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

Mehanna, Mai; Wang, Zhiying; Gong, Yan; McDonough, Caitrin W.; Beitelshees, Amber L.; Gums, John G.; Chapman, Arlene B.; Schwartz, Gary L.; Bailey, Kent R.; Turner, Stephen T.; Cooper‐DeHoff, Rhonda M.

doi:10.1093/ajh/hpz022

Cited by 10 publications

(17 citation statements)

References 38 publications

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“…Previous studies demonstrate that PRA is a predictive biomarker of BP response to antihypertensive agents particularly in European American hypertensive patients [ 5 , 6 , 7 , 8 ]. Patients with lower PRA (< 0.65 ng/mL/h) achieve greater BP reductions in response to thiazide diuretics than β-blockers, whereas those with higher PRA (≥ 0.65 ng/mL/h) respond better to β-blockers than thiazide diuretics [ 9 , 10 , 11 ]. However, PRA, other clinical factors and the genetic variants identified to date, including those related to PRA, only explain about 3–4% of the total variability in the BP trait [ 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolomics Signature of Plasma Renin Activity and Linkage with Blood Pressure Response to Beta Blockers and Thiazide Diuretics in Hypertensive European American Patients

et al. 2021

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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 β-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 (β = −1.7 ± 0.6, p = 0.006) and sphingosine-1-phosphate was associated with reduced hydrochlorothiazide SBP response (β = 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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Section: Introductionmentioning

confidence: 99%

Metabolomics Signature of Plasma Renin Activity and Linkage with Blood Pressure Response to Beta Blockers and Thiazide Diuretics in Hypertensive European American Patients

et al. 2021

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“…22 Recently, we and others demonstrated that PRA is statistically significantly associated with BP response to multiple antihypertensives and that patients-especially EAs-with higher-PRA vs. lower-PRA categories have different BP responses to antihypertensive medications. 9,10,14 Moreover, we have shown that a PRA cutoff point of 0.60 ng/mL/hr, a cutoff point originally established in a cohort of EA patients decades ago, 23 has a sensitivity of 48.3% and a specificity of 85.1% to predict the BP response to chlorthalidone vs. metoprolol in EA patients with primary uncomplicated HTN. 14 The clinical utility of PRA as a biomarker was evaluated in a prospective study of 73 resistant patients with HTN followed for 1 year.…”

Section: Discussionmentioning

confidence: 89%

“…9,10,14 Moreover, we have shown that a PRA cutoff point of 0.60 ng/mL/hr, a cutoff point originally established in a cohort of EA patients decades ago, 23 has a sensitivity of 48.3% and a specificity of 85.1% to predict the BP response to chlorthalidone vs. metoprolol in EA patients with primary uncomplicated HTN. 14 The clinical utility of PRA as a biomarker was evaluated in a prospective study of 73 resistant patients with HTN followed for 1 year. This study showed that PRA-guided antihypertensive medication selection resulted in significantly fewer antihypertensive medications required to control BP.…”

Section: Discussionmentioning

confidence: 99%

“…13 Recently, we demonstrated that a PRA cutoff point of 0.60-0.65 ng/mL/hr is a predictive biomarker of BP response with good sensitivity and specificity in European American (EA) patients with uncomplicated HTN. 14 However, it is important to prospectively assess the value of utilizing PRA as a biomarker in a systematic practical treatment algorithm to improve the precision of antihypertensive therapy in both untreated and treated patients with uncontrolled HTN. Therefore, the objective of this pilot study was to assess the effect of a pragmatic implementation of a personalized antihypertensive treatment smartphone app, used to guide the selection of physiologically optimal HTN treatment based on PRA biomarker and treatment factors, on improving BP reduction and BP control in EA patients with uncomplicated HTN.…”

Section: Pra-based Smartphone App For Maximizing Bp Controlmentioning

confidence: 99%

“…Recently, we demonstrated that a PRA cutoff point of 0.60–0.65 ng/mL/hr is a predictive biomarker of BP response with good sensitivity and specificity in European American (EA) patients with uncomplicated HTN 14 . However, it is important to prospectively assess the value of utilizing PRA as a biomarker in a systematic practical treatment algorithm to improve the precision of antihypertensive therapy in both untreated and treated patients with uncontrolled HTN.…”

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Optimizing Precision of Hypertension Care to Maximize Blood Pressure Control: A Pilot Study Utilizing a Smartphone App to Incorporate Plasma Renin Activity Testing

Mehanna

Chen

Gong

et al. 2020

Clinical Translational Sci

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Only half of patients with hypertension (HTN) respond to any given antihypertensive medication. Heterogeneity in pathophysiologic pathways underlying HTN is a major contributor. Personalizing antihypertensive therapy could improve blood pressure (BP) reduction. The objective of this study was to assess the effect of pragmatic implementation of a personalized plasma renin activity (PRA)-based smartphone app on improving BP reduction. Patients with untreated or treated but uncontrolled HTN were recruited. BP and PRA were measured at baseline with final BP measured at 6 months. Patient's information was entered into the app and treatment recommendations were returned. Clinicians were at liberty to follow or disregard the app's recommendations. BP levels and percent BP control among patients whose clinicians did and did not follow the app's recommendations were compared using independent t-test and Fisher's exact test, respectively. Twenty-nine European American patients were included (38% women) with mean age of 52 ± 9 years and median PRA of 1.3 ng/mL/hr (interquartile range 0.5-3.1 ng/mL/hr). Participants whose clinicians followed the app's recommendations (n = 16, 55%) as compared with those whose clinicians did not (n = 13, 45%), had a greater reduction in 6-month systolic BP (−15 ± 21 vs. −3 ± 21 mm Hg; adjusted-P = 0.1) and diastolic BP (−8 ± 8 vs. −1 ± 8 mm Hg; adjusted-P = 0.04). BP control at 6 months tended to be greater among patients whose clinicians accepted the app's recommendations vs. those whose clinicians did not (63% vs. 23%, P = 0.06). This pilot study demonstrates that acceptance of the app's recommendations was associated with a greater BP reduction. Future studies to confirm these pilot findings are warranted. Hypertension (HTN) is one of the most common chronic diseases, affecting ~ 45.6% of the US adults aged 20 years old and over. 1 It is considered a major risk factor for multiple cardiovascular adverse outcomes, including angina, heart failure, stroke, and myocardial infarction, 2 and has been also associated with target organ damage and a high global mortality rate. 2,3 Despite the availability of multiple antihypertensive drugs, all of which have blood pressure

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Shared genetic etiology and antagonistic relationship of plasma renin activity and systolic blood pressure in a Korean cohorts

Jung

Kim

2022

Genomics

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

Cited by 10 publications

References 38 publications

Metabolomics Signature of Plasma Renin Activity and Linkage with Blood Pressure Response to Beta Blockers and Thiazide Diuretics in Hypertensive European American Patients

Metabolomics Signature of Plasma Renin Activity and Linkage with Blood Pressure Response to Beta Blockers and Thiazide Diuretics in Hypertensive European American Patients

Optimizing Precision of Hypertension Care to Maximize Blood Pressure Control: A Pilot Study Utilizing a Smartphone App to Incorporate Plasma Renin Activity Testing

Shared genetic etiology and antagonistic relationship of plasma renin activity and systolic blood pressure in a Korean cohorts

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