C-X-C Motif Chemokine Ligand 16 Is a Potent Predictor of Outcomes in Dialysis Patients

2021 ◽  
pp. 1-10
Author(s):  
Wenjin Liu ◽  
Lulu Wang ◽  
Xiurong Li ◽  
Chaoqing Gao ◽  
Jianmei Zhou ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Cardiovascular Events ◽  
Inflammatory Marker ◽  
Adverse Outcomes ◽  
Categorical Variables ◽  
Major Adverse Cardiovascular Events ◽  
Dialysis Patients ◽  
Potent Predictor ◽  
All Cause Mortality ◽  
Chemokine Ligand

<b><i>Introduction:</i></b> C-X-C motif chemokine ligand 16 (CXCL16) is an inflammatory marker that has been found to be predictive of outcomes in patients with cardiovascular disease. Our previous work has also demonstrated its relation to cardiac injury in dialysis patients. However, it is yet unclear whether there is an association between CXCL16 and adverse outcomes in dialysis patients. We aimed to evaluate its prognostic value along with several traditional inflammatory markers in the current study. <b><i>Methods:</i></b> This is a multicenter longitudinal study of prevalent dialysis patients. Circulating inflammatory markers including CXCL16, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 (IL-6) were measured using a multiplex assay. The primary outcomes were all-cause mortality and a composite of major adverse cardiovascular events (MACEs). The associations between biomarkers and outcomes were analyzed using Cox proportional hazards regression models. <b><i>Results:</i></b> Of the 366 participants with available plasma samples, the average age was 52.5 (±12.1) years, and there were 160 (43.7%) female participants. For all-cause mortality, logarithmically transformed CXCL16, IL-6, and CRP were independent predictors after adjustment for covariates. When the 3 markers were included in the same model, CXCL16 was the only one remaining its significance. For MACEs, logarithmically transformed CXCL16 and IL-6 were significant predictors when analyzed separately and CXCL16 was an independent predictor even after adjustment for IL-6. When the biomarkers were analyzed as categorical variables, only CXCL16 was associated with both outcomes. Adding CXCL16 to established risk factors improved risk prediction as revealed by Net Reclassification Index (NRI). <b><i>Conclusion:</i></b> Using a multimarker approach, we determined that CXCL16 is a potent predictor of all-cause mortality and cardiovascular events in dialysis patients. Our data suggest CXCL16 may improve risk stratification and could be a potential interventional target.

Impact of dialysis modality on major adverse cardiovascular events and all-cause mortality: a national population-based study

2020 ◽  
Author(s):  
Ping-Jen Hu ◽  
Yu-Wei Chen ◽  
Tzu-Ting Chen ◽  
Li-Chin Sung ◽  
Mei-Yi Wu ◽  
...  
Keyword(s):  
Propensity Score ◽  
Study Design ◽  
Cardiovascular Events ◽  
Objective Assessment ◽  
Major Adverse Cardiovascular Events ◽  
Time Varying ◽  
Dialysis Patients ◽  
Score Study ◽  
Design For All ◽  
All Cause Mortality

Abstract Background Only few studies with inconsistent results comparing the relative risk of cardiac mortality between peritoneal dialysis (PD) and hemodialysis (HD). Switches between renal replacement therapy (RRT) modalities render objective assessment of survival benefits a greater challenge. Methods Data were retrieved from Taiwan’s National Health Insurance Database from 1 January 2006 to 31 December 2015. We included 13 662 and 41 047 long-term dialysis patients in a propensity score matching study design and a time-varying study design, respectively, to compare major adverse cardiovascular events (MACEs) between patients receiving PD and HD. We also included 109 256 dialysis patients to compare the all-cause mortality among different RRT modalities. Results For MACE, the hazard ratio (HR) for PD patients compared to HD patients was 0.95 [95% confidence interval (CI) 0.89–1.02] in the propensity score study design and 1.06 (95% CI 1.01–1.12) in the time-varying study design. For all-cause mortality, the HR for PD patients compared to HD patients was 1.09 (95% CI 1.05–1.13) in the propensity score study design and 1.13 (95% CI 1.09–1.17) in the time-varying study design. The HR for death was higher at a level of statistical significance for females (1.21, 95% CI 1.15–1.28), patients ≥65 years old (1.30, 95% CI 1.24–1.36) and diabetes mellitus (DM; 1.28, 95% CI 1.22–1.34). Conclusions The HR for MACE is significantly higher among PD patients in time-varying design analysis. In addition, all-cause mortality was higher in PD patients compared to patients with HD, especially in those who were aged ≥65 years, female or DM.

