Showing papers by "Roland E. Schmieder published in 2012"

Renal sympathetic denervation for treatment of drug-resistant hypertension: one-year results from the Symplicity HTN-2 randomized, controlled trial

Abstract: Background—Renal sympathetic nerve activation contributes to the pathogenesis of hypertension. Symplicity HTN-2, a multicenter, randomized trial, demonstrated that catheter-based renal denervation produced significant blood pressure lowering in treatment-resistant patients at 6 months after the procedure compared with control, medication-only patients. Longer-term follow-up, including 6-month crossover results, is now presented. Methods and Results—Eligible patients were on ≥3 antihypertensive drugs and had a baseline systolic blood pressure ≥160 mm Hg (≥150 mm Hg for type 2 diabetics). After the 6-month primary end point was met, renal denervation in control patients was permitted. One-year results on patients randomized to immediate renal denervation (n=47) and 6-month postprocedure results for crossover patients are presented. At 12 months after the procedure, the mean fall in office systolic blood pressure in the initial renal denervation group (−28.1 mm Hg; 95% confidence interval, −35.4 to −20.7; P<...

Renal Hemodynamics and Renal Function After Catheter-Based Renal Sympathetic Denervation in Patients With Resistant Hypertension

Abstract: Increased renal resistive index and urinary albumin excretion are markers of hypertensive end-organ damage and renal vasoconstriction involving increased sympathetic activity. Catheter-based sympathetic renal denervation (RD) offers a new approach to reduce renal sympathetic activity and blood pressure in resistant hypertension. The influence of RD on renal hemodynamics, renal function, and urinary albumin excretion has not been studied. One hundred consecutive patients with resistant hypertension were included in the study; 88 underwent interventional RD and 12 served as controls. Systolic, diastolic, and pulse pressure, as well renal resistive index in interlobar arteries, renal function, and urinary albumin excretion, were measured before and at 3 and 6 months of follow-up. RD reduced systolic, diastolic, and pulse pressure at 3 and 6 months by 22.7/26.6 mm Hg, 7.7/9.7 mm Hg, and 15.1/17.5 mm Hg ( P for all r =−0.46; P P =0.037/0.017) at 3- and 6-month follow-up. Mean cystatin C glomerular filtration rate and urinary albumin excretion remained unchanged after RD; however, the number of patients with microalbuminuria or macroalbuminuria decreased. RD reduced blood pressure, renal resistive index, and incidence of albuminuria without adversely affecting glomerular filtration rate or renal artery structure within 6 months and appears to be a safe and effective therapeutic approach to lower blood pressure in patients with resistant hypertension.

ESH Position Paper: Renal denervation ^ an interventional therapy of resistant hypertension

Abstract: Experts from the European Society of Hypertension prepared this position paper in order to summarize current evidence, unmet needs and practical recommendations on the application of percutaneous transluminal ablation of renal nerves [renal denervation (RDN)] as a novel therapeutic strategy for the treatment of resistant hypertension. The sympathetic nervous activation to the kidney and the sensory afferent signals to the central nervous system represent the targets of RND. Clinical studies have documented that catheter-based RDN decreases both efferent sympathetic and afferent sensory nerve traffic leading to clinically meaningful systolic and diastolic blood pressure (BP) reductions in patients with resistant hypertension. This position statement intends to facilitate a better understanding of the effectiveness, safety, limitations and issues still to be addressed with RDN.

23Na Magnetic Resonance Imaging of Tissue Sodium

Abstract: Hypertension is linked to disturbed total-body sodium (Na+) regulation; however, measuring Na+ disposition in the body is difficult. We implemented 23Na magnetic resonance spectroscopy (23Na-MR) and imaging technique (23Na-MRI) at 9.4T for animals and 3T for humans to quantify Na+ content in skeletal muscle and skin. We compared 23Na-MRI data with actual tissue Na+ content measured by chemical analysis in animal and human tissue. We then quantified tissue Na+ content in normal humans and in patients with primary aldosteronism. We found a 29% increase in muscle Na+ content in patients with aldosteronism compared with normal women and men. This tissue Na+ was mobilized after successful treatment without accompanying weight loss. We suggest that, after further refinements, this tool could facilitate understanding the relationships between Na+ accumulation and hypertension. Furthermore, with additional technical advances, a future clinical use may be possible.

