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Annals of Clinical & Laboratory Science 34:416-422 (2004)
© 2004 Association of Clinical Scientists

Body Fluid Distribution in Elderly Subjects with Congestive Heart Failure

Giuseppe Sergi1, Lucia Lupoli1, Stefania Volpato1, Roberta Bertani2, Alessandra Coin1, Egle Perissinotto3, Irene Calliari4, Emine Meral Inelmen1, Luca Busetto1 and Giuliano Enzi1
1 Department of Medical and Surgical Sciences, Division of Geriatrics; 2 Department of Chemical Processes of Engineering, Faculty of Engineering; 3 Department of Environmental Medicine and Public Health; and 4 Department of Mechanical and Management Innovation; University of Padua, Padua, Italy

Address correspondence to Giuseppe Sergi, M.D., Clinica Geriatrica, Ospedale Giustinianeo, via Giustiniani 2, 35100, Padova, Italy; tel 39 049 821 8492; fax 39 049 821 1218; e-mail giuseppe.sergi{at}unipd.it


   Abstract
Top
 Abstract
Introduction
 Methods and Materials
 Results
 Discussion
 References
 
The aims of this study were to investigate body fluid changes in elderly patients suffering from congestive heart failure (CHF) and to identify the fluid measurement that best characterizes fluid overload states in CHF patients by comparison with normal hydration in the elderly. In a case-controlled experimental design, 72 elderly subjects (65–98 yr), 38 healthy and 34 with CHF, were studied. Total body water (TBW) and extracellular water (ECW) were determined by dilution methods; fat-free mass (FFM) and fat mass (FM) were determined by dual-energy X-ray absorptiometry (DEXA). In healthy subjects, the FFM hydration expressed as TBW%FFM (males 72.0 ± 4.3 vs females 72.4 ± 5.0%) and ECW%TBW (males 47.3 ± 3.4 vs females 47.8 ± 5.1) were similar in both genders. ECW in liters for FFM and for TBW (ECW%TBW), corrected for body weight, was greater in the group with CHF than in the control group, in both sexes. Among the relative fluid measures, only ECW%TBW [odds ratio (OR) 1.5] independently predicted fluid retention. Having an ECW%TBW greater than 50% corresponded to an OR of about 10. In conclusion, elderly patients suffering from CHF have a characteristic increase in body fluid levels, mainly affecting the extracellular compartment, and ECW%TBW is a useful indicator of fluid retention.

(received 13 September 2004; accepted 15 September 2004)

Keywords: total body water, extracellular water, fat-free mass, fluid overload, aging


   Introduction
Top
 Abstract
 Introduction
Methods and Materials
 Results
 Discussion
 References
 
Congestive heart failure (CHF) is a frequent pathology in the elderly and is associated with fluid overload. Previous studies on fluid retention in acute CHF in young and middle-aged adults recognized a prevalent expansion of the extracellular compartment [1–3]. Fluid changes in elderly patients with CHF have been less well investigated, however.

What is known about hydration status in health and disease in adults cannot be applied to elderly people because of changes in body composition and fluid compartmentalization occurring with aging [4]. Several studies have demonstrated that aging coincides with a reduction in total body water (TBW) and intracellular water (ICW) due to fat-free mass loss and an increase in extracellular water (ECW) and ECW/TBW ratio [4–8]. These physiological fluid changes make it necessary to investigate normal hydration and fluid retention in the elderly with a view to distinguishing fluid imbalance from normality.

It is important to gain an exhaustive knowledge of fluid changes in the elderly with CHF, now that indirect, repeatable, and non-invasive methods for estimating fluid compartments, such as bioelectrical impedance analysis (BIA), have become available [9–11]. These methods could be used in clinical practice to assess fluid overload in CHF and the effects of medications.

The aims of the present study were to investigate fluid changes in elderly patients suffering from symptomatic heart failure by comparison with healthy elderly individuals, and to identify the fluid measurement that best characterizes fluid overload in elderly CHF patients.


