Diurnal patterns of triglycerides, free fatty acids, blood sugar, and insulin during carbohydrate-induction in man and their modification by nocturnal suppression of lipolysis.

Previous studies have shown that carbohydrate induction of hypertriglyceridemia in normal subjects occurs at night and appears to be related to a rise of free fatty acids after diurnal feeding of high-carbohydrate formula diet. The present investigation was undertaken to observe the effect on 24-h triglyceride, free fatty acid, blood sugar, and plasma insulin profiles of inhibition of nocturnal lipolysis by glucose or nicotinic acid in normal subjects and in patients with type IV hyperlipoproteinemia. In 10 normal subjects and 10 patients with primary type IV hyperlipoproteinemia, plasma triglyceride, free fatty acid, blood sugar, and insulin levels were followed in short intervals for 24 h while a 2,400 cal, 80% carbohydrate, fat-free formula diet was given in six equal portions during the day (control experiments). This procedure was repeated in the same subjects, 10 of whom (5 normal subjects and 5 patients) received additional feedings of glucose between 2000 and 0600 h while the other 10 persons (5 normal subjects and 5 patients) were given nicotinic acid by intravenous infusion during the same time interval. Both procedures resulted in maintained lowering of free fatty acid levels over 24 h. Mitigation of carbohydrate-induced hypertriglyceridemia appeared to result from the additional glucose in normals and in patients. Nicotinic acid abolished the nocturnal rise of plasma triglyceride levels which in the control studies of normal subjects had resulted in approximate doubling of triglyceride levels in 24 h. The effectiveness of nicotinic acid in inhibiting nocturnal lipolysis and preventing carbohydrate-induction of hypertriglyceridemia might have consequences for management of endogenous hypertriglyceridemia.

Myocardial perfusion and regression of coronary artery disease in patients on a regimen of intensive physical exercise and low fat diet.

This intervention program tested the applicability and effects of intensive physical exercise and a low fat diet on progression of coronary atherosclerotic lesions and stress-induced myocardial ischemia in patients with stable angina pectoris. Eighteen patients participated in this program for 1 year; they consumed a low fat, low cholesterol diet (less than 20 energy % fat, cholesterol less than 200 mg/day) and exercised for greater than 3 h/week. Change in coronary morphology was assessed by angiography and digital image processing; stress-induced myocardial ischemia was measured by thallium-201 scintigraphy. Results were compared with those in patients receiving "usual care." In the intervention group, significant regression of coronary atherosclerotic lesions was noted in 7 of the 18 patients; no change or progression was present in 11 patients. In patients receiving usual care, regression was detected in only 1, with no change or progression in 11 patients (different from intervention, p less than 0.05). There was a significant reduction in stress-induced myocardial ischemia, which was not limited to patients with regression of coronary atherosclerotic lesions. Thus, regular physical exercise and a low fat diet may retard progression of coronary artery disease; however, improvement of myocardial perfusion may be achieved independently from regression of stenotic lesions.

Various intensities of leisure time physical activity in patients with coronary artery disease: effects on cardiorespiratory fitness and progression of coronary atherosclerotic lesions.

