{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T03:43:59Z","timestamp":1773805439212,"version":"3.50.1"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21H03386"],"award-info":[{"award-number":["21H03386"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Leukocyte count in peripheral blood is an acute-phase reactant and is associated with the risk of atherosclerotic diseases. Blood lipid profile, a major risk factor of cardiovascular disease, is known to be associated with leukocyte count, but it remains to be determined how this association is affected by other factors including lifestyle and age. The subjects were 11261 Japanese middle-aged men (30~65 years old) who had received health checkup examinations. The relationships of leukocyte count with lipid-related indices (ratio of LDL cholesterol to HDL cholesterol [LDL-C\/HDL-C], ratio of triglycerides to HDL cholesterol [TG\/HDL-C] and cardiometabolic index [CMI]) were investigated. Leukocyte count, LDL-C\/HDL-C, TG\/HDL-C and CMI were significantly higher in smokers than in nonsmokers, while leukocyte count and LDL-C\/HDL-C were significantly lower in regular drinkers than in nondrinkers. Both in overall subjects and subjects without habits of smoking and drinking, LDL-C\/HDL-C, TG\/HDL-C and CMI were significantly higher in the 2nd and 3rd tertiles for leukocyte count than in the 1st tertile and tended to be higher with an increase of the tertile. Odds ratios for high TG\/HDL-C and high CMI of the 3rd vs. 1st tertiles for leukocyte count tended to be lower with an increase of age, and odds ratios for high TG\/HDL-C and high CMI of the interaction term, consisting of age (60~65 vs. 30~39 years) and tertile (3rd vs. 1st tertiles for leukocyte count), were significantly lower than the reference level. In conclusion, leukocyte count is associated with lipid-related indices, and the associations are independent of smoking and alcohol drinking and tend to be weaker with an increase of age in Japanese middle-aged men.<\/jats:p>","DOI":"10.1371\/journal.pone.0281185","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T18:28:05Z","timestamp":1675189685000},"page":"e0281185","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Associations between leukocyte count and lipid-related indices: Effect of age and confounding by habits of smoking and alcohol drinking"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6142-9976","authenticated-orcid":true,"given":"Ichiro","family":"Wakabayashi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"issue":"10","key":"pone.0281185.ref001","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1016\/j.jacc.2004.07.056","article-title":"Leukocyte count and coronary heart disease: implications for risk assessment","volume":"44","author":"M Madjid","year":"2004","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"pone.0281185.ref002","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1194\/jlr.P067686","article-title":"Association of peripheral differential leukocyte counts with dyslipidemia risk in Chinese patients with hypertension: insight from the China Stroke Primary Prevention Trial","volume":"58","author":"Y Liu","year":"2017","journal-title":"J Lipid Res"},{"issue":"5","key":"pone.0281185.ref003","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.jacl.2019.07.003","article-title":"The association of plasma lipids with white blood cell counts: Results from the Multi-Ethnic Study of Atherosclerosis","volume":"13","author":"YC Lai","year":"2019","journal-title":"J Clin Lipidol"},{"issue":"3","key":"pone.0281185.ref004","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.tem.2012.10.008","article-title":"Hypercholesterolemia links hematopoiesis with atherosclerosis","volume":"24","author":"O Soehnlein","year":"2013","journal-title":"Trends Endocrinol Metab"},{"issue":"1","key":"pone.0281185.ref005","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/oxfordjournals.aje.a114227","article-title":"The leukocyte count: associations with intensity of smoking and persistence of effect after quitting","volume":"123","author":"DB Petitti","year":"1986","journal-title":"Am J Epidemiol"},{"issue":"12","key":"pone.0281185.ref006","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1093\/oxfordjournals.aje.a116045","article-title":"Host and environmental factors influencing the peripheral blood leukocyte count","volume":"134","author":"J Schwartz","year":"1991","journal-title":"Am