Effect of Lean Body Mass, Fat Mass, Blood Pressure, and Sexual Maturation on Left Ventricular Mass in Children and Adolescents
Statistical, Biological, and Clinical Significance
Background Left ventricular hypertrophy has been established as an independent risk factor for the development of cardiovascular morbidity and mortality. It is clear that left ventricular mass increases during childhood and adolescence with body growth. The extent to which other factors, such as obesity, stage of sexual maturation, and level of blood pressure, determine left ventricular mass has been controversial.
Methods and Results The study was a cross-sectional evaluation of the relationship of left ventricular mass determined by echocardiography with lean body mass and fat mass determined by dual-energy x-ray absorptiometry, which is the most valid and reliable method for determination of body composition in children and adolescents. The relationship of left ventricular mass with the stage of sexual maturation and with systolic and diastolic blood pressure was also evaluated. Two hundred one subjects (105 boys, 96 girls; 103 white and 98 black) 6 to 17 years old were studied. Age (r=.72), height (r=.81), weight (r=.84), body surface area (r=.87), sexual maturation (r=.75), lean body mass (r=.86), fat mass (r=.54), systolic BP (r=.58), and diastolic BP (r=.48) were all univariate correlates of left ventricular mass. In a multiple regression analysis, only lean body mass, fat mass, and systolic blood pressure were statistically significant independent correlates of left ventricular mass. Lean body mass alone explained 75% of the variance of left ventricular mass, whereas fat mass and systolic blood pressure explained only 1.5% and 0.5% of the variance, respectively. Lean body mass was the strongest determinant of left ventricular mass in all four race-sex groups.
Conclusions This study provides an opportunity to separate the effects on left ventricular mass of lean body mass resulting from linear growth from those of fat mass resulting from obesity. Lean body mass, fat mass, and systolic blood pressure all have a statistically significant independent association with left ventricular mass, suggesting that all three play an important biological role in determining left ventricular mass. However, fat mass and systolic blood pressure have only a small impact on left ventricular mass. This indicates that fat mass and blood pressure would be expected to be of only minor clinical importance in determining left ventricular mass in normal children and adolescents.
Left ventricular hypertrophy has been established as an independent risk factor for the development of cardiovascular morbidity and mortality.1 2 3 Therefore, understanding the determinants of left ventricular mass in children and adolescents has become increasingly important. It is clear that left ventricular mass increases during childhood and adolescence with body growth.4 It has also been suggested that other factors, such as ponderosity, blood pressure, and sexual maturation, may have an effect on left ventricular mass. However, the extent to which these other factors have an impact on left ventricular mass has been controversial. For example, some authors have suggested that obesity has a clinically important and potentially modifiable adverse effect on left ventricular mass,5 6 but others have argued that the impact of obesity above that of linear growth is minimal.7 One deficiency of previous research is that investigators have often used body mass index or ponderal index as a measure of obesity. However, body mass and ponderal indexes, which are functions of height and weight alone, incorporate elements of both lean body mass and obesity. Dual-energy x-ray absorptiometry (DEXA) provides a definitive method of accurately determining lean body mass and fat mass and allows investigation of their independent effects on left ventricular mass.8 9 10 11
The purpose of this investigation was to evaluate the effects of lean body mass, fat mass, blood pressure, and sexual maturation on left ventricular mass in children and adolescents. The goal was to determine whether these factors had a statistically significant independent effect on left ventricular mass as well as to judge whether the effect of these factors was likely to be of biological or clinical importance.
The subjects were 201 children and adolescents from 6 to 17 years old. Children and adolescents with abnormalities on physical examination or echocardiography were excluded from the study. Written informed consent was obtained from parents or legal guardians, and verbal assent was obtained from subjects ≥11 years old before their participation in the study. This study was approved by the Institutional Review Board of the Children’s Hospital Medical Center.
Examination included measurement of height; weight; and triceps, subscapular, and suprailiac skinfold thicknesses. Body mass index was calculated as weight/height2.
Dual Energy X-Ray Absorptiometry
DEXA is a relatively new method of assessing body composition in humans. This technology has the potential to provide information about lean body mass as well as total and regional body fat. It uses two x-ray beams that traverse the length of the body. The energy that is collected by the external detector is attenuated by the bone and soft tissue through which it has passed. The flux, or number of photons measured per unit area, is corrected for soft tissue by a linear two-dimensional interpolation, and the corrected values are summed to estimate total body mineral content. Soft tissue is resolved by use of mass attenuation coefficients from tissue equivalent standards for fat and fat-free tissue. DEXA has been shown to provide accurate and precise estimates of total body fat, bone mineral content, and fat-free mass.8 9 10 11 DEXA has been validated against the hydrodensitometry method that has previously been established as the most valid and reliable method for measurement of lean body mass.8
Subjects in this study were scanned with a Hologic (QDR-1000/W) whole-body scanner. For data interpretation, body composition is divided into soft-tissue mass and bone mass. The soft-tissue mass can then be divided into lean body mass and fat mass.
