Central adiposity and hemodynamic functioning at rest and during stress in adolescents

Abstract

OBJECTIVE

To examine the impact of central adiposity upon hemodynamic functioning at rest and during stress in adolescents.

DESIGN

Cross-sectional, correlational study.

SUBJECTS

46 White and 49 Black normotensive adolescents with family histories of essential hypertension.

MEASUREMENTS

Systolic and diastolic blood pressure (SBP, DBP), cardiac output and total peripheral resistance responses were assessed at rest, during postural change, video game challenge and forehead cold stimulation. Specific lower and higher waist-to-hip ratio (WHR) tertiles were created for each gender and then integrated for analyses. This resulted in a lower WHR tertile of 11 Whites and 21 Blacks and an upper WHR tertile of 15 Whites and 17 Blacks.

RESULTS

No differences in age, gender or ethnicity proportions were found between tertile groups (all P > 0.21). The upper WHR group showed greater body weight, waist and hip circumferences, body mass index (BMI), triceps skinfold and body surface area (all P < 0.001). Controlling for peripheral (that is, triceps skinfold) and overall (that is, BMI) adiposity, the upper WHR group exhibited greater SBP (that is, peak response minus mean pre-stressor level) to all three stressors and greater DBP reactivity to postural change and cold pressor (all P < 0.05).

CONCLUSION

Central adiposity appears to adversely influence hemodynamic functioning during adolescence. Underlying mechanisms responsible for these associations require exploration.

Introduction

Obesity has long been recognized as a risk factor for numerous health problems including cardiovascular diseases (CVD).^1,2 Recent findings have indicated that specific fat deposition sites confer differential risks for development of CVD. Specifically, central adiposity (for example waist-to-hip ratio (WHR)) has been identified as a more powerful predictor of essential hypertension (EH), CVD and premature death, than measures of peripheral (for example, triceps skin-folds) or general adiposity (for example, body mass index (BMI)).^3–5 WHR has frequently been used in epidemiological research as a measure of central obesity.^4–6

Exaggerated sympathoadrenal responsivity to stress has been proposed as one mechanism linking central adiposity to CVD.^6,7 Moyer et al ⁸ found increased central adiposity, (that is, high WHR) associated with exaggerated blood pressure reactivity and cortisol release to a battery of acute psychological stressors in women. Other studies involving men and women have found central adiposity, as measured by WHR, to be associated with endocrine aberrations such as deranged steroid hormone secretion⁹ and elevated cortisol output due to increased sensitivity along the hypothalamic-pituitary-adrenal (HPA) axis during stress.¹⁰ Recently, using a sample of normotensive young men, Jern et al ¹¹ observed that increased WHR was associated with increased total peripheral resistance reactivity to a psychological stressor.

Longitudinal epidemiological studies and necropsy findings have shown that the pathogenesis of CVD has its origins in childhood.^12,13 Only a few studies have addressed the relationship between general adiposity and CV responsivity to stress in youth and none have evaluated the role of central adiposity.^14–16 The purpose of this study was to provide an exploratory examination of the impact of central adiposity upon hemodynamic functioning at rest and in response to stress in adolescents with family histories of EH. Studies with such youth are particularly needed as they are at increased risk for development of EH compared to negative family history cohorts.^17–19

Methods

Subjects

From participants in a longitudinal study of the development of EH risk factors,^20,21 95 adolescents with a mean age of 14.8 ± 1.4 y were selected, based upon age (≥13 y). All subjects had a family history of EH defined as having at least one biological parent and one biological grandparent with EH, verified by physician reports or hospital records. All subjects were apparently healthy, normotensive, nondiabetic, nonsmokers and free from chronic disease, based on examination by a pediatrician and parental report of the subject’s medical history. The study was approved by the institutional human assurance committee.

Anthropometric assessments

Informed written consent was obtained and anthropometric measures were collected using established protocols. Weight and height were measured, without shoes, using a Healthometer scale and standard stadiometer. Body mass index (BMI) was calculated as weight/height². Waist circumference was measured at the center of the umbilicus and hip circumference was measured at the level of the greater trochanters (widest point of the buttocks). Two sets of measurements were recorded and averaged, from which WHR was determined. The triceps skinfold was measured three times on the right side of the body with Lange calipers and the readings were averaged.

