Baseline Plasma Renin Activity Research Articles

Integrated metabolomics analysis reveals mechanistic insights into variability in blood pressure response to thiazide diuretics and beta blockers.

Hypertensive patients with a higher proportion of genetic West African ancestry (%GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) and worse response to β-blockers (BBs) than those with lower %GWAA, associated with their lower plasma renin activity (PRA). TDs and BBs are suggested to reduce BP in the long term through vasodilation via incompletely understood mechanisms. This study aimed at identifying pathways underlying ancestral differences in PRA, which might reflect pathways underlying BP-lowering mechanisms of TDs and BBs. Among hypertensive participants enrolled in the Pharmacogenomics Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 trials, we previously identified 8 metabolites associated with baseline PRA and 4 metabolic clusters (including 39 metabolites) that are different between those with GWAA <45% versus ≥45%. In the current study, using Ingenuity Pathway Analysis (IPA), we integrated these signals. Three overlapping metabolic signals within three significantly enriched pathways were identified as associated with both PRA and %GWAA: ceramide signaling, sphingosine 1- phosphate signaling, and endothelial nitric oxide synthase signaling. Literature indicates that the identified pathways are involved in the regulation of the Rho kinase cascade, production of the vasoactive agents nitric oxide, prostacyclin, thromboxane A2, and endothelin 1; the pathways proposed to underlie TD- and BB-induced vasodilatation. These findings may improve our understanding of the BP-lowering mechanisms of TDs and BBs. This might provide a possible step forward in personalizing antihypertensive therapy by identifying patients expected to have robust BP-lowering effects from these drugs.

PSUN53 Using Renin Activity to Guide Mineralocorticoid Receptor Antagonist Therapy in Patients with Low-Renin Hypertension

Abstract Emerging studies show that beyond a phenotype of overt primary aldosteronism, there exists a prevalent phenotype of renin-independent aldosterone production among patients with low-renin hypertension (LRH). Mineralocorticoid receptor antagonist (MRA) therapy to induce an increase in renin is associated with favorable outcomes in primary aldosteronism. Whether a similar approach is beneficial for all patients with low-renin hypertension is not known. We evaluated whether treatment of patients with LRH with MRAs to increase renin is associated with a decrease in blood pressure and/or proteinuria. We have conducted a prospective observational cohort study of consecutive patients from the practice of co-author A.T. between 2005 and 2021. Patients were included if they had hypertension with suppressed (&amp;lt; 1.0 ng/ml/h) plasma renin activity (PRA) and detectable aldosterone levels but favored empiric medical therapy over further diagnostic testing. All patients were subsequently treated with an MRA. MRA was started at 25-50 mg daily of spironolactone (women) or eplerenone (men) and the dose was gradually increased in 25-50 mg increments to target a PRA ≥ 1.0 ng/ml/h or the maximal tolerated dose. Blood pressure, albumin-to-creatinine ratio (ACR), and other patient characteristics at baseline vs. after unsuppressed renin was achieved were compared using a paired-samples t-test. The mean age of 31 study patients who achieved unsuppressed PRA was 67.9 (SD 11.9) and 14 (45.2%) were women. The mean baseline aldosterone was 14.9 ng/dL (SD 9.4); 13 (41.9%) patients had baseline aldosterone &amp;lt; 10.0 ng/dL. Most (21/31; 67.7%) patients had baseline PRA below the assay detection limit. The mean baseline potassium was 4.2 (SD 0.46); one (3.2%) patient had baseline hypokalemia (K &amp;lt; 3.5 mEql/dL). The mean final PRA was 4.78 (SD 5.64) ng/ml/h. The median (IQR) MRA dose required to achieve unsuppressed PRA was 75 (50 to 200) mg. The mean systolic and diastolic blood pressure decreased from 144.9 (SD 14.9) and 79.2 mm Hg (SD 15.0) at baseline to 124.7 (SD 11.1) and 71.5 mm Hg (SD 10.8), respectively, after achievement of unsuppressed PRA (P &amp;lt; 0.001 for both). The mean number of anti-hypertensive medications decreased from 3.4 (SD 1.3) at baseline to 2.5 (SD 1.5) after achievement of unsuppressed PRA (P &amp;lt; 0.001). Among the six (19.4%) patients who had proteinuria, the mean ACR decreased from 179.0 (SD 102.1) at baseline to 36.1 (SD 49.2) mg/g after achievement of unsuppressed PRA (P = 0.007). Three (9.7%) and seven (22.6%) patients had to have their MRA dose decreased due to symptomatic hypotension and hyperkalemia, respectively. These findings suggest that suppressed renin may be sufficient to identify patients who could benefit from MR blockade. Treatment of patients with suppressed renin with sufficient MRA dose to achieve its unsuppression could lower both elevated blood pressure and proteinuria. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

