Obesity increases the risk of chronic diseases such as metabolic syndrome (MS), cardiovascular disease (CVD), hypertension, stroke, coronary heart disease (CHD), type 2 diabetes, and cancer.1 Increased risk of CHD with obesity is related to hypercholesterolemia (elevated total cholesterol and low-density lipoprotein [LDL] cholesterol in combination with low high-density lipoprotein [HDL] cholesterol),2 as well as hypertriglyceridemia, hypertension, and endothelial dysfunction.3
Arterial stiffness, another major risk factor for cardiovascular disease,4 is the impairment of the cushioning function of arteries. This leads to a reduction in the ability to convert the pulsatile blood flow from the heart into a steady and continuous stream throughout the arterial tree.5 Arterial stiffness is an age-related phenomena6 that leads to atherosclerosis because it causes luminal enlargement and thickening of the arteries’ walls (remodeling) and diminishes the elasticity of large elastic arteries. Increased arterial stiffening has been associated with increased blood pressure (BP), hypercholesterolemia, left ventricular hypertrophy, and impaired coronary perfusion, representing an independent risk factor for cardiovascular disease.3,4,7,8 Interestingly, individuals with MS, hypertension, or diabetes also exhibit increased carotid wall thickness and stiffness, which “accelerates” arterial aging, a well confirmed risk factor for CVD.3 Early detection of arterial stiffening may help to reduce cardiovascular disease progression and the risk factors for arterial stiffness associated with morbidity and mortality.9
Augmentation index (AIx), an indicator of arterial stiffness, has been associated with central obesity in children, overweight/obese adolescents and young adults, overweight/obese women, and overweight/obese adult populations from different countries.8,10–14 Since obesity is associated with a greater risk of hyperlipidemia,15 poor BP control, and hypertension,16,17 it may also predict arterial stiffness. Although BMI and abdominal obesity have recently been associated with arterial stiffness in different populations from Croatia, Spain, United States and, Denmark,8,11–13,18 there is a lack of information on the association of obesity and arterial stiffness in Australian women. Therefore, our aim in the present study was to investigate arterial stiffness in overweight/obese women compared with their lean counterparts. Women were initially chosen for this pilot study because the relationship of arterial stiffness and obesity may be sex specific as suggested by recent studies.12,19 We hypothesized that overweight/obese Caucasian women will present greater arterial stiffness compared with the lean group, similar to other populations.
Methods and Procedures
Twenty-six Australian Caucasian women, with a BMI between 18.5 and 34.9 kg/m2, were recruited through local media (pamphlets, posters, and radio announcements) from the community of Perth, Australia. Potential participants were screened by telephone and they attended Curtin University to assess their suitability for the study, at which time the details of the study were explained. Inclusion criteria were age between 18 and 45 years. Australian Caucasian women were clearly defined as those who were born and raised in Australia and lived in the country in the past 10 years, with both parents born in Australia. They had Caucasian genetic background extending for at least 2 generations. Japanese, Asian, Middle Eastern, blacks, and other ethnic groups were excluded from the study. Exclusion criteria included use of hypertensive and lipid-lowering medication, use of steroids, and other agents that may influence lipid metabolism; pregnancy; lactating; use of warfarin; diabetes mellitus; postmenopausal; hypothyroidism and hyperthyroidism; cardiovascular events within the past 6 months; psychological unsuitability; and major systemic diseases. Patients using contraceptives, on estrogen replacement therapy, or presence of polycystic ovary syndrome (PCOS) were excluded (all women included in the study presented with normal ovulatory cycle, which is an indication of absence of PCOS, and were additionally asked whether they have ever been diagnosed with the syndrome). Only women with a stable ovulatory cycle duration over the past 6 months were eligible for the study.20 Patients were screened for estradiol levels >200 pmol/L at day 4 to 7 after ovulation (luteal phase) to ensure they were premenopausal and were assessed (arterial stiffness, bloods measurements) at the same time of their menstrual cycle.
The participants were designated into one of the two groups: overweight and obese (BMI 25 and 34.9 kg/m2) group (n=12), and lean (BMI 18.5 and 24.9 kg/m2) women (n=14). Specific instructions were given to each volunteer to keep their regular habits and nutrition the days before the visit but were asked to refrain from drinking drinks containing caffeine the day before the assessment. The present study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving human patients were approved by the Curtin University human research ethics committee with all the participants giving written informed consent.
