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1.
J Clin Endocrinol Metab ; 105(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31529070

RESUMO

BACKGROUND: Non-classic 21-hydroxylase deficiency is usually diagnosed in post-pubertal women because of androgen excess. Indication of systematic steroid replacement therapy is controversial because the risk of acute adrenal insufficiency is unknown. In order to specify this risk we evaluated the cortisol and aldosterone secretions in response to appropriate pharmacologic challenges. METHODS: In this prospective case-control non-inferiority study we investigated 20 women with non-classic 21-hydroxylase deficiency carrying biallelic CYP21A2 mutations and with serum 17-hydroxyprogesterone (17OHP) >10 ng/mL after stimulation with Synacthen® (tetracosactrin) and 20 age- and body mass index-matched healthy women with 17OHP after Synacthen® <2 ng/mL. Each participant underwent sequentially an insulin tolerance test to evaluate cortisol secretion and a sodium depletion test, obtained by oral administration of 40 mg of furosemide under low sodium diet (<20 mmol during 24 hours), to evaluate renin and aldosterone secretion. FINDINGS: The peak serum cortisol concentration after insulin hypoglycemia was lower in patients than in controls (mean difference -47 ng/mL, 90% CI, -66, P = 0.0026). A peak serum cortisol above a cutoff value of 170 ng/mL was obtained in all controls but only in 55% of patients (P = 0.0039). Twenty-four hours after sodium depletion, blood pressure, plasma sodium, potassium, and serum aldosterone concentrations were comparable between the two groups, but patients had higher stimulated renin concentrations than controls (P = 0.0044). INTERPRETATION: Patients with non-classic 21-hydroxylase deficiency frequently display partial cortisol insufficiency and compensated defect in aldosterone secretion. Their clinical management should systematically include assessment of adrenal functions.

2.
Presse Med ; 48(11 Pt 1): 1265-1268, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31732366

RESUMO

The two main non-iatrogenic causes of secondary hypertension in women of childbearing age are primary aldosteronism and renal fibromuscular dysplasia. It is recommended to look for a secondary hypertension in women who remain hypertensive three months after pregnancy, in patients under 40 years of age or in patients with a grade 3 HTN (BP≥180/110mm Hg) (Professional agreement). It is suggested that the initial assessment of a secondary HTN in women is performed by a HTN specialist; it will include an assessment of renin and aldosterone concentrations and an angio-CT of the renal arteries (or angio-MRI if contraindicated) (Grade C - Class 2).


Assuntos
Displasia Fibromuscular/complicações , Hiperaldosteronismo/complicações , Hipertensão/etiologia , Adulto , Fatores Etários , Aldosterona/sangue , Angiografia por Tomografia Computadorizada , Feminino , Displasia Fibromuscular/diagnóstico , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão/sangue , Hipertensão/diagnóstico , Período Pós-Parto , Artéria Renal/diagnóstico por imagem , Renina/sangue , Fatores Sexuais
3.
Hypertension ; 74(6): 1516-1523, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31656101

RESUMO

The effect of renal artery angioplasty on blood pressure in patients with true resistant hypertension and atherosclerotic renal artery stenosis has not been fully investigated due to the exclusion of these patients from most trials. In this study, we assessed the benefits of renal angioplasty on daytime ambulatory blood pressure (dABP) in this subgroup of patients. Medical records of our hypertension department were retrospectively analyzed from 2000 to 2016. Seventy-two patients were identified with resistant hypertension (dABP >135 or 85 mm Hg despite at least 3 antihypertensive drugs, including a diuretic) and atherosclerotic renal artery stenosis treated by angioplasty. Atherosclerotic renal artery stenosis was unilateral in 57 patients and bilateral in 15 patients. The mean age of the patients was 67.8±11.2 years; dABP was 157±16/82±10 mm Hg despite 4.0±1.0 antihypertensive treatments; estimated glomerular filtration rate was 52 (41-63) mL/min. After renal angioplasty, dABPM decreased by 14.0±17.3/6.4±8.7 mm Hg (P<0.001 for both), and the number of antihypertensive treatments decreased to 3.6±1.4 (P=0.002) with no significant change in estimated glomerular filtration rate. A high baseline systolic dABP and a low body mass index were independent predictors of systolic dABP changes. The decrease in dABP was confirmed in a subgroup of patients at one and 3 years of follow-up (N=31 and N=18 respectively, P≤0.001 for systolic and diastolic blood pressure at both visits). In this retrospective uncontrolled single-center study, angioplasty in patients with atherosclerotic renal artery stenosis and with true resistant hypertension significantly decreased dABP, reducing the need for antihypertensive treatment with no change in estimated glomerular filtration rate.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31536622