FRI521 - Baseline plasma renin activity (PRA) predicts risk of AKI in patients with cirrhosis: a prospective observational study

FRI521 - Baseline plasma renin activity (PRA) predicts risk of AKI in patients with cirrhosis: a prospective observational study

Lack of Effects of Renin-Angiotensin-Aldosterone System Activity and Beta-Adrenoceptor Pathway Polymorphisms on the Response to Bisoprolol in Hypertension.

PurposeThis study examined the effects of plasma renin activity (PRA), angiotensin II (Ang II) and aldosterone (PAC) concentrations as well as common polymorphisms in the β1-Adrenoceptor gene (ADRB1) and the G-protein α-Subunit (Gαs) protein gene the G protein α-Subunit 1 gene (GNAS) on the blood pressure (BP) and heart rate (HR) response to bisoprolol in Chinese patients with hypertension.MethodsPatients with sitting clinic systolic BP (SBP) 140–169 mmHg and/or diastolic BP (DBP) 90–109 mmHg after placebo run-in were treated with open-label bisoprolol 2.5 mg daily for 6 weeks. Patients diagnosed as having primary aldosteronism or renal artery stenosis were excluded. PRA, Ang II and PAC concentrations were measured after the placebo run-in and after 6 weeks of treatment. The Ser49Gly and Arg389Gly polymorphisms in ADRB1 and the c.393C > T polymorphism in GNAS were genotyped by the TaqMan® assay.ResultsIn 99 patients who completed the study, baseline PAC levels were significantly associated with baseline DBP and plasma potassium on univariate but not on multivariate linear regression analysis. PRA, Ang II, and PAC concentrations at baseline were not associated with changes in BP with bisoprolol treatment, but the values were all significantly reduced (PRA −0.141 ± 0.595 ng/mL/h, Ang II −2.390 ± 5.171 pmol/L and aldosterone −51.86 ± 119.1 pg/mL; all P < 0.05) following 6 weeks of bisoprolol treatment. There were no significant differences in BP or HR responses in patients with baseline PRA above or below the PRA cut-point of 0.65 ng/mL/h or the median value of 0.9 ng/ml/hour. There were no significant associations of the ADRB1 and GNAS polymorphisms with the clinic and ambulatory BP and HR responses to bisoprolol.ConclusionBaseline PRA, PAC and Ang II concentrations showed no significant association with the BP response to bisoprolol treatment, but all these parameters were reduced after 6 weeks of treatment with bisoprolol. The two common polymorphisms in ADRB1 and the c.393C > T polymorphism in GNAS had no significant association with the BP and HR response to bisoprolol in these patients.

Increased Dosage of MRA Improves BP and Urinary Albumin Excretion in Primary Aldosteronism With Suppressed Plasma Renin.

PurposeExcessive aldosterone secretion causes a high risk of cardio-cerebrovascular events. Mineralocorticoid receptor antagonist (MRA) is 1 of the treatment strategies for primary aldosteronism (PA). However, current MRA treatment is insufficient because MRA-treated patients with suppressed plasma renin activity (PRA) < 1 ng/mL/h still had a higher risk of cardiovascular disease than those with unsuppressed PRA. This is a prospective interventional study to determine the effects of an increase in MRA dosage on blood pressure (BP) control and urinary albumin excretion (UAE) in MRA-treated PA patients.MethodsThirty-four PA patients were recruited, and 24 patients (6 male, 18 female) completed this study. Serum potassium concentration was assessed every two months to adjust the dosage of MRA safely for 6 months. The primary outcomes were the changes in BP and UAE between baseline and 6 months.ResultsSystolic BP (SBP) and log10UAE decreased significantly as the daily dose of MRA increased. Diastolic BP (DBP) tended to decrease. We divided the PA patients into two groups (baseline PRA < 1 ng/mL/h and baseline PRA ≥ 1 ng/mL/h) according to PRA. In the group with baseline PRA < 1 ng/mL/h but not that with baseline PRA ≥ 1 ng/mL/h, SBP, DBP and log10UAE after 6 months were significantly lower than those at baseline.ConclusionsThe increase in MRA dosage improved BP and UAE in PA patients with suppressed PRA.

