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The association of cadmium and lead exposures with red cell distribution width.

ABSTRACT: Elevated red blood cell distribution width (RDW), traditionally an indicator of anemia, has now been recognized as a risk marker for cardiovascular disease incidence and mortality. Experimental and acute exposure studies suggest that cadmium and lead individually affect red blood cell production; however, associations between environmental exposures and RDW have not been explored. We evaluated relationships of environmental cadmium and lead exposures to RDW. We used data from 24,607 participants aged ?20 years in the National Health and Nutrition Examination Survey (2003-2016) with information on blood concentrations of cadmium and lead, RDW and socio-demographic factors. In models adjusted for age, sex, race/ethnicity, education, poverty income ratio, BMI, alcohol consumption, smoking status and serum cotinine, RDW was increasingly elevated across progressively higher quartiles of blood cadmium concentration. A doubling of cadmium concentration was associated with 0.16 higher RDW (95% CI: 0.14, 0.18) and a doubling of lead concentration with 0.04 higher RDW (95% CI: 0.01, 0.06). Also, higher cadmium and lead concentrations were associated with increased odds of high RDW (RDW>14.8%). The associations were more pronounced in women and those with low-to-normal mean corpuscular volume (MCV) and held even after controlling for iron, folate or vitamin B12 deficiencies. In analysis including both metals, cadmium remained associated with RDW, whereas the corresponding association for lead was substantially attenuated. In this general population sample, blood cadmium and lead exposures were positively associated with RDW. The associations may indicate hemolytic or erythropoietic mechanisms by which exposure increases mortality risk.

SUBMITTER: Peters JL

PROVIDER: S-EPMC7801027 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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The association of cadmium and lead exposures with red cell distribution width.

Peters Junenette L JL Perry Melissa J MJ McNeely Eileen E Wright Robert O RO Heiger-Bernays Wendy W Weuve Jennifer J

PloS one 20210111 1

Elevated red blood cell distribution width (RDW), traditionally an indicator of anemia, has now been recognized as a risk marker for cardiovascular disease incidence and mortality. Experimental and acute exposure studies suggest that cadmium and lead individually affect red blood cell production; however, associations between environmental exposures and RDW have not been explored. We evaluated relationships of environmental cadmium and lead exposures to RDW. We used data from 24,607 participants ...[more]

PMID: 33429420

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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.

Project description:AimLeft ventricular hypertrophy (LVH) is one of the most common types of target organ damage in hypertension. The red blood cell distribution width (RDW) is closely related to many cardiovascular diseases, including hypertension. The aim of this study was to analyze the relationship between the RDW level and LVH in pediatric essential hypertension.Materials and methodsA total of 429 untreated children and adolescents with essential hypertension were recruited and divided into an LVH group (n = 114) and non-LVH group (n = 315) according to left ventricular mass index (LVMI) and relative wall thickness (RWT) by color Doppler ultrasound. Spearman correlation analysis was used to determine the relationship between RDW and LVMI, RWT. The effect of RDW on LVH was determined using a multivariate logistic regression analysis. To assess the predictive value of RDW on LVH, the receiver operating characteristic (ROC) curve was used.ResultsThe level of RDW in children with hypertension in the LVH group was significantly higher than that in the non-LVH group (13.0 [12.0, 13.0] vs. 12.4 [12.0, 13.0] %, P = 0.001). The incidence of low and high quantiles of LVH was 21.0% and 32.0%, respectively. Spearman correlation analysis showed that RDW was positively correlated with C-reactive protein (CRP), LVMI, RWT, and red blood cell (RBC) count (P all < 0.05), and negatively correlated with hemoglobin (HGB) level, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) (P all < 0.05). After adjusting for various confounding factors, a multivariate logistic regression model revealed that RDW was an independent risk factor for LVH (OR = 1.946, 95% CI: 1.324-2.861, P = 0.001). The area under the ROC curve of RDW predicting centripetal hypertrophy was 0.700 (95% CI: 0.541-0.859, P < 0.05) in pediatric essential hypertension.ConclusionsIncreased RDW levels are an independent risk factor for LVH in pediatric essential hypertension, and RDW may be a predictor of LVH in untreated pediatric essential hypertension.

Project description:Rationale: Red cell distribution width (RDW) is a prognostic factor in many diseases; however, its clinical utility remains limited because the relative value of RDW as a biomarker across disease states has not been established. Objectives: To establish an unbiased RDW disease hierarchy to guide the clinical use of RDW and to assess its relationship to cardiovascular hemodynamic and structural parameters. Methods: We performed phenome-wide association studies for RDW in discovery and replication cohorts derived from a deidentified electronic health record in nonanemic individuals. RDW values obtained within 30 days of echocardiogram or right heart catheterization were tested for association with structural and hemodynamic variables. Results: RDW was associated with 263 phenotypes in both men and women in the discovery cohort (n?=?121,530), 48 of which replicated in an independent cohort (n?=?2,039). The strongest associations were observed with pulmonary arterial hypertension (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.9-2.3), chronic pulmonary heart disease (OR, 2.0; 95% CI, 1.9-2.2), and congestive heart failure (OR, 1.9; 95% CI, 1.8-2.0); P?<?1?×?10-74 for all. By echocardiography, RDW was higher in the setting of right ventricular dysfunction than left ventricular dysfunction (P?<?0.001). Measured invasively, mean pulmonary arterial pressure was associated with RDW (21 vs. 33 mm Hg at 25th vs. 75th percentile RDW; P?<?1?×?10-7) and remained strongly significant even when controlling for mean pulmonary capillary wedge pressure (21 vs. 29 mm Hg at 25th vs. 75th percentile RDW; P?<?1?×?10-7). Conclusions: Among 1,364 coded medical conditions, increased RDW was strongly associated with pulmonary hypertension and heart failure. Hemodynamic and echocardiographic phenotyping confirmed these associations and underscored that the most clinically relevant phenotype associated with RDW was pulmonary hypertension. These hypothesis-generating findings highlight the potential shared pathophysiology of pulmonary hypertension and elevated RDW. Elevated RDW in the absence of anemia should alert clinicians to the potential for underlying cardiopulmonary disease.

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The association of cadmium and lead exposures with red cell distribution width.

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The association of cadmium and lead exposures with red cell distribution width.

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