Effect of Aerobic Exercise Training on Patients with

Systemic Arterial Hypertension

ROBERT CADE , M.D. DONALD MARS, M.D.

HERBERT WAGEMAKER, M.D

CHRISTIAN ZAUNER, Ph.D

DAVID PACKER

MALCOLM PRIVETTE, P.A.

MICHAEL CADE JOHN PETERSON, M.D.

DENNIS HOOD-LEWIS, M.D.

Gainesville, Florida

From the Department of Medicine and the Center for Physical and Motor Fitness, University of Florida, Gainesville, Florida. Requests for reprints should be addressed to h. Robert Cade, Professor of Medicine, Box J-224, JHMHC, University of Florida, Gainesville, Florida 32610. Manuscript accepted May 2.1964.

A continuing medical education quiz on this article (one hour of Category 1 credit) appears on page Al 19 of this issue.

One hundred five patients with established diastolic hypertension were enrolled in an exercise program to examine the effect of aer- obic conditioning on blood pressure. In four patients, the decrease in mean blood pressure was less than 5 mm Hg; in all others, there was a significant decline in arterial blood pressure. In 58 patients who were not taking drug medication in the pre-exercise period, mean blood pressure decreased by 15 mm Hg. Of 47 patients re- ceiving drug therapy during the pre-exercise period, 24 were able to discontinue all medication. Mean blood pressure in this group fell from 116.9 f 6.5 mm Hg to 97.2 f 9.2 mm Hg as a result of exercise. In patients still taking antihypertensive drugs, mean pressure de- creased from 120.9 f 28.8 mm Hg to 104.4 f 17.9 mm Hg after three months of exercise. It is concluded that in patients physically and emotionally able to exercise, a significant decline in blood pressure can be achieved.

Hypertension is a major risk factor for development of cardiovascular [l-3], cerebrovascular [l-3], and renovascular [4,5] disease. Al- though blood pressure can usually be lowered by administration of appropriate antihypertensive medication, many patients experience side effects that range from unpleasant symptoms such as headache [ 61, dry mouth [ 71, or lassitude and lethargy [ 81, to incapacitating or potentially lethal complications such as severe depression [9], pan- creatitis [lo], or arrhythmias complicating a myocardial infarction [ 11,121. impotence or decreased libido [ 131, although not in a strict sense incapacitating, is common and cause for bitter and justifiable complaints by many patients. In addition, the financial stress imposed by drug management of even mild hypertension is a cause for concern on the part of both physicians and patients.

For all of the aforementioned reasons, the investigation of non- pharmacologic management of hypertension seemed of interest to us. This report deals with the effects of vigorous aerobic exercise, running two miles per day, on a group of hypertensive patients. Al- though the study was designed to examine the effect of exercise on blood pressure, the data also allow comments on the effect of weight loss in hypertensive patients.

SUBJECTS AND METHODS

Hypertensive subjects (diastolic blood pressure consistently greater than 90 mm Hg) from the outpatient clinic were accepted into the study if it was thought they were physically capable of performing the prescribed exercise program. Roughly half (47) of the patients had well-established diastolic hy- pertension and were receiving various drug regimens. Over 80 percent of these patients had either symptoms or laboratory findings of concern to the

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140- i

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Ffgure 1. Effect of training on blood pressure in 58 hyper- tensive patients who were receiving no ant/hypertensive therapy when enrolled in the study. V = systolic; A = dia- stolic.

patients and their families, which made them amenable to a trial of nondrug therapy. The remaining 58 hypertensive patients were not receiving drug therapy when accepted into the study.

The diastolic blood pressure in all patients was consistently elevated above 90 mm Hg during a two- to three-month period that included at least six observations. Blood pressure was measured during a regularly scheduled afternoon clinic visit between four and 22 hours after exercise. All pressures were measured with patients in a supine position after at least 20 minutes’ rest. Pressure was measured indirectly using a mercury column manometer; the fifth Korotkoff sound was used as an approximation of the diastolic pressure. Mean blood pressure was calculated using one third the pulse pressure plus the diastolic pressure. An exercise-induced decrease of 5 mm Hg or greater in calculated mean blood pressure was considered a positive response. Weight was measured on a beam-balance scale with the patient dressed in street clothing. Percentage of body fat was estimated by skin fold thickness with measurements over the triceps, bi- ceps, subscapular area, and iliac crest, using the tables prepared by Durnin and Warmersly [ 141.

Fifty-eight patients had untreated hypertension (Figure 1). The average age of this group of patients was 39 f 11.4 years; the youngest was 22, the oldest 66 years. Eight were women. Four patients, all men, had de- creases of less than 5 mm Hg in their calculated mean blood pressure. The decreases in systolic (-17.4 mm Hg), diastolic (-14.7 mm Hg), and calculated mean blood pressure (-15.1 mm Hg) were all statistically significant (p CO.05).