   Methods and Materials
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 Abstract
 Introduction
 Methods and Materials
Results
 Discussion
 References
 
This study was conducted in accordance with the Declaration of Helsinki II. The study design was approved by our Ethics Committee and a written informed consent was obtained from each patient.

Subjects.  In a case-controlled experimental design, we studied 72 elders divided into 2 groups: 34 CHF patients and 38 healthy subjects. The CHF patients (20 males and 14 females, mean age 83.9 yr, SD 6.9 yr) satisfied the clinical criteria for a diagnosis of CHF [12] and were recruited among patients admitted to the Geriatric Department of Padua Hospital for acute treatment of symptomatic CHF. We included only CHF patients in class III according to the New York Heart Association (NYHA); the patients all presented significant lower limb edema. In the CHF subjects, the ejection fraction averaged 40 ± 3%. CHF patients with fever, pleural effusion, hepatic failure, renal failure, dysproteinemia, or anemia were excluded.

The healthy subjects (18 males and 20 females, mean age 78.7 yr, SD 7.5 yr) were enrolled as a control group from outpatients coming to our Geriatric Department for a check-up. The good general health and fluid balance of these subjects was determined by their medical history, physical examination, functional ability in daily activities and biochemical parameters. These subjects had no cardiovascular, metabolic, or endocrine diseases, no water or electrolyte disorders, nor were they receiving diuretic treatment. The characteristics of the subjects are shown in Table 1Go.


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  		Table 1. Anthropometric and body composition characteristics of healthy subjects and patients with CHF, by gender.
 
Fluid compartment analysis.  In all subjects, we evaluated total body water and extracellular water by dilution methods and body composition by dual-energy X-ray absorptiometry (DEXA). Total body water (TBW) and extracellular water (ECW) were determined by deuterium oxide dilution and bromide dilution methods, respectively. Subjects received an oral solution containing a known dose (about 50 g) of deuterium oxide (D2O) and 35 mg/kg body weight of sodium bromide (NaBr) diluted in water. At 3 hr after the administration of this solution (equilibration time), venous blood samples were drawn into syringes and transferred into heparinized stoppered tubes. The samples were centrifuged at 3000 rpm for 15 min and the plasma samples obtained were stored at –20°C.

D2O concentration in plasma was determined using an FT infrared spectrophotometer according to Lukaski’s method [13] as modified at our Institute [14]. The TBW value in liters was calculated using the following formula:


where A is the quantity of D20 administered in mg, B is the D2O concentration in mg/L at the equilibration time, and 0.928 is the correction coefficient for non-aqueous exchangeable hydrogen in the body [15].

Bromide concentrations in plasma were measured by an energy-dispersive X-ray fluorescence (EDXRF) spectrometer. The corrected bromide space (CBS) was calculated using the following formula [16]:


where 0.9 is the correction factor for the distribution of bromide in non-extracellular sites, 0.95 is the correction factor for Donnan equilibrium, and 0.94 is the correction factor for the concentration of water in plasma.

Body composition.  Fat-free mass (FFM) and fat mass (FM) were determined using dual energy X-ray absorptiometry (DEXA) with fan-beam technology (Hologic QDR-4500W, Inc). A standardized procedure was used for positioning the patient and using the QDR software. The DEXA scans were analyzed with Hologic software (release #8.21) for body composition evaluation. DEXA is reproducible in determining soft tissue composition [17] and consistent for elderly subjects [18]. Fan-beam DEXA technology for measuring FM and FFM mass has also recently been validated [19–23]. FFM and FM were expressed as the absolute values and as % of total body weight. The body weight resulting from the sum of fat tissue mass, lean tissue mass, and total body bone mineral mass was similar to the body weight determined by conventional weighing.

