[Arterial hypertension, antihypertensive therapy, and visit-to-visit blood pressure variability of elderly nursing home residents]. / Arterielle Hypertonie, antihypertensive Therapie und Visit-to-visit-Blutdruckvariabilität bei älteren Pflegeheimbewohnern.

BACKGROUND AND AIM: Arterial hypertension is a common health problem in older nursing home residents (NHR). The aim of this study was to prospectively analyze blood pressure (BP) patterns, antihypertensive therapy, and visit-to-visit BP variability in NHR. METHODS: BP, visit-to-visit variability (estimated by standard deviation of means) of systolic BP (SBP) were analyzed in 12 nursing homes in Germany. NHR who were at least 65 years old and had no moderate or severe dementia were studied at baseline (T0), after 3 and 6 months, respectively. RESULTS: BP data were available for 177 NHR (mean age 83.8, 69.5% female) at T0.  A total of 90.4% NHR was affected by hypertension. Mean systolic/diastolic blood pressure was 130,1/75,5 mmHg. BP values of ≥ 140/90 mmHg were found in 29.9%, while 33.9% of NHR exhibited SBP values < 120 mmHg. At least one antihypertensive drug was used in 84.2%, and 40.7% of NHR were treated with at least three different drugs. The median of the visit-to-visit SBP variability was 9.05 (Min. 0, Max. 35.78); an influence of age, sex, and type of antihypertensive medication was not found. CONCLUSION: Elderly German NHR showed a high prevalence of hypertension and BP was controlled in 80%. However, a large proportion received intensive BP lowering pharmacotherapy and exhibited SBP values clearly lower than recommend target values between 140 and 150 mmHg particularly for elderly patients over 80 years. Thus, to avoid overtreatment BP should be monitored closely to adapt antihypertensive therapy in this population.

Antipsychotic drugs predominate in pharmacotherapy of nursing home residents with dementia.

INTRODUCTION: The aim of this study was to investigate the frequency of benzodiazepines, antidementia and antipsychotic drug prescriptions in nursing home residents (NHR).Data of a German health insurance company were retrospectively analyzed for the year 2008. METHODS: The study cohort comprised 13,042 NHR (82% women, mean age 83.6 ± 7 years). Following analgetics, antipsychotic drugs were the second most frequently prescribed drug group with 13.3% of all prescriptions. Dementia was diagnosed in 8 017 (61.5%) NHR. Thereof 51.6% received an antipsychotic, 17.3% a benzodiazepine and 15.2% an antidementia pharmaceutical, respectively. 18.1% of NHR with dementia and antipsychotic drug prescriptions were in combined treatment with antidementia pharmaceuticals. The rate of antipsychotic drug prescribing was significantly doubled in NHR with dementia compared to those without this diagnosis (p<0.01); the most frequently prescribed antipsychotics were melperone, risperidone and pipamperone. DISCUSSION: This study demonstrates the wide-spread use of psychotropic drugs in NHR. Moreover, dementia in NHR was associated with antipsychotic drug prescribing in every second patient. This highlights the need for further studies analyzing alternative treatments for dementia-related symptoms.

[Prescribing of antihypertensive drugs to elderly residents of nursing homes in Germany]. / Verordnung von Antihypertensiva bei geriatrischen Pflegeheimbewohnern in Deutschland.

OBJECTIVE: To analyse and evaluate the use of antihypertensive medication in elderly patients of nursing homes in Germany. METHODS: Data from a large German health insurance company were collected in a cross sectional study. Included were all insured persons aged 65 years or older, who were residents of a nursing home between 1 April and 30 June 2007 throughout Germany. Antihypertensive drugs were those classified according to the current guidelines published by the German Hypertension Society. RESULTS: The study comprised 8,685 residents of nursing homes, 84 % women. The mean age was 84 years (range 65 - 106 years). Antihypertensive drug prescriptions accounted for 17 % of all drug prescriptions and about 70 % of all residents received at least one prescription for antihypertensive drugs. The most frequently prescribed antihypertensive drugs were diuretics, of which 70 % were loop diuretics. Potentially inappropriate combinations of antihypertensive drugs were noted in 5.2 % of patients receiving these drugs. CONCLUSION: Antihypertensive drugs account for a notable part (17 %) of all drug prescriptions in elderly residents of nursing homes throughout Germany. These results indicate that only a minority of all residents were treated with potentially inappropriate or potentially harmful drug combinations. However, the relatively high rate of prescriptions for loop diuretics is a matter of potential concern in this vulnerable group of patients.

