(Hypertension. 1996;28:37-41.)
© 1996 American Heart Association, Inc.
Articles |
Correlates of the Hemodynamic Determinants of Blood Pressure
the Division of Cardiology, Department of Pediatrics, University of Cincinnati, College of Medicine, and the Children's Hospital Medical Center, Cincinnati, Ohio.
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Abstract |
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The purpose of this study was to investigate the association of sex, race, lean body mass, and fat mass with the hemodynamic determinants of blood pressure, including stroke volume, heart rate, and total peripheral vascular resistance. The study included 201 subjects aged 6 to 17 years, 105 of whom were male and 98 of whom were black. Lean body mass and fat mass were both significant (P<.05) independent determinants of stroke volume, cardiac output, and total peripheral vascular resistance. However, the direction of the effect of lean body mass was opposite for stroke volume and cardiac output compared with that of total peripheral vascular resistance. The direct relationship of lean body mass with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (regression coefficients, 0.55±0.05 for SBP and 0.47±0.05 for DBP) indicates that the effect of lean body mass on cardiac output may predominate. Lean body mass explained substantially more of the variance of the hemodynamic variables than did fat mass. After control for the effects of body size, male subjects had higher heart rate and cardiac output, and female subjects had higher vascular resistance. White subjects had higher stroke volume and cardiac output, and black subjects had higher peripheral vascular resistance. This study demonstrates that lean body mass is a more important correlate of the hemodynamic determinants of blood pressure than is fat mass and that sex and race have significant independent relationships with the hemodynamic determinants of blood pressure in children and adolescents.
Key Words: hemodynamics • obesity • ethnic groups • adolescents • cardiac output • heart rate • vascular resistance
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Introduction |
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It is well known that body size is associated with the level of blood pressure (BP) in both children and adults.1 2 This relationship has led to the recommendation that BP standards in children and adolescents should account for height.3 It has also been shown that obesity is related to BP level.4 The hemodynamic determinants of BP include cardiac output, which is governed by stroke volume and heart rate, and total peripheral vascular resistance. The relative effects of lean body mass and fat mass on the hemodynamic determinants of BP have not been well studied in children and adolescents. One reason for this is that it has been difficult to measure lean body mass and fat mass in this population. Recently, dual-energy x-ray absorptiometry has been shown to be a simple, valid, and reliable method for determination of lean body mass and fat mass in children.5 6 7 8
Our purpose in this study was to investigate the relative role of lean body mass and fat mass in determining stroke volume, heart rate, and total peripheral vascular resistance in children and adolescents. In addition, we evaluated whether race and sex were significant correlates of the hemodynamic determinants of BP after controlling for the effects of lean body mass and fat mass.
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Methods |
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The investigation was a cross-sectional study of 201 children aged 6 to 17 years. Subjects were recruited from schools in the Cincinnati area and were included in the study after documentation of informed consent by the subject's parent or guardian. This study was approved by the Institutional Review Board of Children's Hospital Medical Center, Cincinnati, Ohio.
Measurements
Anthropometric Measurements
The examination included measurement of height and weight. Body surface area was calculated from height and weight. Lean body mass and fat mass were determined with dual-energy x-ray absorptiometry (DEXA). This method uses two low-energy x-ray beams that traverse the body. The resultant energy collected by the external detector has been attenuated by the body tissue through which it has passed. The number of photons per unit area is corrected for soft tissue by a linear two-dimensional interpolation. The corrected values are then summed for determination of the bone mineral content. Soft tissue is resolved by mass attenuation coefficients derived from tissue equivalent standards for fat-free and fat tissue. DEXA has been shown to provide accurate and precise measurements of bone mineral content, fat-free mass, and total body fat.4 5 6 7 8 DEXA has been validated against the hydrodensitometry method, which has previously been established as the most reliable and valid method for measurement of lean body mass, but it is cumbersome to use.8 In this study, subjects were scanned with a Hologic (QDR-1000/W) whole-body scanner. Body composition was divided into bone mass and soft tissue mass, which was then divided into lean body mass and fat mass.
Blood Pressure
The staff received a standard 16-hour BP measurement training course and were certified according to a previously established protocol.9 BP was measured with the subject seated quietly with the use of auscultation and a mercury sphygmomanometer according to the methods set forth by the Second National Heart, Lung, and Blood Institute Task Force on Blood Pressure Control in Children.10 Three BP measurements were taken in the right arm with an appropriately sized cuff. The onset of the fifth Korotkoff phase was used for determination of DBP. The average of the three measurements was used in the analysis. Mean BP was calculated with the equation Mean BP=DBP+1/3(SBP-DBP). Heart rate was obtained by palpation of the brachial pulse over 30 seconds with the subject seated.
