Publications by authors named "Roland E Schmieder"

391 Publications

The influence of aircraft noise exposure on the systemic and renal haemodynamics.

Eur J Prev Cardiol 2020 Nov 5. Epub 2020 Nov 5.

Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany.

Aims: Epidemiological studies found a link between aircraft noise exposure and increased incidence of arterial hypertension and cardiovascular disease, but the underlying pathophysiological mechanisms are not fully understood. Clinical studies have shown that mental stress affects the systemic and renal haemodynamic, but no such study was performed with noise exposure as stress factor. We analysed systemic and renal effects of 25 min standardized aircraft noise in a sham controlled clinical study including 80 healthy men and 34 male patients with hypertension.

Methods And Results: Systemic haemodynamic parameters were measured using electrocardiography and impedance cardiography. The renal haemodynamic was assessed using steady state input clearance with infusion of para-aminohippuric acid and inulin for glomerular filtration rate and renal plasma flow, respectively. In the systemic circulation of hypertensive patients, there was an increase in total peripheral resistance (TPR) (1420 ± 387 vs. 1640 ± 516 dyn·s·cm-5, P = 0.001) and a decrease in cardiac index (CI) (2.9 ± 0.8 vs. 2.6 ± 0.8 L/(min·m2, P < 0.001) 25 min after the start of noise exposure, which was not present during sham procedure (P = 0.10, P = 0.86). In healthy individuals a procedure induced increase in TPR and decrease in CI was present after noise (TPR: 995 ± 239 vs. 1106 ± 308 dyn·s·cm-5, P = 0.001, CI: 3.6 ± 0.7 vs. 3.3 ± 0.9 L/(min·m2, P < 0.001) and sham application (TPR: P = 0.002, CI: P < 0.001). However, in healthy individuals changes in TPR (P = 0.450) and CI (P = 0.605) from baseline until 25 min after the start of the intervention did not differ between noise and sham exposure. In the renal circulation of hypertensive patients and healthy individuals the response did not differ between noise and sham procedure.

Conclusions: In hypertensive but not healthy men we observed a systemic vasoconstrictive response after aircraft noise exposure accompanied by a decrease in CI. No significant changes were observed in the renal circulation. Our results suggest that male hypertensive patients are more susceptible for noise-induced changes of vascular resistance in the systemic circulation.
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http://dx.doi.org/10.1093/eurjpc/zwaa036DOI Listing
November 2020

Dependency of flow mediated vasodilatation from basal nitric oxide activity.

Clin Physiol Funct Imaging 2021 Feb 23. Epub 2021 Feb 23.

Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.

Flow-mediated vasodilatation (FMD) has become one of the most widely assessed parameters to analyze endothelial and vascular function in cardiovascular medicine. The degree of contribution of nitric oxide (NO) to FMD is inconclusive and varies widely depending on the device used. In this study we used a semi-automatic ultrasound device to analyze to what extent basal NO activity contributes to FMD of the brachial artery. FMD was assessed with the UNEX EF device in a cross-over single blinded randomized study at baseline and then during infusion of either a NO-synthase-inhibitor (NG-monomethyl-L-arginine (L-NMMA)) or saline. The analysis was repeated after 1 week with the alternative infusion of L-NMMA or saline. All measurements were analyzed both automatically and by a technician manually. In total 25 healthy men subjects completed the study. Diastolic blood pressure and heart rate significantly changed during infusion of L-NMMA. Infusion of L-NMMA reduced FMD significantly (-37%, p=0.002). Saline solution had no effect on FMD (+14%, p=0.392). Change in FMD was significantly different between the groups (ΔFMD vs. ΔFMD , p=0.032). There was a statistically significant correlation between automatically analyzed results and those obtained by an experienced technician (FMD : r=0.822, p<0.001; FMD : r=0.645, p=0.007). The influence of NO on FMD is approximately 40% if assessed using the UNEX EF. Prior to use FMD as a marker of endothelial dysfunction we should explore different methods including various duration of forearm ischaemia to increase NO dependency of FMD.
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http://dx.doi.org/10.1111/cpf.12696DOI Listing
February 2021

Renal outcomes and blood pressure patterns in diabetic and nondiabetic individuals at high cardiovascular risk.

J Hypertens 2021 Apr;39(4):766-774

Department of Nephrology and Hypertension, University Hospital, Friedrich-Alexander University, Erlangen, Germany.

Background: Diabetes and hypertension are risk factors for renal and cardiovascular outcomes. Data on the association of achieved blood pressure (BP) with renal outcomes in patients with and without diabetes are sparse. We investigated the association of achieved SBP, DBP with renal outcomes and urinary albumin excretion (UAE) in people with vascular disease.

Methods: In this pooled analysis, we assessed renal outcome data from high-risk patients aged 55 years or older with a history of cardiovascular disease, 70% of whom had hypertension, randomized to The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and to Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease trials investigating telmisartan, ramipril and their combination with a median follow-up of 56 months. Standardized office BP was measured every 6 months, estimated glomerular filtration rate (eGFR) and UAE at baseline, 2 years and study end. Associations of mean achieved BP on treatment were investigated on major renal outcomes including end-stage renal disease (ESRD), decline of eGFR by at least 40%, doubling of creatinine and the composites thereof and on UAE. Analyses were by Cox regression analysis, analysis of variance and Chi2-test. Of 30 937 patients with complete data, 19 450 patients without and 11 487 with diabetes were enrolled between 1 December 2001 and 31 July 2003 and followed until 31 July 2008. Data were pooled as the outcomes for telmisartan 80 mg/day (n = 2903) or placebo (n = 2907) for Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease and ramipril 10 mg/day (n = 8407), telmisartan 80 mg/day (n = 8386) or the combination of both (n = 8334) were similar.

Results: For both those with and without diabetes, the hazard ratios for the composites ESRD or doubling of serum creatinine (707 events overall) and ESRD or 40% eGFR loss (2371 events overall) reached a nadir at achieved SBP of 120 to less than 140 mmHg, and increased with higher and lower SBP with similar relative risk with or without diabetes. For example, risk for the former composite reached a hazard ratios 3.06 (confidence interval 1.90-4.92) with a mean achieved SBP more than 160 mmHg compared with 120 to less than 130 mmHg with diabetes and hazard ratios 2.14 (1.09-4.26) without diabetes. In contrast, the development of new microalbuminuria and macroalbuminuria (3002 and 846 events overall) associated linearly over the whole range of achieved SBP (apart from a slight increase in risk at SBP less than 120 mmHg only in those without diabetes). Absolute risks for the composite and albuminuria outcomes were consistently greater in those with diabetes as compared with without diabetes with high event rates over the whole SBP spectrum. The increased renal risk at low SBP was not related to a meaningful reduction of mandated study drugs or open label renin-angiotensin-aldosterone system inhibition.

