Circulating 25-hydroxy-vitamin D and the risk of cardiovascular diseases. Systematic review and meta-analysis of prospective cohort studies

AimsCirculating vitamin D is linked with the risk of cardiovascular disease (CVD). A meta-analysis has yet to explicitly explore correlation between vitamin D and the risk of CVD incidence and recurrent CVD. This meta-analysis examines the association between 25-hydroxy-vitamin D (25(OH)D) and the risk of CVD incidence (fatal, non-fatal, fatal and non-fatal combined events) and the risk of recurrent CVD (fatal, recurrent, and fatal and recurrent combined events). PROSPERO registration-CRD42021251483.Data synthesisA total of 79 studies (46 713 CVD cases in 1 397 831 participants) were included in the meta-analysis, of which 61 studies examined the risk of CVD incidence events, and 18 studies examined risk of recurrent CVD events. The risk of CVD incidence events (RR = 1.34, 95% CI: 1.26–1.43, p < 0.001) and recurrent CVD events (RR = 1.86, 95% CI: 1.46–2.36, p < 0.001) was higher in the lowest than the highest category of circulating 25(OH)D. Dose–response analysis reported a linear association for every 10 ng/ml increment of 25(OH)D and non-fatal CVD incidence events (RR = 0.94; 95% CI = 0.89–0.98, p = 0.005), lower fatal recurrent CVD events (RR = 0.45; 95% CI = 0.32–0.62, p < 0.001) and lower combined recurrent CVD events (RR = 0.80; 95% CI = 0.65–0.97, p = 0.023). A non-linear association was observed between higher 25(OH)D and lower fatal CVD incidence events (P-nonlinear<0.001), lower combined CVD incidence events (P-nonlinear = 0.001), and lower non-fatal recurrent CVD events (P-nonlinear = 0.044).ConclusionsThe lowest category of circulating 25(OH)D was associated with a higher risk of CVD incidence events and recurrent CVD events.     

Hypocalcemia is associated with severe COVID-19: A systematic review and meta-analysis

Background and aimsHypocalcemia is commonly in critically ill patients and studies have shown that hypocalcemia is prevalent in patients with COVID-19. This meta-analysis aimed to evaluate the prognostic performance of hypocalcemia in patients with coronavirus disease 2019 (COVID-19).MethodsWe performed a systematic literature search on PubMed, Scopus, and Embase with keywords “SARS-CoV-2″ OR″COVID-19″ OR ″2019-nCoV” AND “hypocalcemia” up until 10 December 2020. The key exposure was hypocalcemia, defined as serum calcium below study-defined cut-off points. The main outcome was poor outcome, which was a composite of mortality and severity. The effect estimate of the main outcome was reported as odds ratio (OR) and its 95% confidence interval (95% CI). We also generate sensitivity, specificity, positive and negative likelihood ratio (PLR & NLR), diagnostic odds ratio (DOR), and area under curve (AUC).ResultsThere are 2032 patients from 7 studies included in this systematic review and meta-analysis. The incidence of poor outcome in this study was 26%. Serum calcium was lower in patients with poor outcome (mean difference ?0.173 mmol/L [-0.259, ?0.087], p < 0.001; I²: 31.3%). Hypocalcemia was associated with poor outcome (OR 3.19 [2.02, 5.06], p < 0.001; I²: 32.86%); with sensitivity of 0.74 [0.53, 0.88], specificity of 0.54 [0.29, 0.77], PLR of 1.6 [1.1, 2.3], NLR of 0.49 [0.35, 0.66], DOR of 3 [2, 5], and AUC of 0.70 [0.66, 0.74]. In this pooled analysis, the post-test probability was 36% in patients with hypocalcemia and 15% in patients without hypocalcemia.ConclusionHypocalcemia was associated with poor outcome in COVID-19 patients.PROSPERO ID: CRD42020225506.     

Triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular events in the general population: A systematic review and meta-analysis of cohort studies

AimsThe ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) has been regarded as a novel surrogate indicator of insulin resistance and the atherogenic index of plasma. This meta-analysis aimed to evaluate the association between the TG/HDL-C ratio and the incidence of cardiovascular events in the general population.Data synthesisCohort studies reporting the association between the TG/HDL-C ratio and cardiovascular events in the general population were obtained by a systematic literature search of PubMed, Embase and Web of Science databases until April 11, 2021. 13 cohort studies with a total of 207,515 participants were included in this meta-analysis. In a random-effects model, compared with those with the lowest category of the TG/HDL-C ratio, participants with the highest category were independently associated with a higher risk of cardiovascular events (pooled HR: 1.43, 95%CI: 1.26–1.62, I² = 72.9%). For the presence of publication bias detected by the Egger's test (p = 0.011), correction for publication bias using the trim-and-fill method reduced the HR to 1.26 (95%CI: 1.11–1.44). This result was consistent with the finding of the TG/HDL-C ratio analyzed as a continuous variable (pooled HR per unit increment of the TG/HDL-C ratio: 1.08, 95%CI: 1.04–1.12, I² = 67.0%). Subgroup analyses indicated that population gender, geographical region, duration of follow-up, adjustment for other lipid parameters, adjustment for diabetes and categorical number did not significantly vary the relationship.ConclusionElevated TG/HDL-C ratio may be independently associated with an increased risk of cardiovascular events in the general population. More well-designed studies are needed to confirm the current findings.Registration number in PROSPEROCRD42021244583.     

Comparative effectiveness of devices for transcatheter closure of atrial septal defects: Systematic review and network meta-analysis

Atrial septal defect is a common congenital heart disease, producing a left-to-right shunt in the atrial septum; the current preferred treatment is transcatheter device closure. The aim is to conduct a systematic review to synthesize information on the comparative effectiveness and safety of atrial septal defect closure devices. The methods used: a comprehensive search of Ovid MEDLINE®, Embase, and Cochrane Central databases was conducted. Studies comparing procedural and follow-up outcomes of atrial septal defect devices were included. Network meta-analyses were conducted to generate direct and indirect evidence for comparative effectiveness and safety outcomes between devices. The results are as follows: Twelve studies met our inclusion criteria and were compared in network meta-analyses. The meta-analyses evaluated contemporary devices: the AMPLATZER Septal Occluder; the GORE CARDIOFORM Septal Occluder; the Figulla Flexible II Occluder; the CeraFlex Septal Occluder; and the HELEX Septal Occluder. These studies represented 3998 patients. The primary safety and efficacy outcomes were device embolization and follow-up residual shunt, respectively. Secondary clinical outcomes included procedural success and major and minor complications. No differences were found between devices in terms of device embolization and secondary clinical outcomes. Follow-up residual shunt was higher with the HELEX Septal Occluder compared with the AMPLATZER Septal Occluder (odds ratio 2.92, 95% confidence interval 1.12–7.61). To conclude: although most outcomes were similar between devices, evidence was largely based on observational low-quality studies. There were inconsistencies in outcome reporting and definitions; this merits future studies, with head-to-head device comparisons and standardization of outcomes.     

A systematic review and meta-analysis of the COVID-19 associated liver injury

Introduction and ObjectivesThe novel coronavirus disease 2019 (COVID-19) has affected more than 5 million people globally. Data on the prevalence and degree of COVID-19 associated liver injury among patients with COVID-19 remain limited. We conducted a systematic review and meta-analysis to assess the prevalence and degree of liver injury between patients with severe and non-severe COVID-19.MethodsWe performed a systematic search of three electronic databases (PubMed/MEDLINE, EMBASE and Cochrane Library), from inception to 24^th April 2020. We included all adult human studies (>20 subjects) regardless of language, region or publication date or status. We assessed the pooled odds ratio (OR), mean difference (MD) and 95% confidence interval (95%CI) using the random-effects model.ResultsAmong 1543 citations, there were 24 studies (5961 subjects) which fulfilled our inclusion criteria. The pooled odds ratio for elevated ALT (OR = 2.5, 95%CI: 1.6-3.7, I² = 57%), AST (OR = 3.4, 95%CI: 2.3-5.0, I² = 56%), hyperbilirubinemia (OR = 1.7, 95%CI: 1.2-2.5, I² = 0%) and hypoalbuminemia (OR = 7.1, 95%CI: 2.1-24.1, I² = 71%) were higher subjects in critical COVID-19.ConclusionCOVID-19 associated liver injury is more common in severe COVID-19 than non-severe COVID-19. Physicians should be aware of possible progression to severe disease in subjects with COVID-19-associated liver injury.     

