[Prevention of coronary heart diseases in clinical practice. Comment on the recommendations of the Second Joint Task Force of European Societies for Prevention of Coronary Disease]. / Prävention koronarer Herzerkrankungen in der klinischen Praxis. Kommentar zu den Empfehlungen der Second Joint Task Force der Europäischen Gesellschaften zur Koronarprävention.

The Second Joint Task Force of European Societies on Coronary Prevention (EAS-European Atherosclerosis Society, ESC-European Society of Cardiology, ESH-European Society of Hypertension) have established recommendations for the prevention of coronary heart disease in cooperation with the representatives of the International Society of Behavioral Medicine, the European Society of General Medicine/Family Medicine, and the European Heart-Network. These recommendations of the year 1998 are commented by Austrian cardiologists and lipidologists and supplemented with recent clinical findings.

[Cardiovascular sequelae and risks of obesity]. / Kardiovaskuläre Folgen und Risken des Ubergewichts.

Obesity is a well documented separate risk factor for metabolic and vascular diseases which may reduce life expectancy for overweight people. This is expected to create soon a major health economic problem in more or less all western countries because the numbers of morbidly obese people increase steadily. It is a type of visceral android fat deposition which bears a high risk to develop vascular remodelling processes causing coronary and cerebral artery disease with all its consequences. The various biochemical processes which may contribute to cause these vascular lesions in obesity are discussed by the author and the various resulting clinical findings are described. Further the chance is emphasized to reduce by weight reduction the risks of obesity since regression of vascular changes may result by an even moderate loss of weight.

Spontaneous remission of acute myeloid leukemia after infection and blood transfusion associated with hypergammaglobulinaemia.

Spontaneous remissions of acute myeloid leukemia (AML) have been documented in association with infection as well as blood transfusions. Activation of the immune system including an increased number of NK cells and cytokine release have been implicated in the mechanism of this phenomenon. We have observed spontaneous remissions in two patients with AML (one with a t(8;21)-positive M2, one with M5b), both occurring after infection and blood transfusions. The bone marrow showed a reduction of blast cells from 65% to 2% or 40% to 1%, respectively. Remission was accompanied by a marked polyclonal hypergammaglobulinemia in both cases (IgG values of 6420 and 2160 mg/dl, IgA of 802 and 811 mg/dl, respectively). A concomitant increase in bone marrow plasma cells was observed in both patients. Reduction of AML1/ETO PCR positivity from one-step to two-step PCR (approximately 100-fold) was documented in the patient with a t(8;21), while a regression of lymph node and skin leukemic infiltrations occurred in the patient with M5b. One patient relapsed after 4 months, at a time when his serum immunoglobulin levels had markedly decreased. The other patient is in continuous remission after 14 months. These cases suggest a potential role for a humoral immune response in the mechanism of spontaneous remission.

Folic acid supplementation improves erythropoietin response.

Therapy with recombinant human erythropoietin (rhEPO) has become most valuable for the treatment of renal anemia in patients with various chronic renal diseases. For the first time this study presents data showing that rhEPO affects the metabolism of folic acid. There were 13 patients enrolled; they suffered from different chronic renal diseases and showed an impaired responsiveness to rhEPO therapy. Before starting rhEPO therapy the mean corpuscular volume of erythrocytes (MCV) was measured; MCV was 90.4 fl. During rhEPO therapy the MCV increased significantly by 14.8 fl (p < 0.05). The developing macrocytic anemia was overcome when folic acid was administered additionally for a mean period of 3.14 +/- 3 months. Hematocrit (Hct) also responded accordingly. Whereas Hct did not increase adequately during the exclusive treatment with rhEPO, an increase in Hct from 23 +/- 3.3 to 30 +/- 4.2% (p < 0.01) was observed after the addition of folic acid. These results are rather remarkable as folic acid serum levels were clearly within the normal range during the whole study period. So it can be concluded that rhEPO therapy results in an increased demand for folic acid. Even if serum concentrations are within the normal range, the administration of folic acid will enhance the effectiveness of rhEPO therapy so that the rhEPO dosage can be reduced.

