[Differential hypertensive therapy according to the guidelines]. / Leitliniengerechte Differenzialtherapie der Hypertonie.

The goal of antihypertensive therapy is to lower blood pressure and, by doing so, to decrease cardiovascular risk. Life style changes and drugs are available for the treatment of hypertensive patients. In order to reach the target blood pressure, most patients with hypertension need drug treatment in addition to life style changes. In all hypertensive patients, the target blood pressure is <140/90 mmHg. In patients with diabetes mellitus, with chronic renal failure as well as in patients with complications of hypertension and, thereby a very high cardiovascular risk, the target blood pressure is <130/80 mmHg. Diuretics, beta-blockers, calcium antagonists, ACE-inhibitors and angiotensin receptor blockers are the drugs of first choice in the treatment of hypertension. The selection among these drug classes has to consider probable side effects as well as accompanying diseases and complications of hypertension. One should also take into account that most of the beneficial effects of antihypertensive therapy is due to the decrease of blood pressure per se and that the majority of hypertensive patients require the combination of two or more antihypertensive drugs in order to reach the target blood pressure.

[Are beta blockers no longer the medicines of choice for the treatment of hypertension?]. / Verdacht auf höheres Schlaganfallrisiko unter Betablockern. Gehören sie noch zu den ersten Fünf?

Intervention studies indicate that beta blockers as well as diuretics have unfavourable effects on lipid metabolism and lead to new onsets of diabetes mellitus more frequently than ACE inhibitors, AT1 antagonists and calcium antagonists. Moreover, a meta-analysis showed an elevated risk for strokes in hypertensive patients treated with beta blockers. Until the conclusion of other controlled studies, beta blockers will nevertheless retain their important role in the treatment of hypertensive patients with coronary heart disease or heart failure. They should continue to be one of the preferred antihypertensives.

ESH-ESC guidelines for the management of hypertension.

The following is a brief statement of the 2003 European Society of Hypertension (ESH)-European Society of Cardiology (ESC) guidelines for the management of arterial hypertension. The continuous relationship between the level of blood pressure and cardiovascular risk makes the definition of hypertension arbitrary. Since risk factors cluster in hypertensive individuals, risk stratification should be made and decision about the management should not be based on blood pressure alone, but also according to the presence or absence of other risk factors, target organ damage, diabetes, and cardiovascular or renal damage, as well as on other aspects of the patient's personal, medical and social situation. Blood pressure values measured in the doctor's office or the clinic should commonly be used as reference. Ambulatory blood pressure monitoring may have clinical value, when considerable variability of office blood pressure is found over the same or different visits, high office blood pressure is measured in subjects otherwise at low global cardiovascular risk, there is marked discrepancy between blood pressure values measured in the office and at home, resistance to drug treatment is suspected, or research is involved. Secondary hypertension should always be investigated. The primary goal of treatment of patient with high blood pressure is to achieve the maximum reduction in long-term total risk of cardiovascular morbidity and mortality. This requires treatment of all the reversible factors identified, including smoking, dislipidemia, or diabetes, and the appropriate management of associated clinical conditions, as well as treatment of the raised blood pressure per se. On the basis of current evidence from trials, it can be recommended that blood pressure, both systolic and diastolic, be intensively lowered at least below 140/90 mmHg and to definitely lower values, if tolerated, in all hypertensive patients, and below 130/80 mmHg in diabetics. Lifestyle measures should be instituted whenever appropriate in all patients, including subjects with high normal blood pressure and patients who require drug treatment. The purpose is to lower blood pressure and to control other risk factors and clinical conditions present. In most, if not all, hypertensive patients, therapy should be started gradually, and target blood pressure achieved progressively through several weeks. To reach target blood pressure, it is likely that a large proportion of patients will require combination therapy with more than one agent. The main benefits of antihypertensive therapy are due to lowering of blood pressure per se. There is also evidence that specific drug classes may differ in some effect or in special groups of patients. The choice of drugs will be influenced by many factors, including previous experience of the patient with antihypertensive agents, cost of drugs, risk profile, presence or absence of target organ damage, clinical cardiovascular or renal disease or diabetes, patient's preference.

Arterial distensibility, intima media thickness and pulse wave velocity after renal transplantation and in dialysis normotensive patients.

