EP-002 - INTEGRATED METABOLOMICS ANALYSIS REVEALS MECHANISTIC INSIGHTS INTO THE ANCESTRAL DIFFERENCES IN PLASMA RENIN ACTIVITY AMONG PATIENTS WITH HYPERTENSION AND THIAZIDE DIURETICS BLOOD PRESSURE LOWERING EFFECTS.

M. Mehanna¹, Y. Gong¹, C. McDonough¹, S. Smith¹, J. Gums¹, A. Chapman², J. Johnson¹, L. McIntyre¹, R. Cooper-DeHoff¹; ¹University of Florida, Gainesville, FL, USA, ²The University of Chicago, Chicago, IL, USA.

Background: Hypertensive patients with higher genetic West African ancestry (GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) than those with lower GWAA, primarily due to lower plasma renin activity (PRA). TDs reduce BP by increasing sodium excretion. A vasodilator effect of TDs is also proposed, via incompletely understood mechanisms. This study aimed at identifying pathways underlying ancestral differences in PRA, which might reflect pathways underlying TD BP lowering.

Methods: Among hypertensive participants, we previously identified 8 metabolites associated with baseline PRA and 4 metabolic clusters (including 39 metabolites) that are different between those with GWAA < 45% vs ≥ 45%. Using Ingenuity Pathway Analysis (IPA), we integrated these signals.

Results: Three overlapping metabolic signals within significantly enriched pathways were identified, reflecting both PRA and GWAA (Figure). Literature indicates that the identified pathways are linked to salt sensitivity and involved in the regulation of Rho kinase cascade and nitric oxide production, the pathways proposed to underlie TD-induced vasodilatation.

Conclusion: These findings shed light on potential pathways underlying ancestral differences in PRA and improve our understanding of TD BP lowering effects.

Summary of study findings and their connections with proposed mechanisms of TD-induced direct vasodilatation and long-term BP reduction