SPARTE Study: Normalization of Arterial Stiffness and Cardiovascular Events in Patients With Hypertension at Medium to Very High Risk.

[Figure: see text].

Non-invasive evaluation of retinal vascular remodeling and hypertrophy in humans: intricate effect of ageing, blood pressure and glycaemia.

BACKGROUND: Ageing, hypertension and diabetes have an intricate effect on microvascular structure. In the retina, the respective contribution of remodeling and hypertrophy in such process is still unclear. We aimed at disentangling age, blood pressure and glycaemia effects on retinal microcirculation using the non-invasive adaptive optics ophthalmoscopy (AOO). METHODS: We included 429 subjects, distributed into 4 groups according to normal (nBP) or high blood pressure (hBP) and/or normal (nGly) or high fasting glycaemia (hGly). The nBP/nGly group was stratified in age tertiles to isolate the effect of ageing. AOO was used to measure arteriolar wall thickness (WT, µm), arteriolar (aID, µm) and venular internal diameter (vID, µm) and calculate arteriolar wall-to-lumen ratio (WLR), wall cross-sectional area (WCSA, µm2). One-way ANOVA for parametric variables and Kruskal-Wallis test for non-parametric variables were used for comparison among groups. A multivariate regression analysis including age, gender, BP, hGly and antihypertensive treatment was performed to calculate independent predictors of retinal remodeling. RESULTS: WT was increased with ageing (tertile1: 22.5 ± 3.2, tertile2: 24.2 ± 3.5, tertile 3: 25.2 ± 3.8, p = 0.001) and BP (hBP: 25.2 ± 4.1 vs nBP: 23.9 ± 3.7, p = 0.003). aID decreased with BP (hBP: 90.2 ± 13.4 vs nBP: 93.6 ± 11.6, p = 0.013) and increased with glycaemia (hGly: 97.7 ± 12.5 vs nGly: 93.6 ± 11.6, p = 0.002). A multivariate analysis showed independent association of hBP with WLR; hGly with WCSA; ageing with WLR and WCSA. CONCLUSIONS: AOO non-invasively identifies retinal structural changes in human confirming that microvascular remodeling is exclusively related to hypertension, whereas vascular growth is related to ageing and hyperglycaemia.

COVID-19 In-Hospital Mortality and Use of Renin-Angiotensin System Blockers in Geriatrics Patients.

OBJECTIVE: The role of treatment with renin-angiotensin-aldosterone system blockers at the onset of COVID-19 infection is not known in the geriatric population. The aim of this study was to assess the relationship between angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitor (ACEI) use and in-hospital mortality in geriatric patients hospitalized for COVID-19. DESIGN: This observational retrospective study was conducted in a French geriatric department. Patients were included between March 17 and April 18, 2020. SETTING AND PARTICIPANTS: All consecutive 201 patients hospitalized for COVID-19 (confirmed by reverse-transcriptase polymerase chain reaction methods) were included. All nondeceased patients had 30 days of follow-up and no patient was lost to follow-up. METHODS: Demographic, clinical, and biological data and medications were collected. In-hospital mortality of patients treated or not by ACEI/ARB was analyzed using multivariate Cox models. RESULTS: Mean age of the population was 86.3 (8.0) years, 62.7% of patients were institutionalized, 88.6% had dementia, and 53.5% had severe disability (activities of daily living [ADL] score <2). Sixty-three patients were treated with ACEI/ARB and 138 were not. Mean follow-up was 23.4 (10.0) days, 66 (33.8%) patients died after an average of 10.0 days (6.0). Lower mortality rate was observed in patients treated with ACEI/ARB compared with patients not treated with ARB or ACEI (22.2% [14] vs 37.7% [52], hazard ratio [HR] 0.54; 95% confidence interval 0.30-0.97; P = .03). In a multivariate Cox regression model including age, sex, ADL score, Charlson index, renal function, dyspnea, C-reactive protein, and white blood cell count, use of ACEI/ARB was significantly associated with lower in-hospital mortality (HR 0.52 (0.27-0.99), P = .048). CONCLUSION AND IMPLICATIONS: In very old subjects hospitalized in geriatric settings for COVID-19, mortality was significantly lower in subjects treated with ARB or ACEI before the onset of infection. The continuation of ACEI/ARB therapy should be encouraged during periods of coronavirus outbreak in older subjects.

