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Use of Non-Drug Therapy in Treating Hypertension
Use of Non-Drug Therapy in Treating Hypertension
NORMAN M. KAPLAN, M.D. Dallas, Texas
From the University of Texas Health Science Center, Southwestern Medical School, Dallas, Texas. This study was supported by NIH (Preventive Cardiology Academic Award) Number 5-K07HL00596-05. Requests for reprints should be addressed to Dr. Norman M. Kaplan, Department of Internal Medicine, University of Texas Health Science Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235.
96
October 5, 1984
The high degree of risk for cardiovascular disease and the failure of medication to provide adequate protection are the chief considerations in the use of nondrug therapy of hypertension. We shall examine the effects of weight reduction, sodium restriction, exercise, and other such alternatives to blood pressure-lowering medication. If nondrug therapies can lower blood pressure, they will remove the need for drug therapy in some patients and minimize the amount of drugs needed for others. More than ever, nondrug therapies are being considered for the treatment of patients with hypertension. This increasing enthusiasm arises from the confluence of two forces: On the one hand, more people with relatively mild hypertension are being identified, and the evidence that as a group they are at higher risk for cardiovascular disease (CVD) has been confirmed [1]; on the other hand, recently completed large-scale clinical trials of the drug therapy of mild hypertension [2-4] have not demonstrated the degree of protection against the most prevalent cardiovascular complication, coronary heart disease, that was expected from the lowering of blood pressure obtained during these studies [5]. Therefore, although more people are being identified as being at risk, the ability of antihypertensive drugs as they have been used to protect against the risk has been brought into question. Further doubt has arisen from the publication of the mortality rates among 7,610 Japanese men living in Hawaii over 10 years of observation [6]. This study reconfirmed the impact of both systolic and diastolic blood pressure as the most important and independent predictors of total cardiovascular, coronary, and stroke mortality. Higher mortality rates from cardiovascular diseases, however, were observed among those men who received antihypertensive medication at the beginning of the study as compared with untreated men in every category of blood pressure status, from normal to distinctly high levels (Figure 1). Whereas this apparently paradoxic finding was said to reflect more advanced severity of the hypertension and other risk factors before the start of the study, the investigators stated that "after adjustment of age, blood pressure and nine other known risk factors in multivariate logistic analysis, antihypertensive medication remained significant as a risk factor for CVD, coronary heart disease (CHD), and stroke"[6]. Even if there were no doubts about their ability to protect against cardiovascular risk, antihypertensive drugs tend to make people feel worse [7] and induce various biochemical aberrations [8]. An expert committee of the World Health Organization and International Society of Hypertension has recommended that nondrug therapies be used for at least three
The American Journal of Medicine
NEW CONCEPTS IN HYPERTENSION THERAPY SYMPOSIUM-KAPLAN
months in those patients with diastolic blood pressures below 100 mm Hg and indefinitely for those below 95 mm Hg [9]. Although this appears to be an attractive proposition, many practitioners-probably more in the United States than elsewhere [1 0]-do not advocate nondrug therapies for many patients. This may reflect an unwise dependence on drugs as well as a lack of confidence by physicians in the effectiveness and acceptance by patients of nondrug therapies. Let us then examine the evidence about these issues to determine whether this lack of confidence is justified. Before proceeding, we must recognize that adequate trials of the efficacy of nondrug therapies to protect against cardiovascular risks have not been performed; considering the logistic problems, it is not likely that they ever will be. We must, therefore, accept them on the basis of their effectiveness in lowering the blood pressure along with the strong likelihood that they do not increase some risks while they lower the pressure, as drugs might.
0
CVD
8
.. ~
. ~
a.
100
CHD
Stroke
Non-CVD
-
Men on ant1hypertens•ve medtcotion - - - Men nor on medication
eo
.c
i "
60
I
Q
/~-7
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40
Blood pressure status at baseline examination ( N' normotension, B• borderline hypertension, H' definite hypertension
Figure 1. Age-adjusted 10-year mortality rates according to baseline blood pressure status and antihypertensive medication. N = normotension; 8 = borderline hypertension; H = definite hypertension. Reproduced with permission from [6].
