Professional Documents
Culture Documents
A R T I C L E I N F O A B S T R A C T
Article history: Background: The present study aimed to explore the association between RDW and CAS in patients with
Received 17 February 2015 ischemic stroke, expecting to nd a new and signicant diagnosis index for clinical practice.
Received in revised form 9 April 2015 Methods: This cross-sectional study involves 432 consecutive patients with primary ischemic stroke
Accepted 10 April 2015
(within 72 h). All subjects were conrmed by magnetic resonance imaging, and underwent physical
Available online 20 April 2015
examination, laboratory tests and carotid ultrasonography check. Finally, 392 patients were included
according to the exclusion criteria. The odds ratios of independent variables were calculated using
Keywords:
stepwise multiple logistic regression.
Red cell blood distribution width
Carotid artery atherosclerosis
Results: Carotid intimal-medial thickness (IMT) and RDW are both signicantly different between CAS
Ischemic stroke group and control group. Univariate analyses show that high-sensitive C-reactive protein (Hs-CRP) and
RDW (r = 0.436) are both in signicantly positive association with IMT. Stepwise multiple logistic
regression shows that RDW is an independent protective factor of CAS in patients with ischemic stroke.
Compared with the lowest quartile, the second to fourth quartiles are 1.13 (95% CI: 1.133.05), 2.02 (95%
CI: 1.664.67), and 3.10 (95% CI: 2.467.65), respectively.
Conclusion: The present study suggested that RDW level were higher than non-CAS in patients with
primary ischemic stroke. Our results facilitated a bridge to connect RDW with ischemic stroke and
further conrmed the role of RDW in the progression of the ischemic stroke.
2015 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.archger.2015.04.005
0167-4943/ 2015 Elsevier Ireland Ltd. All rights reserved.
H. Jia et al. / Archives of Gerontology and Geriatrics 61 (2015) 7275 73
with ischemic stroke, expecting to nd a new signicant diagnosis Distributional normality of each continuous variable was assessed by
index for clinical practice. the KolmogorovSmirnov test. Between-group differences were
tested by Students t-test or Chi-square test, as appropriate.
2. Methods Correlation coefcients between IMT and other variables were
calculated with Pearsons or Spearmans test, as appropriate. Odds
2.1. Study population ratios (ORs) were computed with multiple logistic regressions.
Collinearity diagnostics within variables was applied before the
In this cross-sectional study, totally 432 consecutive patients regression model was built. Statistical analyses were performed on
with primary ischemic stroke were recruited from the Second SPSS 18.0 (SPSS Inc., Chicago, IL, USA), with the signicance level at
Afliated Hospital of Zhengzhou University from November 2013 P < 0.05.
and October 2014. All subjects were conrmed by magnetic
resonance imaging (MRI), and underwent physical examination,
laboratory tests and carotid ultrasonography check. The exclusion 3. Results
criteria are as follows: (1) history of ischemic stroke; (2)
hemorrhagic stroke, mixed stroke or adenomas apoplexy; (3) 3.1. Baseline characteristics of subjects
second stroke due to other factors (e.g. surgery); (4) severe renal
function impairment, gout, diabetic ketoacidosis, coronary bypass The baseline characteristics are shown in Table 1. Totally 180
surgery or angioplasty; and (5) incapability of communication due CAS patients and 212 non-CAS patients were nally included. The
to severe stroke. According to the above criteria, 40 patients were patients were aged from 60 to 70 years old. The sex ratios were
excluded and 392 patients were included. The study protocol was comparable between groups. IMTs and RDWs are both signicantly
approved by the Ethics Committee at Southern Medical School of different between groups (both P < 0.001). Compared with the
Zhengzhou University. control group, the CAS group tended to be smokers, hypertensive
and higher levels in BMI, waist circumference, SBP, DBP,
2.2. Physical and laboratory examinations triglyceride, total cholesterol, 2hPG, serum creatinine, uric acid,
blood urea nitrogen, Hs-CRP, WBC and hemoglobin (P < 0.05).
The patients demographic characteristics including age, sex, There is no difference in other variables between groups (P > 0.05).
height, weight, waist circumference, alcohol use and smoking The results were shown in Table 1.
status were acquired through a standardized questionnaire.
Smoking was dened as at least one cigarette daily for 1 year 3.2. Univariate analyses
and drinking was dened as at least 50 g of alcohol daily for 1 year.
