Prevalence and Risk Factors for Secondary Hypertension in Young Adults.

BACKGROUND: The prevalence of secondary causes of hypertension in young adults is unknown, and therefore, there is no consensus about the indication of screening of secondary hypertension (2HTN) in this population. The objective was to report the prevalence and the causes of 2HTN in young subjects. METHODS: 2090 patients with confirmed hypertension aged 18 to 40 years with full workup for 2HTN screening were included in this cross-sectional study. We assessed the prevalence of 2HTN and analyzed the factors associated. RESULTS: 619/2090 patients (29.6%) had a 2HTN. The most frequent diagnoses of 2HTN in descending order were primary aldosteronism (n=339; 54.8%), renovascular hypertension (n=114; 18.4%), primary kidney disease (n=80; 12.9%), pheochromocytoma/functional paraganglioma (n=37; 5.9%), hypertension caused by drugs or substances (n=32; 6.0%), and other diagnoses (n=17; 2.7%). Patients with blood pressure <160/100 mm Hg did not have a lower prevalence of 2HTN regardless of the number of treatments. The prevalence of 2HTN was higher in the decade between 30 and 40 years of age than between 18 and 30 years of age (P=0.024). Female sex, hypokalemia, treatment with at least 2 medications, no familial history of hypertension, body mass index <25 kg/m², and diabetes were associated with a higher prevalence of 2HTN. CONCLUSIONS: The prevalence of 2HTN is high among young patients with hypertension (29.6% in our cohort), regardless of age and blood pressure level. All patients with hypertension under 40 years of age should be screened for secondary causes.

Management of arterial hypertension: home blood pressure measurement is a cornerstone for telemonitoring and self-management.

The development of mobile telephones has made it possible to design blood pressure (BP) monitors with data transmission via cellular lines, contributing to the emergence of "e-health". Today, the direct-to-consumer marketing of devices create a new context allowing an algorithmic processing of information for remote decision-making either by the patient or by a healthcare professional. The home BP telemonitoring (HBPT) is the remote transmission of BP values, measured at home and transmitted to the doctor's office or hospital, by means of telehealth strategies. In this context, randomized controlled trials (RCTs) studies have demonstrated HBPT ability in improving patients' compliance and adherence to treatment and in accomplishing better hypertension control rates. The level of evidence for the drop in BP is "moderate" and the place of HBPT is not clearly established in current practice. Digital interventions have the potential to support patient in self-management. This approach presupposes the prior acquisition of skills, the level of which must be adapted to the level of health literacy of each patient. Few of medical applications (mobile apps or web-apps) for hypertension can be regarded as accurate and safe for clinical use and to date, we do not have high quality evidence to determine the overall effect of the use smartphone apps on BP control.

[Out-of-center blood pressure measurements in dialysis patients: Feasibility and comparison of methods]. / Mesures hors centre de la pression artérielle chez les hémodialysés chroniques : faisabilité et comparaison des méthodes.

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA)/European Society of Hypertension (ESH) recommends out-of-center blood pressure measurements, self-blood pressure measurement or ambulatory blood pressure measurement in dialysis patients. However, the feasibility of out-of-center blood pressure measurements in routine care is not known. The objective of our study was to quantify it as "a priori" i.e. the percentage of hemodialysis to whom out-of-center blood pressure measurements can be proposed and who accept it, as "a posteriori", i.e. the percentage of out-of-center blood pressure measurements made and valid. A systematic out-of-center blood pressure measurements program was implemented from April to October 2019 in our chronic hemodialysis structures. It was proposed to each dialysis patient to carry out after education, an self-blood pressure measurement (Omron M3®), from 2 measurements, to 1 to 2minutes interval, mornings and evenings of 6days without dialysis (validity: 15 measures). Apart from arrhythmic patients, to all patients "not eligible" for self-blood pressure measurement (visually impaired, hemiplegic, neuropsychological disorders, language barrier), a 44-hour ambulatory blood pressure measurement (Microlife WatchBP 03®) was proposed separating 2 hemodialysis sessions; measures every 15minutes from 7 a.m. to 10 p.m. and 30minutes from 10 p.m. to 7 a.m. (validity: 40 measurements/day and 14/night). This is a study evaluating practices recommended for routine care in 18-year-old hemodialysis, having given their consent to the collection and analysis of the data. One hundred twenty nine patients were treated with chronic hemodialysis in our structures during the out-of-center blood pressure measurements campaign. Out-of-center blood pressure measurements could not be done in 21 patients (4 deceased, 2 transplanted and 4 absent before evaluation; 7 arrhythmics; 3 refusals and 1 multiple-disabled). Of these 108 patients (sex ratio 1.25; 69.3±13.5 years), 23 were ineligible for self-blood pressure measurement (visually impaired, neuro- and/or psychological disorders, language barrier). Due to 4 self-blood pressure measurement failures, the feasibility of the self-blood pressure measurement (n=81/129) is 62.8 % (CI95% 54.2-70.7). Of the 24 ambulatory blood pressure measurements performed (23 among those not eligible for self-blood pressure measurement and 1 failure of self-blood pressure measurement), 19 were valid. The "a posteriori" feasibility of out-of-center blood pressure measurements (n=100/129) is 77.5 % (CI95% 69.6-83.4). The feasibility of out-of-center blood pressure measurements in hemodialysis patients is good, making the application of the recommendations possible.