PLACEBO EFFECTS
If there is evidence that one or another nondrug therapy works to lower the blood pressure, that evidence must be weighed against claims for an antihypertensive effect from virtually everything that has been tried, including somesuch as dilute hydrochloric acid [11] and cholecystectomy [12]-that almost certainly do not work. Their nonspecific effects probably reflect the progressive decrease in blood pressure that occurs with repeated measurements [13]. This could represent the statistical phenomenon of regression toward the mean or, more likely, the dampening of the psychologic stress of blood pressure measurements. Although placebos may not actually lower the blood pressures when they are recorded by ambulant intra-arterial monitoring [14], there is almost always a decrease in blood pressures taken by routine sphygmomanometry over the first few weeks of any therapy. Therefore, studies to demonstrate the efficacy of any therapy, drug or nondrug, must control for this effect. It may require more readings over a longer time than the four to six weeks most utilize: In the Australian Therapeutic Trial, the blood pressures of the patients receiving placebo therapy continued to decrease throughout the 36 months of observation, although most of the decreases occurred between the third measurement taken at four weeks and the fourth at four months [15]. WEIGHT REDUCTION
Obesity and hypertension are clearly associated: Hypertension is found more frequently among overweight people, and the incidence of hypertension is higher among those who gain weight [16]. The assumption is widely held that weight loss per se is an effective way to lower the
blood pressure. In a survey of all "controlled" studies of various nondrug therapies published through 1981, Andrews et al [17] reported that weight loss had been found to have the greatest effect. As pointed out by Hoven [18], however, there have been pitifully few studies of weight loss and hypertension that come anywhere close to being controlled [19-28]. In fact, there are only four studies wherein weight loss has clearly peen disassociated from dietary sodium restriction. In two of them, by Dahl and co-workers in 1958 [20] and by Andersson et al in 1983 [27], weight loss, even of a significant degree, without sodium restriction was not accompanied by much of a decrease in blood pressure. The study previously used as the best demonstration of the independent action of weight reduction, that by Raisin et al in 1978 [23], suffers from having determined only one 24-hour urine sodium level at the end of the second month of a low-caloric diet that was not specifically designed to maintain a fixed level of sodium intake. There are, however, two more recent studies that show weight loss to be effective even in the absence of sodium restriction. In the 1983 study by Reisin et al [26] it was found that weight loss without sodium restriction was effective; in the study by Maxwell et al [28] it was found that weight loss without sodium restriction was as effective as weight loss with sodium restriction beyond the first week. Obviously, the issue needs further study. There is little doubt that when obese subjects begin a very-low-calorie diet, they usually have a marked diuresis and may show a rather precipitous decrease in blood pressure within 48 hours, which may be mediated by dampening of sympathetic nervous system activity· [29] and is not dependent upon the loss of body fat. With continued weight loss, the
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NEW CONCEPTS IN HYPERTENSION THERAPY SYMPOSIUM-KAPLAN
TABLE I.
Modest Sodium Restriction in Hypertension Sodium Excretion (mmol/day)
BP (mm Hg)
No. of Patients
Before
Alter
Duration
Before
Alter
Parijs et al 1973 [31] Carney et al 1975 [32]
17 19
191 205
93 >120(3) <120(12)
4wk 8wk
147/98 163/106
-9/6 -15/7
Magnani et al 1976 [33] Morgan et al 1978 [34]
37 28
191
157
15-21mo 24mo
166/105 160/97
Morgan, Myers 1981 [35]
12M< 105 12F < 105 12M> 105 12M> 105 19 45 18 12
197 146 171 125 191 150 149 143
78 58 85 64 86 37 59 117
-14/14 DBP < 95 in 55% DBP 87 89 103 101 -12/6 -11/6 -10/5 -29/18
Study
MacGregor et al 1982 [36] Beard et al 1982 [37] Watt et al 1983 [38] Silman et al 1983 [39]
reduction in blood pressure is correlated with a decrease in total blood volume and cardiac output even when sodium intake is not reduced [26]. SODIUM RESTRICTION
As amply documented, rigid sodium restriction has long been known to cause a significant decrease in blood pressure [30]. A more practical, moderate reduction of dietary sodium to a level of 70 to 100 mmol a day has recently been found to be accompanied by a more modest but usually significant lowering of the blood pressure (Table 1), although some find no greater effect with such sodium restriction than that seen in other patients studied in parallel who did not reduce sodium intake [38,39]. In most of the studies, weight loss was insignificant so contamination by this variable is not a factor. Again, other nonspecific effects cannot be discounted. Not every hypertensive patient responds to such moderate reduction of sodium intake. Although some have postulated two populations, sodium-sensitive and sodium-resistant [40], there is more likely a continuum of responsiveness, perhaps related to the degree of change in hormonal mechanisms as well as to the age and blood pressure of the patient [41]. Moderate sodium restriction, achievable by deleting most high sodium foods from the diet and adding no extra sodium at the table or in the cooking, has no apparent potential for harm. But more rigid sodium restriction, down to 10 to 50 mmol a day, may not only be difficult for patients to achieve but may so stimulate the renln-angioten-
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8wk
4wk 12wk 8wk 12mo
DBP 97 95 115 111 156/98 142/88 150/91 165/98
sin (42] and sympathetic nervous systems (43] as to limit both the antihypertensive and potassium-sparing effects (44] of more moderate sodium restriction. Beyond the likelihood that moderate sodium restriction will lower the blood pressure of those with hypertension, there is hope that if started during infancy, it might prevent the development of the disease (45]. Even if that does not prove to be true, there seems to be no reason not to encourage the reduction of the unnaturally high levels of sodium that we have only recently begun to consume. The taste preference we acquire for sodium has been shown to diminish after a few months of dietary restriction, so that there should be no permanent discomfort and potentially a great deal of benefit from moderate sodium reduction [46]. POTASSIUM SUPPLEMENTATION
