Antihypertensive efficacy of the angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril.

Drug therapy often fails to control hypertension. Azilsartan medoxomil (AZL-M) is a newly developed angiotensin II receptor blocker with high efficacy and good tolerability. This double-blind, controlled, randomised trial compared its antihypertensive efficacy and safety vs the angiotensin-converting enzyme inhibitor ramipril (RAM) in patients with clinic systolic blood pressure (SBP) 150-180 mm Hg. Patients were randomised (n=884) to 20 mg AZL-M or 2.5 mg RAM once daily for 2 weeks, then force-titrated to 40 or 80 mg AZL-M or 10 mg RAM for 22 weeks. The primary endpoint was change in trough, seated, clinic SBP. Mean patient age was 57±11 years, 52.4% were male, 99.5% were Caucasian. Mean baseline BP was 161.1±7.9/94.9±9.0 mm Hg. Clinic SBP decreased by 20.6±0.95 and 21.2±0.95 mm Hg with AZL-M 40 and 80 mg vs12.2±0.95 mm Hg with RAM (P<0.001 for both AZL-M doses). Adverse events leading to discontinuation were less frequent with AZL-M 40 and 80 mg (2.4% and 3.1%, respectively) than with RAM (4.8%). These data demonstrated that treatment of stage 1-2 hypertension with AZL-M was more effective than RAM and better tolerated.

'If you listen to me properly, I feel good': a qualitative examination of patient experiences of dietetic consultations.

BACKGROUND: There is considerable interest in healthcare research regarding communication skills and some debate surrounding the effectiveness of a patient-centred approach to care. Understanding patient experiences of consultations can help indicate how consultations can be modified to improve effectiveness. At present, there is little research exploring patient experience of dietetic consultations. The present study aimed to achieve a better understanding of patients' experiences of dietetic consultations using qualitative analysis. METHODS: Patients undergoing consultations with a dietitian were invited to discuss their experience of the consultation with a research dietitian who was not involved in their care. Individual interviews and focus groups were conducted and analysed using the Framework approach. RESULTS: Seventeen patients participated and described their experiences of consultations, which were varied and influenced by factors such as information given (resources, explanation, repetition, consistency); their dietitian's approach (prescriptive or nonprescriptive, use of behaviour change skills), behaviour (listening skills, body language) and appointment (expectations, involvement of the multidisciplinary team, length of time); and their own internal experience (confidence, guilt, frustration). Patients agreed that certain factors, such as good communication and rapport, receiving effective and reliable information and resources, and nonjudgmental, regular support, were important factors in creating a positive experience of their consultation. However, they differed in what they believed constituted these factors. CONCLUSIONS: Patients like dietitians to adopt a patient-centred approach, which might be either patient- or practitioner-led, and to take account of what they wanted from consultations, adapting these to meet their individual requirements.

[Diabetes mellitus in cardiac rehabilitation]. / Diabetes mellitus in der kardiologischen Rehabilitation.

Patients in cardiac rehabilitation suffering from diabetes mellitus belong to the group of patients at highest risk for new cardiovascular events and therefore require highly specialized rehabilitation programs. Changes in lifestyle are of great importance to control all relevant cardiovascular risk factors, and patients need to learn healthy lifestyle in special education programs. Furthermore, it is necessary to prepare patients for self-management of their disease in their daily life and work. Physicians should optimize pharmacological treatment in accordance with guidelines in order to minimize secondary end organ damage. To ensure long-term success of cardiac rehabilitation, reliable rehabilitation care should be initiated on discharge of the patient.

[Management of sleep-related abnormal breathing by cardiologists and hospital departments of cardiology]. / Versorgung von Patienten mit obstruktiver Schlafapnoe in kardiologischen Praxen und Kliniken.

