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Thromb Haemost 2016; 115(01): 126-134
DOI: 10.1160/TH15-03-0234
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH Schattauer

Red cell distribution width is associated with future risk of incident stroke

The Tromsø Study
Jostein Lappegård
1   K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
2   Hematological Research Group (HERG), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
,
Trygve S. Ellingsen
1   K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
2   Hematological Research Group (HERG), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
,
Tove Skjelbakken
1   K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
2   Hematological Research Group (HERG), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
3   Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
,
Ellisiv B. Mathiesen
1   K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
4   Brain and Circulation Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
5   Department of Neurology and Neurophysiology, University Hospital of North Norway, Tromsø, Norway
,
Inger Njølstad
1   K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
6   Department of Community Medicine, UiT The Arctic University of Norway, Norway
,
Tom Wilsgaard
6   Department of Community Medicine, UiT The Arctic University of Norway, Norway
,
Jan Brox
1   K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
2   Hematological Research Group (HERG), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
7   Department of Clinical Chemistry, University Hospital of North Norway, Tromsø, Norway
,
Sigrid K. Brækkan
1   K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
2   Hematological Research Group (HERG), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
3   Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
,
John-Bjarne Hansen
1   K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
2   Hematological Research Group (HERG), Department of Clinical Medicine, UiT The Arctic University of Norway, Norway
3   Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
› Author Affiliations Financial support: K. G. Jebsen-Thrombosis Research and Expertise Centre (TREC) is supported by an independent grant from the K. G. Jebsen Foundation. SKB and JBH have received research grants from the Northern Norway Regional Health Authority (URL: http://www.helse-nord.no). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Further Information

Publication History

Received: 16 March 2015

Accepted after major revision: 03 July 2015

Publication Date:
22 November 2017 (online)

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Summary

Red cell distribution width (RDW), a measure of the variability in size of the circulating erythrocytes, is associated with cardiovascular morbidity and mortality. We aimed to investigate whether RDW was associated with incident stroke and case fatality in subjects recruited from the general population. Baseline characteristics were obtained from 25,992 subjects participating in the fourth survey of the Tromsø Study, conducted in 1994/95. Incident stroke was registered from inclusion until December 31, 2010. Cox regression models were used to calculate hazard ratios (HR) with 95 % confidence intervals (95 % CI) for stroke, adjusted for age, sex, body mass index, smoking, haemoglobin level, white blood cell count, thrombocyte count, hypertension, total cholesterol, triglycerides, self-reported diabetes, and red blood cell count. During a median follow-up of 15.8 years, 1152 participants experienced a first-ever stroke. A 1 % increment in RDW yielded a 13 % higher risk of stroke (multivariable HR: 1.13, 95 % CI: 1.07–1.20). Subjects with RDW in the highest quintile compared to the lowest had a 37 % higher risk of stroke in multivariable analysis (HR: 1.37, 95 % CI: 1.11–1.69). Subjects with RDW above the 95-percentile had 55 % higher risk of stroke compared to those in the lowest quintile (HR: 1.55, 95 % CI: 1.16–2.06). All risk estimates remained unchanged after exclusion of subjects with anaemia (n=1102). RDW was not associated with increased risk of death within one year or during the entire follow-up after an incident stroke. RDW is associated with incident stroke in a general population, independent of anaemia and traditional atherosclerotic risk factors.