[Impaired hypertension control in France: What the nephrologist needs to know]. / La dégradation inquiétante du contrôle de l'hypertension artérielle en France : notre alerte à destination des néphrologues.

In France, 1 adult out of 3 is affected by hypertension and only 1 hypertensive out of 4 achieves blood pressure targets (<140/90mmHg). This proportion is significantly better in similar countries (e.g. England, Germany, the USA). Nephrologists are particularly concerned since although more than 90 % of Chronic Kidney Disease (CKD) stages 3 and 4 patients are hypertensive, the CKD-REIN cohort shows that in France more than 1 out of 2 patients with CKD remains with a blood pressure above 140/90mmHg. This report, based on the latest French studies and surveys, raises an important warning about the situation in France, discusses the main reasons for these results and offers some suggestions for improvement. Otherwise we risk a dramatic increase in the incidence of myocardial infarction, stroke, dependency and dementia in the coming years.

Mutation affecting the conserved acidic WNK1 motif causes inherited hyperkalemic hyperchloremic acidosis.

Gain-of-function mutations in with no lysine (K) 1 (WNK1) and WNK4 genes are responsible for familial hyperkalemic hypertension (FHHt), a rare, inherited disorder characterized by arterial hypertension and hyperkalemia with metabolic acidosis. More recently, FHHt-causing mutations in the Kelch-like 3-Cullin 3 (KLHL3-CUL3) E3 ubiquitin ligase complex have shed light on the importance of WNK's cellular degradation on renal ion transport. Using full exome sequencing for a 4-generation family and then targeted sequencing in other suspected cases, we have identified new missense variants in the WNK1 gene clustering in the short conserved acidic motif known to interact with the KLHL3-CUL3 ubiquitin complex. Affected subjects had an early onset of a hyperkalemic hyperchloremic phenotype, but normal blood pressure values"Functional experiments in Xenopus laevis oocytes and HEK293T cells demonstrated that these mutations strongly decrease the ubiquitination of the kidney-specific isoform KS-WNK1 by the KLHL3-CUL3 complex rather than the long ubiquitous catalytically active L-WNK1 isoform. A corresponding CRISPR/Cas9 engineered mouse model recapitulated both the clinical and biological phenotypes. Renal investigations showed increased activation of the Ste20 proline alanine-rich kinase-Na+-Cl- cotransporter (SPAK-NCC) phosphorylation cascade, associated with impaired ROMK apical expression in the distal part of the renal tubule. Together, these new WNK1 genetic variants highlight the importance of the KS-WNK1 isoform abundance on potassium homeostasis.

IGF-1 is an independent predictor of retinal arterioles remodeling in subjects with uncontrolled acromegaly.

CONTEXT: Cardiovascular disease is one of the main causes of morbidity in active acromegaly due to the increased prevalence of risk factors and arterial consequences of increased growth hormone levels. No in vivo study has evaluated the consequences of acromegaly on the retinal microvasculature. OBJECTIVE: The aim of this study was to identify in vivo the presence of morphological alterations of retinal arterioles in subjects with acromegaly. PATIENTS AND METHODS: Single-center retrospective study of a cohort of 60 subjects with acromegaly, matched to 60 controls, who were referred for adaptive optics camera (AOC) from September 2014 to December 2016. Of the subjects with acromegaly, 19 had an active disease (AD) and 41 a controlled disease (CD) based on the IGF1 ratio (IGF1r). Retinal arteriolar remodeling was previously assessed using adaptive optics camera (AOC) in order to measure wall-to-lumen ratio (WLR), wall thickness (WT), internal diameter (ID) and wall cross sectional area (WCSA). RESULTS: WLR was significantly higher in AD subjects compared to CD subjects and controls (AD: 0.311 ± 0.06, CD: 0.279 ± 0.04, controls: 0.281 ± 0.04, P = 0.031). A significant positive correlation was observed between WLR and IGF-1r (R2 = 0.215, P < 0.001), even after adjustment for gender, age, systolic blood pressure (SBP) and the presence of dopamine agonist treatment (R2 = 0.406, P < 0.001). Retinal arteriolar anatomical indices were comparable between CD and controls. CONCLUSION: Active acromegaly is associated with the presence of small retinal arteriolar remodeling. These results provide new perspectives to better stratify cardiovascular risk and consequently optimize treatment in acromegaly.

Clinic Versus Ambulatory Blood Pressure in Resistant Hypertension: Impact of Antihypertensive Medication Nonadherence: A Post Hoc Analysis the DENERHTN Study.