Statistical analyses.  All analyses were performed using the SAS software (release #8.2) (SAS Institute, Cary, NC, USA). On account of body frame differences between genders, the fluid compartment and body composition measurements were expressed as mean ± SD for each sex- or disease-specific group. To avoid bias in comparing subjects with different weight and FFM, relative measures (as %) were obtained from instrumentally-assessed variables considering FFM, FM, TBW, and ECW, all divided by weight, and TBW and ECW, both divided by FFM. The normality of the distributions was verified with the Shapiro-Wilk statistic. Differences in mean values of continuous variables between 2 groups were evaluated using Student’s unpaired t-test or approximate t-test, after testing for homogeneity of variances. The level of statistical significance for each 2-sided test was set as p <0.05.

Stepwise logistic regression was performed on continuous relative variables to ascertain the role of some fluid measures in predicting fluid retention states. To avoid confounding effects due to absolute differences in FFM, the TBW as % of FFM (TBW%FFM), ECW as % of FFM (ECW%FFM), and ECW as % of TBW (ECW%TBW) were entered in the sex-specific models as independent variables. CHF was considered the dependent dichotomous variable. Further regression analysis was performed entering these measurements as independent dichotomous variables, using the 75th percentile of their distribution in healthy subjects as the cut-off value.


   Results
Top
 Abstract
 Introduction
 Methods and Materials
 Results
Discussion
 References
 
The anthropometric and body composition characteristics of healthy subjects and patients with congestive heart failure (CHF), by gender, are shown in Table 1Go. Absolute instrumentally-assessed and relative computed TBW and ECW values are given in Table 2Go. All the variables were normally distributed in each sample group.


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  		Table 2. Total body water (TBW) and extracellular water (ECW) of healthy subjects and CHF patients, by gender.
 
There were no gender-related differences in body mass index (BMI) among the healthy subjects. As expected, healthy women had significantly greater fat mass (FM) in kg and as % of body weight (34.3 ± 4.3 vs 22.0 ± 5.4%) compared to healthy men. TBW and ECW values, expressed both in liters and as % of body weight, were consequently higher for male than for female healthy subjects, though FFM hydration expressed as TBW%FFM (72.0 ± 4.3 vs 72.4 ± 5.0%) and body fluid distribution represented by ECW%FFM and ECW%TBW did not differ statistically between genders.

CHF patients had higher mean values for absolute and relative ECW measures than healthy subjects of either gender; eg, ECW%FFM (males: 39.3 ± 6.0 vs 34.1 ± 2.3; females: 45.7 ± 5.9 vs 34.6 ± 4.1) and ECW%TBW (males: 54.8 ± 5.7 vs 47.3 ± 3.4; females: 60.7 ± 6.0 vs 47.8 ± 5.1). Only the female patients had significantly higher TBW in liters, TBW%weight, and TBW%FFM values than the control group, however.

Among the fluid parameters tested, only ECW%TBW independently predicted fluid retention state by stepwise logistic regression (Table 3Go), for both males and females (OR 1.5).


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  		Table 3. Stepwise logistic regression analysis to evaluate the role of TBW as % of FFM (TBW%FFM), ECW as % of FFM (ECW%FFM), and TBW (ECW%TBW) in predicting fluid retention.
 
Entering the same variables expressed as dichotomous variables, the analysis applied to the whole sample population indicated an OR = 10 (95% CI: 3.3–30.3) for subjects with an ECW%TBW greater than 50%. The prevalence of a ECW%TBW >50% in healthy and CHF patients by genders is shown in Fig. 1Go.



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  		Fig. 1. Prevalence (%) of healthy subjects and patients with congestive heart failure (CHF) who have extracellular water >50%, expressed as a percentage of total body water (ECW%TBW).

