Hypertriglyceridemia is Associated With White Blood Cell Count and Red Cell Distribution Width: A Gender Stratified Analysis in a Population-Based Study
AbstractHypertriglyceridemia is a common form of dyslipidemia and is associated with several comorbidities, such as increased risk of pancreatitis and cardiovascular diseases (CVD). The white blood cell (WBC) count is a non-specific inflammatory marker associated with a wide variety of diseases such as diabetes, hypertension, and atherosclerotic cardiovascular disease. The objective of this study was to perform a gender-stratified examination of the association between hypertriglyceridemia and hematological parameters in a large sample of Iranian population. The triglyceride (TG) levels and hematological parameters were measured in 9,780 participants (40% males and 60% females) aged 35-65 years, enrolled in a population-based cohort (MASHAD) study in northeastern Iran. Participants were stratified into three groups based on the definition of hypertriglyceridemia: TG<150 mg/dl (n=6521), TG=150-199 mg/dl (n=1597), and TG≥200 mg/dl (n=1662). A complete blood count (CBC) was obtained for all the subjects. The mean WBC count increased with increasing severity of hypertriglyceridemia among both men and women. Participants with high and very high TG levels had significantly higher WBC count, RBC count, platelet count, hemoglobin, hematocrit, and mean corpuscular hemoglobin concentration and significantly lower RDW. After performing multivariate logistic regression, WBC count and RDW were independently related to hypertriglyceridemia. In conclusion, hypertriglyceridemia is associated with elevated WBC count which may partly explain the observed association between hypertriglyceridemia and CVD.
Chien KL, Fang WH, Wen HC, Lin HP, Lin YL, Lin SW, et al. APOA1/C3/A5 haplotype and risk of hypertriglyceridemia in Taiwanese. Clinica chimica acta; international journal of clinical chemistry. 2008;390(1-2):56-62.
Lai CQ, Tai ES, Tan CE, Cutter J, Chew SK, Zhu YP, et al. The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore. Journal of lipid research. 2003;44(12):2365-73.
Huang M-C, Wang T-N, Liu Y-L, Pa T-H, Tu H-P, Huang Y-C, et al. Effect of SstI polymorphism of the apolipoprotein CIII gene and environmental factors on risks of hypertriglyceridemia in Taiwan aborigines. Circulation Journal. 2006;70(8):1030-6.
Nestel P, Hirsch E. Mechanism of alcohol-induced hypertriglyceridemia. Journal of Laboratory and Clinical Medicine. 1965;66:357-65.
NCEP. 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(19):2486-97.
Linares CL, Pelletier AL, Czernichow S, Vergnaud AC, Bonnefont-Rousselot D, Levy P, et al. Acute pancreatitis in a cohort of 129 patients referred for severe hypertriglyceridemia. Pancreas. 2008;37(1):13-2.
Gan SI, Edwards AL, Symonds CJ, Beck PL. Hypertriglyceridemia-induced pancreatitis: a case-based review. World Journal of Gastroenterology. 2006;12(44):7197.
Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007;115(4):450-8.
Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a metaanalysis of population-based prospective studies. Journal of cardiovascular risk. 1996;3(2):213-9.
Subramanian S, Chait A. Hypertriglyceridemia secondary to obesity and diabetes. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 2012;1821(5):819-25.
Kabagambe EK, Ordovas JM, Tsai MY, Borecki IB, Hopkins PN, Glasser SP, et al. Smoking, inflammatory patterns and postprandial hypertriglyceridemia. Atherosclerosis. 2009;203(2):633-9.
Bessembinders K, Wielders J, van de Wiel A. Severe hypertriglyceridemia influenced by alcohol (SHIBA). Alcohol and alcoholism. 2011;46(2):113-6.
Tabatabaei-Malazy O, Qorbani M, Samavat T, Sharifi F, Larijani B, Fakhrzadeh H. Prevalence of dyslipidemia in iran: a systematic review and meta-analysis study. International journal of preventive medicine. 2014;5(4):373-93.
Whitworth JA. Relationship between white blood cell count and incident hypertension. Am J Hypertens. 2004;17(9):861; author reply -2.