Keywords

Epidemiological studies - stroke - risk factors
 

  • References

  • 1 Rodak BF, Fritsma GA, Doig K. Hematology: Clinical Principles and Applications. Saunders Elsevier; 2007
    Google Scholar
  • 2 Monzon CM, Beaver BD, Dillon TD. Evaluation of Erythrocyte Disorders With Mean Corpuscular Volume (MCV) and Red Cell Distribution Width (RDW). Clinical Pediatrics 1987; 26: 632-638.
    CrossrefPubMedGoogle Scholar
  • 3 Nagajothi NMD, Braverman AMD. Elevated Red Cell Distribution Width in the Diagnosis of Thrombotic Thrombocytopenic Purpura in Patients Presenting with Anemia and Thrombocytopenia. South Med J 2007; 100: 257-259.
    CrossrefPubMedGoogle Scholar
  • 4 Felker GM, Allen LA, Pocock SJ. et al. Red cell distribution width as a novel prognostic marker in heart failure: data from the CHARM Program and the Duke Databank. J Am Coll Cardiol 2007; 50: 40-47.
    CrossrefPubMedGoogle Scholar
  • 5 Zalawadiya SK, Zmily H, Farah J. et al. Red cell distribution width and mortality in predominantly African-American population with decompensated heart failure. J Card Fail 2011; 17: 292-298.
    CrossrefPubMedGoogle Scholar
  • 6 van Kimmenade RR, Mohammed AA, Uthamalingam S. et al. Red blood cell distribution width and 1-year mortality in acute heart failure. Eur J Heart Fail 2010; 12: 129-136.
    CrossrefPubMedGoogle Scholar
  • 7 Poludasu S, Marmur JD, Weedon J. et al. Red cell distribution width (RDW) as a predictor of long-term mortality in patients undergoing percutaneous coronary intervention. Thromb Haemost 2009; 102: 581-587.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Cavusoglu E, Chopra V, Gupta A. et al. Relation between red blood cell distribution width (RDW) and all-cause mortality at two years in an unselected population referred for coronary angiography. Int J Cardiol 2010; 141: 141-146.
    CrossrefPubMedGoogle Scholar
  • 9 Zalawadiya SK, Veeranna V, Niraj A. et al. Red cell distribution width and risk of coronary heart disease events. Am J Cardiol 2010; 106: 988-993.
    CrossrefPubMedGoogle Scholar
  • 10 Arbel Y, Weitzman D, Raz R. et al. Red blood cell distribution width and the risk of cardiovascular morbidity and all-cause mortality. A population-based study. Thromb Haemost 2014; 111: 300-307.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Zalawadiya SK, Veeranna V, Panaich SS. et al. Red cell distribution width and risk of peripheral artery disease: analysis of National Health and Nutrition Examination Survey 1999–2004. Vasc Med 2012; 17: 155-163.
    CrossrefPubMedGoogle Scholar
  • 12 Skjelbakken T, Lappegård J, Ellingsen TS. et al. Red Cell Distribution Width Is Associated With Incident Myocardial Infarction in a General Population: The Tromsø Study. J Am Heart Assoc 2014; 03: e001109.
    CrossrefPubMedGoogle Scholar
  • 13 Borné Y, Smith JG, Melander O. et al. Red cell distribution width in relation to incidence of coronary events and case fatality rates: a population-based cohort study. Heart 2014; 100: 1119-1124.
    CrossrefPubMedGoogle Scholar
  • 14 Tonelli M, Sacks F, Arnold M. et al. Relation Between Red Blood Cell Distribution Width and Cardiovascular Event Rate in People With Coronary Disease. Circulation 2008; 117: 163-168.
    CrossrefPubMedGoogle Scholar
  • 15 Ramírez-Moreno JM, Gonzalez-Gomez M, Ollero-Ortiz A. et al. Relation between red blood cell distribution width and ischaemic stroke: a case-control study. Intern J Stroke 2013; 08: E36-E.
    PubMedGoogle Scholar