Body mass index (BMI) was calculated as weight (kg) divided by In the whole study population, HDL-cholesterol is negatively
height squared (m2). associated with IMT. IMT is positively and signicantly associated
Hypertension was dened as systolic blood pressure (SBP) with BMI, smoking status, SBP, triglyceride, serum creatinine, uric
140 mmHg and (or) diastolic blood pressure (DBP) 90 mmHg
(Chobanian et al., 2003). Diabetes was determined through self-
Table 1
reporting with a validated history or through new diagnosis by an oral Clinical characteristics of ischemic stroke patients with and without CAS.
glucose tolerance test (WHO: fasting plasma glucose 7.0 mmol/L, or
Parameters Carotid artery atherosclerosis P
2-h postprandial glucose 11.1 mmol/L (Kuzuya et al., 2002).
Coronary artery disease was diagnosed from history of myocardial No (n = 212) Yes (n = 180)
infarction or more than 75% narrowing of coronary artery. Age (year) 65.9 10.2 64.8 9.8 0.279
Blood routine indices including red blood cell (RBC) count, Sex (male) 107 (50.5%) 94 (52.2%) 0.729
white blood cell (WBC) count, platelet count, hemoglobin count, Smoking (yes) 47 (22.2%) 61 (33.9%) 0.009
Drinking history (yes) 21 (9.9%) 27 (15.0%) 0.125
RDW and mean corpuscular volume were tested using an
Hypertension (yes) 84 (39.6%) 94 (52.2%) 0.013
automated biochemical analyzer. Serum creatinine level, plasma Coronary artery disease (yes) 25 (11.6%) 19 (10.6%) 0.699
glucose level, serum lipid status (total cholesterol, low- and high- Diabetes mellitus (yes) 28 (13.2%) 26 (14.4%) 0.723
density lipoprotein and triglyceride) and inammatory factors (e.g. Body mass index (kg/m2) 25.8 2.8 26.6 2.5 0.003
high-sensitive C-reactive protein, Hs-CRP) were also determined. Waist circumference (cm) 88.3 8.0 91.4 8.2 <0.001
Systolic blood pressure 138.8 9.3 141.8 10.5 0.003
(mmHg)
2.3. Carotid ultrasonography Diastolic blood pressure 78.5 10.6 80.8 11.2 0.037
(mmHg)
Carotid ultrasonography on each subject was performed by a Triglyceride (mmol/dL) 1.4 0.5 1.7 0.5 <0.001
HDL-cholesterol (mmol/dL) 1.1 0.2 1.0 0.2 <0.001
single sonographer with a commercial machine (ALOCA Prosound
LDL-cholesterol (mmol/dL) 3.2 1.0 3.3 0.9 0.302
a5) with a linear probe at frequency of 7.510.0 Hz. The distal Total cholesterol (mmol/dL) 5.2 0.9 5.4 0.9 0.029
walls from the anterior, lateral and posterior longitudinal walls Fasting plasma glucose 5.6 2.1 5.9 2.3 0.178
were recorded for carotid IMT. Both the left and right common (mmol/dL)
carotid arteries were examined. IMT was calculated as mean of the 2 h postprandial glucose 9.9 3.6 10.6 2.8 0.035
(mmol/dL)
bulb and common carotid segment measurements. Carotid plaque HbA1c (%) 5.9 1.2 6.2 1.8 0.050
was dened as plaque encroaching into the arterial lumen by at Serum creatinine (mmol/dL) 68.3 9.0 74.1 10.5 <0.001
least 0.5 mm or 50% of the surrounding IMT and IMT 1.5 mm Serum uric acid (mmol/L) 353.9 126.3 396.2 125.8 0.001
(Touboul et al., 2012). Blood urea nitrogen (mmol/L) 4.7 1.2 4.9 1.1 0.011
Hs-CRP (mg/dL) 2.3 0.7 2.6 0.9 <0.001
Red blood cell (1012/L) 4.4 0.4 4.6 0.4 <0.001
2.4. Statistical analysis White blood cell (109/L) 5.8 2.4 6.4 2.5 0.016
Red cell distribution width (%) 13.4 0.2 14.2 0.4 <0.001
The patients were divided into a CAS group and a non-CAS Blood platelet (109/L) 210.6 64 205.4 54 0.390
group. Data were reported as mean standard deviation for Hemoglobin (g/L) 155.6 13.4 149.2 14.8 <0.001
IMT (mm) 0.84 0.19 0.98 0.13 <0.001
qualitative variables and as percentages for quantitative variables.