Renal Outcome and New-Onset Renal and Extrarenal Dissections in Patients With Nontrauma Renal Artery Dissection Associated With Renal Infarction.

[Figure: see text].

Organ Transplantation in Hereditary Fibrinogen A α-Chain Amyloidosis: A Case Series of French Patients.

RATIONALE & OBJECTIVE: Fibrinogen A α-chain amyloidosis (AFib amyloidosis) is a form of amyloidosis resulting from mutations in the fibrinogen A α-chain gene (FGA), causing progressive kidney disease leading to kidney failure. Treatment may include kidney transplantation (KT) or liver-kidney transplantation (LKT), but it is not clear what factors should guide this decision. The aim of this study was to characterize the natural history and long-term outcomes of this disease, with and without organ transplantation, among patients with AFib amyloidosis and various FGA variants. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 32 patients with AFib amyloidosis diagnosed by genetic testing in France between 1983 and 2014, with a median follow-up of 93 (range, 4-192) months, were included. RESULTS: Median age at diagnosis was 51.5 (range, 12-77) years. Clinical presentation consisted of proteinuria (93%), hypertension (83%), and kidney failure (68%). Manifestations of kidney disease appeared on average at age 57 (range, 36-77) years in patients with the E526V variant, at age 45 (range, 12-59) years in those with the R554L variant (P<0.001), and at age 24.5 (range, 12-31) years in those with frameshift variants (P<0.001). KT was performed in 15 patients and LKT was performed in 4. In KT patients with the E526V variant, recurrence of AFib amyloidosis in the kidney graft was less common than with a non-E526V (R554L or frameshift) variant (22% vs 83%; P=0.03) and led to graft loss less frequently (33% vs 100%). Amyloid recurrence was not observed in patients after LKT. LIMITATIONS: Analyses were based on clinically available historical data. Small number of patients with non-E526V and frameshift variants. CONCLUSIONS: Our study suggests phenotypic variability in the natural history of AFib amyloidosis, depending on the FGA mutation type. KT appears to be a viable option for patients with the most common E526V variant, whereas LKT may be a preferred option for patients with frameshift variants.

Sequential nephron blockade with combined diuretics improves diastolic function in patients with resistant hypertension.

AIMS: Hypertension is a major contributor to cardiac diastolic dysfunction. Different therapeutics strategies have been proposed to control blood pressure (BP), but their independent impact on cardiac function remains undetermined. In patients with resistant hypertension, we compared the changes in cardiac parameters between two strategies based on sequential nephron blockade (NBD) with a combination of diuretics or sequential renin-angiotensin system blockade (RASB). METHODS AND RESULTS: After a 4-week period where all patients received Irbesartan 300 mg/day + hydrochlorothiazide 12.5 mg/day + amlodipine 5 mg/day, 140 resistant hypertension patients (54.8 ± 11.1 years, 76% men, mean duration with hypertension: 13.1 ± 10.5 years, no previous history of heart failure or current symptoms of congestive heart failure) were randomized 1:1 to the NBD regimen or to the RASB regimen at week 0 (W0, baseline). Treatment intensity was increased at week 4, 8, or 10 if home BP was ≥135/85 mmHg, by sequentially adding 25 mg spironolactone, 20-40 mg furosemide, and 5 mg amiloride (NBD group) or 5-10 mg ramipril and 5-10 mg bisoprolol (RASB group). No other antihypertensive drug was allowed during the study. BP, BNP levels, and echocardiographic parameters were assessed at weeks 0 and 12. The baseline characteristics, laboratory parameters, and plasma hormones (BNP, renin, and aldosterone) and cardiac echocardiographic parameters did not significantly differ between the NBD and the RASB groups. Over 12 weeks, BNP levels significantly decreased in NBD but increased in RASB (mean [CI 95%] change in log-transformed BNP levels: -43% [-67%; -23%] vs. +55% [46%; 62%] in NBD vs. RASB, respectively, P < 0.0001). Similarly, the proportion of patients presenting ≥2 echocardiographic criteria of diastolic dysfunction decreased between baseline and W12 from 31% to 3% in NBD but increased from 19% to 32% in RASB (P = 0.0048). As compared with RASB, NBD induced greater decrease in ambulatory systolic BP (P < 0.0001), pulse pressure (P < 0.0001), and systemic vascular resistance (P < 0.005). In multivariable linear regression analyses, NBD treatment was significantly associated with decreased BNP levels (adjusted ß: -46.41 ± 6.99, P < 0.0001) independent of age, gender, renal function, and changes in BPs or heart rate. CONCLUSIONS: In patients with resistant hypertension, nephron blockade with a combination of diuretics significantly improves cardiac markers of diastolic dysfunction independently of BP lowering.

