Observational studyMedicine2025
Red cell distribution width and hypertension: Associations from NHANES 2021 to 2023 study and MR-PRESSO-adjusted Mendelian randomization analysis.
Observational study in Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Hypertension, a common chronic disease worldwide, has an unclear causal relationship and association pattern with red cell distribution width (RDW), a prognostic marker for cardiovascular events. Traditional observational studies have struggled to clarify this relationship due to confounding factors and reverse causality. A mixed study design integrating observational and genetic evidence was adopted: observational analysis: based on data from National Health And Nutrition Examination Survey 2021 to 2023 (n = 5768), complex sampling-weighted multivariable logistic regression and restricted cubic splines were used to analyze the RDW-hypertension association, with subgroup interaction tests; causal inference: MR-PRESSO-adjusted Mendelian randomization (MR) analysis (hypertension GWAS: ukb-b-12493; RDW GWAS: ebi-a-GCST006804) was performed, using 56 strong instrumental variables (F > 10) to verify the causal direction, supplemented by sensitivity analyses including inverse-variance weighting (IVW) and MR-Egger. Each 1-unit increase in RDW was associated with a 13% increased risk of hypertension (OR = 1.13, 95% CI = 1.05-1.21) after adjustment for 12 covariates in the full model, with a nonlinear threshold effect (P for nonlinearity = .028): the association was stronger when RDW < 13.8% (OR = 1.29, P < .001). After MR-PRESSO adjustment, the IVW method confirmed that hypertension caused an increase in RDW (OR = 1.36, 95% CI = 1.03-1.79, P = .03), with no horizontal pleiotropy (Egger intercept = 0.973). Subgroup analysis showed that the RDW-hypertension association was significant in populations without a history of stroke (OR = 1.14) or coronary heart disease (OR = 1.14) but disappeared in patients with these conditions (interaction P < .05). This study is the first to explore the association between hypertension and RDW via MR-PRESSO-adjusted MR, providing evidence of a potential causal link where hypertension may contribute to increased RDW, and identifies a RDW threshold of 13.8%. RDW can serve as a prognostic marker for cardiovascular events and may be a reference indicator for monitoring the risk of hypertension in populations without cardiovascular complications, pending further validation of its role in the pathological mechanism of hypertension.
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