The present study investigated the impact of acute exercise on FMD and the influences of gender and exercise habit, in 74 young healthy subjects from society. In the present study, we found that FMD was reduced after exercise, and the reduction was observed in female group and subjects who do not exercise 3 or more days a week. There were significant differences according to gender and exercise habit, regarding the impact of acute exercise on FMD.
Impact of exercise on FMD
FMD can be improved by exercise training, which is known for beneficial for cardiovascular diseases [
17,
18,
21,
28]. Although there have been lots of evidence implying the beneficial effect of exercise on endothelial function, the impact of acute exercise on FMD is still inconclusive. Silvestro et al. investigated the preventive effect of vitamin C on endothelial function, and they reported the reduced FMD after exercise in patients with intermittent claudication [
23]. Highly endurance-trained male athletes showed reduced FMD 1 hour after intensive exercise in a study of Rognmo et al. [
24]. Jones et al. reported decrease of FMD after exercise, in a study investigated the diurnal variation of FMD [
22]. In contrast to these reports, sustained increase of FMD after acute exercise was observed in postmenopausal women [
25]. Regarding healthy controls, Cosio-Lima et al. showed acute vasodilatory response after 30-minute walk, comparing FMD between healthy controls and kidney transplant recipients [
26]. In a recent study of Llewellyn et al., some interesting findings were reported [
29]. They found that endothelial function was reduced post-exercise when expressed as percent change in diameter, but the decrease of FMD was attenuated when it was normalized to shear rate (SR).
In the present study, post-exercise FMD was significantly reduced compared with pre-exercise (Figure
4). This result should be interpreted cautiously, because FMD is directly affected by the baseline brachial artery diameter. Exercise induces increase in blood flow and the augmented blood flow causes vasodilation, which directly impacts the magnitude of FMD [
30]. For this reason, there have been efforts to normalize FMD according to SR.
Pyke et al. and
Harris et al. suggested a normalization method for SR [
30‐
32], and it has been accepted as one of the appropriate methods for interpretation of FMD. However, FMD and SR after acute exercise showed weak relationship, suggesting this normalization method should not be applied for post-exercise data [
29]. Instead, we adopted ANCOVA and RM-ANCOVA methods to normalize FMD using the pre-exercise baseline brachial artery diameter as covariance. Figure
2 shows the close correlation of pre-exercise baseline diameters with post-exercise diameters, pre- and post-exercise FMD. These results provide reasonable evidence for using baseline brachial artery diameter to normalize FMD.
Since the burden of acute exercise could affect the degree of vasodilation [
25,
27], and it might have influenced the results of this study, we also analyzed the relationship of exercise duration and METS with FMD (Figure
3). However, the exercise parameters were not associated with FMD measurements, indicating that the burden of exercise in this study did not influence the results.
The reduction of FMD after exercise mainly came from female group and subjects who do not exercise 3 or more days a week. Female group and subjects without regular exercise showed significant reduction of FMD (Figure
5) and ΔFMD was larger in female group (Figure
7). These results might be due to the difference of exercise habit between genders, as most of the subjects with regular exercise were male (Table
1). Nevertheless, ΔFMD showed significant correlation with exercise habit (β = 2.532;
P = 0.027) even the effect of gender was adjusted (Table
3), suggesting the exercise habit is an important factor. The result shown in Figure
6 is another supporting evidence that exercise habit influences post-exercise FMD.
Gender difference in FMD
In the present study, changes of FMD after exercise showed significant gender difference, which is worthy of attention. We should consider the reasons why women had higher pre-exercise FMD and why they had a greater FMD reduction after exercise.
