TY - JOUR
T1 - Large HDL particles negatively associate with leukocyte counts independent of cholesterol efflux capacity
T2 - A cross sectional study in the population-based LifeLines DEEP cohort
AU - Groenen, Anouk G
AU - Bazioti, Venetia
AU - van Zeventer, Isabelle A
AU - Chen, Lianmin
AU - Groot, Hilde E
AU - Balder, Jan-Willem
AU - Zhernakova, Alexandra
AU - van der Harst, Pim
AU - Rimbert, Antoine
AU - Kuivenhoven, Jan Albert
AU - Fu, Jingyuan
AU - Westerterp, Marit
N1 - Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
U2 - 10.1016/j.atherosclerosis.2022.01.008
DO - 10.1016/j.atherosclerosis.2022.01.008
M3 - Article
C2 - 35091264
SN - 0021-9150
VL - 343
SP - 20
EP - 27
JO - Atherosclerosis
JF - Atherosclerosis
ER -