RHEUMATOLOGY
Rheumatology 2014;53:14391445 doi:10.1093/rheumatology/keu022 Advance Access publication 21 March 2014
Original article Clinical usefulness of measuring red blood cell distribution width in patients with systemic sclerosis Nelli Farkas1, Andrea Szabo´2, Veronika Lo´ra´nd3, Dona´t Pe´ter Sarlo´s3, Tu¨nde Minier3, Zolta´n Proha´szka4, La´szlo´ Czirja´k3 and Cecı´lia Varju´3
Methods. One hundred and sixty-eight consecutive SSc patients—62 with dcSSc and 106 with lcSSc—were investigated at baseline and after 1-year of follow-up. Measurements in 93 patients with primary RP and 40 healthy subjects served as controls. Results. The median RDW value of patients with SSc was higher [14.2% (25th75th percentiles 13.514.8%) compared with the group of primary RP patients [13.9% (13.414.4%); P < 0.05) and healthy volunteers [13.6% (13.213.8%; P < 0.01]. dcSSc and anti-topoisomerase antibodypositive cases showed elevated RDW values compared with lcSSc and anti-topoisomerase antibodynegative cases (P < 0.05). RDW showed a positive correlation with inflammatory markers, including ESR (P < 0.05) and CRP (P < 0.05), and a negative correlation with forced vital capacity (P < 0.05) and diffusing capacity of the lung for carbon monoxide (DLCO) (P < 0.05) during the follow-up. An increase in RDW of >5% during follow-up was associated with an average 8.9% decrease in left ventricular ejection fraction (LVEF) and 7% in DLCO and these associations were independent of each other. Conclusion. RDW in SSc may represent an integrative measure of multiple pathological processes including extensive vasculopathy, fibrosis or ongoing inflammation. An increase in RDW may indicate an impairment of cardiorespiratory function. Key words: red blood cell distribution width, RDW, systemic sclerosis, left ventricular ejection fraction, lung fibrosis, vasculopathy, inflammation.
Introduction Red blood cell distribution width (RDW) is a biomarker that quantifies variability in red blood cell size, pointing to the level of anisocytosis in the complete blood count. The normal range of RDW is between 11.5 and 14.5% [1]. Elevated RDW can be present during inflammation and
1 Institute of Bioanalysis, 2Institute of Family Medicine, 3Department of Rheumatology and Immunology, University of Pe´cs, Pe´cs and 4Third Department of Internal Medicine, Semmelweis University, Research Laboratory, Budapest, Hungary.
Submitted 9 September 2013; revised version accepted 20 January 2014. Correspondence to: Cecı´lia Varju´, Department of Rheumatology and Immunology, Clinic Center, University of Pe´cs, Aka´c u. 1, H-7632 Pe´cs, Hungary. E-mail: [email protected]
nutritional deficiencies, and co-morbidities including renal failure also influence RDW [24]. RDW is also a predictor of survival in idiopathic pulmonary arterial hypertension (PAH) [5, 6] and an independent prognostic risk factor in cardiovascular or cerebrovascular events in the general population and in patients with heart failure, coronary heart disease or peripheral atherosclerosis [79]. Furthermore, high RDW is closely associated with the risk of carotid artery atherosclerosis in patients with hypertension [10]. Elevated values of RDW can be found in thalassaemia and in other anaemias, including early stage iron, folate or vitamin B12 deficiency, and also can be present in some types of hepatopathy [1, 2, 9]. SSc is a systemic autoimmune disease with generalized obliterative arterial vasculopathy and microvascular lesions [11]. There is a wide spectrum of organ
! The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]
CLINICAL SCIENCE
Objective. Red blood cell distribution width (RDW) is a biomarker quantifying the variability of red blood cell size in peripheral blood. Elevated RDW has been found to be an independent prognostic factor for cardiovascular events. SSc is characterized by generalized micro- and macroangiopathy. Our aim was to investigate RDW as a potential biomarker for the assessment of the severity of vascular involvement.