Hypertension and atrial fibrillation: diagnostic approach, prevention and treatment. Position paper of the Working Group "Hypertension Arrhythmias and Thrombosis" of the European Society of Hypertension

Abstract: Hypertension is the most common cardiovascular disorder and atrial fibrillation is the most common clinically significant arrhythmia. Both these conditions frequently coexist and their prevalence increases rapidly with aging. There are different risk factors and clinical conditions predisposing to the development of atrial fibrillation, but due its high prevalence, hypertension is still the main risk factor for the development of atrial fibrillation. Several pathophysiologic mechanisms (such as structural changes, neurohormonal activation, fibrosis, atherosclerosis, etc.) have been advocated to explain the onset of atrial fibrillation. The presence of atrial fibrillation per se increases the risk of stroke but its coexistence with high blood pressure leads to an abrupt increase of cardiovascular complications. Different risk models are available for the risk stratification and the prevention of thromboembolism in patients with atrial fibrillation. In all of them hypertension is present and is an important risk factor. Antihypertensive treatment may contribute to reduce this risk, and it seems some classes are superior to others in the prevention of new-onset atrial fibrillation and prevention of stroke. Antithrombotic treatment with warfarin is effective in the prevention of thromboembolic events, although quite recently, new classes of anticoagulants that do not require international normalized ratio monitoring have been introduced with promising results.

Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and difficult to treat arterial hypertension.

Abstract: Obese patients are prone to arterial hypertension, require more antihypertensive medications, and have an increased risk of treatment-resistant arterial hypertension. Obesity-induced neurohumoral activation appears to be involved. The association between obesity and hypertension shows large inter-individual variability, likely through genetic mechanisms. Obesity affects overall cardiovascular and metabolic risk; yet, the relationship between obesity and cardiovascular risk is complex and not sufficiently addressed in clinical guidelines. The epidemiological observation that obesity may be protective in patients with established cardiovascular disease is difficult to translate into clinical experience and practice. Weight loss is often recommended as a means to lower blood pressure. However, current hypertension guidelines do not provide evidence-based guidance on how to institute weight loss. In fact, weight loss influences on blood pressure may be overestimated. Nevertheless, weight loss through bariatric surgery appears to decrease cardiovascular risk in severely obese patients. Eventually, most obese hypertensive patients will require antihypertensive medications. Data from large-scale studies with hard clinical endpoints on antihypertensive medications specifically addressing obese patients are lacking and the morbidity from the growing population of severely obese patients is poorly recognized or addressed. Because of their broad spectrum of beneficial effects, renin-angiotensin system inhibitors are considered to be the most appropriate drugs for antihypertensive treatment of obese patients. Most obese hypertensive patients require two or more antihypertensive drugs. Finally, how to combine weight loss strategies and antihypertensive treatment to achieve an optimal clinical outcome is unresolved.

Impact of Sex on Cardiovascular Outcome in Patients at High Cardiovascular Risk Analysis of the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects With Cardiovascular Disease (TRANSCEND) and the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET)

Abstract: Background—Epidemiological data suggest that sex independently contributes to cardiovascular risk. Clinical trials are often hampered by the enrollment of few female patients. Methods and Results—The Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET) and the parallel Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) included a large proportion of female patients (9378 female versus 22 168 male patients). Differences in male and female patients enrolled in ONTARGET/TRANSCEND were analyzed for the primary 4-fold end point (composite of cardiovascular death, myocardial infarction, stroke, or admission to hospital for heart failure), a secondary 3-fold end point (cardiovascular death, myocardial infarction, stroke), and individual components of the primary composite. Baseline characteristics included age, ethnicity, body mass index, physical activity, tobacco use, alcohol consumption, formal education, clinical ...

