The effect of treatment on the inflammation profile among patients with primary aldosteronism

Objective: Due to direct and indirect effects of aldosterone various pathways of inflammation cascade are activated leading to further end organ damage and higher cardiovascular risk among patients with primary aldosteronism (PA). To what extent the pro-inflammatory effects occur and, more importantly, if they are affected by the PA treatment remain unclear. Therefore, we aimed to analyze the inflammation profile among patients with PA before and after the treatment. Design and method: 46 patients with PA (43% with adrenal adenoma and 57% with bilateral hyperplasia) were included into this study. Patient serum samples were collected at the study entry and 6 months after the treatment of PA was initiated. Demographic, clinical and laboratory data were collected retrospectively. Inflammatory cytokines and proteins were measured in patient’s serum using proximity extension assay (O-link Inflammation panel, Olink Proteomics, Uppsala, Sweden). Results: There were 52% woman and 48% men with a mean age of 50.2±12 years. The median aldosterone-renin-quotient (ARQ) was 96 and the blood pressure values were ranging between 142±17/89±12 mmHg. 6 months following the treatment a significant reduction in blood pressure and ARQ was achieved. Analysis of association between clinical factors and biomarker expression has shown that patients with adrenal adenoma have significantly higher levels of FGF21, whereas female gender was associated with lower expression of pro-inflammatory cytokines such as IL-18, TNFRSF9, CXCL9 and higher expression of protective cytokines such as TWEAK and MCP-4, especially among females with bilateral hyperplasia. According to proteomic analysis at study entry, we have identified 4 patient clusters. Interestingly, young females with adrenal adenoma have composed a separate cluster with significantly higher levels of IL-6, IFN-gamma, MCP-1, MMP1 and FGF21 and robust reduction of these parameters following the treatment. In general, volcano plot analysis of whole study cohort has demonstrated the significant reduction in expression of pro-inflammatory cytokines (EN-RAGE, CCL23, OPG, IL-10, FGF21 etc). Conclusions: The treatment of primary aldosteronism leads to reduced expression of pro-inflammatory proteins. The extent of inflammatory activation as well as response to treatment is highly associated with gender and the cause of aldosterone excess.