  • 16 Kaya A, Isik T, Kaya Y. et al. Relationship Between Red Cell Distribution Width and Stroke in Patients With Stable Chronic Heart Failure: A Propensity Score Matching Analysis. Clin Appl Thromb Hemost 2015; 21: 160-165.
    CrossrefPubMedGoogle Scholar
  • 17 Saliba W, Barnett-Griness O, Elias M. et al. The Association between Red Cell Distribution Width and Stroke in Patients with Atrial Fibrillation. Am J Med 2015; 128: 192.e11-8.
    CrossrefPubMedGoogle Scholar
  • 18 Kim J, Kim YD, Song TJ. et al. Red blood cell distribution width is associated with poor clinical outcome in acute cerebral infarction. Thromb Haemost 2012; 108: 349-356.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Ani C, Ovbiagele B. Elevated red blood cell distribution width predicts mortality in persons with known stroke. J Neurol Sci 2009; 277: 103-108.
    CrossrefPubMedGoogle Scholar
  • 20 Hankey GJ, Jamrozik K, Broadhurst RJ. et al. Long-Term Disability After First-Ever Stroke and Related Prognostic Factors in the Perth Community Stroke Study, 1989–1990. Stroke 2002; 33: 1034-1040.
    CrossrefPubMedGoogle Scholar
  • 21 Go AS, Mozaffarian D, Roger VL. et al. Executive Summary: Heart Disease and Stroke Statistics–2013 Update: A Report From the American Heart Association. Circulation 2013; 127: 143-152.
    CrossrefPubMedGoogle Scholar
  • 22 Hackett ML, Duncan JR, Anderson CS. et al. Health-Related Quality of Life Among Long-Term Survivors of Stroke: Results From the Auckland Stroke Study, 1991–1992. Stroke 2000; 31: 440-447.
    CrossrefPubMedGoogle Scholar
  • 23 Jacobsen BK, Eggen AE, Mathiesen EB. et al. Cohort profile: the Tromso Study. Int J Epidemiol 2012; 41: 961-967.
    CrossrefPubMedGoogle Scholar
  • 24 Braekkan SK, Mathiesen EB, Njolstad I. et al. Family history of myocardial infarction is an independent risk factor for venous thromboembolism: the Tromso study. J Thromb Haemost 2008; 06: 1851-1857.
    CrossrefPubMedGoogle Scholar
  • 25 Malandrino N, Wu WC, Taveira TH. et al. Association between red blood cell distribution width and macrovascular and microvascular complications in diabetes. Diabetologia 2012; 55: 226-235.
    CrossrefPubMedGoogle Scholar
  • 26 Arbel Y, Weitzman D, Raz R. et al. Red blood cell distribution width and the risk of cardiovascular morbidity and all-cause mortality. A population-based study. Thromb Haemost 2014; 111: 300-307.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Azab B, Torbey E, Hatoum H. et al. Usefulness of Red Cell Distribution Width in Predicting All-Cause Long-Term Mortality after Non-ST-Elevation Myocardial Infarction. Cardiology 2011; 119: 72-80.
    CrossrefPubMedGoogle Scholar
  • 28 Chen P-C, Sung F-C, Chien K-L. et al. Red Blood Cell Distribution Width and Risk of Cardiovascular Events and Mortality in a Community Cohort in Taiwan. Am J Epidemiol 2010; 171: 214-220.
    CrossrefPubMedGoogle Scholar
  • 29 Ntaios G, Gurer O, Faouzi M. et al. Red cell distribution width does not predict stroke severity or functional outcome. Intern J Stroke 2012; 07: 2-6.
    PubMedGoogle Scholar
  • 30 Ross R. Atherosclerosis – An Inflammatory Disease. N Engl J Med 1999; 340: 115-126.
    CrossrefPubMedGoogle Scholar
  • 31 Libby P. Inflammation in atherosclerosis. Nature 2002; 420: 868-874.
    CrossrefPubMedGoogle Scholar
  • 32 Lippi G, Targher G, Montagnana M. et al. Relation Between Red Blood Cell Distribution Width and Inflammatory Biomarkers in a Large Cohort of Unselected Outpatients. Arch Pathol Lab Med 2009; 133: 628-632.
