Weight reduction in the management of hypertension: Epidemiologic and mechanistic evidence

Weight reduction in the management of hypertension: Epidemiologic and mechanistic evidence"

EFRAIW WEISIN Department of Medicine, Nepkzrology Section, Louisiana State University School ofMedicine, 1542 Tulane Avenue,

New Orelam, LA, U.S.A. 70112

Received August 1, B 985

REISIN, E. 1986. Weight reduction in the management of hypertension: Epidemiologic and mechanistic evidence. Can. S. Physial. Phmacol . 64: 818-824.

A number of studies have established a close association between increased body mass and elevated blood pressure. The presence of obesity in hypertensive subjects is associated with some hemdynamic, metabolic, and endocrinic characteristics: an increased intravascular volume with a high intracellular body watertinterstitial fluid volume ratio, increased cardiac output, stroke volume, and left ventricular work while peripheral resistance was reduced or normal. Weight Ioss of at Beast 10 kg can reduce blood pressure independently of changes in sodium intake in obese persons of both sexes with mild, moderate, or severe high blood pressure. The fall in arterial pressure in obese hypertensives after weight loss may reverse many of the previously mentioned altered findings and underscore previous epidemiological studies that Rave shown that weight control could be an important measure in the treatment of hypertension.

REISIN, E. 1986. Weight reduction in the management of hypertension: Epidemiologic and mechanistic evidence. Can. J. Bhysiol. Phmacol . 64: 818-824.

Plusieurs Ctudes ont Ctabli une Ctroite association entre l'augmentation de la masse eorporelle et l'dldvation de Ia pression sanguine, La presence d90Msitd chez les sujets hypertensifs est associee 3 certaines caractdxistiques hCmodynamiques, mdtaboliques et endocrines: m e volume intravasculaire accrQ avec un rapport ClevC du volume eau corporelle intracellulairet liquide interstitiel, une accroissement de ddbit cardiaque, volume systolique et travail ventrjiculaire gauche alors que la rdsistance piriphkrique etait rkduite ou n o m l e . Une p r t e de poids d'au moins 10 kg peut rdduire la pression sanguine indkpendament des variations d9absorption de sodium chez les prsonnes ob&ses des deux sexes avec hypertension xtkrjielle lCg$re. moddrke ou skvkre. La chute de pression auterielle chez Ies hypertensifs ob&ses apr&s une perte de goids peut renverser plusieurs des alterations preckdement rnentionnkes et renforcer des etudes CpidCmiol~giques antkrieures ayant mcswtr6 que le contr6le du p i d s pouvait Ctre une mesure importante dans le traitement de 19hypertension.

[Traduit par la revue]

Hypertension and obesity are two directly related pathologi- cal disorders at any age; in childhood, adolescence, and adult- hood (Kannel et al. 11976; Stamler et al. 1978; Epstein 1965), and subjects who gain weight as they get older are at greater risk of being hypertensive (Levi et al. 1946; Kannel et al. 1976; Hsu et al. 1977; Wabkin et al. 1977). Metabolic, endocrinologic, and hernodynamic changes are the previously described meehan- isms used to explain the increase of blood pressure in the obese population (Mann 1974). Consequently the effect sf weight loss in the reduction of blood pressure must be explained based on two different sets of evidence: epidemiologic and mechanistic, which will be discussed in this article.

Epidemiologic evidence Benedict and Woth (1918) first discussed the potential role of

weight control in the reduction of blood pressure in a group of 25 nomotensive subjects, and he showed that a 10- 12% weight loss produced a significant blood pressure drop in 56% of the subjects studied. In the review published by Chiang et al. (19691, 15 of 17 reports demonstrated a reduction in arterial pressure after weight loss. The studies reviewed by those authors included womotewsive or mild hypertensive subjects. Most of these earlier publications showed a considerable weight reduction of more than 10 kg, and two studies (Adlersberg et al. 1946); Fellows 1831) had a long follow-up of 4 and 5 years. Chiang summarized all this previous experience, considering that a more consistent reduction was obtained for systolic than for diastolic blood pressure in obese women with mild to moder-

pr his paper was presented as part of a workshop on Nutritional Management of Hypertension: Controversies and Frontiers, September 6-7, 1985, Harrison Mo% Springs, B .C., Canada.

ate hypertension after a substantial and prolonged weight loss and in combination with salt restriction. Sodium intake, however, was not reported, or was low in each of those studies (Chiang et al. 1969).

One of the main reasons for failure to accept the idea that weight reduction has a causal role in the reduction of high blood pressure has been the claim that the effect of caloric restriction on arterial pressure is mainly due to the concurrent reduction in sodium intake QDAl et al. 1958; Dahl 1972; Paijs et al. 11973). Dahl(1972) observed that most investigators found reductions in blood pressure during the first week of caloric restrictions, before significant weight was lost, and he attributed the effect to reduced sodium ingestion. He and his co-workers has attempted to evaluated the effect of weight loss on high blood pressure in eight human beings by keeping salt intake within the nomal range. They showed that the fall in pressure during the weight reduction program resulted from sodium restriction rather than caloric restriction (D&l et d. 1958). In two of these eight patients, however, blood pressure levels were Iswered coneorn- itant with weight loss. Based on all these experiences, some authors claim that the effect of weight loss ow arterial pressure is small, and that it cannot serve as a substitute for drug therapy (Gifford 19741, or that it is an improbable adjunct to effective therapy (Mann 1974). In an earlier report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (1980) weight control was mentioned only as a part of the treatment of persons with uncomplicated mild hypertension and no additional cardiovascular ksk factors.

