Home blood pressure measurement self-reporting in real-life practices using the Hy-Result app: self-monitoring and digital pathway.

Background: Little real-life information is available on the clinical characteristics of information and communication technologies (ICTs) users, particularly in the context of hypertension and home blood pressure measurement (HBPM). This retrospective observational study describes HBPM practices obtained through the Hy-Result® system, a validated app designed to help patients perform HBPM and understand their results through an automatic interpretation of the readings using web interface. Methods: We analyzed 19,176 HBPM reports (sequence of 1 to 7 days of measurements; 3 in the morning, 3 in the evening) collected in real life circumstances from two groups of users: primary care (Prim) and hypertension center (Hosp). Results: Population: among the 19,176 reports, 63.2% declared receiving antihypertensive medication, having diabetes (15.2%), chronic kidney disease (9.7%) or history of stroke (7.6%). Treated users were older than normotensives [mean ± standard deviation (SD) age 64±12 vs. 58±14 years] with higher prevalence of comorbidities. Compliance with the HBPM schedule: the majority of reports (90.2%) totaled 15 systolic blood pressure (SBP) and diastolic blood pressure (DBP) readings or more, of which 96.1% were Hosp users and 89.3% Prim users, with a significant difference between both groups (P<0.001). The compliance rate for 7 days of measurement was higher in the Hosp group (57.6% vs. 30.5%; P<0.001). Blood pressure (BP) levels: in the 17,289 reports with a minimum of 15 readings, 42.7% had an average SBP and/or DBP above the recommended thresholds (below 135 and/or 85 mmHg), among whom, 36.8% were untreated subjects. Hosp users had better BP control than Prim (P<0.001). Users that are followed in the European Society of Hypertension (ESH) excellence center (Hosp) had better BP control than those in a Prim setting (P<0.001). HBPM oscillometric devices: in both groups, treated patients and untreated users, used the arm cuff devices more frequently than the wrist device. Conclusions: Our real-life study shows that 90% of the HBPM reports include the required minimum number of BP readings to allow the calculation of a reliable average among whom 40% have uncontrolled BP levels. The self-management Hy-Result web app demonstrates significant potential for inclusion in the patient care process and reinforces the patient's engagement to independently monitor and self-reported their BP. When the mean BP is not within the recommended range, the users were automatically prompted by text messages to seek medical advice by the software. Further research should determine the extent to which users adhere to text messages advice.

Revisiting malignant hypertension: rationale and design of the 'HAMA cohort', on behalf of the ESH working group 'hypertension and the kidney'.

BACKGROUND: Malignant hypertension has not disappeared and is associated with a poor prognosis. Yet, so far, it has received limited attention from the medical community. Guidelines are mainly based on expert consensus and low quality evidences. METHOD: We set up a prospective, multicenter, observational cohort of patients with malignant hypertension. We collect at admission medical history, demographic data, ongoing treatment, clinical parameters, symptoms, care pathways, target organ status and at discharge and during follow up treatment administrated, adverse events, blood pressure level, target organ status. We aim to recruit 500 patients with malignant hypertension in 5 years, with a 5-year follow-up. Our primary objective is to assess the 5 years prognosis of these patients. DISCUSSION: The HAMA (Hypertension Arterielle MAligne, meaning malignant hypertension) registry aims to describe the epidemiology and to assess the prognosis of malignant hypertension in a contemporary multidisciplinary cohort, with emphasis on the diversity of current management and care pathway among the different medical specialties. It may help improving our pathophysiological knowledge, and pave the way to update the definition of this particular form of hypertension. The multidisciplinary network developed in the wake of this project is expected to facilitate the set up therapeutic trials, laying the ground for evidence-based recommendations.

Validation and Feasibility of an Automated System for the Assessment of Vascular Structure and Mechanical Properties in the Digital Arteries: An Ultrahigh-Frequency Ultrasound Study.

