Search

Background: Accurate blood pressure (BP) measurement is critical for optimal cardiovascular risk management. Age-related trajectories for cuff-measured BP accelerate faster in women compared with men, but whether cuff BP represents the intraarterial (invasive) aortic BP is unknown. This study aimed to determine the sex differences between cuff BP, invasive aortic BP, and the difference between the 2 measurements. Methods: Upper-arm cuff BP and invasive aortic BP were measured during coronary angiography in 1615 subjects from the Invasive Blood Pressure Consortium Database. This analysis comprised 22 different cuff BP devices from 28 studies. Results: Subjects were 64±11 years (range 40–89) and 32% women. For the same cuff systolic BP (SBP), invasive aortic SBP was 4.4 mm Hg higher in women compared with men. Cuff and invasive aortic SBP were higher in women compared with men, but the sex difference was more pronounced from invasive aortic SBP, was the lowest in younger ages, and the highest in older ages. Cuff diastolic blood pressure overestimated invasive diastolic blood pressure in both sexes. For cuff and invasive diastolic blood pressure separately, there were sex*age interactions in which diastolic blood pressure was higher in younger men and lower in older men, compared with women. Cuff pulse pressure underestimated invasive aortic pulse pressure in excess of 10 mm Hg for both sexes in older age. Conclusions: For the same cuff SBP, invasive aortic SBP was higher in women compared with men. How this translates to cardiovascular risk prediction needs to be determined, but women may be at higher BP-related risk than estimated by cuff measurements.

Arterial stiffness, most often assessed with carotido-femoral pulse wave velocity predicts cardiovascular events but its use in clinical practice remains limited. The 24h ambulatory monitoring of Blood pressure and timing of Korotkoff sounds (QKD interval) allows an automatic assessment of arterial stiffness and is an independent predictor of cardiovascular events in hypertensive patients. The long term follow up of our cohort of hypertensive patients gave us the opportunity to test the consequences of increased arterial stiffness on the incidence of all causes deaths and to define the populations who could benefit of this measurement beyond risk scores. The sample includes 930 patients (502 males, age 53 ± 13 years, baseline risk SCORE2-OP = 6.70 ± 4.97%) with an average follow up of 12.11 ± 7.4 years (0.3–30). In this population 169 cardiovascular events and 155 deaths were recorded. SCORE2-OP, 24h Systolic Blood Pressure and arterial stiffness (QKDh) as a continuous or discontinuous variable (normal or reduced) were significantly and independently linked to the occurrence of cardiovascular events or all cause deaths in multivariate Cox model. ROC curves analysis show that measuring arterial stiffness with QKD method offers the best predictive value in patients with low or very low risk scores.

BACKGROUND Acute and diffuse microvascular damage characterizes malignant hypertension (MHT), the deadliest form of hypertension (HTN). Although its ophthalmological, renal and cardiological repercussions are well known, brain involvement is considered rare with few descriptions, although it is one of the main causes of death. We hypothesized that brain MRI abnormalities are common in MHT, even in patients without objective neurological signs. METHOD We analyzed retrospectively the brain MRI of patients admitted for acute MHT between 2008 and 2018 in Bordeaux University Hospital, regardless of their neurological status. A trained operator analyzed every brain MRI, looking for posterior reversible encephalopathy syndrome (PRES), ischemic stroke, intracerebral hematoma (ICH) and microangiopathy markers. We included 58 patients without neurological signs, 66% were men, and mean age was 45.6 ± 11.3 years. RESULTS Brain MRI were normal in 26% of patients but we found at least one acute abnormality on brain MRI in 29% and an Small Vessel Disease score (SVD score) of two or higher in 52%. In patients with neurological signs, these findings were 9, 53 and 70%, respectively. A PRES was found in 16% of asymptomatic patients and 31% had an ischemic stroke and/or a cerebral hematoma. CONCLUSION PRES, recent hematoma, ischemic stroke and severe cerebral microangiopathy are common findings in MHT patients without neurological signs on admission. The impact of these findings on patient management, and their cerebrovascular and cognitive prognostic value, should be established. Brain MRI might need to become systematic in patients suffering from MHT episodes.

Ambulatory blood pressure monitoring (ABPM) is now considered the gold standard to evaluate BP, and predicts related cardiovascular risk. However, no study has reported the association of long-term changes in ABPM with the incidence of cardiovascular events, therefore the objective of this work. We included patients from the Bordeaux cohort of hypertensive patients, who had undergone at least two ABPM; the first was performed before or after antihypertensive treatment was started, and the second was the last recording available before any cardiovascular event. We included 591 patients (mean age, 54 years) with a 7-year average interval between the first and last ABPM, a 10-year average follow-up, and a total of 111 cardiovascular events. The patients were divided into four groups: G0, first and last 24 h systolic blood pressure (SBP)

