Treating Hypertension in Active Patients: Which Agents Work Best With Exercise?
Randall Swain, MD; Barbara Kaplan, PharmD
THE PHYSICIAN AND SPORTSMEDICINE - VOL 25 - NO. 9 - SEPTEMBER 97
In Brief: Hypertension treatment typically involves drug and nondrug therapies. For patients already exercising and those trying to start, physicians need to be aware of the intricacies of antihypertensive medications, including side effect profiles and whether they are banned by some sports organizations. Although diuretics and beta-blockers have been used in the past by most physicians, in active patients we typically opt for newer agents such as ACE inhibitors, angiotensin-II-receptor blockers, dihydropyridine calcium channel blockers, and alpha-1 blockers. These drugs typically have fewer side effects and impediments to athletic performance. Other drugs may be used in active patients who have other medical problems or when cost is a concern.
Hypertension is one of the leading risk factors for cardiovascular morbidity and mortality. Unfortunately, the percentage of those who have hypertension may be on the rise as more and more Americans remain sedentary. Physicians, therefore, need to promote exercise programs (see "Exercisers: A Healthy Minority," below)—but without unwittingly sabotaging exercise capacity with antihypertensive medications. So in addition to knowing antihypertensive agents' impact on exercise, clinicians need to target therapy for varied hypertensive patients who participate in different sports and types of exercise.
Hypertension Facts and Diagnosis
About 24% of the US population has hypertension—more than 40,000,000 people (1). Since the advent of antihypertensive drugs, the mortality rates for strokes and myocardial infarctions have declined 57% and 50%, respectively (data from the National Center for Health Statistics calculated by the staff of the National, Heart, Lung, and Blood Institute).
Hypertension should not be diagnosed on one blood pressure reading; at least two readings over a few weeks should be confirmed. During measurement, patients should bare an arm and be seated with the arm supported at heart level. They should not have smoked cigarettes or drunk caffeine for 30 minutes prior. The blood-pressure cuff should be of appropriate size; cuffs that are too small may give falsely high readings. Table 1 (not shown) provides classification of blood pressures and recommended follow-up (2).
Athletes at Risk for Hypertension
Although physically fit individuals are less likely to have hypertension, some active people are still at slightly increased risk (see "Blood Pressure Response to Exercise," below). Those who have diseases such as diabetes mellitus and chronic renal disease, for example, are at risk. Also, black and elderly athletes are at higher risk for developing hypertension. Football linemen, boxers, and some weight lifters, all of whom may tend to become obese, also can have high blood pressure. Wheelchair athletes suffering from spinal cord injuries tend to lose autonomic control of blood pressure, which results in wide fluctuations in blood pressure.
Studies have shown that adolescents identified in preparticipation physicals as possibly having increased blood pressures are often chronic hypertensives. Tanji (3) found that 12.2% of 467 adolescent athletes had blood pressures greater than 142/92 during the physical examination. Of these, 79.6% had chronically elevated blood pressures on follow-up. Given these data, we recommend that these individuals be tracked closely; they would likely require treatment and may be noncompliant.
Blood pressure parameters for participation in sports have been suggested in the Bethesda Guidelines (4). Those who have blood pressures of 169/109 mm Hg or less in the absence of target organ or cardiovascular problems are allowed to participate in all sports without restriction because the activity itself reduces blood pressure. People who have higher blood pressures, however, should be restricted from all physical activities that involve heavy straining, such as weight lifting, wrestling, and rowing.
If a patient is identified as borderline hypertensive or mildly hypertensive, nonpharmacologic therapy alone may suffice and should be employed concomitantly even if medications are needed. Nondrug treatment can take several forms:
Exercise. Regular physical activity may both prevent and treat high blood pressure: Sedentary individuals have a 20% to 50% increased chance of developing hypertension (5). Regular aerobic exercise can reduce systolic blood pressure up to 10 mm Hg (6).
Patients do not need strenuous exercise to decrease their blood pressure—walking for 30 to 45 minutes per day may be effective (6). More strenuous activity may mandate an exercise stress test beforehand.
