The effect of aerobic training on endothelium-dependent vasodilatation in patients with coronary artery disease who were revascularized and young men

doi:10.4236/health.2013.510230

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Vol.5, No.10, 1706-1711 (2013) Health

http://dx.doi.org/10.4236/health.2013.510230

The effect of aerobic training on

endothelium-dependent vasodilatation

in patients with coronary artery disease

who were revascularized and young men

Seyed Masoud Seyediyan, Farzaneh Ahmadi*, Babak Hamidian, Ebrahim Hajizadeh,

Afshin Rezazadeh, Ahmad Reza Asare, Mohammad Hasan Adel, Mohammad Nourizadeh

Department of Cardiology, Medical Joundishapour University of Ahvaz, Atherosclerosis Research Center Jondishapour University of

Medical Sciences, Ahvaz, Iran; *Corresponding Author: [email protected]

Received 13 April 2013; revised 15 May 2013; accepted 19 June 2013

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Aim: The aim of this study was to determine the

effect of training on endothelium-dependent

vasodilatation in patients with coronary artery

disease (CAD) after revascularization and heal-

thy young men. Background: Impaired endothe-

lial function has been observed in patients with

CAD and those with CAD risk factors. Studies

have show n that exercise can enhance endothe-

lial function. Methods: This experimental cross-

sectional study was conducted on patients with

CAD (3 months after CABG and PCI) and students

of medical school in 2011. Endothelium depen-

dent dilation of the brachial artery was deter-

mined by using high-resolution vascular ultra-

sonography through flow-mediated vasodilata-

tion (FMD) after induction of ischemia, and the

data were analyzed using SPSS, dependent t-

test and ANCOVA. Findings: The findings show -

ed that at baseline, FMD was reduced in revas-

cularized patients, when compared with healthy

young men, after 8 weeks, and exercise training

significantly improved FMD in patients under-

went training group [from 4.31 ± 1.45 (SD)% to

6.15 ± 0.773 (SD)%, p < 0.05] and substantially

increased the same in healthy young men [from

9.18% ± 1.45% to 11.72% ± 1.72%, p < 0.05]

However, in the control group, the FMD remain-

ed unchanged, and even after aerobic training,

it did not significantly modif y the brachial artery

diameter in these group s. Conclusion : Our study

demonstrates that endothelial dysfunction per-

sisting in CAD patients after revascularization

and aerobic training can improve endothelial

function in different vascular beds in CAD pa-

tients and healthy young men. This may contri-

bute to the benefit of reg ular exercise in pr event-

ing and restricting cardiovascular disease.

Keywords: Endotheli um-Dependent Vasodilatation;

Coronary Artery Disease; Aerobic Training;

High-Resolution Ultrasound;

Flow-Mediated Dilation

1. INTRODUCTION

Currently, most patients with angina pectoris have

their symptoms controlled with medication or by revas-

cularization by PTCA or CABG. Consequently, and with

rare exceptions [1], much of the evidence that exercise

training improves effort tolerance in patients with angina

pectoris was obtained before 1990. Exercise training

increases the exercise time to the onset of angina or even

eliminates angina entirely by at least two mechanisms.

First, exercise training reduces the M.O2 requirements

during submaximal exercise [1-3]. Second, exercise train-

ing reduces endothelial dysfunction [4-6]. Normal coro-

nary arteries dilate with exercise, whereas atherosclerotic

coronary arteries often demonstrate endothelial dysfunc-

tion evidenced by exercise-induced vasoconstriction. Few

large trials have examined the effects of exercise-based

cardiac rehabilitation in patients following PTCA [6,7].

There are very few data for coronary artery disease

and healthy young men. In a previous study, we demon-

strated that in healthy middle age men, 8 weeks of circuit

training did not affect vascular function [8], whereas, bra

chial artery flow mediated dilation (FMD) was enhanced

S. M. Seyediyan et al. / Health 5 (2013) 1706-1711 1707

after a 10 weeks programme of daily aerobic and anaero-

bic exercise training in young military recruits [9], also

in CAD patients who had had a recent acute myocardial

infarction. Aerobic training significantly improved endo-

thelial function, although this beneficial effect was lost

after 1 month of detraining [10]. In addition, regular

aerobic physical training enhanced vascular function in

patients with chronic heart failure [11]. However, there is

very little knowledge about a similar benefit from resis-

tance training on CAD revascuralized patients and heal-

thy young men.

