Catheter-Based Renal Sympathetic Denervation for Resistant Hypertension Durability of Blood Pressure Reduction Out to 24 Months

Renal sympathetic hyperactivity is seminal in the maintenance and progression of hypertension. Catheter-based renal sympathetic denervation has been shown to significantly reduce blood pressure (BP) in patients with hypertension. Durability of effect beyond 1 year using this novel technique has never been reported. A cohort of 45 patients with resistant hypertension (systolic BP GT = 160 mm Hg on GT = 3 antihypertension drugs, including a diuretic) has been originally published. Herein, we report longer-term follow-up data on these and a larger group of similar patients subsequently treated with catheter-based renal denervation in a nonrandomized manner. We treated 153 patients with catheter-based renal sympathetic denervation at 19 centers in Australia, Europe, and the United States. Mean age was 57 +/- 11 years, 39% were women, 31% were diabetic, and 22% had coronary artery disease. Baseline values included mean office BP of 176/98 +/- 17/15 mm Hg, mean of 5 antihypertension medications, and an estimated glomerular filtration rate of 83 +/- 20 mL/min per 1.73 m(2). The median time from first to last radiofrequency energy ablation was 38 minutes. The procedure was without complication in 97% of patients (149 of 153). The 4 acute procedural complications included 3 groin pseudoaneurysms and 1 renal artery dissection, all managed without further sequelae. Postprocedure office BPs were reduced by 20/10, 24/11, 25/11, 23/11, 26/14, and 32/14 mm Hg at 1, 3, 6, 12, 18, and 24 months, respectively. In conclusion, in patients with resistant hypertension, catheter-based renal sympathetic denervation results in a substantial reduction in BP sustained out to GT = 2 years of follow-up, without significant adverse events. (Hypertension. 2011;57:911-917.

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Patient perspectives on treatment adherence in hypertension: Preliminary results of an ESH survey in five countries

OBJECTIVE: The ESH Working group on Lifestyle, Cardiovascular Therapy and Adherence, in partnership with Servier, has developed a web-based questionnaire in different languages to investigate patients' perspectives on hypertension and treatment adherence. The objective of this survey was to decipher patients' perception, motivations and barriers to drug treatment adherence in hypertension. DESIGN AND METHOD: Eligible participants were men and women aged > 18 years, living in France, Germany, Italy, Spain and UK, with a diagnosis of hypertension made by a physician and internet access. Data were collected through patients' websites and organizations from January to March 2022. RESULTS: We included 595 participants (329 women, 55.3%, mean age 65 y); 72% were hypertensive for > 5 years, 93% were treated with antihypertensive medications for > 3 months and 50% had uncontrolled (140/90 mmHg) office BP at 3 months. The median number of all medications taken every day was 4 of which 2 were antihypertensive drugs. On a 10-point Likert scale, participants reported a modest impact of hypertension on their quality of life (3) or social and family life (3.1). The median level of stress was 5.2. In 76.6% of participants home BP was measured several times weekly (25%) or monthly (31%) or more. Antihypertensive medications were stopped unintentionally by 40% or taken irregularly by 44% of patients. The reasons for non-adherence to medications were forgetfulness (45%), side effects (17%) and running out of medications (15%). In 50% of cases, patients do not inform their physicians when stopping medications. The most useful approaches to support adherence reported by participants were single-pill combinations and smaller and cheaper pills. Information on hypertension and its treatment were considered sufficient for 33% of patients. CONCLUSIONS: In patients with internet access and willing to participate, our survey shows that despite having an uncontrolled office 3 month BP in 50% of them, participants report: 1) a modest impact of hypertension on their quality of life and a moderate level of anxiety, 2) frequent and usually non intentional non-adherence to prescribed antihypertensive medications, and 3) the necessity to improve the information provided to them

Hypertension healthcare professional beliefs and behaviour regarding patient medication adherence: a survey conducted among European Society of Hypertension Centres of Excellence.

Little is known on the beliefs, perceptions and practices of hypertension specialists in addressing non-adherence to therapy. Therefore, a survey was undertaken amongst healthcare professionals (HCPs) managing hypertension in the European Society of Hypertension (ESH) Centres of Excellence. Cross-sectional data were obtained between December 2020 and April 2021 using an online anonymous structured questionnaire including 26 questions/136 items, that was sent to all ESH Excellence centres. Overall 67 from 187 centres (37.3%) responded and 200 HCPs from 30 countries answered the questionnaire. Participants (60% men) were mainly physicians (91%) and nurses (8%) from University hospitals (77%). Among physicians, 83% had >10 years professional experience. Average time dedicated to discuss medications was 1-5 min in 48% and 6-10 min in 29% of cases. Interviews with patients about adherence were the most frequently used assessment method. Chemical detection of medications in urine was available in 36% of centres. One third of physicians involved their patients regularly in treatment decisions. The most frequent methods to improve adherence included simplification of medication therapy, more frequent visits, and home blood pressure monitoring. The level of implementation of tools to detect and improve adherence in hypertension management by HCPs in ESH excellence centres is low. Structured educational activities focussing on adherence management and access to the newest objective measures to detect non-adherence might improve these deficits

Is the excess cardiovascular morbidity in pheochromocytoma related to blood pressure or to catecholamines?

