Showing papers by "Roland E. Schmieder published in 2013"

2013 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: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

2013 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: Because of new evidence on several diagnostic and therapeutic aspects of hypertension, the present guidelines differ in many respects from the previous ones. Some of the most important differences are listed below: 1. Epidemiological data on hypertension and BP control in Europe. 2. Strengthening of the prognostic value of home blood pressure monitoring (HBPM) and of its role for diagnosis and management of hypertension, next to ambulatory blood pressure monitoring (ABPM). 3. Update of the prognostic significance of night-time BP, white-coat hypertension and masked hypertension. 4. Re-emphasis on integration of BP, cardiovascular (CV) risk factors, asymptomatic organ damage (OD) and clinical complications for total CV risk assessment. 5. Update of the prognostic significance of asymptomatic OD, including heart, blood vessels, kidney, eye and brain. 6. Reconsideration of the risk of overweight and target body mass index (BMI) in hypertension. 7. Hypertension in young people. 8. Initiation of antihypertensive treatment. More evidence-based criteria and no drug treatment of high normal BP. 9. Target BP for treatment. More evidence-based criteria and unified target systolic blood pressure (SBP) (<140 mmHg) in both higher and lower CV risk patients. 10. Liberal approach to initial monotherapy, without any all-ranking purpose. 11. Revised schema for priorital two-drug combinations. 12. New therapeutic algorithms for achieving target BP. 13. Extended section on therapeutic strategies in special conditions. 14. Revised recommendations on treatment of hypertension in the elderly. 15. Drug treatment of octogenarians. 16. Special attention to resistant hypertension and new treatment approaches. 17. Increased attention to OD-guided therapy. 18. New approaches to chronic management of hypertensive disease

2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension.

Abstract: 1. INTRODUCTION1.1 PrinciplesThe 2013 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines continue to adhere to some fundamental principles that inspired the 2003 and 2007 guidelines, namely to base recommendations on properly conducted studies identified from an ext

2013 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: Abbreviations and acronyms1 Introduction1.1 Principles1.2 New aspects2 Epidemiological aspects2.1 Relationship of blood pressure to cardiovascular and renal damage2.2 Definition and classification ...

Ambulatory Blood Pressure Changes After Renal Sympathetic Denervation in Patients With Resistant Hypertension

Abstract: Background—Catheter-based renal sympathetic denervation (RDN) reduces office blood pressure (BP) in patients with resistant hypertension according to office BP. Less is known about the effect of RDN on 24-hour BP measured by ambulatory BP monitoring and correlates of response in individuals with true or pseudoresistant hypertension. Methods and Results—A total of 346 uncontrolled hypertensive patients, separated according to daytime ambulatory BP monitoring into 303 with true resistant (office systolic BP [SBP] 172.2±22 mm Hg; 24-hour SBP 154±16.2 mm Hg) and 43 with pseudoresistant hypertension (office SBP 161.2±20.3 mm Hg; 24-hour SBP 121.1±19.6 mm Hg), from 10 centers were studied. At 3, 6, and 12 months follow-up, office SBP was reduced by 21.5/23.7/27.3 mm Hg, office diastolic BP by 8.9/9.5/11.7 mm Hg, and pulse pressure by 13.4/14.2/14.9 mm Hg (n=245/236/90; P for all <0.001), respectively. In patients with true treatment resistance there was a significant reduction with RDN in 24-hour SBP (−10.1/−10...

23Na Magnetic Resonance Imaging-Determined Tissue Sodium in Healthy Subjects and Hypertensive Patients