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

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.

Changes in Plasma Renin Activity After Renal Artery Sympathetic Denervation

BackgroundThe renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP. ObjectivesThe purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN. MethodsAnalyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models. ResultsBaseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (−0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (−1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN. ConclusionsPlasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749)

THE CHARACTERISTICS OF PATIENTS SENSITIVE TO MINERALOCORTICOID RECEPTOR ANTAGONISTS

Objective: Primary aldosteronism (PA) is related to various cardiovascular events, thus the treatment of this disease is exceedingly important. From the current guidelines, physicians are encouraged to administrate mineralocorticoid receptor antagonists (MRA) to the patients with bilateral type of this disease, so-called idiopathic hyperaldosteronism (IHA). However, it is recently demonstrated that the benefit of this medicine is only exerted in the patients with enough PRA elevation after MRA treatment. We retrospectively evaluated the predictors for the patients who exceed plasma renin activity (PRA) &gt; 1.0 ng/ml/h at arbitrary chance after MRA administration from baseline characteristics and the result of confirmatory tests. Design and method: Our study protocol was approved by the Ethics Committee of The Jikei University School of Medicine (No. 31-271). 67 patients who received eplerenone for PA are included. We included the patients exceed plasma renin activity (PRA) &gt; 1.0 ng/ml/h at arbitrary chance within a year after MRA administration in Group A, and the patients who did not were included in Group B. Results: The eplerenone dose was comparable in two groups (Group A: 47.7 ± 13.1 v.s. Group B: 46.7 ± 14.4 P = 0.78). The patients in Group A were younger, and baseline PRA was lower in Group A. PRA after furosemide upright test, plasma aldosterone concentration (PAC) after saline infusion test, and PAC and PAC/F (Cortisol) after rapid adrenocorticotropic hormone (ACTH) stimulation test were higher in the Group A. Above all, it is revealed with Receiver operating characteristic curve analyses that PAC/F after rapid ACTH stimulation test at the cut-off value of 12.4 was proved to have the highest Area Under Curve (AUC) among all the indices (AUC 0.770). Conclusions: In conclusion, rapid ACTH stimulation test might be useful for discriminating the patients sensitive to MRA treatment.

TCT CONNECT-417 Impact of Renal Denervation on Plasma Renin Activity and Relationship of Baseline Plasma Renin Activity to Blood Pressure Lowering Response to Renal Denervation in the SPYRAL HTN-OFF MED Pivotal trial

TCT CONNECT-417 Impact of Renal Denervation on Plasma Renin Activity and Relationship of Baseline Plasma Renin Activity to Blood Pressure Lowering Response to Renal Denervation in the SPYRAL HTN-OFF MED Pivotal trial

Racial Differences in Diuretic Efficiency, Plasma Renin, and Rehospitalization in Subjects With Acute Heart Failure.

Black patients have higher rates of hospitalization for acute heart failure than other race/ethnic groups. We sought to determine whether diuretic efficiency is associated with racial differences in risk for rehospitalization after acute heart failure. A post hoc analysis was performed on 721 subjects (age, 68±13 years; 22% black) enrolled in 3 acute heart failure clinical trials: ROSE-AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure), DOSE-AHF (Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure), and CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure). Repeated-measures ANOVA was used to test for a race×time effect on measures of decongestion. Diuretic efficiency was calculated as net fluid balance per total furosemide equivalents. In a subset of subjects, Cox regression was used to examine the association between race and rehospitalization according to plasma renin activity (PRA). Compared with nonblack patients, black patients were younger and more likely to have nonischemic heart failure. During the first 72 to 96 hours, there was greater fluid loss (P=0.001), decrease in NT-proBNP (N-terminal pro-B-type natriuretic peptide; P=0.002), and lower levels of PRA (P<0.0001) in black patients. Diuretic efficiency was higher in black than in nonblack patients (403 [interquartile range, 221-795] versus 325 [interquartile range, 154-698]; P=0.014). However, adjustment for baseline PRA attenuated the association between black race and diuretic efficiency. Over a median follow-up of 68 (interquartile range, 56-177) days, there was an increased risk of all-cause and heart failure-specific rehospitalization in nonblack patients with increasing levels of PRA, while the risk of rehospitalization was relatively constant across levels of PRA in black patients. Higher diuretic efficiency in black patients with acute heart failure may be related to racial differences in activity of the renin-angiotensin-aldosterone system.