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<0.001). In contrast, clinic SBP was almost identical to day-SBP in the adherent group (clinic-SBP-day-SBP difference, 0.1 mm Hg; 95% CI, -3.3 to 3.5 mm Hg; 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.

Early central blood pressure elevation in adult patients with 21-hydroxylase deficiency.

CONTEXT: Controversial data exist on cardiovascular damages in patients with congenital adrenal hyperplasia (CAH). OBJECTIVE: To assess blood pressure and early cardiovascular damages on a large cohort of adult CAH patients and control individuals. DESIGN: Case-control study. SETTING: Referral Center for Rare Disease, Pitié Salpêtrière Hospital, Paris, France. PATIENTS OR OTHER PARTICIPANTS: Fifty-eight women and 26 men with CAH diagnosed in childhood and 85 controls matched-paired for sex, age and smoking status were prospectively included. INTERVENTION: Measurement of large arteries and microcirculatory anatomical and functional indices as well as hormonal status and cardiovascular risk factors evaluation. MAIN OUTCOME MEASURE: The primary objective was to compare carotid intima-media thickness (cIMT) in CAH patients and controls. The secondary objectives were to compare blood pressure (BP), radial augmentation index (rAI), central BP, carotid-femoral pulse wave velocity (PWV), skin microcirculation indices and inflammation parameters in CAH patients and controls. RESULTS: Although PWV and cIMT were identical in patients and controls, higher rAI (64.6 ±â€Š1.7 vs. 59.9 ±â€Š1.6%, P = 0.02) and higher central SBP (101.8 ±â€Š1.5 vs. 95.1 ±â€Š1.5 mmHg, P < 0.001) were observed in CAH patients. Regarding microcirculatory indices, there was a higher functional resting capacity and a lower anatomical capillary density in CAH patients. In multivariate analysis, we found an independant association between CAH and central SBP elevation. CONCLUSION: We found an early rise in central SBP in CAH patients whereas sublinical arterial damages markers were normal. Our study suggest that vascular damages and increased cardiovascular risk could be mainly BP-driven.

3D aortic morphology and stiffness in MRI using semi-automated cylindrical active surface provides optimized description of the vascular effects of aging and hypertension.

BACKGROUND: Clinically, aortic geometry assessment is mainly based on the measurement of maximal diameters at different anatomic locations, which are subsequently used to indicate prophylactic aortic surgery. However, 3D evaluation of aortic morphology could provide volumetric quantification, which integrates both aortic dilatation and elongation and might thus be more sensitive to early geometric changes than diameters. Precise aortic morphology is also required for the calculation of pulse wave velocity (PWVMRI), an established marker of aortic stiffness. Accordingly, we proposed a 3D semi-automated analysis of thoracic aorta MRI data optimizing morphological and subsequent stiffness assessment. METHODS: We studied 74 individuals (40 males, 50 ± 12years): 21 healthy volunteers and 53 patients with hypertension in whom aortic 3D MRI angiography and 2D + t phase-contrast and cine imaging were performed. A semi-automated method was proposed for volumetric aortic segmentation and was evaluated by studying resulting measurements (length, diameters, volumes and PWVMRI) in terms of: 1) reproducibility, 2) correlations with well-established 2D aortic length and diameters, 3) associations with age, carotid-femoral PWV (cf-PWV) and presence of hypertension. RESULTS: The measurements obtained with the proposed method were reproducible (coefficients of variation ≤ 5.1%) and were highly correlated with 2D measurements (arch length: r = 0.80, Bland-Altman mean bias [limits]: 2.7 mm [-25; 30]; PWVMRI: r = 0.95, 0.22 m/s [-1.9; 2.4]). Higher or similar correlations with age were found for the proposed 3D method compared to the 2D approach (arch length: r = 0.47 (2D), r = 0.60 (3D); PWVMRI: r = 0.63 (2D), r = 0.64 (3D)). Moreover, a significant association was found between PWVMRI and cf-PWV (r = 0.49, p < 0.001). All aortic measurements increased with hypertension (p < 0.05) and with age: arch length (+9mm/decade); diameters: ascending (+1.2mm/decade) and descending aorta (+1.0mm/decade); volumes: ascending (+2.6mL/decade) and descending aorta (+4.0mL/decade); PWVMRI (+1.7  m s-1/decade). CONCLUSIONS: A semi-automated method based on cylindrical active surfaces was proposed for the 3D segmentation of the aorta using a single MRI dataset, providing aortic diameters at anatomical landmarks, aortic volumes and the aortic centerline length used for PWV estimation. Such measurements were reproducible and comparable to expert measurements, which required time-consuming centerline delineation. Furthermore, expected relationships with age and hypertension were found indicating the consistency of our measurements.