Weight reduction. Regular physical activity with or without caloric restriction effectively reduces weight. A weight loss even as small as 10 lb reduces blood pressure (7). In addition to lowering blood pressure, weight loss will increase the efficacy of antihypertensive medications.
Other therapies. Not all hypertensive patients are equally responsive to reductions in sodium. The estimated sodium content in an average American diet is approximately 9 g daily; reduction of sodium intake to less than 6 g/day is a reasonable goal in the outpatient setting. Although blood pressure reduction with sodium restriction varies widely, pooled results from several trials observed reductions of 5 to 10 mm Hg when sodium intake was decreased to 6 g/day (8). All hypertensive patients, therefore, should receive counseling on dietary sodium restriction.
Potassium, calcium, and magnesium supplementation may also be somewhat effective in reducing blood pressure (2). We currently do not recommend calcium and magnesium supplementation routinely to male patients, but we do counsel most females to take extra calcium to prevent osteoporosis, and this practice may also help control blood pressure. We do recommend that hypertensive patients replace salt shakers with potassium-containing substitutes and then use them liberally.
Patients should restrict cigarette and alcohol use to gain the full benefit of antihypertensive treatments as well as help lower baseline blood pressure. Other therapies such as biofeedback and relaxation techniques may also prove useful for some patients.
Choosing Specific Drugs
Many physicians are using the old "stepped care" approach to treating hypertension by initiating therapy with diuretics or beta-blockers. In fact, the Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V) (2) included recommendations that these agents be used in most blood pressure patients since they are the only ones that have been clearly shown to reduce all-cause morbidity and mortality. However, the newer and usually better tolerated agents have not been used long enough to accurately assess long-term outcomes such as morbidity and mortality.
Below are specifics about each class of antihypertensive drug. Dosages and side-effect profiles for most agents are listed in table 2; appropriate agents for certain patients and various concomitant conditions are outlined in table 3.
Diuretics were some of the first agents used for blood pressure management. They cause a decrease in plasma and extracellular volume.
Active patients who have diabetes or chronic renal insufficiency may require other medications because thiazide diuretics can cause glucose elevations and thiazides are ineffective at serum creatinines above 2.5 mg/dL. Negative effects on lipids (eg, increased triglycerides) have been a concern to clinicians, but these metabolic changes usually reverse themselves over 1 to 2 years (9).
Thiazide diuretics can also cause fatigue, hypokalemia—which may be exacerbated by exercise—worsening of dehydration, and even severe muscle cramping despite normal serum electrolytes. Large doses theoretically can even decrease cardiac output. Lastly, all diuretics are banned by both the International Olympic Committee (IOC) and the National Collegiate Athletic Association (NCAA) because of their use as urinary masking agents to hide doping agents like anabolic steroids (10).
Thiazide diuretics are very inexpensive in generic form and are some of the most effective drugs for black and elderly patients because of these patients' sensitivity to salt and fluid volume status. Diuretics also may provide symptomatic relief for patients with congestive heart failure who may exercise in cardiac rehabilitation programs.
Bottom line: Thiazide diuretics are not a good choice for most endurance athletes. Their use should probably be considered only for elderly or black patients who have difficulty with blood pressure control, those who have congestive heart failure, or those who need inexpensive medication.
The other class of medications recommended by the JNC V report for first-line use are the beta-blockers. These agents work by decreasing cardiac output. Labetalol hydrochloride has the additional action of causing peripheral vasodilation by blocking alpha-1 receptors on the vasculature.
Unfortunately for endurance athletes, these medications have profound negative effects on exercise performance. They can reduce cardiac output, oxygen consumption (VO2 max), maximum heart rate, and duration and intensities of maximum exercise sessions (11,12). They also cause reductions in training-induced gains in aerobic fitness (11). One study (12) found the decrease in exercise duration with beta-blockers to be 38%.
Use of beta-blockers such as pindolol that have intrinsic sympathetic activity reportedly decreases the incidence of bradycardia and negative metabolic effects and allows for some gains in VO2 max with training (8% gain with pindolol vs 24% placebo vs 0% propranolol) (11).
