Plasma Renin Activity Is a Predictive Biomarker of Blood Pressure Response in European but not in African Americans With Uncomplicated Hypertension.

Abstract

BACKGROUND:

Interindividual variability in blood pressure (BP) response to antihypertensives has been reported. Although plasma renin activity (PRA) is a potential biomarker for personalizing antihypertensive therapy in European American (EA) and African American (AA) hypertensives, clinical utility of PRA-guided prescribing is incompletely understood.

METHODS:

Using systematic-phased approach, PRA's clinical utility was assessed. After categorizing by baseline PRA, clinic systolic BP (SBP) responses to metoprolol and chlorthalidone were compared in 134 EAs and 102 AAs enrolled in the Pharmacogenomics Evaluation of Antihypertensive Responses-2 (PEAR-2) trial. Receiver operating characteristic (ROC) analysis was conducted in EAs. Data from PEAR-2 AAs were used to estimate an optimal PRA cut point using multivariable linear regression models. The derived cut point in AAs was tested in a meta-analysis of 2 independent AA cohorts, and its sensitivity and specificity were assessed.

RESULTS:

EAs with PRA < 0.65 ng/ml/hour had a greater decrease in SBP to chlorthalidone than metoprolol (by -15.9 mm Hg, adjusted P < 0.0001), whereas those with PRA ≥ 0.65 ng/ml/hour had a greater decrease in SBP to metoprolol than chlorthalidone (by 3.3 mm Hg, adjusted P = 0.04). Area under ROC curve (0.69, P = 0.0001) showed that PRA can predict SBP response among EAs. However, we observed no association between PRA and SBP response in PEAR-2 AAs. Among independent AA cohorts, those with PRA ≥ 1.3 ng/ml/hour (PEAR-2-derived cut point) responded better to atenolol/candesartan than hydrochlorothiazide (meta-analysis P = 0.01). However, sensitivity of the derived cut point was 10%.

CONCLUSIONS:

PRA at the previously established 0.60-0.65 ng/ml/hour cut point is an effective predictive biomarker of BP response in EAs. However, we were unable to identify PRA cut point that could be used to guide antihypertensive selection in AAs.

TRIAL REGISTRATION:

NCT01203852, NCT00246519, NCT00005520.

• Authors: Mai Mehanna, Zhiying Wang, Yan Gong, Caitrin W McDonough, Amber L Beitelshees, John G Gums, Arlene B Chapman, Gary L Schwartz, Kent R Bailey, Julie A Johnson, Stephen T Turner, Rhonda M Cooper-DeHoff
• Journal: American journal of hypertension (Am J Hypertens) Vol. 32 Issue 7 Pg. 668-675 (06 11 2019) ISSN: 1941-7225 [Electronic] United States
• PMID: 30753254 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: © American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Antihypertensive Agents
• Biomarkers
• Renin
• Metoprolol
• Chlorthalidone

Topics

• Adolescent
• Adult
• Black or African American
• Aged
• Antihypertensive Agents (therapeutic use)
• Biomarkers (blood)
• Blood Pressure (drug effects)
• Chlorthalidone (therapeutic use)
• Clinical Decision-Making
• Essential Hypertension (blood, drug therapy, ethnology, physiopathology)
• Female
• Humans
• Male
• Metoprolol (therapeutic use)
• Middle Aged
• Patient Selection
• Predictive Value of Tests
• Randomized Controlled Trials as Topic
• Renin (blood)
• Treatment Outcome
• United States (epidemiology)
• White People
• Young Adult