 

   Discussion
Top
 Abstract
 Introduction
 Methods and Materials
 Results
 Discussion
References
 
The present study compared fluid changes in geriatric patients with acute CHF versus the hydration state and body water distribution in healthy elderly subjects. The FFM hydration in the control group showed a wide range (64.5–83.8%) with a mean TBW%FFM of 72.2%. These results are comparable with the value of 72.5% found in the elderly by Mazariegos et al [4] and confirm findings in our previous study [24] where, using reference methods, elderly subjects had a mean TBW%FFM of 71.9%. Consistent with previous reports [24,25], the ECW in our healthy subjects was about 25% of body weight, with higher values for males because of their higher fat-free mass, while ECW as % of FFM was similar in the two genders (about 34%). ECW was about 47% of TBW in both genders. Previous studies found ECW/TBW values for the elderly ranging from 0.43 to 0.52 [9,18,26,27]; these figures are higher than in younger adults, where ECW accounts for about 42% of TBW [5], thus confirming age-related fluid distribution changes.

Some authors agree there is a relative increase in ECW associated with a relative decrease in ICW with aging [5,28]. These changes may be explained either by an increase in FM (where ECW/ICW is 4:1) or by skeletal muscle atrophy, both of which are characteristic of old age [4)]

Our healthy elderly subjects had similar values for TBW%FFM, ECW%FFM, and ECW%TBW, regardless of gender and differences in body composition, demonstrating a relatively constant fat-free mass hydration, so the hydration values of our control group could be useful for reference in the elderly to identify cases of dehydration or fluid retention.

In elderly patients with CHF, the clinical signs of fluid overload were confirmed by dilution methods that revealed an increase in body fluids, especially in females.

TBW%Wt does not seem useful in detecting fluid retention states. TBW as % of body weight is influenced by body composition, particularly by FFM/FM ratio, and men with CHF had a greater FM (albeit not significantly so) than healthy males, so their fluid retention could be masked by more fat influencing the TBW%Wt value.

FFM hydration, expressed as TBW%FFM, also fails to point to fluid retention, because a higher FFM value may be due to a higher TBW. For example, for a healthy subject a 10% increase in TBW due to water overload results in a TBW%FFM increase of only about 2%. Therefore, this ratio increases significantly only in severe fluid retention conditions, as seen in females with CHF. The comparison with other studies is difficult, because the relationship between body fluids and FFM has been inadequately studied in CHF patients.

Our results show that ECW is the most important compartment involved in fluid retention. This expansion of the extracellular compartment in CHF cases is confirmed by higher ECW%TBW values uninfluenced by any differences in body composition and fat mass. In fact, ECW as % of TBW was about 7% and 13% higher for CHF males and females, respectively, than for the control group.

Previous studies dealing with fluid distribution in CHF produced contradictory results, probably due to the degree of heart failure, the different methods used, and the clinical evidence of fluid overload. Steele et al [25] evaluated body fluids in 12 elderly patients with chronic heart failure and found no significant changes in TBW and ECW, compared to healthy elderly subjects, but their patients presented no clinical signs of fluid retention. Stellato et al [3] used a BIA method and found an increase in ICW and a decrease in ECW, by comparison with controls, in 23 adult males with end-stage heart failure, while TBW was nearly identical between patients and controls. As in Steele’s study [25], these patients had no clinical signs of fluid overload, because they were receiving drastic diuretic therapy.

On the other hand, previous studies of body fluids in CHF patients with clinical signs of fluid retention gave results similar to ours. Aidargalieva et al [29] observed an increase in ECW in 32 patients with heart failure exhibiting signs of fluid overload. A previous study of ours [30] showed a higher ECW in middle-aged patients with fluid retention due to heart or kidney failure, but we did not distinguish between the 2 groups of patients. Soderberg et al [2] indirectly confirmed our finding that administering diuretics to patients with acute CHF induces a reduction in ECW that is the most important factor in their weight loss. The usefulness of estimating ECW as an index of fluid retention is also demonstrated by logistic regression analysis. ECW%TBW values above 50 are independently associated with 10-fold higher likelihood of fluid retention. We consider ECW%TBW a good parameter for identifying fluid retention since it is relatively constant in conditions of water equilibrium and is uninfluenced by gender or nutritional status.