High efficacy of low-dose albumin infusion in the prevention of paracentesis-induced circulatory dysfunction

BackgroundLarge-volume paracentesis (LVP) is a main pillar in treating patients with tense ascites. Without plasma expanders use, paracentesis-induced circulatory dysfunction (PICD) is a common complication with decreased survival. The aim was to compare low-dose albumin (2 g/L ascitic fluid removed n = 85) with standard-dose albumin (6 g/L ascitic fluid removed, n = 25) for prevention of PICD. Liver function tests, urea, creatinine, CBC, and abdominal ultrasonography were done. Plasma renin activity (PRA) was measured at baseline and on the 6th day post-LVP. The delta change (Δ) = day 6 variable minus baseline variable value. PICD was defined as increase in PRA of > 50% of the baseline value.ResultsPatients in low-dose albumin group were mainly Child B compared with Child C (85.9% vs. 52%; p = 0.001), underwent less paracentesis volume (9.78 ± 3.56 vs. 12.52 ± 3.6 L; p = 0.001), but had higher baseline PRA (859.62 ± 1151.34 vs. 165.93 ± 95.34 pg/mL; p = 0.001). In both groups, the PRA increased at day 6 compared with the baseline (1141.57 ± 1433.01 vs. 859.62 ± 1151.34 pg/mL; p = 0.01) and (192.21 ± 80.99 vs. 165.93 ± 95.34 pg/mL; p = 0.01) respectively. Both groups were comparable for Δ PRA (281.95 ± 851.4 vs. 26.28 ± 30.2 pg/mL; p = 0.102) and PRA percent increase (10.97 ± 30.77 vs. 12.57 ± 14.87; p = 0.844). They had comparable PICD incidence (24.7% vs. 12%; p = 0.27). Females were more liable for PICD occurrence than males (OR 2.91, 95% CI 1.125–7.547, p = 0.028) and so Child B patients than Child C (OR 8.4, 95% CI 1.072–65.767, p = 0.043).ConclusionLow-dose albumin infusion is comparable to the standard-dose albumin for the prevention of PICD.

Pathophysiology and Prevention of Paracentesis-induced Circulatory Dysfunction: A Concise Review.

Annually, 10% of cirrhotic patients with ascites develop refractory ascites for which large-volume paracentesis (LVP) is a frequently used therapeutic procedure. LVP, although a safe method, is associated with circulatory dysfunction in a significant percentage of patients, which is termed paracentesis-induced circulatory dysfunction (PICD). PICD results in faster reaccumulation of ascites, hyponatremia, renal impairment, and shorter survival. PICD is diagnosed through laboratory results, with increases of >50% of baseline plasma renin activity to a value ≥4 ng/mL/h on the fifth to sixth day after paracentesis. In this review, we discuss the pathophysiology and prevention of PICD.

Baseline Plasma Aldosterone Level and Renin Activity Allowing Omission of Confirmatory Testing in Primary Aldosteronism.

Previous studies have proposed cutoff value of baseline plasma aldosterone concentration (bPAC) under renin suppression that could diagnose primary aldosteronism (PA) without confirmatory testing. However, those studies are limited by selection bias due to a small number of patients and a single-center study design. This study aimed to determine cutoff value of bPAC and baseline plasma renin activity (bPRA) for predicting positive results in confirmatory tests for PA. The multi-institutional, retrospective, cohort study was conducted using the PA registry in Japan (JPAS/JRAS). We compared bPAC in patients with PA who showed positive and negative captopril challenge test (CCT) or saline infusion test (SIT) results. Patients with PA who underwent CCT (n = 2256) and/or SIT (n = 1184) were studied. The main outcomes were cutoff value of bPAC (ng/dL) and bPRA (ng/mL/h) for predicting positive CCT and/or SIT results. In patients with renin suppression (bPRA ≤ 0.3), the cutoff value of bPAC that would give 100% specificity for predicting a positive SIT result was lower than that for predicting a positive CCT result (30.85 vs 56.35, respectively). Specificities of bPAC cutoff values ≥ 30.85 for predicting positive SIT and CCT results remained high (100.0% and 97.0%, respectively) in patients with bPRA ≤ 0.6. However, the specificities of bPAC cutoff values ≥ 30.85 for predicting positive SIT and CCT results decreased when patients with bPRA > 0.6 were included. Confirmatory testing could be omitted in patients with bPAC ≥ 30.85 in the presence of bPRA ≤ 0.6.