Hemodynamic assessments

After anthropometric measurements were completed, subjects were fitted with an appropriate sized blood pressure (BP) cuff on the right arm. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were monitored with a Dinamap Vital Signs Monitor (Model 1846SX: Critikon, Inc. Tampa, FL) which has been validated for use at rest and during laboratory stressors.^22,23 Subjects were instrumented with two sets of tetrapolar electrodes (one current emitting and one sensing) interfaced with a noninvasive thoracic electrical bioimpedance system (NCCOM-3 Model 6; Bo-Med Medical Manufacturing Ltd, Irvine, CA). This system has been validated via comparison with simultaneous cardiac output (CO) values derived from oximetric measurements using the Fick equation.^24,25 Cardiac output was calculated every successive 12 QRS complexes with the NCCOM, while the Dina-map was inflating and calculating BPs. These values were averaged to provide one measurement for each BP evaluation. Blood pressure and CO values were measured simultaneously and used to calculate total peripheral resistance (TPR):

$$\text{TPR}=([\text{SBP}+2\times \text{DBP}])\text{hskip}50\text{pt}\text{CO}\text{expressed}\text{as}\text{mm}\text{Hg}min)$$

Following fitting of the hemodynamic monitoring equipment, the subject was placed in a supine position with their head propped up on a pillow and instructed to relax as completely as possible for 15 min. All hemodynamic responses were simultaneously measured at the end of the 11th, 13th and 15th minute. Following this, three stressors were presented in the following order: postural change, video game and forehead cold stimulation. A 5 min supine prestressor period preceded each stressor with hemodynamic parameters assessed every other minute. Details of the stressor protocols are presented elsewhere.^20,21 Briefly, for the postural change stressor, the subject stood and placed the right arm at a 90° angle across the trunk and hemodynamic responses were recorded at 1 min intervals for 3 min. The 5 min video game challenge was based upon the protocol of Murphy et al.²⁶ The subject remained supine with a 68.5 cm color television positioned at an appropriate height and angle for viewing the video game ‘Breakout’ (Atari, Inc.). Three sets of hemodynamic readings were obtained during 1st, 3rd and 5th minute of the video game challenge, in which monetary incentive was used to increase involvement. The forehead cold stressor consisted of having a plastic bag of crushed ice and water (3–5°C) placed across the subject’s forehead for 1 min, while the subject was in a supine position. One set of hemodynamic readings was obtained during the last 30–40 s of stimulation, after which the ice pack was removed.

Hemodynamic data were reduced by computing mean scores for measures obtained during the initial supine rest and for each prestressor period. Reactivity change scores were then calculated by subtracting mean values obtained during the prestressor period immediately preceding the stressor from the peak reading obtained during the stressor.

Results

Anthropometric and demographic characteristics

Specific lower and higher WHR tertiles were created for each gender and then integrated for analysis. This resulted in a lower WHR tertile of 11 Whites (five male) and 21 Blacks (11 male) and an upper WHR tertile of 15 Whites (nine male) and 17 Blacks (seven male). Descriptive characteristics of the lower and upper WHR groups are presented in Table 1. There were no significant differences between the two groups in age (P > 0.83) or height (P > 0.79). The upper WHR group showed greater body weight, body surface area, BMI, waist and hip circumferences, and triceps skinfolds (all P < 0.001). The use of integrated gender-specific WHR tertiles, resulted in comparable distributions by gender between the two groups. Although there was a higher proportion of Blacks in the lower WHR tertile than in the upper tertile, differences in the proportions by WHR tertile group were not statistically significant (P > 0.30). There were overall gender differences in adiposity, with males having a greater WHR, lower triceps skinfold and lower hip measures (all P < 0.03). No race differences were observed in any of the anthropometric measures (all P > 0.07).

Table 1.