AIM: Structural and mechanical properties of the arterial wall are altered in patients with renal failure. The ageing process of the arterial wall appears to be accelerated in patients with end-stage renal failure. The mechanisms responsible for reduced arterial compliance and distensibility in dialysis patients and renal transplant recipients without hypertension remain to be evaluated. METHODS: Thirty-five normotensive dialysis patients (D), 35 normotensive renal transplant recipients (T) and 35 healthy volunteers (N) matched for age, sex and blood pressure as controls were enrolled into the study. The arterial blood pressure of all patients was < 140/90 mmHg. The dialysis patients and renal transplant recipients were eligible for the study if the serum creatinine level was < 2 mg/dL. In all subjects, fasting concentrations of serum creatinine, total cholesterol, HDL-cholesterol, LDL-cholesterol and hemoglobin and glucose were determined at enrollment to the study. Blood pressure was measured using an automatic sphygmomanometer. Pulse wave velocity (PWV) was evaluated using non invasive automatic Complior device. The vessel wall properties of the left common carotid artery were studied using multigate pulsed Doppler system. With this method, the end-diastolic diameter (d) and the systolic increase of vessel diameter (distension DELTAd) were measured. From these data the relative systolic increase of vessel diameter (DELTAd/d) and the arterial wall distensibility coefficient (DC) were calculated. RESULTS: Systolic blood pressure (SBP) and central pulse pressure (CPP) were significantly higher in T than in D and N group, respectively 138 +/- 18 mmHg and 59 +/- 16 mmHg vs 128 +/- 13 mmHg and 49 +/- 12 mmHg and 132.12 mmHg and 51 +/- 10 mmHg. The d did not change significantly between all groups. The distension DELTAd was significantly lower in patients group D and T, respectively 466 +/- 38 microm and 511 +/- 37 microm than in controls. Similarly DELTAd/d was in these groups significantly lower than in healthy volunteers, respectively D 6.33 +/- 0.5%, T 6.9 +/- 0.4% vs N 9.15 +/- 0.5%. DC was also significantly lower in D and T than in N groups, respectively D 17.91 +/- 1.5 10-3/kPa and T 18.92 +/- 1.3 10-3/kPa and N 24.28 +/- 0.51-3/kPa. Significant differences were found in the increase of the intima-media thickness (IMT) of carotid artery for dialyzed patients and renal transplant recipients in contrast to the control group, but there were no differences between the patients. PWV in both patient groups was statistically significant higher than in control group correspondingly D 11.1 +/- 1.03 m/s and T 13.3 +/- 1.13 m/s, N 9.4 +/- 0.89 m/s. There was a significant correlation between the change of DC, PWV and CPP in T group (n = 35; r = -0.43; P < 0.01 and n = 35; r = 0.48; P < 0.05). In the T group also an important correlation between PWV and IMT complex (n = 35; r = 0.49, P < 0.001) was found. CONCLUSIONS: The elastic and structural properties of arterial wall in dialysis patients and renal recipients are decreased. End-stage renal disease accelerates arterial stiffening despite of arteriosclerosis and hypertension. Renal transplantation does not reverse loss of elastic and morphologic properties of arteries found in patients with end-stage renal insufficiency.

The parathyroid hormone-2 receptor is expressed on human leukocytes and down-regulated in hyperparathyroidism.

BACKGROUND: Parathyroid hormone (PTH) has specific effects on function, migration and proliferation of human leukocytes. These effects may contribute to accelerated atherosclerosis and impaired immune response observed in patients with renal insufficiency. Recently, a new G protein-coupled receptor with substantial implications for vascular function--the PTH2 receptor (PTH2-R)--has been identified, however, expression and distribution in humans and a possible regulation has not yet been studied. We therefore investigated the expression of the PTH2 receptor on human leukocytes in healthy subjects and in patients with hyperparathyroidism. METHODS: PTH2 receptor expression was quantified by flow cytometry (FACS) analysis on monocytes, lymphocytes and granulocytes that were isolated from peripheral blood (hypotonic density gradient centrifugation) and by immunohistochemistry using a specific alpha-PTH2-R antibody produced in rabbit. Results of 22 patients with hyperparathyroidism (12 renal allograft recipients, 10 hemodialysis patients, mean age 43 +/- 8 years) were compared to 22 age and sex-matched healthy controls. RESULTS: Mean relative antigen density of the PTH2 receptor and percentage of positive cells in healthy subjects was 19 +/- 5 and 90 +/- 6% on granulocytes, 5 +/- 2 and 55 +/- 19% on monocytes, and 24 +/- 7 and 21 +/- 7% on lymphocytes. In patients with hyperparathyroidism, mean antigen density was significantly lower on granulocytes and monocytes (17 +/- 4% and 3 +/- 1%, p < 0.01, respectively). The percentage of positive cells and mean expression on lymphocytes was not significantly different. A significant and inverse correlation was found between plasma PTH concentrations and the mean PTH2 receptor expression on granulocytes (r = -0.41, p < 0.05). CONCLUSIONS: The PTH2 receptor is expressed on human granulocytes and--to a lesser degree--on monocytes and lymphocytes. In patients with hyperparathyroidism the PTH2 receptor is down-regulated as function of plasma PTH levels.