Abstract: High dietary salt intake is associated with hypertension; the prevalence of salt-sensitive hypertension increases with age. We hypothesized that tissue Na(+) might accumulate in hypertensive patients and that aging might be accompanied by Na(+) deposition in tissue. We implemented (23)Na magnetic resonance imaging to measure Na(+) content of soft tissues in vivo earlier, but had not studied essential hypertension. We report on a cohort of 56 healthy control men and women, and 57 men and women with essential hypertension. The ages ranged from 22 to 90 years. (23)Na magnetic resonance imaging measurements were made at the level of the calf. We observed age-dependent increases in Na(+) content in muscle in men, whereas muscle Na(+) content did not change with age in women. We estimated water content with conventional MRI and found no age-related increases in muscle water in men, despite remarkable Na(+) accumulation, indicating water-free Na(+) storage in muscle. With increasing age, there was Na(+) deposition in the skin in both women and men; however, skin Na(+) content remained lower in women. Similarly, this sex difference was found in skin water content, which was lower in women than in men. In contrast to muscle, increasing Na(+) content was paralleled with increasing skin water content. When controlled for age, we found that patients with refractory hypertension had increased tissue Na(+) content, compared with normotensive controls. These observations suggest that (23)Na magnetic resonance imaging could have utility in assessing the role of tissue Na(+) storage for cardiovascular morbidity and mortality in longitudinal studies.

Updated ESH position paper on interventional therapy of resistant hypertension

Abstract: Out of the overall hypertensive population it is estimated that approximately 10% have treatment resistant hypertension (TRH). Percutaneous catheter-based transluminal renal ablation (renal denervation [RDN] by delivery of radiofrequency energy) has emerged as a new approach to achieve sustained blood pressure reduction in patients with TRH. This innovative interventional technique is now available across Europe for severe TRH for those patients in whom pharmacologic strategies and lifestyle changes have failed to control blood pressure below target (usually <140/90 mmHg). In 2012, the "ESH position paper: renal denervation - an interventional therapy of resistant hypertension" was published to facilitate a better understanding of the effectiveness, safety, limitation and unresolved issues. We have now updated this position paper since numerous studies have been published over the last year providing more data about the rationale, therapeutic efficacy and safety of RDN. In the upcoming ESH/ESC guidelines for the management of arterial hypertension, therapeutic options of treatment resistant hypertension will be addressed, but only briefly, and thus it is the focus of this paper to provide detailed and updated information on this innovative interventional technique.

Rationale and design of a large registry on renal denervation: The Global SYMPLICITY registry

Abstract: Aims Hypertension is a global healthcare concern associated with a wide range of comorbidities. The recognition that elevated sympathetic drive plays an important role in the pathogenesis of hypertension led to the use of renal artery denervation to interrupt the efferent and afferent sympathetic nerves between the brain and kidneys to lower blood pressure. Clinical trials of the Symplicity™ renal denervation system have demonstrated that radiofrequency ablation of renal artery nerves is safe and significantly lowers blood pressure in patients with severe resistant (systolic BP >160 mmHg) hypertension. Smaller ancillary studies in hypertensive patients suggest a benefit from renal denervation in a variety of conditions such as chronic kidney disease, glucose intolerance, sleep apnoea and heart failure. Methods and results The Global SYMPLICITY registry, which incorporates the GREAT SYMPLICITY registry initiated in Germany, is being conducted worldwide to evaluate the safety and efficacy of treatment with the Symplicity renal denervation system in real-world uncontrolled hypertensive patients, looking first at subjects with severe resistant hypertension to confirm the results of prior clinical trials, but then also subjects with a wider range of baseline blood pressure and coexisting comorbidities. Conclusions The rationale, design and first baseline data from the Global SYMPLICITY registry are presented.

Cardiac ablation and renal denervation systems have distinct purposes and different technical requirements.

Abstract: Ahmed et al. report the use of a cardiac electrophysiology ablation system for renal denervation in a single-center, single-armed, noncontrolled trial of 10 patients with severe refractory hypertension ([1][1]). Cardiac ablation and renal denervation systems are designed to comply with distinct and