Conclusion: In patients at high cardiovascular risk, SBP levels more than 140 mmHg and less than 120 are associated with increased risk for renal outcomes. Renal risk was greater in diabetes across the whole range of achieved SBP and DBP. These data suggest similar target BP range in patients with and without diabetes to prevent renal outcomes, a frequent complication in high-risk vascular patients.

Clinical Trial Registration: Clinical Trial registration: http://clinicaltrials.gov.Unique identifier: NCT00153101.
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http://dx.doi.org/10.1097/HJH.0000000000002697DOI Listing
April 2021

Renal and intraglomerular haemodynamics in chronic heart failure with preserved and reduced ejection fraction.

ESC Heart Fail 2021 Feb 9. Epub 2021 Feb 9.

Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander-University, Ulmenweg 18, Erlangen-Nuremberg, 91054, Germany.

Aims: Congestive heart failure (CHF) and impaired renal function are two often co-existing medical conditions and associated with adverse cardiovascular outcome. The aim of the current study was to assess renal and intraglomerular haemodynamics by constant infusion input clearance technique in subjects with CHF.

Methods And Results: The group of subjects with CHF consisted of 27 individuals with HFpEF and 27 individuals with HFrEF and were compared with 31 healthy controls. Subjects underwent renal clearance examination to measure glomerular filtration rate (GFR) and renal blood and plasma flow (RBF and RPF) and to calculate intraglomerular haemodynamics such as resistances of the afferent (R ) and efferent arterioles (R ) as well as intraglomerular pressure (P ). Measured GFR was lower in CHF subjects (68.1 ± 10.1 mL/min/1.73 m ) compared with controls (83.6 ± 13.4 mL/min/1.73 m , P  < 0.001) as was P (P  < 0.001). Total renal vascular resistance (RVR) was higher in CHF subjects (87.3 ± 20.1 vs. 73.8 ± 17.1 dyn × s/cm , P  < 0.001) mediated by an increased resistance at the afferent site (3201 ± 1084 vs. 2181 ± 796 dyn × s/cm , P  < 0.001). Comparing HFpEF and HFrEF subjects, R was higher in HFrEF subjects. The severity of CHF assessed by NT-proBNP revealed an inverse association with renal perfusion (RPF r = -0.421, P = 0.002, RBF r = -0.414, P = 0.002) and a positive relation with RVR (r = 0.346, P = 0.012) at the post-glomerular site (R : r = 0.318, P = 0.022).

Conclusions: Renal function assessed by measured GFR is reduced and renal vascular resistance at the preglomerular, afferent site is increased in HFpEF and, to greater extent, in HFrEF. Our data indicate a close cardiorenal interaction in CHF.
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http://dx.doi.org/10.1002/ehf2.13257DOI Listing
February 2021

Identifying Isolated Systolic Hypertension From Upper-Arm Cuff Blood Pressure Compared With Invasive Measurements.

Hypertension 2021 Feb 4;77(2):632-639. Epub 2021 Jan 4.

From the Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia (D.S.P., M.G.S., M.K.A., J.A.B., N.D., P.R.-T., J.E.S.).

Isolated systolic hypertension (ISH) is the most common form of hypertension and is highly prevalent in older people. We recently showed differences between upper-arm cuff and invasive blood pressure (BP) become greater with increasing age, which could influence correct identification of ISH. This study sought to determine the difference between identification of ISH by cuff BP compared with invasive BP. Cuff BP and invasive aortic BP were measured in 1695 subjects (median 64 years, interquartile range [55-72], 68% male) from the INSPECT (Invasive Blood Pressure Consortium) database. Data were recorded during coronary angiography among 29 studies, using 21 different cuff BP devices. ISH was defined as ≥130/<80 mm Hg using cuff BP compared with invasive aortic BP as the reference. The prevalence of ISH was 24% (n=407) according to cuff BP but 38% (n=642) according to invasive aortic BP. There was fair agreement (Cohen κ, 0.36) and 72% concordance between cuff and invasive aortic BP for identifying ISH. Among the 28% of subjects (n=471) with misclassification of ISH status by cuff BP, 20% (n=96) of the difference was due to lower cuff systolic BP compared with invasive aortic systolic BP (mean, -16.4 mm Hg [95% CI, -18.7 to -14.1]), whereas 49% (n=231) was from higher cuff diastolic BP compared with invasive aortic diastolic BP (+14.2 mm Hg [95% CI, 11.5-16.9]). In conclusion, compared with invasive BP, cuff BP fails to identify ISH in a sizeable portion of older people and demonstrates the need to improve cuff BP measurements.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16109DOI Listing
February 2021

12-Month Results From the Unblinded Phase of the RADIANCE-HTN SOLO Trial of Ultrasound Renal Denervation.

JACC Cardiovasc Interv 2020 Dec;13(24):2922-2933

Columbia University Medical Center/NewYork-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, New York, USA.

Objectives: This study reports the 12-month results of the RADIANCE-HTN (A Study of the ReCor Medical Paradise System in Clinical Hypertension) SOLO trial following unblinding of patients at 6 months.

Background: The blood pressure (BP)-lowering efficacy and safety of endovascular ultrasound renal denervation (RDN) in the absence (2 months) and presence (6 months) of antihypertensive medications were previously reported.

Methods: Patients with daytime ambulatory BP ≥135/85 mm Hg after 4 weeks off medication were randomized to RDN (n = 74) or sham (n = 72) and maintained off medication for 2 months. A standardized medication escalation protocol was instituted between 2 and 5 months (blinded phase). Between 6 and 12 months (unblinded phase), patients received antihypertensive medications at physicians' discretion. Outcomes at 12 months included medication burden, change in daytime ambulatory systolic BP (dASBP) and office or home systolic BP (SBP), visit-to-visit variability in SBP, and safety.

Results: Sixty-five of 74 RDN patients and 67 of 72 sham patients had 12-month dASBP measurements. The proportion of patients on ≥2 medications (27.7% vs. 44.8%; p = 0.041), the number of medications (0 vs. 1.4; p = 0.015), and defined daily dose (1.4 vs. 2.2; p = 0.007) were less with RDN versus sham. The decrease in dASBP from baseline in the RDN group (-16.5 ± 12.9 mm Hg) remained stable at 12 months. The RDN versus sham adjusted difference at 12 months was -2.3 mm Hg (95% confidence interval [CI]: -5.9 to 1.3 mm Hg; p = 0.201) for dASBP, -6.3 mm Hg (95% CI: -11.1 to -1.5 mm Hg; p = 0.010) for office SBP, and -3.4 mm Hg (95% CI: -6.9 to 0.1 mm Hg; p = 0.062) for home SBP. Visit-to-visit variability in SBP was smaller in the RDN group. No renal artery injury was detected on computed tomographic or magnetic resonance angiography.

