Showing papers by "Roland E. Schmieder published in 2014"

2013 ESH/ESC Practice guidelines for the management of arterial hypertension

Abstract: ABPMambulatory blood pressure monitoringACEangiotensin converting enzymeARBangiotensin receptor blockerA-Vatrio-ventricularBBbeta-blockerBPblood pressureCHDcoronary heart diseaseCKDchronic kidney d...

Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized clinical trial.

Abstract: Aim The aim of this study was to determine long-term results of renal artery denervation for treatment of treatment-resistant hypertension in the SYMPLICITY HTN-2 study. Methods SYMPLICITY HTN-2 randomized 106 subjects with treatment-resistant hypertension to renal denervation or medical therapy alone. At 6 months, 37 control subjects crossed over to renal denervation. Office blood pressure measurements, antihypertensive medication use, and safety events were followed every 6 months through 3 years. Results Follow-up was available at 36 months in 40 of 52 subjects in the initial renal denervation group and at 30 months in 30 of 37 subjects who crossed over and received renal denervation at 6 months. Baseline blood pressure was 184 ± 19/99 ± 16 mmHg in all treated subjects. At 30-month post-procedure, systolic blood pressure decreased 34 mmHg (95% CI: −40, −27, P < 0.01) and diastolic blood pressure decreased 13 mmHg (95% CI: −16, −10, P < 0.01). The systolic and diastolic blood pressure reduction at 36 months for the initial renal denervation group was −33 mmHg (95% CI: −40, −25, P < 0.01) and −14 mmHg (95% CI: −17, −10, P < 0.01), respectively. Procedural complications included one haematoma, and one renal artery dissection before energy delivery that was treated successfully. Later complications included two cases of acute renal failure, which fully resolved, 15 hypertensive events requiring hospitalization, and three deaths. Conclusion Renal denervation resulted in sustained lowering of blood pressure at 3 years in a selected population of subjects with severe, treatment-resistant hypertension without serious safety concerns. Clinical trial registration NCT00888433.

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

Abstract: The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. (Less)

Effects of saxagliptin on early microvascular changes in patients with type 2 diabetes

Abstract: Background Patients with diabetes mellitus are at increased risk for microvascular complications. Early changes in microcirculation are characterized by hyperperfusion (e.g. in the retina and kidney) and increased pulse wave reflection leading to increased aortic pressure. We investigated the effects of the DPP-4-inhibitor saxagliptin on early retinal microvascular changes.

What the interventionalist should know about renal denervation in hypertensive patients: a position paper by the ESH WG on the interventional treatment of hypertension.

Abstract: Percutaneous catheter-based transluminal renal denervation (RDN) has emerged as a new approach to achieve sustained blood pressure reduction in patients with drug-resistant hypertension. Experts from ESH and ESC in their recently released position papers and consensus document have summarised the current evidence, unmet needs and practical recommendations for the application of this therapeutic strategy in clinical practice. Experts of the ESH Working Group for the interventional treatment of hypertension prepared this position paper in order to provide interventionalists with guidance through the procedure of RDN. Given that there is no established intraprocedural control of ablation success, interventionalists have to be familiar with the aspects related to the anatomy and imaging of the renal arteries, the distribution of renal sympathetic fibres, the special equipment necessary for RDN and the procedural details in order to maximise the success and minimise potential complications.

Blood pressure and low-density lipoprotein-cholesterol lowering for prevention of strokes and cognitive decline: a review of available trial evidence

Abstract: It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these treatments can prevent cognitive decline after stroke.

Mortality and morbidity in relation to changes in albuminuria, glucose status and systolic blood pressure: an analysis of the ONTARGET and TRANSCEND studies.

Abstract: Aims/hypothesis Urinary albumin excretion is a strong predictor of cardiovascular disease. It is uncertain whether improvement from microalbuminuria or deterioration from normoalbuminuria over time in patients with differing changes in glucose and BP change their cardiovascular risk.