Does renal artery supply indicate treatment success of renal denervation

Abstract: Renal denervation (RDN) emerged as an innovative interventional antihypertensive therapy. With the exception of pretreatment blood pressure (BP) level, no other clear predictor for treatment efficacy is yet known. We analyzed whether the presence of multiple renal arteries has an impact on BP reduction after RDN. Fifty-three patients with treatment-resistant hypertension (office BP ≥ 140/90 mmHg and 24-h ambulatory BP monitoring (≥130/80 mmHg) underwent bilateral catheter-based RDN. Patients were stratified into one-vessel (OV) (both sides) and at least multivessel (MV) supply at one side. Both groups were treated on one vessel at each side; in case of multiple arteries, only the dominant artery was treated on each side. Baseline clinical characteristics (including BP, age, and estimated glomerular filtration rate) did not differ between patients with OV (n = 32) and MV (n = 21). Office BP was significantly reduced in both groups at 3 months (systolic: OV −15 ± 23 vs. MV −16 ± 20 mmHg; diastolic: OV −10 ± 12 vs. MV −8 ± 11 mmHg, both p = NS) as well as 6 months (systolic: OV −18 ± 18 vs. MV −17 ± 22 mmHg; diastolic: OV −10 ± 10 vs. −10 ± 12 mmHg, both p = NS) after RDN. There was no difference in responder rate (rate of patients with office systolic BP reduction of at least 10 mmHg after 6 months) between the groups. In patients with multiple renal arteries, RDN of one renal artery—namely, the dominant one—is sufficient to induce BP reduction in treatment-resistant hypertension.

Central Pulse Pressure Is an Independent Determinant of Vascular Remodeling in the Retinal Circulation

Abstract: Pulse pressure has been recognized as a risk factor for stroke. Moreover, it was shown that central pulse pressure relates more strongly to vascular disease and outcome than (peripheral) brachial pulse pressure. Because vascular remodeling in the retinal circulation mirrors the 1 in the cerebral circulation and represents an easy, noninvasive possibility to assess microvascular changes in humans, we analyzed the impact of central pulse pressure on retinal vascular structure in humans. The study cohort comprised 135 nondiabetic patients across a wide range of blood pressure values. Parameter of retinal arteriolar remodeling (wall-to-lumen ratio) was assessed noninvasively and in vivo by scanning laser Doppler flowmetry. Central pulse pressure and augmentation index normalized to a heart rate of 75 beats per minute were assessed by pulse wave analysis. Central pulse pressure correlated with wall-to-lumen ratio (r=0.302; P<0.001), central augmentation index normalized to a heart rate of 75 beats per minute correlated with wall-to-lumen ratio (r=0.190; P=0.028), and in accordance pulse pressure amplification (peripheral pulse pressure/central pulse pressure) was negatively correlated with wall-to-lumen ratio (r=-0.223; P=0.009). In contrast, central mean arterial pressure was not correlated with wall-to-lumen ratio (r=0.110; P=0.203). Multiple regression analysis revealed an independent relationship between wall-to-lumen ratio and central pulse pressure (β=0.277; P=0.009), but not with other classical cardiovascular risk factors. Thus, central pulse pressure, indicative of changes in large conduit arteries is an independent determinant of vascular remodeling in small retinal arterioles. Such a relationship indicates a coupling and crosstalk between the microvascular and macrovascular changes attributable to hypertension.

Catheter-Based Renal Nerve Ablation and Centrally Generated Sympathetic Activity in Difficult-to-Control Hypertensive Patients: Prospective Case Series

Abstract: The recently published article by Brinkmann et al1 attempted to investigate the effect of catheter-based renal denervation (RDN) on blood pressure (BP) and muscle sympathetic nerve activity. The article is of interest; however, some aspects require clarification. In disagreement with several other studies, the authors report no significant overall blood BP lowering effect after RDN in a small group of 12 patients, and not surprisingly did not observe any changes in muscle sympathetic nerve activity. As shown in larger series, procedural success is clearly observed in patients with high BP as a surrogate of increased sympathetic activity. In contrast to the Symplicity trials, the baseline BP herein was 157/85 mm …