RESUMO

CONTEXT: Adrenal venous sampling (AVS) is the key test for subtyping primary aldosteronism (PA), but its interpretation varies widely across referral centers and this can adversely affect the management of PA patients. OBJECTIVES: To investigate in a real life study the rate of bilateral success, identification of unilateral aldosteronism and blood pressure outcomes in PA subtyped by AVS. DESIGN AND SETTINGS: in a retrospective analysis of the largest international registry of individual AVS data (AVIS-2 study) we investigated how different cut-off values of the selectivity (SI) and lateralization index (LI) affected rate of bilateral success, identification of unilateral aldosteronism and blood pressure outcomes. RESULTS: AVIS-2 recruited 1625 individual AVS studies performed between 2000 and 2015 in 19 tertiary referral centers. Under unstimulated conditions, the rate of biochemically confirmed bilateral AVS success progressively decreased with increasing SI cut-offs; furthermore, with currently used LI cut-offs the rate of identified unilateral PA leading to adrenalectomy was as low as < 25%. A within-patient pairwise comparison of 402 AVS performed both under unstimulated and cosyntropin-stimulation conditions showed that cosyntropin increased the confirmed rate of bilateral selectivity for SI cut-offs ≥ 2.0, but with reduced lateralization rates (p < 0.001). Post-adrenalectomy outcomes were not improved by use of cosyntropin or more restrictive diagnostic criteria. CONCLUSION: Commonly used SI and LI cut-offs are associated with disappointingly low rates of biochemically defined AVS success and identified unilateral PA. Evidence-based protocols entailing less restrictive interpretative cut-offs might optimize the clinical use of this costly and invasive test.

5.
Hypertension ; 74(5): 1075-1083, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31495277

RESUMO

Despite the availability of multiple antihypertensive drugs targeting the different pathways implicated in its pathophysiology, hypertension remains poorly controlled worldwide, and its prevalence is increasing because of the aging of the population and the obesity epidemic. Although nonadherence to treatment contributes to uncontrolled hypertension, it is likely that not all the pathophysiological mechanisms are neutralized by the various classes of antihypertensive treatment currently available, and, the counter-regulatory mechanisms triggered by these treatments may decrease their blood pressure-lowering effect. The development of new antihypertensive drugs acting on new targets, with different modes of action, therefore, remains essential, to improve blood pressure control and reduce the residual burden of cardiovascular risks further. However, the difficulties encountered in the conception, development, costs, and delivery to the market of new classes of antihypertensive agents highlights the hurdles that must be overcome to release and to evaluate their long-term safety and efficacy for hypertension only, especially because of the market pressure of cheap generic drugs. New chemical entities with blood pressure-lowering efficacy are thus being developed more for heart failure or diabetic kidney disease, 2 diseases pathophysiologically associated with hypertension. These include dual angiotensin II receptor-neprilysin inhibitors, soluble guanylate cyclase stimulators, nonsteroidal dihydropyridine-based mineralocorticoid receptor antagonists, as well as sodium-glucose cotransporter 2 inhibitors. However, centrally acting aminopeptidase A inhibitors and endothelin receptor antagonists have a dedicated program of development for hypertension. All these emergent drug classes and their potential use in hypertension are reviewed here.


