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Zusammenfassung: Bei Patienten mit arterieller Hypertonie liegt eine Endotheldysfunktion vor. Eine reduzierte Verfügbarkeit von gefäßerweiterndem Stickstoffmonoxid (NO) sowie ein Überschuss an vasokonstriktiven Substanzen (z.B. Endothelin oder Angiotensin II) sind als Ursache der gestörten endothelabhängigen Vasodilatation anzusehen. Das Vorhandensein einer Endotheldysfunktion korreliert mit kardiovaskulären Ereignissen und hat auch prognostische Bedeutung. Die Reduktion des Blutdrucks per se ist nicht ausreichend, um die Endothelfunktion zu verbessern. Die verschiedenen Substanzklassen der Antihypertensiva beeinflussen die Gefäßfunktion in unterschiedlicher Art und Weise

Coronary artery disease is the leading cause of morbidity and mortality in western countries. Its pathogenesis is unknown, but involves enhanced vasoconstriction, increased interaction of platelets and monocytes with the vessel wall, as well as proliferation, migration and extracellular matrix formation of vascular smooth muscle. The endothelium lies in a strategic anatomical position between circulating blood and vascular smooth muscle cells. This supports the concept that dysfunction of these cells significantly contributes to coronary artery disease. Besides other mediators, endothelial cells are a source of nitric oxide and endothelin. Nitric oxide is a vasodilator, an inhibitor of both platelet function and proliferation and migration of vascular smooth muscle. Endothelin is a potent vasoconstrictor that facilitates proliferation. Under pathological conditions, in particular the presence of cardiovascular risk factors, endothelial dysfunction occurs and is a major contributor to the increase in platelet vessel wall interaction, vasoconstriction and proliferation in the coronary system. Endothelium-dependent vasodilation is usually reduced and endothelium-dependent constrictor responses, as well as endothelin production, are augmented. Hence, endothelial cells are important targets and mediators of coronary artery disease

Guidelines for the reduction of cholesterol to prevent atherosclerotic vascular events were recently released by the American Heart Association and the American College of Cardiology. The authors claim to refer entirely to evidence from randomized controlled trials, thereby confining their guidelines to statins as the primary therapeutic option. The guidelines derived from these trials do not specify treatment goals, but refer to the percentage of cholesterol reduction by statin medication with low, moderate, and high intensity. However, these targets are just as little tested in randomized trials as are the cholesterol goals derived from clinical experience. The same applies to the guidelines of the four patient groups which are defined by vascular risk. No major statin trial has included patients on the basis of their global risk; thus the allocation criteria are also arbitrarily chosen. These would actually lead to a significant increase in the number of patients to be treated with high or maximum dosages of statins. Also, adhering to dosage regulations instead of cholesterol goals contradicts the principles of individualized patient care. The option of the new risk score to calculate lifetime risk up to the age of 80 years in addition to the 10-year risk can be appreciated. Unfortunately it is not considered in the therapeutic recommendations provided, despite evidence from population and genetic studies showing that even a moderate lifetime reduction of low-density lipoprotein (LDL) cholesterol or non-HDL cholesterol has a much stronger effect than an aggressive treatment at an advanced age. In respect to secondary prevention, the new American guidelines broadly match the European guidelines. Thus, the involved societies from Germany, Austria and Switzerland recommend continuing according to established standards, such as the EAS/ESC guidelines.

Guidelines for the reduction of cholesterol to prevent atherosclerotic vascular events were recently released by the American Heart Association and the American College of Cardiology. The authors claim to refer entirely to evidence from randomized controlled trials, thereby confining their guidelines to statins as the primary therapeutic option. The guidelines derived from these trials do not specify treatment goals, but refer to the percentage of cholesterol reduction by statin medication with low, moderate, and high intensity. However, these targets are just as little tested in randomized trials as are the cholesterol goals derived from clinical experience. The same applies to the guidelines of the four patient groups which are defined by vascular risk. No major statin trial has included patients on the basis of their global risk; thus the allocation criteria are also arbitrarily chosen. These would actually lead to a significant increase in the number of patients to be treated with high or maximum dosages of statins. Also, adhering to dosage regulations instead of cholesterol goals contradicts the principles of individualized patient care. The option of the new risk score to calculate lifetime risk up to the age of 80 years in addition to the 10-year risk can be appreciated. Unfortunately it is not considered in the therapeutic recommendations provided, despite evidence from population and genetic studies showing that even a moderate lifetime reduction of low-density lipoprotein (LDL) cholesterol or non-HDL cholesterol has a much stronger effect than an aggressive treatment at an advanced age. In respect to secondary prevention, the new American guidelines broadly match the European guidelines. Thus, the involved societies from Germany, Austria and Switzerland recommend continuing according to established standards, such as the EAS/ESC guidelines.