[Isolated systolic hypertension. An independent disease]. / Isolierte systolische Hypertonie. Ein eigenständiges Krankheitsbild.

Hypertension can be classified based on certain criteria, such as severity, existence of specific end-organ damage, or the dominant blood pressure subphenotype so that isolated diastolic hypertension (IDH), mixed systolic-diastolic hypertension (SDH), and isolated systolic hypertensive (ISH) states can be defined. The FRAMINGHAM study was the first to demonstrate a continuous increase of systolic blood pressure with age and a peak of diastolic pressure between 55 and 65 years of age. This results not only in a high prevalence of hypertension of approximately 50-80% beyond the age of 60 but also in a disproportionately high increase in isolated systolic hypertension. ISH develops either as a new condition mostly from the group of primary high-normal blood pressure or secondly through burnout of existing systolic-diastolic hypertension with highly progressive vascular ageing.The pathophysiological background lies in remodeling processes in the macrovascular and microvascular compartments with stiffening of conduit and peripheral arterial vessels. In clinical practice these processes are easy to measure by determining pulse wave velocity (PWV), the augmentation index, and pulse pressure. These parameters are closely related to cardiovascular and cerebrovascular morbidity and mortality ISH is not only a hypertension subphenotype but often indicates significant organ damage or may even be considered to be a secondary form of hypertension characterized by remodeled and stiffened arterial vessel walls and this condition is difficult to treat. It appears therefore that ISH warrants special therapeutic strategies with a focus on antiproliferative, antistiffening, anti-atherosclerotic, and vasodilating actions. As a result of the available data from the results of treatment studies it appears that renin-angiotensin system (RAS) blockers and calcium channel blockers (CCBs) are the preferred drugs for treatment of this condition.

Socio-economic status and the therapeutic effectiveness of antihypertensive treatment--the design of the LEO study.

OBJECTIVE: The risk of arterial hypertension and subsequent cardiovascular disease morbidity and mortality increases with low socio-economic status (SES). Even small differences in blood pressure, whether untreated or despite treatment, account for this substantial difference. Most of the increased risk in the low socio-economic group is due to traditional cardiovascular risk factors such as overweight and obesity, alcohol consumption and a sedentary life style. Intense treatment of arterial hypertension has been shown to overcome these prognostic inequalities. Therefore, drugs with high efficacy, optimal treatment adherence and a low potential for drug-related side effects are needed in order to reduce the cardiovascular risk burden of patients with a low SES. The angiotensin receptor blocker (ARB) olmesartan will be used to investigate the effectiveness of this drug in different socio-economic classes. RESEARCH DESIGN AND METHODS: The LEO (Long-term Effectiveness of Olmesartan in different Socioeconomic groups) study is a large observational long-term study which has been set up to test the effectiveness of olmesartan within this context. The study has a matched-pairs design (1403 patients in both the low and the high socio-economic classes). MAIN OUTCOME MEASURES: The LEO study will test whether this regimen can reduce the SES-related difference in long-term blood pressure control and compliance in the low SES population. CONCLUSIONS: The study may generate valuable information about the antihypertensive effectiveness of olmesartan alone or in combination with hydrochlorothiazide in different socio-economic classes. It will further test whether the drug helps to reduce the inherent inequalities in cardiovascular prognosis between different socio-economic groups. CURRENT STATUS: The study commenced in July 2007. Results are anticipated in December 2008.

Reduced left ventricular mass after treatment of obese patients with sibutramine: An echocardiographic multicentre study.