Therefore, in this study, we have investigated the ef-

fects of an 8-week aerobic training program on systemic

artery vascular function in coronary artery disease (CAD)

patients who have been treated and don’t have apparent

ischemia, and compared the results with the same of

young men, and have demonstrated which is the most

significant improvement in endothelium dependent dila-

tion in all groups.

2. METHODS

2.1. Subjects

The study included 20 men with a history of CAD

from heart clinic of medical science hospital and they

were divided to 10 cases and 10 control groups. The in-

clusion criteria were as follows: the patients must be

known case of CAD, and underwent regular surgical (co-

ronary artery bypass grafting) or non-surgical revascu-

larization (percutaneous transluminal coronary angio-

plasty) with normal or near normal left ventricle ejection

fraction, more than recent 3 month.

On the other hand, patients who had valvular heart dis-

ease, chronic obstructive lung disease, renal and hepatic

dysfunction, asthma, creatinine > 2.5 mg/dl and subjects

performed more than two sessions of light to moderate

exercise per week, were excluded week. Medications did

not change across the course of control or exercise train-

ing periods. Furthermore, 10 young age healthy male

subjects without cardiovascular disease and risks factors

were randomly selected among the students of a medical

school.

The characteristics of revascularization patients and

healthy young subjects enrolled in the study are present-

ed in Table 1. The ethics committee approved the proto-

col and all the subjects gave written informed consent.

2.2. Study Design

All subjects underwent baseline assessment, after

which CAD patients and young men were randomly as-

signed to either remain sedentary or undergo exercise

training for 8 weeks according to the following protocol,

and after 2 months, the assessment was repeated. Pa-

tients and young men were requested to maintain their

diet and other life style behavior for the duration of the

study, and this was confirmed through interview and

questionnaire.

Assessment of vascular function was carried out in a

quiet, temperature-controlled laboratory after an 8-h fast,

12-h abstinence from caffeine, and 24-h abstinence from

alcohol and exercise. For individual subjects, repeat as-

sessments were performed at the same time of the day,

and the time of medication use was not changed. Endo-

thelial function was assessed using a noninvasive tech-

nique proposed by Celermajer et al. [6]. The subjects

were made to rest in supine with nondominant arm ex-

tended and immobilized with foam supports at an angle

of 80˚ from the torso, the heart rate was continuously

monitored with a three-lead electrocardiograph, and the

mean arterial pressure was determined using sphygmo-

manometer (ALPK2, Japan) on the contralateral arm. A

rapid inflation and deflation pneumatic cuff was posi-

tioned on the imaged arm immediately proximal to the

olecranon process to provide a stimulus to forearm ische-

mia. Brachial artery diameters were analyzed at the time

of the ECG monitoring, i.e., at the beginning of QRS

complex (end diastole). The forearm cuff was then in-

flated to 200 mmHg for 5 min. Images were recorded 30

s before cuff deflation and for 2 min after deflation. Bra-

chial artery reactivity was evaluated by two-dimensional

ultrasonography (Siemens 40) with a linear, high-reso-

lution probe (10 MHz). Measurements were performed at

baseline (Figure 1) and during flow-mediated dilation

(FMD) for both patients and young healthy men. Changes

in vessel diameter were calculated for each subject as the

percentage variation of arterial diameter under different

stimuli, when compared with the baseline diameter.

Table 1. Study population.

1, Aerobic training (CAD) G2, Aerobic training (young men) G3, Control (CAD)

mean SD (Standard Deviation)

Age (year) 55 ± 4.33 27.7 ± 4.16 53 ± 6.43

Weight (kg) 82.1 ± 11.98 75 ± 7.84 82.85 ± 14.38

High (m) 1.73 ± 45 1.72 ± 5.51 1.741 ± 6.11

S. M. Seyediyan et al. / Health 5 (2013) 1706-1711

1708

Young men

Tranining Control

FMD

Figure 1. Baseline percentage of FMD in

the three groups (pretest).