Is plasma renin activity associated with worse outcomes in acute heart failure? A secondary analysis from the BLAST-AHF trial.

Neurohormonal activation characterizes chronic heart failure (HF) and is a well-established therapeutic target. Neurohormonal activation may also play a key role in acute HF (AHF). We aim to describe the association between plasma renin activity (PRA) and three AHF outcomes: (i) worsening HF or death through day 5 of hospitalization; (ii) HF rehospitalization or death through day 30; and (iii) all-cause death through day 30. A secondary analysis of the BLAST-AHF trial was performed. Eligible patients had a history of HF, elevated natriuretic peptides, signs and symptoms of HF, systolic blood pressure >120 mmHg, and an estimated glomerular filtration rate between 20-75 mL/min/1.73 m2 . The primary trial was neutral, with no differential effect of study drug by PRA levels. Baseline PRA levels were grouped into tertiles. Adjusted Cox proportional hazard model determined the association of PRA levels with outcomes (α set at P< 0.05). Of 618 randomized patients, 578 (93.5%) had a baseline PRA. PRA was modestly, but significantly, associated with each outcome without adjustment [worsening HF or death through day 5: hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.01-1.23, P= 0.04; HF rehospitalization or death through day 30: HR 1.13, 95% CI 1.02-1.26, P= 0.02; all-cause death through day 30: HR 1.18, 95% CI 1.02-1.37, P= 0.03]. After multivariable adjustment, PRA was only significantly associated with HF rehospitalization or death through day 30 (HR 1.15, 95% CI 1.01-1.32, P= 0.04). Baseline PRA levels are associated with increased risk for the composite of 30-day HF rehospitalization or death in patients with AHF.

Abstract P181: Optimizing Precision of Hypertension Care to Maximize Blood Pressure Control (OPTI-BP): A Pilot Study Utilizing a Smartphone App

Background: About half of patients with hypertension (HTN) respond to any given antihypertensive drug. Discordance in pathophysiologic pathways underlying HTN and anti-HTN mechanism of action are major contributors. Personalizing anti-HTN therapy could optimize blood pressure (BP) control. The objective of OPTI-BP was to assess the pragmatic implementation of a smartphone app used to guide physiologically optimal HTN treatment based on plasma renin activity (PRA). Methods: The smartphone app (PRA-HTN) and PRA testing was implemented in three primary care clinics. Patients with untreated or treated but uncontrolled HTN, aged 18-65 years, were recruited. BP and PRA were measured at baseline (and again as often as needed) with final BP measured at 6 months. PRA level and current anti-HTN meds are entered into the app and recommendations to optimize volume- and RAS blocking meds returned. Providers were at liberty to follow or disregard app recommendations. The primary outcome was BP change from baseline to 6 months. Independent t-test was used to compare BP responses of patients whose clinicians followed the app recommendations vs. those who did not. A multivariable linear regression analysis adjusting for baseline BP, age and sex was also conducted. Results: This analysis includes 29 white patients, including 11 (37.9%) women, with a mean age of 52 ± 9 years and a median baseline PRA of 1.3 ng/mL/hr (IQR 0.5-3.1 ng/mL/hr). Mean baseline BP between patients whose clinicians followed the app recommendations (n=16, 55%) vs. those who did not (n=13, 45%) was not statistically different ( P &gt;0.05). After 6 months, the average BP change among patients whose clinicians followed the app recommendations was -14 ± 20/-7 ± 9 mmHg vs. -5 ± 21/-2 ± 9 mmHg among those who did not. In regression analysis, use of app recommended therapy was associated with greater mean BP difference of -13±8/-9±4 mmHg ( P =0.1/0.02). Conclusion: This pilot study demonstrates that PRA testing and implementation of recommendations from a smartphone app that utilizes PRA to optimize anti-HTN therapy was associated with good BP lowering among a relatively small cohort of patients. Future studies using larger sample sizes are warranted to confirm these preliminary findings.