No attempt was made to alter diet, although several pa- tients reduced caloric intake on their own volition. Likewise, no attempt was made to restrict dietary sodium; intake of sodium was, however, estimated in most patients by mea- surement of 24-hour urine sodium and creatinine excretion. As an appreciable and unknown amount of sodium was lost in sweat, excretion of urinary sodium was not interpret- able.

The blood pressure response in patients who were receiving medication at the beginning of the study is shown in Figure 2, left, for those who were still taking

medication after three months of exericse, and in Flgure 2, right, for patients who were able to discontinue all medication and maintain a satisfactory blood pressure with exercise alone. Of 23 patients taking medication after three months of exercise, only one did not have a decrease of more than 5.0 mm Hg in mean blood pressure; the other patients had a striking decrease in both systolic (-28 mm Hg) and diastolic (-21 mm Hg) as well as calculated mean pressure (16.6 mm Hg). The

mean age of this group was 44 years. The mean age among 24 patients (15 men, nine women) who were able to discontinue medication was 42. Mean systolic pressure in this group fell 22 mm Hg, diastolic fell 18 mm Hg, while calculated mean pressure declined by 18 mm Hg. Again, all changes were statistically significant (p <0.05).

Exercise was initiated by having patients walk one mile Of the 105 patients who completed the study, seven each day for one week. Daily exercise was fhen increased had a diastolic pressure of 115 mm Hg or greater, and

to two miles per day, and this was maintained until patients could comfortably walk the two-mile distance in 40 minutes. Exercise was then intensified to a one-mile walk followed immediately by a one-mile run. Again, when patients were comfortable on that program, the exercise was intensified to two miles of running each day. Young patients were fre- quently able to run two miles each day within three weeks of beginning training, whereas older patients took much longer. On the extreme, two women, one 60 and the other 66 years of age, were not able to run two miles until they had trained for seven and a half and six months, respectively.

Assessment of the patients’ condition was made at two- week intervals, with adjustments in drug intake and intensity of exercise made when appropriate. Evaluation of the effect of exercise on blood pressure was made three months after patients were first able to run two miles per day. These measurements were also made during an outpatient clinic visit under conditions similar to those previously described. Of 135 patients who began the study, 105 reached and maintained the activity level of two miles of running per day for three months or longer. Of the 30 patients who dropped out of the study, 18 did so because of muscle or joint pain caused by running. The other 12 gave no specific reason, but believed drug therapy was better suited to their needs and life-style.

RESULTS

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Figure 2. Left, change in blood pressure due to exercise in 23 patients who were taking antihypertensive medication at the inception of exercise and were still taking medication after three months of training. V = systolic; A = diastolic. Rfght, change in blood pressure due to exercise in 24 patients taking antihypertensive medications at the inception of exercise who were able to discontinue all pharmacologic agents. V = systolic; A = diastolic.

16 had a diastolic pressure that averaged between 105 Fifteen patients who had experienced a significant and 114 mm Hg during the pm-exercise period. The data drop in blood pressure after three months of exercise for the seven patients with severe hypertension are were induced to return to a sedentary life-style for a shown in Table I. lt is apparent that even in patients with period of three to four months. The data from this group severe hypertension, exercise can produce a fall in of patients are shown in Figure 4. During the three- blood pressure. One patient in this group, a 34-yearold month sedentary period, two patients had an additional woman (Patient 4) required no medication to remain slight fall in blood pressure, three had no change, and normotensive, whereas a young man with chronic 10 had a significant increase. Changes from control to glomerulonephritis (Patient 2) required only diuretic exercise and exercise to sedentary were statistically therapy. significant (p <0.05).

Data for patients with moderate hypertension are Five patients had a decrease of less than 5 mm Hg shown in Figure 3. Systolic blood pressure fell from 163 in their mean blood pressure after three months of ex- f 9.9 mm Hg to 130.8 f 14.1 mm Hg, and diastolic ercise. One had chronic membranoproliferative glo- from 108 f 1.9 mm Hg to 84.1 f 9.7 mm Hg. The mean merulonephritis with a glomerular filtration rate of 78 blood pressure fell from 126.9 f 4 mm Hg to 98.1 f ml/per minute. The others had arteriolar nephroscler- 10.9 mm Hg. All values were statistically significant (p osis with a reduced glomerular filtration rate due to <0.05). long-standing idiopathic hypertension. One of these, a

TABLE I Patients with Severe Hypertension

Paiknt Age and Sex Diagnosis Control Blood Prsssure (mm Hg)

Mean Exrrclw Mean A

1 39F Renal artery stenosis 180/118 139 155IlOO 118 -21 2 33M Chronic glomerulonephritis 1701115 133 llOl70 83 -50 3 30M Periarteritis 2001130 153 18Ol128 145 -8 4 34F Idiopathic hypertension 180/120 133 110174 86 -47 5 24M Idiopathic hypertension 160/l 15 130 140195 110 -20 6 28M Idiopathic hypertension 1661116 133 135190 105 -28 7 57M Renal artery stenosis 168/l 16 133 16OIllO 127 -7

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Figure 3. Change in blood pressure due to exercise in 76

patients with moderately severe hypertension. V = systolic; A = diastolic.

