Download 11237-33357-2

EFFECTS OF REGULAR MODERATE EXERCISE ON ARTERIAL STIFFNESS,
PTX3 PROTEIN AND SOME CARDIAC PARAMETERS
Controlled clinical study
‫تأثيرات التمارين الرياضية ذات الدرجة المتوسطة والمستمرة لفترة طويلة والمنتظمة على تصلب‬
‫ وعلى بعض متغيرات القلب‬PTX3 ‫الشرايين وعلى بروتين‬
ABSTRACT
Objectives:This study intends to show some of the effects of long-term and regular
moderate exercise on arterial stiffness, PTX3 protein levels and some cardiac parameters in
individuals of middle and advanced age. Twenty mountaineers between the ages 35 to 68 who
are interested in regular moderate exercise one day a week for 5 to 20 years (mean 10.45
years) were subjects of this study. Twenty sedentary individuals of the same age group were
also included as the control group.
Methods: Each mountaineer and the individuals in the control group was measured for
lipid profile and complete blood count, and underwent echocardiography and exercise stress
test. Central and peripheral pulse wave velocity was measured by measurement device
noninvasively. The plasma Pentraxin 3 protein was assayed by ELISA. This study was
conducted at Erciyes University in 2013.
Results: Metabolic equivalent and plasma Pentraxin 3 protein levels were found to be
significantly higher in mountaineers, compared to the sedentary group. Femoral-ankle pulse
wave velocity carotid-femoral pulse wave velocity, left ventricular end-systolic diameter and
the neutrophil to lymphocyte ratio were found to be significantly lower in mountaineers,
compared to the sedentary group (p < 0.05). A statistically significant and inverse relationship
was found between metabolic equivalent, pentraxin 3 protein levels and carotid-femoral pulse
wave velocity, femoral-ankle pulse wave velocity.
Conclusions: Long-term and regular, moderate exercise significantly decreases
indicators of systemic inflammation and arterial stiffness.
Keywords: Arterial stiffness, pulse wave velocity, pentraxin 3 protein, moderate
exercise, metabolic equivalent, mountaineers.
‫تأثيرات التمارين الرياضية ذات الدرجة المتوسطة والمستمرة لفترة طويلة والمنتظمة على تصلب‬
‫الشرايين وعلى بروتين ‪ PTX3‬وعلى بعض متغيرات القلب‬
‫الملخص‬
‫األهداف ‪ :‬الغاية من هذه الدراسة هي مراقبة تأثيرات التمارين الرياضية ذات الدرجة المتوسطة والمستمرة لفترة طويلة‬
‫والمنتظمة على تصلب الشرايين وعلى بروتين بينتراكسين‪ 3-‬وعلى بعض متغيرات القلب لدى األشخاص ذات األعمار‬
‫المتوسطة والمسنين‪ .‬اشترك في هذه الدراسة ‪ 20‬شخصا ُ من متسلقي الجبال حيث تتراوح أعمارهم بين ‪ 68 – 35‬سنة‬
‫ويجرون تمرينا ً رياضيا ً واحدا ً في األسبوع بانتظام لمدة ‪ 20-5‬سنة (بمعدل ‪ 10.45‬سنة)‪ .‬وتم إشراك ‪ 20‬شخص‬
‫(مجموعة فحص) ممن ال يمارسون الرياضة من نفس فئة األعمار من أجل مقارنة النتائج‪.‬‬
‫الطرق ‪ :‬تم قياس معايير الدهون والتعداد الكامل للدم وتخطيط القلب واختبار شدة الرياضة لدى المشتركين في هذ الدراسة‬
‫من مجموعة الفحص ومن عينة متسلقي الجبال‪ .‬تم قياس سرعة موجات النبض المركزية والطرفية )‪ )PWV‬من خالل‬
‫جهاز قياس غير باضع‪ .‬تم تحديد مستوى ‪ PTX3‬للبالزما من خالل ‪.ELISA‬‬
‫النتائج‪ :‬وجد المكافئ االستقالبي ومستوى ‪ PTX3‬للبالزما لدى فئة متسلقي الجبال مرتفعا ً بشكل ملموس قياسا ً لفئة‬
‫الفحص‪ .‬ووجدت سرعة موجة نبض الفخذي – الكاحلي‪ ،‬وسرعة موجة نبض السباتي – الفخذي وقطر نهاية االنقباض‬
‫البطيني األيسر ونسبة الخاليا اللمفاوية العدلة لدى فئة متسلقي الجبال منخفضة إحصائيا ً بشكل ملموس قياسا ً لفئة الفحص‬
‫(‪ .)p<0.05‬وتم العثور على عالقة عكسية ملموسة إحصائيا ً بين مستويات المكافئ االستقالبي وبروتين بينتراكسين‪3-‬‬
‫من جهة وسرعة موجة النبض السباتي – الفخذي و سرعة موجة النبض الفخذي – الكاحلي من جهة أخرى‪.‬‬
‫االستنتاجات‪ :‬التمارين الرياضية ذات الدرجة المتوسطة والمستمرة لفترة طويلة والمنتظمة تخفض مؤشرات االلتهاب‬
‫المجموعي والتصلب الشرياني بشكل ملموس‪.‬‬
‫الكلمات الدليلية‪ :‬تصلب للشرايين‪ ،‬سرعة موجة النبض‪ ،‬بروتين بينتراكسين‪ ،3-‬تمارين رياضية ذات الدرجة المتوسطة‪،‬‬
