Abstract
AIMS
Arterial pressure transfer to the periphery is accompanied by pulse pressure amplification (PPA). Pulse pressure is influence by body fat. The purpose of the present study was to evaluate any possible inter-relation between body fatness and PPA in healthy subjects.
METHODS
Haemodynamic and wave reflection indices were estimated by pulse wave analysis. Body fat was measured by bio-impedance.
RESULTS
A total of 367 healthy volunteers (136 men and 231 women) was studied. Pulse pressure amplification correlated significantly with percentage of body fat (r = −0.53, P < 0.0001), age (r = −0.62, P < 0.0001), height (r = 0.43, P < 0.0001), heart rate (r = 0.28, P < 0.0001) and mean blood pressure (r = −0.29, P < 0.0001). The association of PPA with body fat was also significant in a multiple linear regression model. Age was an independent predictor of PPA and analysis of study subjects subdivided into two groups, those <50 years and those >50 years showed that body fatness correlated inversely and significantly with PPA in individuals both younger and older than 50 years (r = −0.44, P < 0.0001, r = −0.37, P < 0.0001 respectively). Augmentation pressure was also associated significantly with percentage of body fat in both subgroups (r = 0.48, P < 0.0001 and r = 0.49, P < 0.0001 respectively).
CONCLUSIONS
This study performed on healthy subjects showed that pulse pressure amplification is related to body fatness over a wide age range. Percentage body fat is significantly associated with augmentation pressure, a component of central pulse pressure.
Keywords: augmentation index, augmentation pressure, body fatness, pulse pressure amplification, wave reflection
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
Aortic-brachial pulse pressure amplification (PPA) is a measure of arterial elasticity and it is also an independent cardiovascular risk factor. The PPA is mainly determined by age, height, central and peripheral pressure waveforms characteristics, including measures of arterial stiffness and wave reflection.
WHAT THIS STUDY ADDS
In this study, however, we demonstrate that PPA is also significantly associated with indirect indices of body fatness. As the body fatness is treatable, our findings might be used as a reference for future studies on the effects of body fat reduction on PPA and the PPA-related cardiovascular risk.
Introduction
Increased arterial stiffness is an independent predictor of cardiovascular outcomes [1–3]. Arterial stiffness is influenced by number of factors like age or mean blood pressure and is accelerated by hypertension or renal insufficiency. In most, but not all studies, arterial stiffness is also enhanced by obesity [4–8]. The observed discrepancy in these studies may be at least partly explained by the poor diagnostic performance of body mass index frequently used for assessing body fat content [9]. Moreover, recent analysis showed that the ‘obesity paradox’, the better outcomes for cardiovascular mortality seen in overweight and slightly obese subjects, may be associated with lack of discriminatory power of BMI to differentiate between body fat and lean mass [10, 11]. The exact mechanism by which increased adiposity can enhance arterial stiffness is currently not fully elucidated. However, there are some links between obesity and factors affecting vascular function and structure. High sensitivity C-reactive protein (CRP) is strongly associated with percent body fat [12]. Moreover CRP is correlated with arterial stiffness in apparently healthy subjects [13]. It is also well established that adipose tissue is a rich source of inflammatory cytokines and other factors influencing the arterial wall [14–16].
Pulse pressure (PP, systolic blood pressure – diastolic blood pressure) is considered as a surrogate measure of arterial stiffness and as an important risk factor for cardiovascular outcomes [17]. Peripheral pulse pressure measured at the brachial artery does not equal that obtained at a central artery (e.g. aortic pulse pressure). Physiologically, considerable pulse pressure amplification (PPA) exists between the aorta and the brachial artery [18]. Recent data indicate that a lower PPA may be associated with unfavourable effects on both central arteries and the heart [19]. Pulse pressure amplification is influenced by a number of physiological factors such as age, gender, height and heart rate [17, 20]. It was also shown that both components of PPA, namely peripheral and central pulse pressure as well as measures of wave reflection are related to adiposity [21].
However, little is known about any association between PPA and body fatness. The purpose of the present study was therefore to evaluate the inter-relation between body fatness and pulse pressure amplification in healthy subjects.
Methods
Three hundred and forty-seven healthy volunteers (223 women, 124 men; mean age 50 years, range 19–85 years) were evaluated. The subjects were recruited through a local newspaper advertisement. All the subjects were normotensive and none was taking any medication. Careful medical history taking and physical examination revealed no abnormalities and their resting ECG was completely normal. We did not exclude patients with blood pressure >140/90 on a single measurement from the study. Individuals with a history of hypertension, diabetes or taking any form of chronic medication were excluded from the study. The University Ethics Committee approved the study protocol and written informed consent was obtained from all participants.
