[Hypertension associated with obesity].
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Antihypertensive Agents↗
Biomedical subjects
J Scholze
Publications and source records attributed to J Scholze.
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.
Female↗
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.
Adipose Tissue↗
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.
Antihypertensive Agents↗
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.
Adult↗
[Therapy of obesity-associated hypertension].
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.
Antihypertensive Agents↗
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.
Adolescent↗
[Multifocal nodular fatty infiltration of the liver associated with porphyria and haemochromatosis].
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.
Adenoma↗
[The ALLHAT study (antihypertensive and lipid-lowering treatment to prevent heart attack trial): primary antihypertensive agents - diuretics vs calcium channel blockers vs angiotensin-converting enzyme inhibitors].
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Angiotensin-Converting Enzyme Inhibitors↗
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.
Aged↗
[Pitfalls in hypertension management--misjudgements in diagnosis and therapy].
HISTORY AND CLINICAL FINDINGS: A 71-year-old woman with arterial hypertension, diabetes type 2, peripheral vascular disease and Sjögren's syndrome presented with progressive weakness, dizziness, insomnia, palpitations and headache. These symptoms did not improve by changing her antihypertensive treatment. The patient's general condition was quite normal and there were no signs of acute or chronic cardiopulmonary decompensation. INVESTIGATIONS: Besides arterial hypertension, she also had an elevated body mass index, dyslipoproteinemia, microalbuminuria, diabetic metabolism, left ventricular hypertrophy with signs of an abnormal diastolic cardiac function as well as atherosclerotic lesions (in both carotid arteries) which were identified as the patient's cardiovascular risk factors. Ambulant blood pressure monitoring revealed decreasing BP values for a period of 5 hrs after drug intake but, subsequently, severe hypertensive values (up to 220 mmHg systolic) without adequate decrease at night. Moreover, a hyperkinetic regulation of her circulation was demonstrated by hemodynamic monitoring and assessment of the autonomic nervous system. TREATMENT: By changing drug treatment, i. e. administration of an anti-adrenergic calcium antagonist of the non-dihydropyridine type combined with an ACE inhibitor and a diuretic, respectively, (both given in fixed combinations) led to the normalization of the blood pressure and pulse rate as well as an improvement of the patient's condition. CONCLUSIONS: This case emphasizes the importance of ambulant blood pressure monitoring and an assessment of the heart rate in individually adapted antihypertensive drug therapy. The application of metabolically neutral fixed drug combinations with special regard to associated diseases, organ protection and the patient's compliance resulted in normotensive blood pressure values and an improvement of the quality of life.
Aged↗
[Sibutramine in clinical practice - a PMS-study with positive effects on blood pressure and metabolic parameters].
BACKGROUND AND AIM OF THE STUDY: According to the latest health-survey data of the Robert Koch Institute, more than a fifth of all Germans are obese and about two thirds are overweight. As non-pharmacological therapies have failed to a large extent in the past, this post-marketing surveillance study was conducted to examine the feasibility, safety and efficacy of a medical weight reduction. PATIENTS AND METHODS: 6360 patients with a BMI of at least 30 kg/m(2) or, in the case of further risk factors, of 27 kg/m(2) or more, were included in the trial; the inclusion criteria and exclusion criteria chosen adhered strictly to the directions of use given for sibutramine. Two thirds of the patients had concomitant diseases and/or concomitant risk factors, and 62.4 % used concomitant medications. After being informed about non-medical therapies, the patients received 10 mg sibutramine once daily. After four weeks this treatment could be continued, terminated or increased to a dosage of 15 mg sibutramine per day. RESULTS: The body weight was reduced from 98.4 kg to 88.4 kg within the 12 weeks of treatment, which corresponds to a mean reduction of the BMI of 3.7 kg/m (2) and which was accompanied by clinically relevant reductions of waist and hip measurements. The following metabolic parameters improved significantly: cholesterol, LDL, HDL, triglycerides, blood glucose, HbA1c and uric acid. Whereas the blood pressure of normotensive patients was unchanged during the course of the study, or increased very slightly, for patients presenting with hypertension at baseline a significant decrease in blood pressure could be observed (-7.3/-4.0 mmHg), which was all the more pronounced, the higher the baseline values had been. CONCLUSION: Under real practice conditions, for overweight and obese patients treatment with sibutramine led to significant weight reductions and was well tolerated. The metabolic and cardiovascular risk profile was significantly improved, which was especially beneficial for patients with a high baseline risk.
