[Lipid intervention and coronary heart disease in men less than 56 years of age. The Coronary Intervention Study: CIS]. / Lipid-Intervention und koronare Herzkrankheit bei Männern unter 56 Jahren. Die Coronare Interventions-Studie: CIS.

UNLABELLED: The CIS was undertaken with the aim to evaluate the effects of lipid modifications on angiographic progression and regression of CAD in patients with CAD and hypercholesterolemia. The design included a multicenter randomized, double-blind, parallel, placebo-controlled comparison, with target and safety limits for adjusting the trial medication depending on the LDL cholesterol level (LDL-C) achieved, i.e., up to 40 mg of simvastatin (S) or placebo (P) daily, add-on medication (up to 3 x 4 g Colestyramin), and diet counselling. Male patients, average age 49 (< or = 56) years, were included with angiographic CAD and a screening total cholesterol of 207-350 mg/dl, who were not due to undergo coronary bypass surgery or PTCA, who did not suffer from serious other disease (e.g., diabetes mellitus), and who had not undergone coronary bypass surgery previously. RESULTS: All baseline variables were comparable in the treatment groups, with 129 patients taking S and 125 taking P. Of these 254 patients 217 had their final study visit and 207 underwent a second angiography after an average treatment time of 2.3 years under an average daily dose of 37 mg S. 205 pairs of films were available for analysis. Vital information was obtained of all patients until closure of the data bank, half a year after the last study angiography. Five deaths occurred within the study period, 12 through March 15, 1995 (S: 1/6, P: 4/6). 37 patients (S: 18, P: 19) discontinued trial drug and protocol. Concomitant CAD medication was comparable in both groups, except lipid-lowering add-on medication which was significantly higher in the P group (38% versus 13%). Significant changes in lipid levels, on treatment, were observed in the S group amounting to a mean difference in LDL-C of -35%, in Apo-Protein B (ApoB) of -30%, in VLDL-C of -37%, and in triglycerides (TG) of -27%, and in HDL-C of +6%, in comparison to the control group; these differences were even greater in 137 fully compliant patients: -41, -36, -39, -31, and +7%, respectively. Progression in the S group was significantly less, as defined by the two primary target criteria: 1) the minimum obstruction diameter (MOD), determined by quantitative coronary angiography (QCA), decreased about five times less in comparison to the control group (S: by -0.017; P: -0.0954 mm), and 2) the standardized visual global change score (GCS) deteriorated almost three times less in the S group (by +0.20) than in the P group (+0.58). Of the secondary target criteria, the mean lumen diameter (QCA) also developed a significant difference (S: -0.20; P: +0.23 mm; p = 0.0006) with a trend toward regression in the S group. The QCA-%-stenosis deteriorated three- to four-times less in the S group as compared to the control group (S: by 0.69%; P: by 2.73%; p = 0.0022), and the number of patients with angiographic progression was nearly halved (S: 30%; P: 56%; p < 0.0000). These differences were determined by intention to treat analysis (ITT), and they were obtained in spite of lipid lowering add-on medication in 38% of the P patients; they turned out to be more pronounced in 137 fully compliant patients, in an analysis "as treated". The mean decrease in LDL-C serum level caused by S was significantly correlated to the decrease in progression, and multivariate regression analysis of both treatment groups identified LDL-C (or ApoB) and TG as independent predictors of progression. Progression appeared to be most pronounced in low and medium sized lesions, and the beneficial effect of lipid intervention dominated in lesions with 12-56% QCA stenosis severity. A small fraction of patients who suffered from exercise-induced angina, with ST-segment-depression at the beginning of the study, experienced a significant improvement under S as compared to P treatment. Although the study was not designed to show differences in clinical events, the combined number of all major cardiovascular events tended to be less frequent in the S than in the C gr

The effects of simulated akinetic and dyskinetic aneurysms on left ventricular systolic function: clinical implications.

