbA1c (<5.7%), diabetes mellitus range HbA1c (?6.5%) was associated with an increased risk of first-ever stroke with average HR (95% confidence interval) of 2.15 (1.76, 2.63), whereas pre-diabetes mellitus range HbA1c (5.7-6.5%) was not (average HR [95% confidence interval], 1.19 [0.87, 1.62]). For every 1% HbA1c increment (or equivalent), the average HR (95% confidence interval) for first-ever stroke was 1.12 (0.91, 1.39) in non-diabetes mellitus cohorts and 1.17 (1.09, 1.25) in diabetes mellitus cohorts. For every 1% HbA1c increment, both non-diabetes mellitus and diabetes mellitus cohorts had a higher associated risk of first-ever ischemic stroke with average HR (95% confidence interval) of 1.49 (1.32, 1.69) and 1.24 (1.11, 1.39), respectively. CONCLUSIONS:A rising HbA1c level is associated with increased first-ever stroke risk in cohorts with a diabetes mellitus diagnosis and increased risk of first-ever ischemic stroke in non-diabetes mellitus cohorts. These findings suggest that more intensive HbA1c glycemic control targets may be required for optimal ischemic stroke prevention.

SUBMITTER: Mitsios JP

PROVIDER: S-EPMC6015363 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Relationship Between Glycated Hemoglobin and Stroke Risk: A Systematic Review and Meta-Analysis.

Mitsios John Peter JP Ekinci Elif Ilhan EI Mitsios Gregory Peter GP Churilov Leonid L Thijs Vincent V

Journal of the American Heart Association 20180517 11

<h4>Background</h4>Diabetes mellitus is a major risk factor for ischemic stroke. Rising hemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>) levels are associated with microvascular diabetes mellitus complication development; however, this relationship has not been established for stroke risk, a macrovascular complication.<h4>Methods and results</h4>We conducted a systematic review and meta-analysis of observational cohort and nested case-control cohort studies assessing the association between rising H ...[more]

PMID: 29773578

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Project description:ObjectiveThere is widespread agreement about the key role of hemoglobin for oxygen transport. Both observational and interventional studies have examined the relationship between hemoglobin levels and maximal oxygen uptake ([Formula: see text]) in humans. However, there exists considerable variability in the scientific literature regarding the potential relationship between hemoglobin and [Formula: see text]. Thus, we aimed to provide a comprehensive analysis of the diverse literature and examine the relationship between hemoglobin levels (hemoglobin concentration and mass) and [Formula: see text] (absolute and relative [Formula: see text]) among both observational and interventional studies.MethodsA systematic search was performed on December 6th, 2021. The study procedures and reporting of findings followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Article selection and data abstraction were performed in duplicate by two independent reviewers. Primary outcomes were hemoglobin levels and [Formula: see text] values (absolute and relative). For observational studies, meta-regression models were performed to examine the relationship between hemoglobin levels and [Formula: see text] values. For interventional studies, meta-analysis models were performed to determine the change in [Formula: see text] values (standard paired difference) associated with interventions designed to modify hemoglobin levels or [Formula: see text]. Meta-regression models were then performed to determine the relationship between a change in hemoglobin levels and the change in [Formula: see text] values.ResultsData from 384 studies (226 observational studies and 158 interventional studies) were examined. For observational data, there was a positive association between absolute [Formula: see text] and hemoglobin levels (hemoglobin concentration, hemoglobin mass, and hematocrit (P<0.001 for all)). Prespecified subgroup analyses demonstrated no apparent sex-related differences among these relationships. For interventional data, there was a positive association between the change of absolute [Formula: see text] (standard paired difference) and the change in hemoglobin levels (hemoglobin concentration (P<0.0001) and hemoglobin mass (P = 0.006)).ConclusionThese findings suggest that [Formula: see text] values are closely associated with hemoglobin levels among both observational and interventional studies. Although our findings suggest a lack of sex differences in these relationships, there were limited studies incorporating females or stratifying results by biological sex.

Project description:Background: Glycated hemoglobin (HbA1c) has emerged as a useful biochemical marker reflecting the average glycemic control over the last 3 months, and the values are not affected by short-term transient changes in blood glucose levels. However, its prognostic value in the acute neurological conditions such as stroke is still not well-established. The present meta-analysis was conducted to assess the relationship of HbA1c with outcomes such as mortality, early neurological complications, and functional dependence in stroke patients. Methods: A systematic search was conducted for the PubMed, Scopus, and Google Scholar databases. Studies, either retrospective or prospective in design that examined the relationship between HbA1c with outcomes of interest and presented the strength of association in the form of adjusted odds ratio/hazard ratios were included in the review. Statistical analysis was done using STATA version 13.0. Results: A total of 22 studies (15 studies on acute ischemic stroke and seven studies on hemorrhagic stroke) were included in the meta-analysis. For patients with acute ischemic stroke, each unit increase in HbA1c was found to be associated with an increased risk of mortality within 1 year, increased risk of poor functional outcome at 3 months, and an increased risk of symptomatic intracranial hemorrhage (sICH) within 24 h of admission. In those with HbA1c ≥ 6.5%, there was an increased risk of mortality within 1 year of admission, increased risk of poor functional outcomes at 3 and 12 months as well as an increased risk of symptomatic intracranial hemorrhage (sICH) within 24 h of admission. In patients with hemorrhagic stroke, each unit increase in HbA1c was found to be associated with increased risk of poor functional outcome within the first 3 months from the time of admission for stroke. In those with HbA1c ≥ 6.5%, there was an increased risk of poor functional outcome at 12 months. Conclusions: The findings indicate that glycated hemoglobin (HbA1c) could serve as a useful marker to predict the outcomes in patients with stroke and aid in the implementation of adequate preventive management strategies at the earliest.

