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Background: Malignant hypertension has not disappeared and remains the most severe form of hypertension. More than 100 years after its description, many points remain unanswered. Mechanisms, definitions, and optimal treatment are still controversial. In 2019, we decided to launch a prospective multicentre multidisciplinary cohort in France to try to fill these gaps., Method: This study aimed to describe the baseline characteristics of the first 302 included patients and compared these data to already published cohorts. We included patients with severe hypertension associated with severe hypertensive retinopathy and patients filling the HYP MOD (HYPertension MultiOrgan Damage) definition from a broad range of departments (cardiology, nephrology, neurology intensive care unit, emergency department, internal medicine). We collected clinical, biological, imaging, and target organ damage data at admission, along with social and demographic data. We also recorded diagnostic and therapeutic management, adverse events during hospitalization, and characteristics at discharge., Results: We enrolled 302 patients in 32 months (105/year) among 40 centres and different specialties. They mainly included young men (68%, mean age 48.7 ± 14.5 years). Target organ damage involved the eye in 86.7% of patients, kidney in 58.6%, heart in 50%, brain in 32.8%, and Thrombotic Microangiopathy stigmata in 15.6%. Patients with severe retinopathy shared characteristics similar to those included in the most important cohorts already published. We also reported several additional subgroups of interest: one-third of our patients were less than 40 years old, one-third were of non-European origin, 14.3% were included through the multiorgan damage definition, without fundus severe injuries, 22.8% were treated without the use of IV therapy, 40.9% had normal or low renin level, and almost all patients were not on antihypertensive therapy at the time of the enrolment., Conclusion: These preliminary findings already challenge long-standing dogma, raise numerous questions, and provide a solid basis to address them in ancillary studies of the cohort., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Arterial stiffness, an important predictor of cardiovascular event, has two components: one linked to the nonlinear elastic behaviour of the arterial wall and dependent of the blood pressure (BP) at the time of measurement, and the other linked to the structural modifications of the arterial wall as the consequences of the long-term effects of all cardiovascular risk factors, including BP. This second component is certainly the most important one and can be assessed with 24-h ambulatory monitoring of cardio-arm pulse transmission time (QKD method)., Methods: The working hypothesis of this study is that QKD100-60, the value of the QKD for a 100 mmHg SBP and 60 bpm heart rate is independent of 24-h SBP in both normotensive volunteers and treated hypertensive patients, in whom the long-term influence of BP is limited, whereas QKD100-60 is not independent of 24-h SBP in untreated hypertensive patients in whom high BP was able to damage the arterial wall on the long term. So we studied the relationships of QKD100-60 with 24-h BP and heart rate together with age, sex, height in multivariate regression analysis in three groups of patients; normal, untreated and treated hypertensive patients. QKD was measured with Novacor devices., Results: In the normal population (n = 323, aged 29 ± 10 years) and in the treated hypertensive population (n = 425, aged 58 ± 13 years) the QKD100-60 was indeed not significantly related to 24-h SBP. In the untreated hypertensive population (n = 614, aged 51 ± 13 years) the QKD100-60 was weakly but significantly related to 24-h SBP (r = 0.249, P < 0.0001)., Conclusion: Ambulatory monitoring of QKD provides indices of arterial stiffness independent of BP level at the time of measurement and most interestingly of 24-h BP with the potential to refine risk in patients with low traditional risk scores., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Malignant hypertension has not disappeared and is associated with a poor prognosis. Yet, so far, it has received limited attention from the medical community. Guidelines are mainly based on expert consensus and low quality evidences., Method: We set up a prospective, multicenter, observational cohort of patients with malignant hypertension. We collect at admission medical history, demographic data, ongoing treatment, clinical parameters, symptoms, care pathways, target organ status and at discharge and during follow up treatment administrated, adverse events, blood pressure level, target organ status. We aim to recruit 500 patients with malignant hypertension in 5 years, with a 5-year follow-up. Our primary objective is to assess the 5 years prognosis of these patients., Discussion: The HAMA (Hypertension Arterielle MAligne, meaning malignant hypertension) registry aims to describe the epidemiology and to assess the prognosis of malignant hypertension in a contemporary multidisciplinary cohort, with emphasis on the diversity of current management and care pathway among the different medical specialties. It may help improving our pathophysiological knowledge, and pave the way to update the definition of this particular form of hypertension. The multidisciplinary network developed in the wake of this project is expected to facilitate the set up therapeutic trials, laying the ground for evidence-based recommendations., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: 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)., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The RADIANCE-HTN SOLO trial demonstrated a greater reduction in daytime ambulatory SBP at 2 months by endovascular ultrasound renal denervation than sham procedure. We hypothesized that plasma renin and aldosterone concentrations would be associated with the SBP response to renal denervation., Methods: Hypertensive patients were randomized to renal denervation (n = 74) or sham (n = 72) after a 4-week washout of antihypertensive medications. In a 53-patient subset, 2-month and 6-month plasma renin and aldosterone concentration were measured. Dietary sodium was not controlled., Results: Mean age of the 29 treatment and 24 sham patients was 54 years; 62% were men; 17% black. Daytime ambulatory SBP fell in the denervation but not the sham group at 2 months (-7.8 ± 10.7 vs. -0.1 ± 10.1 mmHg; P = 0.048). Baseline plasma renin and aldosterone concentrations were in the low-normal range, did not change significantly at 2 months in either group and did not predict response to renal denervation. At 6 months, after the addition of antihypertensive medications, there was a significant rise in renin in the sham but not the denervation group., Conclusion: Although renal denervation but not sham resulted in a decrease in daytime ambulatory SBP at 2 months, renin and aldosterone concentrations did neither predict the BP response to renal denervation; nor did they fall after denervation. A rise in renin at 6 months in the sham group likely represents confounding from antihypertensive medications. Whether the BP-lowering effect of renal denervation depends on reducing local intrarenal renin release requires further study., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the efficacy and the feasibility of radiofrequency ablation to treat aldosterone-producing adenomas., Methods: In an open prospective bicentric pilot study, patients with hypertension on ambulatory blood pressure measurement, a primary aldosteronism, an adenoma measuring less than 4 cm, and confirmation of lateralization by adrenal venous sampling were recruited. The primary endpoint, based on ABPM performed at 6 months after the radiofrequency ablation, was a daytime SBP/DBP less than 135/85 mmHg without any antihypertensive drugs or a reduction of at least 20 mmHg for SBP or 10 mmHg for DBP., Results: Thirty patients have been included (mean age = 51 ± 11 years; 50% women). Mean baseline daytime SBP and DBP were 144 ± 19 / 95 ± 15 mmHg and 80% received at least two antihypertensive drugs. At 6 months: 47% (95% CI 28-66) of patients reached the primary endpoint, mean daytime SBP and DBP were 131 ± 14 (101-154)/87 ± 10 (71-107) mmHg; 43% of them did not take any antihypertensive drug and 70% of them did not take potassium supplements. Few complications were recorded: four cases of back pain at day 1 postablation; three limited pneumothoraxes, which resolved spontaneously; one lesion of a polar renal artery., Conclusion: Radiofrequency ablation for hypertensive patients with aldosterone-producing adenomas seems to be an emerging promising alternative to surgery. Its efficacy and its feasibility have to be confirmed in a larger sample of patients., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