Vascular and Renal Hemodynamic Changes after Renal Denervation

Abstract: Summary Background and objectives Renal denervation (RDN) has been shown to be effective in reducing BP in treatment-resistant hypertension. Measurement of the renal and sympathetic activity revealed a decrease in sympathetic drive to the kidney and small resistance vessels after RDN. However, the consequences on renal perfusion and renal vascular resistance (RVR), as well as central hemodynamics, are unknown. Design, setting, participants, & measurements Nineteen patients with treatment-resistant hypertension (office BP≥140/90 mmHg, despite at least three antihypertensive drugs [including a diuretic], and diagnosis confirmed by 24-hour ambulatory BP monitoring) underwent RDN between January and October 2011. Renal perfusion and RVR were noninvasively assessed by magnetic resonance imaging with arterial spin labeling, and renal function was assessed by estimating GFR before (day −1), after (day +1), and again after 3 months of RDN. Central hemodynamics was assessed using pulse wave analysis at day −1 and after 6 months of RDN. Results Peripheral office BP (systolic, 158±26 versus 142±23 mmHg, P=0.002; diastolic, 83±13 versus 76±9 mmHg, P=0.02) and mean systolic 24-hour ambulatory BP (159±17 versus 152±17 mmHg, P=0.02) were significantly reduced 6 months after RDN. Renal perfusion was not statistically different between day −1 and day +1 (256.8 [interquartile range (IQR), 241–278] versus 263.4 [IQR, 252–277] ml/min per 100 g; P=0.17) as well as after 3 months (256.8 [IQR, 241–278] versus 261.2 [IQR, 240–285] ml/min per 100 g; P=0.27) after RDN. RVR dropped (432.1 [IQR, 359–525] versus 390.6 [IQR, 338–461] AU; P=0.02), whereas renal function was not statistically different at any time point. Central systolic BP (145±31 versus 131±28 mmHg; P=0.009), diastolic BP (85±18 versus 80±14 mmHg; P=0.03), and central pulse pressure (61±18 versus 52±18 mmHg; P=0.02) were significantly reduced 6 months after RDN. Central augmentation index (24±8 versus 20±8%; P=0.02) was decreased 6 months after RDN. Conclusion The data indicate that RDN significantly reduced peripheral and central BP. Despite reduced systemic BP, renal perfusion and function did not change after RDN.

Determinants of Cardiovascular Risk in Haemodialysis Patients: Post hoc Analyses of the AURORA Study

Abstract: Background: Haemodialysis patients are at high risk for cardiovascular (CV) events. The aim of the current study was to characterise the role of traditional and uraemia-specific CV risk factors in this patient population. Methods: A post hoc analysis of the AURORA trial which enrolled 2,776 haemodialysis patients from 280 centres and had a mean follow-up period of 3.2 years. Determinants of CV endpoints (time to major cardiovascular event (MACE), cardiac event, CV death) were identified by univariate Cox regression analysis. Subsequently, independent determinants were identified by multivariate regression analysis. Results: For the primary endpoint MACE (myocardial infarction, stroke and cardiac death), multivariate analysis revealed that independent determinants were: age (hazard ratio (HR) 1.03 per year), serum phosphate level (HR 1.50 per mmol/l), albumin level (HR 0.94 per g/l), years on haemodialysis (HR 1.03 per year), diabetes mellitus (HR 1.38), preexisting coronary heart disease (HR 1.54) and C-reactive protein (CRP) level (HR 1.14 per mg/l). However, conventional risk factors such as smoking, dyslipidaemia, systolic and diastolic blood pressure and pulse pressure had no significant effect. Conclusions: Although we identify CRP, low albumin, and high phosphorus as risk factors for MACE, lowering CRP did not influence MACE outcomes in our trial. Caution is therefore warranted in implying risk factors being causal in end-stage renal disease.

Effects of manidipine vs. amlodipine on intrarenal haemodynamics in patients with arterial hypertension

Abstract: AIMS Intraglomerular pressure is one of the main drivers of progression of renal failure. Experimental data suggest that there are important differences between calcium channel blockers (CCBs) in their renal haemodynamic effects: manidipine reduces, whereas amlodipine increases intraglomerular pressure. The aim of this study was to investigate the effects of manidipine and amlodipine treatment on intragomerular pressure (Pglom) in patients with mild to moderate essential hypertension.