Conclusions: Despite unblinding, the BP-lowering effect of RDN was maintained at 12 months with fewer prescribed medications compared with sham.
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http://dx.doi.org/10.1016/j.jcin.2020.09.054DOI Listing
December 2020

Reference values of retinal microcirculation parameters derived from a population random sample.

Microvasc Res 2021 03 25;134:104117. Epub 2020 Nov 25.

Department of Nephrology and Hypertension, Friedrich-Alexander-University, Erlangen-Nürnberg, Germany.

Retinal microcirculation reflects retinal perfusion abnormalities and retinal arterial structural changes at relatively early stages of various cardiovascular diseases. Our objective has been to establish reference values for major functional and structural parameters of retinal microcirculation in a randomly selected urban population sample. A total of 398 randomly selected individuals from an urban population aged 25 to 65 years, resident in Pilsen, Czech Republic, were screened for major cardiovascular risk factors. Retinal microcirculation was assessed using scanning laser Doppler flowmetry (SLDF), with data evaluable in 343 patients. Of this number, complete data were available for 256 individuals free from manifest cardiovascular disease, diabetes and drug treatment for hypertension and/or dyslipidemia, constituting the reference value population. Juxtapapillary retinal capillary blood flow has increased significantly with age whereas vessel and luminal diameters have decreased. No sex differences in retinal microcirculation parameters have been found. Therefore, reference values for retinal microcirculation parameters have been established by age groups. Unattended automated office systolic BP, after adjusting for age, correlated significantly with wall-to-lumen ratio (WLR) and wall thickness (WT). Moreover, after adjusting for age and mean BP, a positive relationship has been found between carotid femoral pulse wave velocity and WT, WLR and wall cross-sectional area, indicating the interaction between micro- and macro-vasculature. In conclusion, our study is the first to provide reference values of retinal microcirculation parameters in a random Caucasian population sample. Our results have shown that, at the population level, the first structural changes in retinal microcirculation are those in lumen diameters. Of note, a close relationship between BP and vascular remodeling of retinal arterioles and between aortic stiffness and WLR of retinal arterioles suggests an interaction between micro- and macro-vasculature.
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http://dx.doi.org/10.1016/j.mvr.2020.104117DOI Listing
March 2021

Renal denervation: where do we stand and what is the relevance to the nephrologist?

Nephrol Dial Transplant 2020 Nov 16. Epub 2020 Nov 16.

Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.

Catheter-based renal denervation to reduce high blood pressure (BP) has received well-deserved attention after a recent series of sham-controlled trials reported significant antihypertensive efficacy and very favourable tolerability and safety of the intervention. This emerging treatment option is of high relevance to nephrologists. Patients with chronic kidney disease (CKD) are at elevated risk of cardiovascular adverse events and often present with hypertension, which is very difficult to control with medication. Renal denervation promises a new tool to reduce BP and to prevent loss of renal function in this population. The current review considers the role of the kidney and neurohormonal activation in the development of hypertension and the rationale for renal denervation. The current state of the evidence for the effectiveness and tolerability of the procedure is considered from the nephrologists' perspective, with a focus on the potential future role of renal denervation in the management of CKD patients with hypertension.
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http://dx.doi.org/10.1093/ndt/gfaa237DOI Listing
November 2020

Novel approaches to management of hypertension.

Curr Opin Nephrol Hypertens 2021 Jan;30(1):54-62

Department of Nephrology and Hypertension, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.

Purpose Of Review: Of the roughly 1.4 billion people with hypertension worldwide, only about one in seven has their blood pressure (BP) successfully treated and adequately controlled. This review will focus on new therapeutic approaches of hypertension.

Recent Findings: Several recent clinical studies and guidelines have favoured the assessment of target organ damage and cardiovascular risk scores for the diagnosis and treatment approach of hypertension. Paradigm shifts recommended in the guidelines are the initiation of antihypertensive treatment with combination (not mono) therapy and the recommendation of single-pill combinations (SPC), which improve adherence and result in rapid and effective BP control. In clinical trials with optimized design and renal denervation (RDN) technology, the biological proof of concept has been established. Consistent, durable ambulatory and office BP reductions without procedure associated serious adverse events have been documented. The challenges are now to identify patients who respond best to interventional treatment.

Summary: Major key points in the treatment strategy for hypertension are: individualization of the therapy according to total cardiovascular risk, combination therapy as initial step, recommendation of SPC and RDN as promising interventional therapy.
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http://dx.doi.org/10.1097/MNH.0000000000000668DOI Listing
January 2021

Confounding Factors in Renal Denervation Trials: Revisiting Old and Identifying New Challenges in Trial Design of Device Therapies for Hypertension.

Hypertension 2020 Nov 28;76(5):1410-1417. Epub 2020 Sep 28.

Jichi Medical University School of Medicine, Tochigi, Japan (K.K.).

Recent randomized sham-controlled trials have demonstrated significant blood pressure reductions following renal denervation (RDN) in patients with hypertension, both in the presence and absence of antihypertensive therapy. These new data encouraged us to revisit previously published insights into potential clinical trial confounding factors that informed the design and conduct of forthcoming trials. Initially identified confounders related to procedural technique, medication variability, and selected patient subgroups have been addressed in contemporary trial design. Regarding procedural method and technology, blood pressure reductions may be improved by ensuring circumferential lesion creation in the distal renal arteries and branch vessels. Safety of the RDN procedure has been demonstrated in multiple independent meta-analyses including thousands of treated patients with low reported rates of renal vessel complications and maintenance of renal function. However, a newer generation of RDN trials has also introduced insights related to medication adherence, patient selection, and the definition of treatment response. Evolving evidence indicates that RDN therapy may be considered in higher risk populations of uncontrolled hypertension regardless of ethnicity and in patients expressing a strong preference for a nondrug therapy option. Despite advances in procedural technique and clinical trial conduct, inconsistent antihypertensive-drug adherence behavior remains perhaps the most critical clinical trial design issue for device-based hypertension therapies. As the balance in clinical equipoise increasingly favors RDN, justification of sham-controlled trial designs will be revisited, and novel study designs may be required to evaluate the safety and efficacy of novel devices and procedures intended to address the escalating prevalence of poorly controlled hypertension.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15745DOI Listing
November 2020

How to measure retinal microperfusion in patients with arterial hypertension.