OBJECTIVES: This study was designed to define the effect of different levels of leisure time physical activity on cardiorespiratory fitness and progression of coronary atherosclerotic lesions in unselected patients with coronary artery disease. BACKGROUND: It has been shown in various studies that regression of coronary atherosclerotic lesions can be achieved by means of lipid-lowering drugs, reduction of fat consumption and physical exercise. METHODS: Patients were prospectively randomized either to an intervention group (n = 29) participating in regular physical exercise or to a control group (n = 33) receiving usual care. Energy expenditure in leisure time physical activity was estimated from standardized questionnaires and from participation in group exercise sessions. After 12 months of participation, repeat coronary angiography was performed; coronary lesions were measured by digital image processing. RESULTS: After 1 year, patients in the intervention group achieved an increase in oxygen uptake at a ventilatory threshold of 7% (p < 0.001) and peak exercise of 14% (p < 0.05), whereas a significant decrease was observed in patients in the control group. To achieve significant improvement in cardiorespiratory fitness, approximately 1,400 kcal/week had to be expended in the form of leisure time physical activity (p < 0.001). The mean energy expended in such activity was 1,876 +/- 163 kcal/week in the intervention group and 1,187 +/- 97 kcal/week in the control group (p < 0.001). In the intervention group, regression of coronary artery disease was noted in 8 patients (28%), progression of disease in 3 (10%) and no change in coronary morphology in 18 (62%). In contrast, coronary artery disease progressed at a significantly faster rate in patients in the control group (progression in 45%, no change in 49% and regression in 6%) (p < 0.001 vs. intervention). When the two groups were combined, the lowest level of leisure time physical activity was noted in patients with progression of disease (1,022 +/- 142 kcal/week) as opposed to patients with no change (1,533 +/- 122 kcal/week) or regression of disease (2,204 +/- 237 kcal/week) (p < 0.005). CONCLUSIONS: Measurable improvement in cardiorespiratory fitness requires approximately 1,400 kcal/week of leisure time physical activity; higher work loads are necessary to halt progression of coronary atherosclerotic lesions (1,533 +/- 122 kcal/week), whereas regression of coronary lesions is observed only in patients expending an average of 2,200 kcal/week in leisure time physical activity, amounting to approximately 5 to 6 h/week of regular physical exercise.

Physical training in patients with stable chronic heart failure: effects on cardiorespiratory fitness and ultrastructural abnormalities of leg muscles.

OBJECTIVES: The present study was designed to evaluate the effect of an ambulatory training program on ultrastructural morphology and the oxidative capacity of skeletal muscle and its relation to central and peripheral hemodynamic variables in patients with chronic heart failure. BACKGROUND: Clinical evidence supports the hypothesis that exercise intolerance in patients with chronic heart failure is not only a consequence of low cardiac output, but is also a result of alterations in oxidative metabolism of skeletal muscle. METHODS: Twenty-two patients were prospectively randomized either to a training group (mean [+/-SD] ejection fraction 26 +/- 9%, n = 12) participating in an ambulatory training program or to a physically inactive control group (ejection fraction 27 +/- 10%, n = 10). At baseline and after 6 months, patients underwent symptom-limited bicycle exercise testing, and central and peripheral hemodynamic variables were measured. Percutaneous needle biopsy samples of the vastus lateralis muscle were obtained at baseline and after 6 months. The ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry. RESULTS: After 6 months, patients in the training group achieved an increase in oxygen uptake at the ventilatory threshold of 23% (from 0.86 +/- 0.2 to 1.07 +/- 0.2 liters/min, p < 0.01 vs. control group) and at peak exercise of 31% (from 1.49 +/- 0.4 to 1.95 +/- 0.4 liters/min, p < 0.01 vs. control group). There was no significant change in oxygen uptake at the ventilatory threshold and at peak exercise in the control group. The total volume density of mitochondria and volume density of cytochrome c oxidase-positive mitochondria increased significantly by 19% (from 4.7 +/- 1.5 to 5.6 +/- 1.5 vol%, p < 0.05 vs. control group) and by 41% (from 2.2 +/- 1.0 to 3.1 +/- 1.0 vol%, p < 0.05 vs. control group) after 6 months of regular physical exercise. Cardiac output at rest and at submaximal exercise remained unchanged but increased during maximal symptom-limited exercise from 11.9 +/- 4.0 to 14.1 +/- 3.3 liters/min in the training group (p < 0.05 vs. baseline; p = NS vs. control group). Peak leg oxygen consumption increased significantly by 45% (from 510 +/- 172 to 740 +/- 254 ml/min, p < 0.01 vs. control group). Changes in cytochrome c oxidase-positive mitochondria were significantly related to changes in oxygen uptake at the ventilatory threshold (r = 0.82, p < 0.0001) and at peak exercise (r = 0.87, p < 0.0001). CONCLUSIONS: Regular physical training increases maximal exercise tolerance and delays anaerobic metabolism during submaximal exercise in patients with stable chronic heart failure. Improved functional capacity is closely linked to an exercise-induced increase in the oxidative capacity of skeletal muscle.

