†These authors contributed equally.
Academic Editors: Kostas Tziomalos and Jerome L. Fleg
Background: This study aimed to explore the association between BMI
and/or central obesity parameters and measures of arterial hemodynamics to assess
the effect of obesity on function of large arteries. Methods: Data was
obtained from 634 subjects undergoing health assessment at Ruijin Hospital,
Shanghai. Subjects were divided into 3 groups according to their Body Mass Index
(BMI (kg/m
Obesity is a risk factor for all-cause and cardiovascular mortality. Previous studies have confirmed that obesity increases the incidence of cardiovascular events [1, 2]. However, some long-term follow-up studies have suggested a negative correlation between body mass index (BMI) and prognosis of cardiovascular disease and target organ damage, known as the “obesity paradox” [3, 4]. The obesity paradox may be caused by the confounding of research results by a variety of factors, such as BMI. BMI, one of the most frequently used surrogate anthropometric measures for obesity, does not distinguish between muscle and fat, and poorly reflects body fat distribution [5, 6]. The value of BMI in assessing and diagnosing obesity has been questioned.
Central aortic pressure has been suggested to provide information regarding end-organ damage additional to that provided by conventional brachial artery pressure. Prospective studies have found that central blood pressure can predict vascular events better than peripheral blood pressure, and that it is closely related to cardiovascular and cerebrovascular endpoint events [7, 8]. On the other hand, changes related to damage of vascular structure and function are independent risk factors for the occurrence and development of cardiovascular events and may be better indicators or alternative endpoints for the prediction of cardiovascular risk [7, 9]. Pulse wave velocity (PWV) is currently recognized as the best indicator for noninvasive detection of arterial stiffness, which can effectively reflect functional changes. According to the latest European Society of Hypertension expert consensus on carotid-femoral PWV (cf-PWV) for clinical practice, the cut-off value of cf-PWV for predicting cardiovascular events has been found to be 10 m/s [10].
This study aims to explore the association between different obesity phenotypes and central aortic hemodynamics and vascular stiffness so as to explore a more reasonable way to evaluate the clinical significance of obesity in cardiovascular events and to guide the individualized treatment of obesity.
A total of 653 participants who received a routine physical examination at
Ruijin Hospital from December 2017 to December 2019 were recruited. Nineteen
cases were excluded due to missing data. Finally, 634 cases were included in this
study. The inclusion criteria were age
Patients’ medical history, medication history, smoking history, and biochemical test indicators were collected. Biochemical test indicators included: serum total cholesterol (TC), triglyceride (TG), fasting blood glucose, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c). Definition of smoking was at least one cigarette a day for more than 6 months.
All participants underwent routine physical examinations, including height,
weight, heart rate (HR), waist circumference (WC), and hip circumference (HC),
performed by a trained person using the same tape and platform scale. During the
measurement, the subjects took off their shoes, hat and heavy coats, and stood on
a platform at attention posture. BMI was calculated as BMI = weight
(kg)/height
According to the Guidelines for Prevention and Control of Overweight and Obesity
in Chinese Adults [11], the research subjects were divided into the following
three groups: normal BMI group (BMI
After the participants sat quietly for 5 min, brachial artery blood pressure was
measured by an electronic sphygmomanometer (HEM907, Omron, Kyoto, Japan) 3 times, at
intervals of at least 1 min. Peripheral systolic blood pressure (PSP), peripheral
diastolic blood pressure (PDP), and peripheral pulse pressure (PPP) were
recorded. Peripheral mean arterial pressure (p-MAP) was calculated as (PSP + 2
The diagnosis of hypertension is based on the criteria given in the 2010
Guidelines for Prevention and Treatment of Hypertension in China [13], which is
systolic blood pressure
A pulse wave analysis (PWA) instrument (SphygmoCor-px V8.0, AtCor Medical, New South Wales, Australia) was used for measurement of central aortic pressure and PWV. Participants were in the supine position, with the right upper limb outreaching horizontally at a 45-degree angle to the body. The instrument’s contact probe was placed on the right radial artery where the pulse is strongest, and a continuous radial pulse group of at least 12 s was recorded in real time, translated into central aortic pulse wave by the computer conversion function, which determined the central aortic systolic pressure (CSP), central diastolic pressure (CDP), central pulse pressure (CPP), central mean arterial pressure (c-MAP), central augmentation pressure (CAP), central augmentation index (cAIx), and cAIx@HR75 (cAIx adjusted for 75 heartbeats/min). AIx was defined as the augmentation pressure (CAP) of the central aortic pressure waveform expressed as a percentage of CPP. Pressure pulse amplification was characterized both as the percentage ratio of PPP/CPP and by the difference between PSP and CSP.
