Abstract
The role of the immune system, and hence inflammation, in the pathophysiology of hypertensive patients is not clear. Until now, most clinical and biochemical parameters have failed to predict a positive response to renal denervation (RDN). Our aim was to evaluate the immune response in a cohort of patients treated by RDN, through the analysis of cytokine, chemokine, and growth factor behavior. A population of 21 resistant hypertension patients, treated by RDN, was evaluated at six months and one year. Response was defined as a drop of ≥5 mmHg in ambulatory blood pressure monitoring. Sixty-seven percent and 81% of patients clinically responded after six months and one year, respectively. There were no complications or safety issues. Plasmatic levels of 45 cytokine, chemokine, and growth factors were quantified at four different times, pre- and post-procedure. Baseline characteristics were similar between groups, except that active smoking was more frequent in non-responders at one year. Regulated on activation, normal T cell expressed, and secreted (RANTES/CCL5) levels were significantly lower in responders, both at baseline and at 30 days (p = 0.037), and a level ≤15,496 pg/mL was the optimal cutoff, for prediction of a response. IL-15, IL-17A, IL-27, and leukemia inhibitory factor varied significantly in time, with an acute rise being observed 24 h after RDN. Our group has previously showed that HLA-DR+ double-negative (DN) T cells were significantly lower in responders. There was a positive correlation between IL-13, -27, and -4, and DN T cells, and a negative correlation between the latter and SDF-1α and TNF-α, at baseline. Low plasmatic levels of the chemokine RANTES/CCL5 was the most significant result associated with RDN response and may help to identify the best candidates among patients with true resistant hypertension. Pro-inflammatory cytokines correlated negatively with DN T cells in responders, a finding compatible with an enhanced inflammatory milieu present in this extremely high cardiovascular risk cohort.
Highlights
The identification of specific patient subsets who derive the most benefit from renal denervation (RDN) has been the focus of investigators in recent years
There were no significant differences between responders and non-responders regarding comorbidities such as dyslipidemia, type 2 diabetes or the presence of sleep apnea, but active smoking was more frequent in the group of non-responders at one year (NR1Y) (p = 0.008)
Our study demonstrated that, in spite of lower levels of RANTES that persisted at one year follow-up, this difference was not statistically significant, probably due to the low number of non-responders at this stage
Summary
The identification of specific patient subsets who derive the most benefit from renal denervation (RDN) has been the focus of investigators in recent years. Following the unexpected outcomes of HTN-3 trial [1], three second generation randomized trials on RDN [2,3,4] were carefully constructed and have shown a significant decrease of blood pressure (BP) in a wider cohort of patients, with and without anti-hypertensive drugs, demonstrating efficacy and safety. Angiotensin II binds to angiotensin 1 receptors (AT1), usually present in several immune cells such as T cells, dendritic cells, and macrophages, and determines their differentiation and subsequent pro-inflammatory cytokine production [6]. Pro-inflammatory stimuli trigger endothelial expression of adhesion molecules and increase leucocyte migration, promoting fibrosis and hypertrophy with reduction of vascular luminal diameters [7]
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