‫مكافئ استقالبي‪ ،‬متسلقي الجبال‪.‬‬
INTRODUCTION
Cardiovascular diseases (CVD) remain the leading cause of mortality in modern
societies. Approximately 80% of all CVD deaths are associated with dysfunction and
disorders of arteries1. Increased arterial stiffness, determined invasively, has been shown to
predict a higher risk of coronary atherosclerosis2. The serial noninvasive evaluation of the
arterial stiffness allows early detection of pathologic acceleration of the aging process and
may be useful for prevention of coronary artery disease, which constitutes a major
atherosclerotic complication. Intensive investigations have been continued to assess the state
and the function of large arteries noninvasively for early detection of atherosclerotic damage
to these vessels3. Many methodologies, both invasive and noninvasive, have been applied to
the assessment of arterial elasticity in vivo. Interest in and measurement of the velocity of
arterial wave propagation as an index of vascular stiffness and vascular health dates back to
the early part of the last century. One of the most widely used non-invasive methods is 'pulse
wave velocity' measurement. Carotid-femoral PWV is considered as the ‘gold-standard’
measurement of arterial stiffness4. Habitual aerobic exercise may delay age-associated
increases in central arterial stiffness5. Greater central arterial compliance may contribute to
the lower incidence of cardiovascular disease observed in middle-aged and older men who
exercise regularly6.
The role of the immune system and inflammatory pathways in the development of
atherosclerotic disease is well established, and systemic markers of inflammation appear
useful for indicating elevated cardiovascular disease risk in middle-age7. Recently, pentraxin
3 protein (PTX3), which is mainly produced by endothelial cells, macrophages, and smooth
muscle cells in the atherosclerotic region, has been identified as a substance playing an
important role in cardioprotection and atheroprotection8. Elevated plasma levels of the
pentraxin protein family member C-reactive protein (CRP) are associated with increased risk
of cardiovascular disease in both healthy and high-risk subjects9. Because of the homology
between PTX3 and CRP, the relevance of PTX3 measurement as diagnostic tool has been
investigated in cardiovascular pathology10. PTX3 in humans, like CRP, is a marker of
atherosclerosis and correlates with the risk of developing vascular events. In conclusion, the
integration of the available evidence on the role of PTX3 as cardiovascular biomarker and as
atheroprotective agent suggests that the increased levels of PTX3 in subjects with CVD could
reflect a protective physiologic response that correlates with the severity of the disease10.
It is known that regular aerobic exercise increases metabolic equivalent (MET), causes
left ventricular hypertrophy, reduces arterial stiffness and consequently reduces
cardiovascular diseases 6. We aimed to show some of the effects of long-term and regular
moderate exercise on arterial stiffness, PTX3 levels and some cardiac parameters in middle
and advanced age individuals.
METHODS
This study was conducted at Erciyes University in 2013. The study was performed 20
mountaineers who between the ages 35 to 68 known as the Erciyes Tigers, members of the
Turkish Mountaineering Federation (TDF). Twenty sedentary individuals of the same age
group were also included as the control group.
Inclusion criteria: For mountaineers; interesting regular moderate exercise (tracking)
one day a week for 5 to 20 years. For sedentary individuals; to be the same age group who
have not exercised in the last two years for more than 2 hours a week.