Ultrahigh-frequency ultrasound (UHFUS) allows sharp visualization of human small muscular arteries. This may help in elucidating some aspects of the pathophysiology of arterial aging, such as the stiffness gradient between large and small conduit arteries and its consequences on the microcirculation, as well as vascular diseases affecting medium-sized arteries. However, UHFUS use is still limited, partly because of the lack of validated tools to quantify vascular structure and mechanical properties of small muscular arteries. In this validation study, scans of digital arteries were obtained with UHFUS (VevoMD, Visualsonics-Fujifilm, Toronto, ON, Canada), analyzed using Carotid Studio software (Quipu, Pisa, Italy) and compared with the manual measurement. Agreement between the two techniques on measures of diameter, distension and intima-media thickness (IMT) was evaluated using Bland-Altman analyses; inter- and intra-operator reproducibility was evaluated using coefficients of variation (CVs). Overall, no trend or significant bias was observed between Carotid Studio and manual analysis. All limits of agreement were acceptable. The intra-observer CV of diastolic diameter and IMT were 4.1% and 4.2%, respectively. The inter-observer CV for diastolic diameter and IMT were 7.3% and 5.4%, respectively. Intra- and inter-observer CVs for distension were higher (25.7% and 26.7%, respectively). These results suggest that the Carotid Studio software is a valid and reproducible tool to study UHFUS scans of digital arteries, with potential utility both in rare vascular diseases of medium-sized arteries and in the study of the pathophysiology of arterial aging in general.

Insights from intravascular pressure measurement of renal artery revascularization in patients with fibromuscular dysplasia: The DYSART study.

OBJECTIVE: The indication of percutaneous renal transluminal angioplasty (PTRA) in fibromuscular dysplasia (FMD) is mainly based on renal artery stenosis (RAS) due to atherosclerosis criteria, which are not specific to FMD. Consequently, the selection of patients who could benefit from this treatment and its effectiveness remain uncertain. The aims of this study were to: (1) report the effects of PTRA guided by trans-stenotic pressure measurements on hypertension 7 months after treatment; (2) assess the impact of pressure measurement to guide treatment efficacy in comparison to visual angiographic parameters; and (3) evaluate the reproducibility and accuracy of the stenosis measurement using a 4F catheter in comparison to a pressure guidewire. METHODS: This prospective multi-centric study analyzed 24 patients with hypertension with RAS due to FMD that required PTRA. Clinical, duplex ultrasound, and angiographic indices were collected, and patients were followed up for 7 months (±1 month). Angiographic indices were measured twice both by a pressure guidewire and a 4F catheter. Assessment of procedural and clinical success of angioplasty was performed for all patients. RESULTS: Twenty-three patients (96%) had procedural success (considered as a post-PTRA translesional systolic gradient ≤10 mmHg or reduced by at least 80%) with a significant decrease in the systolic gradient after angioplasty (26.50 mmHg; [interquartile range, 16.75-38.75] vs 0.00 [interquartile range, 0.00-2.00]; P < .01). Three patients (12%) had complications, including two renal artery dissections and one partial renal infarction. Twenty-one patients (88%) were clinical responders to angioplasty at follow-up. Visual stenosis assessment showed a poor correlation with systolic gradient measurement before and after PTRA (R from -0.05 to 0.41; P = 0.06-0.82). High correlations were found between pressure measurements made by a 4F catheter and guidewire (R from 0.64 to 0.89; P ≤ .003). CONCLUSIONS: In patients selected by clinical indicators and duplex ultrasound, reaching a translesional systolic gradient ≤10 mmHg or reduced by at least 80% after angioplasty, promotes a high success rate for PTRA in hypertension due to FMD RAS.

Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases.

Fibromuscular dysplasia (FMD) is an arteriopathy associated with hypertension, stroke and myocardial infarction, affecting mostly women. We report results from the first genome-wide association meta-analysis of six studies including 1556 FMD cases and 7100 controls. We find an estimate of SNP-based heritability compatible with FMD having a polygenic basis, and report four robustly associated loci (PHACTR1, LRP1, ATP2B1, and LIMA1). Transcriptome-wide association analysis in arteries identifies one additional locus (SLC24A3). We characterize open chromatin in arterial primary cells and find that FMD associated variants are located in arterial-specific regulatory elements. Target genes are broadly involved in mechanisms related to actin cytoskeleton and intracellular calcium homeostasis, central to vascular contraction. We find significant genetic overlap between FMD and more common cardiovascular diseases and traits including blood pressure, migraine, intracranial aneurysm, and coronary artery disease.

Renal Outcome and New-Onset Renal and Extrarenal Dissections in Patients With Nontrauma Renal Artery Dissection Associated With Renal Infarction.

[Figure: see text].

Male Sex Is Associated With Cervical Artery Dissection in Patients With Fibromuscular Dysplasia.