The results of this study should be considered with caution, taking into account certain limitations. Since the inclusion criteria were very restrictive, only a small number of patients met the protocol conditions and the sample size was consequently limited. Since our aim was to evaluate unknown scatters in fluid between healthy elderly and CHF patients, we judged the information to be adequate. The effect of physical activity was not considered in relation to body fluid distribution, but the level of physical performance was similar (in terms of independence in activities of daily living) in all healthy subjects, while the CHF patients performed less well because of their heart disease. Alcohol intake was low in all subjects and similar in the 2 groups, so it was not considered in the statistical analysis.

In conclusion, elderly people with CHF have a fluid imbalance characterized by an increase in the extracellular compartment. Among relative measures of fluid distribution, ECW%TBW seems to be the best indicator of CHF, a 10-fold risk being associated with values over 50%. Future studies are needed to confirm these observations in elderly CHF subjects and to support the need for a routine use of non-invasive methods to quantify fluid imbalance and monitor the effects of medication on these patients.


   References
Top
 Abstract
 Introduction
 Methods and Materials
 Results
 Discussion
 References
 

  1. Jaenike JR, Waterhouse C. The nature and distribution of cardiac edema. J Lab Clin Med 1958;52:384–393.[Medline]
  2. Soderberg M, Hahn RG, Cederholm T. Bioelectric impedance analysis of acute body water changes in congestive heart failure. Scand J Clin Lab Invest 2001;61:89–94.[Medline]
  3. Stellato D, Cirillo M, De Santo LS, Maiello C, Marra C, De Vivo F, Anastasio P, Frangiosa A, Cirillo G, Cotrufo M, De Santo NG, Di Iorio B. Body impedance studies in end-stage heart failure. Miner Electrolyte Metab 1999;25:21–23.[Medline]
  4. Mazariegos M, Wang Z, Gallagher D, Baumgartner RN, Allison DB, Wang J, Pierson RN JR, Heymsfield SB. Differences between young and old females in the five levels of body composition and their relevance to the two-compartment chemical model. J Gerontol 1994;49:M201–208.[Abstract]
  5. Aloia JF, Vaswani A, Flaster E, Ma R. Relationship of body water compartments to age, race, and fat-free mass. J Lab Clin Med 1998;132:483–490.[Medline]
  6. Ritz P. Body water spaces and cellular hydration during healthy aging. Ann NY Acad Sci 2000;904:474–483.[Medline]
  7. Schoeller DA. Changes in total body water with age. Am J Clin Nutr 1989;50:1176–1181.
  8. Steen B. Body composition and aging. Nutr Rev 1988;46:45–51.[Medline]
  9. Visser M, Deurenberg P, Van Staveren WA. Multi-frequency bioelectrical impedance for assessing total body water and extracellular water in elderly subjects. Eur J Clin Nutr 1995;49:256–266.[Medline]
  10. Vachè C, Rousset P, Gachon P, Gachon AM, Morio B, Boulier A, Coudert J, Beaufrère B, Ritz P. Bioelectrical impedance analysis measurements of total body water and extracellular water in healthy elderly subjects. Int J Obes 1998;22:537–543.
  11. Bussolotto M, Ceccon A, Sergi G, Giantin V, Benincà P, Enzi G. Assessment of body composition in elderly: accuracy of bioelectrical impedance analysis. Gerontology 1999;45:39–43.[Medline]
  12. Senni M, Tribouilloy CM, Rodeheffer RJ, Jacobsen SJ, Evans JM, Bailey KR, Redfield MM. Congestive heart failure in the community. A study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation 1998;98:2282–2289.[Abstract/Free Full Text]