Patients were asked to visit Curtin University for measurements in a fasted state while wearing light clothing for only one occasion for baseline measures. Body weight (kg) (UM-018 Digital Scales; Tanita, Tokyo, Japan) was recorded in light clothing. Height (m) was measured to the nearest 0.1 cm using a stadiometer (26SM 200 cm; SECA, Hamburg, Germany) without shoes. Waist circumference (cm) was measured in the standing position at the narrowest area between the lateral lower rib and the iliac crest. Hip measurement (cm) was taken at the largest circumference of the lower abdomen. The waist and hip measurements were taken 3 times at baseline and the average at each time point was then reported and used to calculate the waist to hip ratio. Percentage of body fat was then measured with the use of Bio-Electrical Impedance Analysis (BIA) and one skinfold was taken at the point of the triceps by a student trained in anthropometry. Systolic BP (SBP) and diastolic BP (DBP) were measured with an automated, calibrated sphygmomanometer (Dinamap; Compact T, Critikon, Germany) with patients in a supine position after resting for at least 10 minutes. The measurements were taken on the same arm 3 times at 1-minute intervals. These readings were then averaged. A 15 mL of blood sample was taken via venepuncture from patients in the fasting state to measure circulating total cholesterol, HDL cholesterol, triglycerides, and glucose levels. Lipid concentrations were carried out using test kits from Thermo Trace Ltd, Melbourne, Australia, following the standard assay procedures. Raw data was obtained via spectrophotometry, at an absorbance of 490 nm. Final values were established through standard calculations. Serum LDL cholesterol was determined using a modified version of the Friedewald equation21: LDL cholesterol=(TC−HDL×[Triglycerides/5]). Plasma glucose levels were measured using the Randox glucose GOD–PAP kit (Antrim, UK).
Pulse Wave Analysis for AIx
Pulse wave analysis (PWA) was used to assess arterial stiffness and vascular function using the SphygmoCor (AtCor Medical, West Ryde, NSW, Australia). SphygmoCor is a noninvasive device that enables aortic root pressure to be measured during a normal clinical consultation. All PWA measurements were taken in a quiet temperature-controlled room (22°C) after a period of at least 5 minutes of rest. Patients fasted overnight and were asked to refrain from drinking drinks containing caffeine. Only high-quality readings, defined as an in-device quality index of 90% (derived from an algorithm including average pulse height, pulse height variation, diastolic variation, and the maximum rate of rise of the peripheral waveform) and acceptable curves by visual inspection by the investigator were included in the analysis. For each assessment at least 3 measurements were taken and results were averaged.
AIx, an indicator of arterial stiffness, was calculated using the formula: AIx (%)=AP/(SBP−DBP)×100. The reference range provided by the Sphygmocor software was determined from an analysis of 405 healthy individuals in a study by Wilkinson and colleagues.22 All measurements were performed by the same operator. These measurements were taken 3 times with a quality index of at least 90% or more and the readings were averaged.
Statistical analysis was undertaken using SPSS 11 for Windows (SPSS Inc, Chicago, IL). Data were expressed as means with their standard errors and assessed for normality to ensure that the assumptions of the analysis were met. The data were analyzed using the Student t test and multiple linear regression test with Pearson coefficient. Statistical significance was considered at P<.05. A sample size of at least 12 patients per group would provide sufficient power (0.80%) to detect an estimated within- and between-group effect size of 0.56 at a 5% significance level for a pilot study. Recruiting a total of 30 patients (n=15) would allow for a 10% dropout rate.
A total of 26 Australian Caucasian premenopausal women were designated into one of two groups: overweight and obese (BMI from 25 to 34.9 kg/m2) (n=12) and lean (BMI 18.5–24.9 kg/m2) (n=14). Table I shows the clinical characteristics of participants between the two groups. The mean age between the two study groups was assessed due to the existing association between chronic disease risk factors and age, and there was no statistically significant difference between the overweight/obese and lean groups (P=.482). As expected, the average body mass index was significantly higher in overweight/obese women compared with lean participants (P=.001) as well as the percentage of body fat (P=.001). Waist circumference (P=.001) and waist/hip ratio (P=.036) were also significantly higher in the overweight/obese group.
Table I. Clinical Characteristics of Participants
Abbreviations: BMI, body mass index; BP, blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol. Values are means (standard error of the mean). aSignificantly different from lean values (P<.05).