5%year-old man, had a further decline in blood pressure with continued exercise. After six months, his blood pressure was 15 l/94 mm Hg, whereas control values were 160/l 10 mm Hg and readings at three months were 158/104 mm Hg.

In none of the patients who began the study receiving drug therapy was the dose of medication increased, and no new medications were added during the study. of the 23 patients still taking medication after three months of exercise, four were receiving diuretics alone and 14 had decreased or discontinued one major antihyper- tensive drug.

Although the study was not designed to examine the effect of weight loss on blood pressure, weight was measured routinely with each clinic visit. No weight change occurred in 10 percent of the patients; 30 percent gained weight and 60 percent lost weight. Among those patients who lost weight, the range was between 0.25 and 17 pounds with a mean weight loss of 6.3 f 5.6 pounds. Among those who gained weight, the range was from one to 12 pounds with a mean of 5.2 f 4.3 pounds. For the group as a whole, there was an average weight loss of 1.9 pounds. Change in body weight expressed as percentage increase or decrease is shown in Figure 5. The proportion of body weight that was fat, estimated by skin fold thickness for the group as a whole, decreased from 29.3 to 27.7 percent. The decrease in blood pressure with exercise was as great in those patients who gained weight as in those whose weight decreased.

COMMENTS

Our results strongly suggest that hypertension, even severe and of long duration, can be controlled or ame- liorated by aerobic exercise of moderate intensity. Among young hypertensive patients whose disease is of short duration, better than 70 percent can achieve good control of blood pressure with exercise alone, and the dose of major antihypertensive drugs can be de- creased in an additional significant proportion while achieving better control of blood pressure than was possible with medication alone.

Several authors have reported good reduction of blood pressure with dietary weight reduction with [ 151 or without [ 161 restriction of sodium. These studies do not mention exercise as part of the weight reduction program. As most patients attempting to lose weight, however, increase physical activity to abet weight loss, with or without a physician’s recommendation, it seems safe to assume that exercise was at least a part of the regimen for many patients in these studies.

Boyer and Kasch [ 171 have reported a marked de- crease in blood pressure with exercise training. They did not discuss any changes in weight as a result of the program. Blackburn [ 181 stated that exercise for re- duction of blood pressure is useful only as an adjunct to weight loss. On the other hand, Choquette and Fer- guson [ 191 and Krotkiewski et al [20] both reported an exercise-induced reduction of blood pressure inde- pendent of weight change. Our results demonstrate clearly that reduction of blood pressure by an exercise program does not require weight loss, but is as effective in patients who gain weight as in those who lose a sig- nificant amount of body fat.

Blood pressure reduction with exercise in our patients occurred without regard to the severity of the initial el-

CONTROL 3 tax EXC 3 MOS SEDENTARY

Figure 4. Effect of exercise and a return to a sedentary life-style on blood pressure in 15 patients. V = systolic; A = diastolic.

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evation. This is of interest whether exercise is viewed as an adjunct to a drug program or as primary therapy for patients with mild to moderate elevated blood pressure. Indeed, in patients with mild hypertension for whom the risk of drug therapy may approach the ex- pected benefit derived from lowering blood pressure [21], a prescription of exercise may be the ideal therapy.

Evaluating the reduced necessity for pharmacologic agents in quantitative terms proved an exceedingly difficult task, as the spectrum of agents employed was extremely broad and the dosage range was also quite varied. Because we could not calculate an average dose of medication for each patient, we calculated the av- erage cost per patient per day of treatment before and again after three months of exercise. As our study began more than 10 years ago, we have used current drug prices to compare pre- and post-running ex- penses.

For 24 patients undergoing pharmacologic man- agement before exercise who were able to discontinue all medication after physical training, the average daily cost was $3.36; the range was from $0.098 for patients taking only hydrochlorothiazide to $8.46 for a patient with severe hypertension. As these patients were able to discontinue all pharmacologic agents, their treatment cost fell to the cost of one pair of running shoes per year.

If the cost for 23 patients who were still receiving

Percentage of Patients 5

Losing weight n 8 Percentage of Patients

2 Gaining weight

F&urn 5. Wei@t change during an exercise program in 105 hypertensive patients.

