Showing papers by "Roland E. Schmieder published in 2011"

Reappraisal of European guidelines on hypertension management:: A European Society of Hypertension Task Force document

Abstract: ACEangiotensin-converting enzymeBPblood pressureDBPdiastolic blood pressureeGFRestimated glomerular filtration rateESCEuropean Society of CardiologyESHEuropean Society of HypertensionETendothelinIM...

Urinary Sodium and Potassium Excretion and Risk of Cardiovascular Events

Abstract: [HR], 1.53; 95% CI, 1.26-1.86; and 11.2% for 8 g/day; HR, 1.66; 95% CI, 1.312.10), MI (6.8%; HR, 1.48; 95% CI, 1.11-1.98 for 8 g/day), stroke (6.6%; HR, 1.48; 95% CI, 1.09-2.01 for 8 g/day), and hospitalization for CHF (6.5%; HR, 1.51; 1.122.05 for 8 g/day). Lower sodium excretion was associated with an increased risk of CV death (8.6%; HR, 1.19; 95% CI, 1.02-1.39 for 2-2.99 g/day; 10.6%; HR, 1.37; 95% CI, 1.09-1.73 for 2 g/day), and hospitalization for CHF (5.2%; HR, 1.23; 95% CI, 1.01-1.49 for 2-2.99 g/day) on multivariable analysis. Compared with an estimated potassium excretion of less than 1.5 g per day (n=2194; 6.2% with stroke), higher potassium excretion was associated with a reduced risk of stroke (4.7% [HR, 0.77; 95% CI, 0.63-0.94] for 1.5-1.99 g/day; 4.3% [HR, 0.73; 95% CI, 0.59-0.90] for 2-2.49 g/day; 3.9% [HR, 0.71; 95% CI, 0.56-0.91] for 2.5-3 g/day; and 3.5% [HR, 0.68; 95% CI, 0.49-0.92] for 3 g/day) on multivariable analysis. Conclusions The association between estimated sodium excretion and CV events was J-shaped. Compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all CV events, and a sodium excretion of less than 3 g per day was associated with increased risk of CV mortality and hospitalization for CHF. Higher estimated potassium excretion was associated with a reduced risk of stroke.

Changes in Albuminuria Predict Mortality and Morbidity in Patients with Vascular Disease

Abstract: The degree of albuminuria predicts cardiovascular and renal outcomes, but it is not known whether changes in albuminuria also predict similar outcomes. In two multicenter, multinational, prospective observational studies, a central laboratory measured albuminuria in 23,480 patients with vascular disease or high-risk diabetes. We quantified the association between a greater than or equal to twofold change in albuminuria in spot urine from baseline to 2 years and the incidence of cardiovascular and renal outcomes and all-cause mortality during the subsequent 32 months. A greater than or equal to twofold increase in albuminuria from baseline to 2 years, observed in 28%, associated with nearly 50% higher mortality (HR 1.48; 95% CI 1.32 to 1.66), and a greater than or equal to twofold decrease in albuminuria, observed in 21%, associated with 15% lower mortality (HR 0.85; 95% CI 0.74 to 0.98) compared with those with lesser changes in albuminuria, after adjustment for baseline albuminuria, BP, and other potential confounders. Increases in albuminuria also significantly associated with cardiovascular death, composite cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure), and renal outcomes including dialysis or doubling of serum creatinine (adjusted HR 1.40; 95% CI 1.11 to 1.78). In conclusion, in patients with vascular disease, changes in albuminuria predict mortality and cardiovascular and renal outcomes, independent of baseline albuminuria. This suggests that monitoring albuminuria is a useful strategy to help predict cardiovascular risk.

Blood Pressure Targets Recommended by Guidelines and Incidence of Cardiovascular and Renal Events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)

Abstract: Background—Hypertension treatment guidelines recommend that blood pressure (BP) be lowered to 75%) in which BP was reduced to <140/90 or <130/80 mm Hg. After adjustment for demographic and clinical variables, a progressive increase in the proportion of visits in which BP was reduced to <140/90 or <130/80 mm Hg was associated with a progressive reduction in the risk of stroke, new onset of microalbuminuria or macroalbuminuria, and return to normoalbuminuria in albuminuric patients. An increased frequency of BP control to either target did not have an...

