@article {8403, title = {Innate and adaptive immune cell subsets as risk factors for coronary heart disease in two population-based cohorts.}, journal = {Atherosclerosis}, volume = {300}, year = {2020}, month = {2020 05}, pages = {47-53}, abstract = {

BACKGROUND AND AIMS: Cell-mediated immunity is implicated in atherosclerosis. We evaluated whether innate and adaptive immune cell subsets in peripheral blood are risk factors for coronary heart disease.

METHODS: A nested case-cohort study (n~=~2155) was performed within the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS). Cases of incident myocardial infarction (MI) and incident angina (n~=~880 total cases) were compared with a cohort random sample (n~=~1275). Immune cell phenotypes (n~=~34, including CD14 monocytes, natural killer cells, γδ T cells, CD4, CD8 and CD19 lymphocyte subsets) were measured from cryopreserved cells by flow cytometry. Cox proportional hazards models with adjustment for cardiovascular disease risk factors were used to evaluate associations of cell phenotypes with incident MI and a composite phenotype of incident MI or incident angina (MI-angina) over a median 9.3 years of follow-up. Th1, Th2, Th17, T regulatory (CD4CD25CD127), naive (CD4CD45RA), memory (CD4CD45RO), and CD4CD28 cells were specified as primary hypotheses. In secondary analyses, 27 additional cell phenotypes were investigated.

RESULTS: After correction for multiple testing, there were no statistically significant associations of CD4 naive, memory, CD28, or T helper cell subsets with MI or MI-angina in MESA, CHS, or combined-cohort meta analyses. Null associations were also observed for monocyte subsets, natural killer cells, γδ T cells, CD19 B cell and differentiated CD4 and CD8 cell subsets.

CONCLUSIONS: The proportions of peripheral blood monocyte and lymphocyte subsets are not strongly related to the future occurrence of MI or angina in adults free of autoimmune disease.

}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2020.03.011}, author = {Olson, Nels C and Sitlani, Colleen M and Doyle, Margaret F and Huber, Sally A and Landay, Alan L and Tracy, Russell P and Psaty, Bruce M and Delaney, Joseph A} } @article {8658, title = {Natural killer cells, gamma delta T cells and classical monocytes are associated with systolic blood pressure in the multi-ethnic study of atherosclerosis (MESA).}, journal = {BMC Cardiovasc Disord}, volume = {21}, year = {2021}, month = {2021 Jan 22}, pages = {45}, abstract = {

BACKGROUND: Hypertension is a major source of cardiovascular morbidity and mortality. Recent evidence from mouse models, genetic, and cross-sectional human studies suggest increased proportions of selected immune cell subsets may be associated with levels of systolic blood pressure (SBP).

METHODS: We assayed immune cells from cryopreserved samples collected at the baseline examination (2000-2002) from 1195 participants from the multi-ethnic study of atherosclerosis (MESA). We used linear mixed models, with adjustment for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and cytomegalovirus titers, to estimate the associations between 30 immune cell subsets (4 of which were a priori hypotheses) and repeated measures of SBP (baseline and up to four follow-up measures) over 10~years. The analysis provides estimates of the association with blood pressure level.

RESULTS: The mean age of the MESA participants at baseline was 64 {\textpm} 10~years and 53\% were male. A one standard deviation (1-SD) increment in the proportion of γδ T cells was associated with 2.40~mmHg [95\% confidence interval (CI) 1.34-3.42] higher average systolic blood pressure; and for natural killer cells, a 1-SD increment was associated with 1.88~mmHg (95\% CI 0.82-2.94) higher average level of systolic blood pressure. A 1-SD increment in classical monocytes (CD14CD16) was associated with 2.01 mmHG (95\% CI 0.79-3.24) lower average systolic blood pressure. There were no associations of CD4 T helper cell subsets with average systolic blood pressure.

CONCLUSION: These findings suggest that the innate immune system plays a role in levels of SBP whereas there were no associations with adaptive immune cells.

}, issn = {1471-2261}, doi = {10.1186/s12872-021-01857-2}, author = {Delaney, Joseph A C and Olson, Nels C and Sitlani, Colleen M and Fohner, Alison E and Huber, Sally A and Landay, Alan L and Heckbert, Susan R and Tracy, Russell P and Psaty, Bruce M and Feinstein, Matt and Doyle, Margaret F} } @article {9478, title = {Association of Immune Cell Subsets with Incident Hip Fracture: The Cardiovascular Health Study.}, journal = {Calcif Tissue Int}, year = {2023}, month = {2023 Aug 31}, abstract = {

In this study, we aimed to evaluate the association of innate and adaptive immune cell subsets in peripheral blood mononuclear cells (PBMCs) with hip fracture. To conduct this study, we used data from the Cardiovascular Health Study (CHS), a U.S. multicenter observational cohort of community-dwelling men and women aged >= 65 years. Twenty-five immune cell phenotypes were measured by flow cytometry from cryopreserved PBMCs of CHS participants collected in 1998-1999. The natural killer (NK), γδ T, T helper 17 (Th17), and differentiated/senescent CD4CD28 T cell subsets were pre-specified as primary subsets of interest. Hip fracture incidence was assessed prospectively by review of hospitalization records. Multivariable Cox hazard models evaluated associations of immune cell phenotypes with incident hip fracture in sex-stratified and combined analyses. Among 1928 persons, 259 hip fractures occurred over a median 9.7 years of follow-up. In women, NK cells were inversely associated with hip fracture [hazard ratio (HR) 0.77, 95\% confidence interval (CI) 0.60-0.99 per one standard deviation higher value] and Th17 cells were positively associated with hip fracture [HR 1.18, 95\% CI 1.01-1.39]. In men, γδ T cells were inversely associated with hip fracture [HR 0.60, 95\% CI 0.37-0.98]. None of the measured immune cell phenotypes were significantly associated with hip fracture incidence in combined analyses. In this large prospective cohort of older adults, potentially important sex differences in the associations of immune cell phenotypes and hip fracture were identified. However, immune cell phenotypes had no association with hip fracture in analyses combining men and women.

}, issn = {1432-0827}, doi = {10.1007/s00223-023-01126-8}, author = {Elam, Rachel E and B{\r u}zkov{\'a}, Petra and Delaney, Joseph A C and Fink, Howard A and Barzilay, Joshua I and Carbone, Laura D and Saha, Rick and Robbins, John A and Mukamal, Kenneth J and Valderr{\'a}bano, Rodrigo J and Psaty, Bruce M and Tracy, Russell P and Olson, Nels C and Huber, Sally A and Doyle, Margaret F and Landay, Alan L and Cauley, Jane A} }