Background: High blood pressure is one of the most common chronic cardiovascular diseases. Despite a plethora of drugs to lower blood pressure, adequate blood pressure reduction cannot be achieved in many patients with high blood pressure. Ablation of the nerves of the renal arteries is used in these patients. Methods: Renal nerve ablation is a catheter-based, minimally-invasive method which, with the appropriate experience, is relatively easy to carry out, and has already demonstrated very promising results in patients with treatment-resistant hypertension. Results: The data presented in this article confirm that catheter-based renal nerve ablation, used in 38 patients with treatment-resistant hypertension, is a safe and highly effective method of achieving optimal blood pressure stabilisation. Conclusion: It remains to be seen whether the promising results of current studies will be confirmed in the long-term progress and lead to a reduction of cardiovascular morbidity and mortality.

Transcatheter (or percutaneous) renal denervation is a novel technique developed for the treatment of resistant hypertension. So far, only one randomised controlled trial has been published, which has shown a reduction of office blood pressure. The Swiss Society of Hypertension, the Swiss Society of Cardiology, The Swiss Society of Angiology and the Swiss Society of Interventional Radiology decided to establish recommendations to practicing physicians and specialists for good clinical practice. The eligibility of patients for transcatheter renal denervation needs (1.) confirmation of truly resistant hypertension, (2.) exclusion of secondary forms of hypertension, (3.) a multidisciplinary decision confirming the eligibility, (4.) facilities that guarantee procedural safety and (5.) a long-term follow-up of the patients, if possible in cooperation with a hypertension specialist. These steps are essential until long-term data on safety and efficacy are available.

AIMS: Pericardial effusion (PE) is a common finding in cardiac patients with chronic heart failure. The prognostic relevance of a small, haemodynamically non-compromising PE in such patients, however, remains to be determined. METHODS AND RESULTS: All patients referred to our heart failure clinic and having a baseline echocardiography and follow-up clinical visits were included. Patients with a haemodynamically relevant PE, acute myo-/pericarditis, systemic sclerosis, rheumatoid arthritis, heart transplantation, heart surgery within the last 6 months or malignancies within the last 3 years were excluded. Patients with or without a haemodynamically irrelevant PE were compared regarding all-cause mortality as the primary and cardiovascular death or need for heart transplantation as secondary outcomes. A total of 897 patients (824 patients in the control vs. 73 patients in the PE group) were included. In the PE group, left ventricular ejection fraction (LVEF) was lower [31%, interquartile range (IQR): 18.0-45.0] than in controls (34%, IQR: 25.0-47.0; P = 0.04), while the end-systolic diameters of the left ventricle and the left atrium were larger (P = 0.01 and P = 0.001, respectively). Similarly, in patients with PE, the right ventricle (RV) systolic function was lower (P < 0.005 for both the fractional area change and the tricuspid annulus movement), the dimensions of RV and right atrium (RA) were larger (P < 0.05 for RV and P < 0.01 for RA), and the degree of tricuspid regurgitation was higher (P < 0.0001). Furthermore, in the PE group, the heart rate was higher (P < 0.001) and the leukocyte count as well as CRP values were increased (P = 0.004 and P < 0.0001, respectively); beta-blocker use was less frequent (P = 0.04), while spironolactone use was more frequent (P = 0.03). The overall survival was reduced in the PE group compared with controls (P = 0.02). Patients with PE were more likely to suffer cardiovascular death (1-year estimated event-free survival: 86 +

BACKGROUND: There is little knowledge about the effect of dyslipidaemia on the outcome after lung transplantation. Thus, the aim of this retrospective single centre study was to analyse the impact of the plasma lipid profile on mortality in lung transplant recipients. From January 2000 to December 2008 the charts of 172 consecutive lung transplantation recipients were analysed. At baseline and after one year lipid profiles were routinely collected. During the follow-up major cardiovascular events (MCE; beginning of dialysis, cerebrovascular insult or myocardial infarction) were recorded. The follow-up period ended December 2010. FINDINGS: Over all total cholesterol (4.3 +/- 1.6 vs. 5.4 +/- 1.3 mmol/l, p < 0.0001), triglycerides (1.2 +/- 0.7 vs. 2.4 +/- 1.3 mmol/l, p < 0.0001), HDL (1.5 +/- 0.6 vs. 1.7 +/- 0.6 mmol/l, p = 0.003) and TC/HDL ratio (3.0 +/- 1.0 vs. 3.6 +/- 1.2, p = 0.002) increased significantly after 1 year.During the observational period 6.9% (10 patients) suffered a major cardiac event. In univariate analysis MCE was associated with baseline TC: on average the event-group had a 33% higher baseline TC (5.6 vs. 4.2 mmol/l, OR 1.6, CI 1.1 - 2.2, p = 0.02). The total mortality in the observational period was 25% (36 patients overall). In univariate analysis mortality was associated with increased TC/HDL ratio. The non-survivors had on average a 22% higher baseline TC/HDL ratio (3.6 vs. 2.8, HR 2.8, CI 1.2 - 3.5, p = 0.001). There was no association between mortality and TC (p = 0.33), triglycerides (p = 0.34), HDL (p = 0.78) and creatinine (p = 0.73). In a multivariate model the hazard ratio was 1.5 (1.2 - 1.9, p = 0.001) per increase of 0.4 TC/HDL ratio. CONCLUSIONS: This study shows that the total cholesterol before transplantation is associated with the incidence of MCE and the cholesterol/HDL ratio with mortality in lung transplanted recipients.