Beyond salt: lifestyle modifications and blood pressure.

Abstract: Lifestyle changes have been shown to effect significant blood pressure (BP) reductions. Although there are several proposed neurohormonal links between weight loss and BP, body mass index itself appears to be the most powerful mediator of the weight-BP relationship. There appears to be a mostly linear relationship between weight and BP; as weight is regained, the BP benefit is mostly lost. Physical activity, but more so physical fitness (the physiological benefit obtained from physical activity), has a dose-dependent BP benefit but reaches a plateau at which there is no further benefit. However, even just a modest physical activity can have a meaningful BP effect. A diet rich in fruits and vegetables with low-fat dairy products and low in saturated and total fat (DASH) is independently effective in reducing BP. Of the dietary mineral nutrients, the strongest data exist for increased potassium intake, which reduces BP and stroke risk. Vitamin D is associated with BP benefit, but no causal relationship has been established. Flavonoids such as those found in cocoa and berries may have a modest BP benefit. Neither caffeine nor nicotine has any significant, lasting BP effect. Biofeedback therapies such as those obtained with device-guided breathing have a modest and safe BP benefit; more research is needed before such therapies move beyond those having an adjunctive treatment role. There is a strong, linear relationship between alcohol intake and BP; however, the alcohol effects on BP and coronary heart disease are divergent. The greatest BP benefit seems to be obtained with one drink per day for women and with two per day for men. This benefit is lost or attenuated if the drinking occurs in a binge form or without food. Overall, the greatest and most sustained BP benefit is obtained when multiple lifestyle interventions are incorporated simultaneously.

Rosuvastatin in Diabetic Hemodialysis Patients

Abstract: A randomized, placebo-controlled trial in diabetic patients receiving hemodialysis showed no effect of atorvastatin on a composite cardiovascular endpoint, but analysis of the component cardiac endpoints suggested that atorvastatin may significantly reduce risk. Because the AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events) trial included patients with and without diabetes, we conducted a post hoc analysis to determine whether rosuvastatin might reduce the risk of cardiac events in diabetic patients receiving hemodialysis. Among the 731 participants with diabetes, traditional risk factors such as LDL-C, smoking, and BP did not associate with cardiac events (cardiac death and nonfatal myocardial infarction). At baseline, only age and high-sensitivity C-reactive protein were independent risk factors for cardiac events. Assignment to rosuvastatin associated with a nonsignificant 16.2% reduction in risk for the AURORA trial's composite primary endpoint of cardiac death, nonfatal MI, or fatal or nonfatal stroke (HR 0.84; 95% CI 0.65 to 1.07). There was no difference in overall stroke, but the rosuvastatin group had more hemorrhagic strokes than the placebo group (12 versus two strokes, respectively; HR, 5.21; 95% CI 1.17 to 23.27). Rosuvastatin treatment significantly reduced the rates of cardiac events by 32% among patients with diabetes (HR 0.68; 95% CI 0.51 to 0.90). In conclusion, among hemodialysis patients with diabetes mellitus, rosuvastatin might reduce the risk of fatal and nonfatal cardiac events.

New software analyses increase the reliability of measurements of retinal arterioles morphology by scanning laser Doppler flowmetry in humans.

Abstract: Objective The investigation of the retinal arterioles offers the unique opportunity to analyze in vivo arteriolar remodeling in arterial hypertension in humans. We analyzed the reliability of assessing retinal arteriolar morphology with our new version of the software analyses for scanning laser Doppler flowmetry. Method In the test-retest reliability study, 10 eyes of 10 healthy persons were measured during 5 days under routine laboratory conditions with the Heidelberg Retinal Flowmetry. In a second study, interobserver and intraobserver reliability was analyzed from retinal images of 18 patients with three types of arterial hypertension by three readers and the most experienced reader analyzed all images twice on two different days. Images were analyzed by the old and the newly developed software versions. To characterize the reliability, the coefficients of variation were calculated. Results The test-retest study analyzed with the new program showed that the variation coefficients of vessel and lumen diameter, wall thickness, wall/lumen ratio and new calculated parameter: lumen/vessel diameter ratio of retinal arterioles were significantly less than 10%, with the exception of the wall cross-sectional area (12.5%). The interobserver and intraobserver reliability showed in nearly all circumstances coefficients of variations of less than 10% and did not differ across various readers and patient groups. Conclusion The new software 'SLDF version 4.0' clearly improved the reliability of assessing the structural parameters of the retinal arterioles. The application delivers reliable measurements of the retinal arteriolar structure in vivo in humans.