Assuntos
Anti-Hipertensivos/farmacologia , Drogas em Investigação/química , Drogas em Investigação/classificação , Hipertensão/tratamento farmacológico , Neprilisina/efeitos dos fármacos , Aminobutiratos/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Aprovação de Drogas , Sistemas de Liberação de Medicamentos , Feminino , Previsões , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Segurança do Paciente , Tetrazóis/uso terapêutico
6.
Hypertension ; 74(4): 800-808, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31476901

RESUMO

We sought to measure the clinical benefits of adrenal venous sampling (AVS), a test recommended by guidelines for primary aldosteronism (PA) patients seeking surgical cure, in a large registry of PA patients submitted to AVS. Data of 1625 consecutive patients submitted to AVS in 19 tertiary referral centers located in Asia, Australia, Europe, and North America were collected in a large multicenter international registry. The primary end points were the rate of bilateral success, ascertained lateralization of PA, adrenalectomy, and of cured arterial hypertension among AVS-guided and non AVS-guided adrenalectomy patients. AVS was successful in 80.1% of all cases but allowed identification of unilateral PA in only 45.5% by the criteria in use at each center. Adrenalectomy was performed in 41.8% of all patients and cured arterial hypertension in 19.6% of the patients, 2-fold more frequently in women than men (P<0.001). When AVS-guided, surgery provided a higher rate of cure of hypertension than when non-AVS-guided (40.0% versus 30.5%; P=0.027). Compared with surgical cases, patients treated medically needed more antihypertensive medications (P<0.001) and exhibited a higher rate of persistent hypokalemia requiring potassium supplementation (4.9% versus 2.3%; P<0.01). The low rate of adrenalectomy and cure of hypertension in PA patients seeking surgical cure indicates suboptimal AVS use, possibly related to issues in patient selection, technical success, and AVS data interpretation. Given the better outcomes of AVS-guided adrenalectomy, these results call for actions to improve the diagnostic use of this test that is necessary for detection of surgical PA candidates. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01234220.


Assuntos
Glândulas Suprarrenais/irrigação sanguínea , Adrenalectomia , Aldosterona/sangue , Hiperaldosteronismo/sangue , Adulto , Coleta de Amostras Sanguíneas , Feminino , Humanos , Hiperaldosteronismo/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
7.
Presse Med ; 48(12): 1431-1438, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31473027

RESUMO

Resistant hypertension is defined as uncontrolled blood pressure (BP) despite three antihypertensive agents including a diuretic (thiazide diuretic if renal function is normal or loop diuretic in case of chronic kidney disease with eGFR<30mL/min), a renin-angiotensin system blocker (ARB or ACEI) and a calcium channel blocker, at optimal doses. Resistance must be confirmed by out-of-office measurements (ambulatory blood pressure monitoring or home blood pressure monitoring) and patients should be asked about treatment compliance and excessive salt or alcohol intake. If the diagnosis of resistant hypertension is confirmed, the patient should be referred to a hypertension specialist to screen for secondary causes of hypertension as they are frequent in this context. If essential resistant hypertension is confirmed, the mineralocorticoid receptor antagonist, spironolactone, should be added (25 to 50mg daily). In the event of a contraindication to spironolactone, or if adverse effects occur, a beta-blocker, an alpha-blocker, or a centrally acting antihypertensive drug should be prescribed.


