Philippe Gosse

Objective: The CHIRACIC trail supported the beneficial effect of adrenalectomy on hypertension in patients with unilateral adrenal incidentalomas associated with mild autonomous cortisol secretion (MACS). Additional assessments evaluated the impact of adrenalectomy on body weight excess, metabolic abnormalities and quality of life. Design: Multicenter superiority open-label randomized trial comparing adrenalectomy to conservative management. Methods: Following a run-in phase to control hypertension, receive lifestyle advice and treatment for comorbidities, patients underwent a workup including measurement of body mass index, visceral and total fat, fat mass, fasting blood glucose, HbA1c, oral glucose tolerance test, plasma lipids, and quality of life (QoL). Following randomization, assessment of comorbidities and adaptation of their treatment were performed every 3 months for 13 months. Workup was repeated at the end of the study. Results: Forty-eight patients were randomly assigned to adrenalectomy (n = 23) and conservative management (n = 25). 93%, 71% and 90% of patients were overweight/obese, prediabetics/diabetics and dyslipidemic, respectively. There was no statistically significant improvement in anthropometric and metabolic parameters after adrenalectomy as compared to conservative management: 21% and 4% of adrenalectomized and conservatively treated obese/overweight patients lost > 5% of body weight, respectively (difference 22%, 95% CI: −2% to 39%). Glycemic status improved in 44% and 33% of adrenalectomized and conservatively treated dysglycemic patients, respectively (difference 10%, 95% CI: −22% to 43%). Dyslipidemia improved in 20% of adrenalectomized and none of conservatively treated dyslipidemic patients. Changes in QoL were not different between groups. Conclusion: The beneficial effects of adrenalectomy on excess weight, metabolic disorders and QoL demonstrated in the CHIRACIC trial are more limited than those observed for hypertension. Additional randomized interventional studies involving a larger number of patients are needed to support the use of adrenalectomy in the treatment of these comorbidities.

Aims: Primary aldosteronism (PA) screening is difficult in an unselected population of hypertensive patients, as it can be challenging. We report new algorithms based either on risk stratification or machine learning models to improve the screening of PA. Methods and results: 15,507 patients with confirmed hypertension aged 18–65 years with full workup for PA screening were included in this study. We developed PAstrat, a risk stratification-based algorithm by generating patient groups of interest and assess probability of PA in each group, and two different machine learning models, logistic regression and XGBoost. An external cohort of 768 patients was used for validation. The AUC of the ROC curves for the PAstrat algorithm, logistic regression, and XGboost were, respectively, 0.80, 0.82, and 0.83 in the derivation cohort and 0.79, 0.82, and 0.82 in the validation cohort. Only 0.7% of the population (6 of 768) or 4.2% of patients with PA (6 of 142) had PA despite incorrect prediction by PAstrat (negative predictive value, 0.96). Conversely, among the 128 patients who had an indication for PA screening based on age, kalaemia, or drug resistance but not according to the algorithm, only 3 (0.23%) patients had PA. Logistic regression and XGBoost had, respectively, 49 (6.7%) and 84 (10.9%) false negatives (negative predictive value, respectively, 0.87 and 0.88). Conclusion: We developed a risk stratification algorithm for PA screening and compared its performances to machine learning models. Our algorithm demonstrated good sensitivity and negative predictive value for the screening of secondary hypertension, with the added value of great interpretability. Machine learning models lacked explainability and demonstrated a lower negative value in the validation cohort which makes them less easily usable.