Objective Short-term blood pressure variability derived from 24-h ambulatory monitoring is associated with poor cardiovascular prognosis. However, previous analyses of this have clearly been influenced by clinical cofounders, particularly blood pressure (BP) level. Arterial stiffness is a powerful marker of cardiovascular risk, which may influence BP variability. In this study, we assessed the prognostic value of BP variability based on 24-h ambulatory measurements and adjusted for arterial stiffness. Methods Population: Bordeaux cohort of hypertensive patients. Inclusion criteria were 24-h ambulatory BP monitoring at baseline with measurements every 15' day and night, determination of wake-up time and bedtime, and assessment of arterial stiffness with monitoring of Korotkoff sound arrival time. A total of 969 patients (age 54 ± 14 years) with an average follow up of 120 ± 78 months and 178 cardiovascular recorded events were included. Results In univariate survival analyses, the standard deviations of day, night, and 24-h SBP were associated with the occurrence of cardiovascular events. The standard deviation of night-time SBP showed the strongest association with the outcome variable and was entered into multivariate analyses. In multivariate analyses, night-time SBP variability remained significantly associated with the occurrence of cardiovascular events after adjusting for major cardiovascular risk factors, 24-h SBP, and arterial stiffness. BP variability and arterial stiffness showed no significant association. Conclusion Our results suggest that variability of night-time SBP is an important marker of the risk of cardiovascular events in hypertensive patients, independently of average 24-h BP and arterial stiffness.

Primary Aldosteronism (PA) is increasingly considered as a common disease affecting up to 10% of the hypertensive population. Standard of care comprises laparoscopic total adrenalectomy but innovative treatment such as RadioFrequency Ablation (RFA) constitutes an emerging promising alternative to surgery. The main aim of this study is to analyse the cost of RFA versus surgery on aldosterone-producing adenoma patient from the French National Health Insurance (FNHI) perspective.The ADERADHTA study was a prospective pilot study aiming to evaluate both safety and efficacy of the novel use of adrenal RFA on the patients with PA. This study conducted on two French sites and enrolled adult patients, between 2016 and 2018, presenting hypertension and underwent the RFA procedure. Direct medical (inpatient and outpatient) and non-medical (transportation, daily allowance) costs were calculated over a 6-month follow-up period. Moreover, the procedure costs for the RFA were calculated from the hospital perspective. Descriptive statistics were implemented.Analysis was done on 21 patients in RFA groups and 27 patients in the surgery group. The difference in hospital costs between the RFA and surgery groups was €3774 (RFA: €1923; Surgery: €5697 p 0.001) in favour of RFA. Inpatient and outpatient costs over the 6-month follow-up period were estimated at €3,48 for patients who underwent RFA. The production cost of implementing the RFA procedure was estimated at €1539 from the hospital perspective.Our study was the first to show that RFA is 2 to 3 times less costly than surgery. The trial is registered at ClinicalTrials.gov under the number NCT02756754.

Resume But de l’etude Une etude realisee en IRM cardiaque suggere que l’exposition chronique a un pheochromocytome « stable » induit des plages de fibrose et de myocardite ventriculaires gauches. Ces anomalies etant classiquement associees a une alteration de la deformation systolique longitudinale, nous emettons l’hypothese que cette deformation est alteree chez les patients porteurs d’un pheochromocytome. Patients et methode Cette etude cas-temoin retrospective a ete realisee a partir des patients de la base de donnees du CHU de Bordeaux, inclus entre 2008 et 2016. Nous avons compare le global longitudinal strain (GLS), les autres parametres de deformation systolique et les parametres echocardiographiques classiques entre un groupe de patients porteurs de pheochromocytome et un groupe de temoins apparies pour l’âge, le sexe, l’indice de masse corporelle et la pression arterielle systolique moyenne. Resultats L’analyse a porte sur 47 patients et 47 temoins correctement apparies. Nous n’avons pas retrouve de difference statistiquement significative entre les 2 groupes en termes de GLS (−20,7 ± 2,4 % vs −20,2 ± 2,7 %, p = 0,40), de deformation radiale, de masse ventriculaire gauche ou de fonction diastolique. La fraction d’ejection ventriculaire gauche et la deformation circonferentielle etaient significativement plus elevees chez les patients que chez les temoins, le diametre telediastolique significativement plus bas. Conclusion Aucune alteration significative du GLS n’a ete identifiee chez nos patients porteurs d’un pheochromocytome. Plusieurs hypotheses peuvent expliquer ces resultats. La presence de foyers de fibrose et de myocardite etant associes a un pronostic cardiologique pejoratif, une IRM cardiaque systematique pourrait se discuter, dans l’attente d’etudes complementaires.

Malignant hypertension (MHT) still remains a severe condition that requires early recognition and treatment. Over the years, the prevention and treatment of MHT have significantly advanced through the introduction of modern antihypertensive agents. However, in the absence of robust clinical trials, there remain no formal guidelines on the treatment of MHT. This review summarizes the historical background and pathophysiological evidence of MHT, which has led to common practices in its pharmacological management but can also introduce challenges. The current consensus for treatment involves early intravenous infusion of antihypertensive agents, but oral blockers of the renin-angiotensin system may improve the management of MHT, and it offers a suitable treatment option in low-income countries where the condition remains relatively prevalent.

