Extracellular and interstitial fluid volume in obesity with and without associated systemic hypertension

Extracellularand ltiterstitial FluidVolumein Obesity With atid Without AssociatedSystemicHypertension JOCELYNE RAISON, MD, APOSTOLOS ACHIMASTOS, MD, RISK ASMAR, ALAIN SIMON, MD, and MICHEL SAFAR, MD

F&id volumes and cardiac and renal hqnodynamics were investigated in 44 obese men, 22 wfth normal blood pressure and 22 with sustained essential hypertension..For the same degree of obestty hypertensive patients had a higher value in extracellujar (p <0.05) and interstitial fluid (p
MD,

were similar. For the same level of btood pressure, the expansion of extracellular and interstitial fluid volume parajleled the degree of obesity. Thus, obese patients v&h hypertension have an .absolute increase in extracellular and intwstftial fluid volumes. The increase was, related both to the degree of overweight and to the mechanisms of hypertension. (Am J Cardiol 1988; 57:223-228)

A

lteration in partition of fluid volumes in overweight men with systemic hypertension may be related to 2 components*-3: the level of blood pressure (BP] and the degree of obesity. First, the ratio between plasma volume and interstitial fluid volume is reduced and the reduction is directly related to the level of BP.2 Second, the ratio between extracellular fluid volume and total body water is decreased and mainly influenced by body weight reduction.2 Previous studieG3 of the relative contribution of body weight and BP on the partition of fluid volumes have been hampered by the selection of patients, often involving subjects with large increase in body weight but mild elevation in BP? In this investigation, overweight subjects with normal or elevated BP were carefully selected and matched, enabling an adequate estimation of fluid volume and hemodynamic variables.

tained their weight within a 2- to 3-kg range. All were hospitalized for 6 days on a 90-mEq/day sodium diet. On the basis of weight, sodium and urinary output, a steady sodium balance was assumed. Obese patients weighed more than 17% above their ideal weight, defined on the basis of age, sex, height and body build according to Metropolitan Life Insurance tables.4 Subjects were, considered normotensive when, on the basis of usual clinical and biologic investigations, they had a constant diastolic pressure below 90 mm Hg. Patients were considered to have sustained essential hypertension if diastolic pressure repeatedly measured by indirect method was more than 100 mm Hg during the untreated ambulatory period. BP determinations were done using both a normal-sized (14 X 60 cm) and a large pressure cuff (according to the degree of ,obesity),5 thus excluding borderline hypertension in obese patients. Investigations included measurements of blood and urinary electrolytes, creatinine clearance, fasting blood sugar and serum cholesterol and triglyceride levels, liver function tests, urinary vanyl-mandelic acid determinations and timed intravenous pyelography. The 22 hypertensive obese patients were all diagnosed as having moderate essential hypertension. Subjects who had diabetes mellitus requiring insulin, cardiac disease, alcoholism, drug addiction or psychiatric problems were excluded from the study. The mean creatinine clearance rate was 96 f 9 ml/min/1.73 m2 (* standard error of the mean). Classification of patients: The 44 subjects were studied using 2 subclassifications: Classification 1: The 44 subjects were separated into 2 groups: 22 into a normotensive and 22 into a hypertensive obese group. Patients were matched for their overweight. Clinical characteristics are listed in Table I.

Methods Patients: The study was performed in 44 overweight men: 22 normotensive subjects and 22 patients with sustained essential hypertension. The 44 men were untreated or had therapy discontinued at least 4 weeks before the study. During this period, they mainFrom the Diagnosis Center and the Hypertension Research Center, Broussais Hospital, Paris, France. This study was supported by grants from the Institut National de la Sante et de la Recherche Medical (INSERM), 1’Association pour I’Utilisation du Rein Artificiel [AURA] and the Caisse Nationale d’tissurantes Maladies des Travailleurs Salaries (CNAMTS), Paris, France. Manuscript received March 4,1985; revised manuscript received June 6,1985, accepted June 10,1985. Address for reprints: Michel Safar, MD, Hopital Broussais, Centre de Diagnostic, 96 rue Didot, 75654 Paris Cedex 14, France. 223

224

EXTRACELLULAR

TABLE

I

Clinical

AND

INTERSTITIAL

FLUID

VOLUME

Characteristics Obese

Age (yr) Weight (kg) Height (cm) Overweight (% ) BSA (m*) Values are mean f standard BSA = body surface area.

TABLE

Normotensives (n = 22) 41 f3

aaf

Obese

II

Classlticatlon

Hypertensives (n = 22)

l-Study

ot Fluid

Volumes

O&Se Normotensives (n = 22)

Obese Hypettensives

(ll = 22)

45 f 2

2

174f2 31 f3

2.0 f 0.03 error of the mean.

a4 f 2 173i 2 29 f 3 1.95 i 0.03

Plasma volume (PV) (ml) Extracellular volume WV) (ml) Body cellular water WW (ml) Interstitial fluid volume

3,220 f 60 io,580*330

11.570

f

390’

33,310

30.740

f

1,140

7,460f

f

930

250

3,200 f 80

8,860 h 280'

WV) (ml) Total body water (TBW) (ml) PV/IFV EFVlTBW BCW/IFV

43,840f9io 0.45 f 0.02 0.24 f 0.01

42.390 0137 0.28 3.52

l 1,170 l 0.02+ f 0.02'

4.61 f 0.64 & 0.15’ Classification2: The 44subjectswere classified according to level of obesity:thosewho were moderately p <0.05; + p
February