We reported previously (Reisin et al. 1978) the relationship of weight reduction to blood pressure in a controlled study in which salt intake was not restricted. In this group sf patients, in spite of a drastic reduction in calories, sodium intake was maintained at

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165 * 52 mquiv./day. Two months after the hypocalorie diet was stated, the blood pressure levels of 75% of the 24 patients treated with hypocaloric diet only =turned to normal. In the second folow-up period 8-12 months after the hypocaloric diet and with weight reduction maintained at similar level, 52% of the patients maintained normal b l d pressure levels (140190 d g or less; 1 d g = 133 Pa) (Reish and Frohlich 1982). The weight reduction obtained on these two follow-up periods were 9.5 and 12.5 kg, respectively, and they were accompanied by a highly significant reduction in pressure, thereby demon- strating that weight control can be a major factor in treating hypertension in overweight patients. A second group of 57 obese hypertensive patients was treated with hypocaloric diet, but those patients were receiving concomitant regular antihypertensive therapy which had previously been inadequate to control their blood pressure. Two months after the initiation of the diet and when the weight reduction averaged 9.8 kg, the blmd pressure of 6 1 % of patients returned to normal. In the second follow-up 8-12 months after the end of the dietary intervention, 86% of the patients who maintained with weight reduction had normal levels of blood pressure. 'khe remaining 26 patients in our study, receiving antihypertensive medication previously inadequate to control their high blood pressure levels, were considered a control group and did not receive dietetic advice. At the end of the first follow-up period of 6 months all of them remained with unchanged weight and high blmd pressure.

These two studies sumarized the positive and long effect of weight reduction independent of sodium restriction in a large number of patients with mild to severe hypertension and with an initial overweight of more than 20%. Our data indicate that a considerable drop in blood pressure does occur as a consequence of a partial but substantial reduction in the original overweight. We have abolished in our study the previously recognized effect of sodium restriction on the blood pressure by encouraging our patients to maintain a relatively high sodium intake, despite the caloric restriction. We dso have differentiated the effect of caloric restriction from the positive effect of weight reduction, by measuring the final blood pressure for a period of 2-18 months after the caloric restriction diet was discontinued, and with a statistically significant weight reduction maintained. Some of our patients were also treated with antihypertensive drugs during the study period; the possibility that the reduction in blood pressure in those patients was merely due to a better drug compliance was analyzed in our study, and refuted by the similarity sf response in patients treated with diet only, or with diet and a previous unsuccessful drug treatment. The third group of patients, not on a dietary program but receiving antihypertensive drug therapy, served as a control to those patients treated with diet and antihypertensive drugs; the control group did not have any significant changes in their b l d pressure despite a similar follow-up. The result in this group underscores our conclusion that weight control is a potent tool in the control of hypertension in overweight subjects and that weight control migh complement the chug treatment in a considerable part of the hypertensive population (Reisin et al. f 9'78).

Other questions also remain as to what extent the reduction in blood pressure may be accounted for by reduced arm circumfer- ence or familiarity with the procedure used to measure arterial pressure- These possibilities were considered in previous works (Reisin et al. 1983; Raison et al. 1983), in which the decreases in arterial pressure obtained with weight reduction were measured directly by intra-arterial technique, or in which a group of control patients also familiar with the follow-up procedure? but

without changes in weight, did not show any change in blood pressure (Reisin et al. 1983).

Since our first study, other investigators have confirmed the effectiveness of weight reduction independent of salt restriction in the control of hypertension (Tuck et al. 1981; Gillum et al. 1983; Raison et al. 1983; Maxwell et d. 1984; hngford et al. 1985; Macklahon et d. 1985).

Tuck and co-workers (1981) used a low caloric diet for a period of 12 weeks in 25 obese hypertensive patients, 66% or more over the ideal weight. The patients were randomly divided in two groups according to the sodium intake that was either medium (120 mequiv.124 h) or low (40 mequiv.124 h). The average weight reduction obtained was more than 28 kg. Reduc- tion in systolic and diastolic pressures were statistically significant, the reductions were similar in both groups of patients regardless of which sodium diet they followed, and a positive correlation was found between reduction in body weight and arterial pressure in both groups. Acording to Tuck and co-workers (1981) a 10-30% reduction in weight from a previous 63.44% overweight appeared to be sufficient to lower blood pressure. The weight reduction was obtained under a constant sodium intake and a continuous monitoring of sodium urinary excretion.

Maxwell and co-workers (1984) studied the effect of caloric restriction or caloric and sudium restriction diet in a group of 38 obese hypertensive patients followed up for a period of 12 weeks. They concluded that after an initial reduction in blood pressure attributable to negative sodium and water balance, the further blood pressure reduction was produced by an average weight loss of 23 kg. This study was a prospective and randomized design that evaluated the effect of weight reduction with and without sodium restriction, and like the S U ~ J ~ C ~ S in the study published by Tuck et al. (198 I), the population studied had an initial overweight of at least 20% and a mild hypertension.

Both investigators showed a continued pattern of blood pressure decrease during the 12-week study period, a pattern that according to the authors is similar in an analysis, still unpub- lished, of several hundred patients (Maxwell et al. 1984). They did not, however, measure blood pressure after discontinuation of the diet, a procedure necessary for differentiating between weight reduction and caloric restriction effect on blood pressure.

GiIlum et d. (1983) studied a randomized group of obese white men with borderline hypertension treated with caloric restriction and regular sodium intake for a period of 10 weeks, of sodium restrictions and normal caloric intake for a similar period. This study used a careful and randomized design to evaluate the alternate effect of weight reduction and sodium restriction in mild hypertensives. The blood pressure reduction was statistically significant after weight reduction or a sodium restriction, and the effect on blood pressure of the two dietetic approaches appeared to be additive. The population included only white men; therefore a generalization of these previous results to blacks, women, or to moderate-to-severe hypertensives should be cautious, according to the authors.