Assuntos
Anti-Hipertensivos/uso terapêutico , Resistência a Medicamentos , Hipertensão Essencial/tratamento farmacológico , Espironolactona/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Resistência a Medicamentos/efeitos dos fármacos , Quimioterapia Combinada , Hipertensão Essencial/epidemiologia , Humanos , Resultado do Tratamento
8.
J Hypertens ; 37(11): 2216-2224, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31415307

RESUMO

OBJECTIVE: We evaluated the characteristics of patients with treatment-resistant hypertension (TRH) and the prevalence of TRH in a large multicountry sample of specialist tertiary centres. METHODS: The Survey of PatIents with treatment ResIstant hyperTension (SPIRIT) study was a retrospective review of medical records of patients seen at tertiary centres located in Western Europe, Eastern Europe, North America, South America, Australia and Asia. Data on demographics, medical history and medication use were extracted from medical records. Prevalence and incidence of TRH were based upon estimated catchment populations. RESULTS: On thousand, five hundred and fifty-five patients from 76 centres were included, mostly from centres that specialize in hypertension (55%), cardiology (11%) or nephrology (19%). Mean age was 64, 60% were men, 62% were Caucasian, 36% had chronic kidney disease, 41% had diabetes, 12% were smokers and 31% had a previous cardiovascular event. Daytime and night-time ambulatory blood pressure (BP) was the most frequently used measurement for diagnosis (82%). Ninety-five percent of patients were prescribed diuretics, 93% an inhibitor of the renin-angiotensin system, 86% a calcium channel blocker, 74% a beta-blocker and 36% an aldosterone antagonist. The overall estimated mean incidence of TRH was 5.8 per 100 000 per year (ranging between 2.3 and 14.0 across regions) and the corresponding estimated mean prevalence of TRH was 23.9 per 100 000 (ranging between 7.6 and 90.5 across regions). CONCLUSION: Observed variation likely reflects real differences in patient characteristics and physician management practices across regions and specialities but may also reflect differences in patient selection and errors in estimation of catchment population across participating centres.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31369102

RESUMO

BACKGROUND: In rodents, the stimulation of adrenal progesterone is necessary for renal adaptation under potassium depletion. Here, we sought to determine the role of progesterone in adrenal adaptation in potassium-depleted healthy human volunteers and compared our findings with data collected in patients with Gitelman syndrome (GS), a salt-losing tubulopathy. METHODS: Twelve healthy young men were given a potassium-depleted diet for 7 days at a tertiary referral medical centre (NCT02297048). We measured by liquid chromatography coupled to tandem mass spectroscopy plasma steroid concentrations at Days 0 and 7 before and 30 min after treatment with tetracosactide. We compared these data with data collected in 10 GS patients submitted to tetracosactide test. RESULTS: The potassium-depleted diet decreased plasma potassium in healthy subjects by 0.3 ± 0.1 mmol/L, decreased plasma aldosterone concentration by 50% (P = 0.0332) and increased plasma 17-hydroxypregnenolone concentration by 45% (P = 0.0232) without affecting other steroids. CYP17 activity, as assessed by 17-hydroxypregnenolone/pregnenolone ratio, increased by 60% (P = 0.0389). As compared with healthy subjects, GS patients had 3-fold higher plasma concentrations of aldosterone, 11-deoxycortisol (+30%) and delta 4-androstenedione (+14%). Their post-tetracosactide progesterone concentration was 2-fold higher than that of healthy subjects and better correlated to plasma potassium than to plasma renin. CONCLUSION: The increase in 17-hydroxypregnenolone concentration after mild potassium depletion in otherwise healthy human subjects suggests that 17 hydroxylation of pregnenolone prevents the increase in progesterone observed in potassium-depleted mice. The unexpected over-response of non-mineralocorticoid steroids to tetracosactide in GS subjects suggests that the adrenal system not only adapts to sodium depletion but may also respond to hypokalaemia.