Echocardiography
Echocardiographic examination was performed with standard techniques and the subjects in the supine position. Studies were performed with two-dimensional and M-mode echocardiograms. Measurements were made according to the American Society of Echocardiography.11
Stroke Volume
Left ventricular end-diastolic and end-systolic volumes were calculated from M-mode measurements according to the cube formula reported by Meyer et al.12 Stroke volume was determined with this approach, which has been shown to correlate well with invasive and two-dimensional echocardiographic volume measurements.13 14
Cardiac Output
Cardiac output was calculated from stroke volume and heart rate. This method has been shown to correlate well with invasive dye dilution and Doppler methods of cardiac output determination.14 15
Total Peripheral Vascular Resistance
The concurrent determination of cardiac output and mean BP allows the derivation of systemic vascular resistance to blood flow.16 Total peripheral vascular resistance is calculated by the equation TPR (dyne·sxcm-5)=(MBP/CO)x80, where TPR is total peripheral vascular resistance, MBP is mean BP, and CO is cardiac output.
Statistical Analysis
Descriptive statistics are presented with mean±SD for continuous variables. Differences in hemodynamic variables by sex and race were determined by Student's t test for independent samples. Bivariate associations between anthropometric and hemodynamic variables were assessed with Pearson correlation coefficients. Stepwise multiple linear regression was used for evaluation of the independent correlates of the hemodynamic variables. Dummy variables were constructed for sex and race for determination of whether these variables were significant independent correlates of the hemodynamic variables. Independent variables were allowed in the model if their regression coefficients were significantly different from zero. Partial R2 coefficients were used for determination of the relative proportion of the variance of the dependent variable that was explained by each of the independent variables included in the multiple regression model. A two-tailed value of P<.05 was considered statistically significant. Further evaluation included analysis of residuals for determination of whether there were any undetected trends with age.
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Results |
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The subjects in this investigation included 105 boys and 96 girls, aged 6 to 17 years; 103 subjects were white and 98 were black. The mean age was 11.7±2.7 years; height was 1.51±0.17 m; weight was 48.4±20.3 kg; SBP was 108.1±11.9 mm Hg; and DBP was 68.9±11.2 mm Hg. The mean values for lean body mass, fat mass, cardiac output, stroke volume, heart rate, and total peripheral vascular resistance are presented in Table 1
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SBP and DBP were compared by sex and race. It was found that SBP was significantly higher in boys than girls (110.0±12.7 versus 106.0±10.7 mm Hg, P=.02), but there was no significant difference in DBP by sex. Black subjects had significantly higher DBP than white subjects (70.7±12.3 versus 67.2±9.8 mm Hg, P=.03). However, there was no significant difference in SBP by race. The sex and race differences in cardiac output, stroke volume, heart rate, and total peripheral vascular resistance are presented in Table 2.
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Bivariate correlation coefficients for the relationships between body size variables and hemodynamic variables are presented in Table 3. These correlations demonstrated that SBP, DBP, cardiac output, and stroke volume were all directly associated with measures of body size. The strongest correlates were lean body mass and body surface area, whereas fat mass consistently had the weakest association. In contrast, heart rate and total peripheral vascular resistance were inversely associated with measures of body size. Again, fat mass had the weakest association with heart rate and total peripheral resistance, and the correlation coefficient for the relationship between fat mass and heart rate was not statistically significant.
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The results of multiple regression analyses are presented in Table 4. These results indicated that lean body mass was the sole significant determinant of SBP, whereas sex was also included with lean body mass in the regression model to explain the variance of DBP. Lean body mass was also an independent direct determinant of stroke volume, cardiac output, SBP, and DBP. Lean body mass was an independent inverse determinant of total peripheral vascular resistance.
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Fat mass was a significant independent direct correlate of stroke volume and cardiac output and a significant independent inverse correlate of peripheral vascular resistance. Sex was also a significant correlate of stroke volume and cardiac output and an inverse correlate of total peripheral resistance after lean body mass and fat mass were included in the model. These results indicated that after body size was controlled, males had higher stroke volume than females, whereas females had higher total peripheral vascular resistance than males. Race had a significant direct association with cardiac output and heart rate but a significant inverse relationship with total peripheral resistance after the effects of body size were taken into account. These results indicated that after body size was controlled, white subjects had higher heart rate and cardiac output than black subjects, but blacks had higher total peripheral vascular resistance than whites. Examination of residuals plotted against age and ANCOVA indicated that the sex differences seen were consistent over the entire age range studied, and there were no trends with age for the hemodynamic factors investigated after the variables included in the regression analysis had been taken into account.
These results demonstrated that lean body mass was the strongest correlate of all of the hemodynamic variables studied except heart rate. This underscores why lean body mass is such an important determinant of SBP and DBP. Height was the strongest determinant of heart rate, but the multiple regression model including height and race was only able to explain 11% of the variance of heart rate. This indicates that other factors not included in this analysis are likely to be important determinants of heart rate.
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Discussion |
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It is well documented that obesity is associated with elevated BP.4 17 However, it is also well known that other body size measures, such as height, are strong correlates of BP.1 2 3 The relative roles of lean and fat body mass in the determination of BP level have not been investigated in children and adolescents. In the present study, lean body mass was the predominant determinant of SBP and DBP. Sex was also an independent correlate of DBP but not of SBP. These results indicate that observed sex differences in SBP are likely to be due to differences in lean body mass. However, for DBP, sex is significant after lean body mass is included in the regression model, suggesting that there may be additional sex-related factors not included in the present analysis that are associated with DBP.
