The Effect of Antihypertensive Medications on Testing for Primary Aldosteronism

Primary aldosteronism (PA) is a potentially curable form of secondary hypertension caused by excessive renin-independent aldosterone secretion, leading to increased target organ damage and cardiovascular morbidity and mortality. The diagnosis of PA requires measuring renin and aldosterone to calculate the aldosterone-to-renin ratio, followed by confirmatory tests to demonstrate renin-independent aldosterone secretion and/or PA subtype differentiation. Various antihypertensive drug classes interfere with the renin-angiotensin-aldosterone axis and hence evaluation for PA should ideally be performed off-drugs. This is, however, often precluded by the risks related to suboptimal control of blood pressure and serum potassium level in the evaluation period. In the present review, we summarized the evidence regarding the effect of various antihypertensive drug classes on biochemical testing for PA, and critically appraised the issue whether and which antihypertensive medications should be withdrawn or, conversely, might be continued in patients evaluated for PA. The least interfering drugs are calcium antagonists, alpha-blockers, hydralazine, and possibly moxonidine. If necessary, the testing may also be attempted during treatment with beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers but renin and aldosterone measurements must be interpreted in the context of known effects of these drugs on these parameters. Views are evolving on the feasibility of testing during treatment with mineralocorticoid receptor antagonists, as these drugs are now increasingly considered acceptable in specific patient subsets, particularly in those with severe hypokalemia and/or poor blood pressure control on alternative treatment.

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Clinical relevance of central blood pressure - a critical review

VASA ◽

10.1024/0301-1526/a000565 ◽

2016 ◽

Vol 45 (6) ◽

pp. 451-460 ◽

Cited By ~ 4

Author(s):

Michael Kostapanos ◽

Carmel M. McEniery ◽

Ian B. Wilkinson

Keyword(s):

Blood Pressure ◽

Antihypertensive Drug ◽

Clinical Relevance ◽

Beta Blockers ◽

Organ Damage ◽

Cardiovascular Outcomes ◽

Central Blood Pressure ◽

Antihypertensive Medications ◽

Brachial Blood Pressure ◽

Drug Classes

Abstract. Vital organs are exposed to the central rather than the brachial blood pressure. To date, central blood pressure can be assessed noninvasively through the use of several devices. In this review, we critically discuss the clinical relevance of central blood pressure assessment. Considerable evidence suggests that central blood pressure is a better predictor of end-organ damage than brachial blood pressure. However, there is still uncertainty concerning the value of central pressure for predicting cardiovascular outcomes, as the existing studies are underpowered to address this issue. A full synthesis of the available data is needed in this regard. Among the different antihypertensive drug classes, beta-blockers appear to lower central blood pressure less than brachial blood pressure. This difference may, at least in part, explain the reduced efficacy of beta-blockers in the prevention of cardiovascular outcomes compared with the other antihypertensive drug classes, which may lower central and brachial blood pressure to a similar extent. Nevertheless, this differential effect might not be relevant to the newer beta-blockers with vasodilating properties, including nebivolol, celliprolol and carvedilol. However, whether a preferential reduction of central blood pressure results in better outcomes should be further assessed by appropriately powered clinical trials. Other emerging challenges include the assessment of the potential predictive value of central blood pressure variability and the development of new antihypertensive medications based on central blood pressure rather than brachial blood pressure.

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Antihypertensive drug classes have different effects on short-term blood pressure variability in essential hypertension

Hypertension Research ◽

10.1038/hr.2014.33 ◽

2014 ◽

Vol 37 (6) ◽

pp. 585-590 ◽

Cited By ~ 34

Author(s):

Natacha Levi-Marpillat ◽

Isabelle Macquin-Mavier ◽

Anne-Isabelle Tropeano ◽

Gianfranco Parati ◽

Patrick Maison

Keyword(s):

Blood Pressure ◽

Essential Hypertension ◽

Antihypertensive Drug ◽

Blood Pressure Variability ◽

Short Term ◽

Drug Classes

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SAT-558 A Dedicated Endocrine Hypertension Service Increases the Timely Diagnosis of Primary Aldosteronism

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1146 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Jun Yang ◽

Yin Y Lim ◽

Renata Libianto ◽

Jimmy Shen ◽

Morag Jennifer Young ◽

...