Home blood pressure monitoring and e-Health: investigation of patients' experience with the Hy-Result system.

BACKGROUND: Hy-Result is a validated system designed to help patients complying with the home blood pressure monitoring (HBPM) protocol and understanding their blood pressure (BP) readings. It is available as a standalone web application or within a wireless BP monitor app. OBJECTIVE: The aim of the study was to explore patients' experience with Hy-Result. METHODS: Online survey completed by 512 users of the Hy-Result web application or monitor app, and three focus groups with 24 hypertensive patients who monitor their BP at home and use the Hy-Result web application to record their data. We assessed the experience of patients with the functionalities and medical content of Hy-Result, their feelings and expectations, and the impact of Hy-Result on the physician-patient relationship. RESULTS: (1) Functionalities: Over 90% of survey respondents and all focus group participants found Hy-Result easy to use. The main drawback of the web application is the need to manually enter all BP values at once. (2) Medical content: Hy-Result offers information on arterial hypertension and HBPM that most patients found useful. Users found that Hy-Result triggers appropriate reactions to BP readings, including adequately timed general practitioner visits. (3) Feelings and expectations: Over 90% of survey respondents trust Hy-Result and focus group participants understood that text messages are suggestions, not diagnoses. Hy-Result did not cause anxiety or excessive BP measurements. (4) Physician-patient relationship: Three-quarter of survey respondents agreed that Hy-Result may help when talking with their doctor about their BP values but only one-third of those have shown the report to their physician. For focus group participants, using Hy-Result should ideally be a physician prescription. They were aware that Hy-Result does not replace clinical judgment and that physicians still have a decisive role in BP management. CONCLUSION: Most of the users described Hy-Result as an easy-to-use and useful tool. Patients are willing to use it on physician request.

Resistant Hypertension and Atherosclerotic Renal Artery Stenosis: Effects of Angioplasty on Ambulatory Blood Pressure. A Retrospective Uncontrolled Single-Center Study.

The effect of renal artery angioplasty on blood pressure in patients with true resistant hypertension and atherosclerotic renal artery stenosis has not been fully investigated due to the exclusion of these patients from most trials. In this study, we assessed the benefits of renal angioplasty on daytime ambulatory blood pressure (dABP) in this subgroup of patients. Medical records of our hypertension department were retrospectively analyzed from 2000 to 2016. Seventy-two patients were identified with resistant hypertension (dABP >135 or 85 mm Hg despite at least 3 antihypertensive drugs, including a diuretic) and atherosclerotic renal artery stenosis treated by angioplasty. Atherosclerotic renal artery stenosis was unilateral in 57 patients and bilateral in 15 patients. The mean age of the patients was 67.8±11.2 years; dABP was 157±16/82±10 mm Hg despite 4.0±1.0 antihypertensive treatments; estimated glomerular filtration rate was 52 (41-63) mL/min. After renal angioplasty, dABPM decreased by 14.0±17.3/6.4±8.7 mm Hg (P<0.001 for both), and the number of antihypertensive treatments decreased to 3.6±1.4 (P=0.002) with no significant change in estimated glomerular filtration rate. A high baseline systolic dABP and a low body mass index were independent predictors of systolic dABP changes. The decrease in dABP was confirmed in a subgroup of patients at one and 3 years of follow-up (N=31 and N=18 respectively, P≤0.001 for systolic and diastolic blood pressure at both visits). In this retrospective uncontrolled single-center study, angioplasty in patients with atherosclerotic renal artery stenosis and with true resistant hypertension significantly decreased dABP, reducing the need for antihypertensive treatment with no change in estimated glomerular filtration rate.

