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Biomedical subjects

W Kübler

Publications and source records attributed to W Kübler.

At least 109 records · Page 6Linked to original sources
PubMed1998

Activation of coagulation and fibrinolysis after rehabilitative exercise in patients with coronary artery disease.

It has been suggested that blood coagulation be activated and fibrinolytic activity be impaired in patients with coronary artery disease (CAD). With regard to the activation of coagulation and fibrinolysis occurring during exercise in healthy individuals, we examined the hypothesis that rehabilitative exercise in patients with CAD might give rise to an exaggerated activation of coagulation. In 12 patients with angiographically documented CAD without myocardial infarction within the preceding 6 months (male, age 55+/-9 years [SD]) and in 12 healthy controls (male, 52+/-7 years), molecular markers of thrombin, fibrin, and plasmin formation were determined before and after a rehabilitative group exercise session lasting 1 hour. Resting levels of prothrombin fragment 1+2 were lower in patients with CAD (0.67+/-0.2 [SE] vs 1.04+/-0.2 nmol/L, p <0.001) and remained unchanged after exercise, whereas a significant increase was noted in controls (p <0.01). After exercise, plasma levels of thrombin-antithrombin III complexes and of fibrinopeptide A increased significantly in both groups, although there were more pronounced changes in controls. Exercise resulted in a marked generation of plasmin as indicated by plasmin-alpha2-antiplasmin complexes increasing 2.5-fold in patients (p <0.001) and threefold in controls (p <0.001). Repeated experiments in control subjects after administration of aspirin (day 1: 500 mg; days 2 to 5: 100 mg) documented that differences between groups could not be attributed to aspirin medication (100 mg/day) in patients with CAD. We concluded that rehabilitative exercise in patients with CAD beyond the immediate postinfarction period has no detrimental effects on thrombin, fibrin, and plasmin formation.

Adult↗
PubMed1998

[Prevention and treatment of restenosis after percutaneous transluminal coronary angioplasty].

Restenosis is a clinical problem after coronary angioplasty associated with major ischemic events or repeat interventions in 20-50% of the patients undergoing this procedure. Major efforts have been undertaken in the past decade to successfully prevent or treat restenosis but no pharmacologic approach to the problem has as yet been identified to be effective enough in clinical conditions. New strategies to cope with restenosis are targeted by local application of ionizing radiation which markedly reduces cell proliferation after angioplasty in animal experiments. Preliminary clinical trials indicate that endovascular radiation therapy is a safe and effective means to treat restenosis. Randomized, multicenter studies with long follow-up periods are needed to support these early results.

Angioplasty, Balloon, Coronary↗
PubMed1998

[Catheter-assisted techniques for decreasing the rate of restenosis after coronary angioplasty: an overview of radiotherapy].

Restenosis after percutaneous transluminal coronary angioplasty (PTCA) is a clinical problem associated with major ischemic events or repeat interventions in 20-50% of the treated patients. Systemic drug therapy has not yet been shown to prevent restenosis in clinical conditions. However, local therapeutic strategies are evolving, such as the catheter-based delivery of drugs, of antiproliferative genes, or of ionizing radiation. Experimental studies show that radiation therapy reduces restenosis rates, and preliminary clinical trials investigating a small number of patients indicate that, in particular, catheter-based radiation may be safe and effective. Randomized multicenter studies with long follow-up periods are needed to support these early results.

Angioplasty, Balloon, Coronary↗
PubMed1998

Heart failure: is there an energy deficit contributing to contractile dysfunction?