Comparison of Two Noninvasive Devices for Measurement of Central Systolic Blood Pressure With Invasive Measurement During Cardiac Catheterization

Abstract: Recently, a new device for noninvasive assessment of central systolic blood pressure (cSBP) (BPro device with A-Pulse) was approved by the US Food and Drug Administration, but available data are limited. In 52 patients undergoing invasive elective cardiac evaluation, central hemodynamics were measured invasively. Immediately thereafter, radial artery waveforms were sampled by two noninvasive techniques, the BPro and, as a comparator, the SphygmoCor System. Then, central hemodynamics were measured invasively for a second time. The invasively recorded cSBP (137 ± 27 mm Hg) did not differ with both noninvasively assessed cSBP by BPro (136 ± 21 mm Hg, P = .627 vs invasive cSBP) and by SphygmoCor (136 ± 23 mm Hg, P=.694 vs invasive cSBP) and correlated highly between invasively recorded and both noninvasively assessed cSBP. However, using Bland-Altman plots, spreading of compared data of both devices can be found (BPro: 0.87 ± 13 mm Hg vs invasive cSBP; SphygmoCor: 0.77 ± 14 mm Hg vs invasive cSBP). There was an excellent correlation of both noninvasive devices for the calculation of cSBP (r=0.961, P<.001). cSBP differed by only 0.1 ± 6 mm Hg (P=.913) between the two noninvasive devices. Therefore, both noninvasive devices showed an accurate agreement in cSBP compared with invasively measured cSBP.

Tonic Postganglionic Sympathetic Inhibition Induced by Afferent Renal Nerves

Abstract: Other than efferent sympathetic innervation, the kidney has peptidergic afferent fibers expressing TRPV1 receptors and releasing substance P. We tested the hypothesis that stimulation of afferent renal nerve activity with the TRPV1 agonist capsaicin inhibits efferent renal sympathetic nerve activity tonically by a neurokinin 1 receptor-dependant mechanism. Anesthetized Sprague-Dawley rats were instrumented as follows: (1) arterial and venous catheters for recording of blood pressure and heart rate and drug administration; (2) left-sided renal arterial catheter for selective intrarenal administration of the TRPV1 agonist capsaicin (3.3, 6.6, 10, 33*10(-7) m; 10 μL; after 15, 30, 45, and 60 minutes, respectively) to stimulate afferent renal nerve activity; (3) right-sided bipolar electrode for continuous renal sympathetic nerve recording; and (4) specialized renal pelvic and renal artery catheters to separate pelvic from intrarenal afferent activity. Before and after intrarenal capsaicin application, increasing intravenous doses of the neurokinin 1 receptor blocker RP67580 were given. Intrarenal capsaicin decreased integrated renal sympathetic activity from 65.4±13.0 mV*s (baseline) to 12.8±3.2 mV*s (minimum; P<0.01). This sustained renal sympathetic inhibition reached its minimum within 70 minutes and was not directly linked to the transient electric afferent response to be expected with intrarenal capsaicin. Suppressed renal sympathetic activity transiently but completely recovered after intravenous administration of the neurokinin 1 blocker (maximum: 120.3±19.4 mV*s; P<0.01). Intrarenal afferent activity could be unequivocally separated from pelvic afferent activity. For the first time we provide direct evidence that afferent intrarenal nerves provide a tonically acting sympathoinhibitory system, which seems to be rather mediated by neurokinin release acting via neurokinin 1 receptor pathways rather than by electric afferent effects on central sympathetic outflow.