Expert consensus statement on interventional renal sympathetic denervation for hypertension treatment

Abstract: This commentary summarizes the expert consensus and recommendations of the working group 'Herz und Niere' of the German Society of Cardiology (DGK), the German Society of Nephrology (DGfN) and the German Hypertension League (DHL) on renal denervation for antihypertensive treatment. Renal denervation is a new, interventional approach to selectively denervate renal afferent and efferent sympathetic fibers. Renal denervation has been demonstrated to reduce office systolic and diastolic blood pressure in patients with resistant hypertension, defined as systolic office blood pressure ≥ 160 mm Hg and ≥ 150 mm Hg in patients with diabetes type 2, which should currently be used as blood pressure thresholds for undergoing the procedure. Exclusion of secondary hypertension causes and optimized antihypertensive drug treatment is mandatory in every patient with resistant hypertension. In order to exclude pseudoresistance, 24-hour blood pressure measurements should be performed. Preserved renal function was an inclusion criterion in the Symplicity studies, therefore, renal denervation should be only considered in patients with a glomerular filtration rate > 45 ml/min. Adequate centre qualification in both, treatment of hypertension and interventional expertise are essential to ensure correct patient selection and procedural safety. Long-term follow-up after renal denervation and participation in the German Renal Denervation (GREAT) Registry are recommended to assess safety and efficacy after renal denervation over time.

Physician attitudes to blood pressure control: findings from the Supporting Hypertension Awareness and Research Europe-wide survey.

Abstract: OBJECTIVES: The Supporting Hypertension Awareness and Research Europe-wide (SHARE) physician survey aimed to qualify the key challenges that physicians face when trying to get patients to blood pressure (BP) goal. METHODS: The SHARE survey was open to physicians involved in the treatment of patients with hypertension, was anonymous, and was designed to take 15 min to complete. The survey included 45 questions covering physicians' demographic information, views on the BP targets recommended by the European Society of Hypertension-European Society of Cardiology guidelines, opinions on acceptable levels of BP control, and perceptions about the challenges associated with getting patients to BP goal. RESULTS: The survey was conducted between May and December 2009, and 2629 European physicians responded. The mean (± SD) levels of SBP/DBP that physicians were satisfied with, concerned about, or would cause them to take immediate action were 131.6 ± 9.5 /81.9 ± 5.6, 148.9 ± 11.3 / 91.6 ± 5.8, and 168.2 ± 17.1 / 100.1 ± 7.8 mmHg, respectively. Overall, 95.0 and 90.1% of the physicians, respectively, felt that patients SBP/DBP needed to be higher than the guideline recommended goal levels before taking immediate action. CONCLUSION: Clinical hesitation in relation to reducing elevated BP to goal levels is putting patients at increased cardiovascular risk and contributing to the substantial health and economic burden associated with uncontrolled BP. A number of strategies are discussed that have been shown to be effective in countering this problem.

Effects of statin treatment on endothelial function, oxidative stress and inflammation in patients with arterial hypertension and normal cholesterol levels

Abstract: ObjectivePatients with arterial hypertension are characterized by impaired endothelial function and increased cardiovascular risk. Statins have been proposed as a potential treatment option in hypertension, even in those with normal low-density lipoprotein (LDL)-cholesterol levels. We tested whether

Association of (pro)renin receptor gene polymorphism with blood pressure in Caucasian men.

