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

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: 1.19 [95% CI: 1.07–1.32]; 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: 0.84, [95% CI: 0.74–0.09]; 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.

Hypertension Impacts Peripheral Blood Leukocyte Composition

“…Kresovich et al 1 associations are consistent with findings in the animal models, 9 as well as more complex Mendelian Randomization studies. 17 A significant limitation with human studies is the limited access to samples of target organs (kidney, brain, large blood vessels), where some of the alterations related to the immune cell responses may be regulated.…”

“…In this issue of Hypertension , Kresovich et al 1 investigated how the immune system is affected by the presence and occurrence of high blood pressure, comparing women enrolled in the Sister Study with and without a diagnosis of hypertension and those with a de novo diagnosis in a 15-year follow-up. This prospective cohort collected information from 4124 women and prospectively identified incident cases of hypertension.…”

Methylation-Based Biological Age and Hypertension Prevalence and Incidence

“…Two samples of women were selected for DNAm profiling. 32 Women were eligible for DNAm profiling if they self-identified as non-Hispanic White or Black, did not have prevalent cancer at the time of the blood draw, and had baseline blood available. In 2014, blood DNA samples from 2878 self-identified non-Hispanic White women were assayed on the Infinium HumanMethylation450 BeadChip.…”

Hypertension and severe COVID-19

“…Concurring with the opinion of the authors, we believe the quality of blood pressure control can influence the association between hypertension and severe COVID-19. Of late, we understand that the immune system can be affected by hypertension, where patients with hypertension can have higher proportion of neutrophils and lower proportions of lymphocytes, including CD4(+) T-cells, natural killer cells, and B cells, compared to those without hypertension [ 3 ]. In fact, the neutrophil-to-lymphocyte ratio shows a positive correlation with blood pressure in patients with hypertension and is higher in patients without adequate blood pressure control relative to those with adequate blood pressure control [ 4 ].…”