OBJECTIVE: Scant attention has been directed towards quantifying the degree of mechanical disadvantage produced by akinetic and dyskinetic aneurysms. The purpose of this study was to evaluate the mechanical disadvantages of simulated akinetic and dyskinetic aneurysms on left ventricular function. METHODS: An elaborate experimental apparatus consisting of a computer-controlled water pressure chamber in which is suspended a model rubber ventricle was developed. The system has been shown to reproduce accurately the ventricular and aortic pressures found in vivo. In this study, a procedure was designed to simulate akinetic and dyskinetic aneurysms of various sizes on ventricular function. RESULTS: The results indicated that an akinetic aneurysm produces little or no mechanical disadvantage with respect to ventricular pressure since systolic paradox is minimal. However, a dyskinetic aneurysm, irrespective of size, will usually compromise ventricular function due to paradoxical systolic expansion in the bulging aneurysmic sac. In vivo, other factors, such as blood coagulation and rhythm disturbances, may influence these results. CONCLUSIONS: An akinetic aneurysm causes little or no mechanical disadvantage while the dyskinetic aneurysm, irrespective of size. will restrict ventricular function. The experimental simulation system, notwithstanding its limitations, thus provides a unique procedure to quantify akinetic and dyskinetic aneurysms.

The effect of simvastatin on progression of coronary artery disease. The Multicenter coronary Intervention Study (CIS).

BACKGROUND: In several angiographic trials, HMG-CoA reductase inhibitors have shown a beneficial effect on the progression of coronary artery disease. Using 20 mg simvastatin, day-1, a treatment period of up to 4 years was necessary to show a significant reduction in coronary artery disease progression. The question remains however whether higher dosages of simvastatin would be more advantageous in respect to the magnitude of the effect and the required time interval to demonstrate treatment efficacy. METHODS AND RESULTS: In the Coronary Intervention Study (CIS), a multicentre randomized double-blind placebo-controlled study, the effects of lipid-lowering therapy with simvastatin on progression of coronary artery disease in 254 men with documented coronary artery disease and hypercholesterolaemia were investigated. Following a period of lipid-lowering diet, treatment with 40 mg simvastatin or placebo was maintained for an average of 2.3 years. Two primary angiographic endpoints were chosen: the global change score (visual evaluation according to the method of Blankenhorn) and the per patient mean change of minimum lumen diameter (evaluated by the CAAS I system). The mean simvastatin dose was 34.5 mg day-1. In the placebo group, the serum lipids remained unchanged; in comparison to the placebo group the simvastatin group showed a 35% LDL-cholesterol decrease. Coronary angiography was repeated in 205 patients (81%) and 203 film pairs (80%,) were evaluable by quantitative coronary angiography. In the simvastatin and placebo groups, the mean global change scores were +0.20 and +0.58 respectively, demonstrating a significantly slower progression of coronary artery disease in the treatment group (P = 0.02). The change in minimum lumen diameter assessed by computer-assisted quantitative evaluation with the CAAS I system was -0.02 mm in the simvastatin group and -0.10 mm in the placebo group (P = 0.002). In the simvastatin group, there was a significant correlation between the LDL cholesterol levels achieved therapeutically and the per patient mean loss of minimum lumen diameter (r = 0.29; P = 0.003). During the study period, there was no significant difference in the incidence of serious cardiac events (15 of 129 patients in the simvastatin group and 19 of 125 patients in the placebo group, ns). CONCLUSION: Treatment with 40 mg simvastatin day-1 reduces serum cholesterol and slows the progression of coronary artery disease significantly within a short period of treatment time. In the treatment group, retardation of progression is inversely correlated to the LDL-cholesterol levels achieved.

[Experimental simulation of dyskinetic heart wall aneurysms]. / Experimentelle Simulation dyskinetischer Herzwand-Aneurysmen.

A mechanical model for the quantitative investigation of the loss of performance of a ventricle caused by aneurysms of different sizes is described. The model permits an accurate simulation of the geometry of both the ventricle and the aneurysm, as well as the mechanical flow situation as expressed by the changing pattern of the intraventricular pressure. Investigations are limited to a determination of the loss of ventricular performance brought about by the dyskinetic motion of the aneurysm.