Adult↗
[Treatment of hypertension in obesity].
BACKGROUND: Hypertension and obesity are common medical conditions independently associated with increased cardiovascular risk. Many large epidemiological studies have demonstrated associations between body mass index and blood pressure, and there is evidence to suggest, that obesity is a causal factor in the development of hypertension in obese subjects. Weight Reduction and maintenance is an essential first step in the treatment of obesity-associated hypertension. Weight reduction may be achieved by behavior modification, diet, and exercise or by the use of anti-obesity medication. However, the long-term outcomes of weight management programs for obesity are generally poor, and most hypertensive patients will require antihypertensive drug therapy. PATHOPHYSIOLOGY: Obese hypertensive patients often have metabolic abnormalities known to be exacerbated by commonly used antihypertensive agents but also obesity per se is often associated with endorgan damage including left ventricular hypertrophy, glomerular hyperfiltration and microalbuminuria, congestive heart failure or sudden cardiac death. Furthermore they have revealed volume expansion, increased cardiac output, and lower total peripheral resistance than lean patients. Hypertension in obese patients appears to be related to both increased sympathetic nervous system activity and activation of the renin-angiotensin system. Where antihypertensive therapy is necessary, the aim should be to use agents based on the hemodynamic and metabolic background and that have benefits beyond blood pressure lowering and improve the conditions most commonly linked with obesity-associated hypertension, such as hyperlipidaemia, Type II diabetes, left ventricular hypertrophy, coronary artery disease, or congestive heart failure. PHARMACOTHERAPY: Based on their favorable metabolic profiles, it would appear that ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, moxonidine and alpha-blockers can lower blood pressure without worsening the metabolic abnormalities, that is just one aspect of the problem. Yet, most guidelines fail to provide specific advice on the pharmacological management of hypertension in obese patients. This may be due to the fact that there are currently no studies that have addressed the efficacy of specific antihypertensive agents in reducing mortality in obese-hypertensive patients. This paper reviews the theoretical reasons for the differential use of the major classes of antihypertensive agents in the pharmacological management of obesity-related hypertension and also considers the potential role of anti-obesity agents.
Antihypertensive Agents↗
Preactivated monocytes from hypertensive patients as a factor for atherosclerosis?
Recently, we reported our findings regarding the elevated secretion patterns of proinflammatory cytokines obtained from peripheral blood monocytes of hypertensive patients. To investigate the direct impact of these preactivated monocytes, the adhesion of monocytes from normal controls and hypertensive patients to vascular endothelial cell monolayers was determined spontaneously and after in vitro stimulation with either lipopolysaccharide (LPS) or angiotensin II (Ang II), with or without preincubation with the AT1 receptor antagonist eprosartan. Peripheral blood monocytes from 20 patients and 20 healthy individuals were isolated by density gradient centrifugation and plastic adherence; endothelial cells were obtained from human umbilical cords by collagenase digestion. The adhesion was determined by an assay with 51Cr-radiolabeled monocytes. Oxygen species release induced by phorbol myristate acetate (PMA) as a further activation marker was analyzed for monocytes and HUVEC by chemiluminescence (CL). Spontaneous adhesion of monocytes from patients and the adhesion after stimulation with Ang II were significantly increased compared with normal controls (P<0.05). Preincubation with eprosartan diminished the adhesion in both groups to comparable levels. In monocytes, peak levels of PMA and Ang II induced CL analysis were significantly higher in patients (P<0.005). These data indicate that preactivated monocytes from hypertensives may be of pathogenic importance in atherosclerosis.
Adult↗
Choice of drug treatment for obesity-related hypertension: where is the evidence?