10.
PLoS One ; 14(7): e0219266, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291293

RESUMO

INTRODUCTION: Over the past few decades, the prevalence of hypertension has dramatically increased in Sub-Saharan Africa. Poor adherence has been identified as a major cause of failure to control hypertension. Scarce data are available in Africa. AIMS: We assessed adherence to medication and identified socioeconomics, clinical and treatment factors associated with low adherence among hypertensive patients in 12 sub-Saharan African countries. METHOD: We conducted a cross-sectional survey in urban clinics of both low and middle income countries. Data were collected by physicians on demographics, treatment and clinical data among hypertensive patients attending the clinics. Adherence was assessed by questionnaires completed by the patients. Factors associated with low adherence were investigated using logistic regression with a random effect on countries. RESULTS: There were 2198 individuals from 12 countries enrolled in the study. Overall, 678 (30.8%), 738 (33.6%), 782 (35.6%) participants had respectively low, medium and high adherence to antihypertensive medication. Multivariate analysis showed that the use of traditional medicine (OR: 2.28, 95%CI [1.79-2.90]) and individual wealth index (low vs. high wealth: OR: 1.86, 95%CI [1.35-2.56] and middle vs. high wealth: OR: 1.42, 95%CI [1.11-1.81]) were significantly and independently associated with poor adherence to medication. In stratified analysis, these differences in adherence to medication according to individual wealth index were observed in low-income countries (p<0.001) but not in middle-income countries (p = 0.17). In addition, 26.5% of the patients admitted having stopped their treatment due to financial reasons and this proportion was 4 fold higher in the lowest than highest wealth group (47.8% vs 11.4%) (p<0.001). CONCLUSION: This study revealed the high frequency of poor adherence in African patients and the associated factors. These findings should be useful for tailoring future programs to tackle hypertension in low income countries that are better adapted to patients, with a potential associated enhancement of their effectiveness.

11.
J Am Soc Nephrol ; 30(8): 1534-1545, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31285285

RESUMO

BACKGROUND: Gitelman syndrome is a salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive sodium-chloride cotransporter. Previous studies suggested an intermediate phenotype for heterozygous carriers. METHODS: To evaluate the phenotype of heterozygous carriers of pathogenic SLC12A3 mutations, we performed a cross-sectional study of patients with Gitelman syndrome, heterozygous carriers, and healthy noncarriers. Participants measured their BP at home for three consecutive days before hospital admission for blood and urine sampling and an oral glucose tolerance test. RESULTS: We enrolled 242 participants, aged 18-75 years, including 81 heterozygous carriers, 82 healthy noncarriers, and 79 patients with Gitelman syndrome. The three groups had similar age, sex ratio, and body mass index. Compared with healthy noncarriers, heterozygous carriers showed significantly higher serum calcium concentration (P=0.01) and a trend for higher plasma aldosterone (P=0.06), but measures of home BP, plasma and urine electrolytes, renin, parathyroid hormone, vitamin D, and response to oral glucose tolerance testing were similar. Patients with Gitelman syndrome had lower systolic BP and higher heart rate than noncarriers and heterozygote carriers; they also had significantly higher fasting serum glucose concentration, higher levels of markers of insulin resistance, and a three-fold higher sensitivity to overweight. According to oral glucose tolerance testing, approximately 14% of patients with Gitelman syndrome were prediabetic, compared with 5% of heterozygous carriers and 4% of healthy noncarriers. CONCLUSIONS: Heterozygous carriers had a weak intermediate phenotype, between that of healthy noncarriers and patients with Gitelman syndrome. Moreover, the latter are at risk for development of type 2 diabetes, indicating the heightened importance of body weight control in these patients.