Langford and co-workers (1985) studied 325 obese patients (20% overweight) formerly receiving antihypertension therapy for at least 5 years. The therapy was withdrawn in those subjects and replaced by sodium restriction (161 subjects) or weight reduction (89 patients). The results were compared with those of two other groups of patients whose drug therapy was also withdrawn but no change made in their diet (89 patients) or who continued on drug therapy (48 patients). The different groups

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820 CAN. B . BHYSIOL. PHARMACOE. VOL. 64, 1986

studied included patients aged between 56 and 59 yeas, most of them black (62-75%) and women (59-69%). The participants in the weight reduction program lost an average of 4.5 kg after 1 yea follow-up and more than 60% of them remained off medication and nomotensive, but only 35% of the control subjects remained untreated and with n o m d blood pressure. The authors concluded that the most consistent results were in the weight reduction progrm, and when both nutritional changes (weight and sodium restriction) were used the success rate increased for previously treated participants who have with- &awn from therapy with antihypertensive medication. This study was the first one to show the positive effect of weight reduction on the black hypertensive population and the success rate was calculated 1 year after the initiation of the program, when the exclusive effect on the blood pressure of weight reduction a d not caloric restriction was considered.

In a recent publication MacMahon and co-workers (1985) filled an important gag in the series of studies ghat underscore the positive effect of weight loss on blood pressure reduction. In a randomized control trial of 56 obese mild hypertensive patients, results with weight reduction were first compared with results with a dmg intervention (metoprolol 200 mg daily) and a placebo group. After a weight reduction of more than 4 kg was obtained, the systolic/diastolic pressure fell significantly 6 13/80 m d g , p < 0.8CB1/0.04)1). The changes in the systolic pressure in patients after weight loss was greater than in those treated with placebo medication ( p < O.OOl), but did not different from the changes in patients treated with metoprolol (- 18 md-lg). The changes in diastolic pressure in patients who lost weight were significantly greater than the changes obtained with both the metoprolol or placebo medication. These changes are easily interpreted; when using the mechanistic evidence it can be shown that weight loss decreased cardiac output without chang- ing the vascular peripheral resistance and in consequence reduces diastolic blood pressure (Reisin et al. 1983). As is well known, metoprolol decreases cardiac output but increases the vascular peripheral resistance, increasing the diastolic blood pressure (Stenberg et al. 1975). The sodium intake of the study group on hypocaloric diet (1000 kcal) (1 kcal = 4.89 H), however, was not evaluated and the patients probably have a sup~mposed effect of sodium restriction to the weight loss.

Two of the weight reduction studies discussed earlier (Reisin et al. 1978; Tuck et d. 1981) were analyzed together with other nonphmaco%sgical approaches such as muscle relaxation, yoga, exercise, salt restriction, meditation, and biofeedback, md results were compared with those of placebo or drug studies using the meta-analytic technique, in which the effects of treatment are expressed as an effect size calculated from differences between mean arterial pressure in treated and control group, standardized by the variability of the blood pressure in the control group (Andrews et al. 1982). This study concluded that "when reduction in mean blood presure was defined as at least 10 g, 3 months after treatment, three of the nonpmacological approaches - weight reduction, yoga, and muscle relaxation - were the only effective nondmg interventions." The authors considered that the quality of rese'ach in the 13 studies of these treatments was high and '6seems highly improbable that the demonstrated benefit would be an mifact or either publication bias or undetected type B emor" (Andrews et al. 1982).

Hovell (1982) analyzed the results of studies involving 2% interventions in which weight loss was used as a treatment of essential hypertension. Those studies were reviewed and rated

for measurement and experimental design quality. The authors concluded that no study is perfect, but one, our study (Reisin et al. %9"98), was the best among the interventions reviewed.

Only two studies contradicted the positve effect of weight loss on high blood pressure reduction (Haynes et aI. 8984; Fagerberg et al. 1984). One of these works is extensively discussed in the present issue md included mild overweight patients (over 10%) in part nomotensive (diastolic blood pressure 85-89 mmHg) mixed in one group with mild hypertensives (diastolic blood pressure 90-95 r n d g ) . The weight reduction obtained by 363 patients after a prolonged period on hypocaloric diet was meaningful (4 kg) and the blood pressure of those patients failed to fall significantly. The blood pressure measurements used for statistical calculation were obtained in a single visit at a clinic "entry blood pressure9' and at home "end of study b l d pressure." The effect of between-visit variability are more probably mixing a nomotensive with a mild hypertensive population. These results, I believe, reflect the negative effect of a meaningful weight reduction in a population only 10% over the ideal body weight, and with high normal or doubtful mild hypertension (90-95 m H g ) , rather than as the authors concluded, to refute the effective and valuable effect of weight reduction in the mild to severe hypertensive population.

The second work published by Fagerberg et al. (2984) studied the separate and combined effect of caloric and sodium restriction on the regulation of blood pressure in 30 obese patients 28% or more overweight and with mild essential hypertension. The authors concluded that 15 patients, with caloric restriction lost an average of 8 kg in body weight, and their systolic/diastolic blood pressures were only slighly but not significantly reduced

g). The second group of patients also lost an average of 8 kg in body weight but were also maintained with a moderate reduction in sodium intake 89. mmol/24 h and their systolic/diastolic blood pressure fell significantly ( - 71 - 7

g). This study is more complete than the previous one. The authors also studied some mechanistic changes and found a singiffcant fall in urinary noradrenaline excretion in b t h groups of patients following the caloric and sodium restriction diet. These sympathetic changes will be discussed in the present article when, the mechanistic evidence is reviewed. The high alcoholic intake in the population studied by Fagerberg et al. is particularly disturbing because sf the possible effects of alcohol on blood pressure. The population studied was obese with mild hypertension. The initial and final blood pressure measurements were done in only one entry and final visit, and as in the previous study the effect of between-visit variability could be confusing norno- with mild hyper-tensive patients. When the intra-arterial pressure was considered, the slight decrease in diastolic press- we -5 m d g ) was not statisicdly significant in the group of subjects treated with low caloric diet, but with weight reduction

tolic pressures of those patients have normalized (85 In conclusion9 the last two studies failed to show an

effective reduction in blood pressure in obese hypertensive patients, however, the small number of subjects studied, the inclusion of only mild hypertensives, diagnosis based on only one clinic visit, and some patients with relatively high alcoholic intake limited conclusion to a small and specific group of patients rather than refuting findings previously published by others in the two sexes and in obese patients with mild to severe high blood pressure.

