Showing papers by "Roland E. Schmieder published in 2007"

2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: 2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension.

Abstract: Authors/Task Force Members: Giuseppe Mancia, Co-Chairperson (Italy), Guy De Backer, Co-Chairperson (Belgium), Anna Dominiczak (UK), Renata Cifkova (Czech Republic), Robert Fagard (Belgium), Giuseppe Germano (Italy), Guido Grassi (Italy), Anthony M. Heagerty (UK), Sverre E. Kjeldsen (Norway), Stephane Laurent (France), Krzysztof Narkiewicz (Poland), Luis Ruilope (Spain), Andrzej Rynkiewicz (Poland), Roland E. Schmieder (Germany), Harry A.J. Struijker Boudier (Netherlands), Alberto Zanchetti (Italy)

2007 Guidelines for the management of arterial hypertension

Abstract: For several years the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) decided not to produce their own guidelines on the diagnosis and treatment of hypertension but to endorse the guidelines on hypertension issued by the World Health Organization (WHO) and International Society of Hypertension (ISH)1,2 with some adaptation to reflect the situation in Europe. However, in 2003 the decision was taken to publish ESH/ESC specific guidelines3 based on the fact that, because the WHO/ISH Guidelines address countries widely varying in the extent of their health care and availability of economic resource, they contain diagnostic and therapeutic recommendations that may be not totally appropriate for European countries. In Europe care provisions may often allow a more in-depth diagnostic assessment of cardiovascular risk and organ damage of hypertensive individuals as well as a wider choice of antihypertensive treatment. The 2003 ESH/ESC Guidelines3 were well received by the clinical world and have been the most widely quoted paper in the medical literature in the last two years.4 However, since 2003 considerable additional evidence on important issues related to diagnostic and treatment approaches to hypertension has become available and therefore updating of the previous guidelines has been found advisable. In preparing the new guidelines the Committee established by the ESH and ESC has agreed to adhere to the principles informing the 2003 Guidelines, namely 1) to try to offer the best available and most balanced recommendation to all health care providers involved in the management of hypertension, 2) to address this aim again by an extensive and critical review of the data accompanied by a series of boxes where specific recommendations are given, as well as by a concise set of practice recommendations to be published soon thereafter as already done in 2003; …

2007 ESH-ESC guidelines for the management of arterial hypertension - The task force for the management of arterial hypertension of the European society of hypertension (ESH) and of the European society of cardiology (ESC)

Abstract: Authors/Task Force Members: Giuseppe Mancia, Co-Chairperson (Italy), Guy De Backer, Co-Chairperson (Belgium), Anna Dominiczak (UK), Renata Cifkova (Czech Republic) Robert Fagard (Belgium), Giuseppe Germano (Italy), Guido Grassi (Italy), Anthony M. Heagerty (UK), Sverre E. Kjeldsen (Norway), Stephane Laurent (France), Krzysztof Narkiewicz (Poland), Luis Ruilope (Spain), Andrzej Rynkiewicz (Poland), Roland E. Schmieder (Germany), Harry A.J. Struijker Boudier (Netherlands), Alberto Zanchetti (Italy)

Increased Wall:Lumen Ratio of Retinal Arterioles in Male Patients With a History of a Cerebrovascular Event

Abstract: Arterial hypertension is a major risk factor for stroke, and retinal vessels can be regarded as a mirror of the cerebral vasculature. Whether vascular remodeling of retinal arterioles with ageing and hypertension plays a role in cerebrovascular risk stratification has not yet been adequately addressed. In study 1, retinal arteriolar structure was assessed in 182 normotensive volunteers and 117 patients with essential hypertension. In study 2, we compared retinal arteriolar structure among 74 normotensive volunteers, 47 patients with treated essential hypertension, and 18 subjects with a history of a cerebrovascular event. Retinal arteriolar structure was assessed using scanning laser Doppler flowmetry and automatic full-field perfusion imaging analysis. In study 1, wall:lumen ratio of retinal arterioles revealed a significant correlation with age ( r =0.198; P =0.001). In study 2, wall:lumen ratio was highest in patients with a history of a cerebrovascular event compared with treated hypertensive and normotensive subjects (0.46±0.08, 0.36±0.14, and 0.35±0.12; P =0.007). When the treated group with hypertension was divided into 2 subgroups according to the quality of blood pressure control, patients with poor blood pressure control showed higher wall:lumen ratio than subjects with good blood pressure control (0.40±0.13 versus 0.31±0.13; P =0.025). Thus, assessment of wall:lumen ratio of retinal arterioles emerged as an attractive tool to identify treated patients with hypertension with increased cerebrovascular risk.