Influences of "normal" and "prudent" diets on biliary and serum lipids in healthy women.

The differential effect of two diets, taken in synchrony with the menstrual cycles for 2 wk each, on serum and bile lipids was investigated in young healthy women. The "normal" diet was high in cholesterol and total fat, and low in polyunsaturated fat and fiber; the "prudent" diet contained a high proportion of polyunsaturated fat and fiber, but was low in cholesterol and total fat; there was little difference in energy content. Both in whole serum and in low-density lipoprotein the concentrations of cholesterol and apolipoprotein B were almost 30% lower with the "prudent" than with the "normal" diet; HDL-cholesterol was 16.3% lower. Triglycerides were increased, only in the very-low-density lipoproteins while cholesterol and apolipoprotein B did not change much in this fraction. The risk to acquire cholesterol gallstones was not less with the use of the "prudent" diet as originally expected. While using the "prudent" diet five of the women had slightly higher lithogenic indices, in two there were much higher values (greater than 25%), and only in three the lithogenic index was unchanged or slightly lower than with the "normal" diet.

Salt and hypertension: data from the "Heidelberg Study".

Prevalence of hypertension and "intake" of sodium chloride (as estimated from 24-hr urinary Na-excretion) were measured in a random sample (n = 800) of 20- to 40-year-old Heidelberg men. There was a high (14%) prevalence of hypertension and a high (mean = 11.32 g) NcCl intake; both showed, however, no correlation. The lack of a NaCl/blood pressure correlation in this cross-sectional study might be due to intra- and interindividual variability of both parameters and, possibly, to a "threshold" argument concerning the etiological role of sodium in hypertension.

Influence of bezafibrate on plasma lipoproteins, biliary lipids and fecal sterols in healthy men.

The effect of a 4-week treatment with 600 mg/day of bezafibrate in addition to a low-cholesterol, fat-modified diet on plasma lipids and lipoproteins and on biliary lipids and fecal sterols was investigated in 12 healthy men aged 25-39, and compared to the effect of the diet plus placebo, using a double-blind crossover design. The comparison of placebo and treatment values indicated that bezafibrate, beyond the effect of the diet, significantly lowered concentrations of circulating triglycerides (-25.5%), total cholesterol (-25.8%), LDL cholesterol (-19.5%), and apolipoprotein B (-19.9%), and increased apolipoprotein A-II concentrations in serum (+15.0%). There was a tendency towards lower biliary bile acid and cholesterol secretion rates with bezafibrate; lithogenic indices in fasting and stimulated bile were similar with the drug and placebo. Fecal bile acid excretion rate with diet plus bezafibrate was significantly less than with diet plus placebo. The data obtained are in accord with the hypothesis that bezafibrate exerts its effects on cholesterol and bile acid metabolism predominantly by decreasing VLDL secretion, possibly through an enhancement of fatty acid beta-oxidation in the liver.

Treatment of familial hypercholesterolemia with a combination of bezafibrate and guar.

The effect of guar (15.6 g/day), a dietary fibre, and simultaneous administration of bezafibrate (600 mg/day) during dietetic treatment on the plasma lipoproteins and apolipoproteins was investigated in 12 patients with familial hypercholesterolemia (corresponding to the HLP type IIa pattern). Either bezafibrate alone or bezafibrate in combination with guar was administered in a cross-over study for 3 months. Guar led to an additional lowering of the total cholesterol in the plasma by 7% (P less than or equal to 0.05) associated with a fall of the low density lipoprotein cholesterol (LDL-cholesterol (LDL-cholesterol) by 13% (P less than or equal to 0.01) without any changes in the very low density lipoprotein (VLDL) and high density lipoprotein (HDL) cholesterols. In parallel with the decrease in LDL-cholesterol, the apoprotein B also was diminished by 20% (P less than or equal to 0.05). The plasma triglyceride level and the triglyceride distribution within the individual lipoprotein fractions were not altered in any consistent manner by the addition of guar. Neither the fasting plasma glucose level nor the body weight were affected. The side-effects due to guar treatment consisted of slight nausea, meteorism and constipation, but this did not in any of the cases lead to early termination of the study. These results demonstrate that guar exerts its cholesterol-lowering effect in addition to that of bezafibrate.