Contrasting effects of verapamil and amlodipine on cardiovascular stress responses in hypertension.

AIMS: To compare the effects of two long-acting calcium antagonists of different types on cardiovascular stress responses in hypertension. METHODS: One-hundred and forty-five patients with mild to moderate hypertension and a mean (+/- s.e.mean) age of 51 +/- 0.9 years received for 8 weeks the phenylalkylamine verapamil sustained release (240 mg) and the dihydropyridine amlodipine (5 mg) in a double-blind cross-over design, both after 4 weeks of placebo. Blood pressure, heart rate and plasma noradrenaline were monitored during 3 min of sustained isometric handgrip and 2 min of cold pressor. RESULTS: Blood pressure was equally reduced by both drugs. After 3 min handgrip, systolic blood pressure, heart rate and rate-pressure product were lower with verapamil compared with amlodipine. Verapamil attenuated the increases in systolic blood pressure (25 +/- 2 vs 30 +/- 2 mmHg, difference 4.6, 95% CI (1.0, 8.1), P < 0.01) and rate-pressure product (3.1 +/- 0.2 vs 3.6 +/- 0.3 x 10(3) mmHg x beats min(-1), difference 0.5, 95% CI (0.1, 0.9), P < 0.01) during handgrip compared with amlodipine. Similar results were observed during cold pressor. Plasma noradrenaline levels were lower with verapamil compared with amlodipine at rest and after both tests, but the increases in plasma noradrenaline were not significantly different. CONCLUSIONS: Verapamil is more effective in reducing blood pressure and rate-pressure product responses to stress compared with amlodipine. Although plasma noradrenaline is lower with verapamil at rest and after stress, the increase during stress is not different.

The effects of dihydropyridine and phenylalkylamine calcium antagonist classes on autonomic function in hypertension: the VAMPHYRE study.

The aim of the present study was to compare the effects of a long-acting dihydropyridine (amlodipine) and a nondihydropyridine (verapamil) on autonomic function in patients with mild to moderate hypertension. A total of 145 patients with a diastolic blood pressure (BP) between 95 and 110 mm Hg received 8 weeks of verapamil sustained release (240 mg) and amlodipine (5 mg) in a prospective randomized, double blind, cross-over study, both after 4 weeks of placebo. The 24-h autonomic balance was measured by analysis of 24-h heart rate variability and short-term autonomic control of BP by baroreflex sensitivity measurements. Plasma norepinephrine was sampled at rest. Blood pressure was equally reduced from 153/100 mm Hg to 139/91 mm Hg with verapamil and 138/91 mm Hg with amlodipine, P = .50/.59. The low- to high-frequency ratio (LF/HF), reflecting sympathovagal balance, was higher with amlodipine than with verapamil (4.66 v 4.10; P = .001). Baroreflex function was improved by both treatments; however, baroreflex sensitivity (BRS) was significantly higher with verapamil than with amlodipine (8.47 v 8.06 msec/mm Hg; P = .01). Plasma norepinephrine (NE) level was higher with amlodipine than with verapamil (1.59 v 1.32 nmol/L; P < .0001). Amlodipine induces a shift in sympathovagal balance, as measured by heart rate variability indices and plasma NE, toward sympathetic predominance compared with vagal predominance with verapamil. Short-term autonomic control of BP, as assessed by BRS, is more effectively improved by verapamil than by amlodipine. These contrasting effects on autonomic function suggest that the nondihydropyridine calcium antagonist verapamil may have additional beneficial effects beyond lowering BP compared with the dihydropyridine amlodipine.