The investigations were carried out in the morning, alcohol and caffeine having been excluded for the previous 24 h.
Non-invasive assessment of the pressure waveform
The brachial blood pressure was recorded non-invasively with the use of an oscillometric method (Colin BPM 7000, Japan). This measurement was used as a calibration value for radial tonometry. The radial pressure waveform was recorded non-invasively with a piezoelectric tonometer (Colin BPM 7000, Japan) attached to the subject's wrist. The recorded analog signal was sent in real time to SphygmoCor Mx (AtCor Medical, Australia) for on-line reconstruction of a pressure waveform characteristic for an ascending aorta with the use of a validated transfer function. Pulse wave analysis was applied to assess the peripheral and central haemodynamics. The PPA ratio was defined as the peripheral pulse pressure/central pulse pressure. The central pulse pressure consists of two components, pressure at first systolic shoulder (P1) in the arterial pulse waveform and augmentation pressure (AP), the height of the central systolic pressure above P1 (Figure 1).
Figure 1.
Aortic pressure waveform showing central pulse pressure (PP), augmentation pressure (AP) and pressure at first systolic peak (P1)
Amount of body fat
A bio-impedance analyzer (Bodystat 1500, Bodystat Ltd, UK) was used to measure the fat content as a proportion of total body mass. Bio-impedance analysis (BIA) was performed with a single frequency (50 kHz) device.
Statistical analysis
The results are expressed as the mean ± SEM and the Pearson correlation coefficient was calculated. Comparisons between groups were made using the Mann-Whitney test for unpaired observations. The association of PPA with other clinical variables such as age, heart rate, height, mean blood pressure and percent of body fat was examined with the use of multivariable linear regression. All tests were two-sided. The statistical analyses were performed using Statistica 8.0 (Stat Soft Inc, USA), with statistical significance set at P < 0.05.
Results
Table 1 demonstrates the clinical characteristics of the study subjects and the characteristics of the subjects divided into two age groups. The older subjects have a significantly lower PPA but higher mean BP and pressure at P1 as well as an augmentation pressure. Moreover the percent of body fat was higher in subjects older than 50 years.
Table 1.
Characteristics of total study population and groups defined by age
| Characteristics | Total | ≤50 years | ≥50 years | P* |
|---|---|---|---|---|
| Women (n) | 236 | 91 | 140 | |
| Men (n) | 136 | 63 | 73 | |
| Age (years) | 49 ± 0.9 | 37 ± 0.8 | 59 ± 0.5 | <0.0001 |
| Weight (kg) | 72 ± 0.7 | 73 ± 1.0 | 72 ± 0.9 | NS |
| Height (cm) | 168 ± 0.5 | 172 ± 0.7 | 166 ± 0.6 | <0.0001 |
| Waist circumference (cm) | 84 ± 0.6 | 83 ± 1 | 85 ± 0.8 | 0.01 |
| BMI (kg m−2) | 25.3 ± 0.2 | 24.4 ± 0.3 | 26.0 ± 0.3 | <0.0001 |
| Fat (%) | 30 ± 0.4 | 26 ± 0.6 | 33 ± 0.5 | <0.0001 |
| HR (beats min−1) | 68 ± 0.5 | 68 ± 0.7 | 68 ± 0.7 | NS |
| Peripheral SBP (mmHg) | 119 ± 0.8 | 114 ± 0.9 | 122 ± 1.0 | <0.0001 |
| Peripheral DBP (mmHg) | 72 ± 0.5 | 70 ± 0.7 | 74 ± 0.8 | 0.0005 |
| Central SBP (mmHg) | 109 ± 0.8 | 102 ± 0.9 | 114 ± 1.0 | <0.0001 |
| Central DBP (mmHg) | 73 ± 0.5 | 71 ± 0.7 | 75 ± 0.8 | 0.0005 |
| Mean BP (mmHg) | 89 ± 0.6 | 85 ± 0.7 | 92 ± 0.9 | <0.0001 |
| Peripheral PP (mmHg) | 47 ± 0.5 | 45 ± 0.7 | 48 ± 0.7 | 0.0005 |
| Central PP (mmHg) | 36 ± 0.5 | 31 ± 0.6 | 39 ± 0.7 | <0.0001 |
| P1 (mmHg) | 26 ± 0.3 | 25 ± 0.4 | 27 ± 0.4 | <0.003 |
| AP (mmHg) | 9 ± 0.3 | 6 ± 0.4 | 12 ± 0.4 | <0.0001 |
| PPA | 1.33 ± 0.01 | 1.44 ± 0.02 | 1.25 ± 0.01 | <0.0001 |
| AIx (%) | 24 ± 1.0 | 17 ± 1.0 | 29 ± 0.9 | <0.0001 |
Mean BP, mean blood pressure; HR, heart rate; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; PP, pulse pressure; P1, blood pressure at first systolic peak; AP, augmentation pressure; PPA, pulse pressure amplification; AIx, augmentation index (ratio of AP : PP); P, statistical difference *tested between subjects <50 and >50 years of age.