In view of some of these previously mentioned publications, the 1984 report of The Joint National Committee on Detection, Evaluation md Treatment of High Blwd Pressure agrees that

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weight reduction often results in a substanial decrease in blood TABLE 1 . Physiopathological r n m h i s m s involved in obesity-hypr- pressure, even if the ideal body weight is not achieved, md tension, effect s f weight reduction recommends the use of nonph acological approaches, such as weight control, as definitive intervention amad as an adjunct to Obesity- Weight chug therapy in obese hypertensive patients. Endocrine-metabolic mechanismsa hypertension reduction

Mechanistic evidence Previous investigations have suggested various mechanisms

to explain the simultaneous fall in arterial pressure and body weight. (See Table 1 .) Some studies have described adrenergic, metabolic, and endocrinic factors that change daKing low caloric diet (Dole et al. 19563; Dole et al. 195 1 ; D&E amad Love 1954; Dahl et al. 1954; D&l et al. 1958; D&1 1972; Young and Landsberg 1977a, 1977b; Landsberg and Young 1978; Jung et al. 1979; Tuck et d. 198 1 ; Behaven et al. 1980; BeFronzo et al. 197%). Other authors have explained the effect of weight reduction on obese hypertensive patients on the basis of alterations in the fluid volume distribution and hernodynamic changes (Alex- ander et al. 1972; B a c h m et al. 1979; Weisin et al. 1983; Raison et al. 1983).

Na' intake Na'-K' ATPase activity

1' 3. 3.

Adrenergic activity Plasma renin activity

'r I o r OH+

Plasma ddostemne levels -+ 4 or + Plasma insulin csneentration 1' 3. Fluid compartmental and hernodynamic

Intravaseular voolarme Cardiopulmonary blood volume

? 3. 'r 3.

Plasma volumelirmterstitid Wuid volume -+

Intracearllar fluid volumeltotal T

body water Cardiac output

T o r $ o r - +

Total vascular peripheral resistance -+ 4

k f t ventricular strake work ? 1 Enedoc~-iare-me~kpbo&icfa~to~~

The role of the sympathetic nervous system in the metabolic adaptation to fasting has been described previously in animal and clinical studies (Young and Landsberg % 977a91977b, 1978; Eandskrg md Young 1978; June et all. 1979). Suppression of the sympathetic newous system in fasting rats reduces cate- cholamine release from the sympathetic nerve ending or adrenal medulla. This reduction could suppress renal renin release and may therefore partly explain the relationship between the blood pressure reduction and hypocaloric diet (Young and Landsberg 1977~). Confirming these animal studies, Sung et al. (1979) found, in obese nomotensive women on hypocaloric diet with a constant sodium intake, a significant fall in systolic and distolic pressures indicated by a concomitant fall in plasma noradrenaline concentration. Tuck and co-workers (1981) showed in obese hypertensive patients a 563% reduction in levels of plasma mnin activity and a lower but statistically significant decrease in plasma aldosterone level. Those results were explained on the basis of the diminished sympathetic-nehvous-system activity observed in the obese hypertensives during stmation or weight reduction, sympathetic activity that is considered one of the factors regulating the renin release (Davis and Freeman 1976). On the contrary, in one study from our laboratory, weight reduction produced only minor changes in the plasma renin activity, but decreased the levels of norepinephrine. Such changes suggest a lesser adrenergic input involved in the reduction in arterial pressure after weight loss (Weisin et al. 1983).

The relationship between sodium and blood pressure regulation is complex; however, over the past years new studies have emerged with renewed approaches (Laragh md Sealey 1973; Tobian 1972; Opakl and Haber 1974). In normal men, in a sodium-depleted state with activation of the renin angiotensin system, both the systemic pressor responses and renal b l d flow changes become less sensitive to the effect of exogenous mgiotensin 11. In contrast, during salt loading, suppression of the renin-level mgiotensin 11 increases (Hollenberg et a1 . 1974; Hollenberg et al. 1972; Laragh and Sealey 19731, suggesting that in the sodium-depleted state vasconstriction is the predom- inant factor in the control of blood pressure, whereas in the salt-loaded state, volume is more important. Based on this argument, the hypertensive obese patient is characterized by a salt-loaded hypervolemic status.

"Mechmisms: increased, f ; decreased, ; unchanged, -9; not investigated, ?.

Dahl and co-workers (1958) attributed the decrease in merial pressure of obese hypertensive subjects after a drastic reduction in weight to the concomitant decrease in dietary salt. A more recent study showed that a moderate sodium restriction (60-88 mequiv./day) reduced mean supine mer id pressure of essential hypertensive patients (Maceregor et al. 1982). During the first week of fasting, subjects in sodium balance experience a nat- riuretic phase; however, if fasting is prolonged, this phase is followed by a sodium-conservation phase (Boulter et d. 1973). Thus, the decrease in sd t intake concomitant with a low caloric diet is one of the factors responsible for lowering arterial pressure. When these two factors were separated, however, and a high sodium intake was maintained, the fall in arterial pressure was still evident, indicating that other factors together with reduction in salt intake may be implicated in the fall of arterial pressure after weight loss (Reisin et al. 1978; Reisin et aH. 1983; Tucket al. 1981; Raison et al. 1983).