scholarly journals β-blockers in hemodialysis: simple questions, complicated answers

2020 ◽  
Author(s):  
Gregory L Hundemer ◽  
Manish M Sood ◽  
Mark Canney
Keyword(s):  
Cardiovascular Events ◽  
Population Based ◽  
Major Adverse Cardiovascular Events ◽  
Maintenance Hemodialysis ◽  
High Risk Population ◽  
Dialysis Patients ◽  
Term Survival ◽  
All Cause Mortality ◽  
Β Blocker ◽  
Β Blockers

Abstract In this issue of the Clinical Kidney Journal, Wu et al. present the results of a nationwide population-based study using Taiwanese administrative data to compare safety and efficacy outcomes with initiation of bisoprolol versus carvedilol among patients receiving maintenance hemodialysis for &gt;90 days. The primary outcomes were all-cause mortality and major adverse cardiovascular events over 2 years of follow-up. The study found that bisoprolol was associated with a lower risk for both major adverse cardiovascular events and all-cause mortality compared with carvedilol. While the bulk of the existing evidence favors a cardioprotective and survival benefit with β-blockers as a medication class among dialysis patients, there is wide heterogeneity among specific β-blockers in regard to pharmacologic properties and dialyzability. While acknowledging the constraints of observational data, these findings may serve to inform clinicians about the preferred β-blocker agent for dialysis patients to help mitigate cardiovascular risk and improve long-term survival for this high-risk population.

scholarly journals Patterns of multimorbidity and their effects on adverse outcomes in rheumatoid arthritis: a study of 5658 UK Biobank participants

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e038829
Author(s):  
Ross McQueenie ◽  
Barbara I Nicholl ◽  
Bhautesh D Jani ◽  
Jordan Canning ◽  
Sara Macdonald ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Outcome Measures ◽  
Primary Outcome ◽  
Adverse Outcomes ◽  
Major Adverse Cardiovascular Events ◽  
Uk Biobank ◽  
Long Term Conditions ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Clinical Records

ObjectiveTo investigate how the type and number of long-term conditions (LTCs) impact on all-cause mortality and major adverse cardiovascular events (MACE) in people with rheumatoid arthritis (RA).DesignPopulation-based longitudinal cohort study.SettingUK Biobank.ParticipantsUK Biobank participants (n=502 533) aged between 37 and 73 years old.Primary outcome measuresPrimary outcome measures were risk of all-cause mortality and MACE.MethodsWe examined the relationship between LTC count and individual comorbid LTCs (n=42) on adverse clinical outcomes in participants with self-reported RA (n=5658). Risk of all-cause mortality and MACE were compared using Cox’s proportional hazard models adjusted for lifestyle factors (smoking, alcohol intake, physical activity), demographic factors (sex, age, socioeconomic status) and rheumatoid factor.Results75.7% of participants with RA had multimorbidity and these individuals were at increased risk of all-cause mortality and MACE. RA and >4 LTCs showed a threefold increased risk of all-cause mortality (HR 3.30, 95% CI 2.61 to 4.16), and MACE (HR 3.45, 95% CI 2.66 to 4.49) compared with those without LTCs. Of the comorbid LTCs studied, osteoporosis was most strongly associated with adverse outcomes in participants with RA compared with those without RA or LTCs: twofold increased risk of all-cause mortality (HR 2.20, 95% CI 1.55 to 3.12) and threefold increased risk of MACE (HR 3.17, 95% CI 2.27 to 4.64). These findings remained in a subset (n=3683) with RA diagnosis validated from clinical records or medication reports.ConclusionThose with RA and other LTCs, particularly comorbid osteoporosis, are at increased risk of adverse outcomes, although the role of corticosteroids could not be evaluated in this study. These results are clinically relevant for the monitoring and management of RA across the healthcare system, and future clinical guidelines for RA should acknowledge the importance of multimorbidity.