Exclusion criteria: Metabolic bone disease, arthritis, diabetes, liver disease, kidney
failure, corticosteroid use, smoking, use of alcohol and body mass index over 24.9 kg/m2.
Twenty mountaineers between the ages 35 to 68 known as the Erciyes Tigers,
members of the Turkish Mountaineering Federation (TDF) who are interested in regular
moderate exercise (tracking) one day a week for 5 to 20 years (mean 10.45 years), and 20
sedentary individuals of the same age group were included as the control group in this study.
The control group consisted of volunteers who haven’t exercised in the last two years for more
than 2 hours a week. Subjects with the presence of any of the following were excluded:
metabolic bone disease, arthritis, diabetes, liver disease, kidney failure, corticosteroid use,
smoking, use of alcohol and body mass index over 24.9 kg/m2.
All the mountaineers and the control groups were measured for lipid profile and
complete blood count, also underwent echocardiography. Exercise stress test was performed
with Bruce protocol. MET values were calculated according the Bruce Protocol MET chart.
Arterial stiffness was measured by PulseTrace PWV device (Micro medical
PulseTrace, Rochester, 2009, UK). Distance between carotid-femoral arteries was used for
central stiffness (cfPWV) and distance between femoral-tibialis posterior arteries was used for
periferal stiffness (faPWV). An average of three measurements was taken. Serum levels of
PTX3 was determined by BOST brand commercial kit (catalog no: EK0861) with sandwich
type ELISA kit.
Ethical Consent: This study approved by Erciyes University Medical Faculty Ethical
Commitee (2012/704). The study was performed according to the Helsinki Charter. All
subjects gave their written informed consent to participate.
Statistical Analyses: Statistical analyses were made by means of IBM SPSS v22 by the
Biostatistical Department of the School of Medicine of Erciyes University. The distribution of
the data was found to comply with parametric tests and the mean ± standard deviation values
were obtained. The independent students’s test was conducted to compare the groups by
taking into consideration the homogeneity of the variation coefficients. The pearson’s
correlation coefficients were used in the correlation analysis. The statistical significance level
was p < 0.05.
RESULTS
There were no statistically significant differences at the demographic characteristics
(Table 1), and haematologic and biochemical parameters (Table 2) between the two
groups. MET (Table 1) and plasma PTX3 levels were found to be significantly higher in
mountaineers, compared to the sedentary group (p < 0.05) (Figure 3). Femoral-ankle pulse
wave velocity (faPWV), carotid-femoral pulse wave velocity (cfPWV), left ventricular endsystolic diameter and the neutrophil to lymphocyte (N/L) ratio were found to be significantly
lower in mountaineers, compared to the sedentary group (p < 0.05) (Figure 1, 2). A
statistically significant and inverse relationship was found between MET, PTX3 levels and
cfPWV, faPWV (p < 0.05) (Table 3).
Table 1: Age, body mass index (BMI), exercise and cardiovascular parameters
Mountaineers
(n=20)
p
Sedentary controls
(n=20)
Age (year)
52.75± 8.24
51.80± 5.99
0.68
BMI
27.85± 2,55
27.47± 1.31
0.55
Maximal heart rate
166.50 ± 9.58
163.95 ± 7.02
0.34
MET
12,95 ± 2.91
11.31 ± 1.46
< 0.03
Ejection fraction
64.00± 1.63
61.00± 1.63
0.21
Left ventricular end-systolic diameter
(mm)
2.98 ±0.11
3.32 ±0.13
< 0.05
Left ventricular end-diastolic diameter
(mm)
4.59± 0.16
4.60± 0.15
0.97
Mountaineers (n=20)
Sedentary controls (n=20)
p
Hb (g/dl)
14.9 ± 1.64
15.3 ± 0.39
0.3
Hematocrit (%)
44.89 ± 0.74
45.82 ± 1.21
0.4
Triglycerides (mg/dL)
161.08 ± 16.39
152.42 ± 24.33
0.7
Cholesterol (mg/dL)
201.60 ± 6.32
211.07 ± 11.29
0.4
LDL (mg/dL)
121.51 ± 6.12
145.11 ± 17.90
0.5
HDL (mg/dL)
48.50 ± 3.61
50.64 ± 2.95
0.6
Table 2: Haematological, biochemical parameters
Table 3: Correlation between PT3, MET and PVW
MET
carotid-femoral PWV
femoral-ankle PWV
1
.943**
-.820**
-477**
femoral-ankle PWV (m/s)
.943**
1
-.832**
-502**
PTX3 (ng/ml)
-.820**
-.832**
1
323*
MET
-.477**
-.502**
.323*
1
carotid-femoral PWV (m/s)
PTX3
* Correlation is significant at the 0.05 level (2-tailed). ** Correlation is significant at the 0.01 level (2-tailed).