Cf-PWV was measured by two trained study personnel using applanation tonometry with a Millar transducer and SphygmoCor CVMS system (AtCor Medical PtyLtd, Sydney, Australia). cf-PWV measurement was performed by sequential placement of the transducer on the femoral artery and carotid artery and determining transit time between the two pulses in reference to the R wave of the ECG. cf-PWV was calculated as the measured distance from the suprasternal notch to the femoral artery minus the distance from the suprasternal notch to the carotid artery divided by the pulse transit time [PWV = distance(m)/transit time(s)] by the integrated software, which automatically processed each set of pulse waves and ECG data.
According to the European Society of Hypertension expert
consensus on cf-PWV for clinical practice, cf-PWV
SPSS 26.0 software package (SPSS, Chicago, IL, USA) and Excel were used for
statistical analysis. Continuous variables are expressed as mean
A total of 634 participants was studied, including 393 males (62.0%). The mean
age of the enrolled population was (52.03
In the general population, there were statistically significant differences in
PSP, PDP, CSP, CDP, CAP, cAIx, PPP/CPP and PSP-CSP among the three BMI groups
(p
Total | Normal weight | Overweight | Obese | p-value | |
BMI |
24 kg/m |
BMI | |||
N | 634 | 230 | 256 | 148 | |
Men (%) | 393 (62.0%) | 102 (44.3%) | 180 (70.3%) | 111 (75%) | |
Age, y | 52.03 |
52.56 |
52.93 |
49.64 |
0.025 |
Smoker (%) | 114 (18.0%) | 24 (10.4%) | 57 (22.3%) | 33 (22.3%) | 0.001 |
Antihypertensive treatment (%) | 254 (40%) | 68 (29.6%) | 118 (46.1%) | 68 (45.9%) | |
ACEI/ARB | 144 (18.0%) | 27(11.7%) | 55 (21.5%) | 32 (21.6%) | 0.008 |
Bata-blockers | 21 (3.3%) | 4(1.7%) | 13 (5.1%) | 4 (2.7%) | 0.133 |
Calcium Antagonists | 88 (13.9%) | 14 (6.1%) | 40 (15.6%) | 34 (23.0%) | |
Diuretics | 2 (0.3%) | 1 (0.4%) | 0 (0%) | 1 (0.7%) | 0.518 |
TG, mmol/L | 2.00 |
1.55 |
2.10 |
2.55 |
|
TC, mmol/L | 4.88 |
4.88 |
4.92 |
4.83 |
0.761 |
HDL-C, mmol/L | 1.15 |
1.26 |
1.09 |
1.08 |
|
LDL-C, mmol/L | 3.21 |
3.19 |
3.26 |
3.18 |
0.591 |
Glucose, mmol/L | 5.79 |
5.54 |
5.89 |
5.99 |
0.039 |
Height, cm | 167.29 |
166.07 |
167.91 |
169.65 |
|
Weight, kg | 71.97 |
59.73 |
73.59 |
88.73 |
|
BMI, Kg/m |
25.59 |
21.85 |
25.94 |
30.79 |
|
WC, cm | 91.18 |
83.04 |
92.10 |
102.24 |
|
HC, cm | 97.95 |
92.76 |
98.37 |
105.26 |
|
WHtR, % | 0.55 |
0.50 |
0.55 |
0.60 |
|
WHR, % | 0.93 |
0.90 |
0.94 |
0.97 |
|
PSP, mmHg | 131.67 |
128.08 |
133.14 |
134.69 |
0.001 |
PDP, mmHg | 76.38 |
72.97 |
77.63 |
79.53 |
|
PPP, mmHg | 55.29 |
55.12 |
55.52 |
55.16 |
0.936 |
CAP, mmHg | 11.61 |