Other negative aspects of beta-blockers in active patients include masking of hypoglycemic response in diabetic exercisers and worsening of asthma or worsening or unmasking of exercise-induced asthma. Patients also report general fatigue, which is not well tolerated by active people. There is also an increased incidence of hyperkalemia (13) with aerobic exercise as well as disturbances in heat dissipation during activities in hot weather (14).
Negative metabolic effects in people who have diabetes or hyperlipidemia were initially thought to limit the utility of beta-blockers, but recent in-depth studies have shown that increases in triglycerides and decreases of high-density lipoprotein (HDL) cholesterol are minimal and disappear after 12 months of therapy (9).
Beta-blockers are banned by both the NCAA for riflery and shooting and the IOC for the biathlon, bobsled, luge, ski jumping, and freestyle skiing in the Winter Olympics and diving, equestrian, fencing, gymnastics, shooting events, sailing, and synchronized swimming in the Summer Olympics (10). These agents have been used to reduce tremor and performance anxiety and improve accuracy in these skill events.
Bottom line: Beta-blockers should be reserved for use in nonendurance athletes and in those who have coronary artery disease.
Central Alpha-2 Agonists
Another older class of agents includes the centrally acting alpha-2 agonists. They act in the central nervous system by stimulating receptors that inhibit the increase of vascular tone. They have no known specific negative effects on exercise other than causing fatigue, sedation, and dry mouth, although the product information for guanfacine hydrochloride claims a lower incidence of these side effects compared with clonidine hydrochloride and methyldopa.
Another problem with using alpha-2 agonists is that if a patient forgets to take the medication, rebound hypertension can result. Long-acting patches are available that usually increase compliance and convenience, but they are more expensive. Orthostatic hypotension may be a problem after endurance events in the heat. These agents have neutral metabolic effects.
Bottom line: The alpha-2 agonists are inexpensive (except for the patches), but their use is restricted because of orthostatic hypotension and sedative effects. They may be considered for nonendurance athletes.
These drugs work by blocking alpha-1 receptors, a process that dilates the arteries. The initial representative agent, prazosin, seemed to commonly cause problems with orthostatic hypotension, first-dose syncope, and even tachyphylaxis or the gradual loss of effectiveness. The newer agents in the class do not seem to have the same side-effect profiles and are well tolerated by patients.
The alpha-1 blockers have favorable metabolic effects: They can reduce low-density lipoprotein (LDL) cholesterol by 11 mg/dL, lower triglycerides by 25 mg/dL, and increase HDL cholesterol by 25 mg/dL (9). These positive metabolic changes were maintained throughout a 4-year study period. These agents also have the added benefit of causing the alpha-1 receptors controlling the prostatic urethra to decrease tone, thereby relieving symptoms of benign prostatic hypertrophy in affected patients.
There is conflicting evidence regarding the alpha-1 blockers' effect on exercise. Gillin et al (15) found no effect of 1 mg/day of doxazosin mesylate on cardiac output or aerobic exercise performance in 16 essentially untrained subjects. However, another study (16) using larger doses of doxazosin (4 mg/day) on 16 trained individuals found that the subjects' VO2 max was reduced by 3 ± 1 mL/kg/min (p = .0004), and that 5,000-m running time increased by 43 ± 12 seconds (p = .04). Although this difference seems small, it would be important to elite athletes. However, the small population studied may result in an overestimation of doxazosin's effect.
Bottom line: Alpha-1 blockers remain a good choice for most active patients, although definitive studies are needed before recommending them in elite endurance athletes. They remain an excellent choice for active older patients who have symptoms of benign prostatic hypertrophy.
Angiotensin-converting enzyme (ACE) inhibitors work by blocking the formation of angiotensin II, which is an important intermediary in the development of hypertension through its effect on aldosterone and direct effects on the vasculature. These agents are excellent for blood pressure reduction and are generally well tolerated. The most common adverse drug reaction is cough (10% to 15% of users).
ACE inhibitors are essentially metabolically neutral and have the added benefit of preventing nephropathy in patients who have diabetes. These drugs are contraindicated in pregnant patients and those desiring pregnancy because their use during the second and third trimester may result in severe fetal injury or even fetal death.