2.3. Exercise Training Program

After baseline evaluation (Figure 1), the patients and

young men were randomized to receive aerobic training

(Group 1 [G1], 10 patients) (Group 2 [G2], 10 young men)

or as control not receiving the training (Group 3, [G3], 10

patients). The subjects in G1 and G2 underwent moder-

ated aerobic training thrice a week for 1 week at Tapesh

cardiac rehabilitation center. Each session included a

10-min warm up, 30 min of running on a treadmill with

telemetry monitoring and intensity set at 60% - 70% of

peak exercise heart rate measured in the second ECG

stress testing, and a 10-min cool down. G3 patients

avoided regular physical activity. Cardiac rhythm was

continuously monitored on a four-channel telemetry sys-

tem in all trained subjects (patient and young men) and

in all sessions throughout the trial. Patients and young

men in the aerobic training groups were also encouraged

to gradually increase their daily physical level.

2.4. Follow up

All tests were repeated after 2 months and the results

were compared with those of the baseline tests. The

training program in trained subjects was stopped at this

point. The arterial vasoreactivity and treadmill (Bruce pro-

tocol) tests were repeated again. Pharmacological ther-

apy remained unchanged throughout the study.

2.5. Statistical Analysis

Statistical analyses were performed with SPSS software

(version 17.0 for Windows). The data are presented as

mean ± SD. Baseline values were compared using

ANOVA and t-test to determine whether there were sig-

nificant differences among the three groups, and all the

data were analyzed from baseline to post-test using de-

pendent t-test in each group. In addition, Tukey’s post-

test, was used to study whether the magnitude of brachial

artery reactivity differed among the trained groups and

control group (young men and patients) over time (base-

line and after 8 weeks). A value of p < 0.05 was consid-

ered as statistically significant, and the authors had full

access to and take responsibility for the integrity of the

data. All the authors have and agree to the data presented

in the manuscript.

2.6. Results

None of the metabolic parameters considered was sig-

nificantly different between G1 and G3 (patients group),

but the young healthy men exhibited significant differ-

ences.

2.7. Brachial Arterial Vasoreactivity

At the initial evaluation, the baseline diameter of the

brachial artery did not differ significantly among the

three groups: 3.81 ± 0.19 SD in G1, 3.9 ± 0.41 SD in G2,

and 4.17 ± 0.76 SD in G3. In the CAD patients and

young healthy men, the basal brachial artery was not sig-

nificantly different between untrained and trained groups

(Table 2). After cuff release, we assessed FMD re-

sponses in all the groups, and the results exhibited that

the FMD responses were significantly impaired in the

CAD patients, when compared with healthy young men:

4.31 ± 1.15 SD for G1, 9.18 ± 1.45 SD for G2, and 4.64 ±

1.81 SD for G3 (Figure 2). Aerobic training significantly

increased the FMD response to forearm ischemia: (6.15

± 0.77 SD; p < 0.05) for G1, (11.72 ± 1.72 SD, p < 0.05)

for G2, and did not significantly change in the untrained

CAD patients (control group).

3. DISCUSSION

In this study, the effects of moderate aerobic training

on endothelial function through the FMD assessment are

compared with the patients with artery diseases, who had

open-heart surgery, and healthy young men with no ex-

ercise activity.

Our research has several finding as following:

Firstly, in accordance to the previous reports, endothe-

lial function can be reliably assessed by FMD in brachial

artery. However, this test was first introduced by German

scientist celermajor in which it is illustrated that FMD

reduction and brachial artery have a direct relationship

with cardiovascular diseases and risk factors or athero-

sclerosis [12]. In addition, one of the findings in the pre-

vious reports has been confirmed that the CAD patients,

who had history of myocardial infarction or Coronary

artery disease, had significantly lower FMD in com-

parison to healthy people [13]. In fact, our results are

consistent with their findings.

Secondary, regular physical activities have a strong

S. M. Seyediyan et al. / Health 5 (2013) 1706-1711 1709

Table 2. Brachial reactivity results at baseline and follow up.