UNLABELLED: Alterations in myocardial energy metabolism have been demonstrated in both animal experiments and clinical observations. Whether these changes contribute to heart failure has been a longstanding and controversial issue. I. The creatine kinase (CK) system and the high energy phosphates under physiological conditions and in acute heart failure: 1. According to in vivo and in vitro experiments the myocardial creatine/creatine phosphate (Cr/CP) system is directly linked to mitochondrial oxidative phosphorylation via the mitochondrial CK. 2. The shift in the mass action ratio of the CK reaction with increasing myocardial oxygen consumption enables marked stimulation of mitochondrial respiratory function via the Cr/CP system with almost maintained free energy of the adenosine triphosphate/adenosine diphosphate (ATP/ADP) system. 3. In acute heart failure the depressed myocardial content mainly of CP can be considered as an adaptive mechanism related to increased oxygen demands. II. The CK system and the high energy phosphates in chronic heart failure: 1. The alterations observed in the CK system in chronic heart failure cannot be interpreted in terms of an "energy deficit" (i.e., the excess of what is spent over what is received on energy). 2. "Energy reserve" (i.e., energy kept back for future use, to fill an emergency) is markedly reduced in heart failure. 3. Under steady state conditions decreased "energy reserve" cannot be expected to contribute to heart failure. Under stress conditions, however, this mechanism is manifest by reducing contractile reserve. 4. The mechanisms by which decreased "energy reserve" induces depression of contractile reserve is not elucidated. III. Heart failure related to alterations in energy metabolism (mitochondrial diseases, stunned, and hibernating myocardium): 1. The phenotype of mitochondrial diseases is predominantly determined by neurological disorders and myopathies. Therefore, the patients are rarely referred to a cardiologist, although the cardiac involvement may ultimately determine the patients' prognosis. 2. Stunned and hibernating myocardium are characterized by prolonged contractile dysfunction in the presence of reversibly damaged myocardium. The underlying mechanisms and its triggers are unknown. INTERPRETATIONS: 1. The reduced energy reserve in heart failure may be considered to contribute to the progression of the disease. 2. As an alternative, however, it can likewise represent a mechanism to protect the endangered myocardium from overload.

Adenosine Diphosphate↗
PubMed1998

Polarized expression of heterologous membrane proteins transfected in a human endothelial-derived cell line.

The generation and maintenance of cell polarity in endothelial cells is poorly understood, partly because of a lack of a permanent endothelial in vitro model system. Here we evaluated the spontaneously immortalized human endothelial-derived cell line ECV304 as an in vitro model system for the study of the polarized expression of heterologous membrane proteins. Several stable ECV304 clones were generated by calcium phosphate transfection/G418 selection with cDNAs encoding membrane proteins of known cell surface distribution in the epithelial Madin Darby canine kidney (MDCK) cell line: influenza hemagglutinin and uvomorulin/E-cadherin were used as markers for the apical, respectively lateral cell membrane, the human lymphocyte surface marker CD7 served as an example of a circumferentially distributed membrane protein. Analysis of the transfected ECV304 clones using conventional and confocal immunofluorescence microscopy and immunoelectron microscopy revealed the same membrane distribution of the heterologous proteins in ECV304 cells as in MDCK cells. This polarized expression of heterologous membrane proteins in the endothelial-derived ECV304 cell line indicates efficient protein sorting/membrane trafficking mechanisms. The apical, lateral and basal cell membrane domains could be distinguished in ECV304 cells by confocal immunofluorescence microscopy. The permanent endothelial-derived ECV304 cell line may be a useful in vitro model system for the study of endothelial cell polarity.

Animals↗
PubMed1998

Frequency and phenotypes of familial dilated cardiomyopathy.

OBJECTIVES: This prospective study was performed to analyze the frequency and clinical characteristics of idiopathic dilated cardiomyopathy (DCM). BACKGROUND: Despite several previous reports on families with DCM, most cases are still believed to be sporadic, and specific clinical findings of the familial form are not well defined. METHODS: In 445 consecutive patients with angiographically proven DCM, we obtained detailed family histories to construct pedigrees and examined 970 first- and second-degree family members. RESULTS: Familial DCM was confirmed in 48 (10.8%) of the 445 index patients and was suspected in 108 (24.2%). The 156 patients with suspected or confirmed familial disease were younger at the time of diagnosis (p < 0.03) and more often revealed electrocardiographic changes (p = 0.0003) than patients with nonfamilial disease. Among the families of the 48 index patients with confirmed familial disease, five phenotypes of familial DCM could be identified: 1) DCM with muscular dystrophy; 2) juvenile DCM with a rapid progressive course in male relatives without muscular dystrophy; 3) DCM with segmental hypokinesia of the left ventricle; 4) DCM with conduction defects; and 5) DCM with sensorineural hearing loss. CONCLUSIONS: Up to 35% of patients with DCM may have an inherited disorder. Distinct clinical phenotypes can be observed in some families, suggesting a common molecular cause of the disease.

Adult↗
PubMed1998

Elevated serum concentrations of cardiac troponin T in acute allograft rejection after human heart transplantation.

