The Relationship Between Cardiorespiratory Fitness and Arterial Stiffness in Middle-Aged Men with Abdominal Obesity

Abstract

Background:

Abdominal obesity increases rapidly after middle age in Korean men, and there is an associated trend toward increasing levels of cardiovascular disease (CVD). The purpose of this study was to examine the effect of cardiorespiratory fitness (CRF) on arterial stiffness in men with abdominal obesity.

Methods:

A total of 387 middle-aged men (ages 42–59 years) with abdominal obesity participated in this cross-sectional study. Abdominal obesity was defined as a waist circumference ≥90 cm. Arterial stiffness was derived from brachial/ankle pulse wave velocity (baPWV). A treadmill exercise test was conducted to directly assess CRF using the peak oxygen uptake. Blood glucose, blood pressure, lipids, C-related protein (CRP), and baPWV were measured at rest.

Results:

CRF was inversely associated with baPWV (r = −0.340, P = 0.014) and CRP level (r = −0.325, P = 0.026). In addition, high CRF was associated with a lower triglyceride level (r = −0.219, P = 0.030) and a higher high-density lipoprotein cholesterol level (r = 0.317, P = 0.019).

Conclusions:

These results demonstrated that high CRF was inversely associated with arterial stiffness in men with abdominal obesity. These results suggest that maintaining a high level of CRF can help middle-aged men with abdominal obesity to improve blood factors related to CVD.

Introduction

The incidence of obesity is increasing worldwide, with its prevalence more than doubling between 1980 and 2012.¹ In Korea, the prevalence of obesity has increased over the past 10 years from 20.6% to 24.6% in men and from 16.2% to 17.3% in women, between 2006 and 2015.²

Obesity, particularly abdominal obesity, increases health risk, with more intra-abdominal fat associated with an increased risk of insulin resistance and arteriosclerosis.^3
–5 Also, abdominal obesity is known to be closely related to the early onset of cardiovascular disease (CVD) and mortality.^6,7

Diseases that are associated with abdominal obesity are mostly related to blood lipids and vascular function. Excessive fat in the abdomen can cause dyslipidemia, including high neutral fat concentration and low high-density lipoprotein cholesterol (HDL-C).⁸ Also, central abdominal fat and waist circumference are strongly associated with type 2 diabetes.⁹ In addition, selective accumulation of fat around the abdomen is known to have a harmful effect on endothelial function.^5,10 Obesity reduces vascular elasticity due to an increase in intravascular inflammation and changes in endothelial function, with an increase in the arterial intima-media thickness and a decrease in the arterial lumen diameter.^11,12 Consequently, endothelial dysfunction can trigger arteriosclerosis and ultimately progress to coronary artery or cerebrovascular diseases.^13
–15

Various tests and indices are used for the early diagnosis and detection of arteriosclerosis. One such method is pulse wave velocity (PWV), in which arterial stiffness is estimated as an arbitrary distance divided by the time taken for the blood to travel this distance. Since measurement of the aortic and brachial/ankle PWV (baPWV) is both noninvasive and economic, it is very commonly used to predict CVD.^16,17 An increased PWV indicates the pathological state of a vascular injury, and it is known to be a risk factor for CVD and increased mortality.¹⁸ Recent meta-analyses have shown that an index of endothelial function and arterial stiffness, or baPWV, is a significant predictor of cardiovascular events independent of conventional cardiovascular risk factors.^19
–21

High cardiorespiratory fitness (CRF), an index of physical function, is highly effective in reducing CVD mortality.²² It is known to reduce the risk of both the early onset of CVD and early mortality.^23,24 Hence, CRF and arterial stiffness (a factor predicting CVD), are negatively correlated.^15,25

Abdominal obesity increases rapidly after middle age in Korean men, and there is an associated trend toward increasing levels of CVD. To prevent and reduce CVD, it is important to investigate the correlation between CRF and arterial stiffness in middle-aged men with abdominal obesity.