AIM: In obesity, left ventricular hypertrophy is frequently observed, especially in the presence of hypertension. Following body weight reduction, the left ventricular mass (LVM) is reduced. It is not known to which extent this occurs after treatment with sibutramine. METHODS: In this multicentre trial, 195 male and female patients (18-65 years of age, body mass index 30-40 kg/m2) were treated for 12 weeks with either 15 mg/day sibutramine or placebo. They were advised to follow mildly hypocaloric reducing diets. Exclusion criteria were blood pressure values >180/110 mmHg and tachycardia (heart rate > or =100 beats/min). Echocardiography in M-mode was performed to determine LVM as well as systolic function. RESULTS: Body weight was reduced by 6.9 +/- 0.3 kg under sibutramine and by 2.1 +/- 0.6 kg under placebo; body fat was reduced by 5.2 +/- 0.4 kg and 1.6 +/- 0.7 kg respectively. In the sibutramine group, LVM was reduced by 10.9 +/- 24.2 g; LVM indexed for body surface area was reduced by 2.3 +/- 11.8 g/m2 and LVM indexed for body height was reduced by 2.5 +/- 6.0 g/m(2.7). In the placebo group, LVM and LVM indices were not significantly changed. Changes in LVM correlated with reductions in body weight and initial LVM but not with changes in blood pressure or heart rate. CONCLUSIONS: After 3 months of treatment with sibutramine, obese patients lost about three times as much of body weight and LVM than patients treated with placebo. Therefore, sibutramine may be recommended not only to reduce body weight but also to obtain a regression of the LVM in obese patients with and without hypertension.

The effect of oral glucose loads on tissue metabolism during angiotensin II receptor and beta-receptor blockade in obese hypertensive subjects.

AT1 receptor blockers and ACE inhibitors decrease the risk for new onset diabetes mellitus. The phenomenon could be related to a direct angiotensin II effect on tissue metabolism. To address the issue, we recruited eighteen obese hypertensive patients. Patients were randomized to double-blind treatment with either valsartan (n = 8) or atenolol (n = 10) for thirteen weeks. They underwent an oral glucose tolerance test before and during active treatment, while metabolism was monitored through subcutaneous and intramuscular microdialysis and indirect calorimetry. After glucose ingestion, venous glucose and insulin concentrations increased rapidly while systemic free fatty acid concentrations were suppressed. Dialysate glucose and lactate concentrations increased briskly in adipose tissue and in skeletal muscle. Dialysate glycerol decreased profoundly in both tissues. Respiratory quotient increased markedly after glucose ingestion. These responses were identical at baseline and during active treatment either drug. We conclude that AT1 receptor blockade in obese hypertensive patients has no effect on interstitial glucose supply, lipolysis, and substrate oxidation. One possible explanation is that angiotensin II levels in obese hypertensives are not sufficient to elicit the metabolic changes that have been observed after direct angiotensin II application. The exact mechanism by which inhibition of the renin-angiotensin-aldosterone system decreases the diabetes risk remains unresolved and requires further study.

Initiation of hypertension treatment with a fixed-dose combination or its monocomponents -- does it really matter?

Despite efforts to diagnose and treat hypertension effectively, the goal of lowering blood pressure (BP) levels is rarely achieved, as treatment is often initiated with a single antihypertensive agent. The aim of this study was to assess the safety and efficacy of a first-line fixed-dose combination treatment compared with treatment with its monocomponents over a period of 4 weeks. Patients (n = 149) with essential hypertension were randomised to receive 2.5 mg of either ramipril or felodipine ER or the fixed-dose combination of ramipril 2.5 mg/felodipine ER 2.5 mg over a 4-week treatment period. BP and heart rate were measured by conventional methodology and 24-hour ambulatory blood pressure measurements. Treatment with the fixed-dose combination was significantly more effective in reducing systolic and diastolic BP (-15.8/-9.2 mmHg) compared with its monocomponents, ramipril (-7.6/-3.8 mmHg) and felodipine ER (-8.0/-5.0 mmHg). No significant difference could be observed in the occurrence of a greater fall in systolic and diastolic BP 6 h after the first dose of the three study medications. The adverse effects reported were mild, and less number of patients in the fixed-dose combination complained of adverse events. It can be concluded that initiating antihypertensive treatment with a low fixed-dose combination of ramipril/felodipine ER is more effective and safe when compared with treatment with its monocomponents.