Participation preferences of patients with acute and chronic conditions.

Abstract: Background There is little knowledge as to whether the chronicity of a disease affects patients desire for participation. Aim To study whether participation preferences vary according to the type of disease. Design, participants and methods Data of 1393 patients from six trials with different medical conditions (hypertension, depression, breast cancer, schizophrenia, multiple sclerosis, minor traumas) were pooled and analysed, using multiple regression analysis controlling for socio-demographic variables. Results Younger age, better education as well as female gender accounted for a small but statistically significantly greater desire to participate. Patients suffering from multiple sclerosis (MS) exhibited significantly higher participation preferences than the other diagnostic groups. There were no major differences between the other diagnostic groups. Age, gender, education and diagnosis explained only 14% of the variance. Conclusions We found no clear differences between chronic and acute conditions. However, patients suffering from MS, a chronic condition, were clearly different from all other diagnostic groups. The reasons for this difference remain unclear. The predictive value of socio-demography and type of illness is low.

Impact of telmisartan versus ramipril on renal endothelial function in patients with hypertension and type 2 diabetes.

Abstract: OBJECTIVE—One of the earliest signs of vascular change is endothelial dysfunction, which is also known to provoke albuminuria and to predict cardiovascular prognosis. The aim of this study was to analyze the effects of renin-angiotensin system (RAS) blockade on renal endothelial function. RESEARCH DESIGN AND METHODS—In a multicenter, prospective, double-blind, forced-titration, randomized study, 96 patients with type 2 diabetes, hypertension, glomerular filtration rate >80 ml/min, and normo- or microalbuminuria were treated once daily with 40/80 mg telmisartan or 5/10 mg ramipril for 9 weeks. RESULTS—The mean ± SE fall in renal plasma flow (RPF) in response to intravenous NG-monomethyl-l-arginine (l-NMMA), reflecting the magnitude of nitric oxide (NO) activity, increased with telmisartan from 71.9 ± 9.0 ml/min before therapy to 105.2 ± 9.7 ml/min at the end of treatment (P CONCLUSIONS—In patients with type 2 diabetes, telmisartan and ramipril both increased NO activity of the renal endothelium significantly, which in turn may support the preservation of cardiovascular and renal function.

Low-grade albuminuria and cardiovascular risk : what is the evidence?

Abstract: Microalbuminuria (MA), conventionally defined as a urinary albumin excretion (UAE) of 30–300 mg/day, is recognised as a marker of endothelial dysfunction. Furthermore, it represents an established risk factor for cardiovascular morbidity and mortality and for end-stage renal disease in individuals with an adverse cardiovascular risk profile. It is common in the general population, particularly in patients with diabetes mellitus or arterial hypertension. There is growing evidence from prospective observational trials that UAE levels well below the current MA threshold (“lowgrade MA”) are also associated with an increased risk of incident cardiovascular disease and allcause mortality. Even in apparently healthy individuals (without diabetes or hypertension), such an association has been shown. As albuminuria screening assays that are reliable even in the lower ranges are commercially available, there may be an important clinical role for MA in disease screening, comparable to the role of blood pressure and lipid screening. MA is modifiable, and the inhibition of the renin-angiotensin system by ACE inhibitors and AT1 receptor antagonists has been shown to result in a lower incidence of cardiovascular events.

Plasma renin and the antihypertensive effect of the orally active renin inhibitor aliskiren in clinical hypertension.

