CLINICAL INVESTIGATION The effects of changes in physical activity on major cardiovascular risk factors, hemodynamics, sympathetic function, and glucose utilization in man: a controlled study of four levels of activity

The effects of four levels of activity on heart rate, blood pressure, cardiac index, total peripheral resistance index (TPRI), norepinephrine (NE) spillover rate, insulin sensitivity, and levels of lipids and some hormones were studied in 12 normal subjects. The randomized periods were (1) 4 weeks of below-sedentary activity, (2) 4 weeks of sedentary activity, (3) 4 weeks of 40 min of bicycling three times per week, and (4) 4 weeks of similar bicycling seven times per week. Exercise three times per week reduced resting blood pressure by 10/7 mm Hg (p < .01) and it was reduced by 12/7 mm Hg after exercise seven times per week (both p < .01). This was associated with reduction in TPRI, an increase in cardiac index, and cardiac slowing. At the highest level of activity, NE spillover rate, an index of sympathetic activity, fell to 35% of the sedentary value (p < .001) in eight of 10 subjects. In two other subjects NE spillover rate rose, although blood pressure and TPRI were reduced. Metabolic changes included lowering of total cholesterol, but high-densitv lipoprotein level was unchanged. Insulin sensitivity rose by 27% after exercise three times per week, icut --ec" Ted to sedentary levels with seven times per week exercise. Maximum oxygen uptake inceasec i crly with activity. Exercise performed three times per week lowers blood pressure and should reduce ardiovascular risk. The same exercise seven times per week enhances physical performance with little further reduction in cardiovascular risk factors. Exercise is potentially a major nonpharmacologic method of lowering blood pressure. Circulation 73, No. 1, 30-40, 1986. REGULAR PHYSICAL EXERCISE is generally recommended for the prevention of cardiovascular disease, largely on the basis of epidemiologic studies.`l The benefits of exercise may be due to reduction in some of the risk factors or through other effects.'-' There has been a diversity of views about the extent of the benefit, the physiologic basis for such an action, and the amount of exercise that is required. Some studies have suggested that a prolonged and intense effort is required,2 while from others it would appear that adequate benefit is conferred by a few minutes of leisure-time activity.3 Many physiologic studies that have examined the effects of exercise on blood pressure and lipid levels From the Clinical Research Unit, Alfred Hospital and Baker Medical Research Institute, Prahran, Victoria, Australia. Supported by the Institute Grant to the Baker Medical Research Institute from the NH and MRC of Australia. Address for correspondence: Dr. G. L. Jennings, Clinical Research Unit, Alfred Hospital and Baker Medical Research Institute, Commercial Rd., Prahran, Victoria, 3181. Australia. Received July 2, 1985; revision accepted Sept. 12, 1985. 30 have used longitudinal experimental designs, which tend to confound the effects of exercise with those due to associated changes in body weight, sodium intake, and familiarity with the measurement procedures. '-10 It has been hard to draw firm conclusions about which of these are most important in reducing conventional risk factors. An additional problem is the short-term effect of exercise, which may make it hard to interpret the mechanisms underlying blood pressure falls during longitudinal studies. The purpose of the present investigation was to examine in the same normal sedentary subjects the effects of four different levels of activity on a number of circulatory, metabolic, and hormonal variables in a manner that would avoid some of the confounding effects, that were present in previous studies. The four levels of activity chosen were (1) below-normal sedentary activity, (2) normal sedentary activity, (3) bicycling for 40 min 3 times per week, and (4) similar bicycling seven times per week. Each level of regular CIRCULATION by gest on A ril 4, 2017 http://ciajournals.org/ D ow nladed from PATHOPHYSIOLOGY AND NATURAL HISTORY-EXERCISE activity was maintained for 4 weeks and the order of treatments in the different subjects was randomized according to a Latin-square experimental design to eliminate bias in the order of administration. We paid close attention to the maintenance of constant body weight and salt intake at the different levels of activity. We assessed the effects of exercise from measurements of circulatory, metabolic, autonomic, and hormonal variables 48 hr after completing a particular 4 week activity period to avoid the confounding effects of a short-term bout of exercise on the results. We also examined how the latter affected the performance during short-term, graded steady-state exercise. Methods Twelve normal subjects participated in the study, which was performed with the approval of the Alfred Hospital Clinical Ethics Committee. The subjects had sedentary occupations and none had participated in regular vigorous leisure time activity in the previous year. Eleven were men and the average age was 22 years (range 19 to 27 years). The protocol involved four consecutive 1 month periods at each of the four levels of activity referred to in the introduction: (1) below-sedentary activity (during the second half of the period of reduced activity the subjects were admitted to hospital for 2 weeks rest), (2) normal sedentary activity, (3) normal activity plus three standard exercise periods weekly, and (4) normal activity plus daily standard exercise periods. The order of these periods was randomized and the allocation followed a 4 X 4 Latin square for each set of four subjects. The standard exercise periods were strictly supervised and consisted of 40 min exercise on an electrically braked bicycle ergometer. A five min warm-up was followed by 30 min at a workload of 60% to 70% of the previously determined maximum work capacity (Wmax) and a 5 min cool down. Heart rate was monitored from the electrocardiogram and the workload was adjusted to maintain heart rate during exercise within the range of 120 to 150 beats/min. The subjects took no medications and kept factors other than physical activity as constant as possible during the study. Weight was measured weekly and 24 hr urinary sodium excretion was measured monthly. Dietary advice was available to assist subjects in maintaining stable weight and sodium intake. Food intake was assessed from 3 day food diaries compiled during each period. During the studies, however, little intervention was necessary. At the end of each month (48 hr after the end of each 4 week period) a series of measurements was obtained by staff members who were unaware of the previous month's activity level (figure 1). During the period of reduced activity when the subjects were in the hospital they remained within the vicinity of their beds, but were actually in bed only during normal sleeping periods. On the study days the subjects attended the laboratory at 8 A.M. after fasting overnight. On day 2 after completing each study period, a 22-gauge butterfly cannula was inserted into a forearm vein of each subject and blood was taken immediately for ambulant measurement of plasma renin activity (PRA), serum electrolytes, blood lipids, hemoglobin, packed cell volume (PCV), and white cell count. The subjects then rested supine and a further sample for determination of PRA was collected 90 min later. An infusion of a tracer dose of tritiated norepinephrine (NE) was commenced in the opposite arm for measurement of spillover and clearance rate at steady-state 90 min later (see below). This was followed by infusions of glucose and insulin for measurement of insulin sensitivity by the glucose-clamp method (see below). In months involving three or seven times per week exercise, a normal bout of exercise was performed after all testing on day 2. Normal sedentary activity was carried out on day 3 after all study periods. Hemodynamic measurements and exercise tests were obtained on the following day (day 4) and again 48 hr after the last bout of exercise. On arrival in the laboratory, the subjects rested for 20 min and then supine measurements of heart rate, blood pressure, cardiac output, and oxygen consumption were made. Hormone measurements at this time included those of prolactin, cortisol, thyroid, and growth hormones. This was followed by a sprint exercise test to determine Wmax. The subjects rested for 1 hr and then a steadystate exercise test was performed. Heart rate, blood pressure, cardiac output, and oxygen consumption were measured at rest and at the end of each 4 min level of exercise during the steadystate protocol. Cardiovascular measurements. Before entry into the study,