Departments of Cancer Epidemiology and Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.K.K.).
Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC (J.K.K., Z.X., K.M.O., C.G.P., D.P.S., J.A.T.).
Hypertension. 2023 Jan;80(1):43-53. doi: 10.1161/HYPERTENSIONAHA.122.20001. Epub 2022 Oct 19.
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.
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.
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]; =0.03; naïve CD4+ T cell, adjusted HR: 0.88 [95% CI: 0.78-0.99]; =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]; =0.001) and lower proportions of CD4+ helper T cells (adjusted odds ratio: 0.90 [95% CI: 0.81-1.00] =0.05), natural killers (adjusted odds ratio: 0.82 [95% CI: 0.74-0.91]; <0.001), and B cells (adjusted odds ratio: 0.84 [95% CI: 0.74-0.96]; =0.01).
These observations suggest that shifts in lymphocyte subsets occur before hypertension development, followed by later changes to neutrophils and additional lymphocytes.
高血压的发生和发展涉及多个生物学系统,其中可能包括免疫谱的变化。高血压是否与外周免疫细胞组成有关,尚未在大型人类队列中进行研究。
我们通过对 4124 名女性的细胞类型特异性 DNA 甲基化数据进行反卷积,估计了淋巴细胞和髓系谱系中 12 种白细胞亚群的循环比例。基线时高血压的状态定义为当前使用降压药物和血压测量,而新的高血压病例在随访期间通过年度健康问卷确定。
在基线时无高血压的女性中,较高的 B 细胞和较低的幼稚 CD4+辅助 T 细胞比例与随后高血压发生的风险增加相关(B 细胞;调整后的 HR:1.17[95%CI:1.02-1.35];=0.03;幼稚 CD4+T 细胞,调整后的 HR:0.88[95%CI:0.78-0.99];=0.04)。基线时的血压测量也与 B 细胞呈正相关,与幼稚 CD4+辅助 T 细胞呈负相关。与血压正常的女性相比,高血压女性的中性粒细胞循环比例较高(调整后的优势比:1.18[95%CI:1.07-1.31];=0.001),CD4+辅助 T 细胞比例较低(调整后的优势比:0.90[95%CI:0.81-1.00];=0.05)、自然杀伤细胞(调整后的优势比:0.82[95%CI:0.74-0.91];<0.001)和 B 细胞(调整后的优势比:0.84[95%CI:0.74-0.96];=0.01)。
这些观察结果表明,淋巴细胞亚群的变化发生在高血压发生之前,随后是中性粒细胞和其他淋巴细胞的变化。