Background Cervical artery dissection (CeAD) is a frequent manifestation of fibromuscular dysplasia (FMD). However, risk factors for CeAD are unknown. We investigated factors associated with CeAD in the ARCADIA (Assessment of Renal and Cervical Artery Dysplasia) registry. Methods and Results The ARCADIA registry includes women or men aged ≥18 years, with a diagnosis of renal, cervical, or intracranial artery FMD, who were prospectively recruited at 16 university hospitals in France and Belgium. Diagnosis of acute or past CeAD at inclusion was established on imaging according to standard diagnostic criteria. Associations between potential determinants and CeAD were assessed by logistic regression analyses. Among 469 patients (75 men) with FMD, 65 (13.9%) had CeAD. Patients with CeAD were younger, more likely to be men, have a history of migraine, and less likely to have a history of hypertension than patients without CeAD. In the multivariable analysis, male sex (odds ratio [OR], 2.66; 95% CI, 1.34-5.25), history of migraine (OR, 1.90; 95% CI, 1.06-3.39), age ≥50 years (OR, 0.41; 95% CI, 0.23-0.73), history of hypertension (OR, 0.35; 95% CI, 0.20-0.64), and involvement of ≥3 vascular beds (OR, 2.49; 95% CI, 1.15-5.40) were significantly associated with CeAD. To validate the association between CeAD and sex, we performed a systematic review. We collected additional data on sex from 2 published studies and unpublished data from the US Registry for Fibromuscular Dysplasia and the European/International FMD Registry. In the pooled analysis (289 CeAD, 1933 patients), male sex was significantly associated with CeAD (OR, 2.04; 95% CI, 1.41-2.95; I2=0%). Conclusions In patients with FMD, male sex and multisite involvement are associated with CeAD, in addition to other previously known risk factors. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02884141.

Rare loss-of-function mutations of PTGIR are enriched in fibromuscular dysplasia.

AIMS: Fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD) are related, non-atherosclerotic arterial diseases mainly affecting middle-aged women. Little is known about their physiopathological mechanisms. We aimed to identify rare genetic causes to elucidate molecular mechanisms implicated in FMD and SCAD. METHODS AND RESULTS: We analysed 29 exomes that included familial and sporadic FMD. We identified one rare loss-of-function variant (LoF) (frequencygnomAD = 0.000075) shared by two FMD sisters in the prostaglandin I2 receptor gene (PTGIR), a key player in vascular remodelling. Follow-up was conducted by targeted or Sanger sequencing (1071 FMD and 363 SCAD patients) or lookups in exome (264 FMD) or genome sequences (480 SCAD), all independent and unrelated. It revealed four additional LoF allele carriers, in addition to several rare missense variants, among FMD patients, and two LoF allele carriers among SCAD patients, including one carrying a rare splicing mutation (c.768 + 1C>G). We used burden test to test for enrichment in patients compared to gnomAD controls, which detected a putative enrichment in FMD (PTRAPD = 8 × 10-4), but not a significant enrichment (PTRAPD = 0.12) in SCAD. The biological effects of variants on human prostaclycin receptor (hIP) signalling and protein expression were characterized using transient overexpression in human cells. We confirmed the LoFs (Q163X and P17RfsX6) and one missense (L67P), identified in one FMD and one SCAD patient, to severely impair hIP function in vitro. CONCLUSIONS: Our study shows that rare genetic mutations in PTGIR are enriched among FMD patients and found in SCAD patients, suggesting a role for prostacyclin signalling in non-atherosclerotic stenosis and dissection.

The European/International Fibromuscular Dysplasia Registry and Initiative (FEIRI)-clinical phenotypes and their predictors based on a cohort of 1000 patients.

AIMS: Since December 2015, the European/International Fibromuscular Dysplasia (FMD) Registry enrolled 1022 patients from 22 countries. We present their characteristics according to disease subtype, age and gender, as well as predictors of widespread disease, aneurysms and dissections. METHODS AND RESULTS: All patients diagnosed with FMD (string-of-beads or focal stenosis in at least one vascular bed) based on computed tomography angiography, magnetic resonance angiography, and/or catheter-based angiography were eligible. Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46 ± 16 years (12% ≥65 years old), 86% were hypertensive, 72% had multifocal, and 57% multivessel FMD. Compared to patients with multifocal FMD, patients with focal FMD were younger, more often men, had less often multivessel FMD but more revascularizations. Compared to women with FMD, men were younger, had more often focal FMD and arterial dissections. Compared to younger patients with FMD, patients ≥65 years old had more often multifocal FMD, lower estimated glomerular filtration rate and more atherosclerotic lesions. Independent predictors of multivessel FMD were age at FMD diagnosis, stroke, multifocal subtype, presence of aneurysm or dissection, and family history of FMD. Predictors of aneurysms were multivessel and multifocal FMD. Predictors of dissections were age at FMD diagnosis, male gender, stroke, and multivessel FMD. CONCLUSIONS: The European/International FMD Registry allowed large-scale characterization of distinct profiles of patients with FMD and, more importantly, identification of a unique set of independent predictors of widespread disease, aneurysms and dissections, paving the way for targeted screening, management, and follow-up of FMD.