Renal Denervation in a Hypertensive Patient With End‐Stage Renal Disease and Small Arteries: A Direction for Future Research

Abstract: Sympathetic overactivity plays a crucial pathogenetic role in the maintenance and aggravation of arterial hypertension in patients with end-stage renal disease (ESRD). Renal denervation has been shown to be effective and safe in reducing blood pressure (BP) in patients with treatment-resistant hypertension; however, there are only case reports in hypertensive patients with ESRD and data are lacking about possibility of renal denervation in small renal arteries. A woman with uncontrolled treatment-resistant hypertension on chronic hemodialysis underwent bilateral native kidney, catheter-based renal denervation. Both native renal arteries were <4 mm. After 6 months without any change of antihypertensive medication or hemodialysis parameters, the authors observed a remarkable BP reduction of 38/30 mm Hg (from baseline 172/100 mm Hg to 134/70 mm Hg) as evaluated by 24-hour ambulatory BP monitoring. The authors report that renal denervation seems to be effective in controlling hypertension in patients with ESRD, even in cases of small renal arteries.

Dual RAAS suppression: recent developments and implications in light of the ALTITUDE study.

Abstract: Rudolf A de Boer,1 Michel Azizi,2 AH Jan Danser,3 Genevieve Nguyen,4 Jurg Nussberger,5 Luis M Ruilope,6 Roland E Schmieder7 and Massimo Volpe8 1University Medical Center Groningen, Department of Cardiology, University of Groningen, the Netherlands 2Universite Paris-Descartes, Assistance Publique des Hopitaux de Paris, Departement d’Hypertension Arterielle, France 3Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, the Netherlands 4Centre for Interdisciplinary Research in Biology (CIRB), France 5Division of Angiology and Hypertension, Centre Hospitalier Universitaire Vaudois, Switzerland 6Hypertension Unit, Hospital 12 de Octubre and Department of Public Health and Preventive Medicine, Universidad Autonoma, Spain 7University Hospital Erlangen, Nephrology and Hypertension, Germany 8Division of Cardiology, Department of Clinical and Molecular Medicine, University of Rome “Sapienza”and IRCCS Neuromed, Italy Email: r.a.de.boer@umcg.nl RAAS Working Group Update

Impaired increase of retinal capillary blood flow to flicker light exposure in arterial hypertension.

Abstract: We hypothesized that the increase of retinal capillary blood flow (RCF) to flicker light exposure is impaired in subjects with arterial hypertension. In 146 nondiabetic untreated male subjects with (n=50) or without (n=96) arterial hypertension, RCF was measured before and after flicker light exposure noninvasively and in vivo using scanning laser Doppler flowmetry. In addition, in a subgroup of 28 subjects, the change of RCF to flicker light exposure was again assessed during parallel infusion of nitric oxide synthase inhibitor N-monomethyl-L-arginine (L-NMMA). The increase of RCF to flicker light exposure was lower in patients with untreated hypertension compared with normotensive subjects when expressed in absolute terms (7.69±54 versus 27.2±44 AU; P adjusted=0.013) or percent changes (2.95±14 versus 8.33±12%; P adjusted=0.023). Systolic (β=-0.216; P=0.023) but not diastolic blood pressure (β=-0.117; P=0.243) or mean arterial pressure (β=-0.178; P=0.073) was negatively related to the percent change of RCF to flicker light exposure, independently of other cardiovascular risk factors. In the subgroup of 28 subjects, the increase of RCF to flicker light exposure was similar at baseline and during parallel infusion of L-NMMA when expressed in absolute terms (20.0±51 versus 22.6±56 AU; P=0.731) or percent changes (7.12±16 versus 8.29±18%; P=0.607). The increase of RCF to flicker light exposure is impaired in arterial hypertension. In the subgroup of the total study cohort, nitric oxide was not a major determinant of the increase of RCF to flicker light exposure.

Microalbuminuria independently correlates to cardiovascular comorbidity burden in patients with hypertension.

