Association of peripheral differential leukocyte counts with dyslipidemia risk in Chinese patients with hypertension: insight from the China Stroke Primary Prevention Trial

The aim of the present study was to examine the association between peripheral differential leukocyte counts and dyslipidemia in a Chinese hypertensive population. A total of 10,866 patients with hypertension were enrolled for a comprehensive assessment of cardiovascular risk factors using data from the China Stroke Primary Prevention Trial. Plasma lipid levels and total leukocyte, neutrophil, and lymphocyte counts were determined according to standard methods. Peripheral differential leukocyte counts were consistently and positively associated with serum total cholesterol (TC), LDL cholesterol (LDL-C), and TG levels (all P < 0.001 for trend), while inversely associated with HDL cholesterol levels (P < 0.05 for trend). In subsequent analyses where serum lipids were dichotomized (dyslipidemia/normolipidemia), we found that patients in the highest quartile of total leukocyte count (≥7.6 × 109 cells/l) had 1.64 times the risk of high TG [95% confidence interval (CI): 1.46, 1.85], 1.34 times the risk of high TC (95% CI: 1.20, 1.50), and 1.24 times the risk of high LDL-C (95% CI: 1.12, 1.39) compared with their counterparts in the lowest quartile of total leukocyte count. Similar patterns were also observed with neutrophils and lymphocytes. In summary, these findings indicate that elevated differential leukocyte counts are directly associated with serum lipid levels and increased odds of dyslipidemia. The aim of the present study was to examine the association between peripheral differential leukocyte counts and dyslipidemia in a Chinese hypertensive population. A total of 10,866 patients with hypertension were enrolled for a comprehensive assessment of cardiovascular risk factors using data from the China Stroke Primary Prevention Trial. Plasma lipid levels and total leukocyte, neutrophil, and lymphocyte counts were determined according to standard methods. Peripheral differential leukocyte counts were consistently and positively associated with serum total cholesterol (TC), LDL cholesterol (LDL-C), and TG levels (all P < 0.001 for trend), while inversely associated with HDL cholesterol levels (P < 0.05 for trend). In subsequent analyses where serum lipids were dichotomized (dyslipidemia/normolipidemia), we found that patients in the highest quartile of total leukocyte count (≥7.6 × 109 cells/l) had 1.64 times the risk of high TG [95% confidence interval (CI): 1.46, 1.85], 1.34 times the risk of high TC (95% CI: 1.20, 1.50), and 1.24 times the risk of high LDL-C (95% CI: 1.12, 1.39) compared with their counterparts in the lowest quartile of total leukocyte count. Similar patterns were also observed with neutrophils and lymphocytes. In summary, these findings indicate that elevated differential leukocyte counts are directly associated with serum lipid levels and increased odds of dyslipidemia. Atherosclerosis is a multi-step chronic inflammatory disease. Largely characterized by the formation of lipid and immune-cell-containing plaques in the intima of large and mid-sized arteries (1Libby P. Lichtman A.H. Hansson G.K. Immune effector mechanisms implicated in atherosclerosis: from mice to humans.Immunity. 2013; 38: 1092-1104Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar), it is often the underlying cause of CVDs and stroke (1Libby P. Lichtman A.H. Hansson G.K. Immune effector mechanisms implicated in atherosclerosis: from mice to humans.Immunity. 2013; 38: 1092-1104Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar, 2Hansson G.K. Hermansson A. The immune system in atherosclerosis.Nat. Immunol. 2011; 12: 204-212Crossref PubMed Scopus (1610) Google Scholar, 3Legein B. Temmerman L. Biessen E.A. Lutgens E. Inflammation and immune system interactions in atherosclerosis.Cell. Mol. Life Sci. 2013; 70: 3847-3869Crossref PubMed Scopus (213) Google Scholar). Traditionally, atherosclerosis was thought to result from passive lipid accumulation in the arterial vessel wall. However, a growing body of evidence suggests that the pathogenesis of atherosclerosis is much more complex than formerly believed. Immune cells and inflammation play a key role in its pathogenesis in conjunction with hyperlipidemia (4Schaftenaar F. Frodermann V. Kuiper J. Lutgens E. Atherosclerosis: the interplay between lipids and immune cells.Curr. Opin. Lipidol. 2016; 27: 209-215Crossref PubMed Scopus (158) Google Scholar). However, how lipids interact with the immune system is largely unknown. There is some limited evidence (5Tall A.R. Yvan-Charvet L. Cholesterol, inflammation and innate immunity.Nat. Rev. Immunol. 