: 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.

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.

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.

Background: 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., Method: 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., Results: 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., Conclusion: 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.

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.

Objective: To evaluate a patient questionnaire (HY-QUEST) to be completed at home before consulting in a hypertension clinic for the first time., Methods: HY-QUEST is a questionnaire translated into patient language of the items from a standardized computerized medical record used since 1975 and regularly updated. This questionnaire contains 97 closed and seven free-text questions designed to evaluate cardiovascular risk and possible secondary hypertension, and to guide therapeutic strategy. One hundred and thirty-three new patients were asked to complete it at home and to bring it with them to their first visit in the hypertension clinic. The primary end-point was completeness of the answers. Other end-points were legibility and correctness of the answers., Results: Questionnaires were available for 128 out of 133 patients (96%). More than 80% of the 97 closed questions were answered in 121 out of 128 questionnaires [94.6%; 95% confidence interval (CI) 90.7-98.5] and no question had a response rate less than 85%. The answers were legible in 85% of the closed questions and the concordance rate with the physician's assessment was 94%. Among the 101 treated patients, 72 (71.3%; 95% CI 62.5-80.1) were able to provide the correct names, doses and schedule of their antihypertensive treatments., Conclusion: The HY-QUEST questionnaire can be completed by most patients with few missing or incorrect answers. It is well accepted by patients and provides useful information to orient the first consultation in a hypertension clinic. Whether the same approach is feasible and useful in primary care remains to be investigated.