Downloaded from http://rheumatology.oxfordjournals.org/ at West Virginia University, Health Science Libraryy on July 19, 2015
Abstract
Nelli Farkas et al.
Patients and methods One hundred and sixty-eight consecutive Hungarian (Caucasian) patients (147 females and 21 males; 62 with dcSSc, 106 with lcSSc) were included in the study (Table 1). At the baseline examination the mean age of patients with SSc was 55.1 years (S.D. 12.7), the mean disease duration was 8.1 years (S.D. 7.2) and the mean follow-up was 6.8 years (S.D. 4.0). Patients were divided into diffuse and limited cutaneous subsets by the criteria of LeRoy et al. [19]. During the follow-up, the DMARD treatment of patients had not changed significantly. Four deaths caused by SSc were recorded during the investigative 1-year period. Six patients were lost to follow-up and one of died for reasons other than SSc.
At baseline and after 1 year, pulmonary function tests, echocardiography and the Scleroderma Study Group Activity Index (EScSG) [20] were performed within 6 weeks of the blood test. Clinical characteristics included the presence of subcutaneous calcinosis, telangiectasia, skin hypo-/ hyperpigmentation and active skin ulcers. Modified Rodnan skin score (MRSS) [21], ESR, CRP, ANA, ACA, anti-DNA topoisomerase I (anti-topo I) and anti-CCP autoantibodies were also measured. Haematological parameters and red blood cell indices, including RDW, mean cell volume, mean haemoglobin concentration and mean corpuscular haemoglobin concentration, were measured using a Siemens Advia 120 Haematology System (Bayer Diagnostic, Tarrytown, NY, USA). Internal organ manifestations were recorded according to a standard protocol as previously described [13]. Each early diffuse SSc case and patients having a forced vital capacity (FVC) 25 mmHg at rest or >30 mmHg on exertion in the absence of an increase in the pulmonary capillary wedge pressure (
Rheumatology 2014;53:14391445 doi:10.1093/rheumatology/keu022 Advance Access publication 21 March 2014
Original article Clinical usefulness of measuring red blood cell distribution width in patients with systemic sclerosis Nelli Farkas1, Andrea Szabo´2, Veronika Lo´ra´nd3, Dona´t Pe´ter Sarlo´s3, Tu¨nde Minier3, Zolta´n Proha´szka4, La´szlo´ Czirja´k3 and Cecı´lia Varju´3
Methods. One hundred and sixty-eight consecutive SSc patients—62 with dcSSc and 106 with lcSSc—were investigated at baseline and after 1-year of follow-up. Measurements in 93 patients with primary RP and 40 healthy subjects served as controls. Results. The median RDW value of patients with SSc was higher [14.2% (25th75th percentiles 13.514.8%) compared with the group of primary RP patients [13.9% (13.414.4%); P < 0.05) and healthy volunteers [13.6% (13.213.8%; P < 0.01]. dcSSc and anti-topoisomerase antibodypositive cases showed elevated RDW values compared with lcSSc and anti-topoisomerase antibodynegative cases (P < 0.05). RDW showed a positive correlation with inflammatory markers, including ESR (P < 0.05) and CRP (P < 0.05), and a negative correlation with forced vital capacity (P < 0.05) and diffusing capacity of the lung for carbon monoxide (DLCO) (P < 0.05) during the follow-up. An increase in RDW of >5% during follow-up was associated with an average 8.9% decrease in left ventricular ejection fraction (LVEF) and 7% in DLCO and these associations were independent of each other. Conclusion. RDW in SSc may represent an integrative measure of multiple pathological processes including extensive vasculopathy, fibrosis or ongoing inflammation. An increase in RDW may indicate an impairment of cardiorespiratory function. Key words: red blood cell distribution width, RDW, systemic sclerosis, left ventricular ejection fraction, lung fibrosis, vasculopathy, inflammation.