BACKGROUND AND OBJECTIVES: In the general population there is a high prevalence of sleep-related disorders of breathing (sleep apnea). In addition to being leading symptom of excessive day-time sleepiness they are also important predictors are cardiovascular disease such as arterial hypertension, heart failure, cardiac arrhythmias and stroke. Are the cardiologists the specialists who recognize such patients and refer them to diagnostic procedures and treatment? METHODS: We sent out a questionnaires to cardiologists in private practice, to hospitals with cardiology departments and to cardiology rehabilitation units in Germany in order to assess the knowledge about sleep apnea and of the current diagnostic and therapeutic procedures in patients with suspected sleep apnea. All cardiology rehabilitation units and every other practice and cardiology department listed in the reference book 'Medführer' were approached. RESULTS: 98% of 388 cardiologists with private practice were found to know about the disorder sleep apnea. 94.3% routinely asked their patients about any sleep disorder and specifically about excessive day-time sleepiness. More than half of the cardiologists (59.3%) questioned patients about possible sleep apnea as part of their interview, but only 32.7% carried out tests with a portable sleep apnea monitor. Most patients were referred to a sleep center. In 60% of the cardiology departments a portable sleep apnea monitor was used. Further diagnostic investigation followed in collaborating sleep centers (66.4%), because only 22.4% of the departments had a sleep laboratories. The main focus was on the diagnosis of abnormal sleep due to central or obstructive disorders of breathing. More than two thirds of the cardiology departments initiate nocturnal ventilation treatment. CONCLUSION: Cardiologists in private practice and cardiologists in hospital departments know about sleep-related abnormal breathing. The use of portable sleep apnea monitors and of polysomnography in special as parts of sleep centers within cardiology departments should be improved.

Efficacy and safety of losartan 100 mg or losartan 100 mg plus hydrochlorothiazide 25 mg in the treatment of patients with essential arterial hypertension and CV risk factors: observational, prospective study in primary care.

BACKGROUND: Patients with high cardiovascular risk are prevalent in ambulatory care. To achieve adequate blood pressure control, such patients require higher drug doses and/or combination therapy. We aimed to assess the efficacy and safety of losartan 100 mg as monotherapy or in fixed-dose combination with hydrochlorothiazide 25 mg. DESIGN AND METHODS: Multicentre, prospective, open observational study over 13 weeks in patients with essential hypertension, whose blood pressure was not adequately controlled despite pretreatment. Main outcome parameters were the systolic (SBP) and diastolic (DBP) blood pressure reduction, the rate of normalized patients at study end compared to baseline, and the number and type of adverse events (AEs). RESULTS: Of the 7702 documented patients, 53.1% (N = 4088) were men, with a mean age of 63.5 +/- 10.7 years. Comorbidities were frequent (diabetes mellitus in 57.4% [N = 4418], coronary heart disease in 30.3% [N = 2330], left ventricular hypertrophy in 28.2% [N = 2172], heart failure in 14.0% [N = 1079], and peripheral arterial disease in 9.0% [N = 690]). Patients received losartan 100 mg in 45.7% (N = 3521), losartan/HCTZ in 53.8% (N = 4143); additional antihypertensive drugs were given in 45.5% (N = 3505). Physicians reported somewhat lower target values than those stipulated by the guidelines (irrespective of age, gender, and concomitant diseases except for diabetes). Mean SBP/DBP decreased from a baseline value of 158/93 mmHg by 24/12 mmHg at study end. The BP lowering effect was similar in subgroups by treatment or comorbidity, respectively, however target attainment rates were substantially higher in non-diabetic patients. Metabolic and renal parameters (fasting glucose, HbA(1c), serum creatinine and albumin in urine) showed trends for improvement. Tolerability was very good, as only 0.43% (N = 33) experienced an AE (in 0.31% [N = 24] serious AEs), and 0.08% (N = 6) discontinued therapy due to reasons related to study drug. CONCLUSION: In high-risk patients, treatment with losartan 100 mg or losartan/HCTZ 100/25 mg was effective and well tolerated, irrespective of comorbidity. These findings from a real-life setting are in line with those from randomized controlled trials.

[Effect of weight loss on blood pressure]. / Wie effektiv lässt sich damit der Blutdruck senken?

The treatment of arterial hypertension is based on changes in lifestyle and above all weight loss. The expected reduction of systolic and diastolic blood pressure through weight loss is greater the higher the starting blood pressure. For patients who are not successful through calorie reduction and sport, weight loss can be enhanced with pharmacotherapy. Various substance-dependent blood pressure reactions have been observed that must be monitored. The blood pressure of patients who have undergone surgical intervention for weight loss decreases significantly to the upper normal range.

Vascular and Alzheimer-type pathology in an autopsy study of African-Americans.