Item does not contain fulltextBackground: It is generally accepted that pheochromocytoma is associated with an increased cardiovascular risk. This is however not based on studies with an appropriate control group of patients with essential hypertension. Aim of the Study: We examined whether patients with pheochromocytoma have an excess cardiovascular morbidity as compared to hypertensive patients. Methods: In a retrospective case-control study we reviewed the medical charts of 109 pheochromocytoma patients for cardiovascular events within 5 years prior to the diagnosis. These patients were matched to control patients with essential hypertension for gender and year of birth and diagnosis. Outcome variables were ischemic heart disease, cerebrovascular accidents, and transient ischemic attacks. Classical cardiovascular risk factors were also assessed. Results: A significantly higher rate of patients with pheochromocytoma suffered a cardiovascular event (13.8%; 95% confidence interval: 7.9%-21.6%) as compared to hypertensive patients (1.1%, 95% confidence interval: 0.1%-3.9%) (P < .001). Blood pressure level was lower in pheochromocytoma patients (153/91 +/- 35/15 mm Hg) than in hypertensive patients (170/103 +/- 18/8 mm Hg) (P < .001), even after correction for use of antihypertensive medication (P < .02). The difference in event rates could not be attributed to differences in other cardiovascular risk factors. Conclusions: Pheochromocytoma patients have a clearly higher rate of cardiovascular events than patients with essential hypertension. This cannot be attributed to differences in blood pressure or other cardiovascular risk factors. The most likely explanation for the excess event rate is the prolonged exposure to the toxic effects of tumoral catecholamines. These data underpin the importance of a timely diagnosis and treatment of pheochromocytoma

Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial

Background The distinction between unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia as causes of primary aldosteronism is usually made by adrenal CT or by adrenal vein sampling (AVS). Whether CT or AVS represents the best test for diagnosis remains unknown. We aimed to compare the outcome of CT-based management with AVS-based management for patients with primary aldosteronism. Methods In a randomised controlled trial, we randomly assigned patients with aldosteronism to undergo either adrenal CT or AVS to determine the presence of aldosterone-producing adenoma (with subsequent treatment consisting of adrenalectomy) or bilateral adrenal hyperplasia (subsequent treatment with mineralocorticoid receptor antagonists). The primary endpoint was the intensity of drug treatment for obtaining target blood pressure after 1 year of follow-up, in the intention-to-diagnose population. Intensity of drug treatment was expressed as daily defined doses. Key secondary endpoints included biochemical outcome in patients who received adrenalectomy, health-related quality of life, cost-effectiveness, and adverse events. This trial is registered with ClinicalTrials.gov, number NCT01096654. Findings We recruited 200 patients between July 6, 2010, and May 30, 2013. Of the 184 patients that completed follow-up, 92 received CT-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist) and 92 received AVS-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist). We found no differences in the intensity of antihypertensive medication required to control blood pressure between patients with CT-based treatment and those with AVS-based treatment (median daily defined doses 3.0 [IQR 1.0-5.0] vs 3.0 [1.1-5.9], p=0.52; median number of drugs 2 [IQR 1-3] vs 2 [1-3], p=0.87). Target blood pressure was reached in 39 (42%) patients and 41 (45%) patients, respectively (p=0.82). On secondary endpoints we found no differences in health-related quality of life (median RAND-36 physical scores 52.7 [IQR 43.9-56.8] vs 53.2 [44.0-56.8], p=0.83; RAND-36 mental scores 49.8 [43.1-54.6] vs 52.7 [44.9-55.5], p=0.17) for CT-based and AVS-based treatment. Biochemically, 37 (80%) of patients with CT-based adrenalectomy and 41 (89%) of those with AVS-based adrenalectomy had resolved hyperaldosteronism (p=0.25). A non-significant mean difference of 0.05 (95% CI -0.04 to 0.13) in quality-adjusted life-years (QALYs) was found to the advantage of the AVS group, associated with a significant increase in mean health-care costs of (sic)2285 per patient (95% CI 1323-3248). At a willingness-to-pay value of (sic)30 000 per QALY, the probability that AVS compared with CT constitutes an efficient use of health-care resources in the diagnostic work-up of patients with primary aldosteronism is less than 0.2. There was no difference in adverse events between groups (159 events of which nine were serious vs 187 events of which 12 were serious) for CT-based and AVS-based treatment. Interpretation Treatment of primary aldosteronism based on CT or AVS did not show significant differences in intensity of antihypertensive medication or clinical benefits for patients after 1 year of follow-up. This finding challenges the current recommendation to perform AVS in all patients with primary aldosteronism

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 CTA, MRA and/or catheter-based angiography were eligible.Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46\ub116 years (12% 6565yo), 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 6565yo had more often multifocal FMD, lower eGFR 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.TRANSLATIONAL PERSPECTIVE: Fibromuscular dysplasia (FMD) is nowadays considered as a systemic arterial disease, warranting brain-to-pelvis vascular imaging in all patients. However, most current evidence is derived from a limited number of expert centres. Furthermore, one size may not fit all. Based on analysis of the first thousand patients enrolled in the European/International FMD registry (46 centres; 22 countries) we characterized distinct patient profiles according to FMD subtype, age and gender and identified predictors of widespread disease, aneurysms and dissections, paving the way for individualized management and follow-up. Further studies will allow refining patient characterization according to ethnicity, genetic profile and imaging biomarkers