Therefore, the purpose of this study is to ascertain the relationship between peak oxygen uptake (an indicator of CRF) and arterial stiffness in middle-aged men with abdominal obesity. We hypothesized that low arterial stiffness is associated with high CRF level and so can prevent CVD relatively.

Methods

Participants

We evaluated 387 men (ages 42–59 years) who visited the Samsung Medical Center, Health Medical Center, in Seoul, Korea, between March 2016 and March 2017 for routine medical examinations.

These routine examinations, used for the prevention and/or early detection of disease, consisted of a general physical examination, anthropometric measurements, blood pressure (BP), electrocardiography, blood analysis, and an exercise stress test with concurrent metabolic gas analysis. All testing was completed in one visit.

In accordance with the guidelines presented by the Korean Society for the Study of Obesity, abdominal obesity, operationally defined as a waist circumference ≥90 cm, was required for inclusion in the study.²⁶ Waist circumference, defined as the minimum abdominal circumference between the lower edge of the rib cage and the iliac crests, was measured according to a standardized procedure.

The exclusion criteria were the presence of overt CVD (coronary heart disease, stroke), prediabetes or diabetes, hypertension (or taking any antihypertensive medications), cancers, the current use of hormone therapy, and habitual cigarette smoking. Informed consent was obtained from all patients before health screening, and the study was approved by the Samsung Medical Center Institutional Review Board.

Anthropometrics

Resting systolic and diastolic BP was measured in a supine position using a digital BP monitor (Dinamap PRO 100; Milwaukee, WI) during quiet rest. Participants rested for at least 5 min before the measurements. The lowest value from two measurements was used as resting BP.

Blood samples were collected in the morning after a 12-hr overnight fast. Subjects did not consume alcohol or exercise at least 24 hr before blood draws. Samples were analyzed in the hospital clinical laboratory.

High-sensitivity C-related protein (CRP) was measured using a CRP (II) Latex X2 turbidimetric method (Hitachi-747; Hitachi, Tokyo, Japan).

Arterial stiffness

After at least 15 min of rest in the supine position, bilateral brachial and ankle BP and heart rate (HR) were simultaneously measured by an automated vascular testing device (VP-1000) that has been validated against manual measurements of pulse wave velocity.²⁷

The pulse waveforms were recorded for 10 sec. On the basis of the foot-to-foot interval of waveforms at the oscillometric cuffs, the pulse transit time between the right arm and the right ankle, and between the right arm and the left ankle was calculated. Then, the PWV across two arterial segments was determined by dividing the relevant body distances by the time taken to travel over the segment (m/sec).

Cardiorespiratory fitness

CRF was measured directly using the VO₂ peak obtained during maximal treadmill testing (Quinton 4500; Cardiac Science Corp., Bothell, WA). The graded exercise testing was conducted using a Bruce or modified Bruce protocol.²⁸

The analysis of VO₂ peak was based on dynamic breath-by-breath measurements using a JAEGER system (Jaeger Oxycon Delta, Wurzburg, Germany). During exercise, HR was recorded continuously and BP was assessed at the end of each stage and at peak exercise. The VO₂ peak was defined as the highest value for the plateau in oxygen uptake and expressed relative to body weight (mL/kg/min).

Statistical analysis

All data are presented as mean ± standard deviation. Variables that were not normally distributed [CRP, insulin, triglyceride (TG), and low-density lipoprotein cholesterol] were log transformed.

Pearson's bivariate correlation coefficients were used to determine the association between the dependent variable, PWV, and the independent variables. In addition, one-way analysis of variance was performed to determine whether there were any differences in PWV according to fitness level. Statistical significance was set at P < 0.05.

All analyses were conducted using the Statistical Package for Social Sciences software, version 18.0 (SPSS, Chicago, IL).

Results

The participant characteristics are summarized in Table 1.

Table 1.