BACKGROUND: The prevalence of secondary causes of hypertension in young adults is unknown, and therefore, there is no consensus about the indication of screening of secondary hypertension (2HTN) in this population. The objective was to report the prevalence and the causes of 2HTN in young subjects. METHODS: In this cross-sectional study, 2090 patients with confirmed hypertension aged 18 to 40 years with full workup for 2HTN screening were included. We assessed the prevalence of 2HTN and analyzed the factors associated. RESULTS: Among 2090 patients, 619 (29.6%) had a 2HTN. The most frequent diagnoses of 2HTN in descending order were primary aldosteronism (n=339; 54.8%), renovascular hypertension (n=114; 18.4%), primary kidney disease (n=80; 12.9%), pheochromocytoma/functional paraganglioma (n=37; 5.9%), hypertension caused by drugs or substances (n=32; 6.0%), and other diagnoses (n=17; 2.7%). Patients with blood pressure P =0.024). Female sex, hypokalemia, treatment with at least 2 medications, no familial history of hypertension, body mass index <25 kg/m², and diabetes were associated with a higher prevalence of 2HTN. CONCLUSIONS: The prevalence of 2HTN is high among young patients with hypertension (29.6% in our cohort), regardless of age and blood pressure level. All patients with hypertension under 40 years of age should be screened for secondary causes.

Arterial stiffness is an independent predictor of cardiovascular events in different populations. Destiffening appears to be possible through the control of the main cardiovascular risk factors, with however important individual variations. There are so far too few data available on the prognostic importance of changes in arterial stiffness. We tested the consequences of changes in arterial stiffness assessed with the QKD method on the incidence of cardiovascular events in a cohort of hypertensive patients. The change of QKD_100-60 was calculated as the difference between baseline and last follow-up value. Patients were classified as group 0 with stable or increased QKD_100-60 and group 1 with decreased QKD_100-60 (increased arterial stiffness). The prognostic of these two groups was analysed with a Cox model including age, baseline QKD_100-60, 24 h SBP (baseline and change), delay between first and last recording, sex, diabetes, smoking, and hypercholesterolemia. We included 555 essential hypertensive patients with 24 h ambulatory measurement of BP and QKD at baseline and follow-up. The follow-up period was 12.28 ± 7.38 years with an average time between baseline and last recording of 8.86 ± 6.48 years. 94 cardiovascular events occurred. The group with increased arterial stiffness shows the double risk of occurrence of cardiovascular event than the group with stable or reduced arterial stiffness independently of other factors including changes in 24 h SBP.

Introduction A major issue confronting clinicians treating hypertension in pregnancy is the limited number of pharmacological options. Endovascular catheter-based renal denervation (RDN) is a new method to lower blood pressure (BP) in patients with hypertension by reducing the activity of the renal sympathetic nervous system. Drugs that affect this system are safe in pregnant women. So there is reasonable evidence that RDN performed before pregnancy should not have deleterious effects for the fetus. Because the efficacy of RDN may be greater in younger patients and in women, we may expect a larger proportion of BP normalisation in young hypertensive women, but this remains to be proven. Our primary objective is to quantify the proportion of BP normalisation with RDN in this population. Methods and analysis WHY-RDN is a multicentre randomised sham-controlled trial conducted in six French hypertension centres that will include 80 women with essential hypertension treated or untreated, who are planning a pregnancy in the next 2 years and will be randomly assigned to RDN or classic renal arteriography and sham RDN in a ratio of 1:1. The primary outcome is the normalisation of 24-hour BP (Ethics and dissemination WHY-RDN has been approved by the French Ethics Committee (Tours, Region Centre, Ouest 1- number 2021T1-28 HPS). This project is being carried out in accordance with national and international guidelines. The findings of this study will be disseminated by publication. Trial registration number ClinicalTrials.gov, NCT05563337.

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 QKD_100-60, 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 QKD_100-60 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 QKD_100-60 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 QKD_100-60 was indeed not significantly related to 24-h SBP. In the untreated hypertensive population (n = 614, aged 51 ± 13 years) the QKD_100-60 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.

Arterial stiffness, most often assessed with carotido-femoral pulse wave velocity predicts cardiovascular events but its use in clinical practice remains limited. The 24 h 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, 24 h 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.

Purpose 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. Methods 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. Results 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. Conclusion 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.

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.