OBJECTIVES: This study evaluates the concept and diagnostic efficacy of using serum troponin T for the detection of cardiac graft rejection. BACKGROUND: Cardiac troponin T is a cardiospecific myofibrillar protein, which is only detectable in the circulation after cardiac myocyte damage. It might be expected to be released during acute heart allograft rejection, allowing noninvasive rejection diagnosis. METHODS: In 35 control subjects and in 422 samples from 95 clinically unremarkable heart allograft recipients more than 3 months postoperatively, troponin T serum concentrations were compared to the histological grade of acute graft rejection in concurrent endomyocardial biopsies. RESULTS: Mean troponin T serum concentrations were identical in control subjects (23.2 +/- 1.4 ng/liter) and in heart transplant recipients without graft rejection (International Society for Heart and Lung Transplantation [ISHLT] grade 0; 22.4 +/- 1.7 ng/liter). Mean troponin T concentrations increased in parallel with the severity of graft rejection (ISHLT grade 1: 27.8 +/- 1.8 ng/liter; grade 2: 33.2 +/- 2.7 ng/liter; grade 3A: 54.6 +/- 6.5 ng/liter; grade 3B and 4: 105.4 +/- 53.7 ng/liter; p < 0.001 for grades 3 and 4 vs. grades 0 and 1). The proportion of positive samples also increased in parallel with rejection severity, reaching 100% in rejections of grade 3B and 4. Sensitivity and specificity for the detection of significant graft rejection (ISHLT grade 3/4) were 80.4% and 61.8%, respectively. The negative predictive value was most remarkable with 96.2%. Intraindividual longitudinal analysis of troponin T levels and biopsy results in 15 patients during long-term follow-up confirmed these findings. CONCLUSIONS: The present data demonstrate that acute allograft rejection after human heart transplantation is often associated with increased serum concentrations of troponin T. All cases of serious forms of graft rejection would have been detected before the development of clinical symptoms. Measurement of troponin T levels may become a useful ancillary parameter for noninvasive rejection diagnosis, being most valuable in the exclusion of severe cardiac graft rejection.

Acute Disease↗
PubMed1998

Differential rate and potassium-dependent effects of the class III agents d-sotalol and dofetilide on guinea pig papillary muscle.

The class III agents d-sotalol and dofetilide have been shown to exhibit differential effects in large controlled clinical trials. The aim of this study was to investigate the basic electrophysiological properties of these two antiarrhythmia agents in an in vitro experimental model with regard to potential antiarrhythmic and proarrhythmic action. Using standard microelectrode techniques, we evaluated the electrophysiological effects of d-sotalol and dofetilide on action potential parameters recorded from guinea pig papillary muscle at 2.5 mM, 3.5 mM, and 5.6 mM extracellular potassium concentrations. The following parameters were recorded: resting membrane potential (RMP), action potential amplitude (APA), action potential duration at 90% repolarization (APD 90), and maximum upstroke velocity (Vmax). Under all conditions studied, both d-sotalol and dofetilide exhibited highly selective reverse rate-dependent class III action. In contrast to dofetilide, the class III activity of d-sotalol was markedly influenced by changes in extracellular potassium concentrations, predominantly at low pacing rates. Hypokalemia enhanced the action potential-prolonging effects of d-sotalol, whereas hyperkalemia diminished this effect. In addition, reverse rate dependence associated with dofetilide was significantly more pronounced than reverse rate dependence associated with d-sotalol. Our observations provide a potential electrophysiological basis for differential antiarrhythmic and proarrhythmic mechanisms associated with these two drugs.

Action Potentials↗
PubMed1998

Radiocontrast-induced natriuresis associated with increased urinary urodilatin excretion.