J Epidemiol"},{"key":"pone.0281185.ref007","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.pmedr.2016.08.009","article-title":"Current cigarette smoking is a reversible cause of elevated white blood cell count: Cross-sectional and longitudinal studies","volume":"4","author":"T Higuchi","year":"2016","journal-title":"Prev Med Rep"},{"issue":"2","key":"pone.0281185.ref008","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/occmed\/kqg029","article-title":"Association between lifestyle and white blood cell count: a study of Japanese male office workers","volume":"53","author":"N Nakanishi","year":"2003","journal-title":"Occup Med (Lond)"},{"issue":"5","key":"pone.0281185.ref009","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/0002-8703(85)90224-8","article-title":"Lipids, diabetes, and coronary heart disease: insights from the Framingham Study","volume":"110","author":"WB Kannel","year":"1985","journal-title":"Am Heart J"},{"issue":"8","key":"pone.0281185.ref010","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1161\/01.CIR.96.8.2520","article-title":"Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction","volume":"96","author":"JM Gaziano","year":"1997","journal-title":"Circulation"},{"issue":"6","key":"pone.0281185.ref011","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1161\/01.ATV.17.6.1114","article-title":"Relation of high TG-low HDL cholesterol and LDL cholesterol to the incidence of ischemic heart disease. An 8-year follow-up in the Copenhagen Male Study","volume":"17","author":"J Jeppesen","year":"1997","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"7","key":"pone.0281185.ref012","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S0009-9120(01)00263-6","article-title":"The plasma parameter log (TG\/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL))","volume":"34","author":"M Dobi\u00e1sov\u00e1","year":"2001","journal-title":"Clin Biochem"},{"issue":"6","key":"pone.0281185.ref013","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1067\/mhj.2002.126119","article-title":"Significance of small dense low-density lipoproteins and other risk factors in patients with various types of coronary heart disease","volume":"144","author":"S Koba","year":"2002","journal-title":"Am Heart J"},{"key":"pone.0281185.ref014","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cca.2014.08.042","article-title":"The \"cardiometabolic index\" as a new marker determined by adiposity and blood lipids for discrimination of diabetes mellitus","volume":"438","author":"I Wakabayashi","year":"2015","journal-title":"Clin Chim Acta"},{"key":"pone.0281185.ref015","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.cca.2015.04.020","article-title":"Association between cardiometabolic index and atherosclerotic progression in patients with peripheral arterial disease","volume":"446","author":"I Wakabayashi","year":"2015","journal-title":"Clin Chim Acta"},{"issue":"12","key":"pone.0281185.ref016","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.5551\/jat.62730","article-title":"The risk of fasting triglycerides and its related indices for ischemic cardiovascular diseases in Japanese community dwellers: the Suita Study","volume":"28","author":"A Higashiyama","year":"2021","journal-title":"J Atheroscler Thromb"},{"issue":"3","key":"pone.0281185.ref017","doi-asserted-by":"crossref","first-page":"307","DOI":"10.5114\/ceji.2019.89608","article-title":"Changes in leukocyte profile and C-reactive protein concentration in overweight and obese adolescents after reduction of body weight","volume":"44","author":"M Rumi\u0144ska","year":"2019","journal-title":"Cent Eur J Immunol"},{"key":"pone.0281185.ref018","first-page":"794","article-title":"Metabolic syndrome-definition and diagnostic criteria in Japan","volume":"94","year":"2005","journal-title":"Nihon Naika Gakkai Zasshi"},{"issue":"16","key":"pone.0281185.ref019","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1161\/CIRCULATIONAHA.109.192644","article-title":"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 Atherosclerosis Society; and International Association for the Study of Obesity","volume":"120","author":"International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart","year":"2009","journal-title":"Circulation"},{"key":"pone.0281185.ref020","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.cca.2022.04.009","article-title":"Associations between polycythemia and