74 H. Jia et al. / Archives of Gerontology and Geriatrics 61 (2015) 7275
Table 3
Multiple logistic regression for CAS in patients with ischemic stroke.
inammation markers (e.g. interleukin-6, -10) and oxidative stress between inammatory and non-inammatory diarrhea. Digestive Diseases and
Sciences, 58(2), 504508.
materials were not reported. Third, our study involved the Kohler, J. J., Cucoranu, I., Fields, E., Green, E., He, S., Hoying, A., et al. (2009). Transgenic
population with primary ischemic stroke, but not with other mitochondrial superoxide dismutase and mitochondrially targeted catalase pre-
types of stroke or cardiovascular disease. Therefore, it should be vent antiretroviral-induced oxidative stress and cardiomyopathy. Laboratory In-
vestigation, 89, 782790.
cautious when the ndings are applied into other populations. But Kuzuya, T., Nakagawa, S., Satoh, J., Kanazawa, Y., Iwamoto, Y., Kobayashi, M., et al.
this might strengthen our results because of excluding some (2002). Report of the Committee on the classication and diagnostic criteria of
confounders. Finally, our results suggest a positive relationship diabetes mellitus. Diabetes Research and Clinical Practice, 55, 6585.
Lappe, J. M., Horne, B. D., Shah, S. H., May, H. T., Muhlestein, J. B., Lappe, D. L., et al.
between RDW and IMT in patients with ischemic stroke, but (2011). Red cell distribution width, C-reactive protein, the complete blood count,
cannot clearly illustrate the biological mechanism. Prospective and mortality in patients with coronary disease and a normal comparison popu-
studies focusing on the role of RDW on the development of CAS are lation. Clinica Chimica Acta, 412(23-24), 20942099.
Li, Z. Z., Chen, L., Yuan, H., Zhou, T., & Kuang, Z. M. (2014). Relationship between red
needed.
blood cell distribution width and early-stage renal function damage in patients
with essential hypertension. Journal of Hypertension, 32(12), 24502455. 2456.
5. Conclusion Lippi, G., Targher, G., Montagnana, M., Salvagno, G. L., Zoppini, G., Guidi, G. C., et al.
(2009). Relation between red blood cell distribution width and inammatory
biomarkers in a large cohort of unselected outpatients. Archives of Pathology &
In conclusion, the present study suggested that RDW level were Laboratory Medicine, 133, 628632.
higher than non-CAS in patients with primary ischemic stroke. Our Patel, K. V., Ferrucci, L., Ershler, W. B., Longo, D. L., & Guralnik, J. M. (2009). Red blood
results facilitated a bridge to connect RDW with ischemic stroke cell distribution width and the risk of death in middle-aged and older adults.
Archives of Internal Medicine, 169, 515523.
and further conrmed the role of RDW in the progression of the Perlstein, T. S., Weuve, J., Pfeffer, M. A., & Beckman, J. A. (2009). Red blood cell
ischemic stroke. distribution width and mortality risk in a community-based prospective cohort.
Archives of Internal Medicine, 169, 588594.
Piechota, W., & Piechota, W. (2005). Correlation of high-sensitivity CRP concentration
Conict of interest with the extent of coronary atherosclerosis in men with symptoms of ischemic
heart disease. Polski Merkuriusz Lekarski, 18(107), 511515.
There is no interest conict. Ramirez-Moreno, J. M., Gonzalez-Gomez, M., Ollero-Ortiz, A., Roa-Montero, A. M.,
Gomez-Baquero, M. J., Constantino-Silva, A. B., et al. (2013). Relation between
red blood cell distribution width and ischemic stroke: A casecontrol study.
Acknowledgements International Journal of Stroke, 8(6), E36.
Sangoi, M. B., Guarda, N. S., Rodel, A. P., Zorzo, P., Borges, P. O., Cargnin, L. P., et al.
(2014). Prognostic value of red blood cell distribution width in prediction of in-
We thank all our colleagues working in the Second Afliated hospital mortality in patients with acute myocardial infarction. Clinical Laboratory,
Hospital of Zhengzhou University. 60(8), 13511356.
Savoiu, G., Dragan, S., Cristescu, C., Serban, C., Noveanus, L., Ionescu, D., et al. (2009).
References Measurement of plasma ox-LDL and carotid IMT may represent useful markers for
atherosclerosis and may represent potential targets for therapeutic interventions.
Revista Medico-Chirurgicala a Societatii de Medici si Naturalisti din Iasi, 113(2), 397
Almer, G., Frascione, D., Pali-Scholl, I., Vonach, C., Lukschal, A., Stremnitzer, C., et al.
401.