Objective: We validated against invasive measurements a measure of central SBP based on the QKD interval. The present objective is a comparison to the SphygmoCor device., Materials and Methods: A first cohort was used to redefine an algorithm for estimating ascending aorta SBP (cSBP) with respect to SphygmoCor. This algorithm was then tested in a second cohort under static conditions and in a third cohort during a head-up tilt to study blood pressure variations., Results: The first cohort (36 patients, mean age: 46 ± 20 years, SBP: 114 ± 19 mm Hg) defined the estimation algorithm as cSBP =62.687+1.35 × meanBP-0.207 × heart rate-0.251 × height-0.1 × QKD (mean difference with SphygmoCor=0 ± 7 mmHg).In the second cohort (105 patients, mean age: 51 ± 19 years, SBP: 132 ± 22 mmHg), the average difference between the two techniques was 2 ± 6 mm Hg (R=0.93). The dynamic cohort included 31 patients (mean age: 49 ± 23 years, SBP: 110 ± 19 mmHg) with 224 pairs of measurement. We studied the changes in central blood pressures compared with the basal state of each of the two techniques during head-up tilt. With QKD, the average cSBP was 104 ± 19 mmHg, the average variation was -13.00 mmHg ± 15 (range 7-74 mmHg). With SphygmoCor, average cSBP was 10  mmHg ± 18, the average variation was -14 mmHg   ± 16 (range 2-81 mmHg). The variations in blood pressure with the two techniques were well correlated (R=0.93)., Conclusion: cSBP estimation based on the QKD interval is comparable in precision to the SphygmoCor. Its ability to measure cSBP variations suggests that it could be employed for ambulatory measurements over 24 h.

Objective: Left ventricular hypertrophy (LVH) is a marker of cardiovascular risk. However, the progression of the risk as a function of the course of the LVH has only been the subject of few studies., Methods: We report the consequences of the evolution of the left ventricular mass (LVM) in a cohort of hypertensive patients whose LVM was measured before any antihypertensive treatment., Results: We followed up for an average of 12 years, 763 hypertensives with LVM measurement by echocardiography on inclusion. In this population, 117 cardiovascular complications occurred and the initial LVM appeared to be the most powerful marker of risk. A cutoff of 51 g/m(2.7) for the LVM index (LVMI) offered the best compromise of sensitivity and specificity in the prediction of complications. A second determination of LVM was carried out in 436 patients on average 5 years after inclusion. In this sub-group, 82 complications were recorded after an average interval of 13 years. The 51 g/m(2.7) value of LVMI over the follow-up offered the same sensitivity (74%) and specificity (52%) in the prediction of complications. The progression of the LVM was related to the occurrence of complications independently of the basal value and other risk factors., Conclusions: We confirm LVMI as a powerful risk factor in hypertension with a cutoff of 51 g/m(2.7), which offers the same sensitivity and specificity whether the LVM was determined before or during treatment. The progression of LVM, on average 5 years after the initial measurement had a prognostic value independent of the initial determination.

Background: The measurement of central blood pressure (BPc) has become a matter of importance. Several therapeutic trials have noted a different protective effect against cardiovascular complications with different antihypertensive strategies, but an identical decrease in brachial BP (BPb). A possible explanation lies in the different effects of the treatments on BPc. We propose a new noninvasive method for the automatic measurement of BPc based on the QKD interval, an arterial stiffness marker., Materials and Methods: This study was carried out on patients referred for cardiac catheterization. We simultaneously measured the central SBP (SBPc) invasively with a pigtail probe, and the BPb by a cuff coupled with recording of the QKD interval. Two cohorts were studied, one to define an algorithm of SBPc estimation and one to validate this algorithm., Results: The first cohort included 65 patients. We performed 136 simultaneous measurements. In the multivariate analysis, four variables were significantly correlated with SBPc: mean BPb (mBPb), QKD, height and heart rate (HR) with the following regression equation: SBP = 105 + 1.29 × mBPb - 0.39 × HR - 0.30 × height - 0.11 × QKD. This equation estimated 81% of the variance of the invasive SBPc ± 13 mmHg. This algorithm was then tested in another cohort of 80 patients. Difference between measured and estimated SBPc was 2 ± 14 mmHg., Conclusion: This study showed that it is possible to estimate SBPc by simultaneous measurement of QKD and BPb. If further studies confirm these results, a noninvasive ambulatory method of monitoring of SBPc could be employed in clinical practice.