12.45 |
11.95 |
9.72 |
0.001 |
HR, beat/min | 69.67 |
69.62 |
69.07 |
70.76 |
0.299 |
cAIx, mmHg | 25.78 |
27.50 |
26.28 |
22.24 |
|
cAIx@HR75, mmHg | 23.25 |
24.96 |
23.42 |
20.25 |
|
CSP, mmHg | 120.03 |
117.17 |
121.68 |
121.64 |
0.009 |
CDP, mmHg | 77.61 |
74.21 |
78.84 |
80.76 |
|
CPP, mmHg | 42.42 |
42.97 |
42.84 |
40.87 |
0.197 |
PPP/CPP (%) | 1.33 |
1.31 |
1.32 |
1.37 |
|
PSP-CSP, mmHg | 11.63 |
10.91 |
11.46 |
13.05 |
0.001 |
cf-PWV, m/s | 8.30 |
8.02 |
8.35 |
8.62 |
0.012 |
Data are mean |
In the overall study population, using BMI, WC, WHtR and WHR as continuous
independent variables, PSP, PDP, and CDP, cf-PWV were all positively associated
with each one (p
BMI | WC | WHtR | WHR | |||||
r | p | r | p | r | p | r | p | |
PSP | 0.176 |
0.161 |
0.179 |
0.105 |
0.008 | |||
PDP | 0.244 |
0.207 |
0.190 |
0.087 |
0.028 | |||
p-MAP | 0.198 |
0.149 |
0.164 |
0.063 | 0.112 | |||
PPP | 0.01 | 0.792 | 0.025 | 0.532 | 0.066 | 0.097 | 0.061 | 0.124 |
HR | 0.075 | 0.06 | 0.061 | 0.125 | 0.073 | 0.065 | 0.01 | 0.796 |
CSP | 0.134 |
0.001 | 0.096 |
0.016 | 0.148 |
0.069 | 0.083 | |
CDP | 0.241 |
0.200 |
0.184 |
0.080 |
0.044 | |||
c-MAP | 0.198 |
0.149 |
0.164 |
0.063 | 0.112 | |||
CPP | –0.053 | 0.181 | –0.067 | 0.094 | 0.027 | 0.49 | 0.018 | 0.643 |
PPP/CPP | 0.145 |
0.194 |
0.058 | 0.143 | 0.064 | 0.109 | ||
PSP-CSP | 0.141 |
0.216 |
0.104 |
0.009 | 0.119 |
0.003 | ||
CAP | –0.112 |
0.005 | –0.181 |
–0.042 | 0.289 | –0.06 | 0.13 | |
cAIx | –0.134 |
0.001 | –0.209 |
–0.071 | 0.075 | –0.090 |
0.024 | |
cAIx@75 | –0.113 |
0.005 | –0.206 |
–0.045 | 0.256 | –0.098 |
0.014 | |
cf-PWV | 0.121 |
0.002 | 0.217 |
0.267 |
0.258 |
|||
BMI | 1 | 0.701 |
0.691 |
0.363 |
||||
PSP, peripheral systolic blood pressure; PDP, peripheral diastolic blood
pressure; PPP, peripheral pulse pressure; p-MAP, peripheral mean arterial
pressure; CSP, central aortic systolic pressure; CDP, central diastolic pressure;
c-MAP, central mean arterial pressure; CPP, central pulse pressure; CAP, central
augmentation pressure; cAIx, central augmentation index; cAIx@HR75, cAIx adjusted
to heart rate of 75 bpm; cf-PWV, carotid-femoral pulse wave velocity. BMI, body
mass index; WC, waist circumference; HC, hip-circumference; WHR, waist–hip
ratio; WHtR, waist–height ratio; HR, Heart rate. *p |
Participants were divided into three groups according to the BMI compared with groups with central obesity assessed by WC and WHR. We found that the results of the two groups were relatively consistent with the obese BMI class agreeing with higher WC and WHR in males reaching 98.2%, but less (94.6%, 91.9% respectively) in females (Tables 3,4).