Blood Press 2021 Feb 24;30(1):4-19. Epub 2020 Sep 24.

Department of Human Physiology and Pathophysiology, University Warmia and Mazury, Olsztyn, Poland.

Purpose: Assessment and monitoring of changes in microcirculatory perfusion, perfusion dynamic, vessel structure and oxygenation is crucial in management of arterial hypertension. Constant search for non-invasive methods has led the clinical focus towards the vasculature of the retina, which offers a large opportunity to detect the early phase of the functional and structural changes in the arterial hypertension and can reflect changes in brain vasculature. We review all the available methods of retinal microcirculation measurements including angiography, oximetry, retinal vasculature assessment software, Optical Coherence Tomography Angiography, Adaptive Optics and Scanning Laser Doppler Flowmetry and their application in clinical research.

Materials And Methods: To further analyse the applicability of described methods in hypertension research we performed a systematic search of the PubMed electronic database (April 2020). In our analysis, we included 111 articles in which at least one of described methods was used for assessment of microcirculation of the retina in hypertensive individuals.

Results: Up to this point, the methods most commonly published in studies of retinal microcirculation in arterial hypertension were Scanning Laser Doppler Flowmetry followed shortly by Optical Coherence Tomography Angiography and retinal vasculature assessment software.

Conclusions: While none of described methods enables the simultaneous measurement of all microcirculatory parameters, certain techniques are widely used in arterial hypertension research, while others gain popularity in screening.
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http://dx.doi.org/10.1080/08037051.2020.1823816DOI Listing
February 2021

Alcohol-mediated renal sympathetic neurolysis for the treatment of hypertension: The Peregrine™ infusion catheter.

Cardiovasc Revasc Med 2020 Sep 7. Epub 2020 Sep 7.

CardioVascular Center Frankfurt, Frankfurt, Germany; Anglia Ruskin University, Chelmsford, UK. Electronic address:

Renal sympathetic denervation using conventional non-irrigated radiofrequency catheters has potential technical shortcomings, including limited penetration depth and incomplete circumferential nerve damage, potentially impacting therapeutic efficacy. Against this background, second generation multi-electrode, radiofrequency and ultrasound renal denervation systems have been developed to provide more consistent circumferential nerve ablation. Irrigated catheters may allow deeper penetration while minimizing arterial injury. In this context, catheter-based chemical denervation, with selective infusion of alcohol, a potent neurolytic agent, into the perivascular space, may minimize endothelial, intimal and medial injury while providing circumferential neurolysis. Animal studies demonstrate pronounced renal norepinephrine level reductions and consistent renal nerve injury after perivascular alcohol infusion using the Peregrine Catheter. Early clinical studies demonstrated significant blood pressure reductions and a reasonable safety profile. Randomized sham-controlled trials (NCT03503773, NCT02910414) are underway to examine whether the aforementioned theoretical advantages of alcohol-medicated denervation with the Peregrine System™ Kit translate into clinical benefits.
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http://dx.doi.org/10.1016/j.carrev.2020.09.003DOI Listing
September 2020

Visit-to-visit blood pressure variability and renal outcomes: results from ONTARGET and TRANSCEND trials.

J Hypertens 2020 Oct;38(10):2050-2058

Population Health Research Institute, Hamilton Health Science, McMaster University, Hamilton, Ontario, Canada.

Aims: There is conflicting evidence on whether in treated hypertensive patients the risk of renal outcomes is associated with visit-to-visit SBP variability. Furthermore, limited evidence is available on how important is SBP variability for prediction of renal outcomes compared with on-treatment mean SBP. We addressed these issues in 28 790 participants of the Ongoing Treatment Alone and in combination with Ramipril Global End point Trial and Telmisartan Randomized AssessmeNt Study in ACE iNtolerant Subjects with Cardiovascular Disease trials.

Methods And Results: SBP variability was expressed as the coefficient of variation of the mean with which it showed no relationship. SBP variability and mean values were obtained from five visits during the first 2 years of treatment after the end of the titration phase. Incidence of several renal outcomes (end-stage renal disease, doubling of serum creatinine, new microalbuminuria, new macroalbuminuria and their composite) was calculated from the third year of treatment onward. Patients were divided in quintiles of SBP-coefficient of variation (SBP-CV) or mean SBP, which exhibited superimposable mean blood pressure and SBP-CV values, respectively. A progressive increase of SBP-CV was not accompanied by a parallel increase in a widely adjusted (baseline and on-treatment confounders) risk of most renal outcomes (end-stage renal disease, new macroalbuminuria, new microalbuminuria and their composite) in the subsequent on-treatment years. In contrast, the adjusted risk of most renal outcomes increased progressively from the lowest to the highest quintile of on-treatment mean SBP. Progression from lowest to highest mean on-treatment SBP, but not SBP-CV, was also associated with a less frequent return to normoalbuminuria in patients with initial micro or macroalbuminuria. Renal outcome prediction was slightly improved by the combined use of SBP-CV and mean SBP quintiles.

Conclusion: Visit-to-visit SBP variability had no major predictive value for the risk of renal outcomes, which, in contrast, was sensitively predicted by mean on-treatment SBP. A further slight increase in prediction of renal outcomes was seen by combining on-treatment mean SBP and variability.
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http://dx.doi.org/10.1097/HJH.0000000000002567DOI Listing
October 2020

Differences in patient and physician perspectives on pharmaceutical therapy and renal denervation for the management of hypertension.

J Hypertens 2021 Jan;39(1):162-168

Department of Cardiovascular Medicine, Centre Hospitalier Princese Grace, Monaco.

Objective: To study patient and physician attitudes to pharmaceutical therapy and renal denervation for the management of hypertension.

Methods: Data were analyzed from 19 market research studies in Western Europe and the United States conducted between 2010 and 2019 to obtain quantitative and qualitative perspectives. The analysis incorporated insights from 2768 patients and the experiences of 1902 physicians either actively performing or interested to perform device procedures, or hypertension specialists who would refer patients for a device-based intervention.

Results: Referring cardiologists and proceduralists were more likely to recommend the renal denervation procedure to patients with higher BP levels and a greater number of antihypertensive medications. Physicians perceived patient reluctance towards a procedure as an important obstacle to recommending renal denervation as a treatment option for uncontrolled hypertension. Patient interest in the renal denervation procedure did not correlate with BP severity (P = NS), and the highest preference for the procedure was in patients diagnosed with hypertension but not receiving treatment (P < 0.001). Patients who perceived high BP as a major problem (P = 0.029) and those who experienced side effects attributed to their BP medications (P = 0.006) had a higher preference for renal denervation.