AIMS: Catheter-based renal nerve ablation (RNA) using radiofrequency energy is a novel treatment for drug-resistant essential hypertension. However, the local endothelial and vascular injury induced by RNA has not been characterized, although this importantly determines the long-term safety of the procedure. Optical coherence tomography (OCT) enables in vivo visualization of morphologic features with a high resolution of 10-15 microm. The objective of this study was to assess the morphological features of the endothelial and vascular injury induced by RNA using OCT. METHODS AND RESULTS: In a prospective observational study, 32 renal arteries of patients with treatment-resistant hypertension underwent OCT before and after RNA. All pre- and post-procedural OCT pullbacks were evaluated regarding vascular changes such as vasospasm, oedema (notches), dissection, and thrombus formation. Thirty-two renal arteries were evaluated, in which automatic pullbacks were obtained before and after RNA. Vasospasm was observed more often after RNA then before the procedure (0 vs. 42%, P < 0.001). A significant decrease in mean renal artery diameter after RNA was documented both with the EnligHTN (4.69 +/- 0.73 vs. 4.21 +/- 0.87 mm; P < 0.001) and with the Simplicity(R) catheter (5.04 +/- 0.66 vs. 4.57 +/- 0.88 mm; P < 0.001). Endothelial-intimal oedema was noted in 96% of cases after RNA. The presence of thrombus formations was significantly higher after the RNA then before ablation (67 vs. 18%, P < 0.001). There was one evidence of arterial dissection after RNA with the Simplicity(R) catheter, while endothelial and intimal disruptions were noted in two patients with the EnligHTN catheter. CONCLUSION: Here we show that diffuse renal artery constriction and local tissue damage at the ablation site with oedema and thrombus formation occur after RNA and that OCT visualizes vascular lesions not apparent on angiography. This suggests that dual antiplatelet therapy may be required during RN

BACKGROUND: There are only a few trials for the very elderly population (>79 years). No consensus, which blood pressure (BP) goals and substances should be applied, has been found yet. This survey was undertaken to investigate how octogenarians are treated and attain BP targets in the Swiss primary care. METHODS: Data from 4594 hypertensive patients were collected within 7 days. Eight hundred and seventy-seven patients met the requirement to be >79 years. We assessed substances/combinations and investigated pulse pressure and target blood pressure attainment (TBPA) using three different recommendations [Canadian Hypertension Education Program (CHEP), Swiss Society of Hypertension (SSH), European Society of Hypertension-European Society of Cardiology (ESH-ESC)]. Secondarily, we compared TBPA attained by angiotensin-converting enzyme inhibitor (ACEI)/diuretic (D), angiotensin receptor blocker (ARB)/D and calcium channel blocker (CCB)/D with any other dual therapy and investigated whether Ds/beta-blockers (BBs) or Ds/renin angiotensin-converting enzyme inhibitors (RAAS-Is) lead to higher TBPA. Finally, we assessed the impact of drug administration, practical work experience, location and specialization of GPs on TBPA. RESULTS: Octogenarians attained target blood pressure (TBP) between 44% (ESH-ESC) and 74% (SSH). Optimal/normal BP was reached in 22.8% of patients. Pulse pressure <65 mmHg was shown in 66.4% of patients. Monotherapy was most commonly applied followed by dual single-pill combination with ARB/D (46.5%) or ACEI/D (36.0%). No benefit in TBPA was found comparing a RAASI/D and CCB/D treatment with any other dual combination. There was also no difference between BB/D and RAAS-I/D combination therapy and between single-pill combination and dual free combinations. CONCLUSIONS: GPs adhere to the use of substances proven in outcome trials and attain high TBP. No difference in meeting BP goals could be found using different drug classes. There is an unmet need to ha

