Benjamin D Horne1,2, Joseph B Muhlestein1,3, Sterling T Bennett4,5, Joseph Boone Muhlestein3, Kurt R Jensen1, Diane Marshall1, Tami L Bair1, Heidi T May1, John F Carlquist1,3, Matthew Hegewald6, Stacey Knight1,7, Viet T Le1, T Jared Bunch1,8, Donald L Lappé1,3, Jeffrey L Anderson1,3, Kirk U Knowlton1,9. 1. Intermountain Heart Institute, Intermountain Medical Center, Salt Lake City, Utah, USA. 2. Department of Biomedical Informatics and. 3. Cardiology Division, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA. 4. Intermountain Central Laboratory, Intermountain Medical Center, Salt Lake City, Utah, USA. 5. Department of Pathology, University of Utah, Salt Lake City, Utah, USA. 6. Pulmonary Division, Department of Internal Medicine, Intermountain Medical Center, Salt Lake City, Utah, USA. 7. Genetic Epidemiology Division, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA. 8. Department of Internal Medicine, Stanford University, Palo Alto, California, USA. 9. Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego, San Diego, California, USA.
Abstract
BACKGROUND: The red cell distribution width (RDW) is associated with health outcomes. Whether non-RDW risk information is contained in RBC sizes is unknown. This study evaluated the association of the percentage of extreme macrocytic RBCs (%Macro, RBC volume > 120 fl) and microcytic RBCs (%Micro, RBC volume < 60 fl) and the RDW-size distribution (RDW-sd) with mortality and morbidity. METHODS: Patients (females, n = 165,770; males, n = 100,210) at Intermountain Healthcare were studied if they had a hematology panel between May 2014 and September 2016. Adjusted sex-specific associations of %Macro/%Micro and RDW-sd with mortality and 33 morbidities were evaluated. RESULTS: Among females with fourth-quartile values of %Macro quartile and %Micro (referred to throughout as 4/4), there was an average of 7.2 morbidities versus 2.9 in the lowest risk (LR1) categories, 1/1, 1/2, 2/1, and 2/2 (P < 0.001). Among males, those in the 4/4 category had 8.0 morbidities, while those in the LR1 had 3.4 (P < 0.001). Cox regressions found %Macro/%Micro (4/4 vs. LR1, females: hazard ratio [HR] = 1.97 [95% CI = 1.53, 2.54]; males: HR = 2.17 [CI = 1.72, 2.73]), RDW-sd (quartile 4 vs. 1, females: HR = 1.33 [CI = 1.04, 1.69]; males: HR = 1.41 [CI = 1.10, 1.80]), and RDW (quartile 4 vs. 1, females: HR = 1.59 [CI = 1.26, 2.00]; males: HR = 1.23 [CI = 0.99, 1.52]) independently predicted mortality. Limitations include that the observational design did not reveal causality and unknown confounders may be unmeasured. CONCLUSIONS: Concomitantly elevated %Macro and %Micro predicted the highest mortality risk and the greatest number of morbidities, revealing predictive ability of RBC volume beyond what is measured clinically. Mechanistic investigations are needed to explain the biological basis of these observations. FUNDING: This study was supported by internal Intermountain Heart Institute funds and in-kind support from Sysmex America Inc.