Keyword(s):

Blood Pressure ◽

Primary Care ◽

Primary Aldosteronism ◽

Pressure Control ◽

Organ Damage ◽

Antihypertensive Medications ◽

Endocrine Hypertension ◽

Treatment Naïve ◽

Hypertension Diagnosis ◽

The Impact

Abstract Background: Primary aldosteronism (PA) accounts for 3.2-12.7% of hypertension in primary care but is often diagnosed late, if at all. A delayed or missed diagnosis leads to poor blood pressure control and greater cardiovascular risk that could be averted with targeted treatment. An Endocrine Hypertension Service (EHS), encompassing an education program, streamlined diagnostic tests and dedicated PA clinic, was developed to address this issue. Aims: To analyse the impact of Victoria’s first dedicated EHS on the pattern of PA diagnoses. Methods: Socio-demographic and clinical data from all patients who attended the EHS since July 2016 (N=267) was collected prospectively. Patients were divided into Year 1 (Y1), Year 2 (Y2), and Year 3 (Y3), based on their first visit. Results: The proportion of referrals from primary care increased (20% in Y1 to 52% in Y3) with more referrals being made for treatment-naive hypertension (3% in Y1 to 19% in Y3). Patients with a hypertension diagnosis of 5 years or less at the time of referral to EHS increased from 34% in Y1 to 45% in Y3 whilst the percentage of patients with a hypertension diagnosis of more than 10 years decreased from 50% in Y1 to 35% in Y3. Consistent with an earlier presentation, the proportion of patients with end-organ damage at the time of referral decreased from 44% in Y1 to 29% in Y3. Almost a third of the PA patients had unilateral disease; all of those who underwent adrenalectomy had biochemical cure. Patients with bilateral PA were treated with spironolactone. Their systolic/diastolic blood pressure decreased by 15/12 mmHg in Y1, 17/13 mmHg in Y2 and 23/11 mmHg in Y3; while the mean number of antihypertensive medications decreased from 2.9 to 1.8 in Y1, 2.7 to 2.0 in Y2 and 2.2 to 1.6 in Y3 Conclusion: The EHS has facilitated an increase in referrals for PA screening from primary care, resulting in the earlier diagnosis of PA, when less complications are present, and optimised patient outcomes. A broader uptake of such a clinical service, integrated with education outreach, will bridge the gap between the reported high prevalence of PA and the actual low diagnostic rates.

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Anesthetic Management of the Hypertensive Patient: Part II

Anesthesia Progress ◽

10.2344/anpr-65-03-17 ◽

2018 ◽

Vol 65 (3) ◽

pp. 206-213 ◽

Cited By ~ 1

Author(s):

Russell Yancey

Keyword(s):

Blood Pressure ◽

Enzyme Inhibitors ◽

Angiotensin Receptor Blockers ◽

Anesthetic Management ◽

Angiotensin Converting Enzyme Inhibitors ◽

Antihypertensive Medications ◽

Converting Enzyme Inhibitors ◽

Anesthesia Providers ◽

Treatment Of Hypertension ◽

Important Health

Hypertension is an important health challenge that affects millions of people across the world today and is a major risk factor for cardiovascular disease. It is critical that anesthesia providers have a working knowledge of the systemic implications of hypertension. This review article will discuss the medical definitions of hypertension, the physiology of maintaining blood pressure, outpatient treatment of hypertension, anesthetic implications, and the common medications used by anesthesia providers in the treatment of hypertension. Part I provided an overview of hypertension and blood pressure regulation. In addition, drugs predominantly affecting control of hypertension via renal mechanisms such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and renin-inhibiting agents were discussed. In part II, the remaining major antihypertensive medications will be reviewed as well as anesthetic implications of managing patients with hypertension.

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KCNJ5 Somatic Mutation Is a Predictor of Hypertension Remission After Adrenalectomy for Unilateral Primary Aldosteronism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00531 ◽

2019 ◽

Vol 104 (10) ◽

pp. 4695-4702 ◽

Cited By ~ 11

Author(s):

Leticia A P Vilela ◽

Marcela Rassi-Cruz ◽

Augusto G Guimaraes ◽

Caio C S Moises ◽

Thais C Freitas ◽

...