AimsFlavanol-rich chocolate (FRC) is beneficial for vascular and platelet function by increasing nitric oxide bioavailability and decreasing oxidative stress. Congestive heart failure (CHF) is characterized by impaired endothelial and increased platelet reactivity. As statins are ineffective in CHF, alternative therapies are a clinical need. We therefore investigated whether FRC might improve cardiovascular function in patients with CHF.Methods and resultsTwenty patients with CHF were enrolled in a double-blind, randomized placebo-controlled trial, comparing the effect of commercially available FRC with cocoa-liquor-free control chocolate (CC) on endothelial and platelet function in the short term (2 h after ingestion of a chocolate bar) and long term (4 weeks, two chocolate bars/day). Endothelial function was assessed non-invasively by flow-mediated vasodilatation of the brachial artery. Flow-mediated vasodilatation significantly improved from 4.98 ± 1.95 to 5.98 ± 2.32% (P = 0.045 and 0.02 for between-group changes) 2h after intake of FRC to 6.86 ± 1.76% after 4 weeks of daily intake (P = 0.03 and 0.004 for between groups). No effect on endothelial-independent vasodilatation was observed. Platelet adhesion significantly decreased from 3.9 ± 1.3 to 3.0 ± 1.3% (P = 0.03 and 0.05 for between groups) 2 h after FRC, an effect that was not sustained at 2 and 4 weeks. Cocoa-liquor-free CC had no effect, either on endothelial function or on platelet function. Blood pressure and heart rate did not change in either group.ConclusionFlavanol-rich chocolate acutely improves vascular function in patients with CHF. A sustained effect was seen after daily consumption over a 4-week period, even after 12 h abstinence. These beneficial effects were paralleled by an inhibition of platelet function in the presence of FRC only.Trial Registration ClinicalTrials.gov Identifier: NCT00538941.

The consumption of a high amount of fruits and vegetables was found to be associated with a lower risk of coronary heart disease and stroke. Epidemiologically, a similar relationship has been found with cocoa, a naturally polyphenol-rich food. Obviously, double blind randomized studies are difficult to perform with cocoa and chocolate, respectively. However, intervention studies strongly suggest that cocoa has several beneficial effects on cardiovascular health, including the lowering of blood pressure, the improvement of vascular function and glucose metabolism, and the reduction of platelet aggregation and adhesion. Several potential mechanisms through which cocoa might exert its positive effects have been proposed, among them activation of nitric oxide synthase, increased bioavailability of nitric oxide as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on blood pressure and vascular function.

Selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) as well as acetaminophen belong to the most widely prescribed therapeutic agents worldwide. Their efficacy in pain relief notwithstanding, the use of NSAIDs is associated with an increased cardiovascular risk, which can be partly attributed to their blood pressure raising potential. Adequately powered placebo-controlled trials specifically evaluating the cardiovascular safety of NSAIDs vs. selective COX inhibitors are currently underway. This review summarizes the current knowledge on the cardiovascular effects of NSAIDs and acetaminophen, and their potential clinical consequences.

Analgetika sind die am häufigsten verschriebenen Medikamente. Neben ihrer analgetischen Wirksamkeit sind diese Arzneimittel mit einem erhöhten kardiovaskulären Risiko assoziiert, das nicht zuletzt auch auf eine durch die Wirksubstanzen selbst bedingte Erhöhung des Blutdrucks zurückzuführen ist. Epidemiologische und klinische Studien zeigten bereits, dass viele nicht-selektive nicht-steroidale-Antirheumatika und selektive Cyclooxygenase-2-Hemmer mit einer Erhöhung des Blutdrucks und einem erhöhten kardiovaskulären Ereignis einhergehen. Leider fehlten bislang Ergebnisse von prospektiven, randomisierten klinischen Studien mit klinisch relevanten Endpunkten, insbesondere bezüglich des möglichen Zusammenhangs zwischen kardiovaskulären Ereignissen und Analgetika zu eruieren. Dieses Review soll einen kurzen Überblick über klinische Daten bezüglich der Wirkung des Analgetikums Paracetamol auf den Blutdruck und die klinische Bedeutung verschaffen. = Analgesic drugs, non-steroidal anti-inflammatory drugs and paracetamol (acetaminophen) in particular, belong to the most widely prescribed therapeutic agents. Beside their efficacy in pain relief, these drugs were recently linked to increased cardiovascular risk. Indeed, epidemiological and clinical studies showed that non-selective non-steroidal anti-inflammatory drugs, as well as selective cyclooxygenase-2 inhibitors both may increase blood pressure and cardiovascular events. However, the effect of paracetamol (acetaminophen) on blood pressure and cardiovascular health should not be neglected, too. Unfortunately, long-term randomized controlled trials appropriately powered to evaluate cardiovascular outcomes are lacking. This review summarizes the available data about the effect of paracetamol in particular, on blood pressure and other cardiovascular outcomes.