The effects of clinical characteristics on pulse pressure amplification and wave reflection
As shown in Table 2, PPA correlated significantly with percentage of body fat. The analysis of data from all subjects demonstrated that PPA correlated significantly with age, height, heart rate, mean blood pressure and BMI but not with waist circumference or waist to hip ratio (WHR). Data from all subjects were used to construct a multiple linear regression model (Table 3) with PPA as the dependent variable and age, mean blood pressure, height, heart rate and percent body fat as independent variables. PPA was negatively associated with age, mean BP and percent body fat and positively associated with heart rate and height. This model explained the 63% variance in PPA observed in the study. It was also noted (Table 4) that percent body fat correlated significantly with the subject's age, augmentation pressure, peripheral and central pulse pressure.
Table 2.
Univariate association between pulse pressure amplification and clinical characteristics
| PPA | ||
|---|---|---|
| Characteristics | Correlation coefficient | P |
| Age | −0.62 | <0.0001 |
| Height | 0.43 | <0.0001 |
| Percent body fat | −0.53 | <0.0001 |
| Waist circumference | −0.03 | NS |
| WHR | −0.03 | NS |
| BMI | −0.16 | 0.02 |
| HR | 0.28 | <0.0001 |
| BP mean | −0.29 | <0.0001 |
BP mean, mean blood pressure; WHR, waist to hip ratio; BMI, body mass index; HR, heart rate.
Table 3.
Regression coefficients of multiple linear regression with changes in pulse pressure amplification as dependent variables and age, mean blood pressure, heart rate, height and body fatness as independent variables
| Unstandarized coefficient | ||||
|---|---|---|---|---|
| Covariate | B | SE | Standarized coefficients | Significance level (P value) |
| Age (years) | −0.005 | 0.001 | −0.40 | <0.0001 |
| HR (beats min−1) | 0.008 | 0.001 | 0.40 | <0.0001 |
| Height (cm) | 0.005 | 0.001 | 0.23 | <0.0001 |
| BP mean (mmHg) | −0.003 | 0.001 | −0.18 | <0.0001 |
| Percent of body fat | −0.005 | 0.001 | −0.21 | <0.0001 |
r2 = 0.63, P < 0.0001, BP mean, mean blood pressure; HR, heart rate.
Table 4.
Univariate association between percentage of body fat, clinical and pulse wave characteristics
| All subjects | <50 years of age | >50 years of age | ||||
|---|---|---|---|---|---|---|
| Characteristic | r | P | r | P | r | P |
| Age (years) | 0.49 | <0.0001 | 0.42 | <0.0001 | 0.1 | NS |
| AP (mmHg) | 0.59 | <0.0001 | 0.48 | <0.0001 | 0.49 | <0.0001 |
| PPA | −0.53 | <0.0001 | −0.44 | <0.0001 | −0.37 | <0.0001 |
| Peripheral PP | 0.23 | <0.0001 | −0.03 | 0.7 | 0.3 | <0.0001 |
| Central PP | 0.45 | <0.0001 | 0.24 | 0.003 | 0.4 | <0.0001 |
AP, augmentation pressure; PPA, pulse pressure amplification; PP, pulse pressure.
The effects of clinical characteristics on pulse pressure amplification and wave reflection in subjects below and above 50 years of age
Age is the main determinant of PPA (Table 2) and augmentation pressure (r = 0.58, P < 0.0001). In multiple regression analysis age and percent of body fat but not BMI were independently associated with PPA (Table 5). Similarly in multiple regression analysis age and percent of body fat but not BMI were independent predictors of augmentation pressure (Table 6). In a group of subjects <50 years the PPA correlated inversely with age (Table 4). However, in the group of healthy individuals over 50 years of age, the association between age and PPA was no longer significant. Similarly the percentage of body fat correlated with age in younger subgroup but not in the older subjects (Table 4). Augmentation pressure was associated significantly with the percentage of body fat in both subgroups (Table 4). Moreover body fatness correlated, inversely, and significantly with PPA in individuals younger and older than 50 years (Table 4). Multiple linear regression model showed that in subjects below 50 years of age mean BP, heart rate, height, percent body fat and age were independently associated with PPA (r2 = 57%) (data not shown). In subjects >50 years of age mean BP, heart rate, height and percent body fat were also independently associated with PPA (r2 = 61%) (data not shown).