Abstract: The renin–angiotensin system is a major regulatory system of cardiovascular and renal function. Recently, (pro)renin receptor [(P)RR] was identified as new component of the renin–angiotensin system. The IVS5+169C>T polymorphism of the (P)RR gene was shown to be associated with blood pressure (BP) in

Serum levels of the Th1 chemoattractant interferon-gamma-inducible protein (IP) 10 are elevated in patients with essential hypertension

Abstract: Growing evidence shows that inflammation has a pivotal role in the pathophysiology of essential hypertension (EH). Although it has been acknowledged that target organ damage involves an inflammatory response, most work has focused on the role of macrophages, but T lymphocytes have recently become the center of interest. The goal of our study was to evaluate the role of T-cell-specific cytokines in the pathogenesis of EH. The study examined 39 patients with EH (57.7±6.8 years, systolic blood pressure (SBP) 157.5±11.8 mm Hg, diastolic blood pressure 92.2±12.9 mm Hg, mean arterial pressure 113.9±12.6 mm Hg) and 30 healthy, normotensive controls (55.2±4.9 years). Blood was drawn from a peripheral vein, and serum levels of interferon-inducible protein (IP)-10 and interleukins (IL)-4, -7 and -13 were measured by a multiplexing assay. Hypertensive patients had significantly higher levels of IP-10, IL-4, IL-7 and IL-13 than control subjects. When the patients were classified into tertiles according to their serum IP-10 levels (T1: 41.2-94.1 pg ml(-1); T2: 103.4-162.5 pg ml(-1); T3: 171.7-443.5 pgml(-1)), the patients classified into the highest tertile also had the highest blood pressure. In a correlation analysis, plasma IP-10 concentration was significantly associated with SBP (r=0.59, P<0.001). Furthermore, hypertensives with microalbuminuria, an early sign of hypertensive target organ damage, had the highest IP-10 levels. A stepwise multivariate regression analysis revealed IP-10 as the strongest independent predictor of SBP (P=0.01). In conclusion, our study provides new insights into the pathophysiological mechanisms in EH linking inflammation and IP-10. However, these preliminary results need to be confirmed in larger trials.

Renal protection with angiotensin receptor blockers: where do we stand.

Abstract: The increasing burden on health care providers from chronic kidney disease (CKD) is due to the escalating prevalence of obesity, hypertension and type 2 diabetes. The gradual decline in kidney function in the presence of these risk factors is also associated with increased cardiovascular disease. Excess angiotensin II production by the renin-angiotensin system is responsible, at least in part, for development of hypertension and for damage in the kidneys and the cardiovascular system. Pharmacological targeting of the renin-angiotensin system not only reduces blood pressure, but may also provides more direct vascular protection. Angiotensin receptor blockers (ARBs) are better tolerated than angiotensin-converting enzyme inhibitors and, thus, may be a more practical therapeutic option. Clinical studies have demonstrated the efficacy of irbesartan, losartan, telmisartan and valsartan in the management of CKD. All ARBs tested to date have proved effective in improving at least some aspects of renal dysfunction. Few within-class comparative studies exist. Telmisartan provides superior reductions in proteinuria to losartan, however, even when blood pressures are equalized with concomitant antihypertensives. This superiority is probably linked to higher receptor affinity, longer plasma half-life and higher lipophilicity of telmisartan compared with other ARBs. The reduction of proteinuria with ARBs is also linked to improved cardiovascular outcomes. After a decade of research, there is now substantial evidence to show that the use of ARBs provides an efficacious treatment option for the prevention of renal disease progression in patients with hypertension and/or diabetes.

Reduction in basal nitric oxide activity causes albuminuria.

