Proteins in the pathway from high red blood cell width distribution to all-cause mortality.
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ABSTRACT: Background
The pathophysiological mechanisms underlying the association between red blood cell distribution width (RDW) and all-cause mortality are unknown. We conducted a data-driven discovery investigation to identify plasma proteins that mediate the association between RDW and time to death in community-dwelling adults.Methods
At baseline, 962 adults (women, 54·4%; age range, 21-98 years) participated in the InCHIANTI, "Aging in the Chianti Area" study, and proteomics data were generated from their plasma specimens. Of these, 623 participants had proteomics data available at the 9-year follow-up. For each visit, a total of 1301 plasma proteins were measured using SOMAscan technology. Complete data on vital status were available up to the 15-year follow-up period. Protein-specific exponential distribution accelerated failure time, and linear regression analyses adjusted for possible covariates were used for mortality and mediation analyses, respectively (survival data analysis).Findings
Baseline values of EGFR, GHR, NTRK3, SOD2, KLRF1, THBS2, TIMP1, IGFBP2, C9, APOB, and LRP1B mediated the association between baseline RDW and all-cause mortality. Changes in IGFBP2 and C7 over 9 years mediated the association between changes in RDW and 6-year all-cause mortality.Interpretation
Cellular senescence may contribute to the association between RDW and mortality.Funding
This study was funded by grants from the National Institutes of Health (NIH) and the National Institute on Aging (NIA) contract and was supported by the Intramural Research Program of the NIA, NIH. The InCHIANTI study was supported as a 'targeted project' by the Italian Ministry of Health and in part by the U.S. NIA.
SUBMITTER: Osawa Y
PROVIDER: S-EPMC8784626 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundHigher red blood cell distribution width (RDW) levels are associated with mortality in patients with chronic obstructive pulmonary disease (COPD). However, more convincing evidence is still lacking, and the relationship between hemoglobin-to-red blood cell distribution width ratio (HRR) and mortality in patients with COPD remains unclear.MethodsThis study is a prospective cohort study that includes 3,745 adult patients with COPD from the National Health and Nutrition Examination Survey (NHANES) database spanning from 1999 to 2018 in the United States. COX proportional hazards regression analysis, Kaplan-Meier survival curves and restricted cubic spline models were employed to investigate the association of RDW and HRR levels with mortality. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to evaluate the accuracy of RDW and HRR in predicting mortality in patients with COPD.ResultsHigher RDW level was positively associated with increased risk of all-cause mortality (HR = 1.16, 95% CI = 1.11-1.21, P < 0.001), cardiovascular disease (CVD) mortality (HR = 1.13, 95% CI = 1.06-1.21, P < 0.001), and chronic lower respiratory disease (CLRD) related mortality (HR = 1.15, 95% CI = 1.05-1.25, P = 0.003) after adjusting for various potential confounders. HRR was inversely associated with all-cause mortality (HR = 0.14, 95% CI = 0.08-0.25, P < 0.001), CVD mortality (HR = 0.12, 95% CI = 0.05-0.31, P < 0.001). HRR has no significant correlation with CLRD-related mortality. The time-dependent ROC curve showed that RDW exhibited area under the curves (AUCs) of the 5- and 10-year survival rates were 0.707 and 0.714 for all-cause mortality and 0.686 and 0.698, respectively, for CVD mortality. HRR yielded AUCs of the 5- and 10-year survival rates were 0.661 and 0.653 for all-cause mortality and 0.654 and 0.66, respectively, for CVD mortality.ConclusionHigher RDW levels were positively associated with an increased risk of mortality in patients with COPD. HRR levels were negatively correlated with the risk of all-cause and CVD mortality. The predictive value of HRR for mortality in these patients is lower than that of RDW.
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Project description:In hemodialysis patients, a native arteriovenous fistula (AVF) is the preferred form of permanent vascular access. Despite recent improvements, vascular access dysfunction remains an important cause of morbidity in these patients. In this prospective observational cohort study, we evaluated potential risk factors for native AVF dysfunction. We included 68 patients with chronic renal disease stage 5 eligible for AVF construction at the Department of General and Vascular Surgery, Central Clinical Hospital Ministry of Internal Affairs, Warsaw, Poland. Patient characteristics and biochemical parameters associated with increased risk for AVF failure were identified using Cox proportional hazards models. Vessel biopsies were analyzed for inflammatory cells and potential associations with biochemical parameters. In multivariable analysis, independent predictors of AVF dysfunction were the number of white blood cells (hazard ratio [HR] 1.67; 95% confidence interval [CI] 1.24 to 2.25; p<0.001), monocyte number (HR 0.02; 95% CI 0.00 to 0.21; p = 0.001), and red blood cell distribution width (RDW) (HR 1.44; 95% CI 1.17 to 1.78; p<0.001). RDW was the only significant factor in receiver operating characteristic curve analysis (area under the curve 0.644; CI 0.51 to 0.76; p = 0.046). RDW>16.2% was associated with a significantly reduced AVF patency frequency 24 months after surgery. Immunohistochemical analysis revealed CD45-positive cells in the artery/vein of 39% of patients and CD68-positive cells in 37%. Patients with CD68-positive cells in the vessels had significantly higher white blood cell count. We conclude that RDW, a readily available laboratory value, is a novel prognostic marker for AVF failure. Further studies are warranted to establish the mechanistic link between high RDW and AVF failure.