When more fresh foods are consumed to lower sodium intake, the intake of potassium will almost always increase since it is the predominant cation in most fresh foods. For most hypertensive subjects an additional intake of potassium may prove beneficial since there is considerable experimental evidence and a growing amount of clinical data that additional potassium will lower the blood pressure [47]. In one carefully performed study, the addition of 60 mmol a day of potassium chloride resulted in a 4 percent decrease in mean supine blood pressure compared with the results of a placebo [48].The investigators state: "This increase in potassium intake could be achieved with a potassium-based salt substitute and a moderate increase in vegetable and fruit consumption." The initial effect of potassium supplementation probably
NEW CONCEPTS IN HYPERTENSION THERAPY SYMPOSIUM-KAPLAN
involves a natriuresis, but a more persistent antihypertensive action may occur by other mechanisms [49]. OTHER DIETARY CHANGES
A number of recent studies have pointed to possible antihypertensive effects of various additions and deletions to the diet. Of these, the evidence for more calcium and less saturated fat seems the strongest. Calcium Supplementation. Hypertensive subjects may ingest less calcium, and the intake of additional calcium may lower the blood pressure [50]. This view has been supported by some [51 ,52] but denied by others [53]. The prudent course would be to maintain a high calcium intake, avoiding a reduction in milk and cheese products in attempting to reduce dietary sodium intake. For those with low dietary calcium, the use of supplements may prove helpful. Magnesium. Hypomagnesemia may accompany and aggravate hypokalemia. The addition of 15 mmol a day of magnesium for six months was shown to lower the blood pressure by an average of 12/8 mm Hg in 18 hypertensive subjects receiving long-term diuretic therapy compared with no change in another 19 patients who did not receive magnesium [54]. Fat, Fiber, and Vegetarian Diets. Controlled trials among small groups of hypertensive patients have disclosed a seemingly significant lowering of blood pressure with various maneuvers, including (1) a reduction of total fat with an increase in the ratio of polyunsaturated to saturated fat, which may lower blood pressure by increasing the synthesis of vasodilatory prostaglandins [55]; (2) a lacto-ovo-vegetarian diet [56] (this effect has been related to the high potassium content of a vegetarian diet [57]); an increase in fiber that could decrease sodium intake [58]. A reduction in dietary protein intake may prove beneficial, particularly in those with underlying renal disease, since high protein intake has been shown to increase glomerular capillary pressure and flow, thereby presumably advancing the progress of glomerular sclerosis [59]. RELAXATION AND MEDITATION
Various relaxation techniques-including transcendental meditation, yoga, biofeedback, and muscle relaxationhave been shown to reduce the blood pressure of hypertensive patients at least transiently. In the survey of Andrews et al [17], yoga and muscle relaxation were found to have significant blood pressure-lowering effects but not meditation and biofeedback. Recent studies have demonstrated that such procedures are applicable to and generally effective in the general hypertensive population [60]. Perhaps the most impressive study is that of Patel et al [61], who identified hypertensive subjects in a screening program at an English industrial firm and randomly assigned half to a biofeedback-aided relaxation program for eight weeks while
the other half served as controls. Both at the end of the active relaxation program and six months later (during which time the subjects had been asked to continue to practice relaxation but had not been seen), the blood pressures of the treated group were significantly lower. Moreover, both plasma renin and aldosterone levels were lower at eight weeks in those undergoing relaxation, suggesting the changes were occurring in at least one of the mechanisms controlling the blood pressure. Patients who elicit the relaxation response have higher plasma norepinephrine levels after stress but no greater· increases in pulse or blood pressure, suggesting a lesser end-organ responsivity to adrenergic stimulation [62]. Thus, there seems to be good reason to try one or another form of relaxation therapy with many patients. There seems to be little to lose and perhaps a great deal to gain, although short-term effects may not be maintained, and continued surveillance is needed. EXERCISE
Many people are walking, jogging, and performing various other exercises in hopes of achieving various goals related to cardiovascular fitness. A reduction in elevated blood pressure may be one of these goals [63]. Although there is no good evidence that this will happen, there seems to be no reason to curtail reasonable isotonic exercise in patients with mild to moderate hypertension. In particular, in hypertensive adolescents a significant lowering of blood pressure may be achieved by exercise [64]. On the other hand, isometric exercise may be harmful. During isometric or static exercise-pushing, pulling, lifting-both the diastolic and systolic pressures and heart rate increase in response to reflexes that abruptly withdraw vagal tone and increase peripheral resistance [65]. MODERATION OF ALCOHOL CONSUMPTION
The blood pressure appears to increase slowly but progressively with the intake of increasing amounts of alcohol, with an average increase of 2 mm Hg in diastolic levels noted among those who consumed an average of 30 ml a day of ethanol [66]. Those who drink more than an average of 1 oz a day of ethanol may have significant increases in blood pressure that will usually come down very quickly when they stop drinking [67]-unless the patient experiences alcohol withdrawal symptoms that may provoke a marked pressor response [68]. On the other hand, there is convincing evidence that the intake of 1 to 2 oz of ethanol a day will protect against coronary heart disease, possibly by the increase in cardioprotective high density lipoprotein-cholesterol levels that accompany the intake of ethanol [69]. Thus the likely protection against coronary heart disease may outweigh the potential harm of a 2 to 4 mm Hg increase in blood pressure that is usually seen with regular intake of 1 to 2 oz a day of ethanol.