Primary aldosteronism is responsible for a major cardiovascular risk that can be avoided by specific treatment. A better characterization of the hypertensive population with primary aldosteronism would not only improve the overall diagnosis but also allows a better selection of patients requiring adrenal vein sampling (AVS).Creation of a prospective single-center Bordeaux ABORDAGE study of hypertensive patients with primary aldosteronism who underwent AVS. Primary aldosteronism was diagnosed according to the recommendations of the SFE/SFHTA. Peripheral and central blood pressure measurements were performed with mercury sphygmomanometer, SphygmoCor applanation tonometer and ambulatory blood pressure measurement. An adrenal computed tomography and an unstimulated AVS were performed in each patient.One hundred and eighty-eight patients were included in our study. They were mostly men (61.7%), with a mean age of 48.7 ± 10.5 years, BMI of 29.7 ± 5 kg/ m2 and duration of hypertension of 101.5 ± 84 months. AVS was selective in 82.3% of patients and lateralization was concordant with CT in only 35.4% of patients. Lateralized secretion was significantly associated with a marked biological primary aldosteronism and hypertension. In multivariate analysis, no variable specifically differentiated patients with aldosterone lateralization.The ABORDAGE population description is consistent with the data found in the literature. These characteristics are ultimately those expected in essential hypertension population, which therefore, could explain part of the underdiagnosis of primary aldosteronism. Only AVS is able to predict the lateralization of secretion with a post adrenalectomy recovery of about 90% in case of lateralization. The generalization of AVS would, therefore, increase the proportion of patients with primary aldosteronism cured.

Summary Background Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. Methods In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18–75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov , NCT02649426 . Findings Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (−8·0 mm Hg [IQR –16·4 to 0·0] vs –3·0 mm Hg [–10·3 to 1·8]; median between-group difference –4·5 mm Hg [95% CI –8·5 to –0·3]; adjusted p=0·022); the median between-group difference was –5·8 mm Hg (95% CI –9·7 to –1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. Interpretation Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. Funding ReCor Medical.

Clinic-ambulatory blood pressure (BP) difference is influenced by patients- and device-related factors and inadequate clinic-BP measurement. We investigated whether nonadherence to antihypertensive medications may also influence this difference in a post hoc analysis of the DENERHTN trial (Renal Denervation for Hypertension). We pooled the data of 77 out of 106 evaluable patients with apparent resistant hypertension who received a standardized antihypertensive treatment and had both ambulatory BP and drug-screening results available at baseline after 1 month of standardized triple therapy and at 6 months on a median of 5 antihypertensive drugs. After drug assay samplings on study visits, patients took their antihypertensive treatment under supervision immediately after the start of the ambulatory BP recording, and supine clinic BP was measured 24 hours post-dosing; both allowed to calculate the clinic minus daytime ambulatory systolic BP (SBP) difference (clinic-SBP–day-SBP). A total of 29 (37.7%) were found nonadherent to medications at baseline and 38 (49.4%) at 6 months. At baseline, the mean clinic-SBP–day-SBP difference in the nonadherent group was 12.7 mm Hg (95% CI, 7.8–17.7 mm Hg, P P =0.947). Similar observations were made at 6 months. Using receiver operating characteristics curves, we found that a 6 mm Hg cutoff of clinic-SBP–day-SBP difference had 67% sensitivity and 69% specificity to predict nonadherence to the triple therapy at baseline. In conclusion, a large clinic-SBP–day-SBP difference may help discriminating between adherence and nonadherence to treatment in patients with resistant hypertension. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01570777.

Malignant hypertension, the most severe form of hypertension, is defined by high blood pressure and acute ischemic organ damage. It has a worse prognosis than other forms of hypertension, especially in black patients. New tools to assess organ damage, especially that of the heart and brain, are now available and may contribute to a better evaluation of these patients. This report improves knowledge of the characteristics of involved organs to facilitate diagnosis and to evaluate the effectiveness of our treatment protocol.The Bordeaux registry, started in 1995, recruited 168 patients. In addition to evaluations of their eyes and kidneys, these patients had a systematic evaluation of their hearts with ECG and echocardiography and, since 2007, a systematic brain MRI. Blood pressure was lowered with a protocol based on blockers of the renin-angiotensin system started at a very low-dose with forced titration over 48 h. Only an oral route was used for antihypertensive medication.Systematic MRIs found significant brain damage in 93% of patients. Heart involvement was highly prevalent: 82% had left ventricular mass more than 60 g/m, and 56% had systolic dysfunction (estimated by global longitudinal strain). Renal involvement and thrombotic microangiopathy were respectively present in 55 and 15% of patients. Median follow-up was 48 months. Renal survival at 5 years was 90.8%, similar to other studies.Malignant hypertension is a systemic disease causing severe damage to the brain, heart, kidneys and eyes, even in absence of symptoms. Renin-angiotensin system blockers seem to be the cornerstone of treatment.

Hypertensive emergencies are those situations where very high blood pressure (BP) values are associated with acute organ damage, and therefore, require immediate, but careful, BP reduction. The type of acute organ damage is the principal determinant of: (i) the drug of choice, (ii) the target BP, and (iii) the timeframe in which BP should be lowered. Key target organs are the heart, retina, brain, kidneys, and large arteries. Patients who lack acute hypertension-mediated end organ damage do not have a hypertensive emergency and can usually be treated with oral BP-lowering agents and usually discharged after a brief period of observation.