Intake of legumes and cardiovascular disease: A systematic review and dose–response meta-analysis

AimsTo summarize the evidence on the association between the intake of legumes and the risk of cardiovascular disease (CVD) overall, coronary heart disease (CHD) and stroke, and to identify optimal intake levels for reduced disease risk through a systematic review and dose–response meta-analysis.Data synthesisWe have systematically searched PubMed, Scopus and Web of Science up to March, 2022 for the retrieval of intervention and observational studies (PROSPERO Reg. number: CRD42021247565). Pooled relative risks (RRs) comparing extreme categories of intake were computed using random-effects models. One-stage dose–response meta-analyses were also performed using random-effects models. 22 831 articles were screened resulting in 26 eligible observational studies (21 prospective cohort and 5 case–control studies). When comparing extreme categories of intake, the consumption of legumes was inversely associated with CVD (n = 25: RR = 0.94; 95%CI:0.89,0.99) and CHD (n = 16: RR = 0.90; 95%CI:0.85,0.96), but not with stroke (n = 9: RR = 1.00; 95%CI:0.93,1.08). We further found evidence for an inverse dose–response association with CHD, increasing in magnitude up to an intake of 400 g/week, after which the benefit seems to level-off.ConclusionsThe intake of legumes was associated with a reduced risk of CVD and CHD, but not with stroke, among individuals with the highest consumption levels. An intake level of 400 g/week seemed to provide the optimal cardiovascular benefit. Further research is needed to better understand the role of legumes in stroke subtypes.     

Granulocyte-colony stimulating factor in acute-on-chronic liver failure: Systematic review and meta-analysis of randomized controlled trials

Background and aimsA dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF.MethodsSystematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60–90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator.ResultsThe initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I² = 74%, Chi² = 11.57, p = 0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio = 0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio = 0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF.ConclusionIn a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF. The beneficial effects observed in Asian studies, as opposed to the European region, suggest that specific populations may benefit from further research aiming to identify certain subgroups with favourable outcomes when using G-CSF.     

Coffee consumption and cardiovascular diseases and mortality in patients with type 2 diabetes: A systematic review and dose–response meta-analysis of cohort studies

AimsTo evaluate the long-term consequences of coffee drinking in patients with type 2 diabetes.Data synthesisPubMed, Scopus, and Web of Sciences were searched to November 2020 for prospective cohort studies evaluating the association of coffee drinking with risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. Two reviewers extracted data and rated the certainty of evidence using GRADE approach. Random-effects models were used to estimate the hazard ratios (HRs) and 95% CIs. Dose–response associations were modeled by a one-stage mixed-effects meta-analysis. Ten prospective cohort studies with 82,270 cases were included. Compared to those with no coffee consumption, the HRs for consumption of 4 cups/d were 0.79 (95%CI: 0.72, 0.87; n = 10 studies) for all-cause mortality, 0.60 (95%CI: 0.46, 0.79; n = 4) for CVD mortality, 0.68 (95%CI: 0.51, 0.91; n = 3) for coronary heart disease (CHD) mortality, 0.72 (95%CI: 0.54, 0.98; n = 2) for CHD, and 0.77 (95%CI: 0.61, 0.98; n = 2) for total CVD events. There was no significant association for cancer mortality and stroke. There was an inverse monotonic association between coffee drinking and all-cause and CVD mortality, and inverse linear association for CHD and total CVD events. The certainty of evidence was graded moderate for all-cause mortality, and low or very low for other outcomes.ConclusionsDrinking coffee may be inversely associated with the risk of mortality in patients with type 2 diabetes. However, more research is needed considering type of coffee, sugar and cream added to coffee, and history of CVD to present more confident results.Registry and registry numberThe protocol of this systematic review was registered at Open Science Framework (https://osf.io/8uaf3, registered form: osf.io/xur76, registration DOI: 10.17605/OSF.IO/8UAF3).     

Mesenteric panniculitis is associated with cardiovascular risk-factors: A case-control study

BackgroundThis study evaluated the prevalence of cardiovascular risk-factors in patients with mesenteric panniculitis.AimsTo determine whether cardiovascular risk-factors and mesenteric panniculitis are associated.MethodsRetrospective, matched case-control study of patients referred to Meir Medical Center, Israel, 2014–2019, who underwent computerized tomography scan, were diagnosed mesenteric panniculitis by radiologic criteria. They were compared to two, matched case-control groups: hospitalized patients without mesenteric panniculitis and the general population based on Israeli Ministry of Health surveys. Patients with active malignancy, IBD or significant intra-abdominal morbidity were excluded.ResultsOf 376 patients with mesenteric panniculitis diagnosed by computerized tomography, 187 were included. Compared to hospital patients, they had higher incidence of dyslipidemia (77.5%/56.7%), hypertension (52.4%/40.6%), obesity (body mass index>30) (60.4%/30.5%) and nonalcoholic fatty liver disease (42.2%/16.6%). Similar differences were observed compared to the general population. In multivariable logistic regression, dyslipidemia, obesity, and nonalcoholic fatty liver disease were independent predictors for mesenteric panniculitis.ConclusionsPatients with mesenteric panniculitis have more cardiovascular risk-factors compared to a case-control group and to the general population. This suggests that mesenteric panniculitis is clinically significant and may be part of the metabolic morbidity burden. This association should be further explored.     