DISCUSSION
Arterial stiffness is an indication of atherosclerosis and is caused by thickening of the
arterial wall and loss of elasticity. It especially effects large arteries. Histopathological studies
of these arteries show increased collagen and alteration of elastin structures11. Increased
arterial stiffness is not only an indication of vascular aging, but is also a predictor of target
organ damage and increased cardiovascular events12. There are 3 different mechanisms
affecting arterial stiffness. Injury of the elastic structure (elastic fibres) of the arterial wall,
distortion of the endolthelium / smooth muscle mechanism, and increased mean arterial
pressure. Age, gender, cardiovascular diseases and risk factors (hypertension, coronary artery
disease, peripheral artery disease, cardiac failure, cardiac syndrome X, endothelial
dysfunction), endocrinological and metabolic disorders (diabetes mellitus, impaired glucose
tolerance, dislipidemia, metabolic syndrome, hypothyroidism, hyperhomocisteinemia), dietary
and lifestyle habits (obesity, smoking, coffein, high sodium intake) are structural effects of
arterial stiffness. The collagen-elastin balance in the arterial wall with increased stiffness has
been shown to increase histopathologically in favour of collagen13. Hypertension or increased
intraluminal pressure induces collagen formation and facilitates increased stiffness14. Arterial
stiffness represents the cumulative effect of cardiovascular risk factors, including aging, on the
arterial wall. The arterial pulse wave velocity is determined to a large extent by
the arterial elastic modulus. The gold-standard measure of arterial stiffness, pulse wave
velocity (PWV), reflects the speed of pressure pulse transmission along the arterial wall15.
Aortic PWV was used as a measure of the stiffness of the central arteries, whereas leg and arm
PWV were used as measures of peripheral arterial stiffness5. As the propagation of the
pressure wave in elastic tubes occurs at a definite velocity, it is possible to measure arterial
stiffness through the pulse wave velocity (PWV). Aortic stiffness is approximated by the
carotid to femoral pulse wave velocity (typical value: 8 m/s)16.
Higher levels of physical activity and cardiorespiratory fitness have been found to be
associated with a decreased incidence of and mortality from coronary heart disease17.
However, effects of physical activity on the functional properties of arteries have
contradictory results. Some researchers have demonstrated that regular aerobic exercise is
efficacious in preventing and reversing arterial stiffening in healthy adults5,6,18. They report
that through regular aerobic exercise cardiorespiratory fitness develops, arterial stiffness and
cardiovascular risk factors and cardiovascular mortality are reduced1. With daily brisk
walking, previously sedentary middle-age/older adults show reduced stiffness and improved
EDD (endothelium-dependent dilatation). The mechanisms underlying the effects of regular
aerobic exercise on large elastic artery stiffness with ageing are largely unknown, but are
likely to include changes to the composition of the arterial wall1. Furthermore, studies report
that decreased arterial stiffness may be associated with factors related to vasodilatation,
increased gene expression and decreased oxidative stress19. Regular aerobic exercise is
associated with a reduced risk of CVD in middle-aged and older adults20. Regular aerobic
exercise benefits the reversal of arterial stiffness in middle aged and older individuals and
decrease of age-associated cardiovagal baroreflex sensitivity6,21.
Several long-term studies provide evidence of reductions in central and peripheral
arterial stiffness with endurance exercise training in both young22 and older23 individuals. A
few months of resistance training significantly reduces central arterial compliance in healthy
men21 but effects of resistance training on the compliance of the peripheral muscular artery
(ie, femoral artery) were not apparent. Adults who regularly perform aerobic exercise have
less large elastic artery stiffness and largely preserved vascular endothelial function with
aging1. It has been speculated that rather than structural characteristics in the arterial wall that
take a long time to change, the alterations in the contractile states of the smooth muscle cells
may be a potential mechanism underlying improvements in arterial stiffness with regular
exercise19. In contrast, Schmidt-Trucksuss et al. indicated that femoral arterial lumen diameter
and compliance (via an ultrasound imaging device and simultaneous applanation tonometry)
in endurance-trained males were significantly higher than those in age-matched sedentary
counterparts24. Dinneno et al. observed an expansion of the femoral arterial lumen diameter in
previously sedentary middle-aged and elderly men after a 3-month aerobic exercise
intervention (primarily walking). The expansion of arteries seems to relate to structural
remodeling or reduced vascular smooth muscular tone and leads to decreasing peripheral
arterial stiffness25.