Efficacy, safety and tolerability of lovastatin and bezafibrate retard in patients with hypercholesterolemia.

Hyperlipidemia has turned out to be the most important risk factor for coronary heart disease and necessitates frequently lipid lowering long-term treatment. Therefore, efficacy and tolerability of hypolipemic drugs are of great interest. The objective of the present study was to compare the safety, tolerability and effect on plasma lipids of Lovastatin and Bezafibrate retard in patients with hypercholesterolemia. 99 patients with total cholesterol of > or = 250 mg/dl after a 4 week standard lipid-lowering diet were treated another 4 weeks with placebo and then randomized to 400 mg Bezafibrate retard or 20 to 80 mg Lovastatin given once a day for 12 weeks. Mean changes from baseline in total cholesterol, LDL cholesterol and triglycerides were significantly reduced, in HDL cholesterol increased in both treatment-groups (p < or = 0.01). The effects of Lovastatin on total cholesterol and LDL cholesterol were more pronounced than those of Bezafibrate retard (p < or = 0.01), while Bezafibrate had a larger effect on triglycerides (p < or = 0.05). The frequency of clinical adverse experiences was low and similar among treatment groups, the frequency of laboratory adverse experiences was higher in the Lovastatin group. One patient in the Bezafibrate group was withdrawn because of nausea, one patient in the Lovastatin group because of GGT elevation.

[Acute management of myocardial infarct patients in Austria (cross-sectional study of 8 intensive care units)]. / Akutversorgung von Herzinfarktpatienten in Osterreich (Querschnittsuntersuchung an 8 Intensivstationen).

8 Austrian Intensive Care Units provided data from 6,317 cases (including 1,667 cases with acute myocardial infarction) admitted during 1990 and 1991 for a documentation system offered by the Austrian Heart Foundation. Significant differences were observed between the units concerning admission policies and the use of diagnostic methods. 71% of the AMI cases were first infarctions, 10% were Non-Q-infarcts. The median of the prehospital period varied between 2.5 and 6.5 hours. The evaluation of the admission mode showed that on average 42% of the AMI cases had contact to their G.P. before hospital admission, this figure varying, however, between 24 and 90% in different areas. It seems that this contact takes place to a much lower extent in big cities. On average G.P. contact before hospital admission in AMI resulted in doubling of the duration of the prehospital period. Thrombolytic treatment was applied in 24.7% of AMI cases with a variation between 13.9 and 48.4% in the different centers. It is suggested that regular use of this kind of quality control should offer means for optimizing the acute care of infarct patients on a regional and on a national level.

[Left ventricular function in young type I diabetic patients. A Doppler echocardiography study]. / Die Linksventrikelfunktion bei jungen Typ I-Diabetikern. Eine Doppler-echokardiographische Studie.

Systolic and diastolic left ventricular function was assessed by M-mode and pulsed Doppler echocardiography in 10 young type I diabetic patients without late complications and maximal diabetes duration of 5 years and in 10 healthy persons. Fractional shortening, a measure of systolic ventricular function, was significantly lower in diabetics than in controls (33.9 +/- 2.9 vs. 37.9 +/- 4.9; p less than 0.05). Fractional shortening decreased significantly with advancing diabetes duration (R = -0.819; p less than 0.01). Indexes of diastolic ventricular function (isovolumetric relaxation period and transmitral flow velocity pattern) were not significantly different in the two groups, but 3 patients had 1 parameter (3x isovolumetric relaxation period) and another patient had 2 parameters (isovolumetric relaxation period and early diastolic peak velocity E-E') outside the normal range. Follow-up studies should define the clinical significance of these alterations of systolic and diastolic left ventricular function.