Acute effects of haemodialysis on endothelial function and large artery elasticity.

BACKGROUND: Disturbances of functional properties of large arteries contribute to increased cardiovascular morbidity and mortality in patients with end-stage renal disease. However, it is not clear whether haemodialysis per se acutely affects mechanical vessel wall properties or endothelial function. METHODS: Twenty-five chronic haemodialysis patients (mean+/-standard error of the mean (SEM): age 52+/-5 years; time on dialysis 63+/-7 months; blood pressure 132+/-4/72+/-2 mmHg) were studied before and immediately after a haemodialysis (HD) session using a polysulphone dialyser (ultrafiltration 1460+/-54 ml), as well as on the following day. Blood pressure was measured with an automatic sphygmomanometer and applanation tonometry. End-diastolic diameter and distension of the brachial and carotid arteries were measured by Doppler frequency analysis of vessel wall movements in M-mode using a multigate pulsed Doppler system and aortic pulse wave velocity (PWV) by an automatic device (Complior). Endothelial function was determined as brachial artery flow-mediated dilation (FMD) and compared with endothelium-independent nitroglycerine-induced dilation (NMD). RESULTS: FMD was 7.9+/-1.8% in patients before HD and did not change significantly after HD or in the dialysis-free intervall (6.7+/-2.1 and 7.1+/-2.0%, respectively; NS). The same was true for NMD and PWV (12.6+/-0.8 m/s before HD, 12.8+/-0.8 m/s after HD, and 11.9+/-0.7 m/s on the HD-free day). Carotid distensibility coefficients decreased significantly during HD (from 18.1+/-1.9 x 10(-3)/kPa to 16.7+/-2.2 x 10(-3)/kPa, P<0.05) and increased again on the HD-free day (19.8+/-2.4 x 10(-3)/kPa). However, when corrected for blood pressure by tonometry, isobaric carotid distensibility did not change significantly. Brachial artery distensibility also did not show significant acute changes. CONCLUSIONS: Haemodialysis per se did not have a significant effect on endothelial function or large artery mechanical vessel wall properties in patients on maintenance dialysis therapy.

Risk assessment and treatment benefit in intensively treated hypertensive patients of the hypertension Optimal Treatment (HOT) study.

BACKGROUND: The Hypertension Optimal Treatment (HOT) Study provided information about cardiovascular events in 18,790 hypertensives, subjected to pronounced blood pressure lowering for a mean of 3.8 years. METHODS AND RESULTS: The HOT Study data have been further analysed after risk stratification of the patients (1999 World Health Organization and International Society of Hypertension guidelines criteria): (i) no patients of the HOT Study were classified as low risk, 50% were classified as medium risk, 20.2% as high risk and 29.8% as very high risk; (ii) incidence of cardiovascular events in these patients with excellent blood pressure control [92% had diastolic blood pressure (DBP) < or = 90 mmHg] remained proportional to pretreatment risk. The relative risk of very high- versus medium-risk strata was between two and three both when HOT Study patients were considered independently of, or within the DBP target group they had been randomized to; and (iii) event rates in all risk strata were calculated to be much lower (possibly 60% lower) than rates expected from baseline risk calculated approximately by the Framingham equation. CONCLUSIONS: The low event rate in HOT Study patients is likely to result from pronounced blood pressure lowering, and is not explained by a lower risk profile than in previous controlled trials of antihypertensive treatment. The persistence of a risk gradient despite intensive blood pressure lowering suggests a combination of blood pressure control with other strategies of risk correction and the need to initiate antihypertensive therapy before complications develop.

Arterial distensibility and pulse wave velocity in patients with primary hyperparathyroidism before and after parathyroidectomy.