Sitosterol in juvenile type II hyperlipoproteinemia.

The effect of beta-sitosterol on plasma lipids and lipoproteins was evaluated in a randomized double-blind cross-over trial in 15 children and adolescents with familial hypercholesterolemia over a period of 6 months. Twelve patients completed the study, with good adherence to drug intake. Sitosterol lowered the plasma total choelsterol by 6%, LDL cholesterol by 7% and HDL cholesterol by 15% (P less than 0.05). This insufficient response of total and LDL cholesterol and the marked fall of HDL cholesterol appears to advise against the use of beta-sitosterol granulate in juvenile type II hyperlipoproteinemia.

The effect of bezafibrate on the fibrinolytic enzyme system and the drug interaction with racemic phenprocoumon.

The influence of a new hypolipidaemic agent, bezafibrate, on anticoagulant requirements and fibrinolysis was studied in 15 patients with hyperlipidaemia on long-term treatment with racemic phenprocoumon. Our results suggest a dose-dependent augmentation of the anticoagulant response to the coumarin drug. Treatment with bezafibrate at 450 and 600 mg daily required a reduction of the phenprocoumon dose by 18.5 and 33.5%, respectively. Correspondingly, the serum level of phenprocoumon decreased by 11.6 and 35.3%. No evidence for an altered drug elimination of racemic phenprocoumon could be found during treatment with bezafibrate. The results support the hypothesis that bezafibrate and analogous hypolipidaemic drugs enhance the response to oral anticoagulant drugs by increasing the affinity of the receptor site for coumarins or the rate of degradation of the vitamin-K-dependent clotting factors. The investigation of the fibrinolytic enzyme system demonstrated an increase of the fibrinolytic activity by enhancing the activity of the plasminogen activator. The lysis time for euglobulin clot was reduced significantly, plasma fibrinogen only moderately. The antiplasmin activity could not be altered substantially by a decrease of alpha1-antitrypsin and a slight increase of alpha2-macroglobulin. In contrast with the inhibition of platelet function the effect of bezafibrate on the fibrinolytic enzyme system showed no dose dependence.

"Low dose" colestipol in children, adolescents and young adults with familial hypercholesterolemia.

The effect of colestipol on plasma lipids and lipoproteins was studied in children, adolescents and young adults with familial hypercholesterolemia. O.125 g or 0.25 g/kg body weight were given in randomized sequence for period of 4 weeks. Total cholesterol was lowered by 13 and 18% with the smaller and larger dose , respectively, and LDL cholesterol lowered by 15% with the smaller and 12% with the larger dose. HDL cholesterol rose by 18 an 32%. LDL composition before and during the study was abnormal due to a markedly reduced triglyceride content. "Low-dose" colestipol is less effective lowering total plasma and LDL cholesterol than conventional doses but may, due to very few side effects, by advantageously used in cases of familial hypercholesterolemia when plasma cholesterol levels after dietary management are only 15-20% above normal.

The association of hyperlipoproteinemia with dysimmunoglobulinemia.

In a study of the immunoglobulin concentrations in an urban population and in patients with hyperlipoproteinemia we observed significant positive correlations between serum triglycerides and IgA independent of sex, age and body weight. In men serum triglycerides also correlated with IgG and IgM, and serum cholesterol with IgA. The prevalence of hyper- and hypoimmunoglobulinemia was significantly higher in hyperlipidemic than in normolipemic subjects. We propose that the occurrence of hyperlipoproteinemia with hypoimmunoglobulinemia may be caused by different pathobiological mechanisms than the occurrence with hyperimmunoglobulinemia.

Acute dietary effects on diurnal plasma lipids in normal subjects.