Abstract: Summary Background: Aliskiren is the first in a new class of orally effective renin inhibitors for the treatment of hypertension. Methods: In 569 patients with mild-to-moderate hypertension, blood pressure (BP), plasma renin activity (PRA) and plasma renin concentration (PRC) were measured before and after 8 weeks of double-blind treatment with once-daily oral doses of aliskiren (150, 300 or 600 mg), irbesartan 150 mg or placebo. Results: Aliskiren 150, 300 and 600 mg and irbesartan 150 mg significantly reduced mean cuff sitting systolic BP (SBP) from baseline (p < 0.001 vs. placebo). Aliskiren 150, 300 and 600 mg significantly reduced geometric mean PRA by 69%, 71% and 75% from baseline respectively (p < 0.05 vs. placebo). Irbesartan 150 mg significantly increased PRA by 109% (p < 0.05 vs. placebo). Aliskiren dose-dependently increased PRC from baseline by 157%, 246% and 497%, at 150, 300 and 600 mg respectively, compared with a 9% decrease with placebo (p < 0.05). PRC increased significantly more with aliskiren 300 and 600 mg compared with irbesartan 150 mg (105%; p < 0.05). Regression analysis showed no significant correlations between baseline PRA and changes in SBP in any of the treatment groups, but interestingly, the slopes of the regression lines between changes in SBP and log-transformed baseline PRA were +2.0 for placebo and −1.5, −1.8 and −2.3 for aliskiren 150, 300 and 600 mg respectively. The slope for irbesartan 150 mg (−1.4) was similar to that for aliskiren 150 mg. Conclusions: Aliskiren reduces SBP and PRA and increases PRC dose-dependently. In contrast, irbesartan reduces SBP but increases both PRC and PRA. As PRA is a measurement of angiotensin I-generating capacity, PRA can be used for measuring the ability of an antihypertensive agent to prevent the generation or action of Ang II, either directly (renin inhibitors, beta-blockers, central α2-agonists) or indirectly (AT1-receptor blockers, ACE inhibitors).

Analysis of NO-synthase expression and clinical risk factors in human diabetic nephropathy

Abstract: Background. Changes of renal nitric oxide (NO) production have been associated with glomerular hyperfiltration, vascular permeability, albuminuria, glomerulosclerosis and tubulointerstitial fibrosis. Several studies demonstrated an up- as well as downregulated expression of NO-synthases (NOS) in experimental diabetic nephropathy. It is still not yet specified whether the regulation and activity of NOS is changed in human diabetic nephropathy. Methods. Renal biopsies and clinical data of 45 patients with diabetic nephropathy and of 10 control subjects were investigated. Glomerular and cortical endothelial NOS (eNOS) and inducible NOS (iNOS) expression were assessed by immunohistochemical staining and related to clinical data such as the duration of diabetes, insulin therapy and arterial hypertension, albuminuria/proteinuria, eGFR according to the formula modification of diet in renal disease (MDRD), presence of vascular complications or diabetic retinopathy. Results. The mean age of patients at biopsy was 60.3 years and the mean duration of diabetes 12.9 years. Expression of cortical and glomerular eNOS was increased in type 2 diabetes (P < 0.05). Increased expression of glomerular and cortical eNOS correlated with more severe vascular complications (r = 0.44; P < 0.05). Glomerular eNOS was strongly increased among different degrees of proteinuria (P < 0.01). In contrast to expression levels of eNOS, the glomerular expression pattern of iNOS changed from an endothelial pattern in glomeruli with preserved morphology towards expression predominantly by inflammatory cells. Conclusions. Thus, increased eNOS expression by the renal endothelium could be demonstrated in type 2 diabetic nephropathy, whereas iNOS was unchanged but spatially differentially expressed. The eNOS expression was related to vascular lesions and the degree of proteinuria.

Effect of Rosuvastatin on Outcomes in Chronic Haemodialysis Patients: Baseline Data from the AURORA Study

Abstract: Background: Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). Aims: AURORA (A study to evaluate the Use

Cardiovascular risk reduction by reversing endothelial dysfunction: ARBs, ACE inhibitors, or both? Expectations from the ONTARGET Trial Programme.

Abstract: Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin-angiotensin system (RAS), has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB) and/or angiotensin-converting enzyme (ACE) inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) Programme is expected to provide the ultimate evidence of whether improved endothelial function translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade). Completion of ONTARGET is expected in 2008.

Fourier analysis of the envelope of the ophthalmic artery blood flow velocity: age- and blood pressure related impact.

Abstract: The harmonic content of the envelope waveform of the blood flow velocity in the ophthalmic artery was analyzed in aging and arterial hypertension. The case-control study enrolled 98 healthy men (age: 44.0±15.6 years), 100 healthy women (age: 44.5±19.1 years), which is group 1, and overall 199 hypertensive patients with increased systolic and diastolic blood pressure (in millimeters of mercury) before registration of the blood flow velocity using pulsed Doppler sonography. Group 2 was sufficiently treated (≤140/≤90), group 3 (>140/≤90) and group 5 (>140/>90) were insufficiently treated, and group 4 (>140/≤90) and group 6 (>140/>90) were untreated. Cronbach-α reliability of the calculated spectral coefficient and SI (SI) was 0.88 and 0.93, respectively. In control subjects, the SI was influenced by age (men: 45.1%; women: 50.2%; P P 43 years of age (men: 0.37±0.11; women: 0.26±0.08; P

MDR1 genotype-dependent regulation of the aldosterone system in humans.