Keyword(s):

Blood Pressure ◽

Somatic Mutation ◽

Primary Aldosteronism ◽

Antihypertensive Drugs ◽

Independent Predictor ◽

Blood Pressure Response ◽

Antihypertensive Medications ◽

Unilateral Adrenalectomy ◽

Molecular Features ◽

Endocrine Hypertension

AbstractContextPrimary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure <140/90 mm Hg without antihypertensive drugs) has been reported in approximately 50% of patients with unilateral PA after adrenalectomy. HT duration and severity are predictors of blood pressure response, but the prognostic role of somatic KCNJ5 mutations is unclear.ObjectiveTo determine clinical and molecular features associated with HT remission after adrenalectomy in patients with unilateral PA.MethodsWe retrospectively evaluated 100 patients with PA (60 women; median age at diagnosis 48 years with a median follow-up of 26 months). Anatomopathological analysis revealed 90 aldosterone-producing adenomas, 1 carcinoma, and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 gene was sequenced in 76 cases.ResultsKCNJ5 mutations were identified in 33 of 76 (43.4%) tumors: p.Gly151Arg (n = 17), p.Leu168Arg (n = 15), and p.Glu145Gln (n = 1). HT remission was reported in 37 of 100 (37%) patients. Among patients with HT remission, 73% were women (P = 0.04), 48.6% used more than three antihypertensive medications (P = 0.0001), and 64.9% had HT duration <10 years (P = 0.0015) compared with those without HT remission. Somatic KCNJ5 mutations were associated with female sex (P = 0.004), larger nodules (P = 0.001), and HT remission (P = 0.0001). In multivariate analysis, only a somatic KCNJ5 mutation was an independent predictor of HT remission after adrenalectomy (P = 0.004).ConclusionThe presence of a KCNJ5 somatic mutation is an independent predictor of HT remission after unilateral adrenalectomy in patients with unilateral PA.

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Effectiveness of eplerenone or spironolactone treatment in preserving renal function in primary aldosteronism

Acta Endocrinologica ◽

10.1530/eje-12-0631 ◽

2013 ◽

Vol 168 (1) ◽

pp. 75-81 ◽

Cited By ~ 39

Author(s):

Verena Fourkiotis ◽

Oliver Vonend ◽

Sven Diederich ◽

Evelyn Fischer ◽

Katharina Lang ◽

...

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Primary Aldosteronism ◽

Treatment Initiation ◽

Newly Diagnosed ◽

Antihypertensive Medications ◽

Cross Sectional ◽

Spot Urine ◽

Treatment Regimens ◽

Urine Albumin

ObjectivePrimary aldosteronism (PA) has deleterious effects on kidney function independent of blood pressure levels. Up to now, data on effectiveness of different PA therapies regarding renal function are scarce.Design and methodsThis prospective multi-center study included 29 patients with newly diagnosed PA evaluated before and 1 year after treatment initiation, and a second cohort including 119 patients who were evaluated 5.3 and 6.8 years after treatment initiation. Glomerular filtration rate (GFR), spot urine albumin excretion/urinary creatinine (UAE/Ucrea) ratio, biochemical parameters, and 24-h blood pressure were measured. In a larger cross-sectional cohort, renal function was evaluated depending on the type of treatment (adrenalectomy (ADX; n=86); spironolactone (n=65); and eplerenone (n=18)).ResultsGFR and UAE/Ucrea ratio significantly decreased in newly diagnosed PA patients after treatment initiation. In the second cohort, GFR and UAE/Ucrea ratio did not change during study period, and blood pressure was well controlled. In the larger cross-sectional cohort, no differences were seen in GFR and UAE/Ucrea ratio between PA patients on different treatment regimens. However, eplerenone treatment showed lower potassium levels and higher number of required antihypertensive medications.ConclusionsRenal dysfunction with elevated albuminuria was seen in PA patients and was reversible after treatment initiation. Medical therapies with spironolactone or eplerenone seem to be as effective as ADX regarding renal function and blood pressure; however, sufficient daily doses need to be given.

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Prospective Screening for Primary Aldosteronism in Patients With Suspected Obstructive Sleep Apnea

Hypertension ◽

10.1161/hypertensionaha.120.16902 ◽

2021 ◽

Author(s):

Min Ru Chee ◽

Jesse Hoo ◽

Renata Libianto ◽

Stella M. Gwini ◽

Garun Hamilton ◽

...

Keyword(s):

Blood Pressure ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Primary Aldosteronism ◽

