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      Gender Dictates the Relationship between Serum Lipids and Leukocyte Counts in the National Health and Nutrition Examination Survey 1999–2004

      research-article
      1 , * , 2
      Journal of Clinical Medicine
      MDPI
      serum lipids, cholesterol, leukocytes, gender, NHANES

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          Abstract

          Dyslipidemias and leukocytosis are associated with cardiovascular disease and immune disorders. Mechanistic studies have shown lipoprotein metabolism to play a significant role in the regulation of atherosclerosis development and leukocyte activation, whereas lipid-lowering treatments have been shown to exert beneficial anti-inflammatory and immunomodulatory effects in clinical trials. However, the relationship between clinical markers of lipid metabolism and leukocyte counts has not been extensively evaluated at the population level. We aimed to determine whether clinical blood lipid measures are associated with leukocyte counts in the general U.S. population represented in the National Health and Nutrition Examination Survey (NHANES) 1999–2004, and whether differences exist between men and women ( n = 5647). We observed a strong positive linear trend between serum triglycerides vs. blood lymphocyte and basophil counts in both men and women, whereas a positive trend between monocytes vs. triglycerides and lymphocytes vs. total cholesterol and LDL-cholesterol (LDL-C) was only detected in women. Conversely, HDL-C was inversely associated with a greater number of leukocyte subsets in men, whereas inverse trends between HDL-C vs. lymphocytes were observed in both men and women. In multiple regression models, a 10% increase in total cholesterol, LDL-C, and triglycerides was associated with a predicted 1.6%, 0.6%, and 1.4% increase in blood lymphocyte counts in women, respectively, whereas no relationship was observed in men. In both men and women, a 10% increase in triglycerides was additionally associated with higher lymphocyte, neutrophil, and basophil counts, whereas 10% increases in HDL-cholesterol were associated with significantly lower lymphocyte, neutrophil, eosinophil, and basophil counts in men, in addition to lower lymphocyte and monocyte counts in women. These findings suggest that clinical lipid markers may be used to predict blood leukocyte distributions, and that a gender-specific relationship exists between distinct classes of serum lipids and immune cell subsets.

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          Most cited references65

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          Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary. Expert Panel on the Identification, Evaluation, and Treatment of Overweight in Adults.

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            ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation.

            Elevated leukocyte cell numbers (leukocytosis), and monocytes in particular, promote atherosclerosis; however, how they become increased is poorly understood. Mice deficient in the adenosine triphosphate-binding cassette (ABC) transporters ABCA1 and ABCG1, which promote cholesterol efflux from macrophages and suppress atherosclerosis in hypercholesterolemic mice, displayed leukocytosis, a transplantable myeloproliferative disorder, and a dramatic expansion of the stem and progenitor cell population containing Lin(-)Sca-1(+)Kit+ (LSK) in the bone marrow. Transplantation of Abca1(-/-) Abcg1(-/-) bone marrow into apolipoprotein A-1 transgenic mice with elevated levels of high-density lipoprotein (HDL) suppressed the LSK population, reduced leukocytosis, reversed the myeloproliferative disorder, and accelerated atherosclerosis. The findings indicate that ABCA1, ABCG1, and HDL inhibit the proliferation of hematopoietic stem and multipotential progenitor cells and connect expansion of these populations with leukocytosis and accelerated atherosclerosis.
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              Leukocyte count and coronary heart disease: implications for risk assessment.

              Inflammation is a key feature of atherosclerosis and its clinical manifestations. The leukocyte count is a marker of inflammation that is widely available in clinical practice. This paper reviews the available epidemiologic evidence for a relationship between the leukocyte count and coronary heart disease (CHD). Numerous epidemiologic and clinical studies have shown leukocytosis to be an independent predictor of future cardiovascular events, both in healthy individuals free of CHD at baseline and in patients with stable angina, unstable angina, or a history of myocardial infarction. This relationship has been observed in prospective and retrospective cohort studies, as well as in case-control studies. It is strong, consistent, temporal, dose-dependent, and biologically plausible. The relationship persists after adjustment for multiple CHD risk factors, including smoking. Elevated differential cell counts, including eosinophil, neutrophil, and monocyte counts, also predict the future incidence of CHD. Leukocytosis affects CHD through multiple pathologic mechanisms that mediate inflammation, cause proteolytic and oxidative damage to the endothelial cells, plug the microvasculature, induce hypercoagulability, and promote infarct expansion. In summary, leukocytosis has been consistently shown to be an independent risk factor and prognostic indicator of future cardiovascular outcomes, regardless of disease status. The leukocyte count is inexpensive, reliable, easy to interpret, and ordered routinely in inpatient and outpatient settings. However, its diagnostic and prognostic utility in CHD is widely unappreciated. Further studies are needed to assess the true impact of leukocytosis on CHD, compare it with other inflammatory markers such as C-reactive protein and lipoprotein phospholipase A(2) levels, and promote its use in CHD prediction.

                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                15 March 2019
                March 2019
                : 8
                : 3
                : 365
                Affiliations
                [1 ]Department of Biology, Fairfield University, Fairfield, CT 06824, USA
                [2 ]Department of Nutrition and Dietetics, The State University of New York Plattsburgh, Plattsburgh, NY 12901, USA; tvanc001@ 123456plattsburgh.edu
                Author notes
                [* ]Correspondence: candersen@ 123456fairfield.edu ; Tel.: +1-203-254-4000
                Author information
                https://orcid.org/0000-0001-9774-5030
                Article
                jcm-08-00365
                10.3390/jcm8030365
                6463027
                30875952
                fe04a64a-b1dd-44dc-bc80-c7c8fd84614c
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 February 2019
                : 12 March 2019
                Categories
                Article

                serum lipids,cholesterol,leukocytes,gender,nhanes
                serum lipids, cholesterol, leukocytes, gender, nhanes

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