Background
The properties in the arterial tree which are of importance for cardiovascular health, do change over a lifetime [
1]. There is a progressive stiffening of arteries along with healthy ageing, and this has been described in several longitudinal cohort studies [
2‐
4]. The mechanical stress by the repetitive pulsations causes the elastin lamellae in the media to become frayed and fractured and the collagen fibers to increase. The elastic arteries respond with stiffening and dilation [
5]. Arterial stiffness is associated with cardiovascular disease (CVD) risk factors and it is suggested that blood pressure and central body fatness plays an important role [
4]. A systematic review indicates that obesity in children and adolescents is associated with greater arterial stiffness, as compared to healthy BMI controls [
6]. A previous population-based study showed a positive association between local stiffness in the carotid and femoral arteries, all-cause mortality, and incidence of cardiovascular events [
7]. An increase in carotid intima media thickness (cIMT) is also associated with many traditional risk factors and is considered to be a surrogate marker of atherosclerosis and increased risk of CVD [
8]. Hypertension is suggested to be the risk factor that contributes most to an increase in cIMT, probably through medial hypertrophy [
9].
Since the arterial properties is not uniform along the arterial tree it is important to measure arterial stiffness at different arterial sites [
7]. Since atherosclerosis is common in the carotid artery, carotid stiffness can be of particular interest [
10]. Increased carotid stiffness is associated with atherosclerotic plaque presence and stroke risk [
11]. Carotid-femoral pulse wave velocity (cfPWV), which is a measurement of regional aortic stiffness, reflects the properties in a combination of elastic and muscular arteries. Local measurements from the carotid artery gives an understanding of stiffening in an elastic part of the arterial tree [
7]. Therefore this present study will focus on local stiffness measurements and IMT in the elastic common carotid artery.
There are several descriptors of local carotid stiffness. The change in vessel diameter between systole and diastole is the absolute distention (systolic diameter (D
s) – diastolic diameter (D
d), μm). The distention is included together with local pulse pressure in the calculation of arterial distensibility (kPa
− 1) [
11]. The distensibility measures the ability of the arteries to expand in response to changes in blood pressure caused by cardiac relaxation and contraction. A formula that in addition to blood pressure also takes into account the arterial wall thickness, is Young’s elastic modulus (kPa). The cIMT is used as a surrogate for total arterial wall thickness in the Young’s elastic modulus formula [
10]. Finally, β Stiffness index (unit-less), an index that accounts for the effect of blood pressure, by including the logarithm of the systolic to diastolic ratio in the equation, can be used to assess local arterial stiffness. The formulas for the local stiffness measurements are presented below [
1]:
Arterial distensibility: (Ds- Dd) / ((Systolic pressure (Ps) – Diastolic pressure (Pd)) x Dd).
Young’s elastic modulus: ((Ps- Pd) x Dd)) / ((Ds- Dd) x h) were h is the arterial wall thickness.
β Stiffness index: (Dd ln(Ps/Pd)) / (Ds- Dd).
For interpretation, lower values of arterial distensibility and higher values of Young’s elastic modulus and β stiffness index, indicate stiffer vessels [
11]. Because of pulse pressure amplification in young subjects, with a higher blood pressure in the peripheral arteries, it is of importance to use the local blood pressure from the same site as the relative diameter change is measured. The gold standard is to use the local blood pressure in the calculations of the different descriptors of local carotid elasticity [
10]. The use of brachial pulse pressure may overestimate pulse pressure in central arteries, which results in false lower values of arterial distensibility and false higher values of Young’s elastic modulus and β stiffness index [
12].
Obesity has nearly tripled worldwide during the last four decades and is of growing concern since it is a risk factor for CVD and several other non-communicable diseases [
13]. According to WHO Body Mass Index (BMI) definitions [
14], the Public Health Agency of Sweden reported in 2016 that 51% of the total Swedish population was overweight, and that overweight and obesity was increasing mostly in the age group between 16 and 29 years [
15]. In addition to BMI, body composition can be assessed by measuring waist circumference, and the percentage of body fat can be assessed using an impedance body composition analyzer. Given the important role of arterial stiffness in CVD [
7] and the worldwide increasing prevalence of overweight and obesity [
13], it is important to find simple and useful methods for early identification of young adults with stiffening of the arterial tree, and increased CVD risk. It is of interest to explore how the body composition measurements (BMI, percentage of body fat, and waist circumference) are associated with local stiffness in the common carotid artery, measured by ultrasound and analyzed using B-mode edge wall tracking [
16].
Aim
The aim of the present study was to explore the hypothesis that local measurements of the common carotid artery are associated with body composition. The measurements used were thickness (cIMT) and stiffness, i.e., arterial distensibility, Young’s elastic modulus, and β stiffness index. The study was carried out in a subsample of healthy young women and men from the Swedish Lifestyle, Biomarkers, and Atherosclerosis (LBA) Study.
Discussion
The main finding in the LBA subsample of healthy young individuals is that body composition measurements, especially BMI and percentage of body fat, are positively associated with a stiffer common carotid artery, in both young women and men.
Methodological aspects
A decrease of arterial wall elasticity is a useful and early predictor for vascular disease. However, there is no precise direct method for the determination [
24]. A lack of standards and the use of many different measures of local stiffness makes it difficult to compare different study results. Of the three local stiffness measurements that were calculated from the common carotid artery in the present study, arterial distensibility was the measure with the strongest associations with the body composition measurements, BMI, percentage of body fat, and waist circumference, in both women and men. The discrepancy between the three different local stiffness measurements is explained by the variables included in the calculations. When taking into account the intima media thickness that is included in the calculation of Young’s elastic modulus, associations with body composition measurements get weaker (in women) or disappear (in men). This could however be either a power issue because of the lower number of male individuals in the LBA subsample or the fact that the variation of cIMT in this young and healthy cohort was very low.