The effects of different dietary carbohydrates and different dietary fats as well as of differently spaced dietary constituents on 24-h plasma free fatty acids and triglycerides were determined in healthy young males. If, in an isocaloric diet containing 15-20% protein, 37% fat and 43--48% carbohydrates, sucrose is compared with glucose, 24-h plasma triglycerides are significantly higher with the former carbohydrate. When palm oil (mainly 16 : 0 fatty acids) is compared with olive oil (mainly 18 : 1 fatty acids), 24-h triglycerides are significantly higher with the latter. If the carbohydrate component of a mixed meal is removed, alimentary lipemia is considerably greater. Our findings supplement long term studies regarding the effect of different dietary fats and carbohydrates on plasma lipids and allow calculation of "upper normal limits" for 24-h plasma triglycerides and free fatty acid patterns on isocaloric diets of "prudent" composition.

Influence of diet on high-density lipoproteins.

Evidence of a relation between diet and high-density lipoprotein (HDL) levels in humans comes from numerous cross-sectional and experimental studies. Evaluation of data from cross-sectional nutrition and health surveys sometimes yields different results for men and women but usually demonstrates positive correlations of HDL cholesterol levels with total energy intake, alcohol consumption, dietary cholesterol and total and animal fat, and negative correlations of HDL with dietary carbohydrates (simple sugars) and, in some instances, plant fats. Short-term dietary manipulation produced confirmatory evidence of a causal relation between diet and HDL with regard to several of these factors; however, there are few long-term data. The underlying mechanisms as well as the relation of HDL manipulation to cardiovascular health are still to be defined, particularly because the functions and fates of the HDL molecule may vary according to its composition and turnover, which are not reflected by the HDL cholesterol concentration. Furthermore, some relations between diet and HDL may only be the result of other metabolic consequences of dietary change, for instance, triglyceride metabolism and other lipoproteins. Although there is consistent evidence that a high HDL cholesterol level is indicative of a low risk of coronary heart disease in industrialized populations, evidence is inconclusive that manipulation of HDL leads to an alteration of risk.

Association between lipoprotein(a) and progression of coronary artery disease in middle-aged men.

The association between lipoprotein(a) (Lp[a]) and progression of coronary artery disease (CAD) compared with other serum lipids was evaluated in 104 patients with angiographically proven coronary atherosclerosis. Patients were randomized to either an intervention or a control group. The 12-month intervention program consisted of a low-fat diet and daily physical exercise. Patients in the control group received "usual care" by their private physician. Eighty-three patients (36 in the intervention and 47 in the control group) underwent repeat angiography after 1 year. Angiographically documented net regression was seen in 13 patients (8 in the intervention and 5 in the control group), no change was seen in 40 patients (21 in the intervention and 19 in the control group) and progression was noted in 30 patients (7 in the intervention and 23 in the control group). No correlation could be shown between Lp(a) and angiographically documented progression of the disease. In a multivariate analysis including metabolic variables, group assignment, age and smoking habits, only assignment to the intervention group (p = 0.0075) and a decrease in total cholesterol (p = 0.0167) were independently associated with the course of the disease. Patients with or without previous myocardial infarction (70 vs 34) did not differ in Lp(a) levels (median 9.15 vs 14.25 mg/dl). Patients with Lp(a) > 25 mg/dl were younger than patients with Lp(a) < or = 25 mg/dl (52 vs 55 years; p < 0.03), indicating a connection between Lp(a) and the development of premature CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of intensive physical exercise and low-fat diet on collateral vessel formation in stable angina pectoris and angiographically confirmed coronary artery disease.