The use of ACE inhibitors results in the build-up of bradykinin, and some experts think this induces a susceptibility to exercise-induced asthma. ACE inhibitors have also been associated with anaphylaxis (17). A susceptible atopic patient taking ACE inhibitors and exercising aerobically may have an increased risk of exercise-induced anaphylaxis. In addition, ACE inhibitors used with diuretics can result in severe hypotension if the diuretic dose is not decreased. As a result, endurance athletes using both medications must be monitored for volume depletion in the heat to prevent orthostatic hypotension.
Studies on trained hypertensive athletes have shown that ACE inhibitors do not seem to adversely affect exercise parameters (18). Though one study (19) showed small decreases in some aspects of performance, it involved only 10 healthy males.
Bottom line: Overall, ACE inhibitors are excellent choices for most active patients (especially those who have diabetes). Because elderly and black athletes typically have low renin states, these patients do not respond well to ACE inhibitors unless these agents are combined with diuretics. Atopic individuals should perhaps avoid these agents.
Like ACE inhibitors, angiotensin-II-receptor antagonists act on the renin-angiotensin-aldosterone system. Angiotensin-II-receptor antagonists block angiotensin II at the receptor level, thereby preventing elevations in bradykinins and virtually eliminating the cough side effect. Limited use of this new class of antihypertensives has shown that they are similarly effective for treating hypertension, and they are thought to be metabolically neutral.
Bottom line: Although no studies have looked at the effects of angiotensin-II-receptor antagonists on athletic performance, they would seem to be similar to the ACE inhibitors in lack of negative effects. They may even be useful in atopic patients because they do not increase endogenous bradykinins.
Calcium Channel Blockers
The three classes of calcium channel blockers have differing pharmacodynamic effects. The phenylalkylamines (verapamil hydrochloride), benzothiazepines (diltiazem hydrochloride), and the dihydropyridines (nifedipine and others) are all metabolically neutral. Verapamil causes less arterial dilation than the other calcium channel blockers. It decreases left ventricular contractility and restricts heart rate, although to a lesser extent than the beta-blockers. The main side effect with verapamil is constipation.
The dihydropyridines, for which nifedipine was the prototype, almost exclusively affect the arterial tree when causing vasodilation. These agents either do not affect the heart rate or cause a reflex increase. They often result in a reflex lower-extremity edema. Diltiazem has effects on both the conducting system and arterial tree but to a lesser degree, and this may minimize the appearance of either side effect.
There have been multiple recent reports of increased cardiovascular mortality with calcium channel blockers in those taking them for blood pressure. However, all reports appear to be associated with the use of short-acting agents, and there have been no reports of large numbers of patients with unexpected adverse cardiovascular events while taking agents that have long half-lives or sustained-release systems. We no longer recommend any agents that have short half-lives, unless they are available as sustained-release systems.
No known studies to date have shown a significant negative effect of calcium channel blockers on exercise. However, verapamil and diltiazem may lower maximum heart rate attained with exercise. A 1991 study (12) of 14 hypertensive athletes taking 240 mg of verapamil per day showed a decrease in maximum heart rate compared with placebo (163 versus 158 beats per minute), but this finding was not statistically significant. In a study (18) of 10 healthy, nonhypertensive men, 20 mg of nifedipine was given 3 hours before maximum exercise and did effect a small but statistically significant decrease in both maximum work load (4%) and exercise duration (6%), but not in oxygen consumption.
Bottom line: Long-acting calcium channel blockers, especially dihydropyridines, are excellent choices for most active patients, especially those who have asthma or heart disease. We avoid short-acting calcium channel blockers because of safety concerns, especially the possibility of increased mortality. We also avoid verapamil and, to a lesser extent, diltiazem, because they may restrict maximum heart rate.
Direct vasodilators, such as hydralazine hydrochloride and minoxidil, act directly on the blood vessels to dilate them, thereby reducing arterial blood pressure. Vasodilators are rarely chosen for most routine hypertension treatment since, when used alone, they result in severe reflex tachycardia and fluid retention. This may necessitate additional agents like diuretics and beta-blockers to control side effects.