Hypertension and obesity are common medical conditions independently associated with increased cardiovascular risk. Many large epidemiological studies have demonstrated associations between body mass index and blood pressure, and there is evidence to suggest that obesity is a causal factor in the development of hypertension in obese individuals. Consequently, all hypertension management guidelines consider weight reduction as a first step in the management of increased blood pressure in obese individuals. Weight reduction may be achieved by behaviour modification, diet and exercise, or by the use of anti-obesity medications. However, the long-term outcomes of weight management programmes for obesity are generally poor, and most hypertensive patients will require antihypertensive drug treatment. Some classes of antihypertensive agents may have potentially unwanted effects on some of the metabolic and haemodynamic abnormalities that link obesity and hypertension, yet most hypertension guidelines fail to provide specific advice on the pharmacological management of obese patients. This may be because there are currently no studies examining the efficacy of specific antihypertensive agents in reducing mortality in obese hypertensive patients. This paper reviews the theoretical reasons for the differential use of the major classes of antihypertensive agents in the pharmacological management of obesity-related hypertension and also considers the potential role of anti-obesity agents.
Antihypertensive Agents↗
Diffuse infiltrative lymphocytosis syndrome in a patient with anti-52-kd Ro/SSA and human immunodeficiency virus type 1.
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Acquired Immunodeficiency Syndrome↗
Preactivated peripheral blood monocytes in patients with essential hypertension.
The purpose of this study was to investigate the possible involvement of human peripheral blood monocytes in the pathology of hypertensive disease. We determined the in vitro secretion patterns of proinflammatory cytokines obtained from isolated peripheral monocytes from normal controls and from hypertensive patients either after in vitro stimulation with angiotensin II (Ang II) with or without preincubation with an Ang II type 1 receptor antagonist (losartan) or after stimulation with lipopolysaccharide. Blood samples were obtained from 22 patients with essential hypertension (before any drug administration or after interruption of antihypertensive therapy) and from 24 normotensive healthy individuals used as a control group. Peripheral blood monocytes were isolated by density gradient centrifugation and plastic adherence. The state of monocyte activity was determined by the capacity to secrete tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6, (IL-6) either spontaneously or after stimulation. Cytokine concentrations were determined in culture supernatants by specific ELISA. Proinflammatory cytokine levels were assessed by semiquantitative reverse transcribed polymerase chain reaction. After stimulation with Ang II, the IL-1beta secretion of peripheral blood monocytes was significantly increased in hypertensive patients versus healthy individuals (P<0.05). In contrast, in monocytes preincubated with losartan before exposure to Ang II, IL-1beta secretion was diminished in both groups to comparable levels. The secretion of IL-1beta and TNF-alpha was significantly increased in peripheral blood monocytes from hypertensive patients versus healthy individuals after stimulation with lipopolysaccharide (TNF-alpha, P<0.02; IL-1beta, P<0.05). Upregulation of IL-1beta and TNF-alpha secretion in peripheral blood monocytes from hypertensive patients was also seen at the RNA level. Our results indicate preactivated peripheral blood monocytes in hypertensive patients. Ang II may be directly involved in the process of monocyte activation.
Adult↗
Antihypertensive profiles with ascending dose combinations of ramipril and felodipine ER.
The aim of the study was to identify the most appropriate dosage combination of ramipril and felodipine ER (an extended release tablet) for mild-to-moderate hypertension. Hypertensive patients (N = 507) with supinediastolic blood pressure (DBP) values between 100-115 mm Hg were included in a randomized, multicenter, double-blind study of 3x4 factorial design with a 2-4 week single-blind, placebo run-in and 6 week active treatment phase. The patients were randomized to 12 groups: placebo, ramipril (2.5, 5, 10 mg), felodipine ER (5, 10 mg), or ramipril-felodipine ER combinations (2.5/5 mg, 2.5/10 mg, 5/5 mg, 5/10 mg, 10/5 mg, 10/10 mg). Although the greatest reductions in blood pressure were observed with ramipril-felodipine ER (10/10 mg), consideration of the antihypertensive efficacy and safety factors suggest that the ramipril-felodipine ER (5/5 mg) combination has the best efficacy/tolerability ratio of the combinations tested. The incidence of adverse events with ramipril-felodipine ER combination therapy was similar to that with felodipine ER monotherapy, but peripheral edema, tachycardia and vasodilatation occurred less frequently with ramipril-felodipine ER (5/5 mg) combination than with felodipine ER monotherapy. The combination of ramipril-felodipine ER (5/5 mg) can be considered to be the most suitable option for hypertensive patients with an inadequate response to either of the monocomponents.
Adult↗