Exploring the Plasma Fatty Acid Signature of Primary Aldosteronism: Comparison with Essential Hypertension and Longitudinal Therapy Effects

Background/Objectives: Fatty acids (FAs) play crucial roles in human physiology, and their levels have been associated with hypertension, although with inconsistent findings. Primary Aldosteronism (PA), a common, often underdiagnosed form of secondary hypertension, carries a higher risk of organ damage compared to essential hypertension (EH). This study aimed to compare plasma FA profiles of patients with unilateral PA and EH and explore the impact of therapies. Methods: Participants were recruited at the Hypertension Unit of Verona University Hospital. PA diagnosis/subtype was confirmed according to guidelines. Blood samples were collected at enrollment and at follow-up (after treatment with a mineralocorticoid receptor antagonist (MRA) and adrenalectomy). Plasma long- and very-long-chain FAs were extracted and analyzed using gas chromatography. Results: Each sample was assessed for a panel of 19 selected FA species. Compared to EH (n = 60), PA patients (n = 22) exhibited lower plasma levels of behenic acid (p = 0.03), total monounsaturated fatty acids (p = 0.02), specifically palmitoleic (p = 0.005) and erucic acids (p = 0.02), and higher levels of ω6 polyunsaturated fatty acids (PUFAs, p = 0.02). Longitudinal analysis in PA patients showed that MRAs decreased total saturated FAs (pADJ = 0.01) and increased total PUFAs (pADJ = 0.006), and these changes were largely maintained even after adrenalectomy. Conclusions: This pilot study reveals significant alterations in the plasma FA profiles of PA patients compared to EH, suggesting a more prominent inflammatory state in PA. Both pharmacological and surgical interventions induced a positive shift in the FA profile of PA patients. These findings highlight the potential of FAs as biomarkers for PA risk stratification and may offer novel therapeutic opportunities.