AIMS: There is evidence that secondary hyperparathyroidism alters arterial vessel wall properties. However, it is unclear whether effects of parathyroid hormone (PTH) on the vascular wall are direct or permissive and related to hypertension and renal failure. To assess early direct effects of PTH on large artery wall properties isobaric distensibility (DC), pulse wave velocity (PWV) and intima-media thickness (IMT) were studied before and after parathyroidectomy (Ptx) in patients with primary hyperparathyroidism (pHPT). METHODS: DC and IMT of the brachial and carotid artery were measured by echo-tracking and tonometry, PWV by the automatic Complior-device at baseline and 6 months after Ptx in 20 patients with pHPT (data mean +/- SEM, age 45+/-5 years, PTH 240+/-61 ng/l). Cardiovascular risk factors like diabetes, hypertension, renal insufficiency and hypercholesterolemia were excluded. Twenty healthy volunteers matched for age, sex and blood pressure served as controls. RESULTS: Six months after Ptx, PTH decreased to normal; however, blood pressure levels and vessel wall parameter remained unchanged. At baseline, there were no significant differences in brachial and carotid IMT (0.48+/-0.04 and 0.62+/-0.04 mm vs. 0.47+/-0.06 and 0.61+/-0.06 mm), radial and aortic PWV (9.1+/-0.4 and 9.9+/-0.7 m/s vs. 9.2+/-0.5 and 10.0+/-0.6 m/s), brachial and isobaric carotid DC (10.1+/-1.4 and 19.5+/-3.4 10(-3)/kPa vs. 9.1+/-0.9 and 20.4+/-3.2 10(-3)/kPa) or artery diameter between patients and controls. CONCLUSIONS: Structural and viscoelastic properties of large arteries are not disturbed and not influenced by parathyroidectomy in patients with early pHPT devoid of hypertension and renal disease. We conclude that increased PTH levels per se are not associated with alterations of mechanical arteriall wall properties; permissive factors like renal insufficiency may be necessary to mediate vessel wall alterations in patients with hyperparathyroidism.

Alterations in calcium and magnesium content of red cell membranes in patients with primary hypertension.

A cellular calcium-magnesium antagonism seems to be involved in the pathogenesis of primary hypertension. Total plasma, intracellular, and membranous calcium (Ca) and magnesium (Mg) contents were determined in 39 untreated patients with essential hypertension (EH) and 40 normotensive healthy subjects (NT). Membranous and intracellular measurements were performed in erythrocytes. Ca and Mg contents were measured by atomic absorption spectroscopy and membrane protein was determined according to Bradford's method as a membranous reference. There was no significant difference in plasma Ca (NT: 2.60 +/- 0.15 v EH: 2.64 +/- 0.17 mmol/L) and Mg concentrations (NT: 0.83 +/- 0.12 v EH: 0.87 +/- 0.14 mmol/L) in the studied groups. Intracellular Mg (NT: 1.72 +/- 0.15 mmol/L v EH: 1.64 +/- 0.19 mmol/L) and Ca (NT: 2.06 +/- 0.20 mmol/L v EH: 2.10 +/- 0.24 mmol/L) contents were also not significantly different between groups. Membrane Ca content was significantly increased in the EH group (2.23 +/- 0.32 micromol/g membranous protein) compared to controls (1.05 +/- 0.30 micromol/g membranous protein, P < .01). On the contrary, membranous Mg content was significantly decreased compared to controls (0.31 +/- 0.09 v 0.50 +/- 0.10 mmol/g membranous protein content, P < .01). The Ca/Mg ratio in membranes was significantly increased in EH as compared to healthy subjects (P < .01) and correlated to mean arterial blood pressure values (r = 0.47, P < .01). We conclude that the membranous alterations of Ca and Mg metabolism, shown by increased Ca/Mg ratio in red cell membranes of hypertensive subjects, may play a role in the pathogenesis of primary hypertension.

Effect of fluvastatin on endothelium-dependent brachial artery vasodilation in patients after renal transplantation.