Background: The multicenter, international, randomized, blinded, sham-controlled RADIANCE-HTN SOLO trial (A Study of the ReCor Medical Paradise System in Clinical Hypertension) demonstrated a 6.3 mm Hg greater reduction in daytime ambulatory systolic blood pressure (BP) at 2 months by endovascular ultrasound renal denervation (RDN) compared with a sham procedure among patients not treated with antihypertensive medications. We report 6-month results after the addition of a recommended standardized stepped-care antihypertensive treatment to the randomized endovascular procedure under continued blinding to initial treatment. Methods: Patients with a daytime ambulatory BP ≥135/85 mm Hg and Results: A total of 69/74 RDN patients and 71/72 sham patients completed the 6-month ambulatory BP measurement. At 6 months, 65.2% of patients in the RDN group were treated with the standardized stepped-care antihypertensive treatment versus 84.5% in the sham group ( P =0.008), and the average number of antihypertensive medications and defined daily dose were less in the RDN group than in the sham group (0.9±0.9 versus 1.3±0.9, P =0.010 and 1.4±1.5 versus 2.0±1.8, P =0.018; respectively). Despite less intensive standardized stepped-care antihypertensive treatment, RDN reduced daytime ambulatory systolic BP to a greater extent than sham (−18.1±12.2 versus −15.6±13.2 mm Hg, respectively; difference adjusted for baseline BP and number of medications: −4.3 mm Hg, 95% confidence interval, −7.9 to −0.6, P =0.024). There were no major adverse events in either group through 6 months. Conclusions: The BP-lowering effect of endovascular ultrasound RDN was maintained at 6 months with less prescribed antihypertensive medications compared with a sham control. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02649426.

Native coarctation of the aorta (CoA) and recoarctation (reCoA) after initial surgical repair are frequently associated with hypertension (HT). Most CoA cases are amenable to transcatheter balloon angioplasty with stent implantation; however, the impact of stenting on arterial blood pressure (BP) is variable. We carried out a retrospective study to identify the predictive factors for residual HT despite optimal endovascular treatment. Patients who had undergone stent implantation for native CoA or reCoA with a pressure gradient of >20 mm Hg between the upper and lower limbs, between 2007 and 2015, were included. The geometry and level of hypoplasia of the aortic arch were determined by non‐invasive imaging, and BP measurements were performed pre‐ and post‐procedure. Thirty consecutive patients (median age: 18.5 years; 76.7% male) were included. Twenty‐three patients had HT before the procedure and 14 (46.7%) had post‐procedural HT despite optimal endovascular treatment. Residual HT post‐stenting was associated with longer stent length and gothic arch geometry. Age and body mass index (BMI) were also associated with residual HT. The pathologic association of abnormal arch geometry and aortic stent placement may lead to a loss of aortic compliance that is further increased by high BMI and older age. Determination of a patient's aortic arch anatomy and clinical profile can assist in defining those at high risk of residual HT despite optimized isthmic stent implantation.

Isolated systolic hypertension (ISH) is the most common form of hypertension and is highly prevalent in older people. We recently showed differences between upper-arm cuff and invasive blood pressure (BP) become greater with increasing age, which could influence correct identification of ISH. This study sought to determine the difference between identification of ISH by cuff BP compared with invasive BP. Cuff BP and invasive aortic BP were measured in 1695 subjects (median 64 years, interquartile range [55–72], 68% male) from the INSPECT (Invasive Blood Pressure Consortium) database. Data were recorded during coronary angiography among 29 studies, using 21 different cuff BP devices. ISH was defined as ≥130/

Renal denervation (RDN) is effective in lowering blood pressure (BP) in patients with hypertension. The issue remains how to best identify potential responders. Ambulatory BP monitoring may be useful. Baseline nighttime systolic BP (SBP) ≥136 mm Hg and its variability (SD) ≥12 mm Hg in DENER-HTN trial or 24-hour heart rate ≥73.5 bpm in SPYRAL HTN-OFF MED Trial were shown to predict the BP response to RDN. We applied these criteria to the patients with hypertension in the sham-controlled RADIANCE-HTN SOLO trial to predict the BP response to ultrasound RDN at 2 months while patients were maintained off medications. BP responders were defined as: clinical with 24-hour SBP 90% irrespective of definition) but low sensitivity (from 9.1% to 30% depending on the definition) to predict responders; the heart rate criterion had insufficient predictive value. This analysis suggests the potential role of nighttime SBP and its variability to predict BP response to RDN in patients with hypertension. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02649426.

Primary aldosteronism is characterized by hypertension, frequent hypokalemia, and an inappropriately high aldosterone-to-renin ratio (ARR) [1,2]. Aldosterone-producing adenoma (APA or Conn syndrome) is one of the main causes of primary aldosteronism [3]. Laparoscopic total-adrenalectomy is an option to normalize or at least improve blood pressure (BP) control, hypokalemia, and normalize the ARR [4,5]. However, the reported result of surgery is around 50% of clinical cure rate with an overall complication rate of 9.5% [2,6–8]. An efficient but less invasive alternative technique could be the use of radiofrequency ablation (RFA). RFA is widely used to treat solid neoplasms, especially in patients not only with primary or secondary malignancies of the liver, the lung, the kidney, and the breast but also for primary and metastatic adrenal neoplasms, including adrenocortical carcinomas [9–15]. More recently, RFA has been used for patients with primary aldosteronism and unilateral adenoma [16–25]. These studies focused on hormonal resolution of primary aldosteronism, computed tomography (CT) aspects, and safety data after RFA but the putative positive impact on BP control was not clearly depicted [16–25]. The aim of this study is, therefore, to assess whether RFA improves ambulatory BP control in patients with hypertension because of primary aldosteronism and unilateral adrenal adenoma. Normal potassium, ARR values and safety of the procedure are the secondary outcomes.