Objective: ECG is commonly employed to identify left ventricular hypertrophy (LVH) and a high risk of cardiovascular events (CVE) in hypertensive patients. However, the multiplicity of the existing criteria does not simplify interpretation of the data. We compared a number of common criteria in hypertensive patients by taking as references left ventricular mass (LVM) measured by echocardiography and prediction of incident CVE., Methods: The population was a cohort of 958 hypertensive patients (mean age 48 years) recruited before any treatment and having benefited from an ECG and an echocardiography. We evaluated their outcomes at regular intervals. We examined the relationships between several ECG criteria of LVH and LVM as well the occurrence of CVE., Results: Among the various parameters tested (Sokoloff, Cornell, Cornell product) the simple measurement of the RaVL wave offered the best correlations to LVM and the best prediction of the existence of an echocardiographic LVH (receiver-operating characteristic curves). Its alterations were best correlated with the changes in LVM during the follow-up period. Moreover, this simple measurement offered the best performance for the prediction of the occurrence of CVE (123 events after a mean lapse of 12 years)., Conclusion: In the interpretation of an ECG in the hypertensive patient, the single measurement of the R wave in aVL gives results at least as good as those of more complicated indices, which do not appear to contribute further to the diagnosis of LVH and the prediction of cardiovascular risk.

Objectives: To assess the consequences of malignant hypertension and its evolution with antihypertensive treatment., Background: Malignant hypertension can be considered as a model of the effects of very high blood pressure and renin-angiotensin levels on target organs. However, the consequences on the heart have been little studied., Methods: The consequences of malignant hypertension on left-ventricular function and its evolution with treatment were assessed with echocardiography in a prospective study between January 2004 and June 2009., Results: During the study period, 46 patients were referred to our unit for malignant hypertension of whom 25 could be included in the echocardiographic study. These patients showed at baseline important left-ventricular hypertrophy and alteration in systolic function. Global longitudinal strain was the most sensitive tool to assess impaired systolic function and was significantly reduced in 13 patients (<12.8, 52%). Short-term follow-up (1-3 months) showed a rapid improvement in systolic function together with significant hypertrophy regression. With a follow-up of 11 months on average all patients had recovered a normal global longitudinal strain with further but incomplete regression of hypertrophy., Conclusions: Our study highlights the significant impact of malignant hypertension on systolic function of the left ventricle, and the ability of this ventricle to quickly recover normal systolic function under antihypertensive treatment.

Introduction: Stiffness of the large arteries plays a role in the development of left ventricular hypertrophy (LVH), although there are few data on this relation in the general population. The cohort of the Prognostic Indicator of Cardiovascular and Cerebrovascular Events study is a representative population of 65-year-old individuals in which this relation can be examined., Method: To evaluate arterial stiffness, we used the ambulatory measure of the QKD interval that enables calculation of an isobaric index of arterial stiffness, QKD100-60. We analyzed its relationship with electrocardiographic criteria of LVH and left atrial remodeling on 775 individuals in the Prognostic Indicator of Cardiovascular and Cerebrovascular Events cohort., Results: We demonstrated a significant relationship between arterial stiffness and prevalence of electrocardiographically determined LVH and atrial remodeling, independent of 24-h blood pressure. Individuals belonging to the highest quartile of arterial stiffness (QKD100-60 <195 ms) had double the risk of ECG anomalies., Conclusion: This study is further support of a link between arterial stiffness and the risk of LVH or atrial remodeling in the general population. This risk is independent of age and 24-h blood pressure.

Objectives: In the absence of malignant hypertension, the mechanisms for the decline in renal function in hypertensive patients are not well known. Several recent studies, essentially cross-sectional, point to a role for an increase in arterial stiffness and its corollary, the increased pulse pressure (PP), in barotrauma of the renal glomerulus., Methods: We examined relations between the PP measured on consultation or by 24-h ambulatory blood pressure monitoring and the long-term decline in renal function in a population of essential hypertensive patients initially untreated, with normal renal function and without proteinuria. We evaluated the renal outcome of 375 patients of mean age 49 years in a baseline state over a mean follow-up period of 14 years., Results: At follow up, the glomerular filtration rate estimated from the modification of diet in renal disease formula was below 60 ml/min per 1.73 m2 in 51 of these patients, two of whom required dialysis. The blood pressure parameter best correlated with subsequent renal failure, independently of other factors of risk such as age or type 2 diabetes, was the PP measured either in consultation or by ambulatory blood pressure monitoring before starting treatment., Conclusion: The PP either measured on consultation or by ambulatory monitoring emerged as an independent determinant of the decline in renal functions in this population, pointing to the possibility of barotrauma of the glomeruli from increased arterial stiffness.