Hypertension and obesity are generally associated with im- paired glucose tolerance and nondependent diabetes (Medalie et al. 1975; Jarret et al. 1978; Bmet-Connor et al. 198 B ; Modan et d. 1985). Deprivation of f w d or carbohydrate restriction, on the other hand, reduced plasma insulin concentration within a day, and this reduction was explained by an increase in insulin receptor numbers and increased affinity of the receptor for the insulin (Grey and Kipinis 197 1 ; Bar and Roth 1977; Angel and Roncari 1978). The hyprinsulinemia in the obese, according to kFronzo (1981), produces an increased renal sodium reten- tion. The link between obesity and hypertension is explained on the basis of three theories: (1) tissue insulin resistance alters the internal sodium and potassium distribution and produces increased peripheral vascular resistance; (2) the hyperglycemia that accompanies hyperinsulinemia may increase peripheral vascular resistance by increasing intracellular osmolality through enhanced positive diffusion of glucose; and (3) the insulin has a stimulatory effect on the sympathetic venous system that leads to hypertension (Smet et al. 1978; Voors et al. 1981; Winquist et al. 1982; Christensen 1983; Friedman 1983). Nevertheless, studies showing the causal effect sf reduced insulin concentration on obese hypertensive patients remain lack- ing.

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822 CAN. J . BHYSHOL. PHARMACOL. VOL. 64, 1986

Changes in intravascular and extraceNukar.fluid volume In conclusion, most of the circulatory alterations associated h v i o u s studies on obese hypertensive patients have shown

an absolute increase in plasma and total blood volume (Alexan- der 1963; 1964; Backman et al. 1973; Reisin et al. 1983); however, others have shown that the intravascular volume may be normal if it is calculated by deviation from deskable weight or ideal weight (Messerli et al. 198 1).

After weight loss, intravascular fluid volume was found to decrease significantly in nomotensive and hypertensive patients (Alexander and Peterson 1972; Backman et al. 1979; Reisin et d. 1983; Raison et al. 1983). Alexander and Peterson (1972) reported that in nine grossly obese nomotensive and hypertensive patients, after a prolonged period of weight reduction the average total blood volume fell from 7.8 to 6.1 L (g < 0.25). B a c h a n et al. (1979) found similar changes in 22 extremely obese nomotensive patients, after weight reduction following jejunoileostomy. We reported earlier that in obese hypertensive patients, moderate weight reduction ( + l o kg) produced a decrease in total and central cardiopulmonary blood volumefrom5.7 to5.1 L ( p < 0.01)andfrom2.5 to2.3L(g < 0.0 I), respectively. These differences, however, were abolished when the results were expressed as total and central blood volume related to body weight (Weisin et d. 1983). These findings might be related to the lack of definition of appropriate indices to express hemodynamic values for patients having different body weights (Reisin et al. 1983). Raison and co- workers (1983) showed that the plasma volume/interstitial fluid volume and the intracellular fluid volume/totd body ratios significantly increased after weight loss, changes that they considered to express a shift of fluid volume from the intracellular to the interstitial space.

Hemdp~namie changes B a c b m et d. (1973) and Alexander et al. (1962) showed

that end-diastolic volume of both ventricles is increased in obesity. Alexander therefore suggested that obesity represents a "high-output state" that may result ultimately in the development of congestive heart failure. In contrast, Backman suggested that increased circulatory volume can contribute to the raised filling pressures, but it is unlikely that decreased ventricular compliance and (or) impending cardiac failure are the major reasons for the increased end-diastolic volume. Total peripheral resistance was normal (to Bow-normal) in obese patients, and it remained unchanged after weight reduction. In one hypertensive overweight patient, however, the total peripheral resistance was reduced after weight loss. After weight reduction the average total blood volume fell by 1 -7 E, but only 0.42 L of this mount was expressed in relation to lean body mass. When blood volume was expressed in terns of body weight (in kg), however, it increased from 50 to 6 1 mL (Alexander et al . 1962).

The ventricular distention reported by Alexander was demonstrated roentgenographically and by indirect evidence of decrease in left ventricular cavity dimensions. Totd body oxygen consumption (as indicated by arteriovenous oxygen difference) decreased (58%) after weight reduction, and heat rate and stroke volume decreased in 60% of the patients (Alexander et al. 1962).

B a c h a n and co-workers (1979) reported their experience with a group of 22 morbidly obese nomotensive patients 2 yeas after jejunoileostomy . Associated with an average weight loss of 58 kg were the following reduced indices: oxygen consumption, cardiac output, left ventricular stroke work, heart size, and systemic arterial pressure. These reductions were unaccompa- nied by any change in total peripheral resistance.

with marked obesity seem to be reversible with weight loss. Thus, the reduced M y oxygen uptake appears to reflect a decreased metabolic demand associated with loss of tissue mass and circulatory blood volume.

In an earlier publication we described that a relatively small reduction in weight (2 10 kg), regardless of sodium intake, in obese hypertensive patients produces falls in cardiac output, left ventricular stoke work, and mean inka-arterial blood pressure without changes in total peripheral resistance (Reisin et al. 1983), findimgs that were confirmed by other authors (Raison et al. 1983; Achimastos et al. 1984).

ConcHusions An association between overweight and hypertension is a

consistent epidemiological finding, at any age, sex, or racial origin, and subjects who gain weight as they get older are at greater risk of k i n g hypertensive. Early studies have shown a reduction in merial pressure after weight loss; however, the concurrent effects of caloric and sodium restriction were con- fused with the positive effect of weight loss on blood pressure. Since 1978 several authors have confirmed the effectiveness of weight reduction in the control of hypertension; this effect was independent of sodium restriction but required a weight reduction of at least 10 kg. The effect has been proven in both sexes, in whites and blacks, in patients with mild to severe hypertension, and in subjects with an overweight of 20% or more over the ideal body weight. When the weight reduction was maintained, according to our study the control of blood pressure remained effective in some of the patients for at least 18 months after the end of the caloric restriction diet. Apparently, weight reduction, even if partial, was more effective in the obese patients with moderate to severe hypertension than in those with mild or high normal levels of blood pressure. Two recent studies that have failed to show a reduction of blood pressure have used mild hypertensives probably mixed with nomotensive subjects, and one group of authors obtained only a meaningful weight loss (4 kg) in their study population, which probably explained their failure to obtain a blood pressure reduction.