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Project description:Background:High red blood cell distribution width (RDW) is associated with worse outcome in diverse scenarios, including in critical illness. The Sabadell score (SS) predicts in-hospital survival after ICU discharge. We aimed to determine RDW's association with survival after ICU discharge and whether RDW can improve the accuracy of the SS. Design:Retrospective cohort study. Setting: general ICU at a university hospital. Patients:We included all patients discharged to wards from January 2010 to October 2016. Methods:We analyzed associations between RDW and variables recorded on admission (age, comorbidities, severity score), during the ICU stay (treatments, complications, length of stay (LOS)), and at ICU discharge (SS). The primary outcome was hospital mortality. Statistical analysis included multivariable logistic regression and receiver operating characteristic curve (ROC) analyses. Results:We discharged 3366 patients to wards; median ward LOS was 7 [4-13] days; ward mortality was 5.2%. Mean RDW at ICU discharge was 15.4?±?2.5%. Ward mortality was higher at each quartile of RDW (0.7%, 2.9%, 7.5%, 10.3%; area under ROC 0.81). A logistic regression model with Sabadell score obtained an excellent accuracy for ward mortality (area under ROC 0.863), and the addition of RDW slightly improved accuracy (AUROC 0.890, p?<?0.05). Recursive partitioning demonstrated higher mortality in patients with high RDW at each SS level (1.6% vs. 0.3% in SS0, 9.7% vs. 1.1% in SS1, 21.9% vs. 9.7% in SS2), but not in SS3. Conclusion:High RDW is a marker of severity at ICU discharge and improves the accuracy of Sabadell score in predicting ward mortality except in the more extreme SS3.
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Project description:Red cell distribution width (RDW) is an index of red blood cell volume variability that has historically been used as a marker of iron deficiency anemia. More recently, studies have shown that elevated RDW is associated with higher mortality risk in the general population. However, there is lack of data demonstrating the association between RDW and mortality risk in hemodialysis (HD) patients. We hypothesized that higher RDW is associated with higher mortality in HD patients.Retrospective observational study using a large HD patient cohort.109,675 adult maintenance HD patients treated in a large dialysis organization from January 1, 2007, to December 31, 2011.Baseline and time-varying RDW, grouped into 5 categories: <14.5%, 14.5% to <15.5%, 15.5% to <16.5%, 16.5% to <17.5%, and ?17.5%. RDW of 15.5% to <16.5% was used as the reference category.All-cause mortality.Mean age of study participants was 63±15 (SD) years and the study cohort was 44% women. In baseline and time-varying analyses, there was a graded association between higher RDW and incrementally higher mortality risk. Receiver operating characteristic, net reclassification analysis, and integrated discrimination improvement analyses demonstrated that RDW is a stronger predictor of mortality as compared with traditional markers of anemia, such as hemoglobin, ferritin, and iron saturation values.Lack of comprehensive data that may be associated with both RDW and HD patient outcomes, such as blood transfusion data, socioeconomic status, and other unknown confounders; therefore, the possibility of residual confounding could not be excluded. Also, lack of information for cause of death; thus, cardiovascular mortality outcomes could not be examined.In HD patients, higher RDW is associated with incrementally higher mortality risk. RDW is also a stronger predictor of mortality than traditional laboratory markers of anemia. Further studies are needed to determine the mechanisms underlying the association between RDW and mortality.