Abstract: OBJECTIVE The barrier function of the glomerular filter has been studied for decades. Albuminuria reflects a malfunction of this barrier, and in animals dysfunctional endothelial nitric-oxide (NO) synthase results in albuminuria. We aimed to analyze the importance of NO for the glomerular barrier function in humans. RESEARCH DESIGN AND METHODS To assess the effect of endothelial dysfunction on albuminuria, we measured the urine albumin-to-creatinine ratio (UACR) both before and after the blockade of NO synthases (NOSs) with systemic infusion of N G-monomethyl-l-arginine (l-NMMA) in two distinct study populations. In population A, 62 hypertensive patients with type 2 diabetes and, in population B, 22 patients with hypercholesterolemia but without hypertension or type 2 diabetes were examined. All subjects had normal renal function. RESULTS There was a significant increase in the UACR in response to NOS inhibition with l-NMMA in hypertensive patients with type 2 diabetes (study population A) and in patients with hypercholesterolemia (study population B). Linear regression analyses revealed that the change in mean arterial presssure in response to l-NMMA was not related to the increase in the UACR in response to l-NMMA in either population, even after adjusting for filtration fraction. CONCLUSIONS NOS inhibition provokes albuminuria that is unrelated to changes in blood pressure. It is noteworthy that this finding was evident in patient groups prone to endothelial dysfunction and albuminuria. Thus, acute deterioration of endothelial function by reducing NO activity causes an increase in albuminuria.

Validation of a therapeutic scheme for the treatment of resistant hypertension.

Abstract: We tested the hypothesis that a therapeutic strategy of substituting the diuretic (most commonly hydrochlorothiazide) with chlorthalidone (50 mg/day), and, if needed, the calcium channel blocker with the highest dose of the most commonly used calcium antagonist (amlodipine 10 mg), and adding on top a direct renin inhibitor (aliskiren 300 mg) is effective to treat resistant hypertensive patients not responding to spironolactone. The scheme was tested in a group of 76 patients who had true treatment resistant hypertension (24-hour mean blood pressure ≥130/80 mm Hg while receiving three or more drugs). An effective response to spironolactone was defined as 24-hour ambulatory systolic blood pressure (SBP) drop by more than 20 mm Hg, and was obtained with 25–50 mg in 60 patients (78.9%). In patients with inadequate response to spironolactone (n = 16), we administered the triple combination plus the remaining therapy, a mean decrease of 29 mm Hg (95% CI 11–48; P = .004) for SBP and 12 mm Hg (95% CI: 4–20 mm Hg) for diastolic BP were observed. In only 1 of 16 patients (6%), the response was considered as insufficient. These data indicate the need for further testing this scheme that looks really promising to treat resistant hypertensive patients not responding to spironolactone.

Basal nitric oxide activity is an independent determinant of arteriolar structure in the human retinal circulation.

Abstract: Objective: Experimental data indicate that nitric oxide might play a role in structure and remodeling of peripheral small arteries and arterioles. We hypothesized that retinal arteriolar structure is modulated by basal nitric oxide activity. Methods: The study cohort comprised 97 male untreated patients with normal and elevated blood pressure but without clinical evidence for cardiovascular disease. The changes of retinal capillary blood flow (RCF) to nitric oxide synthase inhibitor N-monomethyl-L-arginine (L-NMMA), that reflects basal nitric oxide activity of retinal vasculature, and to flicker light, that in part nitric oxide dependently provokes retinal vasodilatation, and parameters of retinal arteriolar structure, for example wall-to-lumen ratio (WLR), were assessed noninvasively and in vivo by scanning laser Doppler flowmetry. Results: Participants were stratified according to the median WLR of retinal arterioles into two groups. In the group with WLR above the median RCF in response to infusion of L-NMMA decreased to a smaller extent (−3.82 ± 26 vs. −26.0 ± 45 arbitrary units and −0.83 ± 8.4 vs. −5.88 ± 11%, P = 0.004 and P = 0.015; respectively), whereas RCF in response to flicker light did not differ significantly compared to the counter group (22.2 ± 56 vs. 39.8 ± 51 arbitrary units and 7.42 ± 15 vs. 11.9 ± 14%, P = 0.112 and P = 0.149). In the whole study cohort WLR of retinal arterioles was related with the decrease of RCF to L-NMMA infusion [when expressed in absolute terms (r = 0.252, P = 0.013) and in percentage change (r = 0.213, P = 0.036)] and inversely related with the change of RCF to flicker light [when expressed in absolute terms (r = −0.203, P = 0.048) but not clearly when expressed in percentage change (r = −0.161, P = 0.120)]. Adjustment for major cardiovascular risk factors and changes of systemic hemodynamics in response to L-NMMA infusion revealed an independent relationship between WLR of retinal arterioles and percentage change of RCF to L-NMMA infusion (β = 0.300, P = 0.007). Conclusion: Basal nitric oxide activity emerged as an independent determinant of arteriolar remodeling in the human retinal circulation in vivo.

