Association of Red Blood Cell and Platelet Parameters with Metabolic
                    Syndrome: A Systematic Review and Meta-Analysis of 170,000
                    Patients

Aysal Mahmood; Saba Samad; Hoorain Haider; Wardah Hassan; Rabeea Mushtaq; Aimen Perwaiz; Abraish Ali; Muhammad Azharuddin

doi:10.1055/a-2241-5361

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2024; 56(07): 517-525
DOI: 10.1055/a-2241-5361

Original Article: Endocrine Care

Association of Red Blood Cell and Platelet Parameters with Metabolic Syndrome: A Systematic Review and Meta-Analysis of 170,000 Patients

Aysal Mahmood

¹Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan

,

Saba Samad

¹Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan

,

Hoorain Haider

¹Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan

,

Wardah Hassan

¹Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan

,

Rabeea Mushtaq

¹Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan

,

Aimen Perwaiz

¹Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan

,

Abraish Ali

¹Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan

,

Muhammad Azharuddin

²Hematology and Oncology, USMD Hospital at Arlington, Arlington, USA

› Author Affiliations

Abstract

This systematic review and meta-analysis aim to establish associations between metabolic syndrome (MetS) and erythrocyte and platelet markers, contributing to improved diagnostic tests for identifying individuals at risk. Observational studies and Randomized Controlled Trials (RCTs) were included. The standardized mean difference (SMD) and 95% confidence intervals (CI) of erythrocyte and platelet markers between individuals with and without MetS were used as effect size (inverse variance model). Methodological quality assessment was conducted using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane Risk of Bias tool 2.0 for RCTs. The analysis included 51 articles. Compared to controls, individuals with MetS exhibited significantly higher concentrations of mean red blood cell count [Standardized Mean Difference (95% CI): 0.15 (0.13−0.18); p<0.00001], hemoglobin [0.24 (0.18−0.31); p<0.00001], blood platelet count [5.49 (2.78–8.20); p<0.0001], and red blood cell distribution width [(0.55 (0.05–1.04); p=0.03]. Regarding mean platelet volume [0.16 (– 0.03 to 0.35); p=0.10] and platelet-to-lymphocyte ratio (PLR) [7.48 (–2.85–17.81); p=0.16], a non-significant difference was observed in patients with MetS. There was no statistically significant difference in hematocrit counts between the two groups [0.47 (–0.40 to –1.34); p=0.29]. Biomarkers such as mean red blood cell count, hemoglobin, blood platelet count, and RDW are associated with higher levels in patients in MetS, whereas mean platelet volume and PLR tend to be lower. These markers can potentially provide new avenues for early diagnosis of MetS.