2015; 15: 104-116Crossref PubMed Scopus (804) Google Scholar, 6Simon A. Cholesterol metabolism and immunity.N. Engl. J. Med. 2014; 371: 1933-1935Crossref PubMed Scopus (39) Google Scholar) showing that increased levels of LDL promote cholesterol accumulation in the matrix beneath the endothelial cell layer of blood vessels (7Moore K.J. Tabas I. Macrophages in the pathogenesis of atherosclerosis.Cell. 2011; 145: 341-355Abstract Full Text Full Text PDF PubMed Scopus (1814) Google Scholar) and promote an inflammatory response in the artery wall, driving the process of atherosclerosis. This is opposed by HDL, which promotes cellular efflux of cholesterol and reduces inflammation (5Tall A.R. Yvan-Charvet L. Cholesterol, inflammation and innate immunity.Nat. Rev. Immunol. 2015; 15: 104-116Crossref PubMed Scopus (804) Google Scholar). The early inflammatory response to retained cholesterol is enhanced by oxidative modification of the LDL cholesterol (LDL-C) trapped in the vessel wall (7Moore K.J. Tabas I. Macrophages in the pathogenesis of atherosclerosis.Cell. 2011; 145: 341-355Abstract Full Text Full Text PDF PubMed Scopus (1814) Google Scholar). Accumulated oxidized LDL leads to decreased cholesterol efflux from macrophage foam cells (8Ouimet M. Wang M.D. Cadotte N. Ho K. Marcel Y.L. Epoxycholesterol impairs cholesteryl ester hydrolysis in macrophage foam cells, resulting in decreased cholesterol efflux.Arterioscler. Thromb. Vasc. Biol. 2008; 28: 1144-1150Crossref PubMed Scopus (22) Google Scholar), amplifies the toll-like receptor signaling in macrophages (9Stewart C.R. Stuart L.M. Wilkinson K. van Gils J.M. Deng J. Halle A. Rayner K.J. Boyer L. Zhong R. Frazier W.A. et al.CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer.Nat. Immunol. 2010; 11: 155-161Crossref PubMed Scopus (1091) Google Scholar, 10Zhu X. Owen J.S. Wilson M.D. Li H. Griffiths G.L. Thomas M.J. Hiltbold E.M. Fessler M.B. Parks J.S. Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol.J. Lipid Res. 2010; 51: 3196-3206Abstract Full Text Full Text PDF PubMed Scopus (246) Google Scholar), and activates endothelial cells. Activation of arterial endothelial cells leads to recruitment of blood-borne monocytes into atherosclerotic lesion sites within the vessel wall (11Glass C.K. Witztum J.L. Atherosclerosis. the road ahead.Cell. 2001; 104: 503-516Abstract Full Text Full Text PDF PubMed Scopus (2636) Google Scholar, 12Mestas J. Ley K. Monocyte-endothelial cell interactions in the development of atherosclerosis.Trends Cardiovasc. Med. 2008; 18: 228-232Crossref PubMed Scopus (391) Google Scholar) and augments the production of cytokines and chemokines (7Moore K.J. Tabas I. Macrophages in the pathogenesis of atherosclerosis.Cell. 2011; 145: 341-355Abstract Full Text Full Text PDF PubMed Scopus (1814) Google Scholar) that interact with cognate chemokine receptors on monocytes. Accumulation of monocytes and monocyte-derived ma­crophages in the wall of large arteries leads to chronic inflammation and the development and progression of atherosclerosis. A large number of epidemiological studies has intensively evaluated multiple markers of inflammation as potential risk factors for the development of atherosclerosis and CVDs, such as high-sensitivity C-reactive protein (hsCRP), interleukin-6, and total leukocyte and its subset counts [neutrophil counts (13Guasti L. Dentali F. Castiglioni L. Maroni L. Marino F. Squizzato A. Ageno W. Gianni M. Gaudio G. Grandi A.M. et al.Neutrophils and clinical outcomes in patients with acute coronary syndromes and/or cardiac revascularisation. A systematic review on more than 34,000 subjects.Thromb. Haemost. 2011; 106: 591-599Crossref PubMed Scopus (159) Google Scholar, 14Gillum R.F. Mussolino M.E. Madans J.H. Counts of neutrophils, lymphocytes, and monocytes, cause-specific mortality and coronary heart disease: the NHANES-I epidemiologic follow-up study.Ann. Epidemiol. 2005; 15: 266-271Crossref PubMed Scopus (102) Google Scholar), monocyte counts (15Kato A. Takita T. Furuhashi M. Maruyama Y. Kumagai H. Hishida A. Blood monocyte count is a predictor of total and cardiovascular mortality in hemodialysis patients.Nephron Clin. Pract. 2008; 110: c235-c243Crossref PubMed Scopus (20) Google Scholar), and lymphocyte percentages (15Kato A. Takita T. Furuhashi M. Maruyama Y. Kumagai H. Hishida A. Blood monocyte count is a predictor of total and cardiovascular mortality in hemodialysis patients.Nephron Clin. Pract. 2008; 110: c235-c243Crossref PubMed Scopus (20) Google Scholar)]. Previous studies have found strong evidence of association between the frequency of leukocytes and/or its subsets, or the neutrophil/lymphocyte ratio (NLR) and vascular disease morbidity and mortality. Misialek et al. (16Misialek J.R. Bekwelem W. Chen L.Y. Loehr L.R. Agarwal S.K. Soliman E.Z. Norby F.L. Alonso A. Association of white blood cell count and differential with the incidence of atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) study.PLoS One. 2015; 10: e0136219Crossref PubMed Scopus (15) Google Scholar) prospectively examined the relationship between total white blood cell (WBC) count with incident atrial fibrillation (AF) in the Atherosclerosis Risk in Communities study and found that high total WBC, neutro

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.