Abstract: Microalbuminuria (MAU) is a marker for endothelial dysfunction and a predictor of cardiovascular events. Cardiovascular risk and mortality are mainly influenced by associated morbidities and risk factors. The present analysis aimed to investigate the relationship between the number of cardiovascular comorbidities and both the prevalence of MAU and the extent of albuminuria (measured as urinary albumin excretion, UAE) in 21,867 high-risk hypertensive patients included in the I-SEARCH study. A total of 6,945 patients (32 %) suffered from at least one comorbidity, out of which 5,437 patients (25 %) had one cardiovascular comorbidity, 1,163 (5 %) patients had two, and 345 (2 %) had ≥3. The prevalence of MAU increased from 54 % in patients without cardiovascular comorbidity to 74 % in the presence of ≥3 comorbidities (p < 0.01). In a multivariate analysis, the presence of ≥3 cardiovascular comorbidities nearly doubled the risk for MAU (HR 1.79, CI 1.07–2.68, p = 0.025). Compared to other comorbidities, patients with left ventricular hypertrophy had the highest prevalence of MAU (68 %, p < 0.01). The extent of UAE was related to the number of concomitant disease and increased significantly in patients with ≥3 comorbidities compared to patients with no comorbidity (UAE of 80 mg/L: 12–22 %, p < 0.01; UAE of 150 mg/L: 8–19 %, p < 0.01). In hypertensive patients at high cardiovascular risk, both the prevalence of MAU and the extent of albuminuria increase with the number of comorbidities.

Barriers to cardiovascular risk prevention and management in Germany--an analysis of the EURIKA study.

Abstract: Background and purpose Despite the availability of risk engines to determine cardiovascular risk, risk factor control is suboptimal. Using EURIKA data we compared risk factor control in Germany with that of 11 other European countries (rest of Europe [ROE]) to identify differences and opportunities for improvement. Methods EURIKA was a multinational, cross-sectional study in 12 European countries including Germany from May 2009 to January 2010. Physicians' attitudes to risk factor control based on the 2007 European guidelines on cardiovascular disease (CVD) prevention in a representative cohort of 7641 primary care outpatients aged ≥ 50 years with no CV disease and at least one major CV risk factor were determined. Results Compared to the ROE, German physicians were more frequently male (72.7% vs 62.6%), had a higher mean age (51.7 ± 8.4 vs 47.0 ± 9.7 years), faced higher patient loads (37.9% vs 16.5% had >199 patients/week), and involved other health sector professionals (dieticians, psychologists) less (31.8% vs 41.0% in the ROE). The European Society of Cardiology (ESC) guidelines on CVD prevention were more important for German physicians (60.6% vs 55.9%), while those who didn't use them gave reasons for nonuse as too many (62.5% vs 46.2%), too confusing, unrealistic, or not applicable to their patients. Risk engines were used less (54.5% vs 70.7%), with perceived lack of time (65.5% vs 60.2%) a frequent reason for nonuse. Risk factor control in German patients was inadequate (control rates: hypertension 36.3%, dyslipidemia 30.4%, type 2 diabetes 40.6%, obesity 28.8%) but largely comparable to other ROE countries; however, physicians tended to overestimate control rates. Conclusion EURIKA provides comprehensive data on the status of primary prevention of CVD in clinical practice in Germany and reveals considerable potential for improving the primary prevention of CVD.

Reversibility of the Effects of Aliskiren in the Renal Versus Systemic Circulation

Abstract: Summary Background and objectives Renal hemodynamic effects of inhibitors of the renin-angiotensin system can increase the risk of acute kidney injury under certain conditions. The BP-lowering effects of the renin inhibitor aliskiren are sustained 3–4 weeks after withdrawal. In this study, the reversibility of the renal hemodynamic effects of aliskiren was tested. Design, setting, participants, & measurements In this open-label study, renal perfusion was measured by 1.5-T magnetic resonance imaging–arterial spin labeling in 34 subjects with arterial hypertension before aliskiren (pre-aliskiren), after 4 weeks of aliskiren treatment (300 mg), and 4–5 days (∼2.5–3.0× plasma half-life) after withdrawal (post-aliskiren). Results Aliskiren reduced systolic BP from 152 ± 14 to 139 ± 16 mmHg (P Conclusions After withdrawal of aliskiren, the effects on BP were sustained, whereas increase in renal perfusion was reversed, which was associated with recovery of angiotensin II and aldosterone to pretreatment levels. Renal hemodynamic effects are more readily reversible than systemic effects of aliskiren.