Project description:Background and aimGlycated hemoglobin (HbA1c) is a long-term measure of glucose control. Although recent studies demonstrated a potential association between HbA1c levels and the risk of atrial fibrillation (AF), the results have been inconsistent. The aim of this meta-analysis is to evaluate the utility of HbA1c level in predicting AF.MethodsPubMed and the Cochrane Library databases were searched for relevant studies up to March 2016. Prospective cohort studies and retrospective case-control studies were included. Relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs) of AF development were determined for different HbA1c levels. The random effect model was conducted according to the test of heterogeneity among studies. Subgroup analyses and meta-regression models were carried out to identify potential sources of heterogeneity.ResultsEight prospective cohort studies with 102,006 participants and 6 retrospective case-control studies with 57,669 patients were finally included in the meta-analysis. In the primary meta-analysis, HbA1c levels were not associated with an increased risk of AF whether as a continuous (RR, 1.06; 95% CI, 0.96-1.18) or categorical variable (RR, 0.99; 95% CI, 0.83-1.18). Nevertheless, prospective studies showed about 10% increased risk of AF with elevated HbA1c levels both as a continuous (RR, 1.11; 95% CI, 1.06-1.16) and as a categorical variable (RR, 1.09; 95% CI, 1.00-1.18). In subgroup analyses, pooled results from studies with longer follow-up durations, published after 2012, aged < 63 years, with exclusion of cardiac surgery patients demonstrated an increased risk of AF for every 1% increase in HbA1c levels, while studies conducted in the United States with longer follow-up (more than 96 months), larger sample size and higher quality score (≥6) showed an increased risk of AF for higher HbA1c level as a categorical variable.ConclusionsElevated serum HbA1c levels may be associated with an increased risk of AF, but further data are needed. Serum HbA1c levels might be considered as a potential biomarker for prediction of AF.

Project description:Background and Objectives:Cardiovascular disease (CVD) is a leading cause of death among military veterans with several reports suggesting a link between combat and related traumatic injury (TI) to an increased CVD risk. The aim of this paper is to conduct a widespread systematic review and meta-analysis of the relationship between military combat?±?TI to CVD and its associated risk factors. Methods:PubMed, EmbaseProQuest, Cinahl databases and Cochrane Reviews were examined for all published observational studies (any language) reporting on CVD risk and outcomes, following military combat exposure?±?TI versus a comparative nonexposed control population. Two investigators independently extracted data. Data quality was rated and rated using the 20-item AXIS Critical Appraisal Tool. The risk of bias (ROB using the ROBANS 6 item tool) and strength of evidence (SOE) were also critically appraised. Results:From 4499 citations, 26 studies (14 cross sectional and 12 cohort; 78-100% male) met the inclusion criteria. The follow up period ranged from 1 to 43.6 years with a sample size ranging from 19 to 621901 participants in the combat group. Combat-related TI was associated with a significantly increased risk for CVD (RR 1.80: 95% CI 1.24-2.62; I 2 = 59%, p = 0.002) and coronary heart disease (CHD)-related death (risk ratio 1.57: 95% CI 1.35-1.83; I 2 = 0%, p = 0.77: p < 0.0001), although the SOE was low. Military combat (without TI) was linked to a marginal, yet significantly lower pooled risk (low SOE) of cardiovascular death in the active combat versus control population (RR 0.90: CI 0.83-0.98; I 2 = 47%, p = 0.02). There was insufficient evidence linking combat?±?TI to any other cardiovascular outcomes or risk factors. Conclusion:There is low SOE to support a link between combat-related TI and both cardiovascular and CHD-related mortality. There is insufficient evidence to support a positive association between military combat?±?any other adverse cardiovascular outcomes or risk factors. Data from well conducted prospective cohort studies following combat are needed.

Project description:BackgroundMicrosomal epoxide hydrolase (EPHX1) plays an important role in both the activation and detoxification of PAHs, which are carcinogens found in cooked meat and tobacco smoking. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to quantitatively summarize the relationship between EPHX1 polymorphisms and colorectal cancer (CRC) risk.MethodsTwo investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before June 2012. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for EPHX1 Tyr113His (rs1051740) and His139Arg (rs2234922) polymorphisms and CRC were calculated in a fixed-effects model and a random-effects model when appropriate.ResultsThis meta-analysis yielded 14 case-control studies, which included 13 studies for Tyr113His (6395 cases and 7893 controls) and 13 studies for His139Arg polymorphisms (5375 cases and 6962 controls). Overall, the pooled results indicated that EPHX1 Tyr113His polymorphism was not associated with CRC risk; while the His139Arg polymorphism was significantly associated with decreased CRC risk (Arg/His vs. His/His, OR = 0.90, 95%CI = 0.83-0.98; dominant model, OR = 0.92, 95%CI = 0.85-0.99). The statistically significant association between EPHX1 His139Arg polymorphism and CRC was observed among Caucasians and population-based case-control studies. This association showed little heterogeneity and remained consistently strong when analyses were limited to studies in which genotype frequencies were in Hardy-Weinberg equilibrium, or limited to studies with matched controls. When cumulative meta-analyses of the two associations were conducted by studies' publication time, the results were persistent and robust.ConclusionThis meta-analysis suggests that EPHX1 Tyr113His polymorphism may be not associated with CRC development; while the EPHX1 His139Arg polymorphism may have a potential protective effect on CRC.

Dataset Information

Relationship Between Glycated Hemoglobin and Stroke Risk: A Systematic Review and Meta-Analysis.

Publications

Relationship Between Glycated Hemoglobin and Stroke Risk: A Systematic Review and Meta-Analysis.

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