BACKGROUND: Hypercholesterolemia may affect both endothelial function and arterial distensibility (DC). Renal transplant recipients (NTX) exhibit advanced structural and functional alterations of arterial vessel walls. The aim of this double-blind, randomized trial was to evaluate the effects of fluvastatin (FLU) on brachial artery flow-mediated vasodilation (FMD) and DC in hypercholesterolemic NTX. METHODS: Eighteen NTX received FLU 40 mg/day and 18 NTX placebo (PLA). Before and after six months of treatment, the brachial artery diameter and DC at rest were measured by a Doppler frequency analysis in the M mode, and then changes in diameter during reactive hyperemia (to assess endothelial-dependent FMD) and after 400 microg sublingual nitroglycerin (to assess endothelium-independent vasodilation-NMD). RESULTS: FLU, but not PLA, treatment resulted in significant decreases in total (from 288 +/- 10 to 239 +/- 8 mg/dL, P < 0.05) and low-density lipoprotein cholesterol (from 182 +/- 779 to 138 +/- 8 mg/dL, P < 0.05). Blood pressure did not differ between FLU- and PLA-treated patients and was not affected by either treatment. Also, the brachial artery baseline diameter was not different between groups and was not affected by FLU or PLA. Brachial artery flow at rest and during reactive hyperemia as measured by pulsed Doppler did not differ between groups. Brachial artery FMD increased with FLU from 0.23 +/- 0.08 to 0.54 +/- 0.08 mm (P < 0.05), whereas PLA did not alter FMD (0.22 +/- 0.07 vs. 0.14 +/- 0.05 mm at baseline and after six months of PLA treatment, respectively, P = NS). In contrast, NMD did not change significantly with either treatment (0.76 +/- 0.13 vs. 0.83 +/- 0.15 mm at baseline and after 6 months of FLU treatment, respectively, P = NS, and 0.64 +/- 0.09 vs. 0.66 +/- 0.10 mm at baseline and after 6 months of PLA treatment, respectively, P = NS). Also, brachial artery DC was not altered by FLU (6.4 +/- 1.0 vs. 5.8 +/- 0.6 x 10-3/kPa, P = NS) or PLA treatment (5.8 +/- 0.6 vs. 6.8 +/- 0.8 x 10-3/kPa, P = NS). CONCLUSIONS: In hypercholesterolemic NTX, the HMG-CoA reductase inhibitor FLU significantly improves brachial artery FMD as a measure of endothelial function after six months of treatment. In contrast, FLU does not have a beneficial effect on brachial artery DC.

Increased membraneous calcium concentrations in primary hypertension: a causal link to pathogenesis?

BACKGROUND: Disturbance in calcium metabolism has been suggested in the pathogenesis of hypertension, however, membrane calcium content in humans has not been studied in detail yet in primary hypertension. We compared plasma, intracellular and membrane calcium concentrations in erythrocytes of patients with essential hypertension and in healthy, normotensive control subjects to determine a possible alteration of membrane calcium in primary hypertension. SUBJECTS AND METHODS: Thirty-four never treated patients with essential hypertension were included and 34 healthy, age- and sex-matched volunteers served as controls. Atomic absorption spectroscopy was used for measurement of intracellular and membrane calcium content in erythrocytes and plasmalemmal preparations. RESULTS: Plasma and intracellular Ca(++) concentrations were not significantly different between hypertensives and controls (plasma: 2.59 +/- 0.18 vs2.50 +/- 0.16 mmol/l, intracellular: 1.89 +/- 0.20 mmol/l vs 1.97 +/- 0.24 mmol/l, NS resp., mean +/- s.e.m.). However, membrane calcium content was significantly higher in hypertensive patients compared to control subjects (2.38 +/- 0.28 micromol/g membraneous protein vs0.86 +/- 0.32 micromol/g membrane protein, P < 0.01). Membrane calcium content was correlated to mean arterial blood pressure (r = 0.59, P < 0.01). CONCLUSION: Membrane calcium content is significantly increased in patients with untreated primary hypertension and correlates to blood pressure levels. This data suggest, that an membrane mechanism may contribute to alterations in calcium metabolism and to the pathogenesis of primary hypertension.

A novel assay for determination of diadenosine polyphosphates in human platelets: studies in normotensive subjects and in patients with essential hypertension.