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Project description:AbstractPrevious studies have shown an independent association between increased red cell distribution width (RDW) and mortality after acute myocardial infarction (AMI). However, evidence regarding the predictive significance of repeated measures of RDW in patients with AMI remains scarce. We aimed to investigate the association between the dynamic profile of RDW and in-hospital mortality in patients with AMI.This was a cross-sectional study. We extracted clinical data from the Medical Information Mart for Intensive Care IIIV1.4 database. Demographic data, vital signs, laboratory test data, and comorbidities were collected from the database. The clinical endpoint was in-hospital mortality. Cox proportional hazards models were used to evaluate the prognostic values of basic RDW, and the Kaplan-Meier method was used to plot survival curves. Subgroup analyses were performed to measure mortality across various subgroups. The repeated-measures data were compared using a generalized additive mixed model.In total, 3101eligible patients were included. In multivariate analysis, adjusted for age, sex, and ethnicity, RDW was a significant risk predictor of in-hospital mortality. Furthermore, after adjusting for more confounding factors, RDW remained a significant predictor of in-hospital mortality (tertile 3 vs tertile 1: hazard ratio 2.3; 95% confidence interval 1.39-4.01; P for trend <.05). The Kaplan-Meier curve for tertiles of RDW indicated that survival rates were highest when RDW was ≤13.2% and lowest when RDW was ≥14.2% after adjustment for age, sex, and ethnicity. During the intensive care unit stay, the RDW of nonsurvivors progressively increased until death occurred.Our findings showed that a higher RDW was associated with an increased risk of in-hospital mortality in patients with AMI.
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Project description:BackgroundRed blood cell distribution width (RDW) has emerged as a prognostic factor for mortality in various diseases. Up to now, few studies have focused on the prognostic value of RDW in patients with diabetic foot ulcers (DFUs). This retrospective cohort study aimed to investigate the impact of RDW and RDW/albumin (ALB) ratio on all-cause mortality in patients with DFUs.MethodsThis study included 860 patients with DFUs in a tertiary academic hospital. The associations of RDW and RDW/ALB with all-cause mortality were assessed by multivariable cox regression analyses. The pairwise comparisons of receiver operating characteristic (ROC) curves were performed to compare the predictive performance of RDW and RDW/ALB ratio. Harrell's concordance index, integrated discrimination improvement, and net reclassification improvement were used to estimate the improvements in risk discrimination.ResultsPatients with high RDW and RDW/ALB had lower overall survival rates (all P < 0.001). The multivariable Cox regression revealed that high RDW [adjusted hazard ratio (HR) 2.426, 95% confidence interval (CI): 1.557-3.778, P < 0.001] and high RDW/ALB (adjusted HR 2.360, 95% CI: 1.414-3.942, P = 0.001) were independent associated with high all-cause mortality. In subgroup analyses, the comparative analysis of ROC curves revealed that the discriminating ability of the RDW/ALB ratio was significantly superior to RDW in patients with no severe DFUs or no severe peripheral artery disease, or in young and middle-aged patients (all P < 0.05). Adding RDW and RDW/ALB ratio to base models improved discrimination and risk reclassification for all-cause mortality.ConclusionsRDW and RDW/ALB ratio are robust and independent prognostic markers in patients with DFUs. The RDW/ALB ratio appears to be of more predictive value for mortality in younger and less severely ill patients with DFUs. Both RDW and RDW/ALB ratio can provide incremental predictive value for all-cause mortality over traditional risk factors. RDW and RDW/ALB ratio can be used to identify high-risk patients with DFUs.
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Project description:AimRed blood cell distribution width (RDW) is an important parameter with broad biological implications. However, the study investigating the association between RDW and thyroid function remains sparse and inconsistent. We aimed to investigate the association between RDW and thyroid function in the US population.MethodsA cross-sectional analysis was performed using the data from the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2010. The thyroid parameters investigated were mainly free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), antithyroglobulin antibody (TgAb), and antithyroperoxidase antibody (TPOAb). In the 6,895 adults aged 18 years or older, logistic regression modeling was applied to estimate the association between RDW quartiles and thyroid parameters. Smooth curve fittings and generalized additive models were then performed to address the nonlinear relationship.ResultsThe association between RDW and TSH followed a J-shaped curve, and a significant positive relationship existed in the 12.5%-17.5% range of RDW (β = 0.350, 95% confidence interval (CI): 0.225 to 0.474), which was prominent in females. We further demonstrated a negative association (β = -0.018, 95% CI: -0.030 to -0.005) between RDW and fT3. Moreover, elevated RDW was more likely to be subclinical hypothyroidism. However, there was no obvious association between RDW and fT4.ConclusionThis study confirmed a significant association between RDW and TSH, and future studies are needed to elucidate the underlying mechanisms of the peculiar RDW-fT3 relationship. RDW may be a significant clinical marker of subclinical hypothyroidism.