Table 5.
Regression coefficients of multiple linear regression with changes in pulse pressure amplification as dependent variables and age, body fatness (model 1) or age and body mass index (BMI) as independent variables (model 2)
| Unstandarized coefficient | ||||
|---|---|---|---|---|
| Covariate | B | SE | Standarized coefficients | Significance level (P value) |
| Model 1 | ||||
| Age (years) | −0.006 | 0.00005 | −0.47 | <0.0001 |
| Percent of body fat | −0.007 | 0.0009 | −0.30 | <0.0001 |
| Model 2 | ||||
| Age (years) | −0.008 | 0.0006 | −0.62 | <0.0001 |
| BMI (kg m−2) | −0.0008 | 0.002 | −0.02 | 0.68 |
Model 1 r2 = 45%, P < 0.0001; Model 2 r2 = 38% P < 0.0001.
Table 6.
Regression coefficients of multiple linear regression with changes in amplification pressure as dependent variables and age, body fatness (model 1) or age and body mass index (BMI) as independent variables (model 2)
| Unstandarized coefficient | ||||
|---|---|---|---|---|
| Covariate | B | SE | Standarized coefficients | Significance level (P value) |
| Model 1 | ||||
| Age (years) | 0.17 | 0.002 | 0.38 | <0.0001 |
| Percent of body fat | 0.30 | 0.03 | 0.40 | <0.0001 |
| Model 2 | ||||
| Age (years) | 0.26 | 0.02 | 0.56 | <0.0009 |
| BMI (kg m−2) | 0.11 | 0.07 | 0.07 | 0.11 |
Model 1 r2 = 46% P < 0.0001; Model 2 r2 = 34% P < 0.0001.
Discussion
This study, performed on healthy subjects, showed that pulse pressure amplification is related to body fatness over a wide age range. The percentage of body fat is also significantly associated with the augmentation pressure, a component of central pulse pressure.
Several studies have indicated that pulse pressure is the best single measure of blood pressure for predicting mortality in older people [22]. Recent data have suggested that pulse pressure obtained at the aortic root (invasively or non-invasively) may be a better predictor of CVD risk than the brachial pulse pressure [23, 24]. These results are explained by the fact that central pulse pressure is much more associated with pulsatile stress inflicted on coronary arteries, as well as on the cerebral circulation [25]. The pulse pressure rise from aorta to peripheral arteries is mainly due to the increase in systolic pressure. This amplification is measured as the ratio of peripheral to central pulse pressure.
Arterial stiffness is increased with ageing and central arteries becomes less compliant, in comparison with brachial arteries, leading to a much greater increase in aortic pulse pressure than in peripheral pulse pressure [26]. In these circumstances physiological pulse pressure amplification is attenuated. The PPA in healthy individuals is influenced by a number of factors including age, gender, heart rate and height. Several studies have demonstrated that PPA is inversely related to various cardiovascular risk factors. Nijdam et al. [27] showed that higher PPA reflects lower vascular risk, as reflected by reduced pulse wave velocity (PWV), intima media thickness (IMT) or lower Framingham risk of coronary artery disease (CAD). Adiposity is associated with adverse changes in the arterial wall in both adolescents and adults [28, 29]. Higher levels of visceral fat correlate with greater aortic stiffness, as measured by pulse wave velocity [30]. Mackey et al. [31] demonstrated that in elderly subjects aortic stiffness was positively associated with BMI or waist circumference. Zebekakis et al. [32] showed that across a wide age range the diameter and stiffness of muscular arteries increases with higher BMI while in elastic arteries this relationship is more complex and is influenced by age. Moreover body fat content has a significant association with the characteristics of the aortic and radial pressure waveforms [21]. In our present study PPA amplification was strongly and inversely correlated with the percentage of body fat. This highly significant association was independent of other know determinants of PPA such as age, mean blood pressure, height and heart rate. These findings are in contrast with data obtained by Vergnaud et al. [33] who demonstrated that PPA increased progressively as a function of BMI level. There are several possible explanations for discrepancy between our results and those of Vergnaud et al. [33]. Our population was on average 10 years younger and consisted of healthy subjects while Vergnaud et al. [33] studied treated hypertensives with signs of metabolic syndrome. These patients were also characterized by increased heart rate, one of the main determinants of PPA. Noteworthy, BMI used in this study is regarded as excess weight relative to height and not a direct measure of adiposity. Dual X-ray absorptiometry (DEXA) is often regarded as a ‘gold standard’ for assessing relative body fat content. Bioelectric impedance analysis is a simple method, which shows a very close (r = 0.9) linear relationship with DEXA [34, 35]. Moreover, it has also been demonstrated that BMI, in contrast to bioimpedance, is not very useful in predicting changes in arterial stiffness and wave reflection due to fatness [21]. Similarly in our present study despite the fact that BMI correlated strongly with percent body fat (r = 0.79, P < 0.0001), BMI was a poor predictor of PPA changes in multiple regression analysis. Also waist circumference was not independently associated with PPA.