Background: Because inflammation is known to be related with several cardiovascular diseases, we sought to determine whether C-reactive protein (CRP) might precede the onset of hypertension., Methods: The study population was selected from the Proof study cohort including 1011 individuals initially aged 65 years at baseline and followed for 7 years. CRP, ambulatory blood pressure measurement (ABPM) and casual blood pressure were repeatedly measured during examination. Normotensive individuals were selected according to different measurements of blood pressure, self-reported history of hypertension and use of antihypertensive treatment., Results: Among 335 individuals, considered normotensive at baseline with ABPM (threshold 135/85 mmHg), with no history of hypertension and no use of antihypertensive treatment, the incidence of hypertension was 9.9% 2 years later. The 2-year risk for new-onset hypertension was 18% greater for 1 mg/l increment of CRP (odds ratio, 1.18; 95% confidence interval, 1.01-1.39). This relationship remained after adjustment for low-density lipoprotein cholesterol, BMI and change in CRP between the two examinations but not after adjustment for 24-h systolic ABPM. Among the 160 individuals considered normotensive at baseline with an additional criterion (casual blood pressure below 140/90 mmHg), the incidence of hypertension was 26.9% 2 years later. The 2-year risk for new-onset hypertension was 52% greater for 1 mg/l increment of CRP (odds ratio, 1.52; 95% confidence interval, 1.17-1.96) after adjustment for systolic ABPM, change in CRP and BMI., Conclusion: An elevated baseline CRP value precedes new-onset hypertension at an early stage among an elderly healthy population. Whether CRP measurement can ease the detection of patients likely to develop clinical hypertension remains to be determined.

Objective: Ambulatory blood pressure (BP) monitoring and home blood pressure measurements predicted the presence of target organ damage and the risk of cardiovascular events better than did office blood pressure., Methods: To compare these two methods in their correlation with organ damage, we consecutively included 325 treated (70%) or untreated hypertensives (125 women, mean age = 64.5 +/- 11.3) with office (three measurements at two consultations), home (three measurements morning and evening over 3 days) and 24-h ambulatory monitoring. Target organs were evaluated by ECG, echocardiography, carotid echography and detection of microalbuminuria. Data from 302 patients were analyzed., Results: Mean BP levels were 142/82 mmHg for office, 135.5/77 mmHg for home and 128/76 mmHg for 24-h monitoring (day = 130/78 mmHg; night = 118.5/67 mmHg). With a 135 mmHg cut-off, home and daytime blood pressure diverged in 20% of patients. Ambulatory and Home blood pressure were correlated with organ damage more closely than was office BP with a trend to better correlations with home BP. Using regression analysis, a 140 mmHg home systolic blood pressure corresponded to a 135 mmHg daytime systolic blood pressure; a 133 mmHg daytime ambulatory blood pressure and a 140 mmHg home blood pressure corresponded to the same organ damage cut-offs (Left ventricular mass index = 50 g/m, Cornell.QRS = 2440 mm/ms, carotid intima media thickness = 0.9 mm). Home-ambulatory differences were significantly associated with age and antihypertensive treatment., Conclusion: We showed that home blood pressure was at least as well correlated with target organ damage, as was the ambulatory blood pressure. Home-ambulatory correlation and their correlation with organ damage argue in favor of different cut-offs, that are approximately 5 mmHg higher for systolic home blood pressure.

Objectives: Arterial stiffness increases with age, diabetes and hypertension, and is linked to the occurrence of cardiovascular complications, independently of traditional risk factors. The important influence of age and blood pressure on arterial stiffness and cardiovascular risk complicates analysis of factors involved in increased arterial stiffness. Study of the PROOF cohort supplied further information by analysis of subjects of identical age using a method that eliminates the immediate influence of blood pressure on pulse wave velocity., Methods: The PROOF cohort comprised 1011 subjects, aged 65 years, from the city of Saint-Etienne (France). All benefited from 24-h ambulatory blood pressure monitoring coupled with measurement of QKD interval. Ambulatory Arterial Stiffness Index and QKD(100-60), were calculated for each recording. Measurements were performed again 2 years later., Results: Height-predicted QKD(100-60) was correlated with pulse pressure and the presence of diabetes. We found no significant influence of sex, current smoking or total serum cholesterol. Ambulatory Arterial Stiffness Index, whether it was height predicted or not, only had a significant relationship with blood pressure. Two years later, although the QKD(100-60) remained stable for the overall population, it was reduced in the normotensive subjects. Over the whole population, there was a correlation between the changes in 24-h systolic blood pressure and QKD(100-60)., Conclusion: QKD(100-60), an isobaric index of arterial stiffness, is significantly linked to blood pressure and blood sugar levels in a population of 65-year-old subjects. Two years later, the arterial stiffness increased significantly in the normotensive subjects, whereas it remained stable in the hypertensive subjects.