Abstract: ObjectiveAldosterone plays a major role in the development of both hypertension and heart failure. As aldosterone is a substrate of the ABCB1 (P-glycoprotein) efflux transporter, whose expression and activity has been shown to be linked to the ABCB1 3435C→T polymorphism, we tested the impact of the

High sodium intake modulates left ventricular mass in patients with G expression of +1675 G/A angiotensin II receptor type 2 gene.

Abstract: Objectives In patients with hypertension left ventricular hypertrophy (LVH) is associated with genetic variations of the angiotensin type 2 receptor (AT2R). Hypertension and LVH are often aggravated by salt intake. Our objective was to assess the relationship between AT2R gene variation and salt intake and their impact on left ventricular mass (LVM). Methods and results In 205 subjects with normal or mildly elevated blood pressure, we assessed sodium intake and left ventricular structure and function by echocardiography. Intronic +1,675 G/A polymorphism of the AT2R gene was investigated. A-allele carriers had a greater LVM (P = 0.049) than G-allele carriers. Independent of diet, septal wall thickness was higher in A-allele carriers (P = 0.001). Fractional fibre shortening was greater in A-allele carriers (P = 0.034), and the velocity of circumferential fibre shortening tended to be greater in A-allele carriers (P = 0.057). When the two groups were stratified according to their salt intake, only G-allele carriers displayed a modulating effect of salt intake on LVM. Covariance analysis revealed that there was a trend towards a modulating effect of salt intake on LVM, even after taking blood pressure into account (P = 0.054). Conclusion Our data clearly support the notion that LVM is influenced by AT2R polymorphisms. Furthermore, G-allele carriers in particular appear to be susceptible to a modifying effect of increased salt intake on LVM.

The potential role of prorenin in diabetic nephropathy.

Abstract: Type 2 diabetes is one of the fastest growing epidemics in the world. By the year 2010 approximately 366 million people are expected to be affected and one-third of the patients with type 2 diabetes will develop diabetic nephropathy [1]. Diabetic nephropathy is already the reason for renal replacement therapy in 40% of new patients in the western hemisphere. In addition to hyperglycaemia and increased blood pressure, the renin–angiotensin system (RAS) plays a crucial role in the pathogenesis of diabetic nephropathy [2]. In particular, the RAS has been found to be activated in renal tissue, leading to excessive angiotensin II synthesis [3,4]. Most interesting, in human biopsies of patients with diabetic nephropathy, chymase expression has been found to be increased in glomeruli, suggesting an angiotensin-converting enzyme (ACE)-independent synthesis of angiotensin II in diabetic nephropathy, the consequences of which still need to be specified [5]. Accordingly, prospective trials have shown that angiotensin receptor blockers decrease the progression of diabetic nephropathy and the incidence of end-stage renal disease [6,7]; but why angiotensin receptor blockers could not completely stop the decline of glomerular filtration rate, even when combined with ACE inhibitors, is still unexplained [8]. The lack of a proper dose–response curve for angiotensin receptor blockers could be of importance, since clinical trials have now found that very high doses of angiotensin receptor blockers, beyond that given for lowering blood pressure, reduce proteinuria in diabetic nephropathy more than standard doses [9,10].

Ambulatory blood pressure in hypertensive patients with left ventricular hypertrophy: efficacy of first-line combination perindopril/indapamide therapy.