OBJECTIVE: Diadenosine polyphosphates (APnAs, n = 3-6) are a family of endogenous vasoactive purine dinucleotides which have been isolated from thrombocytes. Diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A) are more potent than diadenosine tetraphosphate (AP4A) and diadenosine triphosphate (AP3A) and cause skeletal muscle vasoconstriction in rats. Little is known about their physiological and pathophysiological significance in humans. The aims of the present study were to compare thrombocyte APnA concentrations in patients with essential hypertension (HYP) and in healthy normotensive humans (CON) using a novel quantitative assay and to assess a possible relationship between thrombocyte APnA concentrations and skeletal muscle vascular resistance. DESIGN AND METHODS: We describe a novel assay for quantification of APnAs in human platelets, involving platelet isolation from human blood, a solid-phase extracting procedure with a derivatized resin, desalting and quantitative determination of the substances with an ion-pair reversed-phase high-performance liquid chromatography (HPLC) system. The structural integrity of the isolated APnAs was confirmed by mixed assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) measurements and co-elution with added standards. The detection threshold for all four APnAs was 1 pmol/l and the inter-assay coefficients of variation were < 11% (n = 12). After venous blood sampling, mean arterial blood pressure (MAP) and forearm blood flow (FBF, using venous occlusion plethysmography) were measured in HYP and CON. Forearm vascular resistance (FVR) was calculated as MAP/FBF. significantly differ in platelet AP3A and AP4A content, but HYP had significantly higher thrombocyte concentrations of AP5A (56 +/- 7 versus 32 +/- 3 ng/microg beta-thromboglobulin, P = 0.003) and AP6A (10 +/- 1 versus 6 +/- 1 ng/microg beta-thromboglobulin, P = 0.015) than CON. HYP had significantly elevated FVR (50 +/- 6 versus 33 +/- 2 arbitrary units, P = 0.01) compared to CON. Significant correlations were found between AP5A and FVR (p = 0.38, P = 0.04) as well as between AP6A and FVR (p = 0.42, P = 0.02). In contrast, there were no significant correlations between APnAs and MAP. CONCLUSIONS: The study shows that thrombocyte concentrations of AP5A and AP6A are elevated in patients with essential hypertension. Vasoconstriction caused by release of AP5A and AP6A from thrombocytes may contribute to the increase of vascular resistance in hypertensive patients.

[Necrobiotic xanthogranuloma with skin and liver amyloidosis]. / Nekrobiotisches Xanthogranulom mit Haut- und Leberamyloidose.

BACKGROUND: Necrobiotic xanthogranuloma is a largely unknown disease. Both the frequency of this disease and the involvement of internal organs have clearly been underestimated until now. CASE REPORT: A patient was admitted because of ulcerating, xanthomatous, subcutaneous nodules, scleritis and conjunctivitis. Laboratory studies revealed an elevated erythrocyte sedimentation rate, a monoclonal IgG-lambda protein, a pancytopenia and later a hypocomplementemia. Furthermore, a hepatosplenomegaly and esophageal varices were found. A skin biopsy specimen showed a granulomatous infiltrate consisting of lymphocytes, histiocytes, plasma cells, foam cells as well as Touton and bizarre-appearing foreign-body giant cells and cholesterol clefts typical of necrobiotic xanthogranuloma besides a deposit of amyloid. A liver biopsy sample disclosed an amyloidosis of the parenchyma, too. Neither a therapy with chlorambucil and prednisolone nor with interferon alpha-2a resulted in improvement. CONCLUSION: Apart from treatment of skin lesions and ophthalmic manifestations further investigations are necessary because necrobiotic xanthogranuloma can be associated with malignancy and can involve internal viscera like lungs, heart and liver.

Antihypertensive treatment in renal transplant patients--is there a role for ACE inhibitors?

During the past two decades great progress was achieved with regards to short-term kidney graft survival. However, long-term graft survival did not improve similarly. Many factors contribute to chronic graft nephropathy eventually resulting in late graft loss, among these arterial hypertension is of major importance. In patients with chronic renal disease of diabetic and non-diabetic origin, angiotensin converting enzyme inhibitors have been convincingly shown to slow the progression of renal failure. The achieved nephroprotection correlates with the reduction of proteinuria by ACE inhibitor treatment. Also in renal transplant patients, ACE inhibitors have been shown unequivocally to reduce urinary protein excretion. The prevention of hyperfiltration, particular in the context of a reduced number of functional nephrons in patients with chronic graft nephropathy, could be important to prolong graft survival after renal transplantation. Moreover, ACE inhibitors may exert beneficial effects on immunologic processes contributing to chronic graft nephropathy. Many studies published in the last decade show convincingly that ACE inhibitors are safe and effective for the treatment of hypertension in renal allograft recipients. However, no data exist so far showing that ACE inhibitors are superior to other antihypertensive drugs in renal transplant patients and that they prolong graft survival. Studies investigating this issue are warranted. Apart from effects on the graft, ACE inhibitors may improve alterations of the cardiovascular system generally observed in renal transplant patients, such as structural alterations of large arteries, left ventricular hypertrophy, disturbed mechanical vessel wall properties and endothelial dysfunction. Therefore, angiotensin converting enzyme inhibitors could reduce cardiovascular morbidity and mortality in kidney transplant patients.