scholarly journals Elevated Osteoprotegerin Concentration Predicts Increased Risk of Cardiovascular Mortality in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 45 (4) ◽  
pp. 565-575
Author(s):  
Qing-xiu Huang ◽  
Jian-bo Li ◽  
Naya Huang ◽  
Xiao-wen Huang ◽  
Yan-lin Li ◽  
...  

Introduction: Studies have shown inconsistent results regarding the association between osteoprotegerin (OPG) concentration and cardiovascular mortality in patients with chronic kidney disease (CKD). This systematic review and meta-analysis aims to investigate the association between OPG concentration and cardiovascular mortality in patients with CKD. Methods: Between January 1970 and February 2020, the PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies investigating the association between OPG concentration and cardiovascular mortality in patients with CKD. Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated using random effects models. Results: In total, 10 studies comprising 2,120 patients (including 1,723 receiving dialysis) with CKD were included. The included studies were considered to be of fair to high quality. Patients in the highest OPG concentration group had a significantly higher risk of cardiovascular mortality (4 studies; adjusted HR, 2.05; 95% CI, 1.39–3.00) than patients in the low OPG concentration group. An increase of 1 pmol/L in OPG concentration was associated with a 4% increased risk of cardiovascular mortality (6 studies; adjusted HR, 1.04; 95% CI, 1.02–1.07). Conclusion: Elevated OPG concentrations are associated with an increased risk of cardiovascular death in patients with CKD.

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254554
Author(s):  
Sultana Shajahan ◽  
Janaki Amin ◽  
Jacqueline K. Phillips ◽  
Cara M. Hildreth

Chronic kidney disease (CKD) is a significant health challenge associated with high cardiovascular mortality risk. Historically, cardiovascular mortality risk has been found to higher in men than women in the general population. However, recent research has highlighted that this risk may be similar or even higher in women than men in the CKD population. To address the inconclusive and inconsistent evidence regarding this relationship between sex and cardiovascular mortality within CKD patients, a systematic review and meta-analysis of articles published between January 2004 and October 2020 using PubMed/Medline, EMBASE, Scopus and Cochrane databases was performed. Forty-eight studies were included that reported cardiovascular mortality among adult men relative to women with 95% confidence intervals (CI) or provided sufficient data to calculate risk estimates (RE). Random effects meta-analysis of reported and calculated estimates revealed that male sex was associated with elevated cardiovascular mortality in CKD patients (RE 1.13, CI 1.03–1.25). Subsequent subgroup analyses indicated higher risk in men in studies based in the USA and in men receiving haemodialysis or with non-dialysis-dependent CKD. Though men showed overall higher cardiovascular mortality risk than women, the increased risk was marginal, and appropriate risk awareness is necessary for both sexes with CKD. Further research is needed to understand the impact of treatment modality and geographical distribution on sex differences in cardiovascular mortality in CKD.


2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Einat Gorelik ◽  
Reem Masarwa ◽  
Amichai Perlman ◽  
Victoria Rotshild ◽  
Mordechai Muszkat ◽  
...  

ABSTRACT Studies reporting an increased risk for cardiac toxicities with macrolide antibiotics have raised concern regarding their cardiovascular safety. We sought to assess the cardiac safety of macrolide antibiotics as a class and of the individual agents by conducting a systematic review and network meta-analysis. Medline, Embase, and the Cochrane Library were searched up to February 2018 for studies reporting on cardiovascular outcomes with macrolides. We followed the PRISMA 2009 guidelines for data selection and extraction. Outcomes were pooled using random-effects models and odds ratios (OR), and 95% confidence intervals (CI) were calculated for arrhythmia, cardiovascular death, and myocardial infarction (MI). A total of 33 studies and data on 22,601,032 subjects were retrieved and included in the current meta-analyses. Macrolide use was not associated with the risk of arrhythmia or cardiovascular mortality. In the primary analysis, macrolide use was associated with a small but statistically significant 15% increase in risk for MI (OR = 1.15 [95% CI, 1.01 to 1.30]). In indirect network meta-analysis, erythromycin and clarithromycin were ranked considerably more likely to be associated with a higher risk for MI and significantly associated with increased risk of MI compared to azithromycin (OR = 1.58 [95% CI, 1.18 to 2.11] and OR = 1.41 [95% CI, 1.11 to 1.81], respectively). Our findings indicate that macrolide antibiotics as a group are associated with a significant risk for MI but not for arrhythmia and cardiovascular mortality. Among the macrolides, erythromycin and clarithromycin were associated with a greater risk of MI. However, it is possible that the association between macrolide use and risk of MI is the result of residual confounding.


2021 ◽  
pp. 1-9
Author(s):  
Jialing Zhang ◽  
Xiangxue Lu ◽  
Han Li ◽  
Shixiang Wang

Background: Existing studies suggested conflicting relationships between serum uric acid (SUA) and mortality in CKD patients. The present meta-analysis aimed to determine whether SUA can be a predictor for mortality in CKD cohorts. Method: A systematical search was conducted on PubMed, EMBASE, and The Cochrane Library to identify studies reporting the relationship between SUA level and all-cause and cardiovascular mortality in CKD populations. In addition, random-effects models were adopted to calculate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Results: On the whole, 29 studies were involved. In the present meta-analysis, patients exhibiting the maximum SUA level showed an association with a significantly higher risk for all-cause mortality (HR, 1.30; 95% CI, 1.06–1.59) compared with patients exhibiting the minimum SUA level. As revealed from the meta-analysis of 8 studies, low level of SUA was another predictor for all-cause mortality in patients with CKD (HR, 1.36; 95% CI, 1.20–1.54). No significant relationship was identified between SUA and cardiovascular mortality. Conclusions: Higher and lower SUA levels are both associated with significantly increased risk of all-cause mortality in patients with CKD. A appreciate dose of treatment of lowering SUA agents should be confirmed.