Keywords

red blood cell - platelet - red blood cell distribution width - erythrocyte

Full Text

References

References
1 Grundy SM, Cleeman JI, Daniels SR. et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112: 2735-2752
2 Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech 2009; 2: 231-237
3 Kassi E, Pervanidou P, Kaltsas G. et al. Metabolic syndrome: definitions and controversies. BMC Med 2011; 9: 1-13
4 Ahmadzadeh J, Mansorian B, Attari MMA. et al. The association between hematological parameters and metabolic syndrome in Iranian men: a single center large-scale study. Diabetes Metab Syndr 2018; 12: 17-21
5 Khan MAB, Hashim MJ, King JK. et al. Epidemiology of type 2 diabetes – global burden of disease and forecasted trends. J Epidemiol. Glob Health 2020; 10: 107-111
6 World Obesity Day 2022 – Accelerating action to stop obesity. Accessed May 18, 2023 https://www.who.int/news/item/04-03-2022-world-obesity-day-2022-accelerating-action-to-stop-obesity
7 Najafzadeh MJ, Baniasad A, Shahabinejad R. et al. Investigating the relationship between haematological parameters and metabolic syndrome: a population-based study. Endocrinol Diabetes Metab 2023; 6: e407
8 Urrútia G, Bonfill X. Declaración PRISMA: una propuesta para mejorar la publicación de revisiones sistemáticas y metaanálisis. Med Clin (Barc) 2010; 135: 507-511
9 Ottawa Hospital Research Institute. Accessed June 12, 2023 https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
10 Sterne JAC, Savović J, Page MJ. et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019; 366: 4898
11 Egger M, Smith GD, Schneider M. et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634
12 Vayá A, Hernández-Mijares A, Bonet E. et al. Association between hemorheological alterations and metabolic syndrome. Clin Hemorheol Microcirc 2011; 49: 493-503
13 Vayá A, Alis R, Suescún M. et al. Association of erythrocyte deformability with red blood cell distribution width in metabolic diseases and thalassemia trait. Clin Hemorheol Microcirc 2015; 61: 407-415
14 Lin JD, Chiou WK, Chang HY. et al. Association of hematological factors with components of the metabolic syndrome in older and younger adults. Aging Clin Exp Res 2006; 18: 477-484
15 Demirtunc R, Duman D, Basar M. Effects of doxazosin and amlodipine on mean platelet volume and serum serotonin level in patients with metabolic syndrome: a randomised, controlled study. Clin Drug Investig 2007; 27: 435-441
16 Farah R, Khamisy-Farah R. Significance of MPV, RDW with the presence and severity of metabolic syndrome. Exp Clin Endocrinol Diabetes 2015; 123: 567-570
17 Liu CC, Ko HJ, Liu WS. et al. Neutrophil-to-lymphocyte ratio as a predictive marker of metabolic syndrome. Medicine (Baltimore) 2019; 98: e17537
18 Nardin M, Verdoia M, Barbieri L. et al. Impact of metabolic syndrome on mean platelet volume and its relationship with coronary artery disease. Platelets 2019; 30: 615-623
19 Korkmaz S. Mean platelet volume and platelet distribution width levels in patients with mild psoriasis vulgaris with metabolic syndrome. Adv Dermatol Allergol 2018; 35: 367
20 Chen YL, Hung YJ, He CT. et al. Platelet count can predict metabolic syndrome in older women. Platelets 2015; 26: 31-37
21 Tavil Y, Sen N, Yazici HU. et al. Mean platelet volume in patients with metabolic syndrome and its relationship with coronary artery disease. Thromb Res 2007; 120: 245-250
22 Kazuhiko K, Naoki S, Youichi K. Increased red blood cells in patients with metabolic syndrome. Endocr J 2006; 53: 711-712
23 Huang LL, Dou DM, Liu N. et al. Association of erythrocyte parameters with metabolic syndrome in the Pearl River Delta region of China: a cross sectional study 2018; 8: 19792
24 Vahit D, Mehmet KA, Samet Y. et al. Assessment of monocyte to high density lipoprotein cholesterol ratio and lymphocyte-to-monocyte ratio in patients with metabolic syndrome. Biomark Med 2017; 11: 535-540
25 Buyukkaya E, Karakaş MF, Karakaş E. et al. Correlation of neutrophil to lymphocyte ratio with the presence and severity of metabolic syndrome. Clin Appl Thromb Hemost 2014; 20: 159-163
26 Huang Y, Zhao L, Yan Y. et al. PBMCs to Stress-Associated miR-18a-5p and miR-22-3p ratios as new indicators of metabolic syndrome. Biomed Res Int 2020;
27 Tang K, Liu H, Jiang K. et al. Predictive value of preoperative inflammatory response biomarkers for metabolic syndrome and post-PCNL systemic inflammatory response syndrome in patients with nephrolithiasis. Oncotarget 2017; 8: 85612
28 Haile K, Kedir R, Timerga A. et al. Role of platelet indices as diagnostic and predictive biomarkers for comorbidity of diabetes and metabolic syndrome in southern Ethiopia: A comparative cross-sectional study. PLoS One 2022; 17: e0277542
29 Uslu AU, Sekin Y, Tarhan G. et al. Evaluation of monocyte to high-density lipoprotein cholesterol ratio in the presence and severity of metabolic syndrome. Clin Appl Thromb/Hemost 2018; 24: 828