  13. Lukaski HC, Johnson PE. A simple, inexpensive method of determining total body water using a tracer dose of D2O and infrared absorption of biological fluids. Am J Clin Nutr 1985;41:363–370.[Abstract/Free Full Text]
  14. Bertani R, Sergi G, Lupoli L, Berton A, Volpato S, Zambon K, Coin A, Enzi G. Measurement of total body water (TBW) through in vivo dilution of tracer compounds: use of D2O and its determination by FT infrared spectroscopy. Ann Chim 2002;92:135–138.[Medline]
  15. Bartoli WP, Davis JM, Pate RR, Ward DS, Watson PD. Weekly variability in total body water using 2H2O dilution in college-age males. Med Sci Sports Exerc 1993;25:1422–1428.[Medline]
  16. Vaisman N, Pencharz PB, Koren G, Johnson JK. Comparison of oral and intravenous administration of sodium bromide for extracellular water measurements. Am J Clin Nutr 1987;46:1–4.[Abstract/Free Full Text]
  17. Lukaski HC. Soft tissue composition and bone mineral status. Evaluation by dual energy x-ray absorptiometry. J Nutr 1993;123(2 Suppl):438–443.
  18. Baumgartner RN, Stauber PM, McHugh D, Koehler KM, Garry PJ. Cross-sectional age differences in body composition in persons 60+ years of age. J Gerontol A Biol Sci Med Sci 1995;50:M307–M316.
  19. Ellis KJ, Shypailo RJ. Bone mineral and body composition measurements: cross-calibration of pencil-beam and fan-beam dual-energy X-ray absorptiometers. J Bone Miner Res 1998;13:1613–1618.[Medline]
  20. Fuerst T, Genant HK. Evaluation of body composition and total body bone mass with the Hologic QDR-4500. Osteoporos Int 1996;6(Suppl):202.
  21. Mazess RB, Barden HS. Evaluation of differences between fan-beam and pencil-beam densitometers. Calcif Tissue Int 2000;67:291–296.[Medline]
  22. Modlesky CM, Evans EM, Millard-Stafford ML, Collins MA, Lewis RD, Cureton KJ. Impact of bone mineral estimates on percent fat estimates from a four-component model. Med Sci Sports Exerc 1999;31:1861–1868.[Medline]
  23. Visser M, Fuerst T, Lang T, Salamone L, Harris TB, for the Health, Aging, and Body Composition Study - Dual-Energy X-Ray Absorptiometry and Body Composition Working Group. Validity of fan-beam dual-energy X-ray absorptiometry for measuring fat-free mass and leg muscle mass. J Appl Physiol 1999;87:1513–1520.[Abstract/Free Full Text]
  24. Sergi G, Perini P, Bussolotto M, Zurlo F, Malvasi L, Carraro R, Del Prato S, Giantin V, Enzi G. Body composition study in the elderly: comparison between tritium dilution method and dual photon absorptiometry. J Gerontol 1993;48:M244–248.
  25. Steele IC, Young IS, Stevenson HP, Maguire S, Livingstone MB, Rollo M, Scrimgeour C, Rennie MJ, Nicholls DP. Body composition and energy expenditure of patients with chronic cardiac failure. Eur J Clin Invest 1998;28:33–40.[Medline]
  26. Steen B, Isaksson B, Svanborg A. Body composition at 70 and 75 years of age: a longitudinal population study. J Clin Exp Gerontol 1979;1:185–200.
  27. Yasumura S, Cohn SH, Ellis KJ. Measurement of extracellular space by total body neutron activation. Am J Physiol 1983;244:R36–40.
  28. Ritz P. Chronic cellular dehydration in the aged patient. J Gerontol 2001;56A:M349–M352.
  29. Aidargalieva NE, Sharashidze ML, Mareev Viu, Suvorov IuI, Kaplan MA. Body water compartments of patients with chronic heart failure and the refractory oedema syndrome. Ter Arkh 1987;59:78–81.
  30. Sergi G, Bussolotto M, Perini P, Calliari I, Giantin V, Ceccon A, Scanferla F, Bressan M, Moschini G, Enzi G. Accuracy of bioelectrical impedance analysis in estimation of extracellular space in healthy subjects and in fluid retention states. Ann Nutr Metab 1994;38:158–165.[Medline]



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