| S-EPMC8805204 | biostudies-literature
Project description:The red cell distribution width (RDW) has been reported to be positively correlated with short-term mortality of pulmonary disease in adults. However, it is not clear whether RDW was associated with the long-term prognosis for acute respiratory failure (ARF). Thus, an analysis was conducted to evaluate the association between RDW and 3-year mortality of patients by the Cox regression analysis, generalized additives models, subgroup analysis and Kaplan-Meier analysis. A total of 2999 patients who were first admitted to hospital with ARF were extracted from the Medical Information Mart for Intensive Care III database (MIMIC-III). The Cox regression analysis showed that the high RDW was associated with 3-year mortality (HR 1.10, 95% CI 1.07, 1.12, P < 0.0001) after adjusting for age, gender, ethnicity and even co-morbid conditions. The ROC curve illustrated the AUC of RDW was 0.651 (95% CI 0.631, 0.670) for prediction of 3-year mortality. Therefore, there is an association between the RDW and survival time of 3 years follow-up, particularly a high RDW on admission was associated with an increased risk of long-term mortality in patients with ARF. RDW may provide an alternative indicator to predict the prognosis and disease progression and more it is easy to get.
| S-EPMC7713121 | biostudies-literature
Project description:ObjectivesThis study aimed to explore the relationship between red blood cell distribution width (RDW) and all-cause mortality in critically ill patients undergoing intra-aortic balloon pumping (IABP) in the intensive care unit (ICU).MethodsThis study retrospectively analyzed data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary endpoint was the 30-day mortality rate, while the secondary endpoint was the in-hospital mortality rate. Restricted cubic splines were used to assess the dose-response relationship. The receiver operating characteristic (ROC) curve and Kaplan-Meier curve analysis were carried out to evaluate the predictive performance of RDW. Moreover, multiple logistic regression analyses and subgroup analyses were conducted to investigate the relationship between RDW and 30-day mortality. Finally, propensity score matching (PSM) was performed to adjust for the imbalance of covariates.ResultsIn total, 732 patients were finally identified from the MIMIC-IV database in this study. The RDW of patients in the non-survivor group was significantly higher compared with those in the survivor group (P < 0.01). Multiple logistic regression analyses corroborated RDW was an independent predictor of all-cause 30-day mortality in critically ill patients post-IABP. Meanwhile, ROC analysis identified an RDW cutoff of 14.2%. High RDW patients exhibited a 131% (OR = 2.31, 95% CI: 1.49-3.61) elevated risk of 30-day mortality after adjusting for confounders in multivariable logistic regression. After PSM, 412 patients were included in the matched cohort. In the original and matched cohorts, the high RDW group had higher 30-day and in-hospital mortality rates, as well as longer ICU stays. Lastly, the area under the ROC curve for 30-day mortality was 0.686, with an optimal cutoff point of 14.2 for RDW (sensitivity: 69.09 % and specificity: 63.32%).ConclusionRDW could be a simple and valuable prognostic tool to predict mortality in critically ill patients after IABP.
| S-EPMC10950574 | biostudies-literature
Project description:Background and Objectives: Hip fractures in the elderly pose a considerable health risk and cause concern. Red blood cell distribution width (RDW) is a valuable marker for identifying patients at high risk of age-related mortality and various disorders and diseases. However, its association with poor patient outcomes following hip fractures has yet to be fully established. Hence, the purpose of this meta-analysis was to investigate and gain a better understanding of the relationship between RDW levels and the risk of mortality after hip fractures. Materials and Methods: PubMed, Embase, Web of Science, and other databases were comprehensively searched until April 2023 to identify relevant studies. The meta-analysis included observational studies finding the association between RDW at admission or preoperation and short-term and long-term mortality rates following hip fractures. The results were presented in terms of odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results: This meta-analysis included 10 studies involving 5834 patients with hip fractures. Patients with preoperative RDW of over 14.5% had higher risks of 1-year (OR: 5.40, 95% CI: 1.89-15.48, p = 0.002) and 3-month (OR: 2.91, 95% CI: 1.42-5.95, p = 0.004) mortality. Higher admission or preoperative RDW was significantly associated with an 11% higher mortality risk after 1 year (HR: 1.11, 95% CI: 1.06-1.17, p < 0.00001). Patients with higher preoperative RDW had a significantly higher risk of 6-month mortality, which was three times that of those with lower preoperative RDW (OR: 3.00, 95% CI: 1.60-5.61, p = 0.0006). Higher preoperative RDW was correlated to a higher 30-day mortality risk (OR: 6.44, 95% CI: 3.32-12.47, p < 0.00001). Conclusions: Greater RDW values at admission or before surgery were associated with a higher risk of short-term and long-term mortality following hip fractures. Because RDW can be easily measured using a routine blood test at a low cost, this parameter is promising as an indicator of mortality in elderly patients with hip fractures.
| S-EPMC10972257 | biostudies-literature