30 Zhao S, Tang J, Shao S. et al. The relationship between benign prostatic hyperplasia/lower urinary tract symptoms and mean platelet volume: the role of metabolic syndrome. Urol Int 2016; 96: 449-458
31 Lee EY, Kim SJ, Song YJ. et al. Immature platelet fraction in diabetes mellitus and metabolic syndrome. Thromb Res 2013; 132: 692-695
32 Yang XJ, Zhang LY, Ma QH. et al. Platelet parameters in Chinese older adults with metabolic syndrome. Endocr Connect 2020; 9: 696
33 Karakaş UG, Ulusoy KS, Uğurlu M. et al. Total white blood cell count, liver enzymes, and metabolic syndrome in schizophrenia. Turk J Med Sci 2016; 46: 259-264
34 Kutlucan A, Bulur S, Kr S. et al. The relationship between mean platelet volume with metabolic syndrome in obese individuals. Blood Coagul Fibrinol 2012; 23: 388-390
35 Maleki A, Rashidi N, Meybodi HA. et al. Metabolic syndrome and inflammatory biomarkers in adults: a population-based survey in western region of Iran. Int Cardiovasc Res J 2014; 8: 156
36 Akboga MK, Canpolat U, Yuksel M. et al. Platelet to lymphocyte ratio as a novel indicator of inflammation is correlated with the severity of metabolic syndrome: a single center large-scale study. Platelets 2016; 27: 178-183
37 Suriyaprom K, Kaewprasert S, Putpadungwipon P. et al. Association of antioxidant status and inflammatory markers with metabolic syndrome in Thais. J Health Popul Nutr 2019; 38
38 Dehghani MR, Rezaei Y, Fakour S. et al. White blood cell count to mean platelet volume ratio is a prognostic factor in patients with non-ST elevation acute coronary syndrome with or without metabolic syndrome. Korean. Circ J 2016; 46: 229
39 Chen H, Xiong C, Shao X. et al. Lymphocyte to high-density lipoprotein ratio as a new indicator of Inflammation and metabolic syndrome. Diabetes Metab Syndr Obes 2019; 12: 2117-2123
40 Anon. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001; 285: 2486-2497
41 Xie QY, Wang MW, Hu ZY. et al. Screening the influence of biomarkers for metabolic syndrome in occupational population based on the lasso algorithm. Front Public Health 2021; 9: 743731
42 Feldman L, Tubach F, Juliard JM. et al. Impact of diabetes mellitus and metabolic syndrome on acute and chronic on-clopidogrel platelet reactivity in patients with stable coronary artery disease undergoing drug-eluting stent placement. Am Heart J 2014; 168: 940-947
43 Battaglia S, Scialpi N, Berardi E. et al. Gender, BMI and fasting hyperglycaemia influence Monocyte to-HDL ratio (MHR) index in metabolic subjects. PLoS One 2020; 15: e0231927
44 Chen T, Chen H, Xiao H. et al. Comparison of the value of neutrophil to high-density lipoprotein cholesterol ratio and lymphocyte to high-density lipoprotein cholesterol ratio for predicting metabolic syndrome among a population in the Southern Coast of China. Diabetes Metab Syndr Obes 2020; 13: 597
45 Raghavan V, Gunasekar D, Rao KR. Relevance of haematologic parameters in obese women with or without metabolic syndrome. J Clin Diagn Res 2016; 10: EC11
46 De Matteis C, Crudele L, Cariello M. et al. Monocyte-to-HDL ratio (MHR) predicts vitamin D deficiency in healthy and metabolic women: a cross-sectional study in 1048 subjects. Nutrients 2022; 14: 347
47 Belli AA, Kara A, Gok SO. Can hematologic parameters be an indicator of metabolic disorders accompanying rosacea?. Acta Dermatovenerol Croatica 2017; 25: 145-150
48 Yasar Z, Buyuksirin M, Ucsular FD. et al. Is an elevated neutrophil-to-lymphocyte ratio a predictor of metabolic syndrome in patients with chronic obstructive pulmonary disease?. Eur Rev Med Pharmacol Sci 2015; 19: 956-962
49 Kasabri V, Al-ghareeb MI, Saleh MI. et al. Proportional correlates of adipolin and cathepsin S in metabolic syndrome patients with and without prediabetes. Diabetes Metab Syndr 2019; 13: 2403-2408
50 Al Saudi RM, Kasabri V, Naffa R. et al. Glycated LDL-C and glycated HDL-C in association with adiposity, blood and atherogenicity indices in metabolic syndrome patients with and without prediabetes. Ther Adv Endocrinol Metab 2018; 9: 311
51 Dong X, Liao Y, Chen K. et al. Elevated red blood cell distribution width in benign prostatic hyperplasia patients with metabolic syndrome. Int J Clin Exp Med 2015; 8: 1213
52 Alberti KGMM, Zimmet P, Shaw J. The metabolic syndrome--a new worldwide definition. Lancet 2005; 366: 1059-1062
53 Hsu CH, Chen YL, Hsieh CH. et al. Hemogram-based decision tree for predicting the metabolic syndrome and cardiovascular diseases in the elderly. QJM 2021; 114: 363-373
54 Fang KC, Cheng YL, Su CW. et al. Higher platelet counts are associated with metabolic syndrome independent of fatty liver diagnosis. J Chin Med Assoc 2017; 80: 125-132
55 Fu YH, Hsu CH, Lin JD. et al. Using hematogram model to predict future metabolic syndrome in elderly: a 4-year longitudinal study. Aging Male 2015; 18: 38-43
56 Monserrat-Mesquida M, Quetglas-Llabrés M, Capó X. et al. Metabolic syndrome is associated with oxidative stress and proinflammatory state. Antioxidants (Basel) 2020; 9: 236