This randomized study was performed to assess the effects of > 3 hours of physical exercise per week and low-fat diet on collateral formation in nonselected patients with coronary artery disease (intervention group, n = 56). Results were compared with those of patients in a control group (n = 57), who received usual care by their private physicians. Coronary lesions were assessed by quantitative coronary angiography at the beginning and after 1 year of study (n = 92). As previously reported, after 1 year there was a significant retardation of progression of coronary artery disease in the intervention group as compared with the control group. In this study, evaluation of collateral formation revealed no significant difference between both groups, and changes in hemodynamic and metabolic variables or leisure time physical activity were not related to changes in collateral formation. Although progression of the disease was significantly related to an increase in collateral formation, regression was significantly related to a decrease in collateral formation (p < 0.00001). Because patients in the intervention group exercised for > 3 hours/week, and patients with regression of coronary artery disease even dedicated 5 to 6 hours to leisure time physical activity per week, these findings question whether an exercise program within the safety tolerance of patients will be able to induce coronary collateralization in the presence of regression of coronary artery disease.

Identification of patients at risk during swimming by Holter monitoring.

Cardiac arrest during swimming accounts for a considerable number of deaths during physical exercise in patients with coronary artery disease. A link between ST-segment depression and cardiac arrest has been observed in previous studies. In this study, exercise-induced myocardial ischemia was assessed in 23 patients with coronary artery disease by bipolar Holter monitoring during swimming, jogging, and treadmill testing. During treadmill testing, Holter monitoring and standard electrocardiograms were simultaneously recorded. Detection of ST-segment depression during swimming was standardized in a group of normal volunteers (n = 7). All patients with silent myocardial ischemia (n = 8) documented by thallium-201 scintigraphy had ST-segment depression during treadmill testing and swimming when recorded by Holter monitoring, whereas the standard electrocardiogram during treadmill testing was negative in 5 patients. Heart rate at 1 mm ST-segment depression was significantly lower during swimming (110 +/- 11 beats/min) than during treadmill testing (documented by standard electrocardiogram) (133 +/- 23 beats/min, p < 0.002) and jogging (125 +/- 21 beats/min, p < 0.03). However, there was no significant difference in heart rate at onset of angina pectoris in symptomatic patients, suggesting a delayed sensation of ischemic symptoms during swimming. The only clinical event in our group during 8 years of swimming occurred during this study. One patient with silent myocardial ischemia developed ST-segment depression during swimming that degenerated into ventricular fibrillation, requiring resuscitation. Therefore, Holter monitoring can be considered a valuable addition in identifying patients with silent myocardial ischemia during swimming, and thus identifying patients at risk for exertion-related life-threatening ventricular tachyarrhythmias.

Silent myocardial ischemia as a potential link between lack of premonitoring symptoms and increased risk of cardiac arrest during physical stress.

The risk of cardiac arrest is increased during strenuous physical exercise in patients with stable coronary artery disease (CAD). Because premonitoring symptoms are rarely observed, silent myocardial ischemia may represent the pathophysiological basis for the induction of malignant ventricular arrhythmias. Holter monitoring was, therefore, performed in 40 consecutive patients entering a randomized intervention trial on progression of CAD. In 20 of 21 participants (95%) in the intervention program greater than or equal to 1 episode of silent myocardial ischemia was observed during the initial training session. The mean duration of silent myocardial ischemia per patient was 25 +/- 13 min/hr of training session. During normal daily activity only 5 patients (24%) experienced greater than or equal to 1 episode of silent myocardial ischemia (p less than 0.001) yielding a mean duration of 0.6 +/- 1.3 minutes of silent myocardial ischemia/hr of ordinary activity per patient (p less than 0.001 vs training session). During a control period of 24 hours without exercise training the incidence (33%) and mean duration of silent myocardial ischemia (0.8 +/- 2.1 min/hr/patient) were similar to those during normal daily activity on the day of the training session. During the training session the occurrence of frequent or repetitive ventricular arrhythmias was related to 10 silent myocardial ischemia episodes detected in 5 patients. During normal daily activity in 1 patient only was the onset of malignant ventricular arrhythmias associated with silent myocardial ischemia (p less than 0.05). Conditions and results of the Holter studies in the control group patients were comparable to those of the patients in the intervention group on the day without physical exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Predictive value of lipid profile for salutary coronary angiographic changes in patients on a low-fat diet and physical exercise program.