Dissemination of a Sjögren's syndrome-associated extranodal marginal-zone B cell lymphoma: circulating lymphoma cells and invariant mutation pattern of nodal Ig heavy- and light-chain variable-region gene rearrangements.

OBJECTIVE: Both the genesis and outgrowth of extranodal marginal-zone B cell lymphomas (MZLs) of the mucosa-associated lymphoid tissue (MALT) type are generally thought to represent antigen-driven processes. We undertook this study to analyze lymphoma progression and dissemination outside of the MALT-type lesions. METHODS: Histopathologic and Ig heavy- and light-chain variable-region gene (V(H/L)) analyses were performed in sequential tissue samples from a patient with primary Sjögren's syndrome (SS) with glandular (parotid) manifestations and subsequent nodal dissemination of a low-grade MZL. RESULTS: This MZL expressed a CD20+,CD27+,sIgM/kappa+,IgD-,CD5-,CD10-,Bcl-6-,CD23-,p53-,p21-,MDM2- phenotype and mutated V(H)1-69/D2-21/J(H)4alpha-V(kappa)A27/J(kappa)2 Ig rearrangements. Notably, circulating lymphoma cells from the parotid glands occurred transiently in the patient's blood, as detected by single-cell polymerase chain reaction. In addition, 2 minor B cell clones (clones 2 and 3, with V(H)3-07/D3-22/J(H)3b-V(lambda)3L/J(lambda)2/3 and V(H)3-64/D3-03/J(H)2-V(kappa)A19/J(kappa)2 rearrangements, respectively) were also detected in the parotid glands and blood, and 1 of these (clone 2) was also detected in the lymph nodes. Ig V(H/L) analyses revealed ongoing (antigen-driven) mutations of the glandular lymphoma rearrangements, but an invariant mutation pattern of their nodal counterparts. CONCLUSION: These data indicate coexpansion and transient (re)circulation of the lymphoma clone and 2 additional glandular B cell clones in a primary SS-associated extranodal MZL. Combined histologic and molecular features of the nodal lymphoma subclone reflect a process of "follicular colonization" that eventually froze the mutation machinery after accumulation of additional (antigen-driven) Ig V(H/L) mutations.

[Therapy of obesity-associated hypertension]. / Therapie des adipösen Hypertonikers.

There is a 50 % prevalence of obesity with arterial hypertension. This ratio can increase up to 80 %, depending on body mass index. Important pathogenetic origins are quantity of visceral body fat along with the activation of neuroendocrineum (sympathicus, renin-angiotensin system), an induction of insulin resistance with hyperinsulinemia, and a direct compression of the medulla by fat deposits in the kidneys, which results in hemodynamic changes and an increase in blood pressure. The primary aim is a reduction in weight by means of a balanced diet and life style modification, which can be augmented by weight reducing medication. Orlistat lowers blood pressure and body weight simultaneously, whereas sibutramine accomplishes this only under certain circumstances. Interestingly, blood pressure increases again over the course of 10 years following weight reducing surgical procedures, despite ongoing weight loss. Antihypertensive differential therapy should be focused on pathophysiology and concomitant and target organ disease. Thus ACE inhibitors (alternatively angiotensin receptor blockers), in combination with low dose diuretics, should be preferentially administered, followed by calcium antagonists. Beta blockers should be used if definite cardiac indications are present.

Influence of Sibutramine on blood pressure: evidence from placebo-controlled trials.