OBJECTIVE: Intravascular radiocontrast agents induce a pronounced diuresis. The aim of the present study was to investigate the (patho-)physiological mechanisms of the radiocontrast-induced diuresis. DESIGN: The fractional excretion of sodium, the urinary excretion of the renal natriuretic peptide urodilatin and the plasma concentration of atrial natriuretic peptide were measured in 42 unselected patients immediately before and after intravascular radiocontrast administration during coronary angiography. SETTING: Cardiac catheterization laboratory of a university hospital. RESULTS: After angiography both the plasma concentration of atrial natriuretic peptide (median post-pre difference: 3.9 pmol L(-1), quartiles -1.2; 7.0) and the urinary excretion of urodilatin (median post-pre difference: 67.0 nmol urodilatin/mol creatinine, quartiles 39.7; 152.1) were increased. The urinary urodilatin excretion was correlated with an increase in the fractional excretion of sodium (median post-pre difference: 1.7%, quartiles 0.6; 3.1). There was no correlation between the serum concentration of atrial natriuretic peptide and urinary sodium excretion. For the radiocontrast-induced increase in both urodilatin and sodium excretion there was no indication for differences between patients without (31) and with (11) intravenous saline infusion. CONCLUSION: The radiocontrast-induced diuresis is a natriuresis which is associated with an increased urinary excretion of urodilatin. The association between natriuresis and urinary urodilatin excretion irrespective of baseline volume status corroborates the hypothesis that urodilatin contributes to the sodium excretion after radiocontrast administration in a paracrine manner. This finding has pathophysiological and potentially therapeutic implications in radiocontrast-induced nephropathy.

Atrial Natriuretic Factor↗
PubMed1998

Radiocontrast-induced DNA fragmentation of renal tubular cells in vitro: role of hypertonicity.

BACKGROUND: Radiocontrast-induced nephropathy is a clinically important complication of invasive cardiological procedures. It has been associated with DNA fragmentation of renal tubular cells, which is a hallmark feature of programmed cell death (apoptosis). We investigated the mechanism of this DNA fragmentation in an in vitro model of radiocontrast cytotoxicity on renal epithelial cells. METHODS: Madin Darby canine kidney (MDCK) cell monolayers were incubated (for 2-8 h) with isoiodine doses (37-111 mg iodine/ml) of the highly hyperosmolal, ionic radiocontrast agent diatrizoate or of the less hyperosmolal, non-ionic substance iopamidol. Mannitol, urea, and NaCl control media of corresponding hyperosmolality were used to evaluate the contribution of hypertonicity, hyperosmolality and/or ionic strength to radiocontrast toxicity. DNA fragmentation was assessed using fluorescence-activated cell sorting (FACS), agarose gel electrophoresis and terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end labelling (TUNEL), cell morphology was analysed in Giemsa-stained cytospins. RESULTS: Diatrizoate induced concentration- and time-dependent DNA fragmentation of MDCK cells which was associated with morphological signs of apoptosis. Cycloheximide (1 microg/ml) did not prevent diatrizoate-induced DNA fragmentation, indicating that it is not dependent on protein synthesis. Diatrizoate-mediated cell death was associated with cell detachment from the tissue culture matrix. However, the DNA fragmentation is not a consequence of cell detachment since the prevention of cell attachment on agarose-coated dishes induced significantly less DNA fragmentation than diatrizoate. Iopamidol caused no detectable DNA breakdown. In contrast, hypertonic mannitol and sodium chloride, but not hyperosmolal urea, induced DNA fragmentation in MDCK cells, albeit less than diatrizoate. CONCLUSIONS: The DNA fragmentation of MDCK cells induced by diatrizoate is related to its hypertonicity in this in vitro model of radiocontrast cytotoxicity. Nuclear disintegration with subsequent cell death may contribute to the pathophysiology of radiocontrast-induced nephropathy, particularly in the hypertonic/hypoxic environment of the renal medulla. The present results underscore the importance of avoiding hyperosmolal urine states in patients at high risk of radiocontrast-induced nephropathy.

Animals↗
PubMed1998

Acute effects of haemodialysis on cutaneous microcirculation in patients with peripheral arterial occlusive disease.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) is an increasing problem in patients on maintenance haemodialysis. Alterations in microvascular perfusion accompany and complicate arteriosclerosis of large vessels and might contribute to the disease process. The aim of the study was to investigate the acute effects of haemodialysis on the cutaneous microcirculation in 26 patients with and without intermittent claudication. METHODS: Cutaneous perfusion was assessed by measuring transcutaneous oxygen pressure (tcPO2) and skin temperature at the dorsum of the foot. After standardized cooling to 15 degrees C of a 2cm2 skin area, the time to reach baseline skin temperature was evaluated as an indirect parameter of reactive hyperaemia. RESULTS: During haemodialysis, tcPO2 dropped significantly in both groups. The decrease in tcPO2 was more pronounced in patients with PAOD (20% vs 15% n.s.). The reactive hyperaemia response was reduced significantly in patients with intermittent claudication indicated by a prolonged time to reach baseline skin temperature after cooling. Values of tcPO2 and reactive hyperaemia did not reach baseline values at the end of haemodialysis in either group. CONCLUSIONS: Nutritive skin perfusion is impaired during haemodialysis. These changes are more pronounced in patients with PAOD and persist after dialysis. These findings are relevant for the treatment of patients with vascular disease on maintenance haemodialysis.