[Angiologic, neurologic and orthopedic findings in vibration exposed chain saw operators]. / Angiologische, neurologische und orthopädische Befunde bei vibrationsexponierten Kettensägenarbeitern.

The present study was designed to evaluate and correlate angiological, neurological and orthopaedic findings in lumberjacks, professionally exposed to vibration by chain-saws with a frequency of 40 to 120 Herz. Raynaud's phenomenon was diagnosed in 16 of 33 subjects. The nerve conduction velocity was delayed in 13 of 32 lumberjacks, the sulcus nervus ulnaris syndrome was diagnosed in 41%, the vibration threshold was abnormal in 10/32 cases. Orthopaedic examination and X-ray studies revealed spondylotic (59%) and spondyloarthritic (65%) alterations of the cervical spine; cysts in bones of the distal upper extremities were observed in 75% of cases. Frequency and severity of angiological, neurological, and orthopaedic pathological findings correlated with the total chain-saw operating time. However, there was no correlation between the presence of digital vascular hyperreactivity and the sulcus nervus ulnaris syndrome or changes in nerve conduction velocity.

Increase in bicycloprostaglandin E2 metabolite in congestive heart failure in response to captopril.

Vasodilating prostaglandins may be increased in patients with chronic congestive heart failure (CHF) to balance out the effects of vasoconstricting forces. Significant increases in plasma levels of bicycloprostaglandin E2 metabolite (PGEm), a chemically stable degradation product of the vasodilating prostaglandin E2, were found in response to captopril (39.4 +/- 7.8 vs. 46.2 +/- 8.2 pg/ml; p less than 0.01). With chronic captopril treatment bicyclo-PGEm remained elevated for 12 h after the last dose after 1 and 2 months (75.5 +/- 5.5; p less than 0.05 and 72.1 +/- 6.3 pg/ml; p less than 0.05, respectively). Upon readministration of captopril during chronic captopril treatment the significant increase of bicyclo-PGEm in response to captopril was sustained, as were changes in plasma renin activity, angiotensin II, and blood pressure. Plasma catecholamines were unchanged with captopril or decreased slightly, vasopressin remained moderately increased throughout. Taken together, the results suggest that vasodilating prostaglandin E2 production might play a part in captopril's beneficial action in chronic congestive heart failure.

[Left heart hypertrophy in arterial hypertension in relation to hemodynamic and humoral factors]. / Linksherzhypertrophie bei arterieller Hypertonie in Relation zu hämodynamischen und humoralen Faktoren.

In patients with arterial hypertension hemodynamic as well as humoral factors may influence the development of left ventricular hypertrophy. We therefore investigated in 23 patients with long standing hypertension (11 females, 12 males, age 50 +/- 13 years) wether left ventricular mass as determined by echocardiography interrelates with hemodynamic or humoral parameters. Left ventricular mass measured 161 +/- 51 g/m2 and correlated significantly with patients' age (r = 0.55, p less than 0.05) and systolic blood pressure (159 +/- 21 mm Hg, r = 0.51, p less than 0.05) but not with diastolic blood pressure (99 +/- 15 mm Hg, r = 0.23, not significant). Plasma renin activity was 0.6 +/- 0.6 ng/ml/h and plasma norepinephrine levels measured 371 +/- 168 ng/l. Neither of these humoral parameters correlated significantly with left ventricular mass. It is concluded that in long standing hypertension left ventricular hypertrophy is determined predominantly by the elevation of systolic blood pressure and the patients' age.

Noninvasive assessment of left ventricular diastolic function by pulsed Doppler echocardiography in young alcoholics.

