Research Blog
August 5, 2024
Welcome to part 7 of ODX's "Functional Age Biomarkers" Series. In the seventh post, you'll learn why RDW is associated with multimorbidity, disability, cognitive impairment, and mortality and why RDW is one of the most significant biomarkers of aging and mortality.
The ODX Functional Age Biomarkers Series
Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN
- Functional Age Biomarkers Part 1: Introduction and Overview
- Functional Age Biomarkers Part 2: Fasting Glucose
- Functional Age BioMarkers Part 3: C-Reactive Protein (CRP)
- Functional Age Biomarkers Part 4: Albumin
- Functional Age BioMarkers Part 5: Alkaline Phosphatase
- Functional Age BioMarkers Part 6: Creatinine
- Functional Age BioMarkers Part 7: Red Cell Distribution Width (RDW)
- Functional Age BioMarkers Part 8: Mean corpuscular volume (MCV)
- Functional Age BioMarkers Part 9: Lymphocytes
- Functional Age BioMarkers Part 10: WBCs
Red cell distribution width (RDW) reflects inflammation and hematological function
Physiological changes associated with elevated RDW
Red cell distribution width (RDW) reflects the degree of variation in size between red blood cells, i.e., anisocytosis. RDW has been used traditionally to differentiate various types of anemias. However, it is also strongly correlated with cardiovascular and all-cause morbidity and mortality as well as specific pathological conditions, including hypertension, atherosclerosis, heart failure, atrial fibrillation, ischemic stroke, pulmonary embolism, diabetes, acute pancreatitis, cancer, liver and kidney failure, Parkinsonism, sepsis, and COVID-19. An elevated RDW is considered a marker of inflammation and elevations are associated with atherosclerotic plaque, platelet activation, atherothrombotic incidents (Ananthaseshan 2022), progression to end-stage renal disease in diabetic subjects (Roumeliotis 2020). An RDW of 14.5% and above was a predictor of ischemic stroke mortality and poorer stroke rehabilitation outcomes in general (Zalyesov 2020).
An elevation in RDW may indicate anemia, abnormal RBC production, or congenital RBC pathology. Increased RDW interferes with RBC functions, namely the transport of oxygen, glucose, carbon dioxide, glucose, and amino acids (Yang 2024). Anemia associated with an elevated RDW is often due to nutrient deficiency (e.g., iron, vitamin B12, folate) or sideroblastic anemia. Anemia of chronic disease, aplastic anemia, and thalassemia heterozygosity are associated with a normal RDW (Jiang 2021).
The RDW is considered a useful biomarker for predicting chronic disease morbidity and mortality in both anemia patients and those without anemia (Beyoun 2021).
RDW and cognitive decline
RDW is closely associated with anemia, which is linked to cognitive decline, impaired reaction time, and impaired reasoning. However, elevated RDW is associated with cognitive impairment, including verbal memory deficits and dementia prevalence, in those without anemia. Elevated RDW also correlates independently with elevated homocysteine, a risk factor for Alzheimer’s disease (Beydoun 2021).
In a study of 550 subjects 65 or older, RDW was negatively correlated with cognitive assessment scores. The most significant correlation observed was between elevated RDW and attention impairment, and researchers consider increased RDW to be a significant and sensitive biomarker of mild cognitive impairment. Elevated RDW has a strong association with Alzheimer’s disease and the inflammatory pathogenesis of Alzheimer’s dementia (Yang 2024).
A J-shaped curve was observed between RDW and dementia, including Alzheimer’s and vascular dementia, despite the absence of anemia in a cross-sectional study of 5,115 subjects aged 65 and older. The risk of dementia was highest in those with an RDW above 14% and lowest with an RDW of 13.1-13.5% (Jiang 2021).
RDW and biological age
Red blood cell biomarkers, including RDW, hemoglobin, and MCHC, are associated with multimorbidity, disability, cognitive impairment, and mortality. RDW is one of the most significant biomarkers of aging and mortality (Jia 2024).
Elevations in RDW may indicate oxidative stress, increased inflammation, reduced RBC lifespan, and anemia, all factors significantly associated with an increased mortality risk. Higher RDW was significantly associated with all-cause, cancer, CVD, and respiratory mortality based on a study of 27,063 participants from the Malmo Diet and Cancer cohort study. Those with the highest RDW were 27% and 39% more likely to die from cancer and cardiovascular disease, respectively (Pan 2019).
A comprehensive review of the literature found that elevated RDW was associated with many biomarkers and conditions related to aging and mortality, including inflammation (CRP, fibrinogen, WBCs), metabolic syndrome, dyslipidemia, ischemic heart disease, hypertension, peripheral artery disease, diabetes (Fava 2019), stroke, (Jiang 2021), impaired kidney function, and nutrient insufficiency. It is considered a significant and independent risk factor for mortality among the general population and a potential indicator of chronic disease (Yousefi 2020)
References
Ananthaseshan, Sharan et al. “Red blood cell distribution width is associated with increased interactions of blood cells with vascular wall.” Scientific reports vol. 12,1 13676. 11 Aug. 2022, doi:10.1038/s41598-022-17847-z
Beydoun, May A et al. “Red Cell Distribution Width, Anemia, and Brain Volumetric Outcomes Among Middle-Aged Adults.” Journal of Alzheimer's disease : JAD vol. 81,2 (2021): 711-727. doi:10.3233/JAD-201386
Fava, Cristiano et al. “The role of red blood cell distribution width (RDW) in cardiovascular risk assessment: useful or hype?.” Annals of translational medicine vol. 7,20 (2019): 581. doi:10.21037/atm.2019.09.58
Jia, Qingqing et al. “A biological age model based on physical examination data to predict mortality in a Chinese population.” iScience vol. 27,3 108891. 3 Feb. 2024, doi:10.1016/j.isci.2024.108891
Jiang, Ziying et al. “Red Cell Distribution Width and Dementia Among Rural-Dwelling Older Adults: The MIND-China Study.” Journal of Alzheimer's disease : JAD vol. 83,3 (2021): 1187-1198. doi:10.3233/JAD-210517
Pan, Jingxue et al. “The relationship between red cell distribution width and all-cause and cause-specific mortality in a general population.” Scientific reports vol. 9,1 16208. 7 Nov. 2019, doi:10.1038/s41598-019-52708-2
Roumeliotis, Stefanos et al. “Red Blood Cell Distribution Width Is Associated with Deterioration of Renal Function and Cardiovascular Morbidity and Mortality in Patients with Diabetic Kidney Disease.” Life (Basel, Switzerland) vol. 10,11 301. 22 Nov. 2020, doi:10.3390/life10110301
Yang, Juan et al. “Red Cell Distribution Width is Related to Mild Cognitive Impairment: A Cross-Sectional Study of Community Residents.” Neurology India vol. 72,1 (2024): 64-68. doi:10.4103/ni.ni_211_22
Yousefi, Bahman et al. “Red Cell Distribution Width as a Novel Prognostic Marker in Multiple Clinical Studies.” Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine vol. 24,1 (2020): 49-54. doi:10.5005/jp-journals-10071-23328
Zalyesov, Eduard et al. “Red Cell Distribution Width as a Predictor of Functional Outcome in Rehabilitation of Older Stroke Patients.” Annals of geriatric medicine and research vol. 24,3 (2020): 211-217. doi:10.4235/agmr.20.0042
Tag(s):
Biomarkers