[Lactovegetarian diet: effect on changes in body weight, lipid status, fibrinogen and lipoprotein (a) in cardiovascular patients during inpatient rehabilitation treatment]. / Die lactovegetabile Diät: Einfluss auf das Verhalten von Körpergewicht, Lipidstatus, das Fibrinogen und Lipoprotein (a) bei Herzkreislaufkranken während einer stationären Rehabilitationsmassnahme.

In this paper, the shortterm influence of a lactovegetarian diet on selected laboratory parameters and motivation of patients in comparison to a conventional, fat-modified and cholesterol-lowered, omnivorous diet during a clinical rehabilitation treatment should be examined. During an average period of 24.2 days the total cholesterol and the LDL-cholesterol fell for a group of 151 patients who had volunteered to sustain a vegetarian diet for the duration of the clinical rehabilitation, significantly higher by a medium level of 31.1 mg/dl (12.5%) versus 16.9 mg/dl (7%) respectively 27.7 mg/dl (14.5%) versus 11.8 mg/dl (6.5%), as compared to a randomly selected control group of 151 patients. The reductions within the groups were also significant. All of the other laboratory parameters such as lipoprotein (a), fibrinogen, uric acid, triglycerides, and HDL-cholesterol did not exhibit any diet-related changes. The weight of the adipose patients could be reduced very significantly through a reduction diet consisting of lactovegetarian food by an average of 3.2 kg versus 1.6 kg (as in the case of the normal, omnivorous diet). All of the dependent values, i.e., circumference of abdomen and hip, and "body-mass-index" (BMI) showed the same highly significant differences. Even after 1 year approximately two-thirds of the patients of the vegetarian group chose the reduction of meat and meat-products in their diet, of which merely a small part, 5.3%, were faithful to the pure lactovegetarian food. Essentially, the favorable effects on the lipid values persisted. The positive effects on the lipid values, the weight, and the motivation of the group of patients with the lactovegetarian diet allow the general recommendation of this diet for heart patients in the course of their clinical rehabilitation.

Electrocardiographic responses to jogging in middle-aged and older men and women.

Recent jogging-related sudden deaths rekindled the concern among health professionals as to the hazards of strenuous exercise. The purpose of this study was to evaluate the extent of rhythm disturbances and myocardial ischemia in older men and women during a typical strenuous jogging session. Twenty-two members of a local jogging club (11 men and 11 women) between the ages of 50 and 66 years participated in the study. The CardioData PR3/ST monitor was employed to record heart rate, rhythm disturbances, J point and ST slope during the course of the run. The men ran a 10 km run and the women a 6 km run at a competitive pace. The mean maximal heart rate during the run was 170 +/- 15 beats/min for the males and 176 +/- 14 beats/min for the females. The mean J point during the run was -3.39 +/- 1.21 mV for the males and -2.97 +/- 0.96 mV for the females. Females showed a significantly lower mean ST slope (3.95 +/- 0.91 mV) during the run than the males (5.56 +/- 1.37 mV, p < 0.05). A number of episodes of premature ventricular beats, both uni- and multifocal, were observed. Exercise testing of sufficient intensity is recommended to detect those persons susceptible to developing serious arrhythmias during strenuous exercise.

Relationship between stature and coronary heart disease in a German male population.

Short stature in men has previously been associated with a higher risk of coronary heart disease. In order to further investigate this observation, the physical characteristics of 4470 German men admitted to the Klinik Roderbirken between 1978 and 1989 with a documented myocardial infarction and with a stenosis greater than or equal to 75% in at least one vessel were compared to those of 711 male controls. Results indicated that the myocardial infarct group was significantly shorter by 1.8 cm than the control group (p less than 0.001). However, discriminant function analysis indicated that height accounted for only 1% of the variance between the cardiac and control patients. Classification analysis further indicated that on the basis of height, the percentage of subjects correctly classified for grouping was no better than 54% for the myocardial infarct patients and 57% for the controls. It was concluded that height exerted a minimal influence on coronary heart disease in this population.