Conclusion: Patients with hypertension often regard the choice of renal denervation to lower BP differently from physicians. A considerable proportion of hypertensive patients, especially those not taking medications, may prefer a device-based approach to reduce their BP.
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http://dx.doi.org/10.1097/HJH.0000000000002592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752236PMC
January 2021

Improved cardiovascular risk prediction in patients with end-stage renal disease on hemodialysis using machine learning modeling and circulating microribonucleic acids.

Theranostics 2020 9;10(19):8665-8676. Epub 2020 Jul 9.

Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany.

To test whether novel biomarkers, such as microribonucleic acids (miRNAs), and nonstandard predictive models, such as decision tree learning, provide useful information for medical decision-making in patients on hemodialysis (HD). Samples from patients with end-stage renal disease receiving HD included in the AURORA trial were investigated (n=810). The study included two independent phases: phase I (matched cases and controls, n=410) and phase II (unmatched cases and controls, n=400). The composite endpoint was cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. miRNA quantification was performed using miRNA sequencing and RT-qPCR. The CART algorithm was used to construct regression tree models. A bagging-based procedure was used for validation. In phase I, miRNA sequencing in a subset of samples (n=20) revealed miR-632 as a candidate (fold change=2.9). miR-632 was associated with the endpoint, even after adjusting for confounding factors (HR from 1.43 to 1.53). These findings were not reproduced in phase II. Regression tree models identified eight patient subgroups with specific risk patterns. miR-186-5p and miR-632 entered the tree by redefining two risk groups: patients older than 64 years and with hsCRP<0.827 mg/L and diabetic patients younger than 64 years. miRNAs improved the discrimination accuracy at the beginning of the follow-up (24 months) compared to the models without miRNAs (integrated AUC [iAUC]=0.71). The circulating miRNA profile complements conventional risk factors to identify specific cardiovascular risk patterns among patients receiving maintenance HD.
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http://dx.doi.org/10.7150/thno.46123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392028PMC
July 2020

Effect of renal denervation in attenuating the stress of morning surge in blood pressure: post-hoc analysis from the SPYRAL HTN-ON MED trial.

Clin Res Cardiol 2020 Aug 1. Epub 2020 Aug 1.

Department of Interventional Cardiology, Piedmont Heart Institute, Atlanta, GA, USA.

Background: Catheter-based renal denervation (RDN) reduces blood pressure (BP) throughout the 24-h period, as reported in several randomized sham-controlled trials. Reduction of BP in the early morning hours is especially important due to increased cardiovascular risks during that time.

Objective: In this report, we examine the impact of RDN on systolic BP (SBP) and diastolic BP (DBP) during the critical morning surge period in a post-hoc analysis of patients in the SPYRAL HTN-ON MED trial.

Methods And Results: Ambulatory BP measurements were collected at baseline and 6 months for treatment and control patient groups over 24-h periods. Average morning BP surge is the difference between average morning BP and average nighttime BP, and the morning surge slope reflects the rate of change of BP from nighttime to morning. Mean morning DBP surge slopes were significantly lower for RDN vs. control groups at 6 months (1.1 vs. 3.6 mmHg/h; p = 0.029). In the RDN group, morning DBP surge slopes were significantly lower at 6 months compared to baseline (1.1 vs. 4.1 mmHg/h; p = 0.006). Similar patterns were observed for mean morning SBP surge slope but did not reach statistical significance.

Conclusions: This decrease in the morning DBP surge slope, an index of the sympathetically-mediated morning BP surge, thus indicates a drop in late morning BP relative to early morning/nocturnal BP in the RDN group. Thus, RDN appears effective in attenuating the slope of morning surge in DBP that might indicate possible benefits in a high-risk hypertensive population.

Clinical Trial Registration: https://www.clinicaltrials.gov (NCT02439775), registered May 12, 2015.
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http://dx.doi.org/10.1007/s00392-020-01718-6DOI Listing
August 2020

Tissue sodium content in hypertension and related organ damage.

J Hypertens 2020 Dec;38(12):2363-2368

Department of Nephrology and Hypertension.

: Most textbooks state that sodium (Na) accumulation goes hand in hand with fluid retention to maintain the environmental isotonicity. In the last century, several studies found, however, that Na is stored in the extravascular space leading to an activation of the monocyte phagocytic system cells that work as a regulator of the interstitial electrolyte homeostasis. Na-MRI was developed to quantify noninvasively, accurately and reliably tissue Na content. In this review, we give an up-to-date overview of clinical studies utilizing this Na-MRI technique to elucidate the importance of tissue Na content in patients with cardiovascular risk factors leading to microvascular and macrovascular complications. Na storage leads ultimately to organ damage such as left ventricular hypertrophy or hypertrophic vascular remodeling of resistance vessels. Elevated Na content in muscle and skin has been detected in patients with treatment resistant hypertension, type 2 diabetes mellitus, acute and chronic heart failure, chronic kidney disease and end-stage renal failure. Pharmacological interventions have shown that a mobilization of extracellular accumulated Na is possible and may emerge as a new therapeutic approach in some diseases.
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http://dx.doi.org/10.1097/HJH.0000000000002580DOI Listing
December 2020

Blood pressure profile, sympathetic nervous system activity, and subclinical target organ damage in patients with polycythemia vera.

Pol Arch Intern Med 2020 08 4;130(7-8):607-614. Epub 2020 Jul 4.

Department of Hypertension, National Institute of Cardiology, Warsaw, Poland

Introduction: Polycythemia vera (PV) is a rare myeloproliferative disease associated with an increased prevalence of hypertension and increased risk of cardiovascular complications. However, the precise mechanisms leading to the elevation of blood pressure (BP) and secondary target organ damage remain poorly understood.

Objectives: The study aimed to evaluate BP profile, assess the activity of the sympathetic nervous system and the renin‑angiotensin system, and provide a comprehensive assessment of subclinical target organ damage in patients with PV.

Patients And Methods: Twenty consecutive patients with newly diagnosed PV and 20 control subjects were included. The following were assessed: BP, levels of catecholamines, urinary and plasma O‑methylated catecholamine metabolites, concentrations of aldosterone and renin. We also assessed microneurography sympathetic nervous system activity (MSNA) and baroreflex control of heart rate as well as subclinical target organ damage.