BACKGROUND: The red cell distribution width (RDW) is associated with health outcomes. Whether non-RDW risk information is contained in RBC sizes is unknown. This study evaluated the association of the percentage of extreme macrocytic RBCs (%Macro, RBC volume > 120 fl) and microcytic RBCs (%Micro, RBC volume < 60 fl) and the RDW-size distribution (RDW-sd) with mortality and morbidity. METHODS:Patients (females, n = 165,770; males, n = 100,210) at Intermountain Healthcare were studied if they had a hematology panel between May 2014 and September 2016. Adjusted sex-specific associations of %Macro/%Micro and RDW-sd with mortality and 33 morbidities were evaluated. RESULTS: Among females with fourth-quartile values of %Macro quartile and %Micro (referred to throughout as 4/4), there was an average of 7.2 morbidities versus 2.9 in the lowest risk (LR1) categories, 1/1, 1/2, 2/1, and 2/2 (P < 0.001). Among males, those in the 4/4 category had 8.0 morbidities, while those in the LR1 had 3.4 (P < 0.001). Cox regressions found %Macro/%Micro (4/4 vs. LR1, females: hazard ratio [HR] = 1.97 [95% CI = 1.53, 2.54]; males: HR = 2.17 [CI = 1.72, 2.73]), RDW-sd (quartile 4 vs. 1, females: HR = 1.33 [CI = 1.04, 1.69]; males: HR = 1.41 [CI = 1.10, 1.80]), and RDW (quartile 4 vs. 1, females: HR = 1.59 [CI = 1.26, 2.00]; males: HR = 1.23 [CI = 0.99, 1.52]) independently predicted mortality. Limitations include that the observational design did not reveal causality and unknown confounders may be unmeasured. CONCLUSIONS: Concomitantly elevated %Macro and %Micro predicted the highest mortality risk and the greatest number of morbidities, revealing predictive ability of RBC volume beyond what is measured clinically. Mechanistic investigations are needed to explain the biological basis of these observations. FUNDING: This study was supported by internal Intermountain Heart Institute funds and in-kind support from Sysmex America Inc.
Authors: Benjamin D Horne; Matthew Hegewald; Joseph B Muhlestein; Heidi T May; Elizabeth J Huggins; Tami L Bair; Jeffrey L Anderson Journal: Respir Care Date: 2015-04-14 Impact factor: 2.258
Authors: Benjamin D Horne; Joseph B Muhlestein; Sterling T Bennett; Joseph Boone Muhlestein; Brianna S Ronnow; Heidi T May; Tami L Bair; Jeffrey L Anderson Journal: Eur J Clin Invest Date: 2015-05-13 Impact factor: 4.686
Authors: J B Muhlestein; D L Lappe; J L Anderson; J B Muhlestein; D Budge; H T May; S T Bennett; T L Bair; B D Horne Journal: Int J Lab Hematol Date: 2016-06 Impact factor: 2.877
Authors: Jason M Lappé; Benjamin D Horne; Svati H Shah; Heidi T May; Joseph B Muhlestein; Donald L Lappé; Abdallah G Kfoury; John F Carlquist; Deborah Budge; Rami Alharethi; Tami L Bair; William E Kraus; Jeffrey L Anderson Journal: Clin Chim Acta Date: 2011-07-27 Impact factor: 3.786
Authors: Benjamin D Horne; Heidi T May; Abdallah G Kfoury; Dale G Renlund; Joseph B Muhlestein; Donald L Lappé; Kismet D Rasmusson; T Jared Bunch; John F Carlquist; Tami L Bair; Kurt R Jensen; Brianna S Ronnow; Jeffrey L Anderson Journal: Eur J Heart Fail Date: 2010-08-12 Impact factor: 15.534
Authors: Omid Fatemi; Rebecca Torguson; Fang Chen; Soha Ahmad; Salem Badr; Lowell F Satler; Augusto D Pichard; Neal S Kleiman; Ron Waksman Journal: Am Heart J Date: 2013-05-16 Impact factor: 4.749
Authors: James G Truslow; Shinichi Goto; Max Homilius; Christopher Mow; John M Higgins; Calum A MacRae; Rahul C Deo Journal: Circ Cardiovasc Qual Outcomes Date: 2022-04-28
Authors: Benjamin D Horne; Joseph B Muhlestein; Heidi T May; Viet T Le; Tami L Bair; Sterling T Bennett; Kirk U Knowlton; Jeffrey L Anderson Journal: Nutrients Date: 2021-12-09 Impact factor: 5.717