Abstract 15895: Machine Learning Algorithms to Predict Major Adverse Cardiovascular Events in Patients Undergoing Orthotopic Liver Transplantation: A Retrospective Cohort Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
vardhmaan jain ◽  
Vikram Sharma ◽  
Agam Bansal ◽  
Cerise Kleb ◽  
Chirag Sheth ◽  
...  
Keyword(s):  
Machine Learning ◽  
Random Forest ◽  
Cardiovascular Events ◽  
Learning Algorithms ◽  
Machine Learning Algorithms ◽  
Major Adverse Cardiovascular Events ◽  
Support Vector ◽  
Post Transplant ◽  
Extreme Gradient Boosting ◽  
All Cause Mortality

Background: Post-transplant major adverse cardiovascular events (MACE) are amongst the leading cause of death amongst orthotopic liver transplant(OLT) recipients. Despite years of guideline directed therapy, there are limited data on predictors of post-OLT MACE. We assessed if machine learning algorithms (MLA) can predict MACE and all-cause mortality in patients undergoing OLT. Methods: We tested three MLA: support vector machine, extreme gradient boosting(XG-Boost) and random forest with traditional logistic regression for prediction of MACE and all-cause mortality on a cohort of consecutive patients undergoing OLT at our center between 2008-2019. The cohort was randomly split into a training (80%) and testing (20%) cohort. Model performance was assessed using c-statistic or AUC. Results: We included 1,459 consecutive patients with mean ± SD age 54.2 ± 13.8 years, 32% female who underwent OLT. There were 199 (13.6%) MACE and 289 (20%) deaths at a mean follow up of 4.56 ± 3.3 years. The random forest MLA was the best performing model for predicting MACE [AUC:0.78, 95% CI: 0.70-0.85] as well as mortality [AUC:0.69, 95% CI: 0.61-0.76], with all models performing better when predicting MACE vs mortality. See Table and Figure. Conclusion: Random forest machine learning algorithms were more predictive and discriminative than traditional regression models for predicting major adverse cardiovascular events and all-cause mortality in patients undergoing OLT. Validation and subsequent incorporation of MLA in clinical decision making for OLT candidacy could help risk stratify patients for post-transplant adverse cardiovascular events.

A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes

2018 ◽  
Vol 25 (8) ◽  
pp. 844-853 ◽  
Author(s):  
Safi U Khan ◽  
Swapna Talluri ◽  
Haris Riaz ◽  
Hammad Rahman ◽  
Fahad Nasir ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Bayesian Network ◽  
Cardiovascular Mortality ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Credible Interval ◽  
Major Adverse Cardiovascular Events ◽  
Pcsk9 Inhibitors ◽  
Adverse Cardiovascular Event ◽  
All Cause Mortality

Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception – September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55–0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62–0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49–0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83–0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77–0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibe + statin (SUCRA, 50%). Conclusion PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.

Plasma Trimethylamine N-Oxide and Risk of Cardiovascular Events in Patients With Type 2 Diabetes

2020 ◽  
Vol 105 (7) ◽  
pp. 2371-2380 ◽  
Author(s):  
Mikael Croyal ◽  
Pierre-Jean Saulnier ◽  
Audrey Aguesse ◽  
Elise Gand ◽  
Stéphanie Ragot ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Tumor Necrosis Factor Receptor ◽  
Density Lipoprotein ◽  
Major Adverse Cardiovascular Events ◽  
Cox Models ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Design And Methods