Abstract 109: Changes in Plasma Renin Activity After Renal Denervation in the Spyral Htn-Off Med Trial

Results from recent sham-controlled clinical trials demonstrate the efficacy of renal denervation (RDN) in blood pressure reduction, however the effects of RDN on the renin-angiotensin system are not clear. We sought to evaluate changes in plasma renin activity (PRA) and serum sodium levels after RDN in the absence of anti-hypertensive medications in the SPYRAL HTN-OFF MED trial. SPYRAL HTN-OFF MED is a randomized, sham-controlled trial to evaluate the impact of RDN in the absence of anti-hypertensive medications. Patients were enrolled with an office systolic BP (SBP) ≥150 and &lt;180 mmHg, office diastolic BP ≥90 mmHg, and a mean 24-hour SBP ≥140 and &lt;170 mmHg. Patients were randomized 1:1 to RDN with the SYMPLICITY Spyral™ catheter (N=38) or sham procedure (N=42). PRA and serum sodium levels were measured at baseline and 3 months post-procedure. Changes were expressed using medians and interquartile ranges and compared between groups using the Mann-Whitney U-test. Change in PRA from baseline to 3 months was significantly greater for the RDN group (n=23) -0.15 ng/mL/h [-0.76, -0.02] compared to the sham control group (n=33) 0.02 ng/mL/h [-0.16, 0.16]; p=0.018 ( Figure ). Comparison of 3-month changes in PRA using a Wilcoxon test stratified by 3 equal groups of baseline PRA also found a significant difference between groups (p=0.033). Changes in sodium levels were similar between groups: 0 mmol/L [-2, 2] (RDN, N=37) vs. 0 mmol/L [-1, 1] (control, N=41), p=0.920). In this sham-controlled feasibility trial, renal denervation was associated with a reduction in PRA but no difference in serum sodium levels was observed. The impact on sodium excretion will need to be assessed in future studies.

The characteristics of captopril challenge test-positive patients using various criteria.

Introduction:The captopril challenge test (CCT) is the major confirmatory test for primary aldosteronism (PA), and frequently carried out because of its convenience. However, it presents false-negative results with a certain probability, and as there are many criteria for CCT, it is not concluded yet which criteria to use.Materials and methods:A total of 71 PA patients were evaluated. We compared CCT-positive and CCT-negative patients in the following three criteria: plasma aldosterone/renin ratio (ARR) >200 after the CCT (criterion 1); plasma aldosterone concentration (PAC) >120 pg/ml after the CCT (criterion 2); and PAC suppression <30% of PAC before CCT (criterion 3).Results:The positive rate was 70.4%, 64.8% and 54.9% for criterion 1, criterion 2 and criterion 3, respectively. With criterion 1, the baseline plasma renin activity was lower, thus baseline ARR was higher in CCT-positive patients. With criterion 2, PAC was higher and estimated sodium intake and K were lower in CCT-positive patients. With criterion 3, K and PAC were lower in CCT-positive patients. Although it was not significant, in the patients with high sodium intake, the positive rate of criterion 1 was higher than that of the other criteria.Conclusions:ARR>200 is the valuable criterion for the diagnosis of PA.

Acute NaCl Loading Reveals a Higher Blood Pressure for a Given Serum Sodium Level in African American Compared to Caucasian Adults.

Purpose: African American individuals are more prone to salt-sensitive hypertension than Caucasian individuals. Small changes in serum sodium (Na+) result in increased blood pressure (BP). However, it remains unclear if there are racial differences in BP responsiveness to increases in serum Na+. Therefore, the purpose of this investigation was to determine if African American adults have altered BP responsiveness to acute changes in serum Na+ compared to Caucasian adults.Methods: We measured beat-by-beat BP, serum Na+, plasma renin activity (PRA), angiotensin II (Ang II), and aldosterone (Aldo) during a 60-min 3% NaCl infusion (hypertonic saline infusion, HSI) in 39 participants (19 African Americans, age: 23 ± 1, 20 Caucasians, age: 25 ± 1). Data reported as African American vs. Caucasian cohort, mean ± SEM.Results: Baseline BP and serum Na+ were similar between groups and increased during HSI in both African American and Caucasian participants (p < 0.01). However, the peak change in serum Na+ was greater in African American participants (Δ5.8 ± 0.34 vs. Δ4.85 ± 0.38 mmol/L, p = 0.03). There was a significant group effect (p = 0.02) and an interaction between race and serum Na+ on systolic BP (p = 0.02). Larger categorical changes in serum Na+ corresponded to changes in systolic BP (p < 0.01) and African American participants demonstrated greater systolic BP responses for a given categorical serum Na+ increase (p < 0.01). Baseline Aldo was lower in African American adults (7.2 ± 0.6 vs. 12.0 ± 1.9 ng/dL, p = 0.03), there was a trend for lower baseline PRA (0.59 ± 0.9 vs. 1.28 ± 0.34 ng/mL/h, p = 0.07), and baseline Ang II was not different (14.2 ± 1.8 vs. 18.5 ± 1.4 pg/mL, p = 0.17). PRA and Aldo decreased during the HSI (p ≤ 0.01), with a greater decline in PRA (Δ–0.31 ± 0.07 vs. Δ–0.85 ± 0.25 ng/mL/h, p < 0.01) and Aldo (Δ–2.5 ± 0.5 vs. Δ–5.0 ± 1.1 ng/dL, p < 0.01) in Caucasian participants. However, the racial difference in PRA (p = 0.57) and Aldo (p = 0.59) reduction were no longer significant following baseline covariate analysis. Conclusion: African American individuals demonstrate augmented serum Na+ to an acute hypertonic saline load and greater systolic BP responsiveness to a given serum Na+. The altered BP response may be attributable to lower basal PRA and Aldo and a subsequently blunted RAAS response during the HSI.