Normal weight | Overweight | Obese | Total N = 241 | c |
p-value | |
BMI |
24 kg/m |
BMI | ||||
WC |
93 (72.7%) | 11 (14.5%) | 2 (5.4%) | 106 (44.0%) | 91.924 | |
WC |
35 (27.3%) | 65 (85.5%) | 35 (94.6%) | 135 (56.0%) | ||
WHR |
52 (40.6%) | 8 (10.5%) | 3 (8.1%) | 63 (26.1%) | 29.737 | |
WHR |
76 (59.4%) | 68 (89.5%) | 34 (91.9%) | 178 (73.9%) | ||
BMI, body mass index; WC, waist circumference; WHR, waist–hip ratio. |
Normal weight | Overweight | Obese | Total N = 393 | c |
p-value | |
BMI |
24kg/m |
BMI | ||||
WC |
71 (69.6%) | 49 (27.2%) | 2 (1.8%) | 122 (31.0%) | 116.43 | |
WC |
31 (30.4%) | 131 (72.8%) | 109 (98.2%) | 271 (69.0%) | ||
WHR |
71 (69.6%) | 49 (27.2%) | 2 (1.8%) | 122 (31.0%) | 116.43 | |
WHR |
31 (30.4%) | 131 (72.8%) | 109 (98.2%) | 271 (69.0%) | ||
BMI, body mass index; WC, waist circumference; WHR, waist–hip ratio. |
Multiple linear regression analysis was performed to evaluate the independent
risk factors of cf-PWV. After adjusting for age, sex, heart rate,
antihypertensive therapy, blood pressure, glucose and LDL-c, when BMI, WC, WHtR,
WHR were separately put into the model, BMI was not an independent risk factor
for cf-PWV (
B | Std. error | Beta | p-value | R | ||
Model 1 | 0.403 | |||||
Sex | 0.267 | 0.141 | 0.067 | 0.058 | ||
Age | 0.069 | 0.006 | 0.429 | |||
PSP | 0.036 | 0.004 | 0.328 | |||
HR | 0.016 | 0.006 | 0.085 | 0.014 | ||
Antihypertensive treatment | 0.181 | 0.137 | 0.046 | 0.188 | ||
LDL-c | –0.034 | 0.078 | –0.015 | 0.659 | ||
Glucose | 0.144 | 0.038 | 0.13 | |||
BMI | 0.022 | 0.018 | 0.044 | 0.22 | ||
Model 2 | 0.413 | |||||
Sex | 0.119 | 0.148 | 0.030 | 0.420 | ||
Age | 0.068 | 0.006 | 0.424 | |||
PSP | 0.035 | 0.004 | 0.322 | |||
HR | 0.015 | 0.006 | 0.081 | 0.018 | ||
Antihypertensive treatment | 0.175 | 0.136 | 0.045 | 0.198 | ||
LDL-c | –0.045 | 0.077 | –0.020 | 0.561 | ||
Glucose | 0.127 | 0.038 | 0.115 | 0.001 | ||
WC | 0.022 | 0.007 | 0.120 | 0.001 | ||
Model 3 | 0.411 | |||||
Sex | 0.263 | 0.138 | 0.066 | 0.057 | ||
Age | 0.066 | 0.006 | 0.413 | |||
PSP | 0.035 | 0.004 | 0.322 | |||
HR | 0.015 | 0.006 | 0.080 | 0.021 | ||
Antihypertensive treatment | 0.169 | 0.136 | 0.043 | 0.215 | ||
LDL-c | –0.042 | 0.077 | –0.018 | 0.583 | ||
Glucose | 0.128 | 0.038 | 0.116 | 0.001 | ||
WHtR | 3.521 | 1.203 | 0.103 | 0.004 | ||
Model 4 | 0.408 | |||||
Sex | 0.187 | 0.145 | 0.047 | 0.197 | ||
Age | 0.066 | 0.006 | 0.411 | |||
PSP | 0.036 | 0.004 | 0.332 | |||
HR | 0.016 | 0.006 | 0.086 | 0.013 | ||
Antihypertensive treatment | 0.179 | 0.136 | 0.045 | 0.190 | ||
LDL-c | –0.040 | 0.077 | –0.018 | 0.603 | ||
Glucose | 0.127 | 0.039 | 0.115 | 0.001 | ||
WHR | 2.312 | 0.924 | 0.092 | 0.013 | ||
cf-PWV, carotid-femoral pulse wave velocity; LDL-c, low density lipoprotein cholesterol; BMI, body mass index; HR, Heart rate; WC, waist circumference; WHR, waist–hip ratio; WHtR, waist–height ratio; PSP, peripheral systolic blood pressure. |
Regarding cf-PWV