PRINCIPLES: Statin therapy reduces cardiovascular morbidity and mortality. However, a substantial residual cardiovascular risk can be observed in patients receiving this therapy due to persisting lipid abnormalities as well as to the lack of a systematic global risk-reduction strategy. The objective of the study was to assess the prevalence of dyslipidemia in a cohort of patients living in Switzerland and receiving statin therapy. METHODS: This cross-sectional study was conducted by 61 primary care physicians, cardiologists, endocrinologists and internists in Switzerland. Patients were consecutive outpatients≥45 years-old, on statin therapy for at least 3 months with available lipid values. A clinical examination and a recording of the latest lipid values on statin therapy were performed in all patients. RESULTS: A total of 473 patients (age 66.3±9.41 years; 61.9% male) were included in the final analysis. Under statin therapy, 40% of the analysed patients had a normal lipid profile, 32.6% presented increased low-density lipoprotein cholesterol (LDL-C) (3.35±0.88 mmol/L), 28.8% low high-density lipoprotein-cholesterol (HDL-C) (0.95±0.18 mmol/L) and 31.1% elevated triglycerides (2.69±1.04 mmol/L). It is of note that the included population was characterised by a high prevalence of cardiovascular risk factors (86.5% patients had 10-year cardiovascular risk>20%). Nevertheless, the lipid lowering therapy was modified in only 15.4% of the patients. CONCLUSION: Persistent dyslipidemia is a reality in statin-treated patients and may contribute to their residual cardiovascular risk. Therefore, comprehensive lipid management should be preferred to aggressive LDL-C lowering alone. Moreover, strategies to assess and modify the global cardiovascular risk of patients should be taken into account as an important component of primary and secondary prevention.

Hintergrund: Die kardiale Resynchronisationstherapie (cardiac resynchronisation therapy, CRT) ist bei Patienten mit schwerer Herzinsuffizienz zu einem Standardbehandlungsverfahren geworden, nicht zuletzt, da in grossen randomisierten Studien eine Reduktion der Morbidität und Mortalität nachgewiesen werden konnte. Es war das Ziel der vorliegenden Studie, die gängige Praxis der CRT unter alltäglichen Bedingungen (im „Real World“ Setting) an einem grossen Schweizer Zentrum zu untersuchen. Methoden: Sämtliche Patienten, bei denen im Zeitraum zwischen 2003 und 2010 ein CRT-Device (CRT-Schrittmacher oder CRT-ICD) am Universitätsspital Zürich implantiert wurde, wurden in diese retrospektive Analyse eingeschlossen. Resultate: 208 Patienten, mit einem mittleren Alter von 63.8 (±10.9) Jahren, 79% davon Männer, wurden in die Studie eingeschlossen. Eine ischämische Ursache der Herzinsuffizienz lag in 49% der Fälle vor, 79% der Patienten waren in NYHA-Klasse III/IV. Die mittlere QRS Dauer lag bei 153ms (± 30ms) und die mittlere EF bei 26 ± 8%. Die mediane Hospitalisationsdauer zur CRT Implantation betrug 2 Tage. Die perioperative Komplikationsrate war niedrig und vergleichbar mit der grosser randomisierter Studien. Unter CRT konnte eine deutliche klinische und echokardiographische Verbesserung erzielt werden. Während sich NYHA-Klasse von 2.8 ± 0.6 auf 2.1 ± 0.7 reduzierte (P<0.00001), verbesserte sich linksventrikuläre Auswurffraktion auf 33 ± 11% (P<0.00001). Sowohl das indexierte enddiastolische Volumen, als auch das indexierte endsystolische Volumen des linken Ventrikels nahmen signifikant ab (P=0.01 bzw. P=0.004). Konklusion: Die vorliegende Studie zeigt, dass die CRT unter „Real World“ Bedingungen effektiv und sicher ist. Obwohl die Schweiz gegenwärtig hinsichtlich der CRT Implantationsrate nur im europäischen Mittelfeld liegt, ist in Anbetracht positiver Studien, wachsender Vertrautheit und guten eigenen Erfahrungen anzunehmen, dass zunehmend Patienten bezüglich der Indika

Epidemiological data show that a regular dietary intake of plant-derived foods reduces the risk of cardiovascular disease. Recent research indeed demonstrates interesting data about cocoa consumption, with high concentrations of polyphenols, and beneficial effects on blood pressure, insulin resistance and platelet function. Although still debated, a range of potential mechanisms through which cocoa might exert their benefits on cardiovascular health have been suggested: activation of nitric oxide, antioxidant, anti-inflammatory, anti-platelet effects, which might in turn improve endothelial function, lipid levels, blood pressure and insulin resistance. This article reviews available data about the effects of the consumption of cocoa and different types of chocolate on cardiovascular health, and outlines potential mechanisms involved on the basis of recent studies.

OBJECTIVES: Intermittent periods of hypoxemia such as during periodic breathing are associated with hypertension and increased sympathetic activity. In patients with sleep apnea syndrome, hypertension is common. Treating apnea improves hypertension and reduces sympathetic outflow. The aim of the present study was to investigate the phenomenon and mechanisms of spontaneous periodic breathing in patients with hypertension. METHOD: We examined 43 hypertensive patients with untreated hypertension without left-ventricular dysfunction, heart failure or sleep apnea syndrome. Muscle sympathetic nerve activity (MSA), heart rate (HR), blood pressure (BP) and respiration were continuously recorded at rest and during cold-pressor testing. Oxygen and a CO2-enriched gas were used to test central and peripheral chemoreceptors, respectively. Baroreceptor gain was measured using the alpha method. RESULTS: Seven out of 43 patients showed spontaneous periodic breathing while awake. No difference in MSA, HR and BP was seen between patients with and without periodic breathing at rest except the breathing pattern. However, the cold-pressor test caused a larger increase of MSA in patients with periodic breathing (203 +/- 62 vs. 62 +/- 8%, P < 0.0001 by ANOVA), as well as systolic (46 +/- 6 vs. 25 +/- 3 mmHg, P = 0.002) and diastolic BP (26 +/- 5 vs. 12 +/- 1 mmHg, P = 0.004, ANOVA). Baroreceptor gain was markedly higher in patients with periodic breathing. Chemoreceptor sensitivity was comparable. CONCLUSION: Spontaneous periodic breathing is relatively common in patients with hypertension and is associated with greatly enhanced responses to cold-pressor testing. We suggest increased baroreceptor gain and sympathetic outflow as a cause for the oscillatory respiration pattern via barorespiratory coupling.

