Phase angle associated with over-hydration in healthy Chinese

Background A body composition monitor (BCM) has a role not only in determining over-hydration (OH) but also as an aid to nutritional assessment. For dialysis patient-specific clinical applications of BCM, it is necessary to clarify the relationship between body composition parameters and OH in healthy Chinese individuals. Methods This cross-sectional study involved 314 healthy individuals with a mean age of 45.713.1 years. BCM measurements were performed while the subjects were fasting. Results The mean OH level was 0.3790.81 L. Lean tissue index (LTI) and Lean tissue mass (LTM) were significantly higher in males (p<0.001), while fat tissue index (FTI) was significantly higher in females (p<0.001). In univariate correlation analysis, FTI, Fat, and ATM had a negative correlation with OH in females and all subjects (p<0.05), while LTM and BCM had a positive correlation in all subjects (p<0.05). There was a significant negative correlation between phase angle (PhA) and OH in males, females, and all subjects (r=-0.634, p<0.001; r=-0.666, p<0.001; r=-0.484, p<0.001, respectively). In multivariate linear regression analysis, PhA (=-1.266, p<0.001), LTM (=0.987, p<0.001), age (=-0.307, p<0.001) were independent predictors of OH. Conclusions This study demonstrated that age, LTM and especially PhA, had important roles in predicting OH in healthy Chinese individuals. In the future, PhA may aid in clinical assessment by helping to titrate dry weight among hemodialysis patients with malnutrition.


Introduction
Fluid abnormalities are commonly observed during maintenance hemodialysis (MHD) in end stage renal disease patients.Chronic volume overload can induce hypertension, left ventricular hypertrophy, heart failure, and pulmonary edema. [1,2] n contrast, chronic volume deficits can induce intradialytic hypotension, muscle cramps, and shock. [3,4] anagement of fluid volume in MHD patients, especially in malnourished individuals, has been a challenge to nephrologists.However, objective methods that evaluate fluid status are limited in clinical practice.In recent years, body composition monitoring (BCM) based on bioimpedance spectroscopy has been used to identify excess fluid retention and to help with nutritional assessments.] Even so, simple reliance on over-hydration (OH) obtained from BCM while ignoring the interaction of other factors may lead to inappropriate management decisions.Although fluid volume varied substantially by age, sex and body composition, there were few studies investigating the role of body composition, including phase angle (PhA) in healthy individuals or MHD patients.For patient-specific clinical applications of BCM, it will be necessary to clarify the relationship between the parameters of body composition and OH.In this study, we began to explore those relationships in healthy Chinese individuals.

Subjects
A total of 314 healthy subjects from the local community who were patients at the Physical Examination Centre of the Baotou Central Hospital were enrolled beween 25 Jul 2018 and 24 Oco 2018(165 female and 149 male; All the induviduals are Han Chinese).They had a mean age of 45.7  13.1 years).Individuals were eligible for inclusion if they were older than 18 years of age and had routine screening tests including fasting blood glucose (FBG), hepatic and renal function tests, and a urinalysis, that all were within normal limits.Those with a history of cerebral infarction, acute myocardial infarction, renal failure, diabetes, rheumatoid arthritis, visible edema, metallic implants, implanted cardiac pacemakers, major amputations of the extremities, HIV infection, or current pregnancy were excluded from this study.All the participants gave their written informed consent prior to enrollment as subjects in the study.This study was approved by the Baotou Central Hospital Clinical Research Ethics Committee.The ethical approval number was [2018 (ethics) 007].

Methods
We used a validated multi-frequency bioimpedance spectroscopy device (Body Composition Monitor [BCM], Fresenius Medical Care, Germany) in healthy subjects as previously reported.Briefly, electrodes were attached to one hand and one foot with the individual in the supine position.In essence, BCM estimates electrical resistance by applying alternating current at 50 different frequencies over a range of 5 to 1000 kHz.Parameters obtained directly through BCM were extracellular water (ECW), intracellular water (ICW), total body water (TBW), overhydration (OH), and the ECW to ICW ratio (E/I), which reflects the fluid balance.Lean tissue mass (LTM), LTI (obtained by dividing LTM by height squared), lipid mass (Fat), adipose tissue mass (ATM), fat tissue index (FTI; calculated by dividing ATM by height squared), body cell mass (BCM), and phase angle (PhA) were used as markers for a nutritional status.BCM measurements were performed in fasting subjects the morning after their blood samples were collected.

Statistical analysis
All continuous variables were expressed as mean  standard deviation (SD).Comparisons between males and females were made using independent t-tests after confirmation of normal distributions for all variables.Pearsons correlation analysis was used to examine correlations between OH and other variables.To assess independent variables associated with OH, we performed multiple linear regression analysis when differences in the variables were significant in the univariate analysis.P-values <0.05 were considered statistically significant for all calculations.Statistical analysis were performed using SPSS for Windows version 19.0 (IBM Corp., Armonk, NY, USA).