In endurance trained male athletes, 54 to 75 years old (V02max = 44±3 ml. kg/min), the
arterial stiffness indexes were significantly reduced relative to their sedentary age peers (AGI,
36% lower, APWV, 26% lower) despite similar blood pressures. Higher physical conditioning
status, indexed by V02max was associated with reduced arterial stiffness, both within this
predominantly sedentary population and in endurance trained older men relative to their less
active age peers19. If long-term aerobic exercise or training has a lasting effect on arterial
stiffness is uncertain. If the answer of the latter is yes, when the effect starts is also uncertain.
Collier et al. found that central pulse wave velocity decreased 8% after aerobic exercise and
remained depressed at this level through 60 minutes of observation, whereas resistance
exercise increased central pulse wave velocity by 9.8% from pre to 40 and 60 minutes
postexercise26. Kingwell et al. reported that a single 30 min cycling bout at 65% VO2max
increased arterial compliance by 40% at 30 min postexercise, but values returned to resting
levels by 60min postexercise27. Cameron at al. found that after training three times/week for 4
weeks using the same protocol, resting arterial compliance (24 h after the last exercise bout)
was elevated by approximately 30%28. In another study, Kingwell et al. Wistar-Kyoto rats
were allowed to train spontaneously in exercise wheels from 4 to 20 weeks of age and aortic
cross-sectional compliance was examined in organ baths29. They concluded that the slope of
the diameter–tension curve was higher in trained rats, which indicated training induced
structural aortic adaptations. They also underlined that while arterial elasticity and fitness
increased in parallel in both human and rat studies, it was not possible to determine whether a
causative relationship existed.
Hayashi et al. studied 17 healthy and sedentary middle-aged men, aged 31–64 years (mean
age: 50 ± 3 yr) similar to the age group in our study. The subjects performed open-air aerobic
exercise training (brisk walk- ing/jogging) for 16 weeks30. Hayashi et al. observed a reduced
PWV as a result of a 16-week long aerobic training however peripheral PWV did not change
significantly and the stiffness of the peripheral artery was difficult to change in short- term
and moderate-intensity aerobic exercise training. Even moderate-intensity aerobic exercise
training could increase femoral arterial diameter25. However peripheral vessels are able to
respond to central artery enlargement in a longer time period. The duration, intensity and
frequency of exercise required to decrease stiffness of the peripheral arteries is not known yet
however we believe that continuous exercises such as endurance training are indicated/are
required. Hayashi et al.21 explained that this was related to the increased elastin content in the
central arteries versus the peripheral vessels and the improved enlargement response of
central arteries to training. It was shown that 16 weeks of aerobic exercise training reduced
the calcium content of elastin and increased the elastin content in the aortic wall in rats31.
There is an inverse and statistically significantly correlation between of MET and
peripheral PWV. In other words, central and peripheral PWV decreases when MET increases.
We speculate that long-term protection/maintenance of the MET value facilitated a lower
peripheral PWV which is an important subject for future investigations.
N/L ratio reflects the balance between the neutrophil and lymphocyte levels in the
body and is an indicator of systemic inflammation32. N/L ratio is an inexpensive, easy to
obtain, widely available marker of inflammation, which can aid in the risk stratification of
patients with various cardiovascular diseases. N/L ratio is reported as an independent
predictor of outcome in stable coronary artery disease, as well as a predictor of short-and long
term mortality in patients with acute coronary syndromes. In patients admitted with advanced
heart failure, high N/L ratio was reported with higher inpatient mortality33. In the present
study, we observed that the N/L ratio was lower in mountaineers. So, this measurement
showed us that prolonged moderate exercise might decrease the risk of long-term mortality.