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The wisest course may be to advise the hypertensive patient to stop all ethanol intake for a few weeks to observe the effect of abstinence. Thereafter, the patient may be advised to consume no more than 1 oz of ethanol a day, that is, 2 oz of 100-proof spirits, 8 oz of wine or 24 oz of beer. If the blood pressure does not increase significantly, the regular consumption of such moderate amounts of ethanol may be condoned since it may do more good than harm. But all should be warned about the dangers of heavier alcohol intake beyond 3 oz a day, which may not only damage the liver and brain but also raise the blood pressure considerably.
SUMMARY Non-drug therapies should be tried with all patients. They will reduce the blood pressure of many hypertensive subjects, in some to a level that is safe enough to eliminate the need for drug therapy. Those patients with mild hy-
pertension may thereby be able to stay off drugs, and those with more severe hypertension may need less medication. At least part of what appears to be an antihypertensive effect of these non-drug therapies may be attributable to the "natural" fall in blood pressure seen when repeated readings are taken. Such decreases may reflect a statistical regression toward the mean, a placebo effect, or a relief of anxiety and stress with time. The phenomenon is probably responsible for much of the initial response to drug therapy as well, so both drugs and non-drugs may be given credit not deserved by either. Although it is true that many patients will not adhere to non-drug therapies, remember that poor compliance is also a major problem with drug treatment. The same techniques known to improve compliance to drug therapy should be used with non-drug therapies: a gentle seduction, not a massive onslaught.
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changes in obese hypertensive subjects during rapid weight loss: comparison of restricted versus unchanged salt intake. Arch Intern Med 1984; 144: 1581-1584. Jung RT, Shetty PS, Barrand M, et al: Role of catecholamines in hypotensive response to dieting. Br Med J 1979; 1: 12-13. Chapman CB, Gibbons TB: The diet and hypertension: a review. Medicine 1949; 29: 29-69. Parijs J, Joossens JV, Vander Linden L, et al: Moderate sodium restriction and diuretics in the treatment of hypertension. Am Heart J 1973; 85: 22-34. Carney S, Morgan T, Wilson M, et al: Sodium restriction and thiazide diuretics in the treatment of hypertension. Med J Aust 1975; 1: 803-807. Magnani B, Ambrosioni E, Agosta R, et al: Comparison of the effects of pharmacological therapy and a low-sodium diet on mild hypertension. Clin Sci 1976; 51: 625s-626s. Morgan T, Adam W, Gillies A, et al: Hypertension treated by salt restriction. Lancet 1978; II: 227-230. Morgan TO, Myers JB: Hypertension treated by sodium restriction. Med J Aust 1981; 2:396-397. MacGregor GA, Markandu N, Best F, et al: Double-blind randemised crossover trial of moderate sodium restriction in essential hypertension. Lancet 1982; II: 351-355. Beard TC, Cooke HM, Gray WR, et al: Randomised controlled trial of a no-added-sodium diet for mild hypertension. Lancet 1982; II: 455-458. Watt GCM, Edwards C, Hart JT, et al: Dietary sodium restriction for mild hypertension in general practice. Br Med J 1983; 286: 432-436. Silman AJ, Locke C, Mitchell P, et al: Evaluation of the effectiveness of a low sodium diet in the treatment of mild to moderate hypertension. Lancet 1983; 1: 1179-1182. Kawasaki T, Delea CS, Bartter FC, et al: The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension. Am J Med 1978; 64: 193-198. Koolen Ml, Bussemaker-Verduyn den Boer E, van Brummelen P: Clinical biochemical and haemodynamic correlates of sodium sensitivity in essential hypertension. J Hypertens 1983; 1 (suppl 2): 21-23. van Brummelen P, Schalekamp M, de Graeff J: Influence of sodium intake on hydrochlorothiazide-induced changes in blood pressure, serum electrolytes, renin and aldosterone in essential hypertension. Acta Med Scand 1978; 204: 151-157. Warren SE, Vieweg WVR, O'Connor DT: Sympathetic nervous system activity during sodium restriction in essential hypertension. Clin Cardiol 1980; 3: 348-351. Ram CVS, Garrett BN, Kaplan NM: Moderate sodium restriction and various diuretics in the treatment of hypertension: effects of potassium wastage and blood pressure control. Arch Intern Med 1981; 141: 1015-1019. Hofman A, Hazebroek A, Valkenburg HA: A randomized trial of sodium intake and blood pressure in newborn infants. JAMA 1983; 250: 370-373. Beauchamp GK, Bertino M, Engelman K: Modification of salt taste. Ann Intern Med 1983; 98 (part 2): 763-769. Treasure J, Plath D: Role of dietary potassium in the treatment of hypertension. Hypertension 1983; 5: 864-872.