Blood Pressure Monitoring ◽

Apnea Hypopnea Index ◽

Hypertension Status ◽

Antihypertensive Medications ◽

Sleep Study ◽

Obstructive Sleep

Several studies have demonstrated a bidirectional relationship between obstructive sleep apnea and primary aldosteronism (PA); however, many of these studies are limited to patients with known obstructive sleep apnea, hypertension, or PA. We evaluated the role of screening for PA in all patients referred for a diagnostic sleep study without selecting for prior diagnoses with these conditions. Plasma aldosterone and renin concentration were measured after an overnight polysomnography. Blood pressure was measured at the sleep center for all patients, while a proportion underwent 24-hour blood pressure monitoring. Of the 85 participating patients, 2 (2.4%) were identified to have likely PA based on an elevated aldosterone:renin ratio and/or clinical characteristics. Another 10 (11.8%) were identified to have possible PA based on their low or normal plasma renin concentration despite taking antihypertensive medications that are known to elevate renin. In participants with both obstructive sleep apnea and hypertension (n=40), the prevalence of likely or possible PA was 30%. However, there was no correlation between aldosterone, rennin, or aldosterone:renin ratio and the apnea-hypopnea index using multiple regression analysis adjusted for interfering medications and hypertension status. The observed high prevalence of possible PA among those with both hypertension and obstructive sleep apnea suggests that they should be routinely screened for PA.

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Genetically Determined Blood Pressure, Antihypertensive Medications, and Risk of Alzheimer’s Disease: A Mendelian Randomization Study

10.21203/rs.3.rs-125105/v1 ◽

2020 ◽

Author(s):

Ya-Nan Ou ◽

Yu-Xiang Yang ◽

Xue-Ning Shen ◽

Ya-Hui Ma ◽

Shi-Dong Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Blood Pressure ◽

Alzheimer's Disease ◽

Lower Risk ◽

Mendelian Randomization ◽

Angiotensin Receptor Blockers ◽

Genome Wide Association Studies ◽

Reverse Causality ◽

Antihypertensive Medications ◽

Genetically Determined

Abstract BackgroundObservational studies suggest that the use of antihypertensive medications (AHMs) is associated with a reduced risk of Alzheimer’s disease (AD); however, these findings may be biased by confounding and reverse causality. We aimed to explore the effects of blood pressure (BP) and lowering systolic BP (SBP) via the protein targets of different AHMs on AD through a two-sample Mendelian randomization (MR) approach.MethodsGenetic proxies from genome-wide association studies of BP traits and BP-lowering variants in genes encoding AHM targets were extracted. Estimates were calculated by inverse-variance weighted method as the main model. MR Egger regression and leave-one-out analysis were performed to identify potential violations. ResultsThere was limited evidence that genetically predicted SBP/diastolic BP level affected AD risk based on 400/398 single nucleotide polymorphisms (SNPs), respectively (all P>0.05). Suitable genetic variants for β-blockers (1 SNP), angiotensin receptor blockers (1 SNP), calcium channel blockers (CCBs, 45 SNPs) and thiazide diuretics (5 SNPs) were identified. Genetic proxies for CCB [odds ratio (OR)=0.959, 95% confidence interval (CI)=0.941-0.977, P<0.001], and overall use of AHMs (OR=0.961, 95% CI=0.944-0.978, P<0.001, SNPs=52) were associated with a lower risk of AD. No notable heterogeneity and directional pleiotropy were identified (all P>0.05). No single SNP was driving the observed effects. ConclusionsThis MR analysis found robust evidence that genetically determined lowering BP was associated with a lower risk of AD and CCB was identified as a promising strategy for AD prevention.

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Anti-Hypertensive Drug Requirements in Continuous Ambulatory Peritoneal Dialysis

Peritoneal Dialysis International ◽

10.1177/089686088400400208 ◽

1984 ◽

Vol 4 (2) ◽

pp. 85-88 ◽

Cited By ~ 25

Author(s):

Michael A. Young ◽

Karl D. Nolph ◽

Sue Dutton ◽

Barbara Prowant

Keyword(s):

Blood Pressure ◽

Peritoneal Dialysis ◽

Retrospective Analysis ◽

Continuous Ambulatory Peritoneal Dialysis ◽

Antihypertensive Drug ◽

Body Fluid ◽

Sodium Balance ◽

Control Blood Pressure ◽

Antihypertensive Medications ◽

Hypertensive Drug

This retrospective analysis documents changes in antihypertensive drug requirements with time on CAPD. In 59 patients who were hypertensive at initiation of CAPD, antihypertensive drug use decreased from almost 1.2 to less than 0.3 drugs per patient during the first month. In this group, the proportion in whom blood pressure was controlled without drugs went from 0% to nearly 60% after 12 months. These results, which most likely reflect control of body -fluid volumes and sodium balance, are similar to those reported with hemodialysis. It has been noted that patients receiving antihypertensive medications to control blood pressure at the initiation of continuous ambulatory peritoneal dialysis (CAPD) frequently require fewer or no anti-hypertensive medications with time on CAPD (1–2). The purpose of this retrospective analysis was to quantitate the extent and the timing of this trend in a CAPD population at a single center.

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