Large HDL particles negatively associate with leukocyte counts independent of cholesterol efflux capacity: A cross sectional study in the population-based LifeLines DEEP cohort

Anouk G Groenen, Venetia Bazioti, Isabelle A van Zeventer, Lianmin Chen, Hilde E Groot, Jan-Willem Balder, Alexandra Zhernakova, Pim van der Harst, Antoine Rimbert, Jan Albert Kuivenhoven, Jingyuan Fu, Marit Westerterp

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Abstract

Background and aims: Leukocytosis, the expansion of white blood cells, is associated with increased cardiovascular risk. Studies in animal models have shown that high-density lipoprotein cholesterol (HDL-c) suppresses leukocytosis by mediating cholesterol efflux from hematopoietic stem and progenitor cells. HDL-c showed a moderate negative association with leukocyte numbers in the UK Biobank and Multi-Ethnic Study of Atherosclerosis. Cholesterol efflux capacity of HDL (HDL-CEC) or HDL particle (HDL-P) number has been proposed as improved inverse predictor of CVD compared to plasma HDL-c. In the LifeLines DEEP (LLD) cohort (n = 962), a sub-cohort representing the prospective population-based LL cohort from the North of The Netherlands, we tested the hypothesis that HDL-CEC and HDL-P were associated with lower leukocyte counts. Methods: We carried out multivariable regression and causal mediation analyses (CMA) to test associations between HDL-c, HDL-CEC, or HDL-P and leukocyte counts. We measured HDL-CEC in THP-1 macrophages and HDL-P and composition using nuclear magnetic resonance. Results: HDL-c associated negatively with leukocyte counts, as did extra-large and large HDL-P, while HDL-CEC showed no association. Each one-standard deviation (SD) increase in extra-large HDL-P was associated with 3.0% and 4.8% lower leukocytes and neutrophils, respectively (q < 0.001). In contrast, plasma concentration of small HDL-P associated positively with leukocyte and neutrophil counts, as did small HDL-P triglycerides (TG) and total plasma TG. CMA showed that the association between S-HDL-P and leukocytes was mediated by S-HDL-TG. Conclusions: The association between HDL-P and leukocyte counts in the general population is dependent on HDL-P size and composition, but not HDL-CEC.

Original languageEnglish
Pages (from-to)20-27
Number of pages8
JournalAtherosclerosis
Volume343
Early online date18 Jan 2022
DOIs
Publication statusPublished - Feb 2022

Keywords

  • Atherosclerosis
  • Composition
  • HDL
  • Leukocyte
  • Lipoprotein
  • Particle size

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