1 Individual Characteristics
Figure 1 showed a histogram of OH in healthy subjects.The mean OH level was 0.3790.81L. Male subjects had significantly higher levels of OH than females (0.505±0.89 versus 0.2660.71L, t=2.692, p=0.007).A total of 247 (78.7%) of the 314 subjects had values that were equivalent to the standard value of healthy Caucasian subjects that have been reported in foreign countries (1.1 to 1.1 L).The data from the study subjects are shown in Table 1.The value of OH in male subjects is higher than in females (t=2.692,p=0.007).The mean age, LTI, LTM, and BCM were significantly higher in the male subjects than in the females (p<0.001).However, the value of FTI (t=-4.474,p<0.001) was significantly higher in females, but Fat (t=-0.629,p=0.530) and BCM (t =-0.624, p=0.533) did not differ significantly between the two groups.The overall mean of the PhA value was 5.6070.71.A highly significant gender difference in the mean PhA value was observed (male versus female: 5.9750.70versus 5.2750.53,t=9.858, p<0.001).Abbreviations: OH, over-hydration; LTM, lean tissue mass; Fat, lipid mass; PhA, phase angle.Abbreviations: OH, over-hydration; LTM, lean tissue mass; Fat, lipid mass; PhA, phase angle.

Discussion
The main findings of the study were as follows: 1) 78.7% of individuals had values equivalent to the standard values of healthy Caucasian subjects in foreign countries (1.1 ~ 1.1 L). 2) There was a significant correlation between PhA (p<0.001) and OH in male, female, and all subjects.3) In multivariate linear regression analysis age, LTM, and PhA were independent predictors of OH, and PhA was the most important predictor of OH.
We found that OH of healthy Chinese subjects (78.7%, Figure 1) was equivalent to the standard value of healthy subjects in foreign countries (-1.1 ~ 1.1 L).According to the brochure of the BCM the reference value of OH is represented by the 10 th to 90 th percentile for healthy Caucasian subjects.In a study of healthy Japanese, 76.3% of the subjects were within the standard value. [8]As such, the use of this measure was thought to be equally suitable for Asians.However, there may be small differences in OH level among ethnic groups, by dietary habits and regions.Therefore, in the future, it will be necessary for us to investigate reference values of healthy Chinese for better application of BCM to clinical practice.
It is known that males have more lean tissue, whereas females have higher fat percentages. [9,10] TI and LTM obtained with the BCM correspond to lean tissue.Fat, FTI and ATM that were obtained with the BCM correspond to adipose tissue.In our study, we also found that the LTI and LTM of males were significantly higher than those of females, while the FTI of females was significantly higher than that of males.But Fat and ATM did not differ significantly between the male and female subjects.In addition to the small size of the study population or racial Therefore, more studies will be needed to elucidate the differences of body composition between healthy Chinese males and females.
[13][14] Adipose tissue contains about 10% water, while muscle contains about 75% water.In our study, we found that adipose tissue (FTI, Fat, and ATM) had a weakly negative correlation with OH in females and all subjects (Table 2) by univariate analysis.The association between adipose tissue and OH was abolished when adding age, gender, LTM, and PhA to the multivariate linear regression analysis (Table 3), which suggested that there may be no correlation between the adipose tissue and OH.Simultaneously, we found that LTI was not associated with OH in univariate analysis (Table 2), while LTM had a positive correlation to OH in all subjects on univariate or multivariate analysis (Table 2, Table 3), which indicated that lean tissue was one of the most important predictors of OH.Consistent with the findings of previous studies, we found that lean tissue contained more water than adipose tissue. [15]Importantly, we found that PhA was highly significant in males, females, and all subjects in the univariate analysis (Table 2, Figure 2C, 2D, 2E).Furthermore it was a significant predictor of OH in multiple linear regression analyses, PhA was the most important predictor of OH according to standardized coefficient in regression equation (Table 3).As far as we know, our study is the first to explore the correlation between the PhA and OH in healthy individuals.
The topic of OH calculation in the healthy Chinese people is important in clinical practice because it will guide adjustment of dry weight in dialysis patients.Recent studies have shown that nutritional status was inversely associated with OH in patients with chronic kidney disease or hemodialysis. [ 13,14] [18][19] There has been growing interest in the use of PhA as a surrogate for LTM in the assessment of nutritional status, because raw bioimpedance is not influenced by hydration status. [20,21] ased on our results, nutritional status (and especially PhA) should be considered when determining specific ultrafiltration volume in hemodialysis patients, in order to decrease adverse events caused by excessive or insufficient ultrafiltration.One limitation of our study was that it was a cross-sectional observational study that included a relatively small number of subjects, and further studies in larger populations will be needed.
In conclusion, age, LTM and PhA were independent predictors for OH, and PhA was the most important predictor in the healthy Chinese people.In the future, use of PhA to titrate dry weight may benefit hemodialysis patients with malnutrition.

Figure 2 .
Figure 2. Pearsons correlation between OH and various parameters in different groups.

Table 1 .
Comparison of parameters derived from BCM between males and females.

Table 2 .
Univariate analysis of subject's characteristics in association with the OH.

Table 3 .
Multiple linear regression analysis of variables influencing the OH