The mechanistic evidence that explains the effect of weigkt loss in the reduction of blood pressure is based in the presence of some hemodynamic endocrine and metabolic characteristics in the obese hypertensives, reversed by weight loss. After weight reduction, intravascualr fluid volume was found to decrease significantly and apparently a shift of fluid volume from the intracehlular $0 the interstitial space has also occurred. The "high-output state" described in the obese hypertensive patients is reversed with weight reduction, but the total peripheral resistance remained unchanged, explaining from the hemodynamic p i n t of view (blood pressure = cardiac output x total peripheral resistance) why blood pressure is reduced after weight loss.

A state of reduced akenergic cxdiovascuIar input produced by weight loss has been suggested as a very strong mechanistic evidence to explain the importance of weight control in the treatment of hypertension. The effect on blood pressure of the two dietetic approaches (caloric and sodium restriction) appeared, according to some studies, to be additive.

ACH~MASTOS, A., I. H. RAISON, I. A. LEVENSON, and M. E. SAFAW. 1984. Adipose tissue cellularity and hemodynamic indexes in obese hypertensive patients with hypertension. Arch. Intern. Meel. 144: 265 - 268.

ADLBRSBERG, D., H. W. COXHER, and J . LAVAL. 1946. Effect of weight reduction on course of arterial hypertension. J . Sinai Hosp. N.Y. 82: 984-992.

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ALEXANDER, J. K. 1963. Obesity and the circulation. Mod. Concepts Cardiovasc. Dis. 32: 799-803.

1964. Obesity and cardiac performance. Am. J. Cardiol. 14: $60- 865.

ALEXANDER, J. K. K. H. AMAD, and V. W. COLE. 1962. Observations on some clinical features of extreme obesity, with particular refer- ence to cardiorespiratogy effects. Am. J. Med. 32: 5 12-523.

ALEXANDER, J. K., and K. L. PETERSON. 1972. Cardiovascular effect of weight reduction. Circulation, 45: 3 10-3 18.

ANDWEWS, G., S. W. MACMAHON, A. AUSTIN, and D. 6. BYRNE. 1982. Hypertension: compavison of drug and non-hg treatments. Br. Med. J. 284: 1523-1526.

ANGEL, A., and D. A. M. RONCAIPP. 1978. Medical complication of obesity. Can. Med. Assoc. J. 119: 1488- 841 1.

BACKMAN, L., V. FREYSGHUSS, D. HALLBERG, and A. MELCHER. 1973. Cardiovascular function in extreme obesity. Acta Med. Scad. 1 9 3 437-446.

1979. Reversibility of c~iovascular changes in extreme obesity. Acta Med. Scand. 205: 367-373.

BAR, R. S., and J. ROTH. 1977. Insulin receptor studies in disease states of man. Arch. Intern. Med. 037: 474-48 1.

BAWRET-CONNOR, E., M. H. CRIQUI, M. K. KLAUBER, and M. HOLDBRWK. 198 1. Diabetes and hypertension in a community of older adults. Am. J. Epidemiol. 113: 276-284.

BENEDICT, F. G., and P. ROTH. 191 8. Effect of a prolonged reduction in diet on twenty-five men. Prm. Natl. Acad. Sci. U.S.A. 4: 149- 158.

BQULTER, P. R., R. F. SPARK, and R. A. ARKY. 1973. Dissociation of the renin aldosterone system and refractoriness to the sodium retain- ing action of minerdocorticoid during starvation in man. J. Clin. Endocrinol. Metab. 38: 248-254.

CHIANG, B. N., L. V. ~ W L M A N , and F. M. EPSTEIN. 1969. Qver- weight and hypertension. A review. Circulation, 39: 483-4143.

CHRISTENSEN, N. J. 1983. Acute effects of insulin on cardiovascular function and noradrenaline uptake and release. Diabetologia, 25: 377-38 1.

DAHL, L. K. 1972. Salt and hypertension. Am. J. Clin. Nutr. 25: 23 1-24.

DAHL, L. K., and R. A. LOVE. 1954. Evidence for relationship between sodium (chloride) intake and human essential hypertension. Arch. Intern. Med. 94: 525-531.

DAHL, E. K., L. SILVER, and R. W. CHRISTIE. 1958. Role of salt in the fall of blood pressure accompanying reduction of obesity. N. Engl. J. Med. 258: 1186-1192.

BAHL, L. K . , B. G. STALL 111, and G. C. COTZIAS. 1954. Metabolic effect of marked sodium restriction in hypertensive patients: changes in total exchangeable sodium and potassium. J. Clin. Invest. 33: 1397-1406.

DAVIS, J. E., and R. H. FREEMAN. 1976. Mechanism regulating renin release. Physiol. Rev. 56: 1-56.

DEFRONZO, R. A. 1981. The effect of insulin on renal sodium metabolism: a review with clinical implication. Diabetdogia, 21: 165- 17 1.

DEFRONZO, R. A., R. A. COOKE, R. ANDRES, G. R. FALOONA, and P. J. DAVIS. 1975. The effect of insulin on renal handling of sodium, potassium, calcium and phosphate in man. J. Clin. Invest. 55: 845-855.