[Short stature as a risk indicator for coronary patients]. / Kleinwuchs als Risikoindikator für Koronarpatienten.

BACKGROUND: Short stature as an indicator of coronary disease in German men is described. PATIENTS AND METHODOLOGY: A total of 4,524 patients investigated by coronary angiography (history of myocardial infarction and at least one vessel greater than or equal to 75% stenotic or occluded on angiography and, in addition corresponding levocardiographic changes) and 722 age-matched test subjects with unremarkable coronary angiographic findings were admitted to the study. RESULTS: The patients with coronary heart disease were, on average, 1.9 cm shorter than those with unremarkable blood vessels. This difference in height was found in particular in the age group between 40 and 60 years old. The reason for this is not known.

Randomized 4-week exercise program in patients with impaired left ventricular function.

BACKGROUND: This study was designed to determine the controlled effects of a short-term exercise rehabilitation program on patients with moderate-to-severe left ventricular dysfunction after a recent myocardial infarction. METHODS AND RESULTS: Thirty-nine male patients 51 +/- 8 years old with a large anterior myocardial infarction less than 10 weeks old were recruited for the study. The patients were randomly assigned to either one of two training or control groups on the basis of their resting ejection fraction: training, less than 30%; control, less than 30%; training, 31-50%; or control, 31-50%. Patients were evaluated for filling pressures, radionuclide ventriculography, heart volume, echocardiography, and work capacity. Patients who underwent training participated in an intensive 4-week in-hospital exercise program, whereas the control patients were restricted to a minimal activity program. Results indicated that there were no significant improvements in resting, submaximal, and maximal hemodynamic measurements as a result of the program. Mean work capacity and peak oxygen consumption improved significantly in the less-than-30% training group but was accompanied by a significant increase in mean pulmonary wedge pressure. Resting ejection fraction improved markedly in both less-than-30% training and control patients, but ejection fraction measures were not associated with work capacity. Training did not cause further deterioration in ventricular function. CONCLUSIONS: It was concluded that in the present study, exercise training had little or no effect on hemodynamic measurements and that the training effects achieved in patients with left ventricular dysfunction are most likely due to corrected impaired vasodilation, not necessarily to cardiac function. The importance of using a control group in this type of study and the wide interindividual variations in training responses are emphasized.

Ambulatory blood pressure and Holter monitoring during tennis play.

The effect of tennis play on blood pressure, heart rate response, and rhythm disturbances was evaluated in 21 men 39 to 61 years of age (M = 49.5 +/- 6.7 yrs). A Holter monitor was utilized for continuous ECG recording during tennis play and a portable ambulatory blood pressure recorder (Spacelabs) was used to measure blood pressures and heart rates periodically during tennis matches. The results indicated that blood pressure response to tennis (singles), although an activity of moderate aerobic intensity, can exert significant increases in systolic and diastolic blood pressure even in those persons who are normotensive at rest. Excessive body weight, and particularly abdominal deposition, appears associated with an increase in diastolic blood pressure to exercise. Few heart rhythm disturbances of consequence were uncovered. A simple submaximal step test such as the Canadian Aerobic Fitness Test, with ECG monitoring, could assist in detecting those individuals susceptible to an exaggerated blood pressure response and to heart rhythm disturbances at exercise.

[Four-week training of patients with large anterior wall infarct: comparison with a randomized untrained control group]. / Vierwöchiges Training bei Patienten mit grossem Vorderwandinfarkt: Vergleich zu einer randomisierten nichttrainierenden Kontrollgruppe.