Adult↗
PubMed1998

Differential effects of d-sotalol on subendocardial Purkinje myocytes isolated from normal or 10 to 14 days postinfarction canine hearts: role of extracellular potassium concentration.

Electrophysiologic properties of surviving Purkinje cardiomyocytes in the late postmyocardial-infarction phase are not well established. By using standard microelectrode techniques, we evaluated the effects of the class III agent d-sotalol on action potential parameters of single Purkinje cardiomyocytes isolated from normal canine hearts or those 10-14 days after infarction. Measurements were obtained at 2.5, 3.5, and 6 mM extracellular potassium concentrations. Action-potential parameters recorded at baseline did not differ significantly between normal and infarct-surviving Purkinje cardiomyocytes. At 3.5 and 6 mM extracellular potassium concentrations, surviving Purkinje cells appeared to be more sensitive to the effects of d-sotalol than normal Purkinje cells. In contrast, at 2.5 mM extracellular potassium concentration, the differential responses of normal and infarct-surviving Purkinje cells to d-sotalol was abolished. Reverse rate dependence was more prominent in normal than in postinfarction Purkinje cells, independent of the extracellular potassium concentration studied. The previously described enhanced sensitivity of subacutely infarcted tissue to class III agents seems to persist on a cellular level 10-14 days after myocardial infarction, even after full normalization of baseline action-potential parameters. Differential membrane-regulation mechanisms, dependent on the extracellular potassium concentrations, may account for the increased susceptibility to antiarrhythmia agents in the late postinfarction phase.

Action Potentials↗
PubMed1998

Adjuvant treatment with ursodeoxycholic acid may reduce the incidence of acute cardiac allograft rejection.

BACKGROUND: The nontoxic bile acid, ursodeoxycholic acid (UDCA), is an effective drug for the treatment of different cholestatic conditions. Furthermore, an immunomodulatory capacity of UDCA has been reported in vitro, as well as in vivo, in different immune-mediated liver diseases and after liver transplantation. METHODS: In this retrospective study, the influence of UDCA on heart transplant rejection was investigated in 21 cardiac allograft recipients receiving UDCA for cyclosporine-induced cholestasis (500 mg administered twice daily, start of therapy within the first postoperative month, duration >8 weeks). Thirty-one patients not receiving UDCA served as control subjects. All patients received triple-maintenance immunosuppression (cyclosporine, azathioprine, prednisolone). For quantitative comparison of rejection severity, the following score was applied: 0, no specific therapy; 1, temporary increase in oral steroids; 2, intravenous steroids; 3, ATG or OKT3 therapy. RESULTS: During the first 6 postoperative months, the number of acute rejection episodes requiring specific anti-rejection therapy was significantly lower in the UDCA group as compared with control subjects (1.38 +/- 1.36 vs 2.74 +/- 1.83 rejection episodes per patient, p = 0.005). The cumulative score was significantly lower in the UDCA group as compared with control subjects (2.38 +/- 2.29 vs 5.06 +/- 3.61, p = 0.004). CONCLUSIONS: These initial data indicate a beneficial effect of adjuvant UDCA treatment in the early phase after heart transplantation probably related to immunomodulating properties of UDCA, which may be used therapeutically after organ transplantation.

Acute Disease↗
PubMed1998

Atrial dispersion of refractoriness.

In contrast to the ventricular myocardium, until recently the electrophysiologic properties of the human atrium had been studied less intensively. Since new, highly effective therapeutic strategies have become available, both clinical and experimental research has been focused on atrial arrhythmias. Experimental data suggest that shortening of the refractory periods and increased dispersion of refractoriness between adjacent areas of the atrium are characteristic for paroxysmal atrial fibrillation. The duration and frequency of atrial fibrillation episodes seem to be associated with persistent electrophysiologic alteration of the atrium. The influence of the autonomic nervous system, antiarrhythmic drugs, and circadian differences also could play a role in the genesis of atrial arrhythmias.