DEHAVEN, J., R. SHERWIN, R. HENDLER, and P. FELIG. 1980. Nit- rogen and sodium balance and sympathetic-nervous system activity in obese subjects treated with a low-caloric protein or mixed diet. N. Engl. J. Med. 302: 477-482.

DOLE, V. P., L. K. DAHL, G. C. COTZIOS, H. A. ELDER, andM. E. UEBS. 1950. Dietary treatment of hypertension: clinical and metabolic studies of patients on rice-fruit diet. J. CBin. Invest. 29: 1189-1206.

DOLE, V. P., L. K. DAHL, G. C. COTZIAS, D. D. DZIEWIATKOWSKI, and C. HARMS. 195 1. Dietary treatment of hypertension II. Sadium depletion as related to therapeutic effect. J. Clin. Invest. 30: 584- 596.

EPSTEIN , F. H . 1965. RevaIence of chronic disease and distribution of

selected physiological variables In a total community of Tecumsek, Michigan. Am. J. Epidemiol. 81: 307-322.

FAGERBERG, B., 0. K. ANDERSON, B. ISAKSSBN, and P. BJORNTOW. 1984. Blood pressure control during weight reduction in obese hypertensive men: separate effects of sodium and energy restriction. Br. Med. J . 228: 11-14,

FELLOWS, H. A. 193 1. Studies of relatively nomal individuals during and after dietary restrictions. Sm. J. Med. Sci. 181: 301-309.

FRIEDMAN, S. M. 1983. Monovalent and divalent ions in vascular tissue. Ann. Intern. Med. 98: 753-758.

GLFM~RD, P. W. 1974. Hypertension. A practical guide to medical management. The hypertension handbood. Merck, S h q and b h m e Inc., West Point, PA. pp. 83- 1 12.

GILLUM, R. F., R. J. RUNEAS, R. W. JEFFERY, D. R. JACOBS, P. J. ELMER, 0. GOMEZ, and H. BLACKBURN. 1983. Nonpharrmacologic- al therapy of hypertension: the independent effect of weight reduction and sodium restriction in overweight borderline hypertensive patients. Am. Heart J. 105: 128- 133.

GREY, N., and D. M. KIPNIS. 197 1 . Effect of diet compostion on the hypersulinemia of obesity. N. Engl. J. Med. 285: 827-831.

HAYNES, A. B., A. C. HARPER, S. R. COSTLEY, M. JOHNSTON, A. G. LOCAN, P. T. FLANAGAN, and D. L. SOCKETT. 1984. Failure of weight reduction to reduce mildly elevated blood pressure: a randomized trail. J. Hypertens. 2: 535-539.

HOLLENBERG, N. K., W. R. CHENITZ, D. F. ADAMS, and G . M. WILLIAM. 1974. Reciprocal influence of salt intake on adrend glommlosa and renal vascular responses to angiotensin I1 in nomal man. J. Clin. Invest. 53: 34-42.

HOLLENBERG, N. K., H. S. SOLOMON, andD. F. ADAMS. 1972. Renal vascular responses to angiotensin and norepinephrine in normal man. Ckc. Res. 31: 750-757.

WOVEEL, M. F. 1982. The experimental evidence for weight loss treatment of essential hypertension: a critical review. Am. J. h b l . Health, 72: 359-368.

HSU, P. H., F. A. L. MATHEWSON, and S. W. ROBBIN. 19'97. Blood pressure and body mass index patterns a longitudinal study. J. Chronic Dis .30: 93- 1 13.

JABRET, R. J., H. KEEN, M. MCCARTNEY, J. H. FULLER, P. J. S. HAMILTON, D. D. REID, and 6. ROSE. 1978. Glucose tolerance and blood pressure in two population samples: their relation to diabetes mellitus and hypertension. J. Epidemiol. 7: 15-24.

JOINT NATIONAL COMMITTEE ON DETECTION, EVALUATION, AND

TREATMENT OF HIGH BLOOD PRESSURE. 1980. The 1988 report of The Joint National Committee on Detection, Evaluation and Treat- ment of High Blood Pressure. Arch. Intern. Med. 148: 1288- 1285.

1984. The 1984 report of The Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure. Arch. Intern. Med. 144: 1045- 1857.

JUNG, R. L., P. S. SHETTY, $/I. BARWAND, B. A. CALLINGHAM, and W. P. T. JAMES. 1979. Role of catechslmines in hypotensive response to dieting. Br. Med. J. 1: 12- 13.

KANNEL, W., N. BRAND, J. SKINNER, T. DAWBER, and P. MCNAMERA. 1976. Relation sf adiposity of blood pressure and development of hypertension: the Franingham Study. Ann. Intern. Med. 68: 48-59.

LANDSBERG, L. and J. Be YOUNG. 1978. Fasting, feeding and regulation of the sympathetic nervous system. N. Engl. J. Med. 298: 1295-1381.

LANGPOKD, G . H . , hf. D. BLAWFOX, A. QBERMAN, C. M. HAWINS, J. D. CURB, G. R. CUTTER, S. WESSERTHEIL-SINOLEER, S. PRESSEL, C. BABCOCK, J. E. ABEWNATHY, J. HOTCHKISS, and M. TYLER, 1985. Dietary therapy slows the return of hypertension after stopping prolonged medication. JAMA (J. Am. Med. Assoc.), 253: 657-669.

LARAGH, J. H. and J. SEALEY. 1973. The renin-angiotensin-aldcsster- one hormonal system and regulation of sodium, potassium and blood pressure homeostasis. Handbook of Physiology, Sect. 8. Edited by J. Orloff and R. W. Berliner. American Physio~ogica~ Society Press, Washington, DC. pp. 83 1-842.

Can

. J. P

hysi

ol. P

harm

acol

. Dow

nloa

ded

from

ww

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824 CAN. J. PHYSHQL. PHARMACOL. VQL. 64, 1986

LEVI, W. L., P. D. WHITE, md W. D. SHQUD. 1946. Overweight: a prognostic significance in relation to hypertension a d cadiovascu- %ar renal disease. J . Am. Med. Assoc. 131: 951-953.