(2013). Interleukin-10: An anti-inammatory marker to target atherosclerotic
Shao, Q., Li, L., Li, G., & Liu, T. (2015). Prognostic value of red blood cell distribution
lesions via PEGylated liposomes. Molecular Pharmaceutics, 10(1), 175186.
width in heart failure patients: A meta-analysis. International Journal of Cardiology,
Ani, C., & Ovbiagele, B. (2009). Elevated red blood cell distribution width predicts
179, 495499.
mortality in persons with known stroke. Journal of the Neurological Sciences, 277(1
Suematsu, N., Tsutsui, H., Wen, J., Kang, D., Ikeuchi, M., Ide, T., et al. (2003). A-oxidative
2), 103108.
stress mediates tumor necrosis factor Induced mitochondrial DNA damage and
Chobanian, A. V., Bakris, G. L., Black, H. R., Cushman, W. C., Green, L. A., Izzo, J. J., et al.
dysfunction in cardiac myocytes. Circulation, 107, 14181423.
(2003). Seventh report of the Joint National Committee on Prevention, Detection,
Sun, X. P., Chen, W. M., Sun, Z. J., Ding, X. S., Gao, X. Y., Liang, S. W., et al. (2014). Impact
Evaluation, and Treatment of High Blood Pressure. Hypertension, 42, 12061252.
of red blood cell distribution width on long-term mortality in patients with ST-
Ekart, R., Hojs, R., Hojs-Fabjan, T., & Balon, B. P. (2005). Predictive value of carotid intima
elevation myocardial infarction. Cardiology, 128(4), 343348.
media thickness in hemodialysis patients. Articial Organs, 29, 615619.
Tonelli, M., Sacks, F., Arnold, M., Moye, L., Davis, B., Pfeffer, M., et al. (2008). Relation
Everson-Rose, S. A., Roetker, N. S., Lutsey, P. L., Kershaw, K. N., Longstreth, W. J., Sacco,
between red blood cell distribution width and cardiovascular event rate in people
R. L., et al. (2014). Chronic stress, depressive symptoms, anger, hostility, and risk of
with coronary disease. Circulation, 117, 163168.
stroke and transient ischemic attack in the multi-ethnic study of atherosclerosis.
Touboul, P. J., Hennerici, M. G., Meairs, S., Adams, H., Amarenco, P., Bornstein, N., et al.
Stroke, 45(8), 23182323.
(2012). Mannheim carotid intima-media thickness and plaque consensus (2004
Ferrucci, L., Guralnik, J. M., Woodman, R. C., Bandinelli, S., Lauretani, F., Corsi, A. M.,
20062011). An update on behalf of the advisory board of the 3rd, 4th and 5th
et al. (2005). Proinammatory state and circulating erythropoietin in persons with
watching the risk symposia, at the 13th, 15th and 20th European Stroke Confer-
and without anemia. The American Journal of Medicine, 118, 1288.
ences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg,
Grant, B. J., Kualkar, D. P., Muti, P., McCann, S. E., Trevisan, M., Freudenheim, J. L., et al.
Germany, 2011. Cerebrovascular Diseases, 34, 290296.
(2003). Relation between lung function and RBC distribution width in a popula-
Vaya, A., Hernandez, V., Rivera, L., Hernandez, J. L., Lago, A., Espana, F., et al. (2014). Red
tion-based study. Chest, 124, 494500.
blood cell distribution width in patients with cryptogenic stroke. Clinical and
Guaricci, A. I., Brunetti, N. D., Di Biase, M., & Pontone, G. (2015). Cardiovascular Clinical
Applied Thrombosis/Hemostasis pii:1076029614547262 (Epub ahead of print
Risk constrains to a powerful primary prevention: Carotid atherosclerosis in toto
25.08.14).
and low dose computed tomography coronary angiography. International Journal of
Wen, Y. (2010). High red blood cell distribution width is closely associated with risk of
Cardiology, 178, 147148.
carotid artery atherosclerosis in patients with hypertension. Experimental & Clini-
Hojs, R. (2000). Carotid intima-media thickness and plaques in hemodialysis patients.
cal Cardiology, 15(3), 3740.
Articial Organs, 24, 691695.
Willeit, P., Thompson, S. G., Agewall, S., Bergstrom, G., Bickel, H., Catapano, A. L., et al.
Karamouzis, I., Saradis, P. A., Karamouzis, M., Iliadis, S., Haidich, A. B., Sioulis, A., et al.
(2014). Inammatory markers and extent and progression of early atherosclerosis:
(2008). Increase in oxidative stress but not in antioxidant capacity with advancing
Meta-analysis of individual-participant-data from 20 prospective studies of the
stages of chronic kidney disease. American Journal of Nephrology, 28(3), 397404.
PROG-IMT collaboration. European Journal of Preventive Cardiology
Kim, D. H., Kang, S. H., Jeong, W. S., Moon, H. S., Lee, E. S., Kim, S. H., et al. (2013). Serum
pii:2047487314560664 (Epub ahead of print 21.11.14).
C-reactive protein (CRP) levels in young adults can be used to discriminate