Thirty-nine male patients (average age 50.8 years +/- 8.4 years) with a large anterior myocardial infarction (average 45.6 days +/- 10.5 days ago) and with moderate to severe left-ventricular dysfunction (RNVA EF less than 50%) participated in the study. The patients were randomly assigned to either a training group or to a control group. They were also subdivided into training/control groups (EF less than 30% and EF = 30-50%). The training program consisted of three to four sessions per day, 5 days a week, at an intensity of up to 1 W/kg body wt. (approximately 4-5 METS). The following evaluations were recorded prior to and following the 4-week training program: relative heart volume (x-ray), echocardiographic data (enddiastolic diameter, ES-distance, and shortening fraction), and exercise stress test (work capacity, heart rate). Filling pressures, cardiac outpout, and stroke volume index were calculated from right-heart catheterization (Swan-Ganz) at rest and during exercise. Results indicate that there were no significant changes in relative heart volume, end-diastolic volume, ES-distance, resting heart rate, PCP at rest, and ejection fraction during exercise as a result of the training program. Shortening fraction showed a tendency to improve (not significant). Work capacity increased by 15 W (p less than 0.05) in the training group and by 28 W (1.5 METS, p less than 0.05) in the EF less than 30% training-group as compared with the control group. Cardiac output at rest decreased by 10% (p less than 0.05). Stroke-volume index increased in the EF greater than 30% training-group, while heart rate was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic equivalents (METS) in exercise testing, exercise prescription, and evaluation of functional capacity.

One metabolic equivalent (MET) is defined as the amount of oxygen consumed while sitting at rest and is equal to 3.5 ml O2 per kg body weight x min. The MET concept represents a simple, practical, and easily understood procedure for expressing the energy cost of physical activities as a multiple of the resting metabolic rate. The energy cost of an activity can be determined by dividing the relative oxygen cost of the activity (ml O2/kg/min) x by 3.5. This article summarizes and presents energy expenditure values for numerous household and recreational activities in both METS and watts units. Also, the intensity levels (in METS) for selected exercise protocols are compared stage by stage. In spite of its limitations, the MET concept provides a convenient method to describe the functional capacity or exercise tolerance of an individual as determined from progressive exercise testing and to define a repertoire of physical activities in which a person may participate safely, without exceeding a prescribed intensity level.

[Long-term course of conservatively and surgically treated patients with an intramural heart infarct]. / Langzeitverlauf konservativ und operativ behandelter intramuraler Herzinfarktpatienten.

Thirty patients with a first nontransmural myocardial infarction (MI) were examined retrospectively. The patients had been treated either surgically or conservatively on the basis of the clinical and morphological findings. Three years following infarction, 28 of the 30 patients were still alive (93.3%). 10 of the 13 patients with one vessel disease and 7 of the 17 patients with two or three vessel disease were gainfully employed. The unfavorable natural course of nontransmural myocardial infarction favors an aggressive diagnostic and therapeutic approach since the survival rate of these patients is only 60 to 70% after three years. The results of this study demonstrates convincingly the economic and social benefits of our diagnostic and therapeutical interventions.

[A survey of the medical and psychosocial status of 140 workers 32 months following myocardial infarct]. / Eine Befragung zur medizinischen und psychosozialen Situation von 140 Arbeiterinnen 32 Monate nach Myokarderstinfarkt.

We suspected there could be different social, psychological, and medical problems for women after a first myocardial infarction than those affecting men. 140 women (56.4 +/- 7 years) were interviewed by questionnaire 32 +/- 8.7 months after myocardial infarction; 83% (n = 119) responded (8.8% of the sample group had died), 12% suffered a reinfarction, and 11% underwent aortocoronary bypass surgery. For 84% of those responding it was harder to do their housework after myocardial infarction, but 73% did it without help. 51.5% showed a mood change that included increasing depression, anxiousness, and insecurity. In 12.5% of the women their relationship with their husband was adversely affected; in 6.6% their relationship with their children worsened. 83% (n = 89) saw their infarction as a result of stress. 45% could not relieve their stress after 32 months. A subjective feeling of stress decrease in 54% was achieved with a quieter life, in 39.5% by resigning their jobs, and in 6.5% by the death of the husband. Concerning somatic risk factors 74% of the smokers stopped smoking; oral contraceptives were discontinued in all cases. 90.5% (n = 97) of the women said they had their serum lipid values checked regularly, but these were only under control in 35%. We conclude the rehabilitation process does not end when patients leave a rehabilitation clinic. Patients should acquire household help, and their family situation should be discussed during their stay in the rehabilitation clinic. Concerning the somatic risk factors, women who survive myocardial infarction require better care and information.