M ~ c G m ~ o w , 6. A., F. E. BEST, J. M. CQNN, N. D. MAWKANBU, D. M. ELDER, G . A. SAGNELEA, and M. SQUIRES. 1982. Double blind randomized crossover trail of moderate sodium restriction in essen- tid hypertension. Lancet, 1: 35 1-354.

M A C ~ ~ A H O N , %. w., L. BERNSTEIN, @. J. MACDBNALB, G . ANDBEWS, R. B. BEWKET. 1985. Comparison of weight reduction with metoprolol in treatment of hypertension in young overweight patients. Lancet, 1: 1233-1252.

MANN, G. V. 1974. The influence of obesity on health. M. Engl. S. Med, 281: 178-185.

MAXWELL, M. H., T. KUSHIWO, L. P. %)BBNFELD, M. L. TUCK, and A. V. WAKS. 1984. B. P. changes in obese hypertensive subjects during rapid weight loss. Comparison of restricted vs. unchanged salt intake. Arch. Intern. Med. 144: 1581-1584.

MEBALIE, J . H., C. M. PAPIER, V. GOLDBOURT, md J. B. HERMAN. 1975. Major factors in the development of diabetes rnellitus in 10 000 men. Arch. Intern. Med. 135: 81 1-817.

M E S S E ~ I , F. H.. B. CHRISTHE, S. G. R. DECARVALMB, G. S. ~ S T H M U N O , D. W. SUAREZ, G. R. DRESLINSKI, and E. D. FROHLICH. 198 1. Obesity and essential hypertension: hemodyna- mics intravascdar volume, sodium excretion and plasma renin activity. Arch. Intern. Med. 141: 81-85.

MODAN, M., H. HALKIN, S. ALMOG, A. LUSKY, M. %HER, A. SHITMT, and Z. PUCHS. 1985. Wy.lperinsulinemia: a link between hypertension obesity and glucose tolerance. J . Clin. Invest. 15: 809-81'7.

OPARIL, S., and E. HABEW. 1974. The renin angiotensin system. N. EngB. J. Med. 281: 389-401.

PARUS, J., J. V. JWSSENS, Lo VAN DEW LINDEN, G . VEWSTREKEN, A. K. P. C. AMERY. 1973. Moderate sodim restriction md diuretics in the treatment sf hypertension. Am. H e a J . 85: 22-34.

RABMN, S. W., F. A. L. MATHEWSON, md P, H. Hsu. 1977. Relation of body weight to development sf ischemic heart disease in a cohort of young North American mean after a 26 y e a observation period: the Manitoba Study. Am. J. C d i o l . 39: 452-458.

WAISON, J . H., A. D. ACHIMASTOS, G. L. LONDON, and M. E. SAFAW. 1983. Intravaxualr volume, extracellular fluid volume and total

body water in obese and non-obese hypertensive man. Am. J . C a - diol. 51: 165-176.

REISIN, E., R. ABEL, M. MODAN, D. S. ~I~VEWBERG, W. E. ELIAHOU, and B. MODAN. 1978. Effect sf weight loss without salt restriction on the ducti ion of blood pressure. Ed. Engl. B. Med. 298: 1-5.

REISIN, E., md E. D. FROWEICH. 1982. Effects of weight reduction on arterial pressure. J. Chronic Dis. 35: 887-2391.

WEISIN, E., E. D. FROHEICH, P. H. MESSERLI, G . %a. D~SLINSKH, F. G . DUNN, M. M. JONES, and H. BATSON, JR. 1983. Cardiovascular change after weight reduction in obesity hypertension. Ann. Intern. Med. 98: 315-319.

STAMLER, R., J. STAMLEW, W. E. RIEDLINGEB, G. ALGERA, and R. H. ROBERTS. 1978. Weight and blood pressure findings in hypertension screening of 1 million Americans. JAMA (J. Am. Med. Assoc.), 248: 1607-3610.

STENBERG, J . , H. WASIR, A. AMERY, R. SANNERSTEDT, and E. WERKO. 1975. Comparative hernodynamic studies in man of adrenergic B 1 -receptor-agents without (H93126 metoprolol) and with (W87107) intrinsic sympathicomirnetic activity. Acta P h m a - mI. Toxicol. 36: 76-84.

TOBIAN, E. 1972. A viewpoint concerning the enigma of hypertension. Am. J. Med. 52: 595-609.

TUCK, M. L., J. SOWERS, E. DORNFELD, G. KLEDZHK, and M. H. MAXWELL. 1981. The effect of weight reduction on blood pressure, plasma renin activity and plasma aldosterone levels in obese patients. N. Engl. J. Med. 304: 12-13.

Vosas, A. W., L. S. WEBBER, R. R. FRERICH, and G. S. BEWENSON. 1981. Body height, and body mass as determinants of basal blood pressure in children: the Bogalusa Hem Study. Am. J. Epideraniol. 8M: 101-108.

WINQUIST, W. J . , R. C. WEBB, md D. F. BOWR. 1982. V~SCU~~W smooth muscle in hypertension. Fed. h s c . Fed. Am. SOC. Exp. Bisl. 41: 2386-2393.

YOUNG, J. B., and L. LANDSBERG. 1977a. Catecholamines and in- termediary metabolism. Clin. Endocrinol. Metab. 6: 559-631.

19773. Suppression of sympathetic nervous system during fasting. Science (Washington, DC), 1%: 1 173-14'75.

1982. Diet-induced chmges in sympathetic nervous system activity, possible implication for obesity and hypertension. J . Cho- nic Dis. 35: 878-2386.

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Weight reduction in the management of hypertension: Epidemiologic and mechanistic evidence