Abstract: Background: Ambulatory blood pressure (BP) is more sensitive than offi ce BP and is highly correlated with the left ventricular mass (LVM) of hypertensive patients with left ventricular hypertrophy (LVH). Methods: In this prospectively designed ancillary study of the PICXEL trial, the effects of fi rst-line combination perindopril/indapamide on ambulatory BP were compared with those of monotherapy with enalapril in 127 patients. Hypertensive patients with LVH received once daily either perindopril 2 mg/indapamide 0.625 mg (n = 65) or enalapril 10 mg (n = 62) for 52 weeks. Dose adjustments were allowed for uncontrolled BP. Twenty-four-hour ambulatory BP and echocardiographic parameters were measured at baseline, week 24, and week 52. Results: At study end, both treatments signifi cantly improved ambulatory BP compared with baseline (p 0.01). Perindopril/indapamide treatment reduced 24-hour and daytime systolic BP (SBP) and pulse pressure (PP) signifi cantly more than enalapril treatment (p < 0.01). No signifi cant between-group differences were noted for diastolic BP (DBP) or for night-time measurements. Trough/peak ratios were higher with perindopril/indapamide than with enalapril (88.5 vs 65.8 for SBP and 86.7 vs 63.9 for DBP, respectively). The global smoothness index was higher with perindopril/indapamide than with enalapril (6.6 vs 5.2 for SBP and 5.6 vs 4.9 for DBP, respectively). With perindopril/indapamide treatment, LVM index was signifi cantly reduced (−9.1 g/m 2 from baseline; p vs baseline <0.001). More patients required dose increases with enalapril (87%) than with perindopril/indapamide (71%). No unusual safety elements were noted. Conclusions: First-line perindopril/indapamide combination decreased ambulatory SBP and PP, and LVM more effectively than enalapril.

Renin inhibitors: Optimal strategy for renal protection

Abstract: Diabetic nephropathy and hypertension are the major causes of chronic kidney disease. The renin system plays a key role in the control of blood pressure (BP), as well as in the regulation of renal and adrenal function. Chronic activation of the renin system can lead to organ damage, particularly renal damage; increasing evidence indicates that suppression of the renin system can provide renal protection. Despite the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), the renin system is not completely suppressed. The direct renin inhibitors (DRIs) provide suppression of the entire renin system at the rate-limiting step. Studies in humans with early DRIs indicated potential renoprotective effects, but these agents failed in clinical development due to poor oral bioavailability. Aliskiren is a new orally active DRI with proven BP-lowering effects. Animal studies indicate that aliskiren may provide renal protection, and data from human studies are anticipated.

[Albuminuria: an indicator of cardiovascular risk].

Abstract: Der Ubertritt von Albumin aus dem Gefaslumen in das umliegende Gewebe stellt immer eine ernsthafte Storung der Integritat des gesamten Gefassystems dar. Klinisch werden diese Veranderungen als „cotton-wool“-Herde in der Retina oder durch das Auftreten von Albumin im Urin erkennbar. Dabei steigt mit der Hohe der Albuminausscheidung das kardiovaskulare Risiko auch schon unterhalb der Schwellenwerte fur Mikroalbuminurie an. Ein Ubertritt von Albumin in das Gewebe stellt einen Hinweis auf eine Storung der Schrankenfunktion der Endothelzellen dar. In der Niere kommt es u.a. zu einer Schadigung von Podozyten, Mesangium- und Endothelzellen, einem Verlust der Ladungsselektivitat und einer veranderten Expression von Matrixproteinen. Diese Veranderungen sind aber nicht nur in den Nieren, sondern auch im Myokard nachweisbar. Die definierten Grenzen fur die Mikroalbuminurie (> 30 mg/24 h) und Proteinurie (> 300 mg/24 h) sind fur die kardiovaskulare Prognose jedoch nur eingeschrankt bedeutsam, da die Risikoerhohung bereits bei einer geringeren Albuminausscheidung beginnt. Die Pravalenz einer Mikroalbuminurie liegt in der Bevolkerung bei etwa 8%, in Hochrisikogruppen dagegen bei bis zu 50% und mehr. Sie ist mit einer Erhohung der kardiovaskularen Morbiditat und Mortalitat verbunden. Eine Reihe von therapeutischen Ansatzen (enge Blutzuckereinstellung, Blutdrucksenkung, Lipidsenker) fuhrt sowohl zu einer Verminderung der Albuminurie als auch zu einer Verbesserung der kardiovaskularen Prognose. Als zentraler Angriffspunkt der kardiovaskularen Protektiongilt die wirksame Hemmung des Renin-Angiotensin-Aldosteron-Systems (RAAS). RAAS-blockierende Substanzen sind nicht nur mit einer Verringerung von Endorganschaden (Herzinsuffizienz, diabetische Nephropathie, zerebrovaskulare Ereignisse) verbunden, sondern konnen auch zu einer Verminderung der Mortalitat fuhren. Die fruhzeitige Diagnose, eine grundliche kardiovaskulare Diagnostik und engmaschige Einstellung der kardiovaskularen Risikofaktoren unter konsequentem Einsatz von RAAS-blockierenden Substanzen erscheinen bei Patienten mit dem Nachweis einer Albuminurie angezeigt.