The authors studied 13 autopsy brains from a larger cohort of 270 African-Americans with a clinical diagnosis of Alzheimer disease (AD), vascular dementia (VaD), or stroke without dementia. Two subjects exhibited changes of pure VaD, 5 had pure AD, and 6 showed a mixture of AD pathology and strokes. Overall, there was good agreement between the pathologic diagnoses and the clinical diagnoses.

[Prevention of arteriosclerosis. Importance of the treatment of arterial hypertension]. / Prävention der Atherosklerose. Stellenwert der Behandlung der arteriellen Hypertonie.

In most European countries and Northern America, cardiovascular diseases induced by atherosclerosis are the most common cause of death in older people. People surviving acute myocardial infarction or stroke suffer often by disabilities or handicaps. The lifelong care of such patients is expensive and plays a major role for increment of costs in public health systems. Prevention of atherosclerosis will reduce cardiovascular morbidity and mortality, enhance quality of life and prolong lifetime of patients. Therefore the worldwide accepted risk factors of atherosclerosis have to be treated consequently and early enough within the meaning of primary prevention. Hypertension is one of the six major cardiovascular risk factors and is defined as elevated blood pressure above 140/90 mmHg. In case of hypertension, diagnostic efforts has to be focussed on detection of additional cardiovascular risk factors, secondary forms of hypertension, end organ damage or associated diseases. All therapeutic strategies are based on life style changes, which cover weight reduction, sodium restriction, controlled alcohol consumption and increment in physical activity. Pharmacotherapy will be added in regard to the global risk of the patient and the success of the life style changes. Selection of antihypertensives and their optimal combination will be determined by associated diseases (compelling indication), side effects and individual response in blood pressure. Goal of treatment is the normalization of blood pressure below 140/90 mmHg independent of age or sex. In diabetics and in case of nephropathy the goal is set lower (below 130/80 mmHg).There is strong evidence that reduction in blood pressure is followed by a decrease in the incidence of myocardial infarction, stroke, heart failure, nephropathy, and even in cardiovascular mortality. The success of antihypertensive therapy is greater in high risk patients like older people, patients with isolated systolic hypertension or diabetics. Risk reduction correlates well with the degree in blood pressure reduction. However, to minimize cardiovascular risk in hypertensives all additional risk factors have to be treated too.

[Recommendations for statin therapy in the elderly]. / Empfehlungen zur Statintherapie im AlterDaten und Konsensus.

Elderly patients are significantly less likely to receive statins than younger patients possibly because of doubts regarding compliance or concerns regarding the increased likelihood of adverse events and drug interactions. Poor compliance can be expected especially in patients suffering from dementia or depression as well as those whose stage of cardiovascular disease exhibits few symptoms. On the other hand, the clinical significance of CHD events is high in the elderly, and 80% of coronary deaths occur in patients aged over 65 years. The average statistical life expectancy of elderly and old patients is often underestimated. The HPS and PROSPER studies showed that statins reduce mortality and morbidity even in very elderly individuals with a high global cardiovascular risk and/or CAD. Patients up to the age of 79 years should be treated according to the same guidelines as younger patients. Statin therapy should only be considered for patients aged 80 years and older who are at a very high risk for cardiovascular events.

Risk evaluation and therapeutical implications of pulse pressure in primary arterial hypertension.

SUMMARY: Analysis of the results raised in the Framingham and the MRFIT study have clearly shown that increased pulse pressure is an independent cardiovascular risk factor. This is valid for all age groups and both sexes. The risk increases with pulse pressures over 60 - 65 mmHg for office blood pressure and 53 mmHg for 24-h-mean of ambulatory blood pressure. Pulse pressure is strongly correlated with systolic blood pressure and will be highest in case of isolated systolic hypertension. Urinary albumin excretion and left ventricular hypertrophy are closely associated with pulse pressure. With elevated pulse pressure cardiovascular risk is increased 2- to 4-fold in relation to age and endpoint. The risk of myocardial infarction is raised more if pulse pressure is associated with low mean arterial blood pressure while risk of stroke is increased with wide pulse pressure and high mean arterial pressure. The risk of pulse pressure can be seen in normotensives and in early pregnancy. Therapeutic management of pulse pressure will be similar to that of systolic blood pressure, since normalization of systolic blood pressure will also lower or normalize pulse pressure. Results of preliminary studies suggest that diuretics are superior to other drugs in decreasing pulse pressure. An increase of pulse pressure during therapy should be avoided since each 10 mmHg increase in pulse pressure will raise the risk of stroke and myocardial infarction about 24 % and 32 %.