2021 ◽  
pp. 174749302110042
Author(s):  
Grace Mary Turner ◽  
Christel McMullan ◽  
Olalekan Lee Aiyegbusi ◽  
Danai Bem ◽  
Tom Marshall ◽  
...  

Aims To investigate the association between TBI and stroke risk. Summary of review We undertook a systematic review of MEDLINE, EMBASE, CINAHL, and The Cochrane Library from inception to 4th December 2020. We used random-effects meta-analysis to pool hazard ratios (HR) for studies which reported stroke risk post-TBI compared to controls. Searches identified 10,501 records; 58 full texts were assessed for eligibility and 18 met the inclusion criteria. The review included a large sample size of 2,606,379 participants from four countries. Six studies included a non-TBI control group, all found TBI patients had significantly increased risk of stroke compared to controls (pooled HR 1.86; 95% CI 1.46-2.37). Findings suggest stroke risk may be highest in the first four months post-TBI, but remains significant up to five years post-TBI. TBI appears to be associated with increased stroke risk regardless of severity or subtype of TBI. There was some evidence to suggest an association between reduced stroke risk post-TBI and Vitamin K antagonists and statins, but increased stroke risk with certain classes of antidepressants. Conclusion TBI is an independent risk factor for stroke, regardless of TBI severity or type. Post-TBI review and management of risk factors for stroke may be warranted.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Takeshi Hasegawa ◽  
Hiroki Nihiwaki ◽  
Erika Ota ◽  
William Levack ◽  
Hisashi Noma

Abstract Background and Aims Patients with chronic kidney disease (CKD) undergoing dialysis are at a particularly high risk of cardiovascular mortality and morbidity. This systematic review and meta-analysis aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in patients with CKD requiring haemodialysis or peritoneal dialysis. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 29 July 2019 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. We included individual and cluster randomised controlled trials (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with placebo or standard care in patients with CKD requiring dialysis. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I2 statistic to measure heterogeneity among the trials in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Results We included 16 trials (14 parallel RCTs and two cross-over trials) involving a total of 1,446 patients. Among included studies, 13 trials compared spironolactone to placebo or standard care and one trial compared eplerenone to a placebo. Most studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials, 1,119 patients: RR 0.45, 95% CI 0.30 to 0.67; moderate certainty of evidence). Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6 trials, 908 patients: RR 0.37, 95% CI 0.22 to 0.64; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 trials, 328 patients: RR 0.38, 95% CI 0.18 to 0.76; moderate certainty of evidence). While aldosterone antagonists had an apparent increased risk of gynaecomastia compared with control (4 trials, 768 patients: RR 5.95, 95% CI 1.93 to 18.3; moderate certainty of evidence), the elevated risk of hyperkalaemia due to aldosterone antagonists was uncertain (9 trials, 981 patients: RR 1.41, 95% CI 0.72 to 2.78; low certainty of evidence). Conclusion Based on moderate certainty of the evidence, aldosterone antagonists could reduce the risk of all-cause and cardiovascular death and morbidity due to cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in patients with CKD requiring dialysis.


2021 ◽  
Author(s):  
Kevin C. Maki ◽  
Meredith L. Wilcox ◽  
Mary R. Dicklin ◽  
Rahul Kakkar ◽  
Michael H. Davidson

Abstract Background Cardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD. Methods The primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥ 12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined. Results The meta-analysis included 38 trials with duration ≥ 12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 8 of other types of interventions. All-cause mortality was reported in 116/2385 (4.86%) subjects in intervention groups and 161/2404 (6.70%) subjects in control groups. The pooled RR estimate of the 24 trials ≥ 12 months with ≥ 1 event in ≥ 1 group was 0.72 (95% CI 0.57 to 0.91, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥ 6 months (31 trials), ≥ 9 months (26 trials), and > 12 months (9 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.66, 95% CI 0.38 to 1.15. Conclusions These results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dev Jegatheesan ◽  
Richard Modderman ◽  
Rathika Krishnasamy ◽  
Allison Tong ◽  
Jeff Coombes ◽  
...  

Abstract Background and Aims Impaired physical fitness is prevalent across the spectrum of kidney disease and is associated with an increased risk of mortality, progression to end-stage kidney disease, falls and hospitalisation. Physical fitness outcomes have been extensively reported in randomised trials involving patients with kidney disease. This study aimed to assess the scope and consistency of physical fitness outcomes and outcome measures reported in kidney disease trials. Method A systematic review of randomised trials reporting physical fitness outcomes in adults with chronic kidney disease not requiring kidney replacement therapy, receiving maintenance haemodialysis or peritoneal dialysis, and kidney transplant recipients was conducted. The scope, frequency and characteristics of physical fitness outcome measures were categorised and analysed. Trials were identified from MEDLINE, Embase and the Cochrane Library from March 2000 to March 2019. Results From 115 relevant trials, 171 outcome measures for 32 outcomes were identified and categorised into five domains of physical fitness: exercise capacity (reported in 83% of trials), physiological-metabolic (57%), neuromuscular fitness (52%), body composition (45%) and cardiorespiratory fitness (19%). Exercise capacity had 53 different outcome measures and at 15 separate time points. The most common outcome measures were the 6-minute walk test (29%), peak oxygen uptake (20%), 1-repetition maximum (19%) and hand-grip strength (11%), with marked inconsistency in the reporting of outcomes between trials. Outcomes were assessed by field-based tests (65%), lab-based tests (31%) and patient-reported measures (4%). Conclusion There is large heterogeneity in the reporting of physical fitness outcomes, with inconsistencies in the use of validated, relevant and patient-important outcome measures.


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