Demographics and Characteristics of the Subjects

Clinical characteristics (n = 387)	Mean ± SD
Age (years)	48.2 ± 4.2
Height (cm)	170.2 ± 5.5
Weight (kg)	80.3 ± 7.5
Body mass index (kg/m²)	27.4 ± 2.3
Abdominal girth (cm)	94.5 ± 4.4
Systolic BP (mmHg)	133.9 ± 20.5
Diastolic BP (mmHg)	87.2 ± 10.3
T-Col (mg/dL)	213.8 ± 37.5
LDL-C (mg/dL)	131.2 ± 32.3
HDL-C (mg/dL)	42.1 ± 11.4
Triglycerides (mg/dL)	152.1 ± 91.2
CRP (mg/dL)	1.85 ± 3.45
Fasting blood glucose (mg/dL)	88.5 ± 8.1
VO₂ peak (mL/kg/min)	29.4 ± 6.2
Brachial/ankle PWV (cm/sec)	1547.1 ± 150.1

BP, blood pressure; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; T-Col, total cholesterol; CRP, C-reactive protein; VO₂ peak, peak oxygen consumption; PWV, pulse wave velocity; SD, standard deviation.

In the male participants, baPWV was found to be significantly correlated with fasting blood glucose, systolic BP, and CRP (r = 0.282, P = 0.013; r = 0.430, P = 0.002; and r = 0.159, P = 0.033, respectively).

CRF measured using VO₂ peak was found to be significantly correlated with HDL-C (r = 0.317, P = 0.019), indicating that better physical capacity leads to significantly higher HDL-C. Also, VO₂ peak was found to be significantly correlated with total cholesterol (T-Col) and CRP (r = −0.203, P = 0.036; r = 0.325, P = 0.026, respectively), as shown in Table 2.

Table 2.

Correlation Analysis for the Association Between Cardiorespiratory Fitness and Lipids, and Brachial/Ankle Pulse Wave Velocity

	Brachial/ankle PWV		VO₂ peak
Characteristics	Pearson r	P-value	Pearson r	P-value
T-Col (mg/dL)	0.105	0.267	−0.203	0.036^*
LDL-C (mg/dL)	0.021	0.351	−0.212	0.743
HDL-C (mg/dL)	−0.212	0.154	0.317	0.019^*
TG (mg/dL)	0.196	0.021^*	−0.219	0.030^*
CRP (mg/L)	0.159	0.033^*	−0.325	0.026^*
Fasting blood glucose (mg/dL)	0.282	0.013^*	−0.043	0.647
Systolic BP (mmHg)	0.430	0.002^*	0.224	0.216
VO₂ peak (mL/kg/min)	−0.340	0.014^*	1.000

P < 0.05 Significant difference from high cardiorespiratory fitness.

In addition, to elucidate the relationship between VO₂ peak and baPWV, we corrected for systolic BP, T-Col, and CRP, and still observed a negative correlation (r = −0.340, P = 0.014), as shown in Fig. 1. This negative correlation indicates that baPWV becomes slower with greater CRF.

FIG. 1.

Association between cardiorespiratory fitness and baPWV. baPWV, brachial/ankle pulse wave velocity.

Discussion

The major finding of this study was that high CRF was inversely associated with arterial stiffness in men with abdominal obesity. Our results suggest that if the abdominal obesity has high CRF level, the lower arterial stiffness may be a possible mechanism contributing to the decrease incidence of CVD.

In Korea, cerebrovascular and CVDs have the second and third highest mortality, respectively. Since these diseases are closely related to arteriosclerosis, analysis of the risk factors for these diseases is important for the prevention of arteriosclerosis.²⁹ Hence, the aims of this study were to confirm whether abdominal obesity (a known risk factor for arteriosclerosis) affected arterial stiffness, and to investigate the correlation between CRF and arterial stiffness.