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MacGregor GA, Smith SJ, Markandu NO, et al: Moderate potassium supplementation in essential hypertension. Lancet 1982; II: 567-570. Overlack A, Muller HM, Kolloch R, et al: Long-term antihypertensive effect of oral potassium in essential hypertension. J Hypertens 1983; I (suppl 2): 165-167. McCarron DA: Calcium and magnesium nutrition in human hypertension. Ann Intern Med 1983; 198 (part 2): 800-805. Ackley S, Barratt-Connor E, Suarez L: Dairy products, calcium, and blood pressure. Am J Clin Nutr 1983; 138: 457-461. Belizan JM, Villar J, Pineda 0, et al: Reduction of blood pressure with calcium supplementation in young adults. JAMA 1983; 249: 1161-1165. Kesteloot H, Geboers J: Calcium and blood pressure. Lancet 1982; 1: 813-815. Dyckner T, Wester PO: Effect of magnesium on blood pressure. Br Med J 1983; 286: 1847-1849. Puska P, Iacono JM, Nissinen A, et al: Controlled, randomised trial of the effect of dietary fat on blood pressure. Lancet 1983; 1: 1-5. Rouse IL, Beilin LJ, Armstrong BK, et al: Blood-pressure-lowering effect of a vegetarian diet: controlled trial in normotensive subjects. Lancet 1983; 1: 5-10. Ophir 0, Peer G, Gilad J, et al: Low blood pressure in vegetarians: the possible role of potassium. Am J Clin Nutr 1983; 37: 755-762. Anderson J: Plant fiber and blood pressure. Ann Intern Med 1983; 98 (part 2): 842-846. Meyer TW, Anderson S, Brenner BM: Dietary protein intake and progressive glomerular sclerosis: the role of capillary hypertension and hyperperfusion in progression of renal disease. Ann Intern Med 1983; 98 (part 2): 832-838. Engel BT, Glasgow MS, Gaarder KR: Behavioral treatment of high blood pressure. Ill. Follow-up results and treatment. Psychosom Med 1983; 45: 23-29. Patel C, Marmot MG, Terry OJ: Controlled trial of biofeedbackaided behavioural methods in reducing mild hypertension. Br Med J 1981; 282: 2005-2008. Hoffman JW, Benson H, Arns PA, et al: Reduced sympathetic nervous system responsivity associated with the relaxation response. Science 1982; 215: 190-192. Bjorntorp P: Hypertension and exercise. Hypertension 1982; 4 (suppl Ill): 111-56-59. Hagberg JM, Goldring D, Ehsani AA, et al: Effect of exercise training on the blood pressure and hemodynamic features of hypertensive adolescents. Am J Cardiol1983; 52: 763-768. Ewing OJ, Irving JB, Kerr F, et al: Static exercise in untreated systemic hypertension. Br Heart J 1973; 35: 413-421. Cooke KM, Frost GW, Stokes GS: Blood pressure and its relationship to low levels of alcohol consumption. Clin Exp Pharmacal Physiol 1983; 10: 229-233. Potter JF, Beevers DG: Pressor effect of alcohol in hypertension. Lancet 1984; 1: 119-122. Saunders JB, Beevers DG, Paton A: Alcohol-induced hypertension. Lancet 1981; II: 653-656. Thornton J, Symes C, Heaton K: Moderate alcohol intake reduces bile cholesterol saturation and raises HDL cholesterol. Lancet 1983; II: 819-821.
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NORMAN M. KAPLAN, M.D. Dallas, Texas
From the University of Texas Health Science Center, Southwestern Medical School, Dallas, Texas. This study was supported by NIH (Preventive Cardiology Academic Award) Number 5-K07HL00596-05. Requests for reprints should be addressed to Dr. Norman M. Kaplan, Department of Internal Medicine, University of Texas Health Science Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235.
