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.2023 Jan;80(1):43-53.
doi: 10.1161/HYPERTENSIONAHA.122.20001. Epub 2022 Oct 19.

Peripheral Immune Cell Composition is Altered in Women Before and After a Hypertension Diagnosis

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Peripheral Immune Cell Composition is Altered in Women Before and After a Hypertension Diagnosis

Jacob K Kresovich et al. Hypertension.2023 Jan.

Abstract

Background: The development and consequences of hypertension involve multiple biological systems that may include changes in immune profiles. Whether hypertension is related to peripheral immune cell composition has not been examined in large human cohorts.

Methods: We estimated circulating proportions of 12 leukocyte subsets from the lymphoid and myeloid lineages by deconvolving cell-type-specific DNA methylation data from 4124 women. Hypertension status at baseline was defined by current use of antihypertensive medication and blood pressure measurements while new incident cases were identified during follow-up via annual health questionnaires.

Results: Among hypertension-free women at baseline, higher B cell and lower naïve CD4+ helper T cell proportions were associated with subsequent increased hazard of hypertension incidence (B cells; adjusted HR: 1.17 [95% CI: 1.02-1.35];P=0.03; naïve CD4+ T cell, adjusted HR: 0.88 [95% CI: 0.78-0.99];P=0.04). Blood pressure measurements at baseline were similarly positively associated with B cells and inversely associated with naïve CD4+ helper T cells. Compared to normotensive women, women with hypertension had higher circulating proportions of neutrophils (adjusted odds ratio: 1.18 [95% CI: 1.07-1.31];P=0.001) and lower proportions of CD4+ helper T cells (adjusted odds ratio: 0.90 [95% CI: 0.81-1.00]P=0.05), natural killers (adjusted odds ratio: 0.82 [95% CI: 0.74-0.91];P<0.001), and B cells (adjusted odds ratio: 0.84 [95% CI: 0.74-0.96];P=0.01).

Conclusions: These observations suggest that shifts in lymphocyte subsets occur before hypertension development, followed by later changes to neutrophils and additional lymphocytes.

Keywords: DNA methylation; blood pressure; hypertension; immunity; immunomethylomics; leukocytes.

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Figures

Figure 1.
Figure 1.. Leukocyte subset characteristics.
Mean circulating proportions of the twelve estimated leukocyte subsets (A). Scatter plots with LOWESS smoothers for the naïve-to-total ratios of CD8+ and CD4+ T cells and B cells; scatter plots and LOWESS smoothers (solid black line) for the neutrophil-to-lymphocyte, lymphocyte-to-monocyte, and CD4-to-CD8 T cell ratios (B). Box plots and age-adjusted P-values for the six major leukocyte subset groups, stratified by self-reported race (C) and menopause status (D).
Figure 2.
Figure 2.. Prospective associations for the leukocyte subsets and incidence of hypertension.
Hypertension incidence associations estimated using weighted Cox regression models treating new-onset hypertension as the outcome. All models treat age as the timescale and adjust for self-reported race, household income, educational attainment, menopause status, exogenous hormone use, parity, and methylation platform. Associations were tested among the six major groups of leukocytes (A) and among the components of granulocytes, T cells and B cells (B).
Figure 3.
Figure 3.. Associations for the leukocyte subsets and measures of blood pressure taken at enrollment.
Blood pressure associations estimated using weighted linear regression models treating the blood pressure measure as the outcome. All models adjusted for age at blood draw, self-reported race, household income, educational attainment, menopause status, exogenous hormone use, parity, and methylation platform. Associations were tested for direct measures of systolic and diastolic blood pressure (A) and for derived measures of pulse pressure and mean arterial pressure (B).
Figure 4.
Figure 4.. Cross-sectional associations for the leukocyte subsets with prevalent hypertension.
Prevalent hypertension associations estimated using separate weighted logistic regression models treating hypertension status at baseline as the outcome and individual leukocyte subsets as predictors. All models adjust for age at blood draw, self-reported race, household income, educational attainment, menopause status, current exogenous hormone use, parity, and methylation platform. Associations were tested among the six major groups of leukocytes (A) and among the components of granulocytes, T cells and B cells (B).
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