M-mode echo recordings of the left ventricle and left ventricular inflow Doppler velocimetry were performed in 34 male alcoholics below age 45 and in 25 nonalcoholic male controls. Groups were well matched for age, body surface area and heart rate. Systolic arterial pressure was slightly higher in alcoholics and none of the subjects studied had cardiorespiratory symptoms. Data from imaging echocardiography (M-mode echo) were comparable in both groups, and fractional shortening, reflecting left ventricular systolic performance, was identical. Left ventricular inflow Doppler velocimetry showed quite different results in alcoholics and control subjects for the early diastolic flow velocity peak (0.52 +/- 0.12 versus 0.61 +/- 0.11 m/s; p less than 0.01) and in peak flow velocities in the atrial contraction phase (0.32 +/- 0.11 versus 0.27 +/- 0.06 m/s; p less than 0.05). The lower ratio of both velocities in patients (1.88 +/- 0.95 versus 2.34 +/- 0.60 m/s; p less than 0.05) suggests that left ventricular distensibility is altered in alcoholics. In addition, isovolumetric relaxation period, reflecting an early diastolic event, was slightly but significantly prolonged in alcoholic subjects (68 +/- 14 versus 56 +/- 10 ms; p less than 0.001). It is concluded that diastolic performance is altered in young alcoholics without cardiorespiratory symptoms showing normal systolic performance, and that these alterations may be an early marker of alcoholic cardiomyopathy.

Development of optimal infusion regimens for epoprostenol using radio labelled platelet uptake over atherosclerotic lesions in man.

1. Epoprostenol (prostacyclin, PGI2) has been evaluated in clinical trials in peripheral vascular disease and other conditions chiefly on the basis of its platelet inhibitory properties. These therapeutic evaluations have proceeded in the absence of evidence as to the optimum infusion regimen for epoprostenol and the choice of schedules of administration has been arbitrary. We have tried to establish an optimum infusion regimen in patients with peripheral vascular disease in terms of maximal inhibition of platelet deposition on atherosclerotic lesions in vivo together with maximal inhibition of platelet aggregation ex vivo. 2. One hundred and twenty three patients with atherosclerotic peripheral vascular disease and increased platelet uptake at atherosclerotic sites were selected. Epoprostenol was administered at a fixed dose of 5 mg kg-1 min-1 for 0.5-24 h daily for 3-7 days. 3. Infusion of epoprostenol for 6 h daily for up to 5 days caused maximum decrease in platelet uptake without tachyphylaxis and without loss of the inhibitory effect of epoprostenol on platelet aggregation responses. Longer daily infusion periods were associated with progressive loss of the anti-aggregatory effect of epoprostenol without any greater decrease in platelet uptake. Shorter daily infusion periods produced smaller decreases in platelet uptake.

Renin-angiotensin-aldosterone system and vasopressin in cyclosporine-treated renal allograft recipients.

Eleven patients, who had undergone renal transplantation and who had hypertension, aged 19-56 years, were treated with cyclosporine and prednisolone. We measured plasma renin activity, aldosterone and vasopressin (RIAs) at the first, second and third week and again 9 to 12 months after transplantation. Plasma renin activity was in the low-normal range throughout (0.31 +/- 0.05, 0.30 +/- 0.03, 0.32 +/- 0.05 ng/ml/h on short- vs. 0.32 +/- 0.04 ng/ml/h on long-term), aldosterone showed a tendency to decrease (114 +/- 27, 72 +/- 18, 71 +/- 11 pg/ml on short- vs. 54 +/- 23 pg/ml on long-term), whereas vasopressin remained moderately increased during the observation period (10.5 +/- 0.8, 10.4 +/- 1.6, 8.9 +/- 0.6 pg/ml on short- vs. 9.6 +/- 1.0 pg/ml on long-term). We then investigated the reactivity of the renin-system in 5 of the patients by stimulating renin release by captopril. Increases in plasma renin activity were only moderate (0.35 +/- 0.03 vs. 0.66 +/- 0.21 ng/ml/h) and blood pressure dropped only slightly (148 +/- 2.0/98 +/- 1.2 vs. 141 +/- 4.6/95 +/- 4.2 mmHg). Levels of plasma aldosterone were significantly suppressed from a low baseline (46.4 +/- 13.5 vs. 25.3 +/- 6.1 pg/ml, p less than 0.05). The increase in vasopressin was unaffected by captopril (9.6 +/- 1.0 vs. 8.8 +/- 0.4 pg/ml). Our results suggest that in renal transplantation patients with good graft function, the activity of the renin system is unaffected by cyclosporine treatment on short- and on long-term. Vasopressin stimulation does not seem to depend on the renin system and might play a role as a vasoconstrictor in the face of a denervated kidney.