Aliskiren for the treatment of essential hypertension under real-life practice conditions: design and baseline data of the prospective 3A registry

Abstract: BACKGROUND: The renin-angiotensin system (RAS) is a key target for blood pressure control and for cardiovascular and renal protection. Aliskiren is the first-in-class direct oral inhibitor of renin that controls the rate-limiting step in the RAS cascade. So far little is known about the use and efficacy of aliskiren in the treatment of essential hypertension under clinical practice conditions. METHODS: The 3A registry was an open, prospective cohort study (observational registry) of 14,988 patients in 899 offices throughout Germany. Consecutive patients were eligible for inclusion if their physician had decided to modify their antihypertensive therapy. This included treatment with aliskiren or an angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB) or agents not blocking the RAS, alone or on top of an existing drug regimen. RESULTS: Mean age of patients was 65 years, their mean body mass index was 28.2 kg/m(2) 53.5% were men, 36% working, 90% in statutory health insurance and 26% in any disease management programme. Patients in the aliskiren and the RAS groups compared with the non-RAS group were older, more often men, had a longer history of hypertension, and had a higher prevalence of comorbidities (diabetes, chronic heart failure, ischaemic heart disease, renal disease). Mean systolic, but not diastolic blood pressure was substantially higher in the aliskiren group (158/91 mmHg vs. 154/89 mmHg in ACE-I/ARB vs. 152/89 mmHg in non-RAS). Mean number of antihypertensive drugs was higher in the aliskiren group compared with the other groups (3.0 drugs vs. 2.5 in ACE-I/ARB vs. 1.6 in non-RAS; p < 0.0001). CONCLUSIONS: In this large cohort of outpatients with hypertension, aliskiren was used mainly in patients with more severe stages of hypertension and those with concomitant diseases such as diabetes mellitus and impaired renal function. The 3A registry will provide important information about the use and efficacy of aliskiren in a real-life setting.

Effect of the rs168924 single-nucleotide polymorphism in the SLC6A2 catecholamine transporter gene on blood pressure in Caucasians.

Abstract: J Clin Hypertens (Greenwich). 2012; 14:293–298. ©2012 Wiley Periodicals, Inc. The NG_016969.1:g.5003A>G promoter polymorphism (rs168924) in the SLC6A2 norepinephrine transporter gene was found to be predictive of the hypertensive status in a Japanese population, but no data are available for Caucasians. Genotyping for rs168924 was performed in 282 young men with normal blood pressure (BP), grade 1 or 2 hypertension. In addition to casual BP, 24-hour ABPM and echocardiography were performed. Multiple regression analysis revealed a significant association of rs168924 genotype with diagnosis of hypertension (P=.044), casual systolic BP (SBP) levels (P=.028), and daytime ambulatory SBP (P=.02). The finding that rs168924 was also significantly associated with diastolic posterior wall thickness (P=.041), an echocardiographic index of hypertensive cardiac target organ damage, further supports the notion that the rs168924 SNP in SLC6A2 in fact might influence BP. Unlike previous findings in a Japanese population, in our Caucasian study cohort the presence of the minor rs168924 G allele was associated with lower prevalence of hypertension. J Clin Hypertens (Greenwich). 2012;00:00–00. ©2012 Wiley Periodicals, Inc.

Wall-to-lumen ratio of retinal arterioles: a reproducible, valid and noninvasive approach for evaluation of early arteriolar changes in arterial hypertension in vivo.