Nephrotoxicity of iodinated contrast media: From pathophysiology to prevention strategies.

Iodinated contrast media (ICM) induced acute kidney injury (AKI) accounts for 11% of cases of AKI and is its third most common cause in hospitalized patients. However, the pathophysiological mechanisms are not yet completely understood. The nephrotoxicity of ICM is partly the consequence of a direct cytotoxic effect on renal tubular epithelial and endothelial cells. It is also the consequence of impaired intrarenal hemodynamics, these two mechanisms being closely linked. The rheological properties of ICM, the volume infused, and the route of administration increase the intrinsic toxicity generated by the contrast media used. Furthermore, various clinical situations increase the risk of developing AKI. There is no specific treatment. Hydration is the cornerstone of prevention. Preventive measures have reduced the incidence of AKI over the last ten years. After an overview of the pathophysiology of the renal toxicity of ICM, we review risk factors and scores, diagnosis, and means of prevention in the light of the 2018 European Society of Urogenital Radiology and the 2018 American College of Radiology guidelines and recent studies on the subject. In addition, a side-by-side comparison of the updated and less conservative guidelines from the Radiology community and the more cautionary attitude from the Nephrology community are also presented.

Home blood pressure measurement and digital health: communication technologies create a new context.

: Ambulatory blood pressure (BP) monitoring is encouraged by all international guidelines for the management of hypertension. Home BP monitoring is the preferred method of the patients. Automated BP devices with remote data transmission have been repeatedly shown to be useful in improving hypertension control in the frame of clinical trials on telemedicine. Recently, new technologies have created a new context. Despite the important number of smartphone apps devoted to BP developed these last 10 years, only two BP monitoring apps refer to the European Society of Hypertension (ESH) Guidelines and have been published in peer-reviewed journals: Hy-Result and ESH CARE. At present, the absence of close collaboration between start-up engineers and healthcare professionals is a risk for patient safety. Therefore, health professionals must become actors in the so-called digital health revolution.

Sex differences in antihypertensive treatment in France among 17 856 patients in a tertiary hypertension unit.

BACKGROUND: Sex differences in antihypertensive treatment have often been highlighted, but whether there is truly a difference or whether this difference is mediated by confounding factors has yet to be deciphered. PATIENTS AND METHODS: We performed a cross-sectional study on the first consultation in the Georges Pompidou Hospital Tertiary Hypertension Unit between July 2000 and June 2015 to explore sex differences in both patient and treatment characteristics over this period. RESULTS: A total of 17 856 patients were included. We observed in both women and men an increase in blood pressure control over time despite having more comorbidities. In conjunction, there was an increasing number of treated patients and treatments per patient. The treatments previously selected by the referring physicians strongly differed by sex: women were more frequently treated with loop diuretics [odds ratio (OR) = 1.2 (95% confidence interval (CI): 1.05-1.37)], thiazide diuretics [OR = 1.13 (95% CI: 1.03-1.23)], aldosterone-receptor blockers [OR = 1.41 (95% CI: 1.24-1.61)], and beta blockers [OR = 1.53 (95% CI: 1.41-1.66)] but less frequently with angiotensin-converting enzyme inhibitors [OR = 0.77 (95% CI: 0.70-0.84)], angiotensin II-receptor blockers [OR = 0.93 (95% CI: 0.86-1.0)], and calcium channel blockers [OR = 0.72 (95% CI: 0.67-0.78)] than men after adjusting for various patient-related confounding factors. CONCLUSION: Blood pressure control has greatly improved over the last 15 years in both men and women. Although the treatment choice remained strongly dependent on sex, this is not justified by a sex-related difference in cardiovascular benefit from antihypertensive treatment.

Cause of renal infarction: a retrospective analysis of 186 consecutive cases.