57 Vichinsartvichai P, Sirirat S. Hematologic parameters as the predictors for metabolic syndrome in perimenopausal and postmenopausal women living in urban area: a preliminary report. Prz Menopauz 2016; 15: 90
58 Alberti KGMM, Eckel RH, Grundy SM. et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International. Circulation 2009; 120: 1640-1645
59 Ding Q, Wang F, Guo X. et al. The relationship between mean platelet volume and metabolic syndrome in patients with type 2 diabetes mellitus: a retrospective study. Medicine 2021; 100: E25303
60 Shanghai C. The suggestion on Chinese metabolic syndrome. [Google Scholar]. Published online. 2004
61 You J, Zhang H, Shen Y. et al. Impact of platelet to lymphocyte ratio and metabolic syndrome on the prognosis of colorectal cancer patients. Onco Targets Ther 2017; 10: 2199
62 Society CD. Suggestions about metabolic syndrome of Chinese diabetes society. Chin. J Diabetes 2004; 12: 156-161
63 Vasil’ev YL, Kytko OV, Smetneva NS. et al. The morphofunctional features of platelets against the background of metabolic syndrome in patients with generalized marginal periodontitis. Diabetes Metab Syndr 2019; 13: 730-733
64 Achmegdanov NM, Butrusova SA, Dedov II. et al. Russian expert’s consensus on metabolic syndrome problem in the Russian Federation: defenition, diagnosis criteria, primary prevention and treatment. Rational Pharmacother Cardiol 2016; 6: 599-606
65 Nakatochi M, Ushida Y, Yasuda Y. et al. Identification of an interaction between VWF rs7965413 and platelet count as a novel risk marker for metabolic syndrome: an extensive search of candidate polymorphisms in a case-control study. PLoS One 2015; 10: e0117591
66 Matsuzawa Y. Metabolic syndrome-definition and diagnostic criteria in Japan. J Atheroscler Thromb 2005; 12: 301
67 Jialal G, Adams-Huet B, Jialal I. Both the platelet count and the platelet: lymphocyte ratio are not increased in nascent metabolic syndrome. Platelets 2019; 30: 1057-1058
68 Wu S, Lin H, Zhang C. et al. Association between erythrocyte parameters and metabolic syndrome in urban Han Chinese: a longitudinal cohort study. BMC Public Health 2013; 13: 989
69 Aoki I, Homori M, Ishikawa K. et al. Stimulatory effect of human insulin on erythroid progenitors (cfu-e and bfu-e) in human cd34+ separated bone marrow cells and the relationship between insulin and erythropoietin. Stem Cells 1994; 12: 329-338
70 Kohsari M, Moradinazar M, Rahimi Z. et al. Association between RBC indices, anemia, and obesity-related diseases affected by body mass index in Iranian Kurdish population: results from a cohort study in western Iran. Int J Endocrinol 2021;
71 Emamian M, Hasanian SM, Tayefi M. et al. Association of hematocrit with blood pressure and hypertension. J Clin Lab Anal 2017; 31: e22124
72 Ellinger VCM, Carlini LT, Moreira RO. et al. Relation between insulin resistance and hematological parameters in a Brazilian sample. Arq Bras Endocrinol Metabol 2006; 50: 114-117
73 Nebeck K, Gelaye B, Lemma S. et al. Hematological parameters and metabolic syndrome: findings from an occupational cohort in Ethiopia. Diabetes Metab Syndr 2012; 6: 22-27
74 Atsma F, Veldhuizen I, de Kort W. et al. Hemoglobin level is positively associated with blood pressure in a large cohort of healthy individuals. Hypertension 2012; 60: 936-941
75 Justo D, Marilus R, Mardi T. et al. The appearance of aggregated erythrocytes in the peripheral blood of individuals with insulin resistance. Diabetes Metab Res Rev 2003; 19: 386-391
76 Lassale C, Curtis A, Abete I. et al. Elements of the complete blood count associated with cardiovascular disease incidence: findings from the EPIC-NL cohort study. Sci Rep 2018; 8: 3290
77 Suslova TE, Sitozhevskii AV., Ogurkova ON. et al. Platelet hemostasis in patients with metabolic syndrome and type 2 diabetes mellitus: cGMP- and NO-dependent mechanisms in the insulin-mediated platelet aggregation. Front Physiol 2015; 5: 501
78 Honing ML, Morrison PJ, Banga JD. et al. Nitric oxide availability in diabetes mellitus. Diabetes Metab Rev 1998; 14: 241-249
79 Ding Q, Wang F, Guo X. et al. The relationship between mean platelet volume and metabolic syndrome in patients with type 2 diabetes mellitus. Medicine (Baltimore) 2021; 100: e25303
80 Lippi G. Genetic and nongenetic determinants of mean platelet volume. Blood 2016; 127: 179-180
81 Vizioli L, Muscari S, Muscari A. The relationship of mean platelet volume with the risk and prognosis of cardiovascular diseases. Int J Clin Pract 2009; 63: 1509-1515
82 Chen YL, Hung YJ, He CT. et al. Platelet count can predict metabolic syndrome in older women. Platelets 2015; 26: 31-37
83 Nebeck K, Gelaye B, Lemma S. et al. Hematological parameters and metabolic syndrome: findings from an occupational cohort in Ethiopia. Diabetes Metab Syndr Clin Res Rev 2012; 6: 22-27

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