Objectives: To determine the prevalence of isolated left ventricular noncompaction (IVNC) as a cause of heart failure and heart transplantation. Methods: There were 960 patients seen in the heart failure clinic from 1987 to 2005, with a complete evaluation including echocardiography at our center (study population, 82% men, mean age 52 years). The following data were collected: type of heart disease, age at echocardiography and at heart transplantation, and frequency of heart transplantation. Echocardiographic diagnosis of IVNC was based on our published criteria. Results: The etiologies of heart failure were coronary artery disease (CAD; 37%), idiopathic dilated cardiomyopathy (33%), valvular heart disease (11%), congenital heart disease (5%), IVNC (3%), hypertensive heart disease (3%), hypertrophic cardiomyopathy (2%), myocarditis (1%), and <1% other diagnoses. Heart transplantation was performed in 253 patients (26%) due to idiopathic dilated cardiomyopathy (42%), CAD (39%), valvular heart disease (5%), congenital heart disease (5%), IVNC (2%), or other etiologies (

OBJECTIVE: Impaired endothelial function was demonstrated in HIV-infected persons on protease-inhibitor (PI)-containing antiretroviral therapy, probably due to altered lipid metabolism. Atazanavir is a PI causing less atherogenic lipoprotein changes. We studied whether endothelial function improves after switching from other PI to atazanavir. DESIGN: Randomized, observer-blind, treatment-controlled trial. SETTING: Three university-based outpatient clinics. PATIENTS: 39 HIV-infected persons with suppressed viral replication on PI-containing regimens and fasting LDL-cholesterol >3mmol/L. INTERVENTION: Patients were randomized either to continue the current PI or change to unboosted atazanavir. MAIN OUTCOME MEASURES: Endpoints at week 24 were endothelial function assessed by flow-mediated vasodilation (FMD) of the brachial artery, lipid profiles, high sensitive C-reactive protein, malondyaldehyde, total antioxidative capacity and oxidized LDL. RESULTS: Baseline characteristics and mean FMD values of the two treatment groups were comparable (3.9+/-1.8% on atazanavir vs. 4.0+/-1.5% in controls). After 24 weeks' treatment, FMD decreased to 3.3+/-1.4% and 3.4+/-1.7%, respectively (all p=n.s.). Total cholesterol improved in both groups (p=<0.0001 and p=0.01, respectively) but changes were more pronounced on atazanavir (p=0.05, changes between groups). HDL and triglyceride levels improved on atazanavir (p=0.03 and p=0.003, respectively) but not in the control group. Serum inflammatory and oxidative stress parameters did not change; oxidized LDL improved significantly in the atazanavir group. CONCLUSIONS: The switch from another PI to atazanavir among treatment experienced patients did not result in improvement of endothelial function despite significantly improved serum lipids. Not only atherogenic lipid profiles but also direct effects of reverse transcriptase inhibitor plus PI-containing combination on the endothelium may affect vascular function. ClinicalTrials.gov Identi

QUESTION UNDER STUDY: The aim of this study was to determine the prevalence of microalbuminuria (MAU) in hypertensive patients attending an office or hospital based cardiologist or internist. An additional aim was to describe associations between MAU and cardiovascular risk factors as well as to investigate the role of pharmacotherapy. METHODS: International, observational, cross-sectional study of 22282 patients with 5605 attendees in Germany and Switzerland at 444 cardiology centers. Inclusion criteria were male and female outpatients, aged > or =18 years with currently treated or newly diagnosed hypertension (> or =140/90 mm Hg at rest on the day of the study visit) and no reasons for false positive dip stick tests. The main outcome measures were the prevalence of MAU, co-morbid cardiovascular risk factors or disease and their association with the presence of MAU, and the role of pharmacotherapy in modulating prevalence of MAU. RESULTS: Prevalence of MAU in Germany and Switzerland (53.1%) was high, but lower when compared to the prevalence in "other countries" (OC, 60.2%). Routine MAU measurement was performed in 52.9% of the practices only (32.9% OC), although physicians regarded MAU to be important for risk assessment and therapeutic decisions. MAU is highly correlated with a wide variety of cardiovascular risk factors and co-morbid cardiovascular conditions including high waist circumference (55.1% [95%CI 56.0; 59.7]), diabetes (59.1% [56.8; 61.3]), atrial fibrillation (62.3% [57.4; 66.9]) and peripheral arterial disease (67.1% [61.6; 72.2]). Angiotensin receptor blockers (ARBs) appeared to be associated with the lowest risk of MAU (52.1%). Calcium channel blockers (CCBs) were used more frequent in patients with MAU (28.7%) than without (23.4%). CONCLUSIONS: Patients with MAU are common in clinical cardiology and its presence is associated with a wide variety of cardiovascular risk factors and co-morbid cardiovascular conditions. A more aggressive multi-factor

