John T. Santinga

Effect of exercise training on glucose tolerance, in vivo insulin sensitivity, lipid and liproprotein concentrations in middle-aged men with mild hypertriglyceridemia

The effects of 9 weeks of aerobic exercise training with maintenance of stable body weight upon insulin sensitivity and upon glucose, lipid, and lipoprotein concentrations were studied in 10 middle-aged men with mild hypertriglyceridemia. Following training, mean maximum oxygen consumption improved from 33.5 +/- 1.9 to 39.3 +/- 1.9 mL/kg/min (means +/- SEM), (P less than 0.01). Glucose concentrations, both fasting and during oral glucose tolerance testing, remained stable but both fasting insulin concentrations and insulin responses to oral glucose decreased (P less than 0.1 and less than 0.01, respectively). In vivo insulin sensitivity improved 25 +/- 6.1% (P less than 0.01) following training. Exercise training resulted in decreases in fasting serum triglyceride concentrations from 203 +/- 12.6 to 126 +/- 9.0 mg/dL (P less than 0.01), primarily as a result of the reduction in VLDL-triglycerides (P less than 0.01). The magnitude in percentage decrease of VLDL-triglycerides was found to be significantly correlated (r = 0.71, P less than 0.05) with the magnitude in percent increase in max VO2. Serum cholesterol levels declined from 211 +/- 8.9 to 193 +/- 11.9 mg/dL (P less than 0.01), and the ratio of HDL-cholesterol to total cholesterol was improved. This study demonstrates that exercise training at a level of intensity feasible for many middle-aged men has beneficial effects on several factors that have been associated with an increased risk of cardiovascular disease.

Self-Management of Heart Disease by Older Adults Assessment of an Intervention Based on Social Cognitive Theory

A randomized, controlled trial involving 636 older individuals was conducted to evaluate an intervention to enhance self-management of heart disease. Program participants experienced less impact of illness on their psychosocial functioning (p <.05), especially their emotional behavior (p < .05) and alertness (p < .01). Compared to controls, male program participants experienced improvements in their physical functioning, specifically their ability to ambulate (p < .05) and the frequency and severity of their symptoms. Female program participants did not experience gains in physical functioning. Most group differences emerged by 12 months and decayed by the 18-month final evaluation. To accurately assess the pattern of change associated with a program of this type, evaluation over at least 18 months following program completion may be needed. Separate interventions for older men and women with heart disease appear warranted, as do follow-up activities at strategic points in time to sustain program effects.

The influence of physical training on glucose tolerance, insulin sensitivity, and lipid and lipoprotein concentrations in middle-aged hypertriglyceridaemic, carbohydrate intolerant men

SummaryThe effects of 9 weeks of moderate intensity exercise training while on a weight-maintaining diet were studied in 19 untrained middle-aged, hypertriglyceridaemic, carbohydrate intolerant men. Initial mean maximum oxygen consumption was low (29.7±1.0 ml-min−1 · kg−1; mean±SEM) and improved (34.2±1.4ml·min−1·kg−1, p<0.01) with exercise training. Fasting glucose, insulin, lipid and lipoprotein concentrations did not change. While the abnormal glucose response to oral glucose did not change with training, insulin concentrations were significantly (p<0.05) lower at 90 and 120 min during the final oral glucose tolerance test. Insulin mediated glucose uptake did not change, indicating that the degree of exercise training failed to improve in vivo insulin sensitivity. Significant associations were found between the following parameters measured: fasting concentrations of triglycerides and insulin, very low density lipoprotein-triglycerides and glucose, and measures of in vivo insulin resistance and fasting insulin levels, suggesting that insulin resistance in these glucose intolerant subjects may play a role in their hypertriglyceridaemia. These data indicate that moderate increases in physical training alone are not sufficient to improve the carbohydrate, insulin and lipid metabolism of hypertriglyceridaemic, glucose intolerant men.