Animals↗
PubMed1998

Augmented platelet aggregation as predictor of reocclusion after thrombolysis in acute myocardial infarction.

RATIONALE: Reocclusion after thrombolysis diminishes the benefits of early reperfusion after acute myocardial infarction (AMI). No clinical or laboratory variables have been identified as predictors for reocclusion yet. METHODS AND RESULTS: To evaluate hemostatic variables as potential risk determinants platelet aggregation (PA, representing platelet activity), thrombin/antithrombin complexes (TAT, representing thrombin generation), and plasminogen activator inhibitor type 1 (PAI-1, representing endogenous fibrinolysis) were determined in 31 patients with AMI at 0, 1, 2. and 12 h after the start of thrombolysis as well as at hospital discharge. Reocclusion (defined as reinfarction or angiographically confirmed, clinically silent coronary reocclusion) occurred in 5 patients within 5-14 days and in 8 patients within 1 year. TAT plasma concentrations were lower in patients with reocclusion than in those without (9.9+/-5.7 vs. 22.9+/-22.2 ng/ml at 2 h, 6.5+/-3.1 vs. 1 1.2+/-6.4 ng/ml at 12 h, means+/-SD, p <0.05 each). Neither concentration nor activity of PAI-1 in plasma differed between both patient groups. However, both slope and maximum of PA (induced by 2 micromol/l ADP) were augmented in patients with reocclusion (slope: 39.4+/-1.7 vs. 32.5+/-7.4 at 2 h, p <0.001; 42.6+/-2.6 vs. 36.6+/-8.9 at 12 h, p <0.01). Results were independent of the thrombolytic agent used (alteplase or reteplase). A PA slope at 2 h higher than the average slope before thrombolysis (37.2+/-5.7) could be identified as best predictor for early (within 5-14 d, p=0.017, sensitivity 1.00, specificity 0.69) and late reocclusion (within 1 y, p=0.009, 0.88 and 0.74, respectively). CONCLUSIONS: Increased PA following coronary thrombolysis appears to be associated with early and late reocclusion. This marker could be useful in identifying patients who may benefit from more aggressive antiplatelet (such as GP IIb/IIIa receptor antagonists), interventional, or both strategies.

Adenosine Diphosphate↗
PubMed1997

Attenuated progression of coronary artery disease after 6 years of multifactorial risk intervention: role of physical exercise.

BACKGROUND: It was the aim of this study to assess the long-term effects of physical exercise and low-fat diet on the progression of coronary artery disease. At the beginning of the study, 113 male patients with coronary artery disease were randomized to an intervention group (n=56) or a control group (n=57); 90 patients (80%) could be reevaluated after 6 years. METHODS AND RESULTS: Patients in the intervention group (n=40) showed a reduction in total serum cholesterol (6.03+/-1.03 versus 5.67+/-1.01 mmol/L; P<.03) and triglyceride levels (1.94+/-0.8 versus 1.6+/-0.89 mmol/L; P<.005) and maintained their initial body mass index (26+/-2 versus 27+/-2 kg/m2; P=NS), but results were not statistically different from the control group (n=50) (total serum cholesterol, 6.05+/-1.02 versus 5.79+/-0.88 mmol/L; triglycerides, 2.25+/-1.28 versus 1.85+/-0.96 mmol/L [both P=NS]; body mass index, 26+/-2 versus 28+/-3 kg/m2 [P<.0001]). In the intervention group, there was a significant 28% increase in physical work capacity (166+/-59 versus 212+/-89 W; P<.001), whereas values remained essentially unchanged in the control group (165+/-51 versus 170+/-60 W; P=NS; between groups, P<.05). In the intervention group, coronary stenoses progressed at a significantly slower rate than in the control group (P<.0001). Energy expenditure during exercise was assessed in a subgroup; patients with regression of coronary stenoses spent an average of 1784+/-384 kcal/wk (approximately 4 hours of moderate aerobic exercise per week). Multivariate regression analysis identified only physical work capacity as independently contributing to angiographic changes. CONCLUSIONS: After 6 years of multifactorial risk intervention, there is significant and persistent improvement in lipoprotein levels and physical work capacity, which results in a significant retardation of disease progression. These beneficial effects appear to be largely due to chronic physical exercise.

Adult↗