[What therapeutic measures ensure long-term effect in coronary heart disease?]. / Für welche therapeutischen Massnahmen ist bei der koronaren Herzkrankheit ein Langzeitnutzen gesichert?

This paper describes the long-term effect of conservative, interventional and surgical treatment in coronary heart disease on the prognosis and on the quality of life. It is difficult to decide if prognosis or quality of life is more influenced by the different therapeutic measures.

[Long-term automatic blood pressure measurement in clinical management]. / Automatische Blutdruck-Langzeitmessung im Klinikbetrieb.

Blood pressure control in arterial hypertension, as has been shown in randomized studies in 43,000 patients, based on a reduction of diastolic blood pressure of 5.8 mm Hg associated with a 40% reduction in stroke, is of substantial prognostic importance. Cardiac events were reduced insignificantly by 9%. Major problems with treatment are the limited acceptance of a lifelong therapy--in the Munich High Blood Pressure Study from 1982 well controlled and effective treatment was found in only 22% of the men and 16% of the women--uncertainty with regard to the indication and the question of whether the observed blood pressure elevation is situational or persistent in particular, in view of one study reporting that after three years of placebo in 48% of patients entered with diastolic values between 95 and 105 mm Hg, the blood pressure was found to lie in the normal range. Blood pressure determinations by the patients themselves may reflect resting values throughout the day but blood pressure fluctuations which can be substantial, can only be detected by ambulatory monitoring. The aim of this study, in addition to assessment of the reliability of the system employed, was to compare the response of the monitored blood pressure in patients with various stages of hypertension and in normal subjects at rest and during physical exertion to identify more accurately those in need of antihypertensive treatment. For ambulatory blood pressure monitoring, the SpaceLabs Model ICR 5200 was used. If Korotkoff sounds are not detected, the unit switches to oscillatory measuring. The storage capacity accommodates 200 measurements of systolic, diastolic and mean arterial pressure, heart rate and time of measurement.(ABSTRACT TRUNCATED AT 250 WORDS)

Accuracy of ambulatory blood pressure monitoring in four exercise situations.

Although ambulatory blood pressure monitoring (ABPM) is still considered in its investigational stage, the technique has become increasingly popular in recent years. The rationale for its utilization is its ability to continuously monitor blood pressure (BP) response to situational stressors occurring over the course of a 24-hour period which cannot be detected by casual measurements. In addition, ABPM eliminates the so-called white-coat auscultatory BP response. However, the accuracy of ABPM under situations which are at the measurement limits of the technical characteristics and/or capabilities of the ABPM equipment, such as in exercise situations commensurate with daily life activities, has not been fully documented. The purpose of this study was to evaluate the accuracy of the Spacelabs ABPM monitor against auscultatory (AUS) determinations in four exercise situations: walking, stair climbing, cycling and a progressive step test (modified Canadian Aerobic Fitness Test). Analyses of variance (ANOVA) were computed to determine if significant differences occurred between ABPM and AUS measurements for systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) over the resting and four exercise conditions. Results indicate that, particularly at low to moderate levels of exercise intensity, there is no statistically significant difference between ABPM and AUS measurements for SBP and HR. In 20 of the 26 resting and exercise determinations, the difference in SBP was less than 6 mmHg. For HR the variation was no greater than 4 bpm. However, there was no such agreement between ABPM and AUS measurements for DBP. As the intensity of the exercise situations increased, there was a tendency for SBP ABPM measurements to register higher readings than those obtained by AUS. The major drawback in ABPM is its sensitivity to artifacts due to arm movement. It was concluded that ABPM, such as provided by the Spacelabs instrument, can provide reasonably accurate readings of SBP and HR, particularly at low to moderate intensities of exercise while at higher exercise intensities ABPM has a tendency to provide consistently lower SBP values than the AUS measurements. DBP ABPM was totally ineffective under any of the exercise conditions chosen for this study.