96
October 5, 1984
The high degree of risk for cardiovascular disease and the failure of medication to provide adequate protection are the chief considerations in the use of nondrug therapy of hypertension. We shall examine the effects of weight reduction, sodium restriction, exercise, and other such alternatives to blood pressure-lowering medication. If nondrug therapies can lower blood pressure, they will remove the need for drug therapy in some patients and minimize the amount of drugs needed for others. More than ever, nondrug therapies are being considered for the treatment of patients with hypertension. This increasing enthusiasm arises from the confluence of two forces: On the one hand, more people with relatively mild hypertension are being identified, and the evidence that as a group they are at higher risk for cardiovascular disease (CVD) has been confirmed [1]; on the other hand, recently completed large-scale clinical trials of the drug therapy of mild hypertension [2-4] have not demonstrated the degree of protection against the most prevalent cardiovascular complication, coronary heart disease, that was expected from the lowering of blood pressure obtained during these studies [5]. Therefore, although more people are being identified as being at risk, the ability of antihypertensive drugs as they have been used to protect against the risk has been brought into question. Further doubt has arisen from the publication of the mortality rates among 7,610 Japanese men living in Hawaii over 10 years of observation [6]. This study reconfirmed the impact of both systolic and diastolic blood pressure as the most important and independent predictors of total cardiovascular, coronary, and stroke mortality. Higher mortality rates from cardiovascular diseases, however, were observed among those men who received antihypertensive medication at the beginning of the study as compared with untreated men in every category of blood pressure status, from normal to distinctly high levels (Figure 1). Whereas this apparently paradoxic finding was said to reflect more advanced severity of the hypertension and other risk factors before the start of the study, the investigators stated that "after adjustment of age, blood pressure and nine other known risk factors in multivariate logistic analysis, antihypertensive medication remained significant as a risk factor for CVD, coronary heart disease (CHD), and stroke"[6]. Even if there were no doubts about their ability to protect against cardiovascular risk, antihypertensive drugs tend to make people feel worse [7] and induce various biochemical aberrations [8]. An expert committee of the World Health Organization and International Society of Hypertension has recommended that nondrug therapies be used for at least three
The American Journal of Medicine
NEW CONCEPTS IN HYPERTENSION THERAPY SYMPOSIUM-KAPLAN
months in those patients with diastolic blood pressures below 100 mm Hg and indefinitely for those below 95 mm Hg [9]. Although this appears to be an attractive proposition, many practitioners-probably more in the United States than elsewhere [1 0]-do not advocate nondrug therapies for many patients. This may reflect an unwise dependence on drugs as well as a lack of confidence by physicians in the effectiveness and acceptance by patients of nondrug therapies. Let us then examine the evidence about these issues to determine whether this lack of confidence is justified. Before proceeding, we must recognize that adequate trials of the efficacy of nondrug therapies to protect against cardiovascular risks have not been performed; considering the logistic problems, it is not likely that they ever will be. We must, therefore, accept them on the basis of their effectiveness in lowering the blood pressure along with the strong likelihood that they do not increase some risks while they lower the pressure, as drugs might.
0
CVD
8
.. ~
. ~
a.
100
CHD
Stroke
Non-CVD
-
Men on ant1hypertens•ve medtcotion - - - Men nor on medication
eo
.c
i "
60
I
Q
/~-7
..:::.__./.
~
>o
40
Blood pressure status at baseline examination ( N' normotension, B• borderline hypertension, H' definite hypertension
Figure 1. Age-adjusted 10-year mortality rates according to baseline blood pressure status and antihypertensive medication. N = normotension; 8 = borderline hypertension; H = definite hypertension. Reproduced with permission from [6].
PLACEBO EFFECTS
If there is evidence that one or another nondrug therapy works to lower the blood pressure, that evidence must be weighed against claims for an antihypertensive effect from virtually everything that has been tried, including somesuch as dilute hydrochloric acid [11] and cholecystectomy [12]-that almost certainly do not work. Their nonspecific effects probably reflect the progressive decrease in blood pressure that occurs with repeated measurements [13]. This could represent the statistical phenomenon of regression toward the mean or, more likely, the dampening of the psychologic stress of blood pressure measurements. Although placebos may not actually lower the blood pressures when they are recorded by ambulant intra-arterial monitoring [14], there is almost always a decrease in blood pressures taken by routine sphygmomanometry over the first few weeks of any therapy. Therefore, studies to demonstrate the efficacy of any therapy, drug or nondrug, must control for this effect. It may require more readings over a longer time than the four to six weeks most utilize: In the Australian Therapeutic Trial, the blood pressures of the patients receiving placebo therapy continued to decrease throughout the 36 months of observation, although most of the decreases occurred between the third measurement taken at four weeks and the fourth at four months [15]. WEIGHT REDUCTION
Obesity and hypertension are clearly associated: Hypertension is found more frequently among overweight people, and the incidence of hypertension is higher among those who gain weight [16]. The assumption is widely held that weight loss per se is an effective way to lower the
blood pressure. In a survey of all "controlled" studies of various nondrug therapies published through 1981, Andrews et al [17] reported that weight loss had been found to have the greatest effect. As pointed out by Hoven [18], however, there have been pitifully few studies of weight loss and hypertension that come anywhere close to being controlled [19-28]. In fact, there are only four studies wherein weight loss has clearly peen disassociated from dietary sodium restriction. In two of them, by Dahl and co-workers in 1958 [20] and by Andersson et al in 1983 [27], weight loss, even of a significant degree, without sodium restriction was not accompanied by much of a decrease in blood pressure. The study previously used as the best demonstration of the independent action of weight reduction, that by Raisin et al in 1978 [23], suffers from having determined only one 24-hour urine sodium level at the end of the second month of a low-caloric diet that was not specifically designed to maintain a fixed level of sodium intake. There are, however, two more recent studies that show weight loss to be effective even in the absence of sodium restriction. In the 1983 study by Reisin et al [26] it was found that weight loss without sodium restriction was effective; in the study by Maxwell et al [28] it was found that weight loss without sodium restriction was as effective as weight loss with sodium restriction beyond the first week. Obviously, the issue needs further study. There is little doubt that when obese subjects begin a very-low-calorie diet, they usually have a marked diuresis and may show a rather precipitous decrease in blood pressure within 48 hours, which may be mediated by dampening of sympathetic nervous system activity· [29] and is not dependent upon the loss of body fat. With continued weight loss, the
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NEW CONCEPTS IN HYPERTENSION THERAPY SYMPOSIUM-KAPLAN
TABLE I.