Peripheral alpha-adrenergic antagonists inhibit the release of catecholamines, which constrict blood vessels. Peripheral alpha-adrenergic antagonists, however, can cause either severe exercise-related or at-rest orthostatic hypotension (guanethidine monosulfate) or depression (reserpine).
Bottom line: We do not recommend using direct vasodilators in the active population. Also, because of the severe side effects possible with peripheral alpha-adrenergic antagonists, these drugs are usually not used to treat hypertension today in any population.
We generally recommend long-acting, newer agents for most active patients: ACE inhibitors, angiotensin-II-receptor blockers, dihydropyridine calcium channel blockers, and sometimes alpha-1-receptor blockers. We do this to minimize side effects and avoid diminishing athletic performance. Physicians also need to know that beta-blockers and diuretics are banned by some sports organizations. Following these suggestions in active patients and sedentary patients who wish to exercise will help maximize compliance.
Exercisers: A Healthy Minority
Surveys reveal that most Americans do not exercise—contrary to the advice of the National Institutes of Health, American College of Sports Medicine, and Centers for Disease Control and Prevention (1). These organizations recommend 30 minutes of accumulated moderate-intensity physical activity on most, if not all, days of the week.
Data from the National Health and Nutrition Examination survey (NHANES III) (2) indicate that 22% of all Americans are totally sedentary during leisure time. The rate is higher in women (27%) than in men (17%), and black women have the highest rate of being totally sedentary (40%). What's more, American habits appear to worsen with age: Only 34% of men and 27% of women over 65 report regular physical activity (3).
Even less favorable are the data for obese people: 37% report no leisure-time physical activity (4). Unless sedentary obese people make major lifestyles changes, their risk for hypertension increases. An even more alarming trend is that the NHANES III data show that obesity rates in American children have been rising—from 7.6% in 1976-80 to 10.9% in 120218-91 to 14% in 120218-94 (5).
Epidemiologic studies have shown that the least fit individuals have a much greater chance of developing cardiovascular diseases such as heart attacks and strokes than physically fit individuals with similar risk factors have (6). Two epidemiologic studies, one in Harvard alumni (7) and one in Norwegian men (8), have shown that regular aerobic exercise has a graded, inverse relationship to all-cause mortality. According to European case-control studies, physically trained subjects are also less likely to experience the onset of hypertension—6% to 8% in the trained population versus 12% to 15% in the general population (9). Among hypertensive patients, trained subjects also had a higher percentage of the mildest form of hypertension—stage 1—than their untrained counterparts (90% vs 75%).
Blood Pressure Response to Exercise
Aerobic exercise normally induces an incremental increase in systolic blood pressure for each increase in the intensity of work. The diastolic blood pressure usually remains stable or may decrease slightly with increased work. In patients who have hypertension or borderline hypertension, aerobic exercise commonly causes increases in diastolic pressure greater than or equal to 10 mm Hg. One theory suggests that normotensive persons who exhibit this increase in diastolic blood pressure during exercise will be more likely to develop hypertension in the future, but this has not been confirmed in large studies.
Blood pressures during weight training are often extremely elevated, depending on the size of the muscle group being worked and the amount of weight being lifted. In one study, (1) subjects had a mean blood pressure during a maximum lift of 311/284 mm Hg, and one individual reached 370/360 mm Hg. Correct breathing techniques to avoid a Valsalva maneuver during the lift can lower the maximum blood pressure to around 12021/175 mm Hg for the same weight. We usually counsel hypertensive patients who want to lift weights to begin only after blood pressure is controlled and then to use high repetitions with light weights.
Dr Swain is an associate professor of family and sports medicine at West Virginia University-Charleston (WVU-Charleston) and Charleston Sports Medicine Associates in Charleston, West Virginia. He is a charter member of the American Medical Society for Sport Medicine. Dr Kaplan is a clinical assistant professor of family medicine and an assistant professor of pharmacy at WVU-Charleston. Address correspondence to Randall Swain, MD, 1201 Washington St E, Suite 108, Charleston, WV 25301.
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