Chronic low-grade inflammation accompanies aging as well as some chronic medical
disorders34. Chronic inflammation that occurs with aging is one of the risk factors for
cardiovascular disease. Systemic inflammatory factors increase with age, which lead to an
increased risk of cardiovascular disease in middle-age and elderly individuals8. Physical
inactivity, as well as aging, may induce systemic inflammation. It has been suggested that
regular physical activity may contribute to lower levels of pro-inflammatory and higher levels
of anti-inflammatory factors. Regular exercise protects against diseases associated with
chronic low-grade systemic inflammation35. This long-term effect of exercise may be ascribed
to the anti inflammatory response elicited by an acute bout of exercise, which is partly
mediated by muscle-derived IL-6. Physiological concentrations of IL-6 stimulate the
appearance in the circulation of the anti-inflammatory cytokines IL-1ra and IL-10 and inhibit
the production of the proinflammatory cytokine CRP and TNFα34. Given that the
atherosclerotic process is characterized by inflammation, one alternative explanation would be
that regular exercise, which offers protection against atherosclerosis, indirectly offers
protection against vascular inflammation and hence systemic low-grade inflammation35.
Although these observations point to a cardiovascular protective effect of PTX3, they also
suggest the possibility that the increased levels of PTX3 in subjects with cardiovascular
disease (CVD) may reflect a protective physiologic response that correlates with the severity
of the disease. Recently, PTX3 has been established as an anti-inflammatory protein in
atherosclerosis10. Measurement of levels of circulating inflammatory factors, in determining
the state of cardiovascular disease may be a useful diagnostic tool34. In previous studies using
PTX3-deficient or PTX3-over expressing mice, it has been shown that PTX3 has an antiinflammatory and/or anti-atherosclerotic role36. Daily regular exercise is known to induce
anti-inflammatory effects and protect against the risk of cardiovascular diseases associated
with chronic low-grade systemic inflammation such as atherosclerosis34, resulting in a
decrease in serum CRP37. 8 weeks of moderate aerobic exercise training (walking and cycling,
30-45min, 3-5 days/wk) increased plasma PTX3 concentration in healthy postmenopausal
middle-aged and elderly women, and this may partly participate in the mechanism underlying
aerobic exercise training-induced anti-inflammatory effect and cardiovascular protection38.
On the other hand, it has been reported that plasma PTX3 concentrations decreased with
exercise training in patients undergoing cardiac rehabilitation39. In another study Miyaki et al.
demonstrated that plasma PTX3 concentrations in young endurance-trained men were higher
than age-matched sedentary controls8. Circulating PTX3 and hsCRP significantly increased
immediately after 70% RE and peak EX, while they did not increase after 70% AT exercise.
Habitual aerobic exercise is thought to have an anti-inflammatory effect. High-intensity
exercises significantly increase circulatory PTX3 as well as CRP. The release from peripheral
neutrophils is suggested to be involved in the exercise-induced plasma PTX3 increase40.
However, it is unclear whether aerobic exercise training affects circulating PTX3
concentrations in healthy middle aged and elderly individuals.
Our results indicate that PTX3 levels in mountaineers who trek for moderate and long
periods were significantly higher than sedentary group. Although the exact mecahnism is not
known, this can be explained by the fact that MET of mountaineers is significantly higher than
the sedentary group. Analysis of the statistically significant inverse correlation between
cfPWV, faPWV and PTX3 supports that long term exercise reduces arterial stiffness and
increases PTX3.
CONCLUSION
Consequently, long-term and regular moderate exercise (tracking) significantly
decreases indicators of systemic inflammation and arterial stiffness, and reduces the risk of
cardiovascular disease with advanced age. This is the first study for investigating the effects
of chronic (5-20 years) moderate exercise on new cardiac disease indicators such as stiffness
and PTX3. Measurement of PWV can be used to detect increase in cardiovascular risk with
old age .
ACKNOWLEDGEMENT
This study was supported by Erciyes University Scientific Research Project
Commission (TTU-2013-4408).
References
1. Seals DR, Walker AE, Pierce GL, Lesniewski LA. Habitual exercise and vascular ageing.
J Physiol 2009; 1(23):5541-5549.
2. Weber T, Auer J, O’Rourke MF, et al. Arterial stiffness, wave reflections, and the risk of
coronary arter disease. Circulation 2004; 109(2):184–189.