PRINCIPLES: Various non-specific questionnaires were used to measure quality of life and psychological wellbeing of patients after organ transplantation. At present cross-organ studies dealing specifically with the psychological response to a transplanted organ are non-existent in German-speaking countries. METHODS: The Transplant Effects Questionnaire TxEQ-D and the SF-36 Quality of Life Questionnaire were used to examine the psychological response and quality of life of 370 patients after heart, lung, liver or kidney transplantation. The organ groups were compared with regard to psychosocial parameters. RESULTS: 72% of patients develop a feeling of responsibility for the received organ and its function. This feeling is even stronger towards the patient's key relationships i.e. family, friends, the treatment team and the donor. 11.6% worry about the transplanted organ. Heart and lung patients report significantly fewer concerns than liver and kidney patients. Overall, only a minority of patients report feelings of guilt towards the donor (2.7%), problems in disclosing their transplant to others (2.4%), or difficulties in complying with medical orders (3.5%). Lung transplant patients show significantly better adherence. CONCLUSIONS: A feeling of responsibility towards those one is close to and towards the donor is a common psychological phenomenon after transplantation of an organ. Conscious feelings of guilt and shame are harboured by only a minority of patients. The fact that heart and lung patients worry less about their transplant might have primarily to do with the greater medical and psychosocial support in this group.

BACKGROUND: The effectiveness of lipid-lowering medication critically depends on the patients' compliance and the efficacy of the prescribed drug. OBJECTIVES: The primary objective of this multicentre study was to compare the efficacy of rosuvastatin with or without access to compliance initiatives, in bringing patients to the Joint European Task Force's (1998) recommended low-density lipoprotein cholesterol (LDL-C) level goal (LDL-C, <3.0 mmol/L) at week 24. Secondary objectives were comparison of the number and percentage of patients achieving European goals (1998, 2003) for LDL-C and other lipid parameters. PATIENTS AND METHODS: Patients with primary hypercholesterolaemia and a 10-year coronary heart disease risk of >20% received open label rosuvastatin treatment for 24 weeks with or without access to compliance enhancement tools. The initial daily dosage of 10 mg could be doubled at week 12. Compliance tools included: a) a starter pack for subjects containing a videotape, an educational leaflet, a passport/goal diary and details of the helpline and/or website; b) regular personalised letters to provide message reinforcement; c) a toll-free helpline and a website. RESULTS: The majority of patients (67%) achieved the 1998 European goal for LDL-C at week 24. 31% required an increase in dosage of rosuvastatin to 20 mg at week 12. Compliance enhancement tools did not increase the number of patients achieving either the 1998 or the 2003 European target for plasma lipids. Rosuvastatin was well tolerated during this study. The safety profile was comparable with other drugs of the same class. 63 patients in the 10 mg group and 58 in the 10 mg Plus group discontinued treatment. The main reasons for discontinuation were adverse events (39 patients in the 10 mg group; 35 patients in the 10 mg Plus group) and loss to follow-up (13 patients in the 10 mg group; 9 patients in the 10 mg Plus group). The two most frequently reported adverse events were myalgia (34 patients, 3% re

Bei Patienten mit arterieller Hypertonie liegt eine Endotheldysfunktion vor. Eine reduzierte Verfügbarkeit von gefäßerweiterndem Stickstoffmonoxid (NO) sowie ein Überschuss an vasokonstriktiven Substanzen (z.B. Endothelin oder Angiotensin II) sind als Ursache der gestörten endothelabhängigen Vasodilatation anzusehen. Das Vorhandensein einer Endotheldysfunktion korreliert mit kardiovaskulären Ereignissen und hat auch prognostische Bedeutung. Die Reduktion des Blutdrucks per se ist nicht ausreichend, um die Endothelfunktion zu verbessern. Die verschiedenen Substanzklassen der Antihypertensiva beeinflussen die Gefäßfunktion in unterschiedlicher Art und Weise