Introduction Red blood cell distribution width (RDW) is a biomarker that quantifies variability in red blood cell size, pointing to the level of anisocytosis in the complete blood count. The normal range of RDW is between 11.5 and 14.5% [1]. Elevated RDW can be present during inflammation and
1 Institute of Bioanalysis, 2Institute of Family Medicine, 3Department of Rheumatology and Immunology, University of Pe´cs, Pe´cs and 4Third Department of Internal Medicine, Semmelweis University, Research Laboratory, Budapest, Hungary.
Submitted 9 September 2013; revised version accepted 20 January 2014. Correspondence to: Cecı´lia Varju´, Department of Rheumatology and Immunology, Clinic Center, University of Pe´cs, Aka´c u. 1, H-7632 Pe´cs, Hungary. E-mail: [email protected]
nutritional deficiencies, and co-morbidities including renal failure also influence RDW [24]. RDW is also a predictor of survival in idiopathic pulmonary arterial hypertension (PAH) [5, 6] and an independent prognostic risk factor in cardiovascular or cerebrovascular events in the general population and in patients with heart failure, coronary heart disease or peripheral atherosclerosis [79]. Furthermore, high RDW is closely associated with the risk of carotid artery atherosclerosis in patients with hypertension [10]. Elevated values of RDW can be found in thalassaemia and in other anaemias, including early stage iron, folate or vitamin B12 deficiency, and also can be present in some types of hepatopathy [1, 2, 9]. SSc is a systemic autoimmune disease with generalized obliterative arterial vasculopathy and microvascular lesions [11]. There is a wide spectrum of organ
! The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]
CLINICAL SCIENCE
Objective. Red blood cell distribution width (RDW) is a biomarker quantifying the variability of red blood cell size in peripheral blood. Elevated RDW has been found to be an independent prognostic factor for cardiovascular events. SSc is characterized by generalized micro- and macroangiopathy. Our aim was to investigate RDW as a potential biomarker for the assessment of the severity of vascular involvement.
Downloaded from http://rheumatology.oxfordjournals.org/ at West Virginia University, Health Science Libraryy on July 19, 2015
Abstract
Nelli Farkas et al.
Patients and methods One hundred and sixty-eight consecutive Hungarian (Caucasian) patients (147 females and 21 males; 62 with dcSSc, 106 with lcSSc) were included in the study (Table 1). At the baseline examination the mean age of patients with SSc was 55.1 years (S.D. 12.7), the mean disease duration was 8.1 years (S.D. 7.2) and the mean follow-up was 6.8 years (S.D. 4.0). Patients were divided into diffuse and limited cutaneous subsets by the criteria of LeRoy et al. [19]. During the follow-up, the DMARD treatment of patients had not changed significantly. Four deaths caused by SSc were recorded during the investigative 1-year period. Six patients were lost to follow-up and one of died for reasons other than SSc.
At baseline and after 1 year, pulmonary function tests, echocardiography and the Scleroderma Study Group Activity Index (EScSG) [20] were performed within 6 weeks of the blood test. Clinical characteristics included the presence of subcutaneous calcinosis, telangiectasia, skin hypo-/ hyperpigmentation and active skin ulcers. Modified Rodnan skin score (MRSS) [21], ESR, CRP, ANA, ACA, anti-DNA topoisomerase I (anti-topo I) and anti-CCP autoantibodies were also measured. Haematological parameters and red blood cell indices, including RDW, mean cell volume, mean haemoglobin concentration and mean corpuscular haemoglobin concentration, were measured using a Siemens Advia 120 Haematology System (Bayer Diagnostic, Tarrytown, NY, USA). Internal organ manifestations were recorded according to a standard protocol as previously described [13]. Each early diffuse SSc case and patients having a forced vital capacity (FVC) 25 mmHg at rest or >30 mmHg on exertion in the absence of an increase in the pulmonary capillary wedge pressure (