Trauma for all: a pilot study of the subjective experience of physical restraint for mental health inpatients and staff in the UK.

Violence and aggression is common in psychiatric inpatient units. Despite the near universal prevalence of restraint, there is very little published research on either the efficacy or the subjective effects of restraint on staff or patients. In this pilot study, semistructured interviews were given to the patients and staff involved in six untoward incidents in which the patient participant had been subject to manual physical restraint. Participants were interviewed as soon as possible after the occurrence of the incidents. The interviews asked the patient and staff participants to identify and discuss the factors that they found helpful and unhelpful during and in the immediate aftermath of these incidents. The incidents generated strong emotions for all concerned. The patients valued staff time and attention but felt that they received too little attention. Both nurses and patients discriminated between permanent and temporary staff. Patients reported feeling upset, distressed and ignored prior to the incidents and isolated and ashamed afterwards. Postincident debriefing was valued by all but was patchy for staff and rarer still for patients. Patients feared the possibility of being restrained. Half of the patients and several staff members reported that the incidents had reawakened distressing memories of previous traumatic events. Further research on the subjective effects of restraint is urgently needed.

[Dietary fats, salt and alcohol drive up blood pressure. Educate hypertensive patient on avoidance]. / Fett, Salz und Alkohol treiben den Blutdruck hoch. Bringen Sie Ihrem Hypertoniker bei, wie man verzichtet.

General non-drug measures today form the accepted basis for every antihypertensive treatment. WHO identifies the most important of these as weight reduction, salt restriction and moderation in the use of alcohol. These measures can effectively lower raised blood pressure and normalize grade I hypertension, especially in borderline cases. The target of these efforts is a weight reduction of at least 5%, restriction of salt to 5-6 g/day and alcohol consumption not exceeding 20 g/day for women and 25 g/day for men. No negative effects are to be expected from these restrictions, which are really nothing more than a return to "normal portions" with regard to eating and drinking habits.

Managing the glucocorticoid dependent inflammatory bowel disease patient.

At this time, standard therapy for treatment of inflammatory bowel disease includes the use of glucocorticoids for moderate to severe Crohn's disease, severe ulcerative colitis, and moderate ulcerative colitis failing mesalamine. Although the majority of patients will have clinical improvement with glucocorticoids, a substantial minority of patients will later flare with attempts to withdraw therapy. Given the numerous potential side effects associated with glucocorticoids, every effort should be made to switch these patients to a less toxic medication. Historically, the most reliable agents have been azathioprine or 6-mercaptopurine. Infliximab is a relatively new medication but would be expected to be beneficial for weaning glucocorticoids for Crohn's disease patients. Methotrexate is another alternative for Crohn's disease. Budesonide and CDP571 are still in developmental phases but likely will be helpful in managing this patient population. Mesalamine, cyclosporine, mycofenalate mofetil, and thalidomide have less data available to support their use but may be helpful for some patients. 6-Thioguanine may be an alternative to patients who do not tolerate 6-mercaptopurine or azathioprine.

Renal fibrosis: collagen composition and assembly regulates epithelial-mesenchymal transdifferentiation.

Type IV collagen is a major component of basement membranes and it provides structural and functional support to various cell types. Type IV collagen exists in a highly complex suprastructure form and recent studies implicate that protomer (the trimeric building unit of type IV collagen) assembly is mediated by the NC1 domain present in the C-terminus of each collagen alpha-chain polypeptide. Here we show that type IV collagen contributes to the maintenance of the epithelial phenotype of proximal tubular epithelial cells, whereas type I collagen promotes epithelial-to-mesenchymal transdifferentiation (EMT). In addition, the recombinant human alpha1NC1 domain inhibits assembly of type IV collagen NC1 hexamers and potentially disrupts the deposition of type IV collagen, facilitating EMT in vitro. Inhibition of type IV collagen assembly by the alpha1NC1 domain up-regulates the production of transforming growth factor-beta1 in proximal tubular epithelial cells, an inducer of EMT. These results strongly suggest that basement membrane architecture is pivotal for the maintenance of epithelial phenotype and that changes in basement membrane architecture potentially lead to up-regulation of transforming growth factor-beta1, which contributes to EMT during renal fibrosis.