Sex differences in adherence to antihypertensive treatment in patients aged above 55: The French League Against Hypertension Survey (FLAHS).

Despite the availability of efficient therapies to reduce the risk of cardiovascular complications, poor adherence to antihypertensive (anti-HTN) drugs is frequent, especially during the first year of treatment and among uncontrolled/resistant hypertensive patients. The aim of the study was to identify factors associated with adherence to anti-HTN treatment and to examine whether they differ across sex. A total of 2743 treated hypertensive participants to the cross-sectional Metascope survey (France, 2015) aged 55 years or more were included. The authors measured adherence to anti-HTN treatment using the 6-item Girerd compliance test. Variations in adherence were examined using the Rao-Scott statistics and Poisson regression. Overall, 63.6% of participants were adherent to anti-HTN treatment. Adherence was more frequent among women than men (69% vs 58%, P < 10-4 ). For both sexes, level of adherence was positively associated with age (P < 10-4 ), but inversely associated with number of anti-HTN tablets, number of tablets taken for metabolic diseases, history of cardiovascular diseases, number of other chronic diseases (all P < 10-4 ). The inverse relationship between adherence and the number of anti-HTN tablets significantly differed between sexes (P < 10-4 ): Adherence decreased sharply when taking two or more anti-HTN tablets in men, whereas the decrease in women was only observed when taking three or more anti-HTN tablets. This study suggests that adherence to anti-HTN treatment is higher among women, decreases with the number of tablets prescribed, and differentially so across sex. Reducing the number of tablets for anti-HTN treatment may improve adherence, especially among men and patients with multiple comorbidities.

Arterial stiffness evaluated by pulse wave velocity is not predictive of the improvement in hypertension after adrenal surgery for primary aldosteronism: A multicentre study from the French European Society of Hypertension Excellence Centres.

BACKGROUND: Predictive factors associated with normal blood pressure (BP) after unilateral adrenalectomy for primary aldosteronism (PA) are not clearly identified. AIMS: To evaluate the predictive value of arterial stiffness before surgery on BP after surgery. METHODS: During 2009-2013, 96 patients with PA due to unilateral adrenal adenoma who underwent surgery were enrolled in a multicentre open-label, prospective study. Aortic pulse wave velocity (PWV) was assessed before surgery. Patients underwent ambulatory blood pressure monitoring (ABPM) before surgery and 6 and 12months after surgery. Twenty-four h SBP/DBP values were compared in subjects with PWV

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

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

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

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

Extracorporeal membrane oxygenation for pheochromocytoma-induced cardiogenic shock.

BACKGROUND: Pheochromocytoma, a rare catecholamine-producing tumor, might provoke stress-induced Takotsubo-like cardiomyopathy and severe cardiogenic shock. Because venoarterial-extracorporeal membrane oxygenation (VA-ECMO) rescue of pheochromocytoma-induced refractory cardiogenic shock has rarely been reported, we reviewed our ICU patients' presentations and outcomes. METHODS: All pheochromocytoma-induced refractory cardiogenic shock cases managed with VA-ECMO (January 2007-March 2015) were prospectively included and reviewed. We also performed a systematic review on this topic. RESULTS: Nine patients (7 women, 2 men; 31-51 [median, 43 (IQR 36-49) years old]) were included; none had a previously known pheochromocytoma. Six of them had medical histories suggestive of the diagnosis: palpitations and headaches for several months for four, multiple endocrine neoplasia syndrome type 1 for one and recurrent Takotsubo disease for one; at hospital admission, all were hypertensive despite cardiogenic shock. Three others had an identified surgical triggering factor. All nine patients rapidly developed refractory cardiogenic shock with very severe left ventricular (LV) impairment (LV ejection-fraction range 5-20%; LV outflow-tract velocity-time integral range 3-8 cm). Seven patients' abdominal computed tomography scans showed pheochromocytoma-suggestive adrenal gland tumors (no scan during ICU stay for 2). Despite VA-ECMO implantation, three patients died of refractory multiple organ failure. For the six others, myocardial function improved and ECMO was removed 3-7 days post-implantation; α- and ß-blockers were progressively introduced. Five survivors underwent pheochromocytoma excision 3 weeks-4 months post-ICU discharge, with satisfactory outcomes. One patient, whose pheochromocytoma was diagnosed 1 year after the index event, underwent uneventful surgical adrenalectomy. Systematic review retrieved 40 cases of pheochromocytoma-induced cardiogenic shock requiring mechanical support (mostly ECMO), with a mortality rate of 7%. Pheochromocytoma was removed surgically after mechanical support weaning in 31 patients and during mechanical support in 5. Four were not operated. CONCLUSIONS: Pheochromocytoma is a rare but reversible cause of cardiogenic shock amenable to VA-ECMO rescue. Adrenal gland imaging should be obtained for all patients with unexplained cardiogenic shock. Lastly, it might be safer to perform adrenalectomy several weeks after the initial catastrophic presentation, once recovery of LV systolic function is complete.

Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial.

BACKGROUND: The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure-lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control. METHODS: One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients. RESULTS: The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was -6.7 mm Hg (P=0.0461) in fully adherent and -7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients. CONCLUSIONS: In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in blood pressure than standardized stepped-care antihypertensive treatment alone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

SFE/SFHTA/AFCE Consensus on Primary Aldosteronism, part 2: First diagnostic steps.

In patients with suspected primary aldosteronism (PA), the first diagnostic step, screening, must have high sensitivity and negative predictive value. The aldosterone-to-renin ratio (ARR) is used because it has higher sensitivity and lower variability than other measures (serum potassium, plasma aldosterone, urinary aldosterone). ARR is calculated from the plasma aldosterone (PA) and plasma renin activity (PRA) or direct plasma renin (DR) values. These measurements must be taken under standard conditions: in the morning, more than 2hours after awakening, in sitting position after 5 to 15minutes, with normal dietary salt intake, normal serum potassium level and without antihypertensive drugs significantly interfering with the renin-angiotensin-aldosterone system. To rule out ARR elevation due to very low renin values, ARR screening is applied only if aldosterone is>240pmol/l (90pg/ml); DR values<5mIU/l are assimilated to 5mIU/l and PRA values<0.2ng/ml/h to 0.2ng/ml/h. We propose threshold ARR values depending on the units used and a conversion factor (pg to mIU) for DR. If ARR exceeds threshold, PA should be suspected and exploration continued. If ARR is below threshold or if plasma aldosterone is<240pmol/l (90pg/ml) on two measurements, diagnosis of PA is excluded.

Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics.

BACKGROUND: In humans, adaptive optics camera enables precise large-scale noninvasive retinal microcirculation evaluation to assess ageing, blood pressure and antihypertensive treatments respective roles on retinal arterioles anatomy. METHOD: We used adaptive optics camera rtx1 (Imagine-Eyes, Orsay, France) to measure wall thickness, internal diameter and to calculate wall-to-lumen ratio (WLR) and wall cross-sectional area of retinal arterioles. This assessment was repeated within a short period in two subgroups of hypertensive individuals without or with a drug-induced blood pressure drop. RESULTS: In 1000 individuals, mean wall thickness, lumen diameter and WLR were 23.2 ±â€Š3.9, 78.0 ±â€Š10.9 and 0.300 ±â€Š0.054 µm, respectively. Blood pressure and age both independently increased WLR by thickening arterial wall. In opposite, hypertension narrowed lumen in younger as compared to older individuals (73.2 ±â€Š9.0 vs. 81.7 ±â€Š10.2 µm; P < 0.001), whereas age exerted no influence on lumen diameter. Short-term blood pressure drop (-29.3 ±â€Š17.3/-14.4 ±â€Š10.0 mmHg) induced a WLR decrease (-6.0 ±â€Š8.0%) because of lumen dilatation (+4.4 ±â€Š5.9%) without wall thickness changes. By contrast, no modifications were observed in individuals with stable blood pressure. In treated and controlled hypertensives under monotherapy WLR normalization was observed because of combined wall decrease and lumen dilatation independently of antihypertensive pharmacological classes. In multivariate analysis, hypertension drug regimen was not an independent predictor of any retinal anatomical indices. Retinal arteriolar remodeling comprised blood pressure and age-driven wall thickening as well as blood pressure-triggered lumen narrowing in younger individuals. CONCLUSION: Remodeling reversal observed in controlled hypertensives seems to include short-term functional and long-term structural changes.