3. Simon AC, Levenson J, Bouthier J, Safar ME, Avolio AP: Evidence of early degenerative
changes in large arteries in human essential hypertension. Hypertension 1985; 7:675-680.
4. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B,
Vlachopoulos C, Wilkinson I, Struijker-Boudier H. Expert consensus document on
arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006;
27(21): 2588-2605.
5. Tanaka H, DeSouza CA, Seals DR. Absence of age-related increase in central arterial
stiffness in physically active women. Arterioscler Thromb Vasc Biol 1998; 18:127–132.
6. Tanaka H, Dinenno FA, Monahan KD, Clevenger CM, DeSouza CA, Seals DR. Aging,
habitual exercise, and dynamic arterial compliance. Circulation 2000; 102:1270-1275.
7. Kritchevsky SB, Cesari M, Pahor M. Inflammatory markers and cardiovascular health in
older adults. Cardiovasc Res 2005; 66:265–275.
8. Miyaki A, Maeda S, Otsuki T, Ajisaka R. Plasma PTX3 concentration increases in
endurance-trained men. Med Sci Sports Exerc 2011; 43(1):12–17.
9. Rolph MS, Zimmer S, Bottazzi B, Garlanda C, Mantovani A, Hansson GK. Production of
the long pentraxin PTX3 in advanced atherosclerotic plaques. Arterioscler Thromb Vasc
Biol 2002; 22:10-14.
10. Norata GD, Garlanda C, Catapano AL. The long pentraxin PTX3: A modulator of the
immuno inflammatory response in atherosclerosis and cardiovascular disease. Trends
Cardiovasc Med 2010; 20:35-40.
11. Zieman SJ, Melenovsky V, Kass DA. Mechanisms, pathophysiology, and therapy of
arterial stiffness. Arterioscler Thromb Vasc Biol 2005; 25(5):932-943.
12. Kingwell BA, Gatzka CD. Arterial stiffness and prediction of cardiovascular risk. J
Hypertens 2002; 20(12):2337-2340.
13. Bagrov AY, Lakatta EG. The dietary sodium-blood pressure plot “stiffness”.
Hypertension 2004; 44: 22–24.
14. Sutton-Tyrrell K, Newman A, Simonsick EM, Havlik R, Pahor M, Lakatta E, Spurgeon
H, Vaitkevicius P. Aortic stiffness is associated with visceral adiposity in older adults
enrolled in the study of health, aging, and body composition. Hypertension 2001; 38:429–
433.
15. Amoh-Tonto CA, Malik AR, Kondragunta V, Ali Z, Kullo IJ. Brachial-ankle pulse wave
velocity is associated with walking distance in patients referred for peripheral arterial
disease evaluation. Atherosclerosis 2009; 206:173-178.
16. Boutouyrie P, Laurent S, Briet M. Importance of arterial stiffness as cardiovascular risk
factor for future development of new type of drugs. Fundam Clin Pharmacol 2008;
22:241–246.
17. Lakka TA, Venalainen JM, Rauramaa R, Salonen R, Tuomilehto J, Salonen JT. Relation
of leisure-time physical activity and cardiorespiratory fitness to the risk of acute
myocardial infarction. New Engl J Med 1994; 330:1549–1554.
18. Vaitkevicius PV, Fleg JL, Engel JH, et al. Effects of age and aerobic capacity on arterial
stiffness in healthy adults. Circulation 1993; 88: 1456–1462.
19. Maeda S, Iemitsu M, Miyaychi T, Kuno S, Matsuda M, Tanaka H. Aortic stiffness and
aerobic exercise: mechanistic insight from microarray analyses. MedSci Sports Exerc
2005; 37: 1710-1716.
20. Mora S, Cook N, Buring JE, Ridker PM & Lee IM . Physical activity and reduced risk of
cardiovascular events: potential mediating mechanisms. Circulation 2007; 116:21102118.
21. Miyachi M, Kawano H, Sugawara J, et al. Unfavorable effects of resistance training on
central arterial compliance: a randomized intervention study. Circulation 2004; 110:28582863.
22. Kakiyama T, Sugawara J, Murakami H, Maeda S, Kuno S, Matsuda M . Effects of shortterm endurance training on aortic distensibility in young males. Med Sci Sports Exerc
2005; 37:267-271.