Objectives To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. Trial design Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Participants will be randomly allocated 1:1:1:1:1 to the following strategies: Arm 1: Control arm Arms 2 to 5: Experimental treatment arms Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial. Participants Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate 5.5 mmol/L or The trial is being conducted in France in the Bordeaux, Corse, Dijon, Nancy, Paris and Toulouse areas as well as in the Grand Duchy of Luxembourg. Participants are recruited either at home, nursing homes, general practices, primary care centres or hospital outpatient consultations. Intervention and comparator The four experimental treatments planned in protocol version 1.2 (April 8th, 2020) are: (1) Hydroxychloroquine 200 mg, 2 tablets BID on day 0, 2 tablets QD from day 1 to 9; (2) Imatinib 400 mg, 1 tablet QD from day 0 to 9; (3) Favipiravir 200 mg, 12 tablets BID on day 0, 6 tablets BID from day 1 to 9; (4) Telmisartan 20 mg, 1 tablet QD from day 0 to 9. The comparator is a complex of vitamins and trace elements (AZINC Forme et Vitalité®), 1 capsule BID for 10 days, for which there is no reason to believe that they are active on the virus. In protocol version 1.2 (April 8th, 2020): People in the control arm will receive a combination of vitamins and trace elements; people in the experimental arms will receive hydroxychloroquine, or favipiravir, or imatinib, or telmisartan. Main outcome The primary outcome is the proportion of participants with an incidence of hospitalisation and/or death between inclusion and day 14 in each arm. Randomisation Participants are randomized in a 1:1:1:1:1 ratio to each arm using a web-based randomisation tool. Participants not treated with an ARB or ACEI prior to enrolment are randomized to receive the comparator or one of the four experimental drugs. Participants already treated with an ARB or ACEI are randomized to receive the comparator or one of the experimental drugs except telmisartan (i.e.: hydroxychloroquine, imatinib, or favipiravir). Randomisation is stratified on ACEI or ARBs treatment at inclusion and on the type of residence (personal home vs. nursing home). Blinding (masking) This is an open-label trial. Participants, caregivers, investigators and statisticians are not blinded to group assignment. Numbers to be randomised (sample size) A total of 1057 participants will be enrolled if all arms are maintained until the final analysis and no additional arm is added. Three successive futility interim analyses are planned, when the number of participants reaches 30, 60 and 102 in the control arm. Two efficacy analyses (interim n°3 and final) will be performed successively. Trial Status This describes the Version 1.2 (April 8th, 2020) of the COVERAGE protocol that was approved by the French regulatory authority and ethics committee. The trial was opened for enrolment on April 15th, 2020 in the Nouvelle Aquitaine region (South-West France). Given the current decline of the COVID-19 pandemic in France and its unforeseeable dynamic in the coming months, new trial sites in 5 other French regions and in Luxembourg are currently being opened. A revised version of the protocol was submitted to the regulatory authority and ethics committee on June 15th, 2020. It contains the following amendments: (i) Inclusion criteria: age ≥65 replaced by age ≥60; time since first symptoms <3 days replaced by time since first symptoms <5 days; (ii) Withdrawal of the hydroxychloroquine arm (due to external data); (iii) increase in the number of trial sites. Trial registration The trial was registered on Clinical Trials.gov on April 22nd, 2020 (Identifier: NCT04356495): and on EudraCT on April 10th, 2020 (Identifier: 2020-001435-27). Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Blood pressure (BP) is a leading global risk factor. Increasing age is related to changes in cardiovascular physiology that could influence cuff BP measurement, but this has never been examined systematically and was the aim of this study. Cuff BP was compared with invasive aortic BP across decades of age (from 40 to 89 years) using individual-level data from 31 studies (1674 patients undergoing coronary angiography) and 22 different cuff BP devices (19 oscillometric, 1 automated auscultation, 2 mercury sphygmomanometry) from the Invasive Blood Pressure Consortium. Subjects were aged 64±11 years, and 32% female. Cuff systolic BP overestimated invasive aortic systolic BP in those aged 40 to 49 years, but with each older decade of age, there was a progressive shift toward increasing underestimation of aortic systolic BP ( P P P

Background Orthostatic hypotension, blood pressure (BP) variability, and arterial stiffness are three markers of cardiovascular risk beyond the average BP. However, the relationships between these three parameters are not well known. Aim To examine the relationships between orthostatic hypotension, BP variability, and arterial stiffness. Methods and results In the Three-City study, a sample of 1151 elderly participants (mean age = 80 ± 3 years) was screened for orthostatic hypotension, undertook home BP and pulse wave velocity (PWV) measurements. We performed logistic regression analyses to look at the associations between orthostatic hypotension and both day-to-day (D-to-D) BP variability quartiles and PWV quartiles. Orthostatic hypotension was detected in 210 participants who were more likely to be hypertensive, exhibit higher BP variability and have increased arterial stiffness. In the multivariate logistic regression analysis, the frequency of orthostatic hypotension increased by 20% with every quartile of D-to-D SBP variability and by 20% with every quartile of PWV. PWV and D-to-D BP variability were not associated. In stratified analysis, the use of beta-blocker changes these relationships: orthostatic hypotension was not associated to PWV anymore but its association with D-to-D SBP variability was apparently stronger. Conclusion In this large sample of elderly individuals, orthostatic hypotension was independently associated with both BP variability and PWV. BP variability being more indicative of a baroreflex dysfunction and PWV being a marker of vascular ageing, these two components would participate to the orthostatic hypotension mechanisms.