ROC curves of PWV predicted by different obesity indicators. WC (AUC = 0.545, p = 0.151); BMI (AUC = 0.500, p = 0.992); WHtR (AUC = 0.577, p = 0.013); WHR (AUC = 0.603, p = 0.001); AUC, Area Under the receiver operating characteristic curve.
In this study, we found that brachial and central SBP and DBP and cf-PWV were
higher with increasing BMI, as were PSP-CSP and PPP/CPP. The higher BMI groups
showed lower CAP and cAIx. BMI had inconsistencies with fat distribution
indicators in obesity diagnosis, especially in females, and was different from
the other obesity-related metabolic phenotypes. After all risk factors were
adjusted, only WC was found to be an independent risk factor for cf-PWV. The ROC
curve showed that WHR may have greater predictive value for vascular stiffness
than BMI, but there was no significant difference between WHR, WHtR and WC.
Although all of the correlations between arterial stiffness measures and obesity
variables are significant, they are weak, with r values
Although some studies have indicated that a higher BMI is frequently accompanied by hypertension, dyslipidemia and endothelial dysfunction [14, 15, 16], some individuals with increased BMI show a decreased risk of mortality [17, 18, 19], a phenomenon that has been called the “obesity paradox”. Our study also showed that in the general or male population, BMI was negatively correlated with CAP and cAIx, and positively correlated with PPP/CPP and CSP. That is, as BMI increases, the amplifying effect of pulse pressure makes male blood vessels appear younger, suggesting that obese people may have better arterial compliance than normal-weight people. In addition, BMI was not found to be an independent predictor for PWV after all risk factors were adjusted. These results were consistent with the obesity paradox to some extent.
These paradoxical results may be due, partly at least, to a limitation of BMI. It is well known that BMI was developed as a measure of weight rather than an index of obesity [20, 21], which may make it misleading in the estimation of body fat content. In our study, the difference between BMI and fat distribution indicators in diagnosing obesity was significant, which suggested BMI should not be used as a core index to evaluate central obesity.
Although BMI has been widely used to measure adiposity in many countries, including Asians, the American Heart Association (AHA) recommended in 2015 that the waist circumference should be used to assess the risk of cardiovascular diseases in Asians, partly because of the low sensitivity of BMI for cardiovascular risk [22]. In patients with coronary heart disease, there was no obesity paradox when body fat ratio (BF%) was used to replace BMI. BF% was associated with a higher risk of major adverse cardiovascular events (MACE), while fat-free mass was associated with a lower risk of MACE, suggesting that BMI was not associated with MACE [23].
