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

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 naive 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; naive 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 naive 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.