Blood pressure was measured by auscultation with mercury sphygmomanometers.12 Systolic and diastolic blood pressures were measured with an appropriate size cuff in the right arm with the subjects seated, with feet on the floor and arm at heart level. Three blood pressure measurements were made, each separated from the next by at least 1 minute. The onset of the fifth Korotkoff phase was used to determine diastolic blood pressure. The average of the three determinations for systolic and diastolic blood pressure was used in the analysis. The staff received a standard 16-hour blood pressure measurement training course and were certified according to a previously established protocol.13
Pubertal staging was determined by physical assessment. Examiners of boys were male and examiners of girls were female. For boys, the maturation assessment included pubic hair stage as defined by Marshall and Tanner14 and determination of testicular volume by means of the Prader orchidometer. Pubertal staging was defined by the criteria of Biro et al,15 combining those two elements to produce a scale of 1 to 4. For girls, maturation staging was performed with staging criteria developed by Garn and Falkner that incorporate pubic hair and areolar development based on Tanner staging principles,16 which were modified to make them suitable for girls of all ethnic groups and body habitus. These methods have been described by Morrison et al17 and result in a scale of 1 to 3: 1, prepubertal; 2, pubertal but premenarcheal; and 3, postmenarcheal.
Echocardiographic examination of the left ventricle was performed by standard techniques with subjects in a supine position. Studies were performed using two-dimensional guided M-mode echocardiograms with transducer frequencies appropriate for body size. Measurements of the left ventricular internal dimension, interventricular septal thickness, and posterior wall thickness were made at end diastole according to the criteria of the American Society of Echocardiography.18 Left ventricular mass was calculated from the equation reported by Devereux et al19 20 derived for American Society of Echocardiography measurements and validated against anatomic measurements.
Descriptive statistics, including mean±SD for continuous variables and proportions for categorical variables, are presented for age, sex, lean body mass, fat mass, anthropometric characteristics, sexual maturation, blood pressure, and echocardiographic measurements for the study cohort. Pearson correlation coefficients were calculated to determine which independent variables had a significant univariate association with left ventricular mass. Stepwise linear regression analysis was used to determine the independence of correlates of left ventricular mass. Independent variables were allowed to remain in the model if the regression coefficient for that variable was significantly different from zero even if the independent variable explained only a small portion of the variance of left ventricular mass. Partial R2 coefficients were used to determine the amount of variance in left ventricular mass explained by each independent variable. A value of P<.05 was used to indicate statistical significance. Sex and racial differences in the correlates of left ventricular mass were evaluated with sex- and race-specific regression models. Because the sample size was reduced in the race- and sex-specific models, a value of P=.10 was used to indicate statistical significance in these models.
Two hundred one subjects were included in the study, 105 boys and 96 girls; 103 subjects were white and 98 were black. The subjects ranged in age from 6 to 17 years. Summary statistics for age, anthropometric variables, blood pressure, and echocardiographic variables are presented in Table 1⇓. The distribution for stage of sexual maturation was 15 (15%) stage 1, 41 (40%) stage II, 27 (26%) stage III, and 19 (19%) stage IV for boys and 39 (44%) stage I, 18 (20%) stage II, and 31 (35%) stage III for girls.
Correlates of Left Ventricular Mass
The Pearson correlation coefficients for the association of various independent variables and left ventricular mass are presented in Table 2⇓. In general, the correlations between independent variables and left ventricular mass were similar by race and sex, so only the overall correlations are reported.