12.
J Hypertens ; 37(11): 2225-2231, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31157746

RESUMO

OBJECTIVES: P-glycoprotein (P-gp), the product of the ABCB1 gene, is involved in the transport of aldosterone and cortisol in adrenal cells in vitro but its physiological role in humans remains controversial. Our objective was to test the influence of P-gp polymorphisms on aldosterone. METHODS: We evaluated plasma aldosterone concentration (PAC), urinary aldosterone, and blood pressure in a cohort of white normotensive men at baseline on diets unrestricted for sodium and potassium and after a 5-day treatment with 500 mg b.i.d. clarithromycin, a P-gp inhibitor. Included were 20 homozygous wild-type (P-gp0), 20 heterozygous (P-gp1), and 20 individuals with combined 2677G>T/A-3435C>T loss-of-function polymorphism of the ABCB1 gene (P-gp2). RESULTS: At baseline, PAC, urinary aldosterone, urinary free cortisol to urine creatinine ratios, and blood pressure did not differ in the three genotypes. After clarithromycin administration, the urinary aldosterone to creatinine ratio increased by an average of 30% in the entire cohort (P < 0.001, n = 60). Increases were pronounced in P-gp1 (+40%; P = 0.014) and P-gp2 individuals (+50%; P = 0.020) but lesser and were NS in P-gp0 individuals (+10%; P = 0.259). PAC also increased from baseline after clarithromycin treatment in all individuals (+19%, P = 0.050); however, the increase in PAC was NS when the three genotypes were analyzed separately. CONCLUSION: In our experimental conditions, the interaction between P-gp inhibition and the ABCB1 genotype, suggests that aldosterone is indeed a physiological endogenous substrate of P-gp in humans and that P-gp interferes with the net equilibrium between aldosterone secretion and elimination processes in humans.Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT01627665.

13.
J Thromb Haemost ; 17(10): 1670-1682, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31215111

RESUMO

BACKGROUND: Rivaroxaban is a direct factor Xa inhibitor with substantial inter-individual pharmacokinetic (PK) variability. Pharmacodynamic (PD) variability, especially assessed with thrombin generation (TG), has been less documented. OBJECTIVES: (i) To assess TG parameter time profiles in healthy volunteers, with TG being studied under different conditions and (ii) to model the relationship between rivaroxaban concentrations and TG parameters and subsequently estimate interindividual variability. METHODS: Sixty healthy male volunteers (DRIVING-NCT01627665) received a single 40-mg rivaroxaban dose. Blood sampling was performed at baseline and 10 predefined time points over 24 h. The TG was investigated with the fully automated ST-Genesia system (Stago), using two tissue-factor (TF) concentrations, in the absence (-), or presence (+) of thrombomodulin (TM) for the lowest one. The PD models were built to characterize the relationships between plasma rivaroxaban concentrations and endogenous thrombin potential (ETP) or peak height induced by the lowest TF concentration. RESULTS: Thrombin generation parameter time profiles with the lowest TF concentration showed a good sensitivity to rivaroxaban, especially +TM (active protein C negative feedback). The relationship between rivaroxaban concentrations and TG parameters was modeled with a sigmoidal relation. Mean rivaroxaban concentrations halving the baseline value of ETP and peak height (-TM) (C50 ) were of 284 and 33.2 ng/mL, respectively: +TM, C50 declined to 19.4 and 13.8 ng/mL, reflecting a powerful inhibitory effect. The estimated C50 population coefficients of variation were of 12.2% (-TM) and 31.3% (+TM) with the peak height models, 34.8% (+TM) with the ETP model. CONCLUSIONS: This low-rivaroxaban to moderate-rivaroxaban PD variability in healthy volunteers contrasts with the substantial PK variability and deserves to be studied in different patient settings.

