Nonclassical Monocytes (CD14dimCD16+) Are Associated With Carotid Intima-Media Thickness Progression for Men but Not Women

Abstract

Objective: Few studies of population-based cohorts have investigated prospective associations of lymphoid and myeloid cell subsets in cardiovascular disease onset and progression. The purpose of this analysis was to determine associations of prespecified myeloid and lymphoid lineage cell subsets with common carotid artery intima-media thickness (IMT) progression. Approach and Results: We performed a prospective case-cohort study of 1195 participants from the Multi-Ethnic Study of Atherosclerosis who had peripheral blood mononuclear cells stored from the baseline examination. Key exposure variables were prespecified subsets of lymphoid and myeloid lineage immune cells, phenotyped by multicolor flow cytometry. The primary outcome was progression from baseline (Exam 1) to year 10 (Exam 5) in common carotid IMT. Higher proportions of nonclassical monocytes (CD14dimCD16++) were significantly associated with IMT progression over 10 years, but classical monocytes (CD14++CD16−), CD4+CD28− T cells, and T helper cells producing IL-17 (interleukin 17; T helper 17 cells) were not associated with significant changes in IMT over 10 years. There were significant interactions between monocyte subsets and sex with respect to IMT progression: in sex-stratified analyses, nonclassical monocytes were associated with significant IMT progression and classical monocytes were associated with significant IMT regression for men, whereas there were no significant associations of monocyte subsets with IMT change for women. Conclusions: Nonclassical monocytes were associated with progression of carotid IMT. There were significant sex differences in associations of monocyte subsets with IMT progression: for men, nonclassical monocytes were associated with IMT progression and classical monocytes were associated with regression, whereas these associations were null for women.

Monocyte subsets, T cell activation profiles, and stroke in men and women: The Multi-Ethnic Study of Atherosclerosis and Cardiovascular Health Study

“…However, outside of this ethnically homogenous Swedish population, sparse data exist regarding prospective associations of circulating leukocyte subsets with incident stroke. Additional unresolved questions include (1) associations of circulating monocyte subsetswhich we have observed as associated with carotid intima-media thickness progression [15] and CD8 + T cell subsets with incident stroke, and (2) associations of circulating leukocyte subsets with ischemic stroke as well as all stroke (combining ischemic and hemorrhagic as previously done [13,14]).…”

“…In this study, we analyzed prospective associations between 28 prespecified leukocyte subsets and incident ischemic stroke in the Multi-Ethnic Study of Atherosclerosis (MESA), a multi-center prospective cohort study based at 6 sites in the United States [16]. Of 6814 participants in MESA, 6793 were free from stroke at baseline (Exam 1;2000; 2193 of these participants had polychromatic flow cytometry and intracellular cytokine staining performed on cryopreserved peripheral blood mononuclear cells (PBMCs; see Online Methods for details) [15,17].…”

“…Our methods for immune profiling of cryopreserved PBMCs have been described previously [15,17], including gating strategies; details regarding sample processing and storage are included in the Supplementary Methods. Briefly, cryopreserved (− 145 • C) cells from the MESA baseline examination were thawed and myeloid and lymphoid lineage cell subsets were measured using polychromatic flow cytometry and intracellular cytokine activation staining.…”

“…Our primary model (Model 1) adjusted for age (years), sex, race/ethnicity, MESA field center, educational attainment, smoking status, alcohol use, systolic blood pressure, body-mass index, and diabetes mellitus. Given our prior findings of significant associations of circulating monocyte subsets with carotid intima-media thickness progression in men but not women [15], we also performed pre-specified sex-stratified analyses using Model 1 covariates for adjustment to evaluate associations of baseline immune cell subsets and incident stroke; we focused on stroke (all) only for these sex-stratified analyses due to limited sample size and related power after stratification.…”

Association of immune cell subsets with cardiac mechanics in the Multi-Ethnic Study of Atherosclerosis

“…Immune cell phenotyping performed in this cohort has been previously described in detail ( 55 , 57 – 59 ). PBMCs were isolated from blood collected in 8 mL citrate CPT tubes (BD Biosciences) during the MESA baseline exam in 2000 to 2002.…”