Abstract Objective Even though trimethylamine N-oxide (TMAO) has been demonstrated to interfere with atherosclerosis and diabetes pathophysiology, the association between TMAO and major adverse cardiovascular events (MACE) has not been specifically established in type 2 diabetes (T2D). Research Design and Methods We examined the association of plasma TMAO concentrations with MACE and all-cause mortality in a single-center prospective cohort of consecutively recruited patients with T2D. Results The study population consisted in 1463 SURDIENE participants (58% men), aged 65 ± 10 years. TMAO concentrations were significantly associated with diabetes duration, renal function, high-density lipoprotein cholesterol, soluble tumor necrosis factor receptor 1 (sTNFR1) concentrations (R2 = 0.27) and were significantly higher in patients on metformin, even after adjustment for estimated glomerular filtration rate (eGFR): 6.7 (8.5) vs 8.5 (13.6) µmol/L, respectively (PeGFR-adjusted = 0.0207). During follow-up (median duration [interquartile range], 85 [75] months), 403 MACE and 538 deaths were registered. MACE-free survival and all-cause mortality were significantly associated with the quartile distribution of TMAO concentrations, patients with the highest TMAO levels displaying the greatest risk of outcomes (P &lt; 0.0001). In multivariate Cox models, compared with patients from the first 3 quartiles, those from the fourth quartile of TMAO concentration had an independently increased risk for MACE: adjusted hazard ratio (adjHR) 1.32 (1.02-1.70); P = 0.0325. Similarly, TMAO was significantly associated with mortality in multivariate analysis: adjHR 1.75 (1.17-2.09); P = 0.0124, but not when sTNFR1 and angiopoietin like 2 were considered: adjHR 1.16 (0.95-1.42); P = 0.1514. Conclusions We revealed an association between higher TMAO concentrations and increased risk of MACE and all-cause mortality, thereby opening some avenues on the role of dysbiosis in cardiovascular risk, in T2D patients.

scholarly journals Sodium glucose cotransporter 2 inhibitors and risk of major adverse cardiovascular events: multi-database retrospective cohort study

BMJ ◽  
2020 ◽  
pp. m3342 ◽  
Author(s):  
Kristian B Filion ◽  
Lisa M Lix ◽  
Oriana HY Yu ◽  
Sophie Dell’Aniello ◽  
Antonios Douros ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Retrospective Cohort ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Major Adverse Cardiovascular Events ◽  
Site Specific ◽  
Sodium Glucose Cotransporter ◽  
All Cause Mortality

Abstract Objective To compare the risk of cardiovascular events between sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world context of clinical practice. Design Multi-database retrospective cohort study using a prevalent new user design with subsequent meta-analysis. Setting Canadian Network for Observational Drug Effect Studies (CNODES), with administrative healthcare databases from seven Canadian provinces and the United Kingdom, 2013-18. Population 209 867 new users of a SGLT2 inhibitor matched to 209 867 users of a DPP-4 inhibitor on time conditional propensity score and followed for a mean of 0.9 years. Main outcome measures The primary outcome was major adverse cardiovascular events (MACE, a composite of myocardial infarction, ischaemic stroke, or cardiovascular death). Secondary outcomes were the individual components of MACE, heart failure, and all cause mortality. Cox proportional hazards models were used to estimate site specific adjusted hazards ratios and 95% confidence intervals, comparing use of SGLT2 inhibitors with use of DPP-4 inhibitors in an as treated approach. Site specific results were pooled using random effects meta-analysis. Results Compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with decreased risks of MACE (incidence rate per 1000 person years: 11.4 v 16.5; hazard ratio 0.76, 95% confidence interval 0.69 to 0.84), myocardial infarction (5.1 v 6.4; 0.82, 0.70 to 0.96), cardiovascular death (3.9 v 7.7; 0.60, 0.54 to 0.67), heart failure (3.1 v 7.7; 0.43, 0.37 to 0.51), and all cause mortality (8.7 v 17.3; 0.60, 0.54 to 0.67). SGLT2 inhibitors had more modest benefits for ischaemic stroke (2.6 v 3.5; 0.85, 0.72 to 1.01). Similar benefits for MACE were observed with canagliflozin (0.79, 0.66 to 0.94), dapagliflozin (0.73, 0.63 to 0.85), and empagliflozin (0.77, 0.68 to 0.87). Conclusions In this large observational study conducted in a real world clinical practice context, the short term use of SGLT2 inhibitors was associated with a decreased risk of cardiovascular events compared with the use of DPP-4 inhibitors. Trial registration ClinicalTrials.gov NCT03939624 .

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