BACKGROUND: Renal infarction can cause abrupt and severe hypertension and less frequently renal failure. Renal infarction results from disruption of renal blood flow in the main ipsilateral renal artery or in a segmental branch. Underlying mechanism is either general, 'embolic' or 'thrombophilic', or local related to primary 'renal artery lesion'. It depends on various causes. In absence of an identified cause, renal infarction is classified as 'idiopathic'. Previous studies report a significant number of 'idiopathic' renal infarction. OBJECTIVE: The aim of this study was to analyze various renal infarction causes. METHODS: Between July 2000 and June 2015, 259 consecutive patients with renal infarction were admitted to our hospital center and retrospectively identified from weekly multidisciplinary round. Main clinical and biological characteristics were extracted from clinical data warehouse. Renal imaging was reviewed by two readers unaware of the diagnosis. RESULTS: Of 259 initially identified patients, 30 were excluded owing to a lack of imaging or clinical data and 43 because iatrogenic renal infarction. In the 186 studied patients, dissection was observed in 76 patients (40.8%) and occlusion in 75 (40.3%). Renal infarction mechanisms were 'renal artery lesion' (n = 151; 81.2%), 'embolic' (n = 17; 9.1%), 'thrombophilic' (n = 11; 5.9%) and 'idiopathic' (n = 7; 3.8%). Predominant renal artery lesions were atherosclerosis disease (n = 52; 34.4%) followed by dissecting hematoma (n = 35; 23.2%) and fibromuscular dysplasia (n = 29; 19.2%). Right and left kidneys were equally involved. CONCLUSION: Renal artery lesion is the most frequent cause of renal infarction. This result underlines the need for extensive arterial exploration to identify the renal infarction mechanism and, in case of renal artery lesion, the underlying vascular disease.

Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial.

BACKGROUND: The DENERHTN (Renal Denervation for Hypertension) trial confirmed the efficacy of renal denervation (RDN) in lowering daytime ambulatory systolic blood pressure when added to standardized stepped-care antihypertensive treatment (SSAHT) for resistant hypertension at 6 months. METHODS AND RESULTS: This post hoc exploratory analysis assessed the impact of abdominal aortic calcifications (AAC) on the hemodynamic and renal response to RDN at 6 months. In total, 106 patients with resistant hypertension were randomly assigned to RDN plus SSAHT or to the same SSAHT alone (control group). Total AAC volume was measured, with semiautomatic software and blind to randomization, from the aortic hiatus to the iliac bifurcation using the prerandomization noncontrast abdominal computed tomography scans of 90 patients. Measurements were expressed as tertiles. The baseline-adjusted difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the RDN and control groups was -10.1 mm Hg (P=0.0462) in the lowest tertile and -2.5 mm Hg (P=0.4987) in the 2 highest tertiles of AAC volume. Estimated glomerular filtration rate remained stable at 6 months for the patients in the lowest tertile of AAC volume who underwent RDN (+2.5 mL/min per 1.73 m2) but decreased in the control group (-8.0 mL/min per 1.73 m2, P=0.0148). In the 2 highest tertiles of AAC volume, estimated glomerular filtration rate decreased similarly in the RDN and control groups (P=0.2640). CONCLUSIONS: RDN plus SSAHT resulted in a larger decrease in daytime ambulatory systolic blood pressure than SSAHT alone in patients with a lower AAC burden than in those with a higher AAC burden. This larger decrease in daytime ambulatory systolic blood pressure was not associated with a decrease in estimated glomerular filtration rate. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

[Text messaging and self-care support of hypertensive patients : first achievements]. / Text messaging et accompagnement des patients hypertendus : premiers acquis.

Text messaging applied to self-care support of hypertensive patients is a new e-health tool available via mobile phones and computers. First validated programs are just emerging. Without being a panacea intended to replace the doctors by machines they could be provide a significant reinforcement of the patient's empowerment for self-monitoring. It is now time to begin their evaluation in real life and in primary care setting.

La technique du text messaging appliquée au suivi des patients hypertendus est un nouvel outil de prise en charge accessible aux patients et consommateurs de soins via les téléphones portables et les ordinateurs. Les premiers programmes validés se font jour. Sans être une panacée destinée à remplacer les médecins par des machines, cette technique pourrait être à l'origine d'un renforcement notable de l'autonomie des patients souhaitant assurer activement leur propre suivi. Il est temps de débuter l'évaluation du text messaging en vie réelle et notamment en pratique de soins primaires.

Clinical and Genetic Spectrum of Bartter Syndrome Type 3.

Bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene (CLCNKB), which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. To study phenotype/genotype correlations, we performed genetic analyses by direct sequencing and multiplex ligation-dependent probe amplification and retrospectively analyzed medical charts for 115 patients with CLCNKB mutations. Functional analyses were performed in Xenopus laevis oocytes for eight missense and two nonsense mutations. We detected 60 mutations, including 27 previously unreported mutations. Among patients, 29.5% had a phenotype of ante/neonatal Bartter syndrome (polyhydramnios or diagnosis in the first month of life), 44.5% had classic Bartter syndrome (diagnosis during childhood, hypercalciuria, and/or polyuria), and 26.0% had Gitelman-like syndrome (fortuitous discovery of hypokalemia with hypomagnesemia and/or hypocalciuria in childhood or adulthood). Nine of the ten mutations expressed in vitro decreased or abolished chloride conductance. Severe (large deletions, frameshift, nonsense, and essential splicing) and missense mutations resulting in poor residual conductance were associated with younger age at diagnosis. Electrolyte supplements and indomethacin were used frequently to induce catch-up growth, with few adverse effects. After a median follow-up of 8 (range, 1-41) years in 77 patients, chronic renal failure was detected in 19 patients (25%): one required hemodialysis and four underwent renal transplant. In summary, we report a genotype/phenotype correlation for Bartter syndrome type 3: complete loss-of-function mutations associated with younger age at diagnosis, and CKD was observed in all phenotypes.

Twenty-Four-Hour Blood Pressure Monitoring to Predict and Assess Impact of Renal Denervation: The DENERHTN Study (Renal Denervation for Hypertension).

The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure (BP) lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report here the effect of denervation on 24-hour BP and its variability and look for parameters that predicted the BP response. Patients with resistant hypertension were randomly assigned to denervation plus stepped-care treatment or treatment alone (control). Average and standard deviation of 24-hour, daytime, and nighttime BP and the smoothness index were calculated on recordings performed at randomization and 6 months. Responders were defined as a 6-month 24-hour systolic BP reduction ≥20 mm Hg. Analyses were performed on the per-protocol population. The significantly greater BP reduction in the denervation group was associated with a higher smoothness index (P=0.02). Variability of 24-hour, daytime, and nighttime BP did not change significantly from baseline to 6 months in both groups. The number of responders was greater in the denervation (20/44, 44.5%) than in the control group (11/53, 20.8%; P=0.01). In the discriminant analysis, baseline average nighttime systolic BP and standard deviation were significant predictors of the systolic BP response in the denervation group only, allowing adequate responder classification of 70% of the patients. Our results show that denervation lowers ambulatory BP homogeneously over 24 hours in patients with resistant hypertension and suggest that nighttime systolic BP and variability are predictors of the BP response to denervation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Copeptin is increased in resistant hypertension.

OBJECTIVES: The participation of vasopressin in the mechanisms of resistant hypertension is unclear. We compared plasma copeptin concentration, a surrogate marker for vasopressin secretion, between patients with resistant hypertension and those with controlled blood pressure (CBP), in a post hoc analysis of the Prise en charge de l'Hypertension Artérielle RESistante au traitement trial. METHODS: After 4-week treatment with irbesartan 300 mg/day, hydrochlorothiazide 12.5 mg/day, and amlodipine 5 mg/day (baseline), 166 patients were classified as having resistant hypertension (n = 140) or CBP (n = 26) by ambulatory BP monitoring. Patients with resistant hypertension were then randomized for 12 weeks of sequential nephron blockade (n = 74) or sequential renin-angiotensin system blockade (n = 66). Plasma copeptin concentration was measured at baseline and week 12 by immunoassay. RESULTS: Baseline plasma copeptin concentration was positively associated with male sex, plasma osmolality, BP, and negatively with glomerular filtration rate. It was higher in the resistant hypertension than in the CBP group [geometric mean 5.7 (confidence interval 95% 5.1-6.4) vs. 2.9 (2.3-3.9) fmol/ml, adjusted P < 0.0001). The relationship between plasma copeptin concentration and urinary osmolality was similar in the two groups. At 12 weeks, plasma copeptin concentration in patients whose BP was controlled by sequential nephron blockade or sequential renin-angiotensin system blockade [6.8 (5.6-8.2) and 4.3 (3.0-5.9) fmol/ml, respectively) remained significantly higher than in patients with CBP at baseline (P < 0.0001 vs. both). CONCLUSION: In patients with resistant hypertension, plasma copeptin concentrations were approximately two-fold higher than those of patients with CBP, after adjustment for plasma osmolality. This difference was not accounted for by renal resistance to vasopressin, suggesting a primary reset of osmostat.