Efficacy and Safety of Pravastatin in the Long-term Treatment of Elderly Patients With Hypercholesterolemia

PURPOSE Elevated cholesterol levels are a major risk factor for coronary heart disease, which remains a significant problem in patients beyond age 65 years. Because drug therapy for the control of hypercholesterolemia in elderly patients is frequently considered to be indicated, we investigated the efficacy and safety of pravastatin in the treatment of elderly subjects with primary hypercholesterolemia. PATIENTS AND METHODS In this 96-week, multicenter, double-blind, placebo-controlled study, 142 subjects (95 women, 47 men) 64 to 90 years of age with elevated cholesterol levels despite dietary intervention were randomized to receive pravastatin 20 mg at bedtime or matching placebo (2:1). Dosage could be doubled after 8 weeks, a bile acid-binding resin could be added after 16 weeks, and nicotinic acid or probucol could be added after 32 weeks, as needed, to adequately lower the low-density lipoprotein cholesterol (LDL-C) levels. RESULTS Significant reductions in the levels of LDL-C (-30.9%), total cholesterol (Total-C; -21.9%), and triglycerides (TG; -16.7%) and significant increases in the levels of high-density lipoprotein cholesterol (HDL-C; 11.3%) were noted in the group receiving pravastatin treatment at 16 weeks (P < or = 0.001 compared with baseline, P < or = 0.01 compared with placebo). The cholesterol-lowering effects of pravastatin were sustained throughout the 96 weeks of the trial. Pravastatin was well tolerated, with an overall incidence of adverse events nearly identical to that of placebo. CONCLUSIONS In this study, pravastatin was well tolerated and effective in lowering LDL-C, Total-C, and TG and in raising HDL-C during long-term treatment of elderly patients with primary hypercholesterolemia.

Comparative effects of physical training and diet in normalizing serum lipids in men with Type IV hyperlipoproteinemia.

The effect mild physical training (PT) (group A), Type IV hyperlipoproteinemia (HLP) diet (group B), and PT plus Type IV HLP diet on serum lipids (group C) in 46 men with Type IV HLP was studied. Significant reductions in mean triglyceride (TG) levels from 163, 229, 196, to 136, 145, 116 mg/100 ml serum were found for groups A, B, and C, respectively. Following six weeks of intervention, cholesterol levels also dropped for all groups with the losses were found for all groups while groups A and C displayed significant reductions in body fatness, but both of these changes appeared independent of lipid reductions. It was concluded that either mild PT or HLP diet or both are effective means of lowering TG levels in Type IV HLP individuals. Furthermore, it appears that patients need to participate regularly in formal programs in order to maintain adherence to these interventions.

An Automated System for ST Segment and Arrhythmia Analysis in Exercise Radionuclide Ventriculography

A computer-based system for interpretation of the electrocardiogram (ECG) in the diagnosis of arrhythmia and ST segment abnormality in an exercise system is presented. The system was designed for inclusion in a gamma camera so that ECG diagnosis could be combined with the diagnostic capability of radionuclide ventriculography. Digitized data are analyzed in a beat-by-beat mode and a contextual diagnosis of underlying rhythm is provided. Each beat is assigned a beat code based on a combination of waveform analysis and RR interval measurement. The waveform analysis employs a new correlation coefficient formula which corrects for baseline wander. Selective signal averaging, in which only normal beats are included, is done for an improved signal-to-noise ratio prior to ST segment analysis. Template generation, R wave detection, QRS window size, baseline correction, and continuous updating of heart rate have all been automated. ST level and slope measurements are computed on signal-averaged data. Arrhythmia analysis of 13 passages of abnormal rhythm by computer was found to be correct in 98.4 percent of all beats. 25 passages of exercise data, 1-5 min in length, were evaluated by the cardiologist and found to be in agreement in 95.8 percent in measurements of ST level and 91.7 percent in measurements of ST slope.