Nakanishi N, Yoshida H, Matsuo Y, Suzuki K, Tatara K. White blood-cell count and the risk of impaired fasting glucose or Type II diabetes in middle-aged Japanese men. Diabetologia. 2002;45(1):42-8.
Jee SH, Park JY, Kim HS, Lee TY, Samet JM. White blood cell count and risk for all-cause, cardiovascular, and cancer mortality in a cohort of Koreans. Am J Epidemiol. 2005;162(11):1062-9.
Shankar A, Mitchell P, Rochtchina E, Wang JJ. The association between circulating white blood cell count, triglyceride level and cardiovascular and all-cause mortality: population-based cohort study. Atherosclerosis. 2007;192(1):177-83.
McPherson RA, Pincus MR. Henry's clinical diagnosis and management by laboratory methods: Elsevier Health Sciences; 2016.
Felker GM, Allen LA, Pocock SJ, Shaw LK, McMurray JJ, Pfeffer MA, et al. Red cell distribution width as a novel prognostic marker in heart failure: data from the CHARM Program and the Duke Databank. Journal of the American College of Cardiology. 2007;50(1):40-7.
Cavusoglu E, Chopra V, Gupta A, Battala VR, Poludasu S, Eng C, 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(2):141-6.
Huang ZS, Chien KL, Yang CY, Tsai KS, Wang CH. Peripheral differential leukocyte counts in humans vary with hyperlipidemia, smoking, and body mass index. Lipids. 2001;36(3):237-45.
Nagasawa N, Tamakoshi K, Yatsuya H, Hori Y, Ishikawa M, Murata C, et al. Association of white blood cell count and clustered components of metabolic syndrome in Japanese men. Circulation journal : official journal of the Japanese Circulation Society. 2004;68(10):892-7.
Nakanishi N, Sato M, Shirai K, Nakajima K, Murakami S, Takatorige T, et al. Associations between white blood cell count and features of the metabolic syndrome in Japanese male office workers. Ind Health. 2002;40(3):273-7.
Rong L. Association of white blood cell count with metabolic syndrome [J]. Journal of Chongqing Medical University. 2006;4:011.
Alipour A, van Oostrom AJ, Izraeljan A, Verseyden C, Collins JM, Frayn KN, et al. Leukocyte activation by triglyceride-rich lipoproteins. Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28(4):792-7.
Ghayour-Mobarhan M, Moohebati M, Esmaily H, Ebrahimi M, Parizadeh SMR, Heidari-Bakavoli AR, et al. Mashhad stroke and heart atherosclerotic disorder (MASHAD) study: design, baseline characteristics and 10-year cardiovascular risk estimation. International journal of public health. 2015;60(5):561-72.
Kazemi-Bajestani SMR, Ghayour-Mobarhan M, Ebrahimi M, Ebrahimi M, Moohebati M, Esmaeili H, et al. C-reactive protein associated with coronary artery disease in Iranian patients with angiographically defined coronary artery disease. Clinical laboratory. 2007;53(1/2):49.
Mirhafez SR, Mohebati M, Feiz Disfani M, Saberi Karimian M, Ebrahimi M, Avan A, et al. An imbalance in serum concentrations of inflammatory and anti-inflammatory cytokines in hypertension. Journal of the American Society of Hypertension : JASH. 2014;8(9):614-23.
Emamian M, Hasanian SM, Tayefi M, Bijari M, Movahedian Far F, Shafiee M, et al. Association of hematocrit with blood pressure and hypertension. J Clin Lab Anal. 2017.
Kazemi-Bajestani SM, Tayefi M, Ebrahimi M, Heidari-Bakavoli AR, Moohebati M, Parizadeh SM, et al. The prevalence of metabolic syndrome increases with serum high sensitivity C-reactive protein concentration in individuals without a history of cardiovascular disease: a report from a large Persian cohort. Ann Clin Biochem. 2017:4563216676842.
Williams L. 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) final report. Circulation. 2002;106(25):3143-.
Alipour A, Gasthuis SF, van Oostrom AJ, Hosp SA, Izraeljan A, Collins J, et al. Triglyceride-mediated Leukocyte Activation: a Potential Mechanism for Atherogenesis. Circulation. 2006;114(Suppl 18):II_341-II_.