Firstly, pre-exercise FMD was significantly higher in female group. This phenomenon was reported by a series of studies, showing similar results. In a study by
Jensen-Urstad and Johansson, FMD was 3.1 ± 2.7% in male subjects and 5.7 ± 3.5% in female subjects at 35 years of age [
33]. It could be inferred that smaller brachial artery diameter and hormonal status have influenced the results, since the smaller vessel shows the greater vasodilator response [
34], and estrogen replacement therapy improves vascular function [
35]. In a study of 2109 healthy adults aged 24 to 39 years by Juonala et al., male gender was an independent negative determinant of FMD [
36]. Another important study by Mizia-Stec et al. provided an explanation regarding the difference in FMD between male and female patients with coronary artery disease [
37]. In that study, FMD was significantly higher in female patients (12.9 ± 6.7 versus 8.9 ± 5.9%; P = 0.034), whereas baseline brachial artery diameter was higher in male patients (4.41 ± 0.6 versus 3.79 ± 0.5 mm; P = 0.012). Since the authors found that FMD was inversely correlated with baseline diameter, they arbitrarily compared the indices of “FMD × baseline diameter”, which were not different between male and female. These results are concordant with those of our study. Based on these evidences from previous studies, we could suggest that higher pre-exercise FMD in female group was come from the difference in baseline artery diameter. It might account for baseline gender difference in endogenous vasodilation and also difference in hormonal status.
Secondly, female subjects showed a greater decrease of FMD after exercise. In the present study, baseline brachial artery diameter was smaller in female group, while the increase of brachial artery diameter after exercise was larger in female. Compared to the baseline diameter, the increment was 4.2% in male and 6.8% in female. We believe that this might have resulted in the greater decrease of FMD after exercise in female group. Additionally, we could suggest that baseline endogenous vasodilation is different between male and female, but this difference is abolished after acute exercise, since vessel diameter is increased to maximum by exercise.
Importantly, we used baseline brachial artery diameter as covariance for ANCOVA or RM-ANCOVA tests. Thus, gender differences and also influences of exercise habit in our study are fairly independent from the influence of baseline diameter. We believe that we could show the important characteristics of acute exercise model of FMD, regardless of baseline diameter.
Clinical implications
The results of the present study have some important points. First, regarding the interpretation of FMD, it should be tailored depending on the gender. Several previous studies and the present study commonly indicate that the impact of exercise on FMD is definitely different according to gender [
16,
17,
38]. It might reflect the low overall physical activity level in female, which eventually impairs the endothelial capacity. Also it should be considered when FMD was used as a surrogate marker of the efficacy of clinical intervention. Second, exercise habit is an important factor determining the response of FMD to acute exercise. It suggests the beneficial effect of exercise on endothelial function, in concordance with previous studies [
17,
18,
21,
28]. In subjects who do not exercise regularly, vascular capacity might be impaired, and therefore, decreasing post-exercise FMD. Third, endothelial dysfunction could be manifested in healthy young adults as a form of impaired post-exercise FMD. Endothelial dysfunction is an early sign of atherosclerosis, and there have been several reports suggesting that endothelial dysfunction is present even in children with risk factors [
5].
Limitations
There are several limitations regarding this study. First, FMD was analyzed by calipers without a system for the automatic evaluation. Since the automatic measurement is more reproducible and less subjective [
39,
40], we should consider the probable bias from manual measurement. Despite the methodological limitation, our study showed evident results. It might be due to the experienced sonographers and rigorously standardized procedure [
41]. Second, detailed assessment of exercise capacity was not done. The qualitative analysis of exercise capacity requires more specific information such as peak oxygen consumption (peak VO
2) or ventilator efficiency (VE/VCO
2), assessed by cardiopulmonary exercise test [
42]. However, any study participants who could not reach at least 85% of age-predicted maximum heart rate in treadmill test were excluded on account of inadequate exercise loads in this study. It is reasonable to assume that this protocol enabled to estimate the impact of acute exercise with adequate load on FMD. Third, study participants were young healthy people. FMD responses to acute exercise in subjects with established cardiovascular risk factors or cardiovascular diseases need to be clarified. Fourth, all of our study participants were Korean ethnicity. There have been several reports suggesting ethnic differences between Asians and Caucasian, however, FMD of healthy young adults was similar in both ethnic groups [
15,
43,
44].