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Cardiorespiratory Fitness, Physical Activity, and
Arterial Stiffness
The Northern Ireland Young Hearts Project
Colin A. Boreham, Isabel Ferreira, Jos W. Twisk, Alison M. Gallagher,
Maurice J. Savage, Liam J. Murray
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Abstract—Poor cardiorespiratory fitness and low physical activity have been identified as determinants of greater arterial
stiffness, a mechanism that can partially explain the association of both variables with increased cardiovascular disease.
However, the nature of these associations are not clear because cardiorespiratory fitness and physical activity can both
mediate and confound the associations of one another with arterial stiffness. This issue was therefore examined in a
population-based cohort of young adults. Subjects included 405 young men and women participating in an ongoing
longitudinal study, the Northern Ireland Young Hearts Project. Pulse wave velocity was used to determine arterial
stiffness in 2 arterial segments (aortoiliac and aortodorsalis pedis) using a noninvasive optical method. Cardiovascular
fitness was estimated with a submaximal cycle test of physical work capacity and physical activity was estimated using
a modified Baecke questionnaire. Associations were investigated with the use of multiple linear regression models with
adjustment for potential confounders and/or intermediate variables. Cardiorespiratory fitness and sports-related physical
activity (but not leisure- and work-related physical activity) were inversely associated with arterial stiffness in young
adults. The associations between sports-related physical activity and arterial stiffness were strongly mediated by
cardiorespiratory fitness, whereas physical activity levels did not disturb the associations between cardiopulmonary
fitness and arterial stiffness. These findings suggest that arterial stiffness-related benefits of exercise are most likely to
accrue if exercise prescription in young adults targets improvements in cardiorespiratory fitness. (Hypertension. 2004;
44:721-726.)
Key Words: young adults 䡲 exercise 䡲 cross-sectional studies 䡲 epidemiology 䡲 arteriosclerosis 䡲 hypertension, arterial
T
he arterial system is a network of vessels designed to
convert the intermittent flow of blood from the heart to a
continuous and steady flow across the arterial tree, thereby
reducing the afterload imposed to the heart. Alterations to this
cushioning function, because of increases in arterial stiffness,
lead to systolic hypertension, left ventricular hypertrophy,
and impaired coronary perfusion,1–3 thereby increasing cardiovascular risk.4 – 6
Several risk factors such as aging, obesity, diabetes, dyslipidemia, have been identified as determinants of arterial stiffness.7–14 Other such risk factors include poor cardiorespiratory
fitness15–20 and low physical activity.21,22 However, the nature of
the associations between cardiorespiratory fitness and physical
activity on the one hand and arterial stiffness on the other is not
well known. They could both confound and/or mediate the
relationships between each other and arterial stiffness or, as has
been suggested, physical activity could favorably influence
arterial stiffness independently of cardiorespiratory fitness.15,18
In addition, cardiorespiratory fitness and/or physical activity
may affect arterial stiffness through a beneficial impact on body
composition (ie, less body fat),23–25 which itself is a strong
determinant of arterial stiffness