Data on the long term evolution of renal function in essential hypertensive patients are scarce, showing a low incidence of end stage renal diseases but without information on how the renal function evolves. Our aim is to describe the long term evolution of renal function and possible trajectories in hypertensive patients. We included patients from an ongoing cohort with essential hypertension, no proteinuria at baseline and no diabetes during follow-up and with at least two creatinine dosages 4 years apart. A long term (average 16 years) follow-up was available in 609 patients (baseline age 51.8 ± 11.1 years, 52 % male, mean office BP 156//95 mmHg). The trajectories of creatinine were modeled through a flexible latent class mixed model. The analysis identified three classes of significantly different trajectories. In the first (n = 560), there was no significant variation of creatinine over time. In the second (n = 40), there was a significant rise of creatinine (117 ± 20 vs 85 ± 17 µmol/l, p

Resume But de l’etude L’hyperaldosteronisme primaire est la premiere cause d’hypertension arterielle secondaire, et entraine de frequentes complications cardiovasculaires. De nombreuses etudes ont etudie la geometrie et la fonction ventriculaire gauche dans cette population, mais la fonction systolique longitudinale est encore mal decrite. Patients et methode Nous avons etudie 35 patients hypertendus porteurs d’un hyperaldosteronisme primaire et 35 d’une hypertension essentielle apparies pour l’âge, le sexe, l’indice de masse corporelle et la pression arterielle sur 24 heures. Ces patients ont beneficie d’une echocardiographie pour mesurer la masse, la geometrie la fraction d’ejection du ventricule gauche, sa deformation systolique longitudinale, circonferentielle et radiale, et sa fonction diastolique. Resultats Les patients atteints d’ hyperaldosteronisme primaire presentaient une masse ventriculaire gauche indexee et une epaisseur relative des parois significativement plus elevees (60,3 ± 16,1 g/m2,7 vs 47,3 ± 18,6, p = 0,003 et 0,44 ± 0,08 vs 0,36 ± 0,06, p = 5 × 10−5), ainsi qu’une fonction systolique longitudinale par le strain bidimensionnel significativement reduite (−17,8 ± 3,4 vs − 20,3 ± 3,6 %, p = 0,004). Il n’y avait pas de differences significatives dans les autres parametres. Conclusion L’hyperaldosteronisme primaire est associe a une deterioration de la fonction systolique longitudinale du ventricule gauche par rapport aux patients hypertendus essentiels. Ce parametre simple et reproductible pourrait etre un marqueur d’atteinte cardiaque et aider au depistage de ces patients.

Hypertensive emergency. Stable incidence for several decades or even increasing (under diagnosed). Early and specific management improves prognosis. Absence of eye damage or lack of access to fundus should not delay or prevent the diagnosis. Multi Organ Damage Hypertension: new definition for an old entity: unusual, sudden and persistent blood pressure rise without threshold and ocular involvement or involvement of at least 3 target organs among brain, heart, kidney or endothelial disease.

Summary Background Early studies suggest that radiofrequency-based renal denervation reduces blood pressure in patients with moderate hypertension. We investigated whether an alternative technology using endovascular ultrasound renal denervation reduces ambulatory blood pressure in patients with hypertension in the absence of antihypertensive medications. Methods RADIANCE-HTN SOLO was a multicentre, international, single-blind, randomised, sham-controlled trial done at 21 centres in the USA and 18 in Europe. Patients with combined systolic–diastolic hypertension aged 18–75 years were eligible if they had ambulatory blood pressure greater than or equal to 135/85 mm Hg and less than 170/105 mm Hg after a 4-week discontinuation of up to two antihypertensive medications and had suitable renal artery anatomy. Patients were randomised (1:1) to undergo renal denervation with the Paradise system (ReCor Medical, Palo Alto, CA, USA) or a sham procedure consisting of renal angiography only. The randomisation sequence was computer generated and stratified by centres with randomised blocks of four or six and permutation of treatments within each block. Patients and outcome assessors were blinded to randomisation. The primary effectiveness endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Patients were to remain off antihypertensive medications throughout the 2 months of follow-up unless specified blood pressure criteria were exceeded. Major adverse events included all-cause mortality, renal failure, an embolic event with end-organ damage, renal artery or other major vascular complications requiring intervention, or admission to hospital for hypertensive crisis within 30 days and new renal artery stenosis within 6 months. This study is registered with ClinicalTrials.gov, number NCT02649426. Findings Between March 28, 2016, and Dec 28, 2017, 803 patients were screened for eligibility and 146 were randomised to undergo renal denervation (n=74) or a sham procedure (n=72). The reduction in daytime ambulatory systolic blood pressure was greater with renal denervation (−8·5 mm Hg, SD 9·3) than with the sham procedure (−2·2 mm Hg, SD 10·0; baseline-adjusted difference between groups: −6·3 mm Hg, 95% CI −9·4 to −3·1, p=0·0001). No major adverse events were reported in either group. Interpretation Compared with a sham procedure, endovascular ultrasound renal denervation reduced ambulatory blood pressure at 2 months in patients with combined systolic–diastolic hypertension in the absence of medications. Funding ReCor Medical.