Multiple Regression Analysis
Multiple regression analysis was used to determine the independence of variables that explain the variance of left ventricular mass. The stepwise regression analysis is presented in Table 3⇓. This analysis demonstrates that lean body mass, fat mass, and systolic blood pressure are significant independent correlates of left ventricular mass. Sexual maturation was a significant univariate correlate of left ventricular mass, but it did not remain significant in the multivariable analysis. The variance of left ventricular mass explained by the model is 77%. Each of the regression coefficients is positive, indicating that increased lean body mass, fat mass, and systolic blood pressure are all associated with increased left ventricular mass. Table 4⇓ presents the percent of variance explained by each of the variables as reflected in the partial R2. These results demonstrate that lean body mass explains most of the variance of left ventricular mass. Although fat mass and systolic blood pressure are statistically significant correlates of left ventricular mass, they explain only a small portion of the variance. Fat mass and systolic blood pressure may have biological significance in determining left ventricular mass in children and adolescents; however, it is unlikely that they have a clinically important impact on left ventricular mass. For example, based on the regression model, an increase in fat mass of 10 kg would result in an increase in left ventricular mass of only 5 g; an increase in systolic blood pressure of 10 mm Hg would result in only a 2.6-g increase in left ventricular mass. In contrast, an increase in lean body mass of 10 kg would result in a 20.2-g increase in left ventricular mass.
The significant independent variables for explaining the variance of left ventricular mass by race and sex are presented in Table 5⇓. Although there are some minor differences by race and sex, lean body mass is clearly the most important correlate of left ventricular mass for whites and blacks, boys and girls. Fat mass is also a significant correlate in each of the models except for whites, in whom it did not reach statistical significance (P<.10). The differences by race and sex must be interpreted cautiously because of decreased sample size for those comparisons.
The determinants of left ventricular mass in children and adolescents have been controversial, and the relative roles of lean body mass, ponderosity, and blood pressure have been debated. The present study provides a more definitive answer to this question because of the use of DEXA, which is the most valid, reliable, and clinically useful method currently available for measurement of body composition in children and adolescents. This allows for separation of the influences of lean body mass and fat mass on left ventricular mass.
In this study, we found that lean body mass and fat mass were both statistically significant correlates of left ventricular mass. However, lean body mass is a much stronger predictor of left ventricular mass than is fat mass. These results are consistent with the findings of Goble et al,7 who reported that body weight but not ponderosity is a strong predictor of left ventricular mass. Goble et al also reported that body fat as measured by suprailiac skinfold thickness was inversely associated with left ventricular mass. However, this finding may be a statistical artifact, because the major variable in their model, weight, includes both elements of lean body mass and fat mass. Thus, it was not possible for them to completely separate their effects. Urbina et al6 reported that the major factor influencing left ventricular mass in the Bogalusa Heart Study was linear growth as determined by height. In addition, they found that weight and measures of ponderosity were significant determinants of left ventricular mass. They suggested that obesity was a clinically important and potentially modifiable determinant of left ventricular mass. However, they did not report the partial correlation coefficients to determine the relative impact of linear growth and obesity. In the Muscatine Study, Malcolm et al5 found significant correlations between left ventricular mass and height, weight, and Quetelet index. In a more recent investigation, investigators from the Muscatine Study used bioelectric impedance analysis to attempt to separate the effects of fat-free body mass in a population of white children 8 to 12 years old.21 They found that 72% of the variability in left ventricular mass was explained by fat-free mass, sum of skinfolds, and peak exercise systolic blood pressure. They reported that fat-free mass explained 50% and sum of skinfolds 15% of the variance of left ventricular mass in boys. In girls, fat-free mass explained 62% of the variance of left ventricular mass, and sum of skinfolds was not an independent predictor of left ventricular mass. In our study, which used DEXA, a more definitive measurement of lean body and fat mass, we found that lean body mass explained 75% of the variance of left ventricular mass overall. We also found that fat mass was a statistically significant but minor predictor of left ventricular mass in both boys and girls.
The results of this study indicate that fat mass is a relatively weak correlate and independently explains only ≈1.5% of the variance of left ventricular mass index. This suggests that fat mass has a relatively minor clinical role in determining left ventricular mass. This is consistent with the findings of Verhaaren et al,22 who reported that when using the bivariate common-factor model in a twin study, they found that specific environmental influences common to weight and left ventricular mass account for <3% of the total variability in white children of both sexes. They also found that >90% of the correlation between weight and left ventricular mass was explained by genetic effects.
Although we have separated the impact of lean body mass and fat mass on left ventricular mass, it is important to remember that lean body mass may also be increased in childhood obesity.23 The mechanism of the increase in lean body mass associated with obesity is poorly understood, but it may be responsible for some of the pathological effects of obesity, such as hypertension24 or left ventricular hypertrophy. The effects of weight loss on lean body mass in obese individuals is also poorly understood. Longitudinal studies will be necessary to better understand these relationships.