Results: At similar levels of BP, BP variability was decreased in the PV group (mean [SD] 24‑hour systolic BP, 9 [3] vs 12 [3] mm Hg; P = 0.003). Patients with PV had lower norepinephrine excretion (mean [SD], 16.54 [6.32] vs 25.46 [12.88] μg/d; P = 0.03) as well as decreased MSNA as assessed by microneurography compared with controls (mean [SD] MSNA, 30.7 [8.7] bursts/min vs 38.7 [5.4] bursts/min; P = 0.007 and MSNA 51.8 [11] bursts/100 beats vs 61.1 [11.3] bursts/100 heart beats; P = 0.04). Baroreflex control of HR was unaltered in the PV group. Increased hemoglobin levels and red blood cell count correlated with decreased retinal capillary flow in patients with PV.

Conclusions: Patients with PV, characterized by high hemoglobin concentrations and hematocrit levels had lower sympathetic nervous activity and decreased BP variability as compared with controls. There was no relationship between hemoglobin plasma concentration, hematocrit level, and target organ damage.
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http://dx.doi.org/10.20452/pamw.15473DOI Listing
August 2020

Relationship Between Ubiquitin-Specific Peptidase 18 and Hypertension in Polish Adult Male Subjects: A Cross-Sectional Pilot Study.

Med Sci Monit 2020 Jun 12;26:e921919. Epub 2020 Jun 12.

Department of Nephrology, Hypertension and Internal Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.

BACKGROUND Arterial hypertension (HT) is a leading cause of cardiac hypertrophy and heart failure. Ubiquitin-specific peptidase 18 (USP18) has been recently described as a factor that prevents myocardial dysfunction. The present study measured serum USP18 levels in normotensive (n=29), isolated diastolic hypertensive (n=20), and systolic-diastolic hypertensive (n=30) male participants and correlated these results with biochemical parameters that are included in routine assessments of patients with hypertension. MATERIAL AND METHODS Seventy-nine men, aged 24 to 82 years (mean=50.8±11.4 years), were included in the study. None of the participants had ever been treated for HT. Blood and urine parameters were assessed using routine techniques. Serum USP18 levels were measured by enzyme-linked immunosorbent assay. RESULTS The means and 95% confidence intervals (CIs) of USP18 levels in the HT(-), iDHT(+), and HT(+) groups were 69.3 (22.1-116.5) pg/ml, 90.1 (29.0-151.3) pg/ml, and 426.7 (163.1-690.3) pg/ml, respectively. In the HT(+) group, the mean serum USP18 level was 6.2-times higher than in the HT(-) group (p=0.014) and 4.7-times higher than in the iDHT(+) group (p=0.19). The partial correlation analysis that was adjusted for risk factors of arteriosclerosis indicated that USP18 levels were correlated with systolic blood pressure, pulse pressure, and heart rate. CONCLUSIONS This preliminary study found that serum USP18 levels were significantly higher in drug-naive male participants with arterial hypertension compared with normotensive controls. USP18 exerts cardiovascular-protective effects. Elevations of USP18 levels may indicate a counterregulatory process that is engaged during increases in pressure in the left ventricle.
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http://dx.doi.org/10.12659/MSM.921919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305785PMC
June 2020

Cardiovascular outcomes, bleeding risk, and achieved blood pressure in patients on long-term anticoagulation with the thrombin antagonist dabigatran or warfarin: data from the RE-LY trial.

Eur Heart J 2020 Aug;41(30):2848-2859

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton Health Sciences - King West, PO Box 2000, Hamilton, Ontario L8N 3Z5, Canada.

Aims: A J-shaped association of cardiovascular events to achieved systolic (SBP) and diastolic (DBP) blood pressure was shown in high-risk patients. This association on oral anticoagulation is unknown. This analysis from RELY assessed the risks of death, stroke or systemic emboli, and bleeding according to mean achieved SBP and DBP in atrial fibrillation on oral anticoagulation.

Methods And Results: RE-LY patients were followed for 2 years and recruited between 22 December 2005 until 15 December 2007. 18.113 patients were randomized in 951 centres in 54 countries and 18,107 patients with complete blood pressure (BP) data were analysed with a median follow-up of 2.0 years and a complete follow-up in 99.9%. The association between achieved mean SBP and DBP on all-cause death, stroke and systemic embolic events (SSE), major, and any bleeding were explored. On treatment, SBP >140 mmHg and <120 mmHg was associated with all-cause death compared with SBP 120-130 mmHg (reference). For SSE, risk was unchanged at SBP <110 mmHg but increased at 140-160 mmHg (adjusted hazard ratio (HR) 1.81; 1.40-2.33) and SBP ≥160 mmHg (HR 3.35; 2.09-5.36). Major bleeding events were also increased at <110 mmHg and at 110 to <120 mmHg. Interestingly, there was no increased risk of major bleeding at SBP >130 mmHg. Similar patterns were observed for DBP with an increased risk at <70 mmHg (HR 1.55; 1.35-1.78) and >90 mmHg (HR 1.88; 1.43-2.46) for all-cause death compared to 70 to <80 mmHg (reference). Risk for any bleeding was increased at low DBP <70 mmHg (HR 1.46; 1.37-1.56) at DBP 80 to <90 mmHg (HR 1.13; 1.06-1.31) without increased risk at higher achieved DBP. Dabigatran 150 mg twice daily showed an advantage in all patients for all-cause death and SSE and there was an advantage for 110 mg dabigatran twice daily for major bleeding and any bleeding irrespective of SBP or DBP achieved. Similar results were obtained for baseline BP, time-updated BP, and BP as time-varying covariate.

Conclusion: Low achieved SBP associates with increased risk of death, SSE, and bleeding in patients with atrial fibrillation on oral anticoagulation. Major bleeding events did not occur at higher BP. Low BP might identify high-risk patients not only for death but also for high bleeding risks.

Clinical Trial Registration:  ClinicalTrials.gov-Identifier: NCT00262600.
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http://dx.doi.org/10.1093/eurheartj/ehaa247DOI Listing
August 2020

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial.

Lancet 2020 05 29;395(10234):1444-1451. Epub 2020 Mar 29.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Background: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications.

Methods: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749.

Findings: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months.

Interpretation: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications.

Funding: Medtronic.
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http://dx.doi.org/10.1016/S0140-6736(20)30554-7DOI Listing
May 2020

Lumen narrowing and increased wall to lumen ratio of retinal microcirculation are valuable biomarkers of hypertension-mediated cardiac damage.

Blood Press 2019 Sep 5:1-10. Epub 2019 Sep 5.

Department of Hypertension and Diabetology, Faculty of Medicine, Medical University of Gdansk, Gdansk, Poland.

