Long term worsening of arterial stiffness from monitoring of QKD interval predicts the occurrence of cardiovascular events.

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 QKD100-60 was calculated as the difference between baseline and last follow-up value. Patients were classified as group 0 with stable or increased QKD100-60 and group 1 with decreased QKD100-60 (increased arterial stiffness). The prognostic of these two groups was analysed with a Cox model including age, baseline QKD100-60, 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.

Endovascular ultrasound renal denervation to lower blood pressure in young hypertensive women planning pregnancy: study protocol for a multicentre randomised, blinded and sham controlled proof of concept study.

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 (<130/80 mm Hg) at 2-month post procedure off treatment. Sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1-ß), expected responder rates of 24% and 3% in the treatment and control group, respectively. Secondary outcomes include the absence of adverse outcomes for a future pregnancy, the variations of BP in ambulatory and home BP measurements and the evaluation of treatment prescribed. 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.

Arterial stiffness (from monitoring of Qkd interval) predict the occurrence of cardiovascular events and total mortality.

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.

Adrenal BORDeAux reGistry: Bordeaux single-center study of hypertensive patients with primary hyperaldosteronism.

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 ±â€Š10.5 years, BMI of 29.7 ±â€Š5 kg/ m2 and duration of hypertension of 101.5 ±â€Š84 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.

Long-term evolution of ambulatory blood pressure and cardiovascular events in hypertensive patients.

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) < 130; G1, first 24 h SBP ≥ 130, last 24 h SBP < 130; G2, first 24 h SBP < 130, last 24 h SBP ≥ 130; and G3, first 24 h SBP ≥ 130, last 24 h SBP ≥ 130 mmHg. Baseline ABPM better predicted future events than the last ABPM. G0 and G2 had similar survival. G1 and G3 had a worse prognosis than G0 and G2, while G1 had an intermediate risk between G0 and G3, indicating some benefit of treatment. In conclusion, our study showed the prognostic value of the first ABPM recorded in hypertensive patients and the persistence of risk when 24 h BP is controlled by antihypertensive treatment.

Neurologically asymptomatic patients frequently present cerebral injuries during malignant hypertension: a MRI study.

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 ±â€Š11.3 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.

Short-term blood pressure variability, arterial stiffness, and cardiovascular events: results from the Bordeaux cohort.

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 ±â€Š14 years) with an average follow up of 120 ±â€Š78 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.

Behavioral abnormalities in the Fmr1-KO2 mouse model of fragile X syndrome: The relevance of early life phases.

Fragile X syndrome (FXS) is a developmental disorder caused by a mutation in the X-linked FMR1 gene, coding for the FMRP protein which is largely involved in synaptic function. FXS patients present several behavioral abnormalities, including hyperactivity, anxiety, sensory hyper-responsiveness, and cognitive deficits. Autistic symptoms, e.g., altered social interaction and communication, are also often observed: FXS is indeed the most common monogenic cause of autism. Mouse models of FXS are therefore of great interest for research on both FXS and autistic pathologies. The Fmr1-KO2 mouse line is the most recent FXS model, widely used for brain studies; surprisingly, little is known about the face validity of this model, i.e., its FXS-like behavioral phenotype. Furthermore, no data are available for the age-related expression of the pathological phenotypes in this mouse line, a critical issue for modelling neurodevelopmental disorders. Here we performed an extensive behavioral characterization of the KO2 model at infancy, adolescent and adult ages. Hyperactivity, altered emotionality, sensory hyper-responsiveness and memory deficits were already present in KO mice at adolescence and remained evident at adulthood. Alterations in social behaviors were instead observed only in young KO animals: during the first 2 weeks of life, KOs emitted longer ultrasonic vocalizations compared to their WT littermates and as adolescents they displayed more aggressive behaviors towards a conspecific. These results strongly support the face validity of the KO2 mouse as a model for FXS, at the same time demonstrating that its ability to recapitulate social autistic-relevant phenotypes depends on early testing ages. Autism Res 2017, 10: 1584-1596. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.