Descriptive characteristics by central adiposity classification

Characteristics	Lower WHR tertile	Upper WHR tertile	P value
Anthropometric/demographic
Age (y)	14.8 ± 1.3	14.8 ± 1.5	> 0.83
Height (cm)	164.4 ± 9.7	163.8 ± 8.3	> 0.79
Weight (kg)	58.1 ± 14.0	77.7 ± 17.4	< 0.001
Body surface area (m2)	1.6 ± 0.2	1.8 ± 0.2	< 0.001
BMI (kg/m2)	21.4 ± 4.5	29.0 ± 6.3	< 0.001
Waist circumference (cm)	26.8 ± 3.1	36.0 ± 5.1	< 0.001
Hip circumference (cm)	36.7 ± 4.2	41.6 ± 5.1	< 0.001
WHK	0.7 ± 0.03	0.9 ± 0.06	< 0.001
Triceps skinfolds (mm)	13.5 ± 9.6	29.1 ± 13.3	< 0.001
Resting hemodynamics
SBP (mmHg)	118.6 ± 10.6	117.0 ± 10.8	> 0.98a
DBP (mmHg)	62.9 ± 7.8	61.9 ± 6.0	> 0.85a
CO (L/min)	8.2 ± 2.1	6.3 ± 2.1	> 0.12a
TPR (mmHg/(L/min))	10.5 ± 3.0	13.9 ± 4.2	> 0.11a

Values are means ± standard deviations. BMI = body mass index; WHR = Waist-to-hip ratio; SBP = systolic blood pressure; DBP = diastolic blood pressure; CO = cardiac output; TPR = total peripheral resistance.

^amaximal P values after covarying triceps skinfolds or BMI.

Hemodynamic characteristics

The means and standard deviations for the hemodynamic parameters at rest are presented in Table 1. Reactivity change scores to the three stressors are presented in Table 2. Initially, a multivariate analysis of covariance was conducted comparing the two WHR groups on all four hemodynamic parameters at initial supine rest and in response to the three stressors. Since the two WHR groups differed in overall (that is, BMI) and peripheral (that is, triceps skinfold) adiposity, these parameters were used as covariates in separate analyses. In this way, any observed differences between the two groups could more readily be attributed to differences in central adiposity, rather than to overall or peripheral adiposity. Significant overall effects were observed for both multivariate analyses (all P < 0.001). A series of univariate analyses of covariance were subsequently conducted covarying either triceps skinfold or BMI.

Table 2.

Reactivity change score comparisons by central adiposity classification

Hemodynamic reactivity	Lower WHR tertile	Upper WHR tertile	P valuea
Postural change
SBP (mmHg)	5.9 ± 10.8	12.7 ± 9.8	< 0.03
DBP (mmHg)	8.1 ± 6.7	14.0 ± 9.6	< 0.01
CO (L/min)	−0.22 ± 1.3	0.7 ± 1.0	> 0.058
TPR (mmHg/(L/min))	0.9 ± 2.3	0.7 ± 2.7	> 0.69
Video game
SBP (mmHg)	7.8 ± 7.1	17.0 ± 11.0	< 0.002
DBP (mmHg)	8.6 ± 7.4	12.7 ± 8.5	> 0.08
CO (L/min)	−0.1 ± 1.1	0.1 ± 0.8	> 0.22
TPR (mmHg/(L/min))	3.6 ± 5.9	4.8 ± 3.8	> 0.80
Cold pressor
SBP (mmHg)	8.2 ± 8.1	14.0 ± 14.8	< 0.11
DBP (mmHg)	13.3 ± 8.9	17.7 ± 8.4	< 0.05
CO (L/min)	−0.94 ± 1.0	−0.34 ± 1.1	> 0.37
TPR (mmHg/(L/min))	5.5 ± 4.4	7.0 ± 4.7	> 0.60

Values are means ± standard deviations. WHR = Waist-to-hip ratio; SBP = systolic blood pressure; DBP = diastolic blood pressure; CO = cardiac output; TPR = total peripheral resistance.

^aMaximal P values after covarying triceps skinfolds or body mass index.

No significant differences were observed between the groups in resting hemodynamics when the triceps skinfold or BMI were statistically controlled (all P > 0.11). With regard to hemodynamic reactivity, both covariate analyses revealed that the upper WHR group exhibited significantly greater SBP reactivity to postural change and video game challenge and greater DBP reactivity to postural change and cold stimulation (all P < 0.05). The upper WHR group also exhibited greater SBP reactivity to forehead cold, when triceps skinfold was covaried (P < 0.04), but a trend was only noted when BMI was controlled (P < 0.11). It should be noted that when the above analyses were also conducted using the mean hemodynamic response rather than peak response in the calculation of reactivity change scores, the same pattern of significant results were observed for each stressor.