Telmisartan in incipient and overt diabetic renal disease.

Abstract: BACKGROUND Renal dysfunction can be regarded as a continuum that extends from endothelial dysfunction to microalbuminuria, macroalbuminuria, end-stage renal disease and ultimately to death. All stages of this continuum are associated with progressively increasing cardiovascular risk. Preventing the development and progression of kidney disease requires rigorous management of blood pressure. Due to the important role of the renin-angiotensin system in the pathogenesis of diabetic renal disease, agents that inhibit this system are recognized as first-line therapy, offering both effective blood pressure lowering and direct actions on the kidney. This review examines the effects of the angiotensin II receptor blocker telmisartan on renal dysfunction. METHODS Renal studies with telmisartan were obtained from a search on Medline and from the authors' literature sources. RESULTS Telmisartan provides renal benefit at all stages of the renal continuum in patients with type 2 diabetes. It improves endothelial function in patients with normoalbuminuria, delays the progression to overt nephropathy in patients with microalbuminuria and reduces proteinuria in patients with macroalbuminuria. Effectiveness of telmisartan is comparable to angiotensin-converting enzyme inhibitors, but with greater tolerability. The effect of telmisartan on protein excretion in diabetic nephropathy appears to be better than that of losartan and equivalent to that of valsartan. In the ONTARGET study, telmisartan provided similar cardiovascular protection to ramipril in a broad at-risk population that included patients with diabetes, while being better tolerated and having fewer treatment discontinuations. CONCLUSION The effects of telmisartan on kidney function support its use in patients with microalbuminuria or overt diabetic nephropathy.

Efficacy and safety of olmesartan medoxomil plus amlodipine in age, gender and hypertension severity defined subgroups of hypertensive patients.

Abstract: Efficacy and safety of olmesartan medoxomil plus amlodipine in age, gender and hypertension severity defined subgroups of hypertensive patients

Folic acid treatment normalizes NOS-dependence of vascular tone in the metabolic syndrome.

Abstract: The metabolic syndrome (MS) increases the risk for the devel-opment of type 2 diabetes and is associated with increased cardiovascular mortality (1–3). Furthermore, MS has been associated with retinopathy and with microalbuminuria even in the absence of frank type 2 diabetes or arterial hyperten-sion (4–7). In those with established type 2 diabetes or arterial hypertension, the additional presence of MS is associated with greater target organ damage including a higher prevalence and severity of microvascular complications (8,9). Thus, in addi-tion to being a precursor of type 2 diabetes, MS itself is associ-ated with the onset and progression of cardiovascular disease, and in particular of microvascular complications.Although obesity and MS often coexist, only two-thirds of the obese subjects develop MS (MS+), and in these, cardio-vascular risk is considerably higher than in those who do not develop MS (MS−) (10). The underlying mechanisms for the increased cardiovascular risk in MS+ are poorly understood. A variety of animal models of MS, including the high-fat feeding model, the fructose-feeding model, and a genetic model of MS (the SHR-cp, a cross between the spontaneously hypertensive rat and a leptin-deficient rat strain) have demonstrated exces-sive nitric oxide (NO) production within the vasculature, per -haps driven by elevated cytokine levels or an increased oxidative stress (11–13). It is important to note, that this increase in basal NO production is not associated with an increase/enhancement of endothelium-dependent vasodilation. In fact, in all of these models, the increase in basal NO production was associated with impaired endothelium-dependent vasodilation (11–13). Thus, basal and stimulated NO release are affected disparately in MS.In human subjects with type 2 diabetes, we previously dem-onstrated increased expression of endothelial NO synthase

The renaissance of the retinal microvascular network assessment in hypertension: new challenges.