Objective: The ERAMS study addressed the value of arterial stiffness in predicting the severity of systemic sclerosis., Methods: ERAMS was a prospective multicentre cohort study including patients with definite systemic sclerosis. Arterial stiffness was measured by the standardized non-invasive QKd 100-60 method. Clinical evaluation, biological measurements, functional respiratory tests and cardiac Doppler echography were performed at inclusion then each year until 3 years' follow-up was completed. Progression was defined as mild (articulations, muscle, oesophagus or skin involvement) or severe (lung, heart or kidney involvement) by a critical event committee. The prediction of severe progression was studied for QKd 100-60 as well as clinical and biological data at baseline by univariate and multivariate analysis., Results: Ninety-nine patients were included (81 women, 18 men, mean age 57 years, standard deviation 12.5). Although their blood pressure profile was normal, half the patients had increased arterial stiffness (QKd 100-60<200 ms). There was a significant relationship between age-adjusted arterial stiffness and decrease in carbon dioxide diffusion (P<0.03) or haemoglobin rate (P<0.01). By univariate analysis, severe progression after 3 years was predicted by age (P=0.04), lung involvement (P=0.04), diffusion of lung carbon oxide (DLCO) (P<0.01), skin score (P=0.02), haemoglobin (P<0.01) and baseline Qkd 100-60 divided into two classes according to the median (P<0.01). By multivariate analysis, only haemoglobin rate [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.2-0.9] and QKd 100-60 (OR 19.6, 95% CI 1.2-308.2) predicted severe progression of systemic sclerosis., Conclusion: The measurement of arterial stiffness by the QKd method is a useful objective method for assessing the prognosis of systemic sclerosis independently from other data.

Objective: To compare the efficacy and safety of once-daily telmisartan and ramipril on blood pressure (BP) reductions during the last 6 h of the dosing interval., Patients and Methods: In a prospective, randomized, open-label, blinded-endpoint study using ambulatory BP monitoring, 801 patients with mild-to-moderate hypertension were randomly assigned to once-daily treatment with telmisartan 80 mg for 14 weeks or ramipril 5 mg for 8 weeks and then force titrated to ramipril 10 mg for the last 6 weeks. Primary endpoints were the reduction from baseline in the last 6-h mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Secondary endpoints included changes in 24-h, morning, daytime and night-time mean ambulatory BP and ambulatory BP response rates., Results: Telmisartan 80 mg produced greater reductions in the last 6-h mean ambulatory SBP and DBP compared with ramipril 5 mg (P < 0.0001) and 10 mg (P < 0.0001), and was superior to ramipril for all secondary ambulatory SBP and DBP endpoints (P < 0.05). Ambulatory BP response rates (24-h mean ambulatory SBP/DBP < 130/80 mmHg or reduction from baseline > or = 10 mmHg) were greater with telmisartan 80 mg (P < 0.01) than with ramipril 5 and 10 mg. Ramipril was associated with a higher incidence of treatment-related cough (5.7 versus 0.5% for telmisartan)., Conclusions: Telmisartan was significantly more effective than ramipril in reducing BP throughout the 24-h dosing interval and particularly during the last 6 h, a time when patients appear to be at greatest risk of cerebro- and cardiovascular events. Both drugs were well tolerated, although ramipril was associated with a higher incidence of cough.

Objective: Few data are available comparing the effects of monotherapy and combination therapy on target organ damage. The PICXEL study compared the efficacy of a strategy based on first-line combination with perindopril/indapamide versus monotherapy with enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients., Methods: In this 1-year multicentre randomized double-blind study, patients received an increasing dosage of perindopril/indapamide (n = 284) or enalapril (n = 272). Changes in blood pressure and echocardiographic measures of LVH were assessed from baseline to the end of treatment. Reading of the echocardiograms was central and blinded for therapy, patient and sequence., Results: Systolic and diastolic blood pressure decreased significantly more in the perindopril/indapamide than in the enalapril group (P < 0.0001 and P = 0.003). The left ventricular mass index decreased by 13.6 +/- 23.9 g/m(2) (mean +/- SD) with perindopril/indapamide (P < 0.0001) and 3.9 +/- 23.9 g/m(2) with enalapril (P < 0.005); these decreases were significantly different (P < 0.0001). The left ventricular internal diameter, posterior and interventricular septal wall thickness decreased significantly with perindopril/indapamide (P < or = 0.0001); the interventricular septal wall thickness decreased significantly with enalapril (P < 0.001). Both treatments were well tolerated., Conclusion: A strategy based on first-line combination with perindopril/indapamide achieved better blood pressure decrease with a significantly greater degree of LVH reduction than a strategy based on monotherapy with enalapril in hypertensive patients with LVH.