Among measurements of arterial stiffness, PWV is a reliable^17,30 and independent predictor for atherosclerosis, cardiovascular risk, and future CVD events.^18,31 Recently, baPWV has been used for assessment of arterial stiffness in humans. It has been shown that baPWV has been correlated with directly measured aortic PWV, and carotid–femoral PWV used as the criterion standard for noninvasive assessment of central arterial stiffness.^21,32

With regard to increases in vascular stiffness, systolic blood pressure (SBP) and PWV are known to gradually increase with age.³³ During aging, blood vessel wall thickening occurs due to hyperplasia of the endothelium, and blood vessel elasticity also decreases. The smoothness of collagen also changes with aging, and all these contribute to changes in the function and structure of blood vessels.^25,33 In addition, increasing arterial stiffness is known to be a major predictor of coronary artery disease, hypertension, impaired glucose tolerance, and diabetes mellitus.^8,15,18

Abdominal obesity is known to negatively influence CVD risk factors, causing arteriosclerosis.^4,6,7 Strasser et al.⁵ had reported that the associations with arterial stiffness were substantially greater for abdominal obesity than general obesity indicators. These results suggest that the accumulation of abdominal fat that occurs in midlife plays an important role in vascular dysfunction.⁵

The increased arterial stiffness observed in abdominal obesity can then cause insulin resistance, dyslipidemia, or increased systemic inflammation.^3,9,10,14

From the results of this study, it was evident that increased baPWV (an indicator of arterial stiffness) is associated with increased TG and CRP.

While studies have shown correlations between high levels of CRF and arterial stiffness,^14,25 there is a lack of research examining the correlation between arteriosclerosis and CRF in Oriental men with abdominal obesity. Nevertheless, previous studies have shown that high levels of CRF prevented arteriosclerosis in men with diabetes and metabolic syndrome.^34,35 In male participants with high levels of CRF, CRP was also significantly lower. In this study, the middle-aged men with high levels of CRF showed low CRP values, resulting in a negative correlation between CRF and CRP.³⁶ In addition, Zou et al. showed that there is a negative correlation between CRF and CRP in a longitudinal study in adults.³⁷ In our study, we similarly found that CRP and CRF were inversely associated. This is thought to be closely related to reducing the incidence of arteriosclerosis, however, the mechanisms involved are unclear.

Berry et al.³⁸ conducted a study in 11,049 male participants to examine the correlation between CRF and CVD risk. They found that the risk of death due to CVD is higher in people with lower CRF than in those with higher fitness.³⁸ Sieverdes et al. showed that the group with higher CRF had significantly lower body mass index (BMI), BP, T-Col, neutral fat, and fasting blood glucose level, and a significantly higher HDL-C than the group with lower CRF.³⁹ In a study of the relationship between CRF and aortic stiffness in women with abdominal obesity, CRF was inversely associated with aortic stiffness.¹² Haapala et al. found an association of increased PWV with low CRF and increased waist circumference in Dutch children and adolescents.⁴⁰ Furthermore, Fernberg et al. recently added the finding of an increased PWV with higher BMI in a small, normal weight population of young adults.⁴¹ In our study, we also compared CRF with PWV and found that in middle-aged men with abdominal obesity it was inversely associated.

This indicates that a high level of CRF has a positive influence on arterial stiffness even in individuals with abdominal obesity. In addition, the correlation analysis performed to aid understanding of the association between CRF and BP, serum lipids, and CRP indicated that high CRF is associated with lower CRP and TG, and higher HDL-C. Such results suggest that maintaining a high level of CRF can help middle-aged men with abdominal obesity to improve blood factors related to CVD.

Increased PWV is a powerful predictor of CVD, in young and older adults, and it is closely related to high mortality from CVD. Consequently, it is thought that maintaining or enhancing CRF through continued aerobic exercise will not only help to control weight but it will also reduce the risk of coronary artery diseases, even in individuals with abdominal obesity.

There are few limitations in this study. First of all, our study population was exclusively South Korean men (Asian); thus, it is unknown whether our findings also apply to different ethnicities and to women. Second, we could not control for physical activity and alcohol consumption. The effect of alcohol consumption or physical activity may potentially confound the relationship between CRF and atrial stiffness. Therefore, future studies are needed to prospectively evaluate this association in the population sample.

Footnotes

Author Disclosure Statement

No conflicting financial interests exist.

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Korean Society for the Study of Obesity (KSSO): 2016 obesity fact sheet. Available from: http://www.kosso.or.kr/file/factsheet_1006new6_web.pdf.

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