Patients with treatment-resistant hypertension report increased stress and anxiety: A worldwide study

Abstract: Objective:Treatment-resistant hypertension (rHTN) is defined as blood pressure (BP) that remains above goal despite compliance with at least three antihypertensive medications including a diuretic all at maximum tolerated doses or BP controlled on at least four drugs. An increased risk for cardiovas

Clinical situations associated with difficult-to-control hypertension.

Abstract: There is no doubt that patients with high blood pressure (BP) are at higher cardiovascular and death risk than those subjects whose BP levels are below the admitted normal threshold. However, most of the epidemiological surveys show that BP is uncontrolled in more than fifty percent of hypertensive subjects. There are several reasons that can justify this lack of hypertension control, some of them depending on the patient, such as therapeutic adherence, or some related to the doctor, due to therapeutic inertia or reluctance to increment the number and doses of antihypertensive drugs. Sometimes the efficacy or adverse effects related to the antihypertensive drugs underlie the uncontrolled hypertension. And, finally, there are some clinical conditions that are associated with difficult-to-control hypertension. Among them, comorbidities such as diabetes, obesity, obstructive sleep apnoea syndrome or chronic kidney disease, but also drug-related hypertension or resistant hypertension. In this article we review the epidemiology and the conditions which are related to poorly controlled hypertension and that can explain why hypertension may become difficult-to-treat.

Local application of tropicamide 0.5% reduces retinal capillary blood flow.

Abstract: Introduction. Scanning laser Doppler flowmetry (SLDF) plays an important role in the study of arterial hypertension, diabetes and stroke. The technology enables non-invasive measurement of the retinal capillary perfusion (RCF), retinal haemodynamics and arteriolar morphology in human. The values can be measured in mydriasis or in non-mydriatic eyes. It is not clear whether the using of vasoactive mydriatica for pupil dilation affects the measured parameters in retina. Acetylcholine, a vasoactive neurotransmitter in human retina, affects the contractility of pericytes using muscarinic receptors and stimulates endothelial synthesis of nitric oxide (NO). We examined whether blockade of the retinal cholinergic receptors by tropicamide affects the RCF. Methods. We measured RCF in both eyes of 13 healthy subjects before and 30 min after the local application of one drop of 0.5% tropicamide to the right eye. The mean age of the group was 44 ± 14 years. The left eye was used as control. RCF was measured b...

Review of direct renin inhibition by aliskiren.

Abstract: Numerous clinical studies have been conducted to analyse the ability of renin-angiotensin system blockade to lower blood pressure and to reduce end-organ damage. In addition to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, direct renin inhibitors emerged as an attractive option to inhibit the renin-angiotensin system and thus to prevent cardiovascular damage. Based on the publication of the most recent available results of ALTITUDE and ASTRONAUT, we review the data with respect to the direct renin inhibitor aliskiren given as an antihypertensive drug, in monotherapy and combination therapy, and the most recent publication analysing the effects of aliskiren on end-organ protection.

The Sympathetic Nervous System in Chronic Kidney Disease

Abstract: Accumulating evidence has shown that the sympathetic nervous system plays an important role in the pathophysiology and progression of several chronic disorders, e.g., arterial hypertension, cardiac arrhythmias, heart failure, and in particular chronic kidney disease (CKD). Experimental and clinical studies provide evidence that sympathetic inhibition using either sympatholytic pharmacotherapy or catheter-based renal denervation has beneficial effects in patients with CKD. Randomized clinical trials are needed to characterize the underlying pathophysiological mechanisms, and systematically evaluate the therapeutic effects of sympathetic inhibition in this high-risk patient population. In this review current knowledge of the role of the sympathetic nervous system in the development and progression of CKD will be summarized, and novel treatment options targeting sympathetic nervous system activity will be discussed.

Interpreting treatment-induced blood pressure reductions measured by ambulatory blood pressure monitoring.