In this study, 113 patients with modestly elevated levels of low-density lipoprotein cholesterol (<210 mg/dl) and coronary artery disease were randomized to an intervention group (n=56) or a control group (n=57). The intervention program consisted of daily exercise and a low-fat diet according to the American Heart Association's recommendation phase III; patients in the control group received "usual care" rendered by their private physician. After 1 year, complete data were available for all 92 patients (intervention: n=40; control: n=52) who underwent repeat coronary angiography. During the study course, patients in the intervention group showed an increase in apolipoprotein A-I(123 +/- 18 vs 129 +/- 20 mg/dl; p < 0.02) and apolipoprotein A-I/B (1.3 +/- 0.4 vs 1.5 +/- 0.4; p <0.01) and a decrease in apolipoprotein B (99 +/- 20 vs 89 +/- 18 mg/dl; p < 0.01), while apolipoprotein A-II remained unchanged (38 +/- 6 vs 38 +/- 6 mg/dl; p=NS). In the control group, there were no significant changes (apolipoprotein A-I, 124 +/- 17 vs 128 +/- 13 mg/dl; apolipoprotein A-II, 38 +/- 6 vs 39 +/- 6 mg/dl; apolipoprotein B, 100 +/- 21 vs 99 +/- 16 mg/dl; apolipoprotein A-I/B, 1.3 +/- 0.3 vs 1.4 +/- 0.5; all p=NS). As previously reported, there was a significant retardation of progression in patients in the intervention group (progression 23%, no change 45%, regression 32%) compared with the control group (progression 48%, no change 35%, regression 17%) (p < 0.05). Although retardation of progression was significantly associated with an increase in apolipoprotein A-I/B and a decrease in apolipoprotein B (p < 0.05), these gave way in multivariate analysis to changes in total cholesterol/high-density lipoprotein cholesterol, absolute levels of low-density lipoprotein cholesterol, and, in a subgroup of patients, to leisure-time physical activity (all p < 0.05). These data demonstrate that an intervention based on a low-fat diet and intensive physical exercise is capable of improving apolipoprotein levels, associated with retardation of progression of coronary artery disease. However, total cholesterol/high-density lipoprotein cholesterol and low-density lipoprotein cholesterol appear superior to apolipoproteins as metabolic markers for effective treatment in patients with coronary artery disease.

Measurement of drug compliance by continuous electronic monitoring: a pilot study in elderly patients discharged from hospital.

OBJECTIVE: A pilot study to assess patient compliance with medication by using a new measurement technique, continuous electronic monitoring. DESIGN: Survey. Compliance monitors were provided to eligible patients at discharge from the hospital to measure drug intake behavior prospectively for a period of 3 weeks. SETTING: Ambulant patient care after discharge from a geriatric hospital, Krankenhaus Bethanien, which is affiliated with the University Clinic, Heidelberg. PATIENTS: A consecutive convenience sample of 18 independently living elderly patients (median age 76 years) completed the study. The patients were on maintenance therapy with cardiac glycosides and/or potassium-sparing diuretics prescribed to be taken once daily. INTERVENTION: The monitoring method provides information about patients' real timing of drug use by continuously recording date and time of openings and closings of the medication containers (monitors). In addition to a standard measure, the percentage of prescribed doses taken, information about regularity of drug use is obtained. RESULTS: Compliance, percentage of prescribed doses taken, was remarkably variable; it ranged from 24% to 100%, 95% CI: 62%-84%. Mean compliance declined from the first to the third week after discharge, 85% vs 69%, 95% CI: 74%-95% and 56%-81%, respectively (P < 0.05). Omissions of doses, the predominant pattern of non-compliance, were observed in 17 of 18 patients. Regularity of dose timing, as defined by the number of interdose intervals within 24 h +/- 15%, varied from 10% to 100%, 95% CI: 46%-76%. CONCLUSIONS: Continuous electronic monitoring revealed highly variable compliance in patients prescribed maintenance therapy. Even with a once-daily regimen, persistent and high compliance cannot be assumed. The monitoring technique may be of great value to research and, possibly, to practical therapeutic management.