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Unbiased Phenome-Wide Association Studies of Red Cell Distribution Width Identifies Key Associations with Pulmonary Hypertension.

ABSTRACT: 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?-74 for all. By echocardiography, RDW was higher in the setting of right ventricular dysfunction than left ventricular dysfunction (P?P?-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?-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.

SUBMITTER: Thayer TE

PROVIDER: S-EPMC6491061 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Unbiased Phenome-Wide Association Studies of Red Cell Distribution Width Identifies Key Associations with Pulmonary Hypertension.

Thayer Timothy E TE Huang Shi S Levinson Rebecca T RT Farber-Eger Eric E Assad Tufik R TR Huston Jessica H JH Mosley Jonathan D JD Wells Quinn S QS Brittain Evan L EL

Annals of the American Thoracic Society 20190501 5

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 disc ...[more]

PMID: 30608875

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Project description:ImportanceHigher levels of red cell distribution width (RDW) are associated with adverse outcomes, especially in selected cohorts with or at risk for chronic disease. Whether higher RDW or the related parameter standard deviation of the red blood cell distribution (SD-RBC) can predict a broader range of outcomes in the general population is unknown.ObjectiveTo evaluate the association of RDW and SD-RBC with the risk of adverse outcomes in people from the general population.DesignPopulation-based retrospective cohort study.SettingHealth care system in a Canadian province (Alberta).ParticipantsAll 3,156,863 adults living in Alberta, Canada with at least one measure of RDW and SD-RBC between 2003 and 2016. Data were analyzed in September 2018.ExposureRDW and SD-RBC, classified into percentiles (<1, 1-5, 5-25, 25-75, 75-95, 95-99, >99).Main outcomesAll-cause death, first myocardial infarction, first stroke or transient ischemic attack, placement into long-term care (LTC), progression to renal replacement therapy (initiation of chronic dialysis or pre-emptive kidney transplantation), incident solid malignancy, and first hospitalization during follow-up.ResultsOver median follow-up of 6.8 years, 209,991 of 3,156,863 participants (6.7%) died. The risk of death increased with increasing RDW percentile. After adjustment, and compared to RDW in the 25th to 75th percentiles, the risk of death was lower for participants in the <25th percentiles but higher for participants in the 75th-95th percentiles (HR 1.42, 95% CI 1.40,1.43), the 95th-99th percentiles (HR 1.86, 95% CI 1.83,1.89) and the >99th percentile (HR 2.18, 95% CI 2.12,2.23). Similar results were observed for MI, stroke/TIA, incident cancer, hospitalization and LTC placement, but no association was found between RDW and ESRD. Findings were generally similar for SD-RBC, except that all associations tended to be stronger than for RDW, and both lower and higher values of SD-RBC were independently associated with ESRD.Conclusion and relevanceRDW and SD-RBC may be useful as prognostic markers for people in the general population, especially for outcomes related to chronic illness. SD-RBC may be superior to RDW.

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.

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Unbiased Phenome-Wide Association Studies of Red Cell Distribution Width Identifies Key Associations with Pulmonary Hypertension.

Publications

Unbiased Phenome-Wide Association Studies of Red Cell Distribution Width Identifies Key Associations with Pulmonary Hypertension.

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