cardiometabolic risk factors in middle-aged men","volume":"531","author":"I. Wakabayashi","year":"2022","journal-title":"Clin Chim Acta"},{"issue":"2","key":"pone.0281185.ref021","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ypmed.2005.08.007","article-title":"Metabolic syndrome in Japanese men and women with special reference to the anthropometric criteria for the assessment of obesity: Proposal to use the waist-to-height ratio","volume":"42","author":"SD Hsieh","year":"2006","journal-title":"Prev Med"},{"issue":"3","key":"pone.0281185.ref022","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.tcm.2019.05.003","article-title":"Blood pressure and the new ACC\/AHA hypertension guidelines","volume":"30","author":"JM Flack","year":"2020","journal-title":"Trends Cardiovasc Med"},{"issue":"6","key":"pone.0281185.ref023","doi-asserted-by":"crossref","first-page":"517","DOI":"10.5551\/jat.15792","article-title":"Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan -2012 version","volume":"20","author":"Japan Atherosclerosis Society","year":"2013","journal-title":"J Atheroscler Thromb"},{"issue":"Suppl 1","key":"pone.0281185.ref024","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.2337\/dc10-S062","article-title":"Diagnosis and classification of diabetes mellitus","volume":"33","author":"Anonymous, American Diabetes Association","year":"2010","journal-title":"Diabetes Care"},{"issue":"1","key":"pone.0281185.ref025","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s12944-019-1098-0","article-title":"Comparison of discrimination for cardio-metabolic risk by different cut-off values of the ratio of triglycerides to HDL cholesterol","volume":"18","author":"I Wakabayashi","year":"2019","journal-title":"Lipids Health Dis"},{"issue":"9","key":"pone.0281185.ref026","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1161\/ATVBAHA.108.179705","article-title":"Inflammation in atherosclerosis","volume":"32","author":"P. Libby","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"pone.0281185.ref027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2020.12.016","article-title":"The association of serum lipid and lipoprotein levels with total and differential leukocyte counts: Results of a cross-sectional and longitudinal analysis of the UK Biobank","volume":"319","author":"B Tucker","year":"2021","journal-title":"Atherosclerosis"},{"issue":"2","key":"pone.0281185.ref028","doi-asserted-by":"crossref","first-page":"e000851","DOI":"10.1161\/JAHA.114.000851","article-title":"Narrowing sex differences in lipoprotein cholesterol subclasses following mid-life: the very large database of lipids (VLDL-10B)","volume":"3","author":"KJ Swiger","year":"2014","journal-title":"J Am Heart Assoc"},{"issue":"9","key":"pone.0281185.ref029","doi-asserted-by":"crossref","first-page":"e0162953","DOI":"10.1371\/journal.pone.0162953","article-title":"Difference in Leukocyte composition between women before and after menopausal age, and distinct sexual dimorphism","volume":"11","author":"Y Chen","year":"2016","journal-title":"PLoS One"},{"issue":"3","key":"pone.0281185.ref030","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1097\/MOL.0000000000000412","article-title":"Ethnicity, lipids and cardiovascular disease","volume":"28","author":"K Gazzola","year":"2017","journal-title":"Curr Opin Lipidol"},{"key":"pone.0281185.ref031","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.yjmcc.2019.11.156","article-title":"Leukocyte profiles across the cardiovascular disease continuum: A population-based cohort study","volume":"138","author":"HE Groot","year":"2020","journal-title":"J Mol Cell Cardiol"},{"issue":"3","key":"pone.0281185.ref032","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3390\/jcm8030365","article-title":"Gender dictates the relationship between serum lipids and leukocyte counts in the National Health and Nutrition Examination Survey 1999\u20132004","volume":"8","author":"CJ Andersen","year":"2019","journal-title":"J Clin Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0281185","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T18:28:35Z","timestamp":1675189715000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0281185"}},"subtitle":[],"editor":[{"given":"Anindita","family":"Dutta","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,1,31]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0281185","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,31]]}}}