Low plasma renin activity is an independent predictor of near-term incidence of hypertension in Asian populations

ABSTRACTBackground: Plasma renin activity is involved in the regulation of body salt content and blood pressure. However, there is a paucity of data regarding the association between low or high plasma renin activity and the development of hypertension.Method: We investigated the relation of baseline plasma renin activity to increases in blood pressure and the incidence of hypertension after four years in 2,146 non-hypertensive individuals from a community-based Korean population (mean age, 50 years), 58% of whom were women. We defined an “increase in blood pressure” as an increment of systolic blood-pressure ≥ 10 mmHg or initiation of antihypertensive drugs and defined “hypertension” as a systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or the use of antihypertensive medications.Results: After 4 years, the increase in blood pressure had increased in 27.9% of the participants, and hypertension had developed in 17.9%. After adjustment, the lowest sex-specific tertile of plasma renin activity was an independent risk factor of an elevation in blood pressure (Adjusted Odds Ratio 1.37, 95% confidence interval 1.07–1.74, p = 0.011) and hypertension (Adjusted Odds Ratio 1.84, 95% confidence interval 1.36–2.50, p < 0.001) compared to the highest sex-specific tertile. The associations between the plasma renin activity and blood-pressure outcomes were evident in adults with especially high urine sodium excretion.Conclusion: Low plasma renin activity was associated with the development of hypertension in the middle-aged Asian population, especially in peoples with high sodium intake.

Genetic Variants Influencing Plasma Renin Activity in Hypertensive Patients From the PEAR Study (Pharmacogenomic Evaluation of Antihypertensive Responses).

Plasma renin is an important regulator of blood pressure (BP). Plasma renin activity (PRA) has been shown to correlate with variability in BP response to antihypertensive agents. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with baseline PRA using data from the PEAR study (Pharmacogenomic Evaluation of Antihypertensive Responses). Multiple linear regression analysis was performed in 461 whites and 297 blacks using an additive model, adjusting for age, sex, and ancestry-specific principal components. Top SNPs were prioritized by testing the expected direction of association for BP response to atenolol and hydrochlorothiazide. Top regions from the BP response prioritization were tested for functional evidence through differences in gene expression by genotype using RNA sequencing data. Regions with functional evidence were assessed for replication with baseline PRA in an independent study (PEAR-2). Our top SNP rs3784921 was in the SNN-TXNDC11 gene region. The G allele of rs3784921 was associated with higher baseline PRA (β=0.47; P=2.09×10-6) and smaller systolic BP reduction in response to hydrochlorothiazide (β=2.97; 1-sided P=0.006). In addition, TXNDC11 expression differed by rs3784921 genotype (P=0.007), and rs1802409, a proxy SNP for rs3784921 (r2=0.98-1.00), replicated in PEAR-2 (β=0.15; 1-sided P=0.038). Additional SNPs associated with baseline PRA that passed BP response prioritization were in/near the genes CHD9, XIRP2, and GHR. CONCLUSIONS: We identified multiple regions associated with baseline PRA that were prioritized through BP response signals to 2 mechanistically different antihypertensive drugs. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00246519.