G1 G

2, G3

Items

Time 0 Follow up Time 0 Follow up Time 0 Follow up

Baseline diameter, mm 3.81 ± 0.196 3.84 ± 0.202 3.9 ± 0.41 3.95 ± 0.33 4.17 ± 0.76 4.18 ± 0.73

FMD% 4.31 ± 1.15 6.15 ± *0.77 9.18 ± 1.45 11.72 ± 1.72* 4.64 ± 1.81 4.66 ± 1.30

G1: Aerobic training patients (CAD) G2: Aerobic training young men, G3: control (CAD); p < 0.05 *mean ± SD (Standard Deviation).

Figure 2. Indicated FMD% in the three groups.

positive link with vascular function by which flow blood

and shears stress would increase the vascular artery.

Moreover, it would also improve endothelium function

as it can increase the amount of NO in vascular [14].

Previous studies show that eight weeks of resistance

training in young men has caused a considerable rise in

FMD [15]. De souza did three month endurance exercise

on the youth who their Endothelium-dependent vaso-

dilatation function was increased by about 30 percent in

the year 2000 [16]. Current research on youths show that

60 to 80 percent increase in maximum heart rate after

two month aerobic exercise would lead to 21 percent

increase in FMD and finally improve endothelium func-

tion which it is in line with Thiken and Suza’s studies.

Of course the survey on stable coronary patients shows

that after eight weeks aerobic and resistance exercises ,a

rise and an improvement on FMD and vascular endothe-

lial-dependent vasodilatation function respectively. Fur-

thermore, Hambrekht executed four weeks aerobic exer-

cises on CAD patients [7] and Vona and his colleagues

performed different types of exercises such as aerobic

and resistance ones on patients who recently had a myo-

cardial infraction [17]. All findings lead to an improve-

ment on the evaluation of coronary endothelial function

via FMD assessment which they were in line with sub-

ject of current research on interventional treatment like

angiography and open heart surgery. Contrary, but Jodin

and his colleagues after three month exercise on CAD

patients could not achieve acceptable result and the FMD

was not altered [18].

Third, endothelium dysfunction deficiency is one of

major dangerous factors in cardiovascular diseases which

through brachial artery FMD measurement or high qua-

lity sonography as alternative to Non-invasive detection

of atherosclerosis patients are used. However, it is con-

sidered as easy method to evaluate coronary endothelial

function in children and siblings in order to predict and

prevent early vascular structural changes [19].

Fourthly, comparison of FMD percentage in both

groups, young men and coronary patients, were predict-

able. However, FMD alterations in CAD patients (con-

trol group), three month after drug treatment and diet,

remained down and after 8 weeks too lowly. Our results

agree with medical therapy (statin) after 10 weeks faield

to improve endothelium-dependent function in CAD pa-

tients [20] but it is unconvienced with Ling and et al.,

short term simvastatin therapy increases endothelial

function in patients with stable CAD [21]. Furthermore,

the exercises considers as method of intervention in car-

diac rehabilitation and vascular disease.

Finally, it was described that the major objectives of

cardiac rehabilitation centre and sports medicine are as

follows:

● decrease the number of deaths and its complications;

● life style improvement;

● prevent their return to health clinics and early pre-

vention and prediction of groups at risk.

4. LIMITATIONS OF STUDY

During the study, there were some restrictions which

we attempted to solve them.

The number of people who were interested in research

involvement was reduced by prolongation of the project.

Additionally, scholar’s movement between these two

clinics (Cardiac rehabilitation clinic and Sports medicine

clinic) caused to increase expenses, project time and lack

of coordination. Finally, some of patients were suffered

from disability and orthopedic disability which they were

removed from the list and replace them with the other

candidates.

S. M. Seyediyan et al. / Health 5 (2013) 1706-1711

1710

5. CONCLUSION

The present study demonstrates endothelial dysfunc-

tion persisting in CAD patients that were revascularized

and aerobic exercise can improve vascular endothelial

function in CAD patients and healthy young men.

6. ACKNOWLEDGEMENTS

The research is taken from the thesis of Dr Hamidian and Dr Haji-

zadeh and the financial and educational supports were received from

the heart and vascular center of university of medical sciences of Joun-

diShapour University and physical education department of Azad Uni-

versity of Shushter Branch.

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