Abstract: Assessment of the retinal microvascular alterations occurring in different diseases and particularly in hypertension, following several years during which it was almost completely forgotten, has recently received a renewed attention both in clinical practice and clinical research setting [1,2]. Important technical developments in the field have certainly contributed to the renaissance of the interest for retinal investigations. Indeed, one of the earlier technical improvements was the introduction of a mydiatric retinography evaluation, based on retinal photographs with semiautomatic quantification of the geometrical and topographical features of the arterial and venous microvessels [3,4]. This approach has been consistently improved and simplified later on with the development of nonmydriatic retinography, providing detailed qualitative information on retinal microcirculation [5,6]. This included data on arteriovenous narrowings, arteriolar narrowings and arteriovenous crossings. Further technical refinements of the method have allowed not only a qualitative but also a quantitative assessment of the retinal network, by providing information on the retinal arteriolar–venular ratio and diameters [7,8], thereby overcoming the subjective assessment of early hypertensive retinopathy by fundoscopy.

Cerebral Microangiopathy in Treatment‐Resistant Hypertension

Abstract: Cerebral microangiopathy is a cause of cognitive impairment and indicates high risk for clinically overt cerebrovascular disease. It develops in patients with or without hypertension, and different pathologies may play a supporting role. In this pilot study, the authors aimed to elucidate risk factors contributing to the deleterious action of hypertension on cerebral small vessels. A cross-sectional study in 42 patients with treatment-resistant hypertension was performed. Microangiopathy was investigated by cerebral magnetic resonance imaging (MRI). Determinants were identified by clinical investigation, computed tomography, intima-media thickness and pulse wave velocity measurement, and urinary albumin excretion. Nineteen of 42 patients had cerebral microangiopathy (23 controls). Patients were different with respect to heart rate (60.5 ± 10.2 vs 69.7 ± 15.1 beats per minute; P = .029) and systolic blood pressure during nighttime (138 ± 13 mm Hg vs 126 ± 18 mm Hg; P = .019). In addition, there were significant differences in pulse wave velocity (10.7 ± 2.0 m/s vs 9.4 ± 1.4 m/s; P = .034), peripheral pulse pressure (70.8 ± 16.3 mm Hg vs 59.2 ± 13.6 mm Hg; P = .016), central pulse pressure (62.9 ± 15.8 mm Hg vs 50.3 ± 14.2 mm Hg; P = .012), and aortic augmentation pressure (15.9 ± 6.0 vs 11.8 ± 6.6; P = .040). Systolic blood pressure and signs of hypertensive vasculopathy such as peripheral and central pulse pressure and pulse wave velocity were associated with cerebral microangiopathy in patients with long-standing treatment-resistant hypertension.

Renal artery denervation for the treatment of hypertension: opening up new horizons.

Abstract: Hypertension is a major global public health concern. Anestimated 30–40% of the adult population in the developedworld suffer from this condition [1, 2]. Currently the role ofinterventional radiology is limited to the few cases inwhich the renin–angiotensin–aldosterone system is acti-vated by renal artery stenosis. However, stenosis of therenal artery accounts for elevated blood pressure in much\5% of patients, and the effect of renal stenting on bloodpressure is not as high as expected in the past [3, 4]. In themajority of patients, hypertension is deemed ‘‘essential,’’meaning that no direct cause can be identified and it isbelieved to be related to both genetic disposition andenvironmental influences. These patients need lifelongpharmacological therapy. Despite a plethora of antihyper-tensive drugs, hypertension remains resistant in a consid-erable number of patients. A new interventional procedure,the catheter-based renal sympathetic denervation (RSD),promises help in such cases of resistant hypertension.There is increasing evidence that renal efferent sympa-thetic nerves and afferent sensory nerves that lie within andimmediately adjacent to the wall of the renal artery arecrucial for initiation and maintenance of systemic hyper-tension [5–8]. Efferent renal sympathetic activation leadsto volume retention via sodium reabsorption, a reduction ofrenal blood flow by pre- and postglomerular vasocon-striction, and activation of the renin–angiotensin–aldosterone system. Afferent renal sensory nerve activitydirectly influences sympathetic outflow from the centralnervous system to the kidneys and other highly innervatedorgans involved in cardiovascular control, such as the heartand peripheral blood vessels, by modulating hypothalamicactivity [9]. Hence, functional denervation of the humankidney by targeting both efferent sympathetic nerves andafferent sensory nerves seems to be a valuable treatmentstrategy for hypertension [10].Renal denervation has been used successfully as atherapeutic strategy to prevent hypertension in a variety ofexperimental models. In humans, radical surgical methodsfor thoracic, abdominal, and pelvic sympathetic denerva-tion were successfully applied as early as the 1930s tolower blood pressure in patients with malignant hyperten-sion. However, the so-called Smithwick intervention wasassociated with high perioperative morbidity and mortalityand long-term complications, such as bowel, bladder, anderectile dysfunction, and severe postural hypotension[11–13].For RSD, the treatment catheter (Symplicity, Ardian,Inc., Palo Alto, CA) is introduced into the renal artery viafemoral access. Radiofrequency ablations lasting up to2 min each are applied to four to six discrete points in therenal artery. To destroy the nerve tissue in the whole cir-cumference of the artery, the tip of the ablation wire has tobe pulled in a helical manner backward toward the renalartery ostium by 5-mm steps between each ablation. Thetreatment is analogical to the radiofrequency ablation ofaberrant nerve bundles in the heart, which has been per-formed for many years. At first for safety reasons, theprocedure was only performed on one artery per session.After establishing the safety of the technique, a simulta-neous bilateral renal artery denervation is normally per-formed [14].