Modest Sodium Restriction in Hypertension Sodium Excretion (mmol/day)
BP (mm Hg)
No. of Patients
Before
Alter
Duration
Before
Alter
Parijs et al 1973 [31] Carney et al 1975 [32]
17 19
191 205
93 >120(3) <120(12)
4wk 8wk
147/98 163/106
-9/6 -15/7
Magnani et al 1976 [33] Morgan et al 1978 [34]
37 28
191
157
15-21mo 24mo
166/105 160/97
Morgan, Myers 1981 [35]
12M< 105 12F < 105 12M> 105 12M> 105 19 45 18 12
197 146 171 125 191 150 149 143
78 58 85 64 86 37 59 117
-14/14 DBP < 95 in 55% DBP 87 89 103 101 -12/6 -11/6 -10/5 -29/18
Study
MacGregor et al 1982 [36] Beard et al 1982 [37] Watt et al 1983 [38] Silman et al 1983 [39]
reduction in blood pressure is correlated with a decrease in total blood volume and cardiac output even when sodium intake is not reduced [26]. SODIUM RESTRICTION
As amply documented, rigid sodium restriction has long been known to cause a significant decrease in blood pressure [30]. A more practical, moderate reduction of dietary sodium to a level of 70 to 100 mmol a day has recently been found to be accompanied by a more modest but usually significant lowering of the blood pressure (Table 1), although some find no greater effect with such sodium restriction than that seen in other patients studied in parallel who did not reduce sodium intake [38,39]. In most of the studies, weight loss was insignificant so contamination by this variable is not a factor. Again, other nonspecific effects cannot be discounted. Not every hypertensive patient responds to such moderate reduction of sodium intake. Although some have postulated two populations, sodium-sensitive and sodium-resistant [40], there is more likely a continuum of responsiveness, perhaps related to the degree of change in hormonal mechanisms as well as to the age and blood pressure of the patient [41]. Moderate sodium restriction, achievable by deleting most high sodium foods from the diet and adding no extra sodium at the table or in the cooking, has no apparent potential for harm. But more rigid sodium restriction, down to 10 to 50 mmol a day, may not only be difficult for patients to achieve but may so stimulate the renln-angioten-
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8wk
4wk 12wk 8wk 12mo
DBP 97 95 115 111 156/98 142/88 150/91 165/98
sin (42] and sympathetic nervous systems (43] as to limit both the antihypertensive and potassium-sparing effects (44] of more moderate sodium restriction. Beyond the likelihood that moderate sodium restriction will lower the blood pressure of those with hypertension, there is hope that if started during infancy, it might prevent the development of the disease (45]. Even if that does not prove to be true, there seems to be no reason not to encourage the reduction of the unnaturally high levels of sodium that we have only recently begun to consume. The taste preference we acquire for sodium has been shown to diminish after a few months of dietary restriction, so that there should be no permanent discomfort and potentially a great deal of benefit from moderate sodium reduction [46]. POTASSIUM SUPPLEMENTATION
When more fresh foods are consumed to lower sodium intake, the intake of potassium will almost always increase since it is the predominant cation in most fresh foods. For most hypertensive subjects an additional intake of potassium may prove beneficial since there is considerable experimental evidence and a growing amount of clinical data that additional potassium will lower the blood pressure [47]. In one carefully performed study, the addition of 60 mmol a day of potassium chloride resulted in a 4 percent decrease in mean supine blood pressure compared with the results of a placebo [48].The investigators state: "This increase in potassium intake could be achieved with a potassium-based salt substitute and a moderate increase in vegetable and fruit consumption." The initial effect of potassium supplementation probably
NEW CONCEPTS IN HYPERTENSION THERAPY SYMPOSIUM-KAPLAN
involves a natriuresis, but a more persistent antihypertensive action may occur by other mechanisms [49]. OTHER DIETARY CHANGES
A number of recent studies have pointed to possible antihypertensive effects of various additions and deletions to the diet. Of these, the evidence for more calcium and less saturated fat seems the strongest. Calcium Supplementation. Hypertensive subjects may ingest less calcium, and the intake of additional calcium may lower the blood pressure [50]. This view has been supported by some [51 ,52] but denied by others [53]. The prudent course would be to maintain a high calcium intake, avoiding a reduction in milk and cheese products in attempting to reduce dietary sodium intake. For those with low dietary calcium, the use of supplements may prove helpful. Magnesium. Hypomagnesemia may accompany and aggravate hypokalemia. The addition of 15 mmol a day of magnesium for six months was shown to lower the blood pressure by an average of 12/8 mm Hg in 18 hypertensive subjects receiving long-term diuretic therapy compared with no change in another 19 patients who did not receive magnesium [54]. Fat, Fiber, and Vegetarian Diets. Controlled trials among small groups of hypertensive patients have disclosed a seemingly significant lowering of blood pressure with various maneuvers, including (1) a reduction of total fat with an increase in the ratio of polyunsaturated to saturated fat, which may lower blood pressure by increasing the synthesis of vasodilatory prostaglandins [55]; (2) a lacto-ovo-vegetarian diet [56] (this effect has been related to the high potassium content of a vegetarian diet [57]); an increase in fiber that could decrease sodium intake [58]. A reduction in dietary protein intake may prove beneficial, particularly in those with underlying renal disease, since high protein intake has been shown to increase glomerular capillary pressure and flow, thereby presumably advancing the progress of glomerular sclerosis [59]. RELAXATION AND MEDITATION