Rationale, Design, and Baseline Characteristics of ARTS-DN : A Randomized Study to Assess the Safety and Efficacy of Finerenone in Patients with Type 2 Diabetes Mellitus and a Clinical Diagnosis of Diabetic Nephropathy

Abstract: Background/Aims: Finerenone decreases albuminuria in patients having heart failure with reduced ejection fraction and mild-to-moderate (stage 2-3) chronic kidney

Disproportional Decrease in Office Blood Pressure Compared With 24-Hour Ambulatory Blood Pressure With Antihypertensive Treatment: Dependency on Pretreatment Blood Pressure Levels

Abstract: The long-term relationship between 24-hour ambulatory blood pressure (ABP) and office BP in patients on therapy is not well documented. From a registry we included all patients in whom antihypertensive therapy needed to be uptitrated. Drug treatment included the direct renin inhibitor aliskiren or an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or drugs not blocking the renin–angiotensin system, alone or on top of an existing drug regimen. In all patients, office BP and 24-hour ABP were obtained at baseline and after 1 year with validated devices. In the study population of 2722 patients, there was a good correlation between the change in office BP and 24-hour ABP (systolic: r =0.39; P r =0.34; P

[Dialysis and ultrafiltration therapy in patients with cardio-renal syndrome: recommendations of the working group "heart-kidney" of the German Cardiac Society and the German Society of Nephrology].

Abstract: Renal failure is common in patients with severe heart failure. This complex pathophysiological interaction has been classified as cardio-renal syndrome. In these patients hydropic decompensation is the main cause of hospitalization. In patients with refractory heart failure, characterized by diuretic resistance and congestion due to volume overload, ultrafiltration has to be considered. In acute decompensated heart failure with worsening of renal function, extracorporeal ultrafiltration is the preferred treatment modality. On the other hand, patients suffering from chronic decompensated heart failure, particularly patients with ascites, will profit from the treatment specific advantages of peritoneal ultrafiltration. Prerequisite for an optimized care of patients with cardio-renal syndrome is the close collaboration among intensive care doctors, cardiologists and nephrologists.

Renal denervation—implications for chronic kidney disease

Abstract: Renal denervation reduces renal inflammation and injury in experimental animals and might have similar effects in patients with chronic kidney disease (CKD). In this Review, the authors discuss the evidence for increased sympathetic tone in patients with kidney disease, the physiology of renal nerves and the potential role of renal denervation as a treatment strategy to attenuate or inhibit the progression of CKD. Catheter-based renal denervation to treat patients with resistant hypertension and chronic kidney disease (CKD) has generated considerable interest. Data from the majority of, but not all, observational studies and randomized controlled trials suggest that the procedure does not impair renal function and can effectively reduce office and ambulatory blood pressure in patients with primary hypertension. The putative beneficial effects of renal denervation seem to result from the interruption of renal efferent and afferent nerves. In patients with resistant hypertension and CKD, interruption of afferent reflexes might lead to a reduction in global sympathetic tone. The subsequent sustained reduction in blood pressure is expected to slow the progression of renal disease. However, renal denervation might also improve glucose metabolism, increase insulin sensitivity and reduce renal inflammation, with renoprotective effects in patients with CKD. Additional large randomized controlled trials of renal denervation in hypertensive and normotensive patients with CKD are required to precisely define the clinical value of the procedure in this population.

Hypertension: How should data from SYMPLICITY HTN-3 be interpreted?

Abstract: The SYMPLICITY HTN-3 trial demonstrated unexpectedly large and small blood pressure reductions in the control and renal denervation groups, respectively. Although this study was well designed, it had several weaknesses and the results are inconclusive, with the exception of the positive signal for renal denervation in non-African-American individuals.

The International Society of Hypertension and World Hypertension League call on governments, nongovernmental organizations and the food industry to work to reduce dietary sodium

Abstract: The International Society of Hypertension and the World Hypertension League have developed a policy statement calling for reducing dietary salt. The policy supports the WHO and the United Nations recommendations, which are based on a comprehensive and up-to-date review of relevant research. The policy statement calls for broad societal action to reduce dietary salt, thus reducing blood pressure and preventing hypertension and its related burden of cardiovascular disease. The hypertension organizations and experts need to become more engaged in the efforts to prevent hypertension and to advocate strongly to have dietary salt reduction policies implemented. The statement is being circulated to national hypertension organizations and to international nongovernmental health organizations for consideration of endorsement. Member organizations of the International Society of Hypertension and the World Hypertension League are urged to support this effort.