Body fat, %
Waist circumference, cm
Hip circumference, cm
Total cholesterol, mmol/L
Cholesterol/HDL ratio, mmol/L
Fasting glucose, mmol/L
Systolic BP, mm Hg
Diastolic BP, mm Hg
Overweight/obese women presented higher total cholesterol levels than the lean group (P=.016), as well as increased triglycerides concentrations (P=.003); however, the HDL cholesterol and LDL cholesterol levels were not different between groups (Table I). Fasting glucose levels were significantly greater in the overweight/obese group compared with the lean group (P=.001). Both SBP (P=.001) and DBP (P=.0001) were significantly higher in the overweight/obese group compared with the lean group. Overweight/obese women had a significantly higher AIx compared with the lean patients (P=.001) (Figure 1).
Multiple linear regression analyses showed a strong and significant association of AIx with anthropometric measures such as BMI, percentage of body fat, waist circumference, and waist to hip ratio in premenopausal women (Table II). AIx was also positively and significantly associated with triglycerides and glucose levels. AIx showed a positive and significant correlation with SBP and DBP (Figure 2A and 2B). AIx was also strongly associated with body weight (Figure 3).
Table II. Association Between Augmentation Index and Clinical Variables
Abbreviations: BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein; r, Pearson coefficient. Multiple linear regression analyses for augmentation index in overweight/obese and lean groups.
Body fat, %
Waist circumference, cm
Total cholesterol, mmol/L
Fasting glucose, mmol/L
To our knowledge, this is the first study measuring arterial stiffness in overweight/obese Australian premenopausal women compared with their lean counterparts. The results showed an increased arterial stiffness in the overweight patients compared with lean patients, as well as a positive association of AIx with measurements of body composition and BP. This suggests that a greater cardiovascular risk in these obese women may be related to arterial stiffness.
This study identified significantly unfavorable lipid profile and increased BP in the overweight/obese patients, compared with the lean group, as well as increased glucose levels. Our findings agree with a previous study with 16 obese and 10 lean American healthy premenopausal women, which observed higher total cholesterol and triglyceride levels, as well as increased BPs and glucose and insulin levels in the obese women.23 In Australia, hypertension is a major health problem and data from the 1999–2000 AusDiab study24 indicated that 30% of the population 25 years and older had high SBP (≥140 mm Hg) or DBP (≥90 mm Hg) or were taking medication to control hypertension. Hypertension is associated with increased risk of coronary heart disease (CHD), stroke, heart failure, and kidney failure.25 Hypercholesterolemia has also been linked to the development of CHD, and hypertriglyceridemia often occurs in relationship with obesity.2
The main finding of this study was that overweight women presented with increased arterial stiffening represented by a higher AIx compared with lean patients (Figure 1). Obesity is a powerful predictor of CHD risk.26 A study with young adults aged 10 to 24 years (n=670, 62% non-Caucasian, 35% male) also found arterial stiffness to be increased in young adults with obesity and obesity-related type 2 diabetes mellitus, even after correction for risk factors, as compared with lean controls.13 In addition, obesity has recently been associated with arterial stiffness in Spanish women18 and Croatian adults.12 The AIx is an indicator of arterial stiffness, which could be a useful screening measurement for identifying high cardiovascular risk in adults.3
AIx is negative in healthy young people, becoming positive, as arteries gradually stiffen6,27 with aging.28 The progressive rate of arterial stiffening is influenced by hypertension, diabetes, and atherosclerosis.29 Evidence suggests that the changes to the endothelium influenced by age and hypertension might be due to their effects on nitric oxide production or release.29l-arginine synthesizes nitric oxide, which is released by endothelial cells. NO has potent vasodilator effects30 and has been proposed to play a role in the antiatherosclerotic process.31 The endothelium is essential for normal vascular physiology, as it is a multifunctional organ coating the interior of blood vessels.32 The disequilibrium between endothelium-derived relaxation and contraction causes endothelial dysfunction, which is a marker for atherosclerosis33and plays an important role in hypertension, diabetes, and thrombosis, contributing to an increase in arterial stiffness.33
In the present study, multiple regression analyses were performed to evaluate whether AIx was correlated with components of metabolic risk factors. AIx was an independent predictor of body composition (BMI, percentage of body fat, waist circumference, and waist to hip ratio) and SBP and DBP response, as indicated by high and statistically significant, standardized regression coefficient values. Our results corroborate with a cross-sectional study that included 31 obese (18 with PCOS) and 39 lean (22 with PCOS) women and showed that (central) obesity, rather than PCOS itself, was associated with increased arterial stiffness.5 Obesity is an important risk factor in cardiovascular disease, and BMI has been associated with enhanced pulse wave velocity and, hence, increased arterial stiffness.34 The Hoorn Study, a population-based cohort study, estimated the relation of precisely measured regional body composition with peripheral and central arterial stiffness in 648 elderly participants (mean age 69.0±6.0 years). This study observed that different fat depots throughout the body might differ with regard to