OBJECTIVE: Sibutramine, a serotonin and norepinephrine transporter inhibitor, is widely used as an adjunctive obesity treatment. There have been concerns that norepinephrine reuptake inhibition with sibutramine could exacerbate arterial hypertension. DESIGN: Combined analysis of two placebo-controlled trials. SUBJECTS: The combined data set consisted of 1336 patients. Of these patients, 966 were randomized to sibutramine and 370 were randomized to placebo. MEASUREMENTS: Body weight, blood pressure, heart rate (HR). RESULTS: Sibutramine reduced body weight regardless of basal blood pressure. In the complete set of patients, systolic blood pressure did not change with either intervention over the 48-week period (-0.1+/-15.5 mmHg with sibutramine, -0.2+/-15.2 mmHg with placebo, P=0.9). The change in diastolic blood pressure over the 48 week period was 0.3+/-9.5 mmHg with sibutramine and -0.8+/-9.2 mmHg with placebo (P=0.049). The blood pressure response was not exacerbated in patients with grade 1 or 2 hypertension or in patients with isolated systolic hypertension. Sibutramine treatment caused a slight increase in supine HR that was sustained throughout the studies. CONCLUSIONS: Sibutramine treatment is unlikely to elicit a critical increase in blood pressure even in hypertensive patients. However, blood pressure and HR should be monitored closely. In patients who experience a clinically significant and sustained increase in blood pressure, the drug should probably be discontinued.

[Multifocal nodular fatty infiltration of the liver associated with porphyria and haemochromatosis]. / Multifokale noduläre Leberverfettung bei Porphyrie und Hämochromatose.

HISTORY AND CLINICAL FINDINGS: A 64-year-old woman suffered from severe fatigue. She was admitted to our outpatient unit for a diagnostic evaluation of multiple liver lesions as well as an adrenal gland tumor. Diabetes mellitus was diagnosed 22 years ago. Clinical evaluation revealed a mild obesity and a facial hypertrichosis. INVESTIGATIONS: Apart from elevated liver enzymes, serum ferritin and transferrin saturation were increased. Suspected haemochromatosis was verified by genetic analyses. Analyses of a 24 hours urine sample revealed typical constellation of a chronic hepatic porphyria. The liver lesions were diagnosed as multifocal fatty infiltrations using computer tomography. The patient refused a liver biopsy. The tumor of the adrenal gland represented an adenoma without endocrine activity. TREATMENT AND COURSE: Repeated phlebotomies were performed for the treatment of haemochromatosis. In the following serum ferritin returned to normal and liver enzymes as well as hyperporphyriuria decreased markedly. Diabetes was better controlled due to decrease of insulin requirements, too. CONCLUSION: This case report highlights the association of hereditary haemochromatosis and chronic hepatic porphyria, which presumably cause multifocal nodal fatty infiltration of the liver. Iron overload is likely the underlying cause, which represents the target for treatment options.

Comparison of immunoglobulin heavy chain rearrangements between peripheral and glandular B cells in a patient with primary Sjögren's syndrome.

Myoepithelial sialadenitis (MESA) of the major salivary glands is a characteristic feature of primary Sjögren's syndrome (pSS). To delineate systemic and organ-specific influences on B cells in a patient with pSS and benign MESA, individual B cells were simultaneously obtained from the peripheral blood and inflamed parotid gland. Immunoglobulin variable heavy chain (VH) rearrangements in single sorted CD19+ B cells were subsequently amplified, sequenced and analysed. Despite the presence of two clonal expansions using VH1-08 and VH2-70 segments, respectively, the majority of glandular B cells were polyclonal, resembling the VH gene usage and mutational pattern of the corresponding blood population. However, striking differences were observed in the proportion of cells expressing mutated VH rearrangements (blood, 28.9% versus parotid, 80.4%; P < 0.0001). Moreover, the glandular productive VH rearrangements differed significantly from their blood counterparts by a higher mutational frequency (P < 0.0001), shorter CDR3 lengths (P = 0.001) and a less frequent usage of JH6 (P = 0.0292), indicating an accumulation of memory B cells in the inflamed parotid. Thus, both preferential influx/homing of memory B cells and local proliferation may contribute to the pattern of benign MESA in pSS. Notably, one of the glandular clonal rearrangements (using VH1-08) was also detected in the patient's peripheral repertoire.