The relationship of lean body mass and fat mass to the determinants of BP, stroke volume, heart rate, and total peripheral vascular resistance have also not been well studied, particularly in children and adolescents. Previous investigations have shown a direct relationship between obesity and cardiac output.18 19 20 However, these studies have usually used body mass index as the measure of obesity. Body mass index includes elements of both fat mass and lean body mass. The present analysis demonstrates that lean body mass and fat mass are both significant correlates of cardiac output. However, lean body mass explains a much larger proportion of the variance (33% versus 3%) of cardiac output than fat mass. This result is probably explained by the fact that fat mass is a tissue with much lower metabolic demand than lean body mass.21 Cardiac output is likely to be regulated by the body's metabolic demand, which is largely determined by lean body mass. The development of obesity may involve increases in both fat mass and lean body mass.22 23 The increase in lean body mass observed with obesity may occur in part to support the increasing fat mass. In this cross-sectional study, it was not possible to partition the true lean body mass from lean mass that may be associated with fat tissue. Longitudinal studies will be needed to delineate these relationships.
As might be expected from the relationships with cardiac output, lean body mass and fat mass are also significant independent correlates of stroke volume, with lean body mass explaining 49% and fat mass 2% of the variance of stroke volume in the multiple regression model. Sex is also a significant independent correlate of stroke volume after lean body and fat mass have been included in the regression model. This indicates that sex differences other than body size have a relationship with stroke volume. This is different from the evaluation of left ventricular mass, in which body size differences between males and females do appear to account for the observed differences in left ventricular mass by sex.24 25 Thus, the mechanisms of the sex difference in stroke volume remain unexplained.
Although the variables included in the multiple regression analysis could explain 52% of the variance of stroke volume, only 11% of the variance in heart rate could be explained. Height was inversely associated with heart rate. This finding is consistent with the known decline in resting heart rate with increasing age over the age range included in this investigation.26 Race is also a significant correlate of heart rate in the present study. This is consistent with the results of previous studies, including the second National Health and Nutrition Examination Survey (NHANES II) and the Coronary Artery Risk Development in Young Adults (CARDIA) study, which showed that young white subjects have higher heart rates than do young black subjects.27 28 This ethnic difference in heart rate has been previously shown to be largest for children, it remains significant but decreases for young adults, and eventually disappears in middle age. The lack of a relationship of fat mass with heart rate in the present study is also consistent with the CARDIA study, which found no relationship between body mass index and heart rate in adults.27
The other major determinant of BP is total peripheral vascular resistance. Both lean body mass and fat mass are significant correlates of vascular resistance; however, they are inversely related. These results indicate that increased lean body mass and increased fat mass are associated with decreased total peripheral vascular resistance. In the present study, race and sex are also independently associated with total peripheral resistance after control for body size. The observed influence of race on vascular resistance is consistent with several previous studies. Arensman et al29 demonstrated that 10-year-old black male subjects had higher systemic vascular resistance both at rest and during exercise than white subjects. In the Bogalusa study, Soto et al30 also found that black males aged 7 to 22 years had higher resistance than white subjects. Dysart et al31 showed that there were ethnic differences in total peripheral vascular resistance in girls with a family history of hypertension that were independent of age, height, weight, and body mass index.
In the present study, lean body mass and fat mass were both found to be significant correlates of stroke volume, cardiac output, and total peripheral vascular resistance. However, the direction of the effect of lean body mass and fat mass was opposite for stroke volume and cardiac output compared with that for total peripheral vascular resistance. This indicates that increased lean body mass and fat mass tend to raise BP by increasing cardiac output but also may tend to lower BP by decreasing vascular resistance. The regression coefficient for lean body mass was positive in the regression models for SBP and DBP. This suggests that the relationship of lean body mass to cardiac output may have a greater overall influence on BP level than the relationship of lean body mass to vascular resistance. In addition, race and sex were both significant independent determinants of cardiac output and total peripheral resistance after the effects of body size were accounted for. White and male subjects tended to have higher cardiac output, whereas black and female subjects tended to have higher total peripheral vascular resistance. Similar findings in previous investigations led Falkner32 to suggest that the racial difference in the resistance component of BP may be contributing to BP elevation at an earlier age in blacks. The results of the present study demonstrate that race, sex, lean body mass, and fat mass are all independently related to the hemodynamic parameters that determine BP and that lean body mass is a more important determinant of the hemodynamic variables than fat mass in normal children and adolescents. Further longitudinal studies that focus on changes in lean body mass, fat mass, and hemodynamic variables will be necessary for evaluation of these interrelationships and understanding of the genesis of BP elevation more completely.
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Acknowledgments |
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This work was supported in part by grant R01-HL-34698 from the National Heart, Lung, and Blood Institute and grant RR08084 from the National Center for Research Resources, General Clinical Research Centers Program, National Institutes of Health.
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Footnotes |
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Reprint requests to Stephen R. Daniels, MD, PhD, Division of Cardiology, Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229.
Received December 21, 1995;
first decision January 23, 1996; first decision March 11, 1996;
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