Clinical Impact of Patient Adherence to a Fixed-Dose Combination of Olmesartan, Amlodipine and Hydrochlorothiazide

Abstract: Recent findings from randomized clinical trials indicate an improved patient adherence and blood pressure (BP) control by using fixed-dose combinations (FDCs) in the treatment of hypertension. The aim of the present study was to verify those data in a large real-world sample of hypertensive patients and to cross-check adherence evaluation performed by physicians and patients self-assessment. A European multi-center, prospective, 24-week, non-interventional study was conducted including 14,979 patients with essential hypertension and new treatment with olmesartan, amlodipine and hydrochlorothiazide as an FDC. Patients’ adherence was measured using the Morisky Medication Adherence Scale (MMAS-8) and a non-standardized questionnaire was used by physicians and patients for self-assessment. The mean age of the patients was 63.9 ± 11.78 years and 46.5 % were women. One or more cardiovascular risk factors were present in 71.9 % of patients and 94.7 % had been treated for hypertension before study entry. Mean adherence to medication by MMAS-8 improved from 6.0 to 6.9 at study end. Corresponding improvements of adherence were seen on physicians’ and patients’ self-assessments throughout the study. Mean decrease of systolic/diastolic BP was 26.4/12.8 mmHg without a relevant difference between the MMAS-8 adherence levels. BP target achievement improved from 55.3 to 67.7 % in patients with low versus high adherence. The overall rate of patients with adverse drug reactions was very low (1.76 %) but more frequent in patients with low adherence. Our data confirm previous clinical trial data on the improvement of medication adherence by switching antihypertensive combination therapy to an FDC and a subsequent improvement in BP target achievement. An observed trend toward a reduction in adverse drug reactions needs to be further investigated in clinical trials.

Heart rate and blood pressure interactions in the development of erectile dysfunction in high-risk cardiovascular patients

Abstract: AimsErectile dysfunction (ED) is associated with cardiovascular risk factors as elevated systolic blood pressure (SBP), resting high heart rate (HR), and endothelial dysfunction and predicts cardiovascular events. However, the interaction between high HR and SBP and the development of ED remains unclear.Methods and ResultsWe evaluated 1015 male patients enrolled in the ED substudy of ONTARGET and TRANSCEND, examining the influence of mean HR and mean SBP obtained over all study visits (mean 10.9±1.4 study visits) and their interaction with ED. In patients without pre-existing ED, new onset ED was detected in 29% of patients below, and 41% of patients above, the median of mean HR (OR 1.72, 95% CI 1.8–2.5, p = 0.0047). In patients with pre-existing ED, high HR had no add-on effect. With or without pre-existing ED, high SBP had no influence after adjustment for covariates (OR 1.03, 95% CI 0.66–1.59, p = 0.91). In a continuous model, it was shown that effects of high HR were prominent at low Kolner (Cologne) ...

Effects of folic acid on renal endothelial function in patients with diabetic nephropathy: results from a randomized trial.

Abstract: Endothelial dysfunction has been shown to promote podocyte injury and albuminuria in diabetes, highlighting the importance of the interaction between renal endothelial cells and podocytes. Folic acid (FA) improves nitric oxide synthase (NOS) function and reduces progression of diabetic nephropathy in animal models. We tested whether high-dose FA treatment improves renal endothelial function and albuminuria in human subjects with incipient diabetic nephropathy. Following a double-blind, randomized, cross-over design, 28 patients with Type 2 diabetes and albuminuria were allocated to 4 weeks’ treatment with placebo and high-dose FA (5 mg/day). Renal nitric oxide (NO) production determined as the response of renal plasma flow (RPF) to NOS inhibition with N G -monomethyl-L-arginine (L-NMMA) (4.25 mg/kg intravenously), renal oxidant stress as response of RPF to vitamin C infusion (3 mg/kg) and albuminuria were determined after each treatment phase. Neither the reduction in RPF to L-NMMA nor the increase in RPF to vitamin C infusion differed between treatment phases (ΔRPF to L-NMMA: −74±71 ml/min per m 2 during placebo compared with −63±56 ml/min per m 2 during FA, P =0.57; ΔRPF to vitamin C: +93±118 ml/min per m 2 compared with +94±108 ml/min per m 2 ; P =0.70). In line with the lack of effect on the renal endothelium, albuminuria was not affected by FA treatment (110±179 mg/day during placebo compared with 87±146 mg/day during FA; P =0.12). High-dose FA treatment does not improve renal endothelial function and fails to reduce albuminuria in human subjects with diabetic nephropathy. Novel treatment options for oxidant stress and endothelial dysfunction in patients with diabetes are urgently needed.

Safety and effectiveness of a fixed-dose combination of olmesartan, amlodipine, and hydrochlorothiazide in clinical practice.

Abstract: Background Clinical trials indicate that the use of fixed-dose combinations (FDCs) is associated with a higher level of treatment adherence and prolonged blood pressure (BP) control. The aim of this study was to document the safety and effectiveness of the FDC olmesartan/amlodipine/hydrochlorothiazide in patients with essential hypertension in clinical practice.