A growing body of evidence suggests that fat distribution may be more important
than overall adiposity. For instance, visceral fat is a strong and independent
predictor of metabolic disorders, such as dyslipidemia, insulin resistance and
type 2 diabetes [24, 25, 26]. Conversely, subcutaneous fat may have a beneficial
effect on metabolism [27]. Increased visceral to subcutaneous fat area ratio
(VSR) was an independent predictor of all-cause mortality, suggesting that the
location of fat deposits may be more important than actual body fat mass [28]. In
this study, using cf-PWV as a gold standard for vascular stiffness, we found that
WC, WHtR and WHR were independent predictors of cf-PWV. In multivariate stepwise
linear regression, WC was the strongest predictor for vascular stiffness. BMI,
however, was not a predictor. Furthermore, when cf-PWV
Some previous studies [29, 30] have found a positive correlation between BMI and PWV, but that blood pressure was the most powerful predictor for PWV. Therefore, after adjusting for cardiovascular risk factors, especially blood pressure, some clinical studies have found no significant correlation or even a negative correlation between BMI and PWV [31, 32, 33]. The reason may be related to the different detection methods of PWV and the difference in the selected pulse wave travel distance. In addition, obese patients with excessive diabetes, hypertension, cardiovascular risk factors and other risk factors may appropriately weaken the correlation between PWV and BMI.
This study has some limitations: (i) As a cross-sectional study with a small sample size, the results need to be further confirmed in prospective studies. (ii) In this study, obesity types were grouped according to BMI, waist circumference, hip circumference and waist-to-hip ratio, without considering different fat distribution and body fat rate, or obesity types associated with metabolic abnormalities. Umbilical cord plane CT scan is currently recognized as the gold standard for visceral fat measurement, but visceral fat was not measured in this study. (iii) Our results show that all obesity measures are weakly associated with atherosclerosis. (iv) The large proportion of people receiving antihypertensive drugs and different antihypertensive drugs may cause possible confounding effects. (v) Blood pressure was taken as the average of three measurements; it is likely inflated by the first value due to initial stimulus or short resting period. It may be better to average the second and third measures. And the cuff sphygmomanometer is cylindrical rather than conical, which may be more appropriate for obese participants with large upper arms. (vi) The study was conducted in an Asian population, and it is not known whether the results will hold true for other ethnic groups.
The higher BMI groups showed lower CAP and cAIx. PSP-CSP and PPP/CPP were also highest in the obese group. BMI had poor consistency with fat distribution indicators in obesity diagnosis, especially in females. After adjusting for all cardiovascular risk factors, only WC was found to be an independent risk factor for cf-PWV. WHR may have greater predictive value for vascular stiffness than other indices of obesity.
BMI, body mass index; WC, waist circumference; HC, hip circumference; WHR, waist–hip ratio; WHtR, waist–height ratio; BP, blood pressure; HR, Heart rate; PSP, peripheral systolic blood pressure; PDP, peripheral diastolic blood pressure; PPP, peripheral pulse pressure; p-MAP, peripheral mean arterial pressure; CSP, central aortic systolic pressure; CDP, central diastolic pressure; c-MAP, central mean arterial pressure; CPP, central pulse pressure; CAP, central augmentation pressure; cAIx, central augmentation index; cAIx@HR75, cAIx adjusted to heart rate of 75 bpm; cf-PWV, carotid-femoral pulse wave velocity. TG, triglyceride; TC, total cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol.
These should be presented as follows: HJC, KQ and JLZ designed the research study. YLH and KQ performed the research, AAdj and AAvo provided help and advice on HJC analyzed the data. HJC, BWT and JLZ analyzed and interpreted data for the work, HJC, QW, YLH and JLZ wrote the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.
All studies were in compliance with the Declaration of Helsinki, the Good Clinical Practice guidelines, and applicable regulatory requirements. All participants provided written informed consent to participate for the respective study, which was approved by the Human Research Ethics Committee at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (Number: 2017(1)-1).
We gratefully acknowledge the invaluable assistance of the physicians of the Department of Geriatrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine; the study would not have been possible without their support.
This research was funded by the National Natural Science Foundation of China (Grant No. 81500190), and Clinical Science and Shanghai Municipal Hospital New FrontierTechnology Joint Project (SHDC12019X20), Shanghai Municipal Commission of Health and FamilyPlanning (Grant No. 2020YJZX0124).
The authors declare no conflict of interest.