    PubMedGoogle Scholar
  • 33 Fujita B, Strodthoff D, Fritzenwanger M. et al. Altered red blood cell distribution width in overweight adolescents and its association with markers of inflammation. Pediat Obesity 2013; 08: 385-391.
    PubMedGoogle Scholar
  • 34 Özcan F, Turak O, Durak A. et al. Red cell distribution width and inflammation in patients with non-dipper hypertension. Blood Press 2013; 22: 80-85.
    CrossrefPubMedGoogle Scholar
  • 35 Öztürk ZA, Ünal A, Yiğiter R. et al. Is increased red cell distribution width (RDW) indicating the inflammation in Alzheimer’s disease (AD)?. Arch Gerontol Geriatr 2013; 56: 50-54.
    CrossrefPubMedGoogle Scholar
  • 36 Förhécz Z, Gombos T, Borgulya G. et al. Red cell distribution width in heart failure: Prediction of clinical events and relationship with markers of ineffective erythropoiesis, inflammation, renal function, and nutritional state. Am Heart J 2009; 158: 659-666.
    CrossrefPubMedGoogle Scholar
  • 37 Adamson JW. The Anemia of Inflammation/Malignancy: Mechanisms and Management. ASH Education Program Book 2008; 2008: 159-165.
    PubMedGoogle Scholar
  • 38 Abdel-Khalek MA, El-Barbary AM, Essa SA-M. et al. Serum Hepcidin: A Direct Link Between Anemia of Inflammation and Coronary Artery Atherosclerosis in Patients with Rheumatoid Arthritis. J Rheumatol 2011; 38: 2153-2159.
    CrossrefPubMedGoogle Scholar
  • 39 Balta S, Demirkol S, Hatipoglu M. et al. Other inflammatory indicators should be kept in mind when assessing red cell distribution width in patients with pneumonia. Am J Emerg Med 2013; 31: 1144-1145.
    CrossrefPubMedGoogle Scholar
  • 40 Balta S, Demirkol S, Hatipoglu M. et al. Red cell distribution width is a predictor of mortality in patients with severe sepsis and septic shock. Am J Emerg Med 2013; 31: 989-990.
    PubMedGoogle Scholar
  • 41 Koskenkorva-Frank TS, Weiss G, Koppenol WH. et al. The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: Insights into the potential of various iron therapies to induce oxidative and nitrosative stress. Free Radical Biol Med 2013; 65: 1174-1194.
    CrossrefPubMedGoogle Scholar
  • 42 Vogiatzi G, Tousoulis D, Stefanadis C. The role of oxidative stress in atherosclerosis. Hellenic J Cardiol 2009; 50: 402-409.
    PubMedGoogle Scholar
  • 43 Ghaffari S. Oxidative stress in the regulation of normal and neoplastic hematopoiesis. Antioxid Redox Signal 2008; 10: 1923-1940.
    CrossrefPubMedGoogle Scholar
  • 44 Yeagle PL. Cholesterol and the cell membrane. Biochim Biophys Acta 1985; 822: 267-287.
    CrossrefPubMedGoogle Scholar
  • 45 Kolodgie FD, Burke AP, Nakazawa G. et al. Free cholesterol in atherosclerotic plaques: where does it come from?. Curr Opinion Lipidol 2007; 18: 500-507.
    CrossrefPubMedGoogle Scholar
  • 46 Lappegård J, Ellingsen TS, Vik A. et al. Red cell distribution width and carotid atherosclerosis progression. The Tromsø Study. Thromb Haemost. 2015 Epub ahead of print.
    PubMedGoogle Scholar
  • 47 Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham Study. Arch Intern Med 1987; 147: 1561-1564.
    CrossrefPubMedGoogle Scholar
  • 48 Petersen P. Thromboembolic complications in atrial fibrillation. Stroke 1990; 21: 4-13.
    CrossrefPubMedGoogle Scholar
  • 49 Adamsson Eryd S, Borne Y, Melander O. et al. Red blood cell distribution width is associated with incidence of atrial fibrillation. J Intern Med 2014; 275: 84-92.
    CrossrefPubMedGoogle Scholar