First experience in analysing pulsatile retinal capillary flow and arteriolar structural parameters measured noninvasively in hypertensive patients.

Abstract: OBJECTIVE Increased pulsatile pressure induces as well as aggravates microvascular damage. Scanning laser Doppler flowmetry allows the noninvasive assessment of both retinal capillary flow (RCF) and arteriolar structural parameters of the retinal circulation. Moreover, pulsatile characteristics of the retinal arterioles can be assessed. METHODS In study 1, reliability of pulsatile RCF and structural parameters were examined in randomly selected patients. In study 2, pulsatile RCF as well as the structural parameters of retinal arterioles were assessed in hypertension grade 1-2 (HT1-2; n = 20) and treatment-resistant hypertension (TRH; n = 19). RESULTS In study 1, test-retest, interobserver and intraobserver reliability of all parameters showed coefficients of variation of less than 10%. In study 2, it was shown that patients with TRH had higher pulse pressure (P = 0.003) and pulsed RCF values (P < 0.001) as patients with HT1-2. Patients with HT1-2 had no change in the vessel diameter, but a significant difference in lumen diameter, resulting in an altered wall thickness (P = 0.001) between systole and diastole. In contrast, patients with TRH showed differences in vessel diameter (P = 0.005) as well as lumen diameter (P = 0.001), resulting in an unaltered wall thickness between systole and diastole. Hence, wall thickness change as a result of pulsed flow regulation observed in HT1-2 was missing in TRH. CONCLUSION We suggest a new reliable tool for evaluating the pulsatility in the retinal circulation in humans, and found significant differences in pulsatile RCF and structural parameters between patients with HT1-2 and those with TRH.

Impact of telmisartan on cardiovascular outcome in hypertensive patients at high risk: a Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease subanalysis.

Abstract: BACKGROUND In the Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease, all patients were at high cardiovascular risk, and a substantial proportion were hypertensive. We performed a post-hoc analysis to explore the hypothesis that telmisartan has a differential action in hypertensive vs. nonhypertensive patients. METHODS The primary four-fold endpoint (composite of cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for heart failure), the secondary three-fold endpoint (cardiovascular death, MI, and stroke), the individual components, new onset of left ventricular hypertrophy (LVH), and new onset of albuminuria were analyzed. RESULTS There was no evidence for a significantly differential treatment effect of telmisartan in hypertensive and nonhypertensive patients for any endpoints, although the occurrence of the secondary three-fold endpoint was significantly lower in the telmisartan group (13.0%) compared with placebo (15.0%, P < 0.05) only in hypertensive patients. Moreover, data from this post-hoc analysis suggest that MI may be less frequent in hypertensive patients treated with telmisartan (3.8 vs. 5.1%; P < 0.05). Telmisartan may also reduce new onset of LVH (nonhypertensive patients P < 0.05; hypertensive patients P < 0.001) in both subgroups, and new onset of microalbuminuria and macroalbuminuria in hypertensive patients (P < 0.001 and P < 0.01, respectively).The effect of telmisartan in hypertensive and nonhypertensive patients at high cardiovascular risk was not different. This post-hoc analysis suggests that MI may be further reduced by telmisartan in hypertensive patients. Further investigations are needed to study the hypotheses raised by this explanatory analysis.

Kommentar zur 2013-ESH/ESC-Leitlinie zum Management der arteriellen Hypertonie

Abstract: Im Juni 2013 wurden die neuen European Society of Hypertension (ESH)/European Society of Cardiology (ESC)-Leitlinien zum Management der arteriellen Hypertonie publiziert. Die Deutsche Hochdruckliga e.V. DHL®/Deutsche Gesellschaft fur Hypertonie und Pravention und die Deutsche Gesellschaft fur Kardiologie (DGK) haben sich erstmalig entschlossen, diese Leitlinien in Form praxisnaher Pocketleitlinien gemeinsam zu ubersetzen. Die DHL/DGK-Pocketleitlinien sind eine genaue Ubersetzung der ESH/ESC-Pocketleitlinien. Mit dem vorliegenden Kommentar, mochten wir uber bedeutende Anderungen der neuen Leitlinien gegenuber den vorpublizierten Versionen informieren. Zusatzlich werden unter Berucksichtigung nationaler Rahmenbedingungen und der Bewertung durch DHL/DGK-Expertenkommissionen einzelne kontroverse ESH/ESC-Empfehlungen diskutiert. Insbesondere werden die Bedeutung der Blutdruckmessung auserhalb der Praxis, neue Zielblutdruckwerte, Anderungen in der medikamentosen Therapie und das Vorgehen bei therapieresistenter Hypertonie besprochen. Abschliesend werden die Limitationen der aktuellen Leitlinien diskutiert.

