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The impact of antihypertensive drugs on blood pressure does not differ according to the sex. There are women-specific conditions or medical conditions encountered more frequently among womens that guide the selection of therapy such as a desire to become pregnant, a pregnancy, a polycystic ovarian syndrome, breast cancer, osteoporosis or migraine., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objectives: We conducted a pilot multicenter double-blind randomized placebo-controlled crossover pharmacodynamic study to evaluate the blood pressure (BP) and the hormonal effects of firibastat, a first-in-class aminopeptidase A inhibitor prodrug, in patients with hypertension., Methods: Thirty-four patients with daytime ambulatory BP of at least 135/85 mmHg and less than 170/105 mmHg, after a 2-week run-in period were randomly assigned to receive either firibastat (250 mg b.i.d. for 1 week uptitrated to 500 mg b.i.d. for 3 weeks) and then placebo for 4 weeks each or vice versa, with a 2-week washout period on placebo., Results: At 4 weeks, daytime ambulatory systolic BP (SBP) decreased by 2.7 mmHg (95% confidence interval -6.5 to +1.1 mmHg) with firibastat versus placebo (P = 0.157). Office SBP decreased by 4.7 mmHg (95% confidence interval -11.1 to +1.8 mmHg) with firibastat versus placebo (P = 0.151). However, more the basal daytime ambulatory SBP was elevated, more the firibastat-induced BP decrease was marked. Firibastat did not influence 24h-ambulatory heart rate. Firibastat had no effect on plasma renin, aldosterone, apelin and copeptin concentrations. No major adverse events occurred. There was one episode of reversible skin allergy with facial edema., Conclusion: In patients with hypertension, a 4-week treatment with firibastat, tended to decrease daytime SBP relative to placebo. Firibastat did not modify the activity of the systemic renin-angiotensin system These results have justified designing a larger, powered trial of longer duration to fully assess its safety and effectiveness., Clinical Trial Registration: http://www.clinicaltrials.gov. NCT02322450.

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., (© 2017 American Heart Association, Inc.)

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., (© 2016 American Heart Association, Inc.)

Background: Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension., Methods: The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777., Findings: Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was -15·8 mm Hg (95% CI -19·7 to -11·9) in the renal denervation group and -9·9 mm Hg (-13·6 to -6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of -5·9 mm Hg (-11·3 to -0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups., Interpretation: In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation., Funding: French Ministry of Health., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Despite a wide choice of effective antihypertensive treatments, blood pressure (BP) in roughly half of hypertensive subjects is not controlled. Resistant hypertension is defined as an uncontrolled BP despite optimal doses of three antihypertensive treatments, including a diuretic. After confirmation of resistant BP using home BP measurement or 24-hour ambulatory BP monitoring (ABPM), patients usually go through a work-up to rule out secondary hypertension. If secondary hypertension is ruled out, the recent European guidelines on hypertension consider baroreceptor stimulation or renal denervation to be possible options. The prevalence of resistant primary hypertension may reach up to 10% in specialized centres. The two proposed non-pharmacological therapeutic strategies have been developed recently to inhibit sympathetic overactivity in resistant hypertension. Among them, baroreceptor activation therapy (BAT) is an innovative approach that interferes with baroreflex function. The first-generation BAT device (Rheos(®); CVRx, Inc., Minneapolis, MN, USA) demonstrated good efficacy in lowering office BP and ABPM, but had an insufficient safety profile due to complex surgery. The second-generation BAT device (Barostim neo™ system; CVRx, Inc.) seems to share the same BP-lowering efficacy but has a better safety profile. We report the first French case of baroreceptor stimulation for hypertension using the Barostim neo™ system. We also discuss the pathophysiological features of and current levels of evidence for this technique., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Many epidemiological studies have demonstrated that resting heart rate is a risk marker but also a risk factor in patients with coronary artery disease and heart failure. In hypertensive subjects free from overt cardiac disease, the question has been less frequently addressed. A few cohort studies have shown that hypertensive patients with a high resting heart rate have an increased risk of all-cause and cardiovascular death. However, intervention trials have not demonstrated that lowering the heart rate is beneficial in hypertensive subjects. Studies with an assessment of ambulatory heart rate tend to demonstrate a better association between cardiovascular outcomes and variables, including nighttime heart rate. Clinical trials comparing beta-blockers with non-slowing antihypertensive drugs have not demonstrated the superiority of the former. Finally, an elevated resting heart rate in hypertensive subjects free from overt cardiac disease seems to be more a risk marker than a risk factor. Although these patients are at high risk, no scientific data exist to support targeting heart rate. In this review, we describe the pathophysiological effects of heart rate, including vascular cell signalling, link with sympathetic activity and influence on central blood pressure, and the prognostic value and management of HR in hypertensive patients free from overt cardiac diseases., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

The field of hypertensive medicine is constantly and rapidly changing, especially with regards to treatment. In view of its high incidence and its complications, it is a major public health concern. This explains the periodic publication of national or international recommendations with the object of informing practitioners of the latest publications in a form applicable to clinical medicine. In France, the "Agence Nationale d'Accréditation et d'Evaluation en Santé" (ANAES) has recently published its recommendations for the management of hypertension. The dominant issues are the recognition of validated electronic sphygmomanometers for measuring the blood pressure in the out-patient setting, the evaluation of individual cardiovascular risk for treatment choice, the value of non-pharmacological interventions, the tailoring of antihypertensive treatment and the abandon of the concept of equal benefit of comparable blood pressure lowering irrespective of the molecule used.

Aim: We report the first experience of Lyon's university hospital regarding renal denervation to treat patients with resistant essential hypertension. Patients and methods: Over a one-year period, 17 patients were treated (12 men, 5 women) with renal denervation. Baseline characteristics were as follows: age 56.5 ± 11.5 years, BMI 33 ± 5 kg/m² and ambulatory blood pressure 157 ± 16/87 ± 13 mmHg with 4.2 ± 1.5 anti-hypertensive treatment. Results: We did not observe per procedural and early complications. After a median follow-up of 3 months and with the same anti-hypertensive treatment, office systolic blood pressure (SBP) and diastolic blood pressure (DBP) decrease respectively of 20 ± 15 (P < 0.001) and 10 ± 13 mmHg (P = 0.014) (n = 17). After six months of follow-up, ambulatory blood pressure (ABPM) decrease of 17.5 ± 14.9 mmHg (P = 0.027) for SBP and of 10.5 ± 9.6 mmHg (P = 0.029) for DBP (n = 6). Among these patients, five of them were controlled (ABPM inferior to 130/80 mmHg) and electrical left ventricular hypertrophy indexes decreased: R wave in aVL lead of 4 ± 3 mm (P = 0.031), Sokolow index of 3 ± 3 mm (P = 0.205), Cornell voltage criterion of 9 ± 7 mm (P = 0.027) and Cornell product of 1310 ± 1104 (P = 0.027). Conclusion: Our results are in accordance with data from other centers. On average blood pressure decreases significantly but important inter individual variations are observed. The procedure seems safe. [ABSTRACT FROM AUTHOR]