14.
Circulation ; 2019 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-30880441

RESUMO

BACKGROUND: The multicenter, international, randomized, blinded, sham-controlled RADIANCE-HTN SOLO trial demonstrated a 6.3 mmHg greater reduction in daytime ambulatory systolic blood pressure (BP) at 2 months by endovascular ultrasound renal denervation (RDN) compared with a sham procedure among patients not treated with antihypertensive medications. We report 6-month results following the addition of a recommended standardized stepped-care antihypertensive treatment (SSAHT) to the randomized endovascular procedure under continued blinding to initial treatment. METHODS: Patients with a daytime ambulatory BP greater ≥135/85 mmHg and <170/105 mmHg after a 4-week discontinuation of up to 2 antihypertensive medications and a suitable renal artery anatomy, were randomized to RDN (n=74) or sham (n=72). Patients were to remain off antihypertensive medications throughout the first 2 months of follow-up unless safety BP criteria were exceeded. Between 2 and 5 months, if monthly measured home BP was ≥135/85 mmHg, a SSAHT was recommended consisting of the sequential addition of amlodipine 5 mg/day, a standard dose of an angiotensin converting enzyme inhibitor/angiotensin receptor blocker, and hydrochlorothiazide 12.5 mg/day, followed by the sequential uptitration of hydrochlorothiazide (25 mg/day) and amlodipine (10 mg/day). Outcomes included the 6-month (i) change in daytime ambulatory systolic BP adjusted for medications and baseline SBP, (ii) medication burden, and (iii) safety. RESULTS: A total of 69/74 RDN patients and 71/72 sham patients completed the 6-month ambulatory BP measurement. At 6 months, 65.2% of patients in the RDN group were treated with the SSAHT vs. 84.5% in the sham group (p=0.008) and the average number of antihypertensive medications and defined daily dose were less in the RDN group than in the sham group (0.9±0.9 vs. 1.3±0.9, p=0.010 and 1.4±1.5 vs. 2.0±1.8, p=0.018; respectively). Despite less intensive SSAHT, RDN reduced daytime ambulatory systolic BP to a greater extent than sham (-18.1±12.2 vs. -15.6±13.2 mmHg, respectively; difference adjusted for baseline BP and number of medications: -4.3 mmHg, 95% confidence interval, -7.9 to -0.6, p=0.024). There were no major adverse events in either group through 6 months. CONCLUSIONS: The BP lowering effect of endovascular ultrasound RDN was maintained at 6 months with less prescribed antihypertensive medications compared with a sham control. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02649426.

15.
J Hypertens ; 37(8): 1722-1728, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30882604

RESUMO

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.

17.
J Hypertens ; 37(2): 229-252, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30640867

RESUMO

This article is a comprehensive document on the diagnosis and management of fibromuscular dysplasia (FMD) which was commissioned by the Working Group 'Hypertension and the Kidney' of the European Society of Hypertension (ESH) and the Society for Vascular Medicine (SVM). This document updates previous consensus documents/scientific statements on FMD published in 2014 with full harmonization of the position of European and US experts. In addition to practical consensus-based clinical recommendations, including a consensus protocol for catheter-based angiography and percutaneous angioplasty for renal FMD, the document also includes the first analysis of the European/International FMD Registry and provides updated data from the US Registry for FMD. Finally, it provides insights on ongoing research programs and proposes future research directions for understanding this multifaceted arterial disease.

18.
Vasc Med ; 24(2): 164-189, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30648921

RESUMO

This article is a comprehensive document on the diagnosis and management of fibromuscular dysplasia (FMD), which was commissioned by the working group 'Hypertension and the Kidney' of the European Society of Hypertension (ESH) and the Society for Vascular Medicine (SVM). This document updates previous consensus documents/scientific statements on FMD published in 2014 with full harmonization of the position of European and US experts. In addition to practical consensus-based clinical recommendations, including a consensus protocol for catheter-based angiography and percutaneous angioplasty for renal FMD, the document also includes the first analysis of the European/International FMD Registry and provides updated data from the US Registry for FMD. Finally, it provides insights on ongoing research programs and proposes future research directions for understanding this multifaceted arterial disease.