The guidelines recommend using the local blood pressure instead of the brachial blood pressure because of the pulse amplification between central and peripheral arterial sites, especially in young individuals [
10]. In the present study, the local blood pressure in the common carotid artery was used in the calculations of the three local stiffness measurements, in opposite to several other studies using the brachial blood pressure [
25‐
28]. One study reported that the brachial pulse pressure correlated well with the local pulse pressure both in women and men but the correlation was weakest in the youngest age group (r = 0.57) [
28]. Since the study population in the present study is between 18 and 25 years, it is of importance to take into account that the stiffness measurements can be affected by the choice of blood pressure (e.g. brachial or carotid) used in the calculations.
Comparisons of measurements in the common carotid artery between women and men
Significant differences were found between women and men in the common carotid artery diameter and cIMT,
p < 0.001 and
p < 0.05 respectively. Women had smaller carotid diameter (as expected) and thinner cIMT than men. In the Young Finns study, the cIMT differed between women and men in the same age group as the LBA subsample, also showing that women had thinner cIMT than men [
29]. The same findings are demonstrated in a healthy sub-population in a multi-center study collecting reference intervals for carotid cIMT measured with echotracking [
30].
Significant differences (p < 0.001) were also found between women and men in the calculated local stiffness measurements in the common carotid artery. Men had lower mean arterial distensibility and higher mean Young’s elastic modulus, and β stiffness index, indicating stiffer arteries than in women. The findings in the present study are in line with results from the Young Finns Study [
27,
31]. They found that men had significantly lower carotid artery distensibility and higher pulse wave velocity, indicating stiffer arteries, compared to women in all age groups (30–36 years, 39–45 years, 46–76 years). The findings are also in line with the gender difference in pulse wave velocity, as a measurement of regional stiffness, which was demonstrated earlier in the LBA study, showing that men had higher pulse wave velocity than women [
32].
Reference values for carotid distensibility coefficient, as a measurement of local arterial stiffness, were published in 2015 [
28], in healthy test subjects, in the ages 15–85 years. The authors calculated carotid distensibility coefficient with artery area instead of diameter and found a negative and non-linear relationship between the carotid distensibility coefficient and age. When looking at the 50th percentile for the test subjects in the age of 20 years, the mean carotid distensibility coefficient was higher in women than in men, which is in line with the findings in the present study. Reference values from a younger age group, 6–18 years, have also been published, showing age- and sex-specific differences in distensibility measurements from the age of 15 years, were girls having higher mean value of carotid distensibility coefficient than boys [
25]
Local measurements of the common carotid artery and the influence of body composition
Previous data from the LBA study indicates that young, Swedish adults with obesity and low cardiorespiratory fitness have significantly higher cfPWV than non-obese adults with medium or high cardiorespiratory fitness [
32]. The present study, with focus specifically on local stiffness in the common carotid artery, shows partly similar results. In the LBA subsample, women and men with BMI ≤ 25 and with lower percentage of body fat, had significantly higher arterial distensibility, indicating more elastic carotid arteries compared to women and men with BMI > 25 and a higher percentage of body fat. There are many instruments for the assessment of percentage of body fat, however there are no well-established cut-off values for the interpretation of the results.
Multiple regression analyses were performed to explore which of the body composition measurements that contributed mostly to the variation in arterial distensibility. The analyses showed that BMI had the highest impact on arterial distensibility in women, and that BMI and percentage of body fat had equal impact on arterial distensibility in men. One explanation to this gender difference could be the different fat distribution in women and men [
33]. A man with a high percent of body fat is more likely to have a central/android fat distribution with fat stored preferentially in the abdominal area. In women it is more common with fat distributed to the hips and thighs [
33]. Abdominal obesity, often assessed with waist-hip ratio, is associated with increased blood pressure, CVD, and diabetes [
13,
34,
35]. This gender difference in fat distribution may explain why percentage of body fat have a greater impact on arterial distensibility in men, than in women.
Strengths and limitations
There are several limitations in the present study, one is the lower number of male individuals. For unknown reasons it was much more difficult to recruit men to the study.
The possible number of edge wall tracking analyses were restricted by limited access to the wall tracking system and quality requirements of the registrations. A greater number of participants in the LBA subsample had been desirable to increase the power in the statistical calculations.
The fact that the individuals included in the study were self-reported healthy is another limitation in the study. We didn’t include individuals with a chronic disease but we accepted for example individuals with obesity, which is a reversible condition and an important risk factor for CVD.
Another limitation that needs to be highlighted is the cross-sectional design in the LBA study that prevents us from drawing conclusions in terms of causality.
One strength in the present study is the age of the population. Healthy young adults are underrepresented in the CVD literature compared to different patient groups. This age group can contribute to the detection of early changes affecting the development of CVD. The young adults in the age of 18–25 years are about to create their own habits and it is of great importance to highlight the benefits of a healthy lifestyle and to detect young adults who need cardiovascular risk follow-up and life-style counseling.
Clinical perspectives
The body composition measurements, BMI, percentage of body fat, and waist circumference are common examinations that are easy to perform. In this age group, the body composition measurements contributed more than age, MAP, and the biomarkers to the variation in arterial distensibility. Our data suggests, that in this age group, BMI is the most simple and still useful tool to identify young adults that need to be further examined for future cardiovascular risk.
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