Aldosterone-Related Myocardial Extracellular Matrix Expansion in Hypertension in Humans: A Proof-of-Concept Study by Cardiac Magnetic Resonance.

OBJECTIVES: This study sought to assess the respective effects of aldosterone and blood pressure (BP) levels on myocardial fibrosis in humans. BACKGROUND: Experimentally, aldosterone promotes left ventricular (LV) hypertrophy, and interstitial myocardial fibrosis in the presence of high salt intake. METHODS: The study included 20 patients with primary aldosteronism (PA) (high aldosterone and high BP), 20 patients with essential hypertension (HTN) (average aldosterone and high BP), 20 patients with secondary aldosteronism due to Bartter/Gitelman (BG) syndrome (high aldosterone and normal BP), and 20 healthy subjects (HS) (normal aldosterone and normal BP). Participants in each group were of similar age and sex distributions, and asymptomatic. Cardiac magnetic resonance including cine and T1 mapping was performed blind to the study group to quantify global LV mass index, as well as intracellular mass index and extracellular mass index considered as a measure of myocardial fibrosis in vivo. RESULTS: Median plasma aldosterone concentration was as follows: PA = 709 pmol/l (interquartile range [IQR]: 430 to 918 pmol/l); HTN = 197 pmol/l (IQR: 121 to 345 pmol/l); BG = 297 pmol/l (IQR: 180 to 428 pmol/l); and HS = 105 pmol/l (IQR: 85 to 227 pmol/l). Systolic BP was as follows: PA = 147 ± 15 mm Hg; HTN = 133 ± 19 mm Hg; BG = 116 ± 9 mm Hg; and HS = 117 ± 12 mm Hg. LV end-diastolic volume showed underloading in BG and overloading in patients with PA (63 ± 13 ml/m2 vs. 82 ± 15 ml/m2; p < 0.0001). Intracellular mass index increased with BP across groups (BG: 36 [IQR: 29 to 41]; HS: 40 [IQR: 36 to 46]; HTN: 51 [IQR: 42 to 54]; PA: 50 [IQR: 46 to 67]; p < 0.0001). Extracellular mass index was similar in BG, HS, and HTN (16 [IQR: 12 to 20]; 15 [IQR: 11 to 18]; and 14 [IQR: 12 to 17], respectively) but 30% higher in PA (21 [IQR: 18 to 29]; p < 0.0001) remaining significant after adjustment for mean BP. CONCLUSIONS: Only primary pathological aldosterone excess combined with high BP increased both extracellular myocardial matrix and intracellular mass. Secondary aldosterone excess with normal BP did not affect extracellular myocardial matrix. (Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism; NCT02938910).

Cortisol and Aldosterone Responses to Hypoglycemia and Na Depletion in Women With Non-Classic 21-Hydroxylase Deficiency.

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.

Adrenal adaptation in potassium-depleted men: role of progesterone?

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.

Resistant Hypertension and Atherosclerotic Renal Artery Stenosis: Effects of Angioplasty on Ambulatory Blood Pressure. A Retrospective Uncontrolled Single-Center Study.

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.

[Malignant hypertension: A bright future]. / L'hypertension artérielle maligne , un futur prometteur.

Malignant hypertension has not disappeared, it has been forgotten. Its incidence is increasing again. It considerably worsens the prognosis of young patients (35 to 55 years old on average). There might be susceptibility factors, several hypotheses are under study. New diagnostic criteria and therapeutic options have been proposed and will have to be validated. Faced with these important challenges for patients, the first prospective multicentric register on this pathology will be set up in France in September 2019.

[Spironolactone in resistant essential hypertension]. / HTA essentielle résistante : place de la spironolactone.

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.

Deep Vascular Phenotyping in Patients With Renal Multifocal Fibromuscular Dysplasia.

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.

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.