Assuntos
Angiografia/normas , Angioplastia/normas , Fármacos Cardiovasculares/uso terapêutico , Displasia Fibromuscular/diagnóstico por imagem , Displasia Fibromuscular/terapia , Angioplastia/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Tomada de Decisão Clínica , Consenso , Displasia Fibromuscular/epidemiologia , Predisposição Genética para Doença , Humanos , Valor Preditivo dos Testes , Fatores de Risco , Resultado do Tratamento
19.
Hypertension ; 73(2): 371-378, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30624987

RESUMO

Arterial fibromuscular dysplasia is a nonatherosclerotic, noninflammatory vascular disease, whose pathophysiology is still unknown. We performed deep image-based vascular phenotyping of nonaffected arteries to look for systemic vascular alterations in fibromuscular dysplasia. This single center cross-sectional study included 50 patients with multifocal renal fibromuscular dysplasia, 50 hypertensive patients, and 50 healthy controls, matched for age, sex, and ethnicity; hypertensive patients were matched also for blood pressure. Brachial artery endothelium-dependent and endothelium-independent dilation were studied by echotracking. Aortic stiffness was assessed by carotid-to-femoral pulse wave velocity. We quantified the presence of supernumerary acoustic interfaces within the common carotid wall by the triple signal (TS) score. We plotted the Young incremental elastic modulus/stress curves for common carotid artery, derived from echotracking and tonometry. Patients with fibromuscular dysplasia had impaired endothelium-independent dilation (adjusted P=0.002), smaller brachial artery diameter but comparable endothelium-dependent dilation and aortic stiffness. The prevalence of TS score >6 was 56%, 40%, 24% in patients with fibromuscular dysplasia, hypertensives, and controls, respectively ( P=0.005). Fibromuscular dysplasia remained significantly associated with TS in the multiple regression model ( P=0.022). Impaired endothelium-dependent dilation was present only in patients with fibromuscular dysplasia, TS score >6 ( P=0.047). Incremental elastic modulus was higher for a given wall stress (80 kPa) in the presence of a TS score >6, especially in fibromuscular dysplasia. In conclusion, nonclinically affected large- and medium-sized arteries in patients with multifocal renal fibromuscular dysplasia exhibit a cluster of diffuse alterations in smooth muscle cell function, arterial geometry, wall characteristics, and mechanical properties. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01935752.


Assuntos
Displasia Fibromuscular/fisiopatologia , Rim/irrigação sanguínea , Artéria Braquial/fisiopatologia , Estudos Transversais , Endotélio Vascular/fisiologia , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/fisiologia , Fenótipo , Rigidez Vascular
20.
Am J Kidney Dis ; 73(4): 566-571, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30527885

RESUMO

Juxtaglomerular cell tumors (JCTs), a rare but potentially curable cause of hypertension, are difficult to diagnose because they may be missed or misidentified as a cyst by computed tomography (CT). Their magnetic resonance imaging (MRI) pattern has not been well described. We report the clinical, biological, and radiologic features of 10 patients with JCTs. Eight were women, and median age was 24.5 years. All had severe hypokalemic hypertension related to marked secondary hyperaldosteronism. Median plasma renin and aldosterone concentrations were 392 (minimum-maximum [min-max], 70.5-4,800) mIU/L and 1,490 (min-max, 671-2,492) pmol/L, respectively. Plasma prorenin concentration was 835.5 (min-max, 133-6,546) mIU/L. Median tumor size was 17.5mm. On CT, JCTs were spontaneously isodense, with little enhancement after contrast media injection. On MRI, JCTs were iso- (7/10) or hypointense (3/10) on T1-weighted images (WIs). On T2-WIs, JCTs were hypointense (2/10), isointense (4/10), or heterogeneously hyperintense (4/10). A thin peripheral "pseudo-capsule" (hypointense on T2-WIs) was observed in 6 of 10 cases. Contrast enhancement was low, slightly heterogeneous, and delayed. On diffusion-WIs, tumors were hyperintense with a restricted apparent diffusion coefficient. When hypertension with secondary hyperaldosteronism remains unexplained after CT, MRI of the kidney should be considered, especially for young women.


Assuntos
Sistema Justaglomerular/patologia , Neoplasias Renais/diagnóstico , Imagem por Ressonância Magnética/métodos , Adolescente , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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