23. Collier SR, Kanaley JA, Carhart R Jr, Frechette V, Tobin MM, Hall AK, Luckenbaugh
AN, Fernhall B. Effect of 4 weeks of aerobic or resistance exercise training on arterial
stiffness, blood flow and blood pressure in pre- and stage-1 hypertensives. J Hum
Hipertens 2008; 22:678-686.
24. Schmidt-Trucksass A, Schmid A, Brunner C, Scherer N, Zach G, Keul J, and Huonker
M. Arterial properties of the carotid and femoral artery in endurance-trained and
paraplegic subjects. J Appl Physiol 2000; 89: 1956-1963.
25. Dinenno FA, Tanaka H, Monahan KD, Clevenger CM, Eskurza I, DeSouza CA, and
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
Seals DR. Regular endurance exercise induces expansive arterial remodelling in the
trained limbs of healthy men. J Physiol 2001; 534.1: 287-295.
Collier SR, Diggle MD, Heffernan KS, Kelly EE, Tobin MM, Fernhall B. Changes in
arterial distensibility and flow-mediated dilation after acute resistance vs. aerobic
exercise. J Strength Cond Res 2010; 24(10): 2846-2852.
Kingwell B, Berry K, Cameron J, Jennings G, Dart A. Arterial compliance increases after
moderate-intensity cycling. Am J Physiol 1997; 273: 2186-2191.
Cameron J, Dart A. Exercise training increases total systemic arterial compliance. Am J
Physiol 1994; 266:693-701.
Kingwell BA, Arnold PJ, Jennings GL, Dart AM. The effects of voluntary running on
cardiac mass and aortic compliance in Wistar- Kyoto and spontaneously hypertensive
rats. J Hypertens 1998; 16:181-185.
Hayashi K, Sugawara J, Komine H, Maeda S, Yokoi T. Effects of aerobic exercise
training on the stiffness of central and peripheral arteries in middle-aged sedentary men.
Jpn J Physiol 2005; 55(4):235-239.
Matsuda M, Nosaka T, Sato M, Ohshima N. Effects of physical exercise on the elasticity
and elastic components of the rat aorta. Eur J Appl Physiol Occup Physiol 1993; 66:122126.
Kalay N, Dogdu O, Koc F, Yarlioglues M, Ardic I, Akpek M ve ark. Hematologic
parameters and angiographic progression of coronary atherosclerosis. Angiology 2012;
63(3):213-217.
Bhat T, Teli S, Rijal J, Bhat H, Raza M, Khoueiry G, Meghani M, Akhtar M, Costantino
T. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev
Cardiovasc Ther 2013; 11(1):55-59.
Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol
2005;98: 1154-1162.
Mathur N, Pedersen BK. Exercise as a mean to control low-grade systemic inflammation.
Mediators Inflamm 2008; ID: 109502.
Dias AA, Goodman AR, DosSantos JL, Gomes RN, Altmeyer A, Bozza PT, Horta M,
Vilcek J, Reis LF. TSG-14 transgenic mice have improved survival to endotoxemia and
to CLP-induced sepsis. J Leukoc Biol 2001; 69:928-936.
Kasapis C, Thompson PD. The effects of physical activity on serum C-reactive protein
and inflammatory markers: a systematic review. J Am Coll Cardiol 2005 45:1563-1569.
Miyaki A, Maeda S, Choi Y, Akazawa N, Tanabe Y, Ajisaka R. Habitual aerobic
exercise increases plasma PTX3 levels in middle-aged and elderly women. Appl Physiol
Nutr Metab 2012; 37:907-911.
Fukuda T, Kurano M, Iida H, Takano H, Tanaka T, Yamamoto Y, Ikeda K, Nagasaki M,
Monzen K, Uno K, Kato M, Shiga T, Maemura K, Masuda N, Yamashita H, Hirata Y,
Nagai R, Nakajima T. Cardiac rehabilitation decreases plasma PTX3 in patients with
cardiovascular diseases. Eur J Prev Cardiol 2012 19(6):1393-1400.
Nakajima T, Kurano M, Hasegawa T, Takano H, Iida H, Yasuda T, Fukuda T, Madarame
H, Uno K, Meguro K, Shiga T, Sagara M, Nagata T, Maemura K, Hirata Y, Yamasoba T,
Nagai R. Pentraxin3 and high-sensitive C-reactive protein are independent inflammatory
markers released during high-intensity exercise. Eur JAppl Physiol 2010; 110:905-910.