Physiologically increased total bilirubin is associated with reduced risk of first myocardial infarction: A meta-analysis and dose-response analysis

AimBilirubin has potential predictive and prognostic value for myocardial infarction (MI), but the clinical evidence remains controversial. We performed this meta-analysis to systematically quantify the relationships between circulating bilirubin levels and the incidence of MI and post–MI adverse events.Data synthesisWe searched the PubMed, Cochrane Library, Embase, and Web of Science databases for ad-hoc studies, published up to October 17, 2020, recording bilirubin before MI (predictive analyses) or adverse events (prognostic analyses). Relative risks (RR) were pooled by a random-effects model. The dose-response analysis was conducted by restricted cubic splines. In patients without previous MI, increased total bilirubin (TB) reduced the risk of long-term (>3 year) first MI by 22% (95% confidence interval [CI]: 0.69–0.88, n = 4). The dose-response analysis indicated that the RR for first MI decreased by 2.7% per each 2 μmol/L increment of TB (three studies, 95% CI: 1.3%–4.1%, P < 0.001), with a cut-off value of 12.60 μmol/L for RR > 1.00. Elevated bilirubin reduced the incidence of first and recurrent MI by 36% (95% CI: 0.42–0.98, n = 7). However, after suffering MI, higher TB concentrations could not decrease the risk of recurrent MI (RR: 1.02, 95% CI: 0.67–1.55, n = 5) and increased the incidence of short-term (<1 year) post–MI major adverse cardiovascular events, all-cause mortality, and cardiovascular mortality, but not long-term (≥1 year).ConclusionHigher TB levels within a physiological range reduced the incidence of long-term first MI, with a cut-off value of 12.60 μmol/L.     

High triglyceride-glucose index is associated with adverse cardiovascular outcomes in patients with acute myocardial infarction

Background and aimsTriglyceride glucose (TyG) index is considered a new surrogate marker of insulin resistance that associated with the development of vascular disease. The aim of this study was to evaluate the prognostic value of TyG index in patients with acute myocardial infarction (AMI).Methods and resultsA total of 3181 patients with AMI were included in the analysis. Patients were stratified into 2 groups according to their TyG index levels: the TyG index <8.88 group and the TyG index ≥8.88 group. The incidence of major adverse cardiovascular events (MACEs) during a median of 33.3-month follow-up were recorded. Multivariable Cox regression models revealed that the TyG index was positively associated with all-cause death [HR (95% CI): 1.51 (1.10,2.06), p = 0.010], cardiac death [HR (95% CI): 1.68 (1.19,2.38), p = 0.004], revascularization [HR (95% CI): 1.50 (1.16,1.94), p = 0.002], cardiac rehospitalization [HR (95% CI): 1.25 (1.05,1.49), p = 0.012], and composite MACEs [HR (95% CI): 1.19 (1.01,1.41), p = 0.046] in patients with AMI. The independent predictive effect of TyG index on composite MACEs was mainly reflected in the subgroups of male gender and smoker. The area under the curve (AUC) of the TyG index predicting the occurrence of MACEs in AMI patients was 0.602 [95% CI 0.580,0.623; p < 0.001].ConclusionHigh TyG index levels appeared to be associated with an increased risk of MACEs in patients with AMI. The TyG index might be a valid predictor of cardiovascular outcomes of patients with AMI.Trial registrationRetrospectively registered.     

Clonal haematopoiesis and cardiovascular diseases: A growing relationship

Central illustration. Clonal haematopoiesis of indeterminate potential (CHIP) occurs particularly in the elderly; it is the result of an acquired mutation occurring in a population of haematopoietic stem cells, conferring a growth advantage to their progeny. Because of the pro-inflammatory phenotype, it favours atherothrombosis, leading to coronary artery diseases such as myocardial infarction, and is also associated with heart failure (ischaemic and non-ischaemic), as well as aortic stenosis, altering the prognosis of CHIP carriers.

     

Underwater versus conventional EMR for colorectal polyps: systematic review and meta-analysis

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