Vergleich von frühen Veränderungen der retinalen Mikrostrombahn und Mikroalbuminurie als Zeichen eines erhöhten kardiovaskulären Risikos

Abstract: INTRODUCTION Prevention of cardiovascular disease is an important goal in clinical medicine and public health. In the process, the diagnosis of early end-organ damage is a priority beside the treatment of classic cardiovascular risk factors. To achieve this, the ophthalmoscopic examination of the retinal vessels plays a prominent role. Alternatively, the quantification of low quantities of albumin in the urine (microalbuminuria) allows the detection of early vascular damage in the kidney. The question is addressed as to whether these two methods are interchangeable or are rather complementary. PATIENTS AND METHODS We examined 226 members of the staff of the University Hospital Erlangen who volunteered to participate in a preventive campaign. A comprehensive history was taken, and height, weight and blood pressure were measured. Analysis of serum lipids and determination of the urinary albumin/creatinine ratio were performed. Fotos of the central fundus were taken with a non-mydriatic camera and analysed by an experienced ophthalmologist in a standardised fashion. The risk for cardiovascular mortality within the next ten years was estimated from age, sex, blood pressure and serum cholesterol using the euroSCORE tables for Germany. RESULTS There was no signficant correlation between the arteriovenous ratio of the retinal vessels and the urinary albumin/creatinine ratio. Neither parameter correlated with the euroSCORE Germany. Arteriovenous crossings and focal narrowing of the retinal vessels were associated signficantly with an elevated euroSCORE risk. CONCLUSIONS In large population-based studies, the arteriovenous ratio and the urinary albumin/creatinine ratio have been confirmed as markers of cardiovascular risk. In our study, there was no correlation between these two parameters. Thus, they seem to present independent risk markers. The presence of arteriovenous crossings and focal narrowing seems to be linked more closely to the classic cardiovascular risk factors from which the euroSCORE is calculated. The ophathlmolscopic examination of retinal vessels and the analysis of urinary albumin/creatinine ratio seem to complement rather than replace each other.

Response to Comment on: Ott et al. Reduction in Basal Nitric Oxide Activity Causes Albuminuria. Diabetes 2011;60:572–576

Abstract: We thank Tsikas et al. (1) for their interest in our recent work. Tsikas et al. comment that we did not provide direct evidence of reduced nitric oxide (NO) synthesis. No direct approach is available in humans. However, N G-monomethyl-l-arginine (L-NMMA) is a specific NO synthase (NOS) inhibitor, i.e., the changes we reported are due to NOS inhibition. In the cited publication by Tsikas et al., long-term (chronic) effects and indirect markers of (systemic) NO metabolism (plasma nitrites and …