Journal
METABOLITES
Volume 11, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/metabo11090645
Keywords
plasma renin activity; metabolomics; hypertension; blood pressure
Categories
Funding
- National Institute of Health (NIH) Pharmacogenetics Research Network grant [U01-GM074492]
- National Center for Advancing Translational Sciences [UL1 TR000064, UL1 TR000454, UL1 TR000135]
- Mayo Foundation
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This study identified metabolic signatures associated with baseline PRA and their linkages with the effects of thiazides and beta-blockers in regulating blood pressure, providing insights into the mechanisms underlying BP response.
Plasma renin activity (PRA) is a predictive biomarker of blood pressure (BP) response to antihypertensives in European-American hypertensive patients. We aimed to identify the metabolic signatures of baseline PRA and the linkages with BP response to beta-blockers and thiazides. Using data from the Pharmacogenomic Evaluation of Antihypertensive Responses-2 (PEAR-2) trial, multivariable linear regression adjusting for age, sex and baseline systolic-BP (SBP) was performed on European-American individuals treated with metoprolol (n = 198) and chlorthalidone (n = 181), to test associations between 856 metabolites and baseline PRA. Metabolites with a false discovery rate (FDR) < 0.05 or p < 0.01 were tested for replication in 463 European-American individuals treated with atenolol or hydrochlorothiazide. Replicated metabolites were then tested for validation based on the directionality of association with BP response. Sixty-three metabolites were associated with baseline PRA, of which nine, including six lipids, were replicated. Of those replicated, two metabolites associated with higher baseline PRA were validated: caprate was associated with greater metoprolol SBP response (beta = -1.7 +/- 0.6, p = 0.006) and sphingosine-1-phosphate was associated with reduced hydrochlorothiazide SBP response (beta = 7.6 +/- 2.8, p = 0.007). These metabolites are clustered with metabolites involved in sphingolipid, phospholipid, and purine metabolic pathways. The identified metabolic signatures provide insights into the mechanisms underlying BP response.
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