Objectives: In addition to the interest of mixing the sequence of echo-exam in a central blinded review, we studied the effect that might result from group-analysis of all echocardiograms simultaneously for each patient, with their sequence kept blind. A priori, this method of reading has the potential of decreasing measurement variability., Methods: We included 630 echocardiograms from 210 hypertensive patients participating in a randomized clinical trial comparing two antihypertensive agents for regression of left ventricular (LV) hypertrophy. Three echocardiograms per patient [selection (4 weeks before; W-4), at inclusion (week 0; W0), and the end of treatment (week 52; W52)], were read twice, according to two methods, blind to centre, patient numbers and sequence of visits: (1) examination of individual serial echocardiograms, (2) examination of all-patient mixed echocardiograms. The first method was expected to increase the power of treatment comparison by reducing variability of measurements of left ventricular mass (LVM)., Results: Pooling echocardiograms of all patients reduces variability of LVM change under treatment: absolute LVM (W52 - W0) standard deviation was reduced by 22%. Nevertheless, despite a good between-methods agreement for LVM values at each visit (intra-class coefficient of correlation from 0.88 to 0.92), LVM change under treatment was reduced even more, by 41%. Thus, the slight decrease of variability induced by gathering the echocardiograms is associated with an even greater reduction of LVM change., Conclusions: According to these findings, the 'full-blind' methodology for a central blinded review in clinical trials appears to produce the maximum power of the study with the lowest sample size.

Objectives: Since cardiovascular complications tend to occur more often in the morning, it is tempting to link this to the surge in blood pressure (BP) on rising. Our objective was to measure BP and heart rate (HR) on rising and compare values with those recorded immediately beforehand and seek variables related to marked changes in the two parameters in a cohort of initially untreated hypertensives., Methods: The 24-h ambulatory BP measurement along with an accurate measurement of the BP on rising (either manually or automatically from the device coupled with a position sensor) was obtained in untreated hypertensives. Left ventricular mass was measured with echocardiography at baseline. Patients were then treated and followed by their general physician and news was obtained at regular intervals., Results: A total of 507 patients with adequate recordings were included. Rising led to a mean increase of 14 mmHg in systolic blood pressure (SBP) and a 13 beats per minute (bpm) increase in HR. This elevation in BP on rising in the morning differed from the alteration in BP on normal changes in position. It was associated with left ventricular hypertrophy at baseline and an increased risk of future cardiovascular complications., Conclusions: Our study confirms the surge in BP on rising in the morning. This elevation in BP is accompanied by an acceleration in cardiac rhythm with no significant correlation between the two parameters. The increase in BP on rising was linked with the overall variability in BP, but was independent of the mean BP over 24 h. It was associated with an increased risk of cardiovascular complications independently of age and average 24-h SBP.

Objective: Large trials on left ventricular hypertrophy (LVH) regression are indispensable to allow accurate evaluation of the different classes of treatments. Such a trial, the LIVE study, gave us the opportunity to examine the influence of the mode of reading of the echo tracings on results and to underline the value of two initial recordings performed at entry., Methods: The LIVE study was designed to compare 1.5 mg indapamide SR with 20 mg enalapril on the regression of LVH evaluated echocardiographically. M-mode tracings of the left ventricle were performed at selection and after a 2 week placebo run-in. Recordings were read by investigators and by three experts all through the study, and finally read again by the three experts blind to treatment and sequence., Results: The two initial examinations produced an estimate of the reproducibility of the measurement of the left ventricular mass (LVM) that can be proposed as an indicator of overall quality provided no patients are excluded. The standard deviation of the differences between these two estimates of LVM was 52 g. These two examinations may also help quantify regression to the mean, which was not significant for the whole group. Knowledge of the sequence of examinations overestimates the change in LVM with treatment, as shown by comparison of measurements carried out during quality control with the measurements made blind (-19 +/- 52 versus -6 +/- 53 g, P <0.01)., Conclusions: The comparison of two initial echoes at entry allow one to define a quality criteria for such trials and to quantify a possible regression to the mean. The reading of recordings with knowledge of sequence significantly overestimates LVM variations on treatment.