Abstract: S mall resistance arteries (small arteries and arterioles with a diameter <350 mm) are major regulators of peripheral vascular resistance, which represents the hemodynamic hallmark of arterial hypertension. According to Hagen-Poiseuille‘s law, flow resistance is inversely related to the fourth power of the vessel. Thus, even mild narrowing (either structural or functional or both) increases total peripheral vascular resistance, and thereby blood pressure. To determine changes in small arteries and arterioles, either within a participant or between participants, media-to-lumen ratio or wall-to-lumen ratio of small resistance arteries and arterioles has been measured [1–3] and found to represent an early phenomenon in the pathophysiology of arterial hypertension [4]. Moreover, in a cohort of 45 never-treated individuals with primary hypertension and 40 normotensive individuals, SBP and DBP were significantly related to media-to-lumen ratio of isolated subcutaneous small arteries and arterioles indicating that the degree of blood pressure elevation is related to the severity of small artery and arteriolar changes [5]. Of most interest and clinical importance, increased media-to-lumen ratio of isolated and in-vitro examined subcutaneous small arteries and arterioles (using a myograph) were found to predict cardiovascular outcome in individuals with arterial hypertension [6–8]. In an Italian study, 128 participants (including 59 individuals with primary hypertension, 17 with pheochromocytoma, 20 with primary aldosteronism, 12 with renovascular hypertension and 20 normotensive individuals with diabetes mellitus)

Achievement of recommended glucose and blood pressure targets in patients with type 2 diabetes and hypertension in clinical practice - study rationale and protocol of DIALOGUE

Abstract: Patients with type 2 diabetes have 2–4 times greater risk for cardiovascular morbidity and mortality than those without, and this is even further aggravated if they also suffer from hypertension. Unfortunately, less than one third of hypertensive diabetic patients meet blood pressure targets, and more than half fail to achieve target HbA1c values. Thus, appropriate blood pressure and glucose control are of utmost importance. Since treatment sometimes fails in clinical practice while clinical trials generally suggest good efficacy, data from daily clinical practice, especially with regard to the use of newly developed anti-diabetic and anti-hypertensive compounds in unselected patient populations, are essential. The DIALOGUE registry aims to close this important gap by evaluating different treatment approaches in hypertensive type 2 diabetic patients with respect to their effectiveness and tolerability and their impact on outcomes. In addition, DIALOGUE is the first registry to determine treatment success based on the new individualized treatment targets recommended by the ADA and the EASD. DIALOGUE is a prospective observational German multicentre registry and will enrol 10,000 patients with both diabetes and hypertension in up to 700 sites. After a baseline visit, further documentations are scheduled at 6, 12 and 24 months. There are two co-primary objectives referring to the most recent guidelines for the treatment of diabetes and hypertension: 1) individual HbA1c goal achievement with respect to anti-diabetic pharmacotherapy and 2) individual blood pressure goal achievement with different antihypertensive treatments. Among the secondary objectives the rate of major cardio-vascular and cerebro-vascular events (MACCE) and the rate of hospitalizations are the most important. The registry will be able to gain insights into the reasons for the obvious gap between the demonstrated efficacy and safety of anti-diabetic and anti-hypertensive drugs in clinical trials and their real world balance of effectiveness and safety.

Guideline adherence in cardiovascular risk assessment and analysis in 15,000 hypertensive German patients in real life: results of the Prospective 3A Registry.

Abstract: The benefit obtained from antihypertensive treatment is related more to overall cardiovascular risk reduction than to blood pressure levels. Accurate implementation of cardiovascular diagnostics is a key step toward assessment of cardiovascular risk. In the 3A Registry study, data about patient history, concomitant diseases, diagnostic procedures, and medications were prospectively collected. A total of 14,738 patients recruited by 899 physicians in 2008 and 2009 were analyzed. Assessment of cardiovascular risk factors and subclinical end-organ damage (SOD) showed broad differences in the implementation of European Society of Hypertension/European Society of Cardiology recommendations. Electrocardiograms were available in 59% of patients, cholesterol in 71.4%, and glucose in 69.7%. Almost all patients (99.6%) had creatinine measurements performed and microalbuminuria was measured in 8.5%. Metabolic syndrome (MS) had been evaluated in 59.7%. Implementation of diagnostic guidelines was highest in hypertensive patients with diabetes, followed by patients with known cardiovascular disease and established chronic renal insufficiency. For hypertensive patients without known comorbidities, the authors estimated that up to 29% had missed SOD (detection rate <50%) and 13% missed MS due to incomplete assessment of risk factors. This large registry study shows that assessment for cardiovascular risk factors and SOD is incomplete. Major efforts are required to improve comprehensive hypertension management as recommended by current guidelines.