Abstract: It is well known that 24-h ambulatory blood pressure monitoring (ABPM) provides a more accurate picture of a patient's blood pressure (BP) compared with clinic BP measurement. Twenty-four-hour ABPM better predicts hypertension-related risks such as end-organ damage including left ventricular hypertrophy, cardiovascular (CV) events and mortality. Threshold BP values for hypertension based on 24-h ABPM results have been established, including daytime and night-time averages. Nevertheless, the relationship between 24-h ABPM and clinic BP measurement in patients on antihypertensive therapy, and in particular how each may change in response to antihypertensive therapy, is less clear. This review will provide an overview of current knowledge on the relation between clinic BP and ambulatory BP reductions in clinical trials on antihypertensive therapies. Reduction in CV risk and its correlation with the magnitude of reduction in both clinic and ambulatory BP are explored. The most striking result is that reduction in clinic BP and ambulatory BP do not correspond in a 1:1 fashion, that is, smaller changes in 24-h ABPM correspond to significantly larger changes in clinic BP.

Poor Glycemic Control Is Related to Increased Nitric Oxide Activity Within the Renal Circulation of Patients With Type 2 Diabetes

Abstract: OBJECTIVE Experimental studies have shown that glucose releases endothelial nitric oxide (NO) and that NO contributes to renal hyperperfusion in models of diabetes. To examine whether this translates into the human condition, we studied the relationship between glycemic control and renal NO activity in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 113 patients with type 2 diabetes and a wide range of HbA 1c concentrations were included. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were determined by constant infusion input clearance. Functional NO activity in the renal circulation was determined as change of RPF to infusion of the NO synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA) (4.25 mg/kg). As additional markers, we measured urinary excretion of NO (UNOx) and l-arginine–to–asymmetrical dimethylarginine (ADMA) ratio in plasma. RESULTS Subjects within the highest tertile of HbA 1c concentration had increased RPF (low, medium, and high tertiles 576 ± 17 vs. 585 ± 22 vs. 627 ± 33 mL/min/m 2 , P = 0.05 by one-way ANOVA), while GFR was similar across tertiles. The response of RPF to NOS blockade was augmented in subjects with higher HbA 1c levels (−55 ± 7 vs. −64 ± 8 vs. −86 ± 8 mL/min, P = 0.04 by one-way ANOVA). Further, l-arginine–to–ADMA ratio and UNOx were increased in subjects with higher HbA 1c levels. CONCLUSIONS In line with experimental evidence, we could demonstrate in humans that poor glycemic control is related to higher NO activity and hyperperfusion of the kidney. The renal NO system may thus be a novel therapeutic target for improving renal hemodynamics in patients with diabetes.

25-hydroxyvitamin D insufficiency is associated with impaired renal endothelial function and both are improved with rosuvastatin treatment.

Abstract: Vitamin D deficiency is nowadays considered as a potential cardiovascular and renal risk factor. We tested the hypotheses that vitamin D deficiency impairs the endothelial function of renal vasculature and whether vitamin D levels and endothelial function can be improved by the treatment with statins. In a double-blind, randomized study of 31 hypercholesterolemic patients with vitamin D insufficiency (<30 ng/ml) were randomly assigned to rosuvastatin (10 mg/d) and placebo for 6 weeks. Basal nitric oxide (NO) activity of the renal vasculature was assessed both before and after the blockade of NO synthases with systemic infusion of N(G)-monomethyl-l-arginine (l-NMMA). In parallel, 25(OH)D was measured. Multiple regression analysis revealed that at baseline 25(OH)D is an independent determinant of basal NO activity as assessed by the decrease in RPF, in response to l-NMMA (β = −0.446, r = 0.015). Compared to placebo treatment, rosuvastatin increased 25(OH)D levels (21.6 ± 4.0 vs. 24.1 ± 8.1 ng/ml, p = 0.039). Basal NO activity was significantly more increased after 6-week therapy with rosuvastatin than with placebo (−94.8 ± 70 vs. −68.2 ± 32 ml/min, p = 0.044), indicating increased basal NOS activity after 6 weeks of rosuvastatin treatment. Basal NO activity in the placebo phase was correlated inversely with 25(OH)D (r = −0.385; p = 0.027). Thus, vitamin D insufficiency is associated with impaired endothelial function in the renal vasculature and both were beneficially influenced by the treatment with rosuvastatin.