Factors Relating to Late Sudden Death in Patients Having Aortic Valve Replacement

The preoperative and postoperative characteristics of a group of 16 patients who died unexpectedly and a control group of 52 late survivors with aortic protheses are reviewed. There were no preoperative differences between the groups for duration of congestive heart failure, electrocardiographic findings, cardiothoracic ratio, or hemodynamic findings. However, on the standard electrocardiogram postoperatively, there were more ventricular arrhythmias in the patients who died suddenly (7 of 16 or 44%) compared with the survivors (5 of 49 or 10%) (p less than 0.05). There were more patients with congestive failure in the study group (10 of 16 or 62%) compared with the controls (4 of 52 or 8%) (p less than 0.05). Patients exhibiting these findings are at risk of sudden death. Arrhythmia monitoring prior to discharge may also be helpful in selecting patients for antiarrhythmia treatment.

Left Ventricular Function in Patients with Ventricular Arrhythmias and Aortic Valve Disease

Forty patients having aortic valve replacement were evaluated preoperatively for ventricular arrhythmia and left ventricular ejection fraction. Arrhythmias were classified as complex or simple using the Lown criteria on the 24-hour ambulatory electrocardiogram; ejection fractions were determined by radionuclide gated blood pool analysis and contrast angiography. The ejection fractions determined by radionuclide angiography were 59.1 +/- 13.1% for 26 patients with simple or no ventricular arrhythmias, and 43.9 +/- 20.3% for 14 patients with complex ventricular arrhythmias (p less than 0.01). Ejection fractions determined by angiography, available for 31 patients, were also lower in patients with complex ventricular arrhythmias (61.1 +/- 16.3% versus 51.4 +/- 13.4%; p less than 0.05). Seven of 9 patients showing conduction abnormalities on the electrocardiogram had complex ventricular arrhythmias. Eight of 20 patients with aortic stenosis had complex ventricular arrhythmias, while 2 of 13 patients with aortic insufficiency had such arrhythmias. It is concluded that decreased left ventricular ejection fraction, intraventricular conduction abnormalities, and aortic stenosis are associated with an increased frequency of complex ventricular arrhythmias in patients with aortic valve disease.

Prognostic significance of exercise-induced left ventricular dysfunction in chronic aortic regurgitation

Twenty-three patients with hemodynamically significant aortic regurgitation (AR) underwent gated equilibrium radionuclide angiography to assess rest and exercise left ventricular ejection fraction (LVEF) before and after aortic valve replacement. Preoperatively, LVEF decreased from 54 +/- 3% at rest to 45 +/- 3% during exercise (p less than 0.001). Two patients died at operation. Postoperatively, after 5.7 +/- 1.6 months, LVEF was 62 +/- 5% at rest and 60 +/- 4% during exercise (difference not significant). Exercise LVEF improved significantly postoperatively (p less than 0.01). The patients were followed for a mean of 30 months (range 1 to 56), after valve replacement and during this period, 13 patients were in functional class I, 5 patients were in class II and 2 patients were in class III. One late death occurred and was unrelated to myocardial failure. Thus, in most patients with AR, exercise LVEF improves after aortic valve replacement. A preoperative decrease in LVEF during exercise in patients with significant AR does not predict a poor postoperative outcome.

Effectiveness of unsupervised and supervised high intensity physical training in normalizing serum lipids in men with type iv hyperlipoproteinemia.

The effect of high intensity physical training (HIPT), conducted in an unsupervised (group A) or supervised (group B) setting, was studied in 23 middle-aged men with Type IV hyperlipoproteinemia (HLP). Following 10 weeks of HIPT intervention, significant metabolic changes were observed such as reductions in both fasting triglyceride and insulin levels, but no changes in fasting serum cholesterol or glucagon levels were found. Other favorable results noted included a significant improvement in physical fitness, as measured by increases in aerobic power, and a decrease in body fatness with only minimal weight losses. There were no significant differences in the results when groups A and B were compared. It was concluded that HIPT is an effective means of lowering fasting triglyceride and insulin levels in Type IV HLP individuals. In addition, such physical training programs can be conducted in either an unsupervised or supervised setting, provided the subjects are highly motivated.