In the course of hypertension, left ventricular hypertrophy and diastolic dysfunction develop very often and may progress toward heart failure. The aim of the study was to analyze the relationship between abnormalities of retinal microcirculation and cardiac damage defined as left ventricular hypertrophy and/or diastolic dysfunction. The study comprised 88 patients with essential hypertension. The group was divided into two subgroups: hypertensives without cardiac damage ( = 55) and with cardiac damage ( = 33). Control group comprised 32 normotensive subjects. Scanning laser Doppler flowmetry was used to evaluate retinal microcirculation. Echocardiography was used to assess cardiac damage. Lumen diameter of retinal arterioles was significantly smaller in patients with cardiac damage vs. controls (77 vs. 84 µm,  = 0.02). Additionally, there was an evident trend with respect to lumen diameter (LD) across all three studied subgroups; i.e.: the smallest dimeters were present in cardiac damage patients, moderate size in hypertensives' without cardiac damage, and the largest diameters in healthy controls ( < 0.01). Lumen diameter was inversely correlated with cardiac intraventricular septum diameter ( = -0.25,  = 0.02), left ventricular mass ( = -0.24,  = 0.02), and left atrial volume ( = -0.22,  = 0.04). Wall to lumen ratio was associated with intraventricular septum diameter ( = 0.21,  = 0.044) and left atrial volume ( = 0.21,  = 0.045). In multivariable regression analysis, lumen diameter was independently associated with intraventricular septum diameter ( = -0.05,  = 0.03), left ventricular mass ( = -1.15,  = 0.04), and left atrial volume ( = -0.42,  = 0.047); wall to lumen ratio was independently associated with intraventricular septum diameter ( = 3.67,  = 0.02) and left atrial volume ( = 30.0,  = 0.04). In conclusion, retinal arterioles lumen diameter and wall to lumen ratio were independent biomarkers of cardiac damage. Retinal examination performed by means of scanning laser Doppler flowmetry might be a valuable tool to improve cardiovascular risk stratification of hypertensive patients.
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http://dx.doi.org/10.1080/08037051.2019.1657769DOI Listing
September 2019

Retinal neurodegeneration in patients with end-stage renal disease assessed by spectral-domain optical coherence tomography.

Sci Rep 2020 03 24;10(1):5255. Epub 2020 Mar 24.

Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany.

Spectral-domain optical coherence tomography (SD-OCT) represents a reliable tool for retinal layer volume and thickness measurement. The aim of this study was to evaluate retinal changes indicating neurodegenerative processes in patients with end-stage renal disease (ESRD) compared to healthy controls. This was a cross-sectional, single-center study comprising 32 ESRD patients and 38 controls. Sectoral retinal nerve fiber layer (RNFL) thickness and retinal layer volumes were obtained by SD-OCT. Age- and gender-adjusted retinal layer volumes such as total retinal volume (p = 0.037), ganglion cell layer volume (GCL, p = 0.003), ganglion cell layer - inner plexiform layer volume (GCL-IPL, p = 0.005) and inner retinal layer volume (IRL, p = 0.042) of the right eye were lower in ESRD patients. Inner plexiform layer volume of both eyes (IPL, right eye: p = 0.017; left eye: 0.044) was reduced, as was RNFL thickness in the temporal superior sector (right eye: p = 0.016). A subgroup analysis excluding patients with diabetes revealed that GCL (p = 0.014) and GCL-IPL volume of the right eye (p = 0.024) and temporal superior sector of the RNFL scan (p = 0.021) in ESRD patients were still significantly thinner. We observed a decrease in several retinal layer volumes and temporal RNFL thickness indicative of retinal neurodegenerative processes in patients with ESRD.
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http://dx.doi.org/10.1038/s41598-020-61308-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093533PMC
March 2020

Retinal arterial remodeling in patients with pheochromocytoma or paraganglioma and its reversibility following surgical treatment.

J Hypertens 2020 08;38(8):1551-1558

Department of Hypertension, Institute of Cardiology, Warsaw.

Objective: Structural abnormalities in resistance arteries are a hallmark of patients with hypertension. In hypertensive patients with pheochromocytoma or paraganglioma (PPGL), it is still a matter of debate whether structural vascular changes are because of elevated blood pressure (BP) or to toxic effects of elevated circulating catecholamines. Hence, the aim of our study was to assess whether catecholamine excess and/or elevated BP affect the structure of small retinal arteries in patients with catecholamine-producing tumors.

Methods: The study included 27 patients with PPGL and 27 hypertensive patients. All patients underwent biochemical tests for catecholamine excess, echocardiography and analyses of scanning-laser-Doppler-flowmetry (SLDF) both at baseline and 12 months following surgical resection of PPGL.

Results: Baseline retinal arterial diameter, arterial wall thickness and wall cross sectional area (WCSA) were higher in patients with PPGL as compared with subjects without PPGL (arterial diameter: 110 ± 16.5 vs. 99.5 ± 10.8 μm, wall thickness: 16.3 ± 6.0 vs. 13.5 ± 4.0 μm, WCSA: 4953.9 ± 2472.8 vs. 3784.1 ± 1446.3 μm, P < 0.05). Significant correlations were noted between wall thickness and WCSA and echocardiographic parameters assessing diastolic and systolic function of left ventricle. No correlations between retinal parameters, BP level and plasma concentrations of metanephrines were observed. In patients with PPGL, there were postoperative decreases in wall thickness (16.4 ± 15.8 vs. 14.8 ± 4.7 μm; P = 0.011) and WLR (0.42 ± 0.13 vs. 0.37 ± 0.10; P = 0.003) at 12 months after surgical removal of tumors.

Conclusion: This is the first study to demonstrate that catecholamine excess is related to thickening of retinal arteries independent of BP and reversible after surgical cure. These data support a role of catecholamines in vascular remodeling in PPGL patients.
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http://dx.doi.org/10.1097/HJH.0000000000002420DOI Listing
August 2020

Arteriovenous fistula thrombosis is associated with increased all-cause and cardiovascular mortality in haemodialysis patients from the AURORA trial.

Clin Kidney J 2020 Feb 11;13(1):116-122. Epub 2019 May 11.

INSERM, Centre d'Investigation Clinique Plurithématique, University Hospital, Lorraine University, Nancy, France.

Background: The impact of arteriovenous fistula (AVF) or graft (AVG) thrombosis on mortality has been sparsely studied. This study investigated the association between AVF/AVG thrombosis and all-cause and cardiovascular mortality.

Methods: The data from 2439 patients with AVF or AVG undergoing maintenance haemodialysis (HD) included in the A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events trial (AURORA) were analysed using a time-dependent Cox model. The incidence of vascular access (VA) thrombosis was a pre-specified secondary outcome.