Objective: To compare the efficacy of indapamide sustained release (SR) 1.5 mg and enalapril 20 mg at reducing left ventricular mass index (LVMI) in hypertensive patients with left ventricular hypertrophy (LVH)., Design: The LIVE study (left ventricular hypertrophy regression, indapamide versus enalapril) was a 1 year, prospective, randomized, double-blind study. For the first time, a committee validated LVH before inclusion, provided on-going quality control during the study, and performed an end-study reading of all echocardiograms blinded to sequence., Setting: European hospitals, general practitioners and cardiologists., Patients: Hypertensive patients aged > or = 20 years with LVH (LVMI in men > 120 g/m2; LVMI in women > 100 g/m2). Data were obtained from 411 of 505 randomized patients., Interventions: Indapamide SR 1.5 mg, or enalapril 20 mg, daily for 48 weeks., Main Outcome Measures: LVMI variation in the perprotocol population., Results: Indapamide SR 1.5 mg significantly reduced LVMI (-8.4 +/- 30.5 g/m2 from baseline; P< 0.001), but enalapril 20 mg did not (-1.9 +/- 28.3 g/m2). Indapamide SR 1.5 mg reduced LVMI significantly more than enalapril 20 mg: -6.5 g/m2, P = 0.013 (-4.3 g/m2 when adjusted for baseline values; P = 0.049). Both drugs equally and significantly reduced blood pressures (P< 0.001), without correlation with LVMI changes. Indapamide SR progressively reduced wall thicknesses throughout the 1-year treatment period. In contrast, the effect of enalapril observed at 6 months was not maintained at 12 months., Conclusions: Indapamide SR 1.5 mg was significantly more effective than enalapril 20 mg at reducing LVMI in hypertensive patients with LVH.

Objective: To study the relationship between serum cholesterol level and left ventricular mass for a population of untreated hypertensive patients., Design: A cross-sectional study., Patients: We studied 273 untreated hypertensive patients without associated diseases consecutively referred for evaluation of blood pressure. All patients underwent M-mode echocardiographic assessment of left ventricular mass, office blood pressure measurement and 24 h ambulatory blood pressure monitoring. Fasting plasma glucose and total cholesterol levels were measured on the same day., Results: We found a weak but significant correlation (r = 0.20-0.26, P < 0.01) between serum cholesterol level and left ventricular wall thickness or left ventricular mass irrespective of the mode of indexation used (height, height2.7 and body surface area). In multivariate analysis this relation remained significant after introduction of sex, age, weight, height, blood pressure and blood glucose level. When data for men and women were analysed separately the relationship between left ventricular mass and cholesterol remained significant for men only., Conclusion: There is a significant and independent positive relationship between serum cholesterol level and left ventricular mass that could contribute to the prognostic value of left ventricular hypertrophy.

Objective: To test the feasibility and utility of instituting centralized echocardiographic quality control during a multicenter study of regression of left ventricular hypertrophy in hypertension., Design and Methods: The LIVE (Left Ventricular Hypertrophy: Indapamide Versus Enalapril) study is an ongoing multicenter, double-blind, controlled study of regression of echocardiographic left ventricular mass index in hypertensive patients with left ventricular hypertrophy (left ventricular mass indexes > 100 g/m2 for women and > 120 g/m2 for men) treated for 1 year with 1.5 mg indapamide sustained-release coated tablets versus 20 mg enalapril. A centralized evaluation committee has validated a prestudy sample echocardiogram from each center, and is now reviewing all videotapes recorded during this study for quality control; final results will be based on a further randomized blinded analysis by this centralized evaluation committee., Results: Since December 1994, 878 patients have been preselected (videoechocardiographic recordings sent for assessment), 645 selected (videoechocardiographic recordings validated), and 576 randomly allocated to treatment. After preliminary quality control, 27% (233) of baseline echocardiograms were rejected by our centralized evaluation committee, and 22% (142) of postinclusion echocardiographic measurements had to be repeated, mainly because they were of poor echogenic quality. Analysis of approved baseline echocardiograms for the first 274 randomly allocated patients with digitized data showed that there was a significant correlation between centralized evaluation committee and investigator calculations of left ventricular mass index (r = 0.76, P < 0.001), with consistently higher values for investigator calculations, independently of level of left ventricular mass index (correlation between difference and mean of investigator and centralized evaluation committee measurements, r = 0.08, P = 0.28). The mean difference was 8 +/- 20 g/m2 (P < 0.001)., Conclusion: Early results of the LIVE study quality control showed that real-time 'live', centralized echocardiographic reading was not only feasible, but also useful for avoiding unquantifiable echocardiograms and overestimation of left ventricular mass index. Thus, real-time, centralized echocardiographic quality control should be recommended for multicenter studies of regression of left ventricular hypertrophy.