TABLE II Patients Still Actively Followed on Exercise Program

Exerctss Exerctse and ma Number Alone Medications

3-5 31 19 12 Diuretics 12 (4)’ Beta-blockers 7 Clonidine 1 Prazosin 1

5-10 37 23 14 Diuretics 14 (9)’ Beta-blockers 4 Clonidine I Hydralazine 2

10-14 11 10 Diuretics 1

l Number of patients receiving diuretics alone, 19 patients triam- terene, eight triamterene and hydrochlorothiazide.

pharmacologic therapy after three months of exercise is considered, the change is similar. Average pre- exercise cost was $4.12 per day (range $0.77 to $8.20). After three months of exercise, the average cost was $2.52 (range $0.185 to $8.20). To this should again be added the cost of one pair of running shoes ($16 to $50) per year.

Although we have discussed data accumulated during a relatively short period of time for each individual pa- tient, 37 of our patients have been followed between five and 10 years, and 11 for greater than 10 years. A number of these patients have discontinued and re- sumed exercise on several occasions, and a few re- turned to pharmacologic therapy only to find that drugs were expensive and produced unpleasant side effects. One man returned to drug therapy three times, and each time, with different medications, (guanethidine, meth- yldopa, propranolol, and clonidine hydrochloride) he became impotent. He has now exercised uninterrup- tedly for three years and at present requires no phar- macologic intervention.

Table II summarizes our long-term observations. Twenty-six patients are no longer followed by us. Due to the nature of our referral system, most of these pa- tients had to travel long distances to clinic and were unwilling to do so just to have their blood pressure measured. Of the patients still seen in our clinic, 31 have been followed between three and five years, 37 between five and 10 years, and 11 between 10 and 14 years. Twenty-seven of these required pharmacologic intervention to maintain a satisfactory blood pressure, whereas 52 relied on exercise alone. Triamterene was taken by all 27 patients in whom pharmacologic inter- vention was required, whereas hydrochlorothiazide was used by eight.

It is easy to demonstrate to most patients that exer- cise is a more pleasant way to control hypertension than is pharmacologic intervention. Even in patients who

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recognize and acknowledge this, however, exercise is frequently interrupted during illness, travel, or frenetic extraneous activity and, once interrupted, physician intervention pointing out statements patients made as to how they felt when running is frequently required before patients will resume exercise. As in the young man mentioned before, a resumption of pharmacologic intervention with unpleasant side effects is the most persuasive and effective argument in favor of exercise we have been able to marshal.

A placebo effect [22] could explain at least part of the drop in blood pressure that occurred in our patients. Unquestionably, we approached each patient with ob- vious enthusiasm for the recommended course of therapy. In addition, perhaps influenced by suggestion, our patients uniformly said they felt better and had more energy as a result of exercise; this, too, could have a placebo effect in lowering blood pressure. Against the suggestion of a placebo effect is the fact that in patients whose pressure became normal during exercise, blood pressure remained at its reduced level for one to three

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2. White PD: Severe hypertension-study of one-hundred pa- 12. tients with cardiovascular complications: follow-up results on fifty controls and fifty patients subjected to Smithwicks 13. Lumbo dorsal sympathectomy. 1941-1946. JAMA 1956; 160: 1027-1206. 14.

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4. Talbott JH, Castleman B, Smithwick RN, Melville RS, Pecora W: Renal biopsy studies correlated with renal clearance observations in hypertensive patients treated by radical sympathectomy. J Clin Invest 1943; 22: 367-394. 16.

5. Moyer JH, Heiir C, Peuy K, Ford RV: The effect of treatment on the vascular deterioration associated with hypertension, with particular emphasis on renal function. Am J Med 1958; 24: 177-192. 17.

6. Pitts NE: The clinical evaluation of prazosin hydrochloride, a new antihypertensive agent. In: Catlon DWK, ed. Pra- 18. zosin-evaluation of a new antihypertensive agent. Pro- ceedings of a Symposium held at the Center Inter-prof- 19. essionel, Geneva March 8, 1974. Amsterdam: Exerpta Medica, 1974; 149-163.

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10. Menzies D, Prystowsky H: Acute hemorrhagic pancreatitis

REFERENCES

790 November 1984 The American Journal of Medlclne Volume 77

months after exercise .ceased and then rose slowly toward pre-exercise control levels.

Both plasma renin activity and prostaglandin con- centration rise during short-term, rigorous exercise, and peripheral resistance falls sharply (Cade R, Zauner C, unpublished observations). Whether the short-term effects of exercise carry over to the long-term state and explain the exercise effect we have observed is not known. We are at present studying the effect of stroke volume, cardiac output, and plasma renin activity and prostaglandin release in an attempt to gain insight into the regulation of peripheral resistance.

The finding that exercise lowers blood pressure significantly in a group of sedentary hypertensive pa- tients suggests that “essential” hypertension is a result primarily of life-style and can be prevented or treated effectively by reasonable physical activity.

ACKNOWLEDGMENT

We thank Dr. Craig Tisher for his review and criticism of this manuscript.

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