Results: During follow-up, 278 AVF and 94 AVG thromboses were documented. VA was restored at 22 ± 64 days after thrombosis (27 patients had no restoration with subsequent permanent central catheter). In multivariable survival analysis adjusted for potential confounders, the occurrence of AVF/AVG thrombosis was associated with increased early and late all-cause mortality, with a more pronounced association with early all-cause mortality {hazard ratio [HR] < 90 days 2.70 [95% confidence interval (CI) 1.83-3.97], P < 0.001; HR > 90 days 1.47 [1.20-1.80], P < 0.001}. In addition, the occurrence of AVF thrombosis was significantly associated with higher all-cause mortality, whether VA was restored within 7 days [HR 1.34 (95% CI 1.02-1.75), P = 0.036] or later than 7 days [HR 1.81 (95% CI 1.29-2.53), P = 0.001].

Conclusions: AVF/AVG thrombosis should be considered as a major clinical event since it is strongly associated with increased mortality in patients on maintenance HD, especially in the first 90 days after the event and when access restoration occurs >7 days after thrombosis. Clinicians should pay particular attention to the timing of VA restoration and the management of these patients during this high-risk period. The potential benefit of targeting overall patient risk with more aggressive treatment after AVF/AVG restoration should be further explored.
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http://dx.doi.org/10.1093/ckj/sfz048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025348PMC
February 2020

Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design.

Clin Res Cardiol 2020 Mar 7;109(3):289-302. Epub 2020 Feb 7.

London School of Hygiene and Tropical Medicine, London, UK.

Background: The SPYRAL HTN clinical trial program was initiated with two 80-patient pilot studies, SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED, which provided biological proof of principle that renal denervation has a blood pressure-lowering effect versus sham controls for subjects with uncontrolled hypertension in the absence or presence of antihypertensive medications, respectively.

Trial Design: Two multicenter, prospective, randomized, sham-controlled trials have been designed to evaluate the safety and efficacy of catheter-based renal denervation for the reduction of blood pressure in subjects with hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) or presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications. The primary efficacy endpoint is baseline-adjusted change from baseline in 24-h ambulatory systolic blood pressure. The primary safety endpoint is incidence of major adverse events at 1 month after randomization (or 6 months in cases of new renal artery stenosis). Both trials utilize a Bayesian design to allow for prespecified interim analyses to take place, and thus, the final sample sizes are dependent on whether enrollment is stopped at the first or second interim analysis. SPYRAL HTN-OFF MED Pivotal will enroll up to 300 subjects and SPYRAL HTN-ON MED Expansion will enroll up to 221 subjects. A novel Bayesian power prior approach will leverage historical information from the pilot studies, with a degree of discounting determined by the level of agreement with data from the prospectively powered studies.

Conclusions: The Bayesian paradigm represents a novel and promising approach in device-based hypertension trials.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02439749 (SPYRAL HTN-OFF MED Pivotal) and NCT02439775 (SPYRAL HTN-ON MED Expansion).
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http://dx.doi.org/10.1007/s00392-020-01595-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042193PMC
March 2020

Changes in Stroke Volume After Renal Denervation: Insight From Cardiac Magnetic Resonance Imaging.

Hypertension 2020 03 3;75(3):707-713. Epub 2020 Feb 3.

From the Department of Internal Medicine/Cardiology (P.L., K.-P.K., K.-P.R., M.v.R., C.B., H.T., S.D., K.F.), Heart Center Leipzig at University of Leipzig, Germany.

Recent trial results support catheter-based renal denervation (RDN) for treatment of hypertension, while the exact mechanisms causing blood pressure to fall remain incompletely understood. Cardiac magnetic resonance imaging was used to assess the effects of RDN on cardiac function in patients with hypertension undergoing RDN and compared with sham treatment. Cardiac magnetic resonance imaging was used to assess stroke volume index, cardiac index, heart rate, systemic vascular resistance index, and stroke work index from aortic flow measurements. Patients with resistant hypertension from a randomized, sham-controlled RDN trial underwent cardiac magnetic resonance imaging before RDN and at follow-up (randomized cohort). Results were then validated in a cohort of patients with resistant hypertension undergoing RDN and cardiac magnetic resonance imaging (validation cohort). In total, 162 patients were included 52 patients in the randomized trial (27 shams) and 110 patients in the validation cohort. In the randomized cohort, stroke volume index was reduced by 4.7±9.8 mL/m in the RDN cohort and remained unchanged in the sham cohort (=0.008 for between-group comparison), while cardiac index and stroke work index tended to be reduced in RDN patients but not in sham patients (-0.10±5.9 versus 0.17±0.51 L/min per m and -7.1±12.5 versus -1.4±10.4 g/m, =0.08 for both). In contrast, systemic vascular resistance index and heart rate remained unchanged after RDN. In the validation cohort, reduction of stroke volume index was confirmed, and cardiac index and stroke work index were also reduced significantly, whereas systemic vascular resistance index and heart rate remained unchanged at follow-up. In this study of patients with resistant hypertension, RDN resulted in a reduction of stroke volume when compared with sham.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14310DOI Listing
March 2020

Influence of Age on Upper Arm Cuff Blood Pressure Measurement.

Hypertension 2020 03 27;75(3):844-850. Epub 2020 Jan 27.

From the Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia (D.S.P., M.G.S., P.O., J.A.B., N.D., R.F., P.R.-T., J.E.S.).

Blood pressure (BP) is a leading global risk factor. Increasing age is related to changes in cardiovascular physiology that could influence cuff BP measurement, but this has never been examined systematically and was the aim of this study. Cuff BP was compared with invasive aortic BP across decades of age (from 40 to 89 years) using individual-level data from 31 studies (1674 patients undergoing coronary angiography) and 22 different cuff BP devices (19 oscillometric, 1 automated auscultation, 2 mercury sphygmomanometry) from the Invasive Blood Pressure Consortium. Subjects were aged 64±11 years, and 32% female. Cuff systolic BP overestimated invasive aortic systolic BP in those aged 40 to 49 years, but with each older decade of age, there was a progressive shift toward increasing underestimation of aortic systolic BP (<0.0001). Conversely, cuff diastolic BP overestimated invasive aortic diastolic BP, and this progressively increased with increasing age (<0.0001). Thus, there was a progressive increase in cuff pulse pressure underestimation of invasive aortic PP with increasing decades of age (<0.0001). These age-related trends were observed across all categories of BP control. We conclude that cuff BP as an estimate of aortic BP was substantially influenced by increasing age, thus potentially exposing older people to greater chance for misdiagnosis of the true risk related to BP.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035100PMC
March 2020