Renal denervation--a valid treatment option despite SYMPLICITY HTN-3.

Abstract: I thank Yutang Wang for his Corres­ pondence (Ethnicity and sympathetic tone: predictors of the blood pressure response to renal denervation? Nat. Rev. Cardiol. doi:10.1038/nrcardio.2014.70­c1)1 on my News & Views article (How should data from SYMPLICITY HTN­3 be inter­ preted? Nat. Rev. Cardiol. 11, 375–376; 2014).2 Wang highlights 11 studies with low­level evidence and a small number of patients (n = 6–17) in which the efficacy of renal denervation for lowering blood pressure was examined. Although Wang acknowledges these study limitations, con­ clusions are still drawn from these reports. In contrast to these small studies, Mahfoud et al. conducted a large, prospective study involving 206 patients, and observed sig­ nificant decreases in office and ambulatory blood pressure with renal denervation after 6 months.3 Data from the SYMPLICITY HTN­1 trial,4 and from the randomized, controlled SYMPLICITY HTN­2 trial,5 both published in 2014, have also dem­ onstrated significant decreases in office blood pressure with renal denervation after 3 years. In my Ne ws & Vie ws ar t i c l e , 2 I aim ed to interpret the results from the SYMPLICITY HTN­3 trial,6 a prospec­ tive, randomized, masked, single­blind study that did not show a significant blood pressure reduction after renal denervation. In my opinion, some of the viewpoints expressed by Wang are not correct. Studies with witnessed intake of medication to exclude patients with poor drug adherence have been published;1 however, this obser­ vation would not help in the interpretation of the SYMPLICITY HTN­3 data,6 because poor drug adherence would have affected both the renal denervation and sham­ controlled groups. Adherence to medical therapy in treatment­resistant hypertension is a serious obstacle. A study involving 79 patients with hypertension demonstrated a nonadherence rate of 25% and 23% at REPLY

Invasive treatment of resistant hypertension: present and future.

Abstract: The underlying pathophysiologic concept of diverse invasive devices to treat resistant hypertension (e.g., sympathetic denervation, carotid sinus nerve stimulation) is known for a long time. Since the pioneering work in the 1940s in humans, innovative techniques have been developed resulting in less invasive treatment procedures and, hence, overcoming serious side effects, which in turn improved safety and lead to more widespread use. Recently, new experimental technologies have been or are under evaluation in experiments and first-in-man studies have been conducted. Data with interventional techniques are rapidly expanding and have to be interpreted with caution. Additional data from randomized potentially sham-controlled studies are urgently needed. This article focuses on the increasing work of different invasive approaches for the treatment of resistant hypertension.

Prevention of electrocardiographic left ventricular remodeling by the angiotensin receptor blocker olmesartan in patients with type 2 diabetes.

Abstract: Objective:To assess the ability of olmesartan (OLM) to prevent or delay left ventricular remodeling and hypertrophy in patients with type 2 diabetes.Methods:This prespecified ECG substudy of Randomised OlmesArtan and Diabetes MicroAlbuminuria Prevention (ROADMAP), which compared OLM with placebo, as

Daytime systolic ambulatory blood pressure with a two-step switch from candesartan to olmesartan monotherapy and the fixed-dose combination of olmesartan/amlodipine in patients with uncontrolled essential hypertension (SEVICONTROL-2).

Abstract: The objective of this study was to investigate the efficacy of the fixed-dose combination olmesartan/amlodipine 40/10 mg in patients with moderate essential hypertension not controlled on candesartan 32 mg. This was a prospective, single-arm, phase IV study. The primary endpoint was the change in mean daytime systolic blood pressure (BP). A total of 77 of 89 screened patients started candesartan 32 mg, 62 olmesartan 40 mg, and 57 olmesartan 40 mg/amlodipine 10 mg. Mean daytime systolic BP was reduced by 9.8±15.2 mm Hg (P<.001) vs candesartan monotherapy. Office BP reduction was 9.2±18.8/5.0±8.9 mm Hg (P<0.001). Treatment goals (<140/90 mm Hg for office and <135/85 mm Hg for ambulatory BP) were achieved in 58.2% and 78.4% of patients, respectively. There was one drug-related adverse event (edema) and no serious adverse events. Patients of Caucasian ethnicity with moderate essential hypertension uncontrolled on candesartan experienced a further drop in BP using olmesartan and amlodipine.