TABLE

III

Classification

SBP (mm Hg) DBP (mm Hg) MAP (mm Hg) Cardiac output (mllmn) Cardiax index (ml/mn/m*) Heart rate (beatsjmin) TPR (dynes s cm-sm2) (dynes s cmm5) RBF (ml/mn) GFR (ml/mn)

l-Cardiac

and Renal

Hemodynamics

Obese Normotensives (n = 22)

Obese Hypertensives (n = 22)

137 75 96 7,260 3,600 75 1,060 2,140 1,510 195

185 101 128 6,890 3,540 75 1,490 2,900 1,500 180

f f f f f f f f f f

3 2 2 260 120 2 50 90 70 15

f rt f zk f f zk & f zk

4’ 3’ 2’ 330 170 3 100 190’ 100 10

* p
1, 1986

TABLE

IV

JOURNAL

Classification

OF CARDIOLOGY

2-Study

of Fluid

Volume

Plasma volume (PV) (ml) Extracellular fluid volume (EFW (ml) Body cell water (BCW) (ml) Interstitial fluid volume

3,170 f

(TBW (ml) PV/IFV EFVlTBW BCWIIFV

310 1,090

7,830 f

WV) (ml) Total body water

42,010 0.42 0.25 4.11

f f f f

Severely Obese (n = 17) 3,400

70

10,430 f 31,420 f

225

57

Volumes

Moderately Obese (n = 27)

f 940

11,790 f 380’ 32,470 f 940

320

8,410

f 350

990 0.01 0.01 0.25

44.290 0.41 0.27 4.07

f 980 f 0.01 f 0.01 f 0.25

* p <0.05. Values are mean f standard error of the mean. Abbreviations as in Table II.

TABLE

volumes (Table IV] and hemodynamic (Table V) were similar.

THE AMERICAN

V

Classification

P-Cardiac

and Renal

Hemodynamics

parameters Moderately Obese (n = 27)

Discussion Fluid volumes are difficult to interpret in subjects who are obese and hypertensive because the adequate reference to body build is difficult to choose for the comparison with normal subjects.1-3 Intravascular volume was expanded when expressed in absolute values but contracted when expressed per unit weight or body surface area .2*3In the present investigation, the problem was partially overcome because the patients were men and were compared for the same degree of overweight. Indeed, major obesity was absent in most of our patients, but the findings are probably more related to most persons with hypertension. The main finding of the study was the absolute increase in extracellular and interstitial fluid volumes in obese men with hypertension. Although not significantly different, the level of intracellular water also appeared to be lower in hypertensive men, suggesting that the overall equilibrium between intracellular, extracellular and total body fluid volumes was different between the 2 groups. Because PV was similar in normotensive and hypertensive men, the increase in IFV could not be exclusively a result of a shift of intravascular volume toward the interstitial space, as previously observed in nonobese hypertensive subjectsY5J6 However, the expanded interstitial space could not be explained on the basis of evident symptoms of congestive heart failure or renal insufficiency: Sodium balance and glomerular filtration rate were within the normal range; in addition, cardiac output and renal blood flow were unaltered in obese subjects with or without hypertension, as previously shown.l’-lg Thus, the possibility remains that the increase in EFV may be related to the degree of obesity itself or to the metabolic and hormonal disorders associated to the alterations of adipose tissue. Obesity in hypertension is the result of an increase in the size (and not in the number] of adipocyteszO In

SEP (mm Hg) DBP (mm Hg) MAP (mm Hg) Cardiac output (CO) (ml/min) Cardiac index (ml/minim*) Heart rate (beatslmin) TPR (dynes s crne5 m*) (dynes s cme5) RBF (ml/min) (mllmin11.73 m2) GFR (ml/min) (ml/min/1.73 m*)

Severely Obese (n = 17)

183 f 5 89 f 3 113f4 7,040 f 270 3,660 f 130 74 f 2

160f7 87 iz 111 f5 7,210 f 3,470 f 75 f

1,290 f 2,490 f

90 150

1,180 f 2,440 f

80 150

1,590 f 1,420 f

120 110

1,420 f 1,200 f

70 60

190 f 181 f

10 10

180 f 163 f

10 10

4 310 130 3

Values are mean f standard error of the mean. Abbreviations as in Table Ill.

patients with obesity and hypertension, fat cell weight, and the degree of overweight are strongly interrelated.20 Further, the degree of obesity is usually associated with several disorders, possibly leading to an expansion of the interstitial space. First, modifications in insulin and steroid metabolisms may favor sodium and water retention.21-23 However, in the present study, this hypothesis may not be relevant because no total body differences were observed between normotensive and hypertensive men. Second, as noted in previous reports,13,24 the excess of EFV may be associated with an increase in lean body mass and conjunctive support according to the severity of obesity. In particular, a decrease in active body mass relative to EFV has been described in unhealthy, grossly obese persons.13 Our finding of expanded EFV in subjects with the most important degree of obesity (Table IV] could reflect this possibility. On the basis of animal experiments, it was believed for a long time that abnormalities of fluid volumes in

228

EXTRACELLULAR

AND INTERSTITIAL

FLUID

VOLUME

hypertension was exclusively related to the mechanisms of the hypertensive vascular disease.z-25 The present investigation indicates that in hypertension in men, such an assumption cannot be maintained. Interference with obesity can also partly explain abnormalities in fluid volumes in hypertension. Acknowledgment: We would like to thank Muriel Lefort, Christine Beretti and Daniele Saque for their excellent technical assistance.

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