Role of neuroendocrine activation for left ventricular hypertrophy in hypertension.

Abstract: T he development of left ventricular hypertrophy (LVH) imparts an adverse prognosis in patients with arterial hypertension [1,2]. A major goal of antihypertensive therapy is, therefore, to achieve reversal of LVH, which has repeatedly been demonstrated to improve prognosis [3–6]. The lowering of blood pressure (BP) is widely viewed as the dominant factor for achieving reduction of an elevated LV mass in hypertension. On the basis of currently available evidence, the European Society of Hypertension Practice Guidelines recommend a target BP value of less than 140/ 90mmHg, regardless of whether LVH is present or not [7]. Interestingly, in an open-label randomized study in 1111 hypertensive patients, electrocardiographic evidence of LVH after 2 years was less frequent in patients with tight BP control (<130 mmHg compared with those with usual BP control of less than 140 mmHg systolic) [8]. In accordance, there is recent evidence that targeting such a lower BP value of less than 130/80 mmHg has beneficial effects on diastolic function in patients with arterial hypertension [9]. As diastolic dysfunction is associated with adverse outcomes independently of LVH [10], target BP may need to be revised in the future for hypertensive patients with hypertensive heart disease. In addition to the role of BP, a positive relationship between level of sodium intake and LV mass was demonstrated decades ago [11]. Although only few data are available, there is some evidence from older studies that sodium restriction causes regression of LVH after several weeks of sodium restriction [12]. More recently, sodium restriction has also been shown to reduce ECG criteria of LVH. However, the fact that this appears to occur very rapidly, within 7 days, is puzzling, and may have more to do with alterations in the conduction of electrical signals through

Chronobiology of blood pressure and chronopharmacotherapy of arterial hypertension

Abstract: Der Blutdruck ist einem zirkadianen Rhythmus unterworfen, der zu einer nachtlichen Absenkung fuhrt. Bei Diabetes, Niereninsuffizienz, linksventrikularer Hypertrophie, Schlafapnoe, Schwangerschaftshypertonie und verschiedenen sekundaren Hypertonieformen kann die nachtliche Absenkung aufgehoben oder in ihr Gegenteil verkehrt sein. Die Diagnostik erfolgt mit Hilfe der 24-h-Blutdruckmessung, die aber in der Praxis noch zu selten fur eine klinische Einschatzung des Patienten und die Therapiesteuerung herangezogen wird. Eine Anpassung der Auswahl und des Einnahmezeitpunkts der antihypertensiven Pharmakotherapie im Hinblick auf den zirkadianen Rhythmus wirkt sich gunstig auf die Blutdruckkontrolle und die kardiovaskulare Morbiditat aus. Das gilt vor allem fur Patienten mit fehlendem nachtlichem Blutdruckabfall oder einem Anstieg, bei denen die abendliche Medikation zu einer Normalisierung des Blutdrucks und der Wiederherstellung der physiologischen zirkadianen Rhythmik beitragen kann. Die vorliegende Arbeit gibt einen aktuellen Uberblick zur Chronopharmakotherapie der arteriellen Hypertonie und gibt praktische Empfehlungen zur Umsetzung dieser Erkenntnisse im klinischen Alltag.

Current status of renal denervation in resistant hypertension

Abstract: Resistant hypertension is a frequent form of arterial hypertension that, with the exception of malignant hypertension, constitutes the most dangerous stage of arterial hypertension. Recently we have improved the detection, diagnosis, and therapy of resistant hypertensives. The technique of renal denervation with a catheter has improved the control of blood pressure in such patients. The technique is simple, safe, and available data indicates that it is effective. More data and longer follow-up of patients are required to promote wide acceptance of this new technique.