their association with arterial stiffness.35 In a population of relatively young firefighters (aged 29.7±8.0 years), an increased BMI (≥29.5 kg/m2) was associated with elevated peripheral BP and arterial stiffness.36 A study with healthy young people reported obesity and BP as the major determinants of arterial stiffness.8 An association between arterial stiffness and resistant hypertension has been found in older individuals.7 In addition to its association with BP,3,7,36 increased arterial stiffening has also been associated with left ventricular hypertrophy, impaired coronary perfusion, and thus an increase in the risk of stroke, heart failure, and myocardial infarction,4 representing an independent risk factor for cardiovascular disease.4 Results from the present study also found AIx to be predictive of higher triglycerides and fasting glucose concentrations, outcomes that are in accordance with previous findings.29
The results of the present study support the concept that central obesity, represented by anthropometric measures, such as BMI, percentage of body fat, waist circumference, and waist/hip ratio, play an important role in the association between obesity and arterial stiffness. Interestingly, a study showed that BMI, waist circumference, and waist/hip ratio were significantly and inverse predictors of arterial stiffness (P<.05) in women (352 healthy patients, including 200 premenopausal women), whereas in men, only BMI inversely predicted arterial stiffness (P<.05). The authors suggest that the relationship of arterial stiffness and obesity may be sex specific; however, they indicate the need for further studies to validate their findings.12 Although a definite mechanism is yet to be elucidated, several factors associated with central obesity may play a role, such as the increased lipolytic activity of visceral adipocytes, increased insulin and pro-inflammatory cytokine levels, greater sympathetic nervous system activity, or even an imbalance between vasodilatory and vasoconstricting substances, all of which have been shown to play key roles in the process of arterial stiffening.37
Identifying a greater arterial stiffness in Australian overweight/obese women is novel as there are no published data in this population. To our knowledge, the only study with overweight Australian women investigated whether two milder phenotypes of PCOS have elevated CVD risk compared with controls and found no differences in the markers of endothelial function or arterial stiffness between phenotypes in the PCOS cohort.38 Studies assessing that overweight/obese individuals are in the high-risk category for chronic disease have been conducted in different populations.5,18 Due to the lack of scientific studies and literature available in the area of overweight/obese Australian women, it has been valuable to assess whether trends observed in other countries were reflected in Australia, considering the significant differences that exist in environmental factors such as lifestyle and climate. Dietary, physical activity, and other lifestyle patterns in Australian women may differ from other populations. Hence, the outcomes related to BP and AI could potentially be different from other societies. However, similar to other population groups, data from this study supported the notion that arterial stiffness is related to body composition, and therefore may be independent of other lifestyle factors.
Study Strengths and Limitations
One strength of this study is that all participants were in the luteal phase. The choice of including only premenopausal women in our study was to prevent the effects of female hormone estradiol on arterial stiffness measurements, as it plays a protective effect in lipoprotein metabolism, but falls substantially after menopause, augmenting arterial stiffening.39 Age might also be a bias, as increased arterial stiffness might be due to age-associated structural changes in the arterial walls,28 depending on elastin and collagen composition, the calcium content of elastin, and changes in vasoconstrictor tone.40 In the present study, there was no statistically significant difference of age between the groups (P=.319), allowing the assumption that any differences found in the results were not age-related, since chronic disease risk factors increase with aging.28 Genre might be a confounding factor in those studies including men and women, as the pulse wave velocity is lower in women than in men due to the vasodilatory and nitric oxide–producing effects of estrogen.41 This study also has some limitations. The small sample size is a limitation of this pilot study and also men were not included in this study. In addition, progesterone levels were not measured, which could have been a better form of identifying the ovulation phase in our participants. Given that this was a pilot study, dietary analysis and sodium intake was not evaluated, which is another limitation of this study.
Collectively, the results of this study provide further information regarding obesity and cardiovascular disease risk factors related to body composition. The data suggest that greater cardiovascular risk in overweight/obese women may be related to increased arterial stiffness, as well as increased BP and cholesterol. From the perspective of cardiovascular risk reduction, lifestyle changes to reduce weight should be high on the list of priorities in the care of women with obesity.
Declaration of Interest: The authors declare that they have no conflicts of interest.
Statement of Financial Disclosure: This study has been funded by Curtin University Internal Funds.
Author Contributions: SRB conducted statistical analyses and had input into the writing of the manuscript. SP conceived, designed, and supervised the study and the statistical analysis and mentored the manuscript.