The role of sexual maturation in determining left ventricular mass has not been studied extensively. In the Muscatine Study, Janz et al21 found that there was a univariate association between testosterone levels and left ventricular mass in both boys (r=.35) and girls (r=.55). Tanner staging was also performed in that study, but the correlation with left ventricular mass is not reported. In their multivariable analysis, testosterone level was not a significant independent correlate of left ventricular mass for either boys or girls. Our results confirm these findings. We did not find a significant independent relationship between sexual maturation and left ventricular mass. This suggests that the impact of sexual maturation on left ventricular mass operates through changes in body size. This is consistent with the results reported by Verhaaren et al22 in the Medical College of Virginia Twin Study. However, a longitudinal study with better biochemical indexes of sexual maturation may be needed to provide a definitive answer to this question.
The role of blood pressure in determining left ventricular mass has also been debated. The relationship is biologically plausible in that the increased afterload associated with elevation of blood pressure presents a stimulus for hypertrophy to reduce the peak systolic wall stress of the left ventricle. We previously reported a significant independent association between measures of afterload and left ventricular mass index in young patients with hypertension.25 However, studies have not always documented a relationship between resting blood pressure and left ventricular mass. For example, we reported that systolic blood pressure at maximum bicycle exercise was a correlate of left ventricular mass index, but resting blood pressure was not, in a population of children and adolescents with essential hypertension.26 Janz et al21 reported similar findings in a population of normal children from the Muscatine Study. Conversely, Goble et al7 found that resting systolic blood pressure was a determinant of left ventricular mass in boys but not in girls. Malcolm et al5 found that resting systolic and diastolic blood pressures were independent predictors of left ventricular mass in a large group of 904 children 6 to 16 years old in the Muscatine Study. They also found that systolic blood pressure was a stronger predictor of left ventricular mass than was diastolic blood pressure. In the Bogalusa Heart Study, Urbina et al6 found univariate associations between systolic and diastolic blood pressures and left ventricular mass, but they did not find that blood pressure was significant in a multivariable analysis of follow-up left ventricular mass after anthropometric variables were included in the regression model.
We found a statistically significant but weak independent association between systolic blood pressure and left ventricular mass after lean body mass and fat mass were included in the overall multiple regression model. This suggests that blood pressure plays a biologically important role in determining left ventricular mass and that the role of blood pressure is additive to that of obesity. This is similar to the findings reported by deSimone et al27 in adults. However, the weakness of the association suggests that resting systolic blood pressure is unlikely to play a clinically significant role in determining left ventricular mass in normal children and adolescents.
We found some differences in the role of blood pressure by race and sex. Diastolic blood pressure was a significant determinant of left ventricular mass in white but not black subjects. Systolic blood pressure was included in the multiple regression model for girls but not for boys. However, these results must be interpreted with caution, because resting blood pressure is only a weak determinant of left ventricular mass and the sample size is reduced in race- and sex-specific analyses. Ambulatory blood pressure monitoring and the response of blood pressure to exercise were not included in the present study but may provide improved explanation of the variance of left ventricular mass.
Left ventricular hypertrophy increases the risk of cardiovascular morbidity and mortality in adults.1 2 3 However, the factors leading to the development of left ventricular hypertrophy are not well established. The early developmental stages in children and adolescents are poorly understood. In any epidemiological investigation, it is important to determine statistical significance to evaluate the role of chance in the observed results. It is also important to assess the likely biological and clinical importance of results that are statistically significant.28 This study provides an opportunity to separate the effects of lean body mass and fat mass on left ventricular mass in a definitive way. It is clear from these results that lean body mass, fat mass, and to a lesser extent, blood pressure all have a statistically significant independent association with left ventricular mass in normal children and adolescents. Sexual maturation apparently does not have a significant association with left ventricular mass independent of body size. This indicates that linear growth, obesity, and blood pressure all are likely to play an important biological role in determining left ventricular mass. However, fat mass and systolic blood pressure appear to have only a small impact on left ventricular mass after the effect of lean body mass is accounted for. This suggests that fat mass and blood pressure are likely to be of only minor clinical importance in determining left ventricular mass in normal children and adolescents. Obesity and blood pressure elevation represent two potentially modifiable factors that affect left ventricular mass. However, preventive measures directed at modifying obesity and blood pressure may have only a limited impact on modifying left ventricular mass in young people.
This study was supported in part by grant R01-HL-34698 from the National Heart, Lung, and Blood Institute and US Public Service Grant RR-08084 from the National Center for Research Resources, General Clinical Research Centers Program, National Institutes of Health.
- Received June 27, 1995.
- Revision received August 16, 1995.
- Accepted September 25, 1995.
- Copyright © 1995 by American Heart Association
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