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. 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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, neutrophil, and monocyte counts were each associated with higher AF risk, while lymphocyte count was inversely associated with AF risk. A study by Sharma et al. (17Sharma K.H. Shah K.H. Patel I. Patel A.K. Chaudhari S. Do circulating blood cell types correlate with modifiable risk factors and outcomes in patients with acute coronary syndrome (ACS)?.Indian Heart J. 2015; 67: 444-451Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar) indicated that among patients with evidence of acute coronary syndrome, those who were hypertensive, diabetic, or habitual smokers had significantly higher levels of total WBC, neutrophil, NLR, and platelet/lymphocyte ratio. The authors also demonstrated that neutrophil, lymphocyte, and total WBC counts, along with their ratios, predicted mortality. However, there is a dearth of reports on the association of total leukocyte and its subset counts with cardiovascular risk factors leading to atherosclerotic vascular diseases in Asian populations. Recently, a cross-sectional study from a population of 2,953 healthy Japanese men and women (18Oda E. Kawai R. Aizawa Y. Lymphocyte count was significantly associated with hyper-LDL cholesterolemia independently of high-sensitivity C-reactive protein in apparently healthy Japanese.Heart Vessels. 2012; 27: 377-383Crossref PubMed Scopus (16) Google Scholar) showed that lymphocyte count was significantly associated with high LDL-C, high TG, and low HDL cholesterol (HDL-C) in men and high LDL-C in women. Moreover, a prospective investigation from a Chinese population involving 1,287 patients with a mean age of 58 years provided convincing evidence that both neutrophil count and the Global Registry of Acute Coronary Events risk score are independent and joint predictors for major adverse cardiovascular events in patients with ST-elevation myocardial infarction (19Zhang S. Wan Z. Zhang Y. Fan Y. Gu W. Li F. Meng L. Zeng X. Han D. Li X. Neutrophil count improves the GRACE risk score prediction of clinical outcomes in patients with ST-elevation myocardial infarction.Atherosclerosis. 2015; 241: 723-728Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar). Our present study design is the first large-scale cross-sectional study in a Chinese hypertensive population to investigate the association between peripheral differential leukocyte counts (total leukocytes, neutrophils, and lymphocytes) and lipid profiles. We hypothesized that participants with elevated leukocyte counts would have increased dyslipidemia. All subjects came from the China Stroke Primary Prevention Trial (CSPPT, clinicaltrials.gov identifier: NCT00794885). The CSPPT was a large community-based, randomized, double-blind, and parallel-controlled with a total of was to with and is more in first stroke than among Chinese with in the CSPPT study were of myocardial heart or the and of the have In the present patients were from the of participants had data on lipid and total leukocyte, neutrophil, and lymphocyte counts, participants who were and Moreover, of leukocyte, neutrophil, and lymphocyte counts were the of 10,866 participants was in The present study was by the of the of was from each data All participants were a that on and and such as and an a blood was from each or were within of and The serum levels of TG, total cholesterol (TC), LDL-C, and were determined with a A blood count leukocytes was within of using a the blood were using a with an was with a in between each and the of the was for All analyses were using and the counts were into to a were as mean or between were using for and for leukocyte counts had a multiple analyses were to the between leukocyte counts and serum lipid levels TC and and confidence of those high lipid levels were by multiple analyses with the lowest quartile as the of lipid levels by leukocyte counts were analyses were also to an for × leukocyte counts on lipid profiles. was as a than or to China for of 2012; Scholar), or with the of lipids were dichotomized TC was as TC high TG was as TG high LDL-C was as LDL-C and low was as for Chinese on Prevention and of in Chinese on and of dyslipidemia in in Scholar). with or who were were as hypertension Chinese hypertension 2015; PubMed Google Scholar). were by the differential leukocyte count quartile as A P was to The cross-sectional population in the study of 10,866 hypertensive patients with an age of years The mean total leukocyte count was × 109 × 109 from × 109 to × 109 the mean neutrophil count was × 109 × 109 from × 109 to × 109 the mean lymphocyte count was × 109 × 109 from × 109 to × 109 The and clinical and of the enrolled subjects by quartile of total leukocyte, neutrophil, and lymphocyte counts are in In summary, patients with higher total leukocyte, neutrophil, and lymphocyte counts consistently showed higher LDL-C, and TG and clinical in total hypertensive leukocytes receptor blood in a blood as multiple showed that TG, and LDL-C levels were positively associated with total leukocyte, neutrophil, and lymphocyte counts for and (all P < However, was inversely associated with total leukocyte, neutrophil, and lymphocyte counts for the factors We found a association between TG, LDL-C, and and differential leukocyte the P for was for TG, LDL-C, and levels a that serum TG, and LDL-C levels increased with total leukocyte, neutrophil, and lymphocyte counts, while levels decreased as total leukocyte, neutrophil, and lymphocyte counts increased in Similar to differential leukocyte counts, TG, and LDL-C levels were positively associated with or counts for multiple while levels were inversely associated with counts We also an association between and lipid were observed serum lipid was as a using in analyses demonstrated for age and and using the lowest quartile of total leukocytes as the the of high TC increased in with the of total leukocytes were and from the to the P < 0.001 for trend). The of high TG were and from the to the (P < 0.001 for trend). The of high LDL-C were and from the to the (P < 0.001 for trend). The of low were and from the to the (P < 0.001 for trend). Similar patterns between leukocyte and lymphocytes) and high TG, and LDL-C levels for and (all P the for low (95% for the association between of total leukocyte count and dyslipidemia by for and (95% for for and (95% for TC TC TG TG LDL-C LDL-C 1.39) for and for and TC TC TG TG LDL-C LDL-C in a (95% for the association between of lymphocyte count and dyslipidemia by for and (95% for for and (95% for TC TC TG TG LDL-C LDL-C for and for and TC TC TG TG LDL-C LDL-C in a (95% for the association between of neutrophil count and dyslipidemia by for and (95% for for and (95% for TC TC TG TG LDL-C LDL-C for and for and TC TC TG TG LDL-C LDL-C in a We the relationship between total leukocyte, neutrophil, and lymphocyte counts and serum lipids among in analyses by showed that the between differential leukocyte counts and high TC and LDL-C in patients (all P However, there was modification of on the of leukocyte counts with high TG or low analyses found between and neutrophil counts on TC and LDL-C (P and P (95% for the association between dyslipidemia and the of leukocyte count by (95% for (95% for for TC TC TG TG LDL-C LDL-C for and TC TC TG TG LDL-C LDL-C in a (95% for the association between dyslipidemia and the of lymphocyte count by (95% for (95% for for TC TC TG TG LDL-C LDL-C for and TC TC TG TG LDL-C LDL-C in a (95% for the association between dyslipidemia and the of neutrophil count by (95% for (95% for for TC TC TG TG LDL-C LDL-C for and TC TC TG TG LDL-C LDL-C in a for and for and for and In the present cross-sectional differential leukocyte counts were consistently and significantly associated with serum LDL-C, TG, and TC levels and increased the odds of high LDL-C, TG, and TC for multiple potential Moreover, study demonstrated that the of total leukocyte, neutrophil, and lymphocyte counts with dyslipidemia were significantly by the of There is evidence that inflammation in both the and of the atherosclerotic process E. 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The authors found that elevated leukocyte count was associated with decreased and increased LDL-C and In to and LDL-C present study that TC and TG levels were also consistently and positively associated with total leukocyte, neutrophil, and lymphocyte counts, in with total leukocyte, neutrophil, and lymphocyte In the age of and and between the study and present study are A large study by et al. M.B. K. Zhang Y. R. between serum cholesterol and of and in the Lipid Res. 2013; Full Text Full Text PDF PubMed Scopus Google Scholar) in 2,953 apparently healthy Japanese patients found that total leukocyte count was significantly associated with high LDL-C, high TG, and low levels in Our on the in a were with the from et al. (18Oda E. Kawai R. Aizawa Y. 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This is in to findings where TG, and LDL-C levels were positively associated with and was and inversely associated with The underlying has to study also demonstrated that elevated leukocyte counts were more significantly associated with increased odds of high TC and LDL-C in patients than in patients with on of lipid by we found for TC and LDL-C blood levels were than TC and LDL-C were to levels TC and LDL-C levels a and were associated with differential leukocyte counts in In a cross-sectional participants from the and the authors demonstrated that the association between WBC count and peripheral artery disease risk was on and L.Y. J.L. Association of white blood cell count and peripheral arterial disease in patients with and risk 2010; PubMed Scopus Google Scholar). is that a more and on the pathogenesis of the between higher WBC count and blood lipids to Previous studies L.Y. J.L. Association of white blood cell count and peripheral arterial disease in patients with and risk 2010; PubMed Scopus Google Scholar) and data showed that differential leukocyte counts were higher in those with The higher differential leukocyte counts in these hypertensive patients the relationship with dyslipidemia. However, the study modification of the association between WBC count and dyslipidemia by A of study is to it is the study to an association of differential leukocyte counts with vascular risk Moreover, population is in that it is a with a of and lipid In the patients were to of is that the interactions between lipids and inflammatory factors are that inflammation with lipid to for atherosclerosis. are also a cross-sectional the of the between elevated differential leukocytes on the risk of dyslipidemia prospective studies on the relationship between elevated differential leukocyte counts and vascular diseases dyslipidemia is in populations. on some inflammatory cytokines such as and monocytes were and found that these inflammatory cytokines significantly increased LDL-C accumulation in vascular cells the LDL receptor Z. of LDL receptor the of inflammatory a for foam cell 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, J.L. Z. of of receptor in vascular cells by inflammatory Thromb. Vasc. Biol. PubMed Scopus Google Scholar). We that would have an association to examine in had data HDL were from a more risk assessment of by inflammatory which would to more to in risk of studies are and we aim to of these in an to in In we found that elevated leukocyte counts were significantly associated with lipid serum TG, LDL-C, and and with an increased odds of high LDL-C, TG, and TC in Chinese hypertensive Moreover, the of in hypertensive patients the relationship between differential leukocyte counts and dyslipidemia. The authors the and of the and of the and of the participants in This study was in with the of the of with atrial fibrillation blood confidence interval China Stroke Primary Prevention Trial blood HDL cholesterol high-sensitivity C-reactive protein LDL cholesterol neutrophil/lymphocyte ratio odds ratio blood total cholesterol white blood cell

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