L’hypertension artérielle (HTA) maligne n’a pas disparu, elle a été oubliée. Son incidence augmente à nouveau. Elle assombrit considérablement le pronostic de jeunes patients (35 à 55 ans en moyenne). Il existe probablement des facteurs de prédisposition, plusieurs hypothèses sont à l’étude. De nouveaux critères diagnostiques et de nouvelles options thérapeutiques ont été proposés, ils devront être validés. Devant ces enjeux importants pour les patients, le premier registre prospectif multicentrique sur cette pathologie va être mis en place en France en Septembre 2019. [Malignant hypertension: A bright future] Malignant hypertension has not disappeared, it has been forgotten. Its incidence is increasing again. It considerably worsens the prognosis of young patients (35 to 55 years old on average). There might be susceptibility factors, several hypotheses are under study. New diagnostic criteria and therapeutic options have been proposed and will have to be validated. Faced with these important challenges for patients, the first prospective multicentric register on this pathology will be set up in France in September 2019.

Objectives: Accurate blood pressure (BP) measurement is critical for appropriate hypertension diagnosis and management. Aortic BP represents pressure loading on vital organs and this can be approximated using upper arm cuff BP. With advancing age, cuff systolic BP (SBP) increases and diastolic BP (DBP) decreases (widening pulse pressure [PP]), but whether age may influence cuff BP compared with invasive BP is unknown and was the aim of this study. Methods: Cuff BP was measured simultaneously, or near-simultaneously, with invasive aortic BP during catheterization in 1696 individuals within the INSPECT consortium (an international collaboration comprising data from 31 studies and 19 different cuff BP devices [17 oscillometric, 2 mercury sphygmomanometry]). Differences in cuff and invasive BP were assessed using mixed models. Results: Subjects were aged 63.3 ± 10.6 years and 32% female. Cuff SBP overestimated invasive aortic SBP in those aged 40–49, but with increasing age there was a progressive increase in the underestimation of aortic SBP (Table). Conversely, cuff DBP systematically overestimated aortic DBP, increasingly with age. Thus, there was a progressively higher error (underestimation) in cuff PP with older age. Adjusting models for sex, mean arterial pressure, heart rate and catheter type did not alter the findings, and no interactions between these parameters and age were found. Conclusion: Cuff BP is progressively more biased with increasing age, exposing older people to greater chance for misdiagnosis of risk related to BP. The findings highlight the need to improve cuff BP methods to ensure all people receive appropriate diagnosis and management of hypertension.

Objective Orthostatic hypotension is a common condition associated with adverse cardiovascular and cognitive prognosis. Screening for orthostatic hypotension consists of blood pressure measurements in supine (or sitting) and standing position during clinical consultations. As orthostatic hypotension is a poorly reproducible clinical condition, it is likely that the simple measurement carried out during consultations underestimates the true prevalence of the condition. The objective of this study is, therefore, to determine whether screening for orthostatic hypotension with home blood pressure measurements (HBPM) may improve orthostatic hypotension diagnosis without compromising the quality of the blood pressure readings. Materials and methods We asked all patients with indications for HBPM in the hypertension unit and in a general medical practice to perform a series of home blood pressure measurements, ending each series with a measurement in standing position. Results We recruited 505 patients of mean age 68 years of which 93% were hypertensive patients. The success rate of HBPM complying with the ESH criteria (12 out of 18 measurements) was 94.5%, which is comparable with previously published series of measurements. Ninety-one percent of patients measured their blood pressure at least once in standing position, and 88% of patients recorded all six standing measurements. Orthostatic hypotension prevalence defined as the presence of one episode of orthostatic hypotension was 37.47%, much higher than orthostatic hypotension prevalence measured in the same cohort in a clinic setting (15%). Conclusion The measurement of blood pressure in standing position during HBPM is feasible without altering the quality of the blood pressure readings in seated position. Our findings show that orthostatic hypotension is significantly more often detected at home by the patient than at the doctor's office, which may allow quicker initiation of preventive and therapeutic strategies.

Hypertensive emergency. Stable incidence for several decades or even increasing (under diagnosed). Early and specific management improves prognosis. Absence of eye damage or lack of access to fundus should not delay or prevent the diagnosis. Multi Organ Damage Hypertension: new definition for an old entity: unusual, sudden and persistent blood pressure rise without threshold and ocular involvement or involvement of at least 3 target organs among brain, heart, kidney or endothelial disease.