Essential hypertension is associated with enhanced biological activity of endothelin-1 (ET-1) and impaired endothelium-dependent vasodilatation. Dihydropyridine calcium antagonists have antioxidant activity in vitro, and they improve endothelial function in vivo. We tested whether calcium antagonists also influence the biological activity of ET-1 in essential hypertensive (EH) patients in the presence and absence of hypercholesterolemia. In 9 healthy subjects (normotensive [NT] subjects, age: 48.3+/-7.6 years; blood pressure: 118+/-8.6/69+/-5.4 mm Hg) and 21 EH subjects (age: 50.0+/-7.8 years; blood pressure: 164.4+/-5.4/103.8+/-4.4 mm Hg), we studied forearm blood flow and its modification induced by intrabrachial administration of ET-1, phenylephrine, acetylcholine, and sodium nitroprusside at baseline and after 24 weeks of treatment with a nifedipine gastrointestinal therapeutic system (30 to 60 mg per day). At baseline, the first dose of ET-1 (0.5 microg/100 mL of forearm tissue per minute) caused a slight vasodilatation in NT but not in EH subjects, whereas the following higher doses caused a comparable dose-dependent vasoconstriction in EH and NT subjects. The effect of acetylcholine was significantly reduced in EH as compared with NT subjects. In contrast, sodium nitroprusside and phenylephrine had similar effects in NT and EH subjects. After chronic treatment with the nifedipine gastrointestinal therapeutic system, the vasoconstrictor effect induced by both ET-1 and phenylephrine was significantly blunted, whereas the response to acetylcholine was significantly increased and the vasodilation to sodium nitroprusside unchanged. Hypercholesterolemic EH subjects showed a further reduced response to acetylcholine compared with normocholesterolemic EH subjects, and the nifedipine gastrointestinal therapeutic system restored the vasodilation to acetylcholine in this subgroup. In conclusion, in EH subjects, chronic treatment with a long-acting dihydropyridine calciu

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Familial hypercholesterolemia (FH) is an autosomal dominant disease which results in 2-3-fold elevated cholesterol levels and in accelerated atherosclerosis. FH is caused by small mutations or larger rearrangements in the low-density lipoprotein receptor (LDLR). Here, we report that screening the LDLR gene in a Swiss family (n = 15) with clinical symptoms of FH by combined single strand conformation polymorphism and long-distance PCR identified a novel 1.3 kb deletion in the LDLR. The deletion eliminated exon 4 of the LDLR presumably by recombination between two identical 25 bp repeats present in intron 3 and 4. The 25 bp sequence in intron 3 is part of an Alu repeat, whereas no homology to Alu repeats was found for the intron 4 region. This 1.3 kb LDLR deletion allele cosegregated with elevated cholesterol levels over three generations. Even on high-dose statin therapy, carriers of the deletion averaged 1.6 times higher cholesterol levels and 1.9 times higher apolipoprotein B-100 (apoB-100) levels than non-carriers who had lipid and apoB-100 levels within the range of the Swiss population. Most affected members of the first and second generation of this family had experienced a first myocardial infarction (MI) before the age of 55 years and most LDLR gene deletion carriers older than 40 years showed severe coronary artery disease (CAD). Hence, we conclude that deletion of exon 4 in the LDLR gene drastically decreases low-density lipoprotein binding leading to severe hypercholesterolemia.

Zusammenfassung: Bei Patienten mit arterieller Hypertonie liegt eine Endotheldysfunktion vor. Eine reduzierte Verfügbarkeit von gefäßerweiterndem Stickstoffmonoxid (NO) sowie ein Überschuss an vasokonstriktiven Substanzen (z.B. Endothelin oder Angiotensin II) sind als Ursache der gestörten endothelabhängigen Vasodilatation anzusehen. Das Vorhandensein einer Endotheldysfunktion korreliert mit kardiovaskulären Ereignissen und hat auch prognostische Bedeutung. Die Reduktion des Blutdrucks per se ist nicht ausreichend, um die Endothelfunktion zu verbessern. Die verschiedenen Substanzklassen der Antihypertensiva beeinflussen die Gefäßfunktion in unterschiedlicher Art und Weise

Coronary artery disease is the leading cause of morbidity and mortality in western countries. Its pathogenesis is unknown, but involves enhanced vasoconstriction, increased interaction of platelets and monocytes with the vessel wall, as well as proliferation, migration and extracellular matrix formation of vascular smooth muscle. The endothelium lies in a strategic anatomical position between circulating blood and vascular smooth muscle cells. This supports the concept that dysfunction of these cells significantly contributes to coronary artery disease. Besides other mediators, endothelial cells are a source of nitric oxide and endothelin. Nitric oxide is a vasodilator, an inhibitor of both platelet function and proliferation and migration of vascular smooth muscle. Endothelin is a potent vasoconstrictor that facilitates proliferation. Under pathological conditions, in particular the presence of cardiovascular risk factors, endothelial dysfunction occurs and is a major contributor to the increase in platelet vessel wall interaction, vasoconstriction and proliferation in the coronary system. Endothelium-dependent vasodilation is usually reduced and endothelium-dependent constrictor responses, as well as endothelin production, are augmented. Hence, endothelial cells are important targets and mediators of coronary artery disease