Recently Majane et al. [8] assessed the impact of age and adiposity on PWV in a sample of African ancestry. In one of their sub-analyses in multivariate models, no single index of adiposity (BMI, WHR, waist circumference, etc.) was independently associated with augmentation index or PPA (data not shown). This lack of association of fatness with PPA may be at least partly explained by the use of traditional markers of fatness as well as that Majane et al. [8] assessed absolute but not relative PPA.
The large body of evidence indicates that arterial stiffness and wave reflection changes with advancing age. Mean arterial pressure increases with age and remains stable in middle-age and older subjects while systolic pressure increases and diastolic pressure falls with advanced age [35]. Because the prognostic implication of pulse pressure is different for different ages, we subdivided the study population into two subgroups namely those <50 and those >50 years of age. We have confirmed an age-related decline in PPA [36]. Moreover, in subjects older than 50 years the PPA did not correlate with age. Body fatness was inversely associated with PPA in the whole population and in both age categories, despite the fact that fatness did not correlate with age in individuals older than 50 years. This latter finding is confirmed by a study by Mott et al. [37] which supported the hypothesis that body fat is lower in elderly persons.
Pulse pressure can be separated into two components: the height of the first systolic peak above diastolic pressure, and the augmentation pressure. As demonstrated recently, pressure at P1 is influenced largely by arterial stiffness while augmentation pressure is affected by wave reflection [38], although this interpretation is the subject of considerable debate [39, 40]. Mitchell et al. [41] showed recently that higher pulse pressure in older subjects is associated predominantly with a larger forward pressure wave. Similarly Davies et al. [42] indicated that arterial reservoir pressure is a major determinant of aortic augmentation index with advanced ageing. Irrespective of these factors our current study showed that body fatness correlates strongly with augmentation pressure, independently of age.
Although the mechanisms by which increased body fatness reduces the PPA could not be determined from our study, there are several possible explanations for this phenomenon. It is well known that endothelial dysfunction can affect wave reflection. Several studies have shown a relationship between obesity and endothelial dysfunction in both adolescents and adults [13, 43]. Moreover a low grade inflammation associated with obesity may affect endothelial function and arterial stiffness, leading to arterial compliance mismatch [21, 33]. It also seems that adiposity may play a role in wave reflection which modulates PPA.
Study limitations
A number of potential limitations need to be addressed. First, central pulse pressure was measured non-invasively based on the reconstruction of the central pressure waveform with the use of a transfer function. However, the function has been verified both in physiological and clinical studies and the way we applied it for central pulse pressure measurement is commonly accepted [44]. Second, body fatness was estimated by bioimpedance. It should be noted that BIA is directly related to the hydration of the body and day-to-day variation in resistance measurements have been reported [45]. Third, waist circumference measurement is a subject of considerable inter- and intra-operator variability [46] which may at least partly explain the lack of independent association of this predictor of adipose tissue with PPA.
In summary, PPA is inversely correlated with body fat content. Amplification pressure, one of the components of central pulse pressure, is also closely associated with body fatness. Since body fatness is a modifiable factor, it is tempting to speculate that changing body fat content may influence the amplification of pulse pressure.
Acknowledgments
The authors are indebted to Profesor Geoffrey Shaw for his editorial assistance.
This study was supported by research grants no. 502-01-01118170-05274 and 502-01-01121176-00243 from University School of Medicine, Poznan, Poland
Competing Interests
There are no competing interests to declare.
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