The prevalence of malignant hypertension has clearly fallen with the advent of anti-hypertensive medication but has remained stable over the past 30-40 years in spite of progress in diagnosis and management of hypertension. A diagnosis of malignant hypertension is usually based on the association of severely elevated blood pressure with a Keith and Wagener stage III or IV retinopathy. We believe that this definition can be reconsidered for several reasons. Although simple and pragmatic, this definition corresponds to a time when there were few techniques for assessment of hypertensive target organ involvement, and does not take into account involvement of kidney, brain and heart; whereas the overall prognosis largely depends on how much they are affected. On the contrary, the acute blood pressure level and especially diastolic should not be a hard diagnostic criterion as it does not itself constitute the prognosis of the condition. We propose to consider that malignant hypertension with retinopathy is only one of a number of possible presentation(s) of acute hypertension with multi organ damage (hypertension multi organ damage (MOD)) and that the recognition of these hypertensive emergencies, when retinopathy is lacking, be based on acute elevation of BP associated with impairment of at least three different target organs. The objective of a new and expanded definition is to facilitate recognition of these true emergencies. The condition is more common than usually perceived and would have a much worse prognosis than the usual forms of hypertension. Early recognition and management of hypertension-MOD are fundamental to any improvement in prognosis.

Objective Atrial fibrillation is the most common arrhythmia, and confers a high risk of stroke and heart failure. Hypertension and ageing are two important risk factors of incident atrial fibrillation and are both associated with increased arterial stiffness. The possible relationship between arterial stiffness and atrial fibrillation is insufficiently documented and is probably complex. We tested these relations in a cohort of hypertensive patients. Methods The population belongs to a registry which includes patients referred before administration of antihypertensive treatment and fulfilling the following criteria: office blood pressure (BP) above 140/90 mmHg, essential hypertension, no history of cardiovascular events, type 1 diabetes or atrial fibrillation, 24-h ambulatory measurement of BP coupled with the measurement of timing of Korotkoff sounds to assess arterial stiffness [indexed theoretical value of QKD interval for a SBP of 100 mmHg, at heart rate (HR) of 60 b.p.m., indexed for height and QRS duration (QKDh)]. An echocardiographic examination was carried out at baseline in the majority of patients. Atrial fibrillation-free survival was analysed with a Cox model including sex, diabetes, smoking, hypercholesterolaemia, QKDh, average 24-h pulse pressure and mean BP, mean 24-h HR, BMI and left atrial diameter (LAD), when available. Results We included 853 patients and recorded 67 new onsets of atrial fibrillation (mean follow-up = 102 ± 62 months). Analysis found three variables significantly and independently linked to the occurrence of atrial fibrillation: age, QKDh and 24-h average HR. When LAD was introduced (n = 480, 35 incident atrial fibrillation), three variables were linked to incident atrial fibrillation: age, QKDh and LAD. Conclusion Arterial stiffness is a strong predictor of future atrial fibrillation in hypertensive patients, independently of age, 24-h pulse pressure and LAD.

The hypothesis that vitamin D (25(OH)D) insufficiency plays a role in occurring of various disease has led to a rise in requests of dosages and to an increase of health-care costs. 25(OH)D insufficiency is associated with increased risk of cardiovascular disease and hypertension in many studies. Animal studies demonstrated that 25(OH)D insufficiency activates renin angiotensin system but corresponding humans data are limited. The aim of the study was to document relationship between 25(OH)D, blood pressure, and renin angiotensin system in hypertensive subjects. In all, 248 hypertensive individuals, 46.8 years (±14), were hospitalized for an etiological assessment of hypertension in this cross-sectional study over two calendar years. 25(OH)D, plasma renin activity, and aldosterone were determined in stringent conditions and blood pressure was measure. Statistical analyses were carried out to analyze the association between 25(OH)D, blood pressure, and renin angiotensin system using linear and logistic regressions with adjustments on relevant variables. In all, 80% of the studied population had a 25(OH)D insufficiency. There were no significant association between 25(OH)D and levels of systolic or diastolic blood pressure, plasma renin activity, and aldosterone whatever the statiscal method used after adjustment. 25(OH)D is not associated with blood pressure and renin angiontensin component in hypertensive subjects. These results corroborate the interventional studies which are for a large majority negatives. A new definition of the 25(OH)D insufficiency in general population is necessary.

International audience; Several studies indicate a potential link between orthostatic hypotension (OH) and incident dementia but without substantial evidence to date. Our objective is to study the association between OH and dementia in a cohort of elderly individuals. To do so, baseline lying and standing blood pressure measurements were taken from 7425 subjects in the Three-City study. These subjects were then followed-up for 12 years. Cox proportional hazard models, adjusted for potential confounders, were used to estimate the risk of incident dementia according to OH status. Sensitivity analysis was performed using the so-called illness-death model, a specific statistical method which takes into account competitive risk with death. OH frequency was found to be around 13%, and 760 cases of dementia were diagnosed during follow-up. We observed significant associations between the presence of OH at baseline and the occurrence of dementia during the follow-up, with an increased risk of at least 25% observed regardless of the OH threshold and the statistical method used. In conclusion, there is an association between OH and dementia. Considering that OH is a common condition and is easy to measure, OH measurements could help to identify subjects with higher risk of dementia. Moreover, reducing OH could be a step to prevent conversion to dementia.

Objective:Prognostic data on short-term blood pressure variability derived from 24-hour ambulatory monitoring are still limited, even though the prognostic value of long-term visit-to-visit variability in blood pressure seems to be established. The main objective of this study is to assess the progn