Various relaxation techniques-including transcendental meditation, yoga, biofeedback, and muscle relaxationhave been shown to reduce the blood pressure of hypertensive patients at least transiently. In the survey of Andrews et al [17], yoga and muscle relaxation were found to have significant blood pressure-lowering effects but not meditation and biofeedback. Recent studies have demonstrated that such procedures are applicable to and generally effective in the general hypertensive population [60]. Perhaps the most impressive study is that of Patel et al [61], who identified hypertensive subjects in a screening program at an English industrial firm and randomly assigned half to a biofeedback-aided relaxation program for eight weeks while
the other half served as controls. Both at the end of the active relaxation program and six months later (during which time the subjects had been asked to continue to practice relaxation but had not been seen), the blood pressures of the treated group were significantly lower. Moreover, both plasma renin and aldosterone levels were lower at eight weeks in those undergoing relaxation, suggesting the changes were occurring in at least one of the mechanisms controlling the blood pressure. Patients who elicit the relaxation response have higher plasma norepinephrine levels after stress but no greater· increases in pulse or blood pressure, suggesting a lesser end-organ responsivity to adrenergic stimulation [62]. Thus, there seems to be good reason to try one or another form of relaxation therapy with many patients. There seems to be little to lose and perhaps a great deal to gain, although short-term effects may not be maintained, and continued surveillance is needed. EXERCISE
Many people are walking, jogging, and performing various other exercises in hopes of achieving various goals related to cardiovascular fitness. A reduction in elevated blood pressure may be one of these goals [63]. Although there is no good evidence that this will happen, there seems to be no reason to curtail reasonable isotonic exercise in patients with mild to moderate hypertension. In particular, in hypertensive adolescents a significant lowering of blood pressure may be achieved by exercise [64]. On the other hand, isometric exercise may be harmful. During isometric or static exercise-pushing, pulling, lifting-both the diastolic and systolic pressures and heart rate increase in response to reflexes that abruptly withdraw vagal tone and increase peripheral resistance [65]. MODERATION OF ALCOHOL CONSUMPTION
The blood pressure appears to increase slowly but progressively with the intake of increasing amounts of alcohol, with an average increase of 2 mm Hg in diastolic levels noted among those who consumed an average of 30 ml a day of ethanol [66]. Those who drink more than an average of 1 oz a day of ethanol may have significant increases in blood pressure that will usually come down very quickly when they stop drinking [67]-unless the patient experiences alcohol withdrawal symptoms that may provoke a marked pressor response [68]. On the other hand, there is convincing evidence that the intake of 1 to 2 oz of ethanol a day will protect against coronary heart disease, possibly by the increase in cardioprotective high density lipoprotein-cholesterol levels that accompany the intake of ethanol [69]. Thus the likely protection against coronary heart disease may outweigh the potential harm of a 2 to 4 mm Hg increase in blood pressure that is usually seen with regular intake of 1 to 2 oz a day of ethanol.
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The wisest course may be to advise the hypertensive patient to stop all ethanol intake for a few weeks to observe the effect of abstinence. Thereafter, the patient may be advised to consume no more than 1 oz of ethanol a day, that is, 2 oz of 100-proof spirits, 8 oz of wine or 24 oz of beer. If the blood pressure does not increase significantly, the regular consumption of such moderate amounts of ethanol may be condoned since it may do more good than harm. But all should be warned about the dangers of heavier alcohol intake beyond 3 oz a day, which may not only damage the liver and brain but also raise the blood pressure considerably.
SUMMARY Non-drug therapies should be tried with all patients. They will reduce the blood pressure of many hypertensive subjects, in some to a level that is safe enough to eliminate the need for drug therapy. Those patients with mild hy-
pertension may thereby be able to stay off drugs, and those with more severe hypertension may need less medication. At least part of what appears to be an antihypertensive effect of these non-drug therapies may be attributable to the "natural" fall in blood pressure seen when repeated readings are taken. Such decreases may reflect a statistical regression toward the mean, a placebo effect, or a relief of anxiety and stress with time. The phenomenon is probably responsible for much of the initial response to drug therapy as well, so both drugs and non-drugs may be given credit not deserved by either. Although it is true that many patients will not adhere to non-drug therapies, remember that poor compliance is also a major problem with drug treatment. The same techniques known to improve compliance to drug therapy should be used with non-drug therapies: a gentle seduction, not a massive onslaught.
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