Discussion

The present findings indicate that increased central fat deposition, as measured by WHR, was associated with increased hemodynamic responsivity during stress in a group of normotensive adolescents with family histories of essential hypertension. Specifically, statistically controlling for peripheral (that is, triceps skinfold) or overall (that is, BMI) adiposity, no significant differences were noted between the two WHR groups on any of the resting hemodynamic parameters. However, the upper WHR group exhibited significantly greater increases in SBP and/or DBP to postural change, video game challenge and forehead cold stimulation. The BP reactivity differences appeared to be due to a combination of changes in vascular (that is, TPR) and myocardial (that is, CO) activity among the upper WHR group, although neither reached statistical significance.

A number of studies have been conducted with youth which examined relationships between adiposity and resting hemodynamics. These studies have generally found various measures of general adiposity (for example, BMI, and summation of multiple skinfold sites) to be positively associated with resting SBP and DBP.^27–29 With regard to central adiposity, Gillum² reported that increased WHR was associated with higher resting SBP and DBP in children aged 6–17 y. In the present study, prior to controlling for peripheral or general adiposity, the upper WHR group exhibited significantly higher resting TPR and lower CO. The latter finding is consistent with the work of Jern et al,¹¹ who observed that central adiposity, as measured by WHR without adjusting for peripheral or general adiposity, was negatively associated with CO at rest in a sample of healthy normotensive men aged 18–22 y.

Of the few youth studies conducted, findings have been mixed with regard to relationships between adiposity and stress reactivity. Alpert et al ¹⁴ found a positive relationship between a measure of general adiposity (that is, BMI) and BP reactivity to dynamic exercise in children aged 6–16 y. Other pediatric studies have not observed significant relationships between measures of body adiposity and various lab stressors including mental arithmetic, handgrip exercise, video game challenge and cold pressor.^15,16 Reasons for discrepancies between these studies may be due, in part, to methodological differences, including the type of adiposity evaluated (for example, general vs central adiposity), subject characteristics (for example pre- vs post-pubertal youth) and the type of stressors used (for example, challenging psychological vs passive physical).

Recent studies in adults have indicated that sympathetic arousal to stress may be one pathway by which central adiposity may be linked to CVD.^8,10 Jern et al¹¹ recently found that central obesity, as measured by WHR, without adjustment for peripheral or general adiposity, was associated with higher TPR responsivity to a psychological stressor in a sample of young healthy normotensive men. Overreactivity of the sympathetic nervous system has been implicated in the pathogenesis of hypertension.^18,21,27 Collectively, our findings involving adolescents and those of Jern et al¹¹ with young adults, suggest that various neuro-hormonal and growth-related changes associated with pubertal maturation (which include significant WHR changes) may be necessary before consistent relationships are observed between sympathetic arousal to stress and central adiposity.

Conclusion

Although the present findings are intriguing, they must be viewed as tentative for several reasons. First, the sample size comprised of youth with strong family histories of EH. Such individuals are more prone to exhibit exaggerated sympathetic arousal to stress, compared to the negative family history cohorts.²¹ Thus, whether the observed positive relationships between central adiposity and BP reactivity would generalize to youth, without family histories of cardiovascular disease, is unknown and deserves empirical evaluation. Second, the WHR, a useful index of central adiposity, is influenced by both subcutaneous and visceral adipose tissue in the abdominal region.³⁰ It is unclear whether the observed relationships are attributable more to visceral adiposity, which was recently identified as the specific type of fat most strongly associated with numerous CVD risk factors.^31,32 Future studies would benefit from inclusion of computed tomography (CT) or magnetic resonance imaging (MRI) of visceral adiposity. Finally, given the exploratory nature of the study, underlying factors which might link hemodynamic stress reactivity with increased central adiposity and eventually to the development of CVD, were not assessed. These include lifestyle factors of sedentary behavior and augmented intake of carbohydrates and sodium, all of which have been associated with increased hemodynamic stress reactivity^15,27 and obesity in youth.^33–35 Likewise, possible imbalances in metabolic and endocrine activity (for example, increased cortisol, decreased insulin sensitivity) were not assessed which have been associated with increased sympathetic arousal to stress and susceptibility to visceral fat accumulation.^8,10,36,37 Nevertheless, the current findings are provocative and support the need for further research examining relationships between hemodynamic stress reactivity, central adiposity and cardiovascular health.