Effect of captopril on renin and blood pressure in cirrhosis.

In hepatic cirrhosis neurohumoral vasoconstrictor systems are activated to compensate for circulatory disturbances. To study the renin-angiotensin-aldosterone system in more detail, angiotensin converting enzyme in 15 patients with advanced liver disease was inhibited with captopril after moderate sodium restriction. Captopril caused an increase in plasma renin activity (p less than 0.005) and a decrease in plasma aldosterone (p less than 0.025) from an elevated baseline, and a moderate drop in systolic (p less than 0.025) and diastolic (p less than 0.05) blood pressure. Hyperreninaemia after captopril was inversely related to the prevailing plasma sodium level (r = -0.66, p less than 0.01), and the changes in both systolic and diastolic blood pressure were correlated with baseline plasma renin activity (r = 0.49, p less than 0.05 for systolic and r = 0.71, p less than 0.01 for diastolic blood pressure). No change occurred in heart rate or in stimulated plasma noradrenaline and vasopressin levels. The data suggest that in these cirrhotic patients the reactivity of the renin-angiotensin-aldosterone system was still intact, although it occurred at a higher level. They confirm the importance of the renin-angiotensin-aldosterone system in arterial blood pressure regulation in cirrhosis.

[Hemodynamic effects of nitroglycerin following acute inhibition of prostaglandin synthesis]. / Hämodynamische Wirkungen von Nitroglycerin nach akuter Hemmung der Prostaglandinsynthese.

The mechanism of action by which nitrates produce vasodilation has not been fully clarified so far. Experimental studies indicate a possible relationship to the prostaglandin system. This study describes the consequences of acute prostaglandin synthesis inhibition on the hemodynamic effects of nitroglycerin in patients with stable angina pectoris. Intravenous application of 1 g acetylsalicylic acid was associated with a small but significant blunting of the pressure decline in the pulmonary and systemic circulation following the sublingual administration of 0.8 mg nitroglycerin. Premedication with 75 mg indomethacin i.m. was followed by a decrease in pressure decline in the pulmonary artery during intravenous nitroglycerin infusion. Significant inhibition of prostaglandin synthesis was shown by a substantial decline in plasma levels of circulating prostaglandin metabolites in both experiments. These results indicate that the mechanism of action of nitroglycerin may be partially mediated by vasodilatory prostaglandins.

Platelet sensitivity to prostacyclin in smokers and non-smokers.

Platelet activating effect of cigarette smoking appears to be important in the development of atherosclerosis. We previously demonstrated a reduced sensitivity of platelets to exogenous prostacyclin (PGI2) in vitro from patients with proven atherosclerotic disease, indicating a possible role of altered platelet function in the development of atherosclerosis. We now hypothesize that cigarette smoking might be an important cause of altered platelet sensitivity to PGI2 observed in patients with atherosclerosis. To test this hypothesis, the response of platelets to exogenous PGI2 was tested in chronic smokers and non-smokers, prior to and after smoking two cigarettes (active smoking) and prior to and after exposure to a tobacco smoke-contaminated atmosphere (passive smoking). This study indicates that platelets of chronic smokers are less sensitive to exogenous PGI2 than platelets of non-smokers. In addition, active as well as passive smoking decreases platelet sensitivity to PGI2 in non-smokers, whereas chronic smokers exhibit no further decline. We conclude that decreased platelet sensitivity to PGI2 might be an important contributing factor to the altered platelet function observed in patients with atherosclerosis.