Wanten GJ, Geijtenbeek TB, Raymakers RA, van Kooyk Y, Roos D, Jansen JB, et al. Medium-chain, triglyceride-containing lipid emulsions increase human neutrophil β 2 integrin expression, adhesion, and degranulation. Journal of Parenteral and Enteral Nutrition. 2000;24(4):228-33.
Wanten G, van Emst-De Vries S, Naber T, Willems P. Nutritional lipid emulsions modulate cellular signaling and activation of human neutrophils. Journal of lipid research. 2001;42(3):428-36.
Van Oostrom A, Sijmonsma T, Rabelink T, Van Asbeck B, Cabezas MC. Postprandial leukocyte increase in healthy subjects. Metabolism: clinical and experimental. 2003;52(2):199-202.
Van Oostrom A, Sijmonsma T, Verseyden C, Jansen E, De Koning E, Rabelink T, et al. Postprandial recruitment of neutrophils may contribute to endothelial dysfunction. Journal of lipid research. 2003;44(3):576-83.
van Oostrom AJ, Rabelink TJ, Verseyden C, Sijmonsma TP, Plokker HW, De Jaegere PP, et al. Activation of leukocytes by postprandial lipemia in healthy volunteers. Atherosclerosis. 2004;177(1):175-82.
van Oostrom AJ, Plokker HW, van Asbeck BS, Rabelink TJ, van Kessel KP, Jansen EH, et al. Effects of rosuvastatin on postprandial leukocytes in mildly hyperlipidemic patients with premature coronary sclerosis. Atherosclerosis. 2006;185(2):331-9.
Saxena R, Madhu SV, Shukla R, Prabhu KM, Gambhir JK. Postprandial hypertriglyceridemia and oxidative stress in patients of type 2 diabetes mellitus with macrovascular complications. Clinica chimica acta. 2005;359(1):101-8.
Cardona F, Túnez I, Tasset I, Garrido-Sánchez L, Collantes E, Tinahones FJ. Circulating antioxidant defences are decreased in healthy people after a high-fat meal. British journal of nutrition. 2008;100(02):312-6.
Cardona F, Tunez I, Tasset I, Murri M, Tinahones FJ. Similar increase in oxidative stress after fat overload in persons with baseline hypertriglyceridemia with or without the metabolic syndrome. Clin Biochem. 2008;41(9):701-5.
Postiglione A, Napoli C. Hyperlipidaemia and atherosclerotic cerebrovascular disease. Current opinion in lipidology. 1995;6(4):236-42.
Le N-A, Walter MF. The role of hypertriglyceridemia in atherosclerosis. Current atherosclerosis reports. 2007;9(2):110-5.
Nieto FJ, Szklo M, Folsom AR, Rock R, Mercuri M. Leukocyte count correlates in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. American journal of epidemiology. 1992;136(5):525-37.
Kannel WB, Anderson K, Wilson PW. White blood cell count and cardiovascular disease: insights from the Framingham Study. Jama. 1992;267(9):1253-6.
Bae JH, Bassenge E, Kim KB, Kim YN, Kim KS, Lee HJ, et al. Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress. Atherosclerosis. 2001;155(2):517-23.
Benitez MB, Cuniberti L, Fornari MC, Gomez Rosso L, Berardi V, Elikir G, et al. Endothelial and leukocyte adhesion molecules in primary hypertriglyceridemia. Atherosclerosis. 2008;197(2):679-87.
Vaya A, Carmona P, Badia N, Hernandez-Mijares A, Bautista D. Association between high red blood cell distribution width and metabolic syndrome. Influence of abdominal obesity. Clin Hemorheol Microcirc. 2011;47(1):75-7.
Vaya A, Sarnago A, Fuster O, Alis R, Romagnoli M. Influence of inflammatory and lipidic parameters on red blood cell distribution width in a healthy population. Clin Hemorheol Microcirc. 2015;59(4):379-85.
Sanchez-Chaparro MA, Calvo-Bonacho E, Gonzalez-Quintela A, Cabrera M, Sainz JC, Fernandez-Labandera C, et al. Higher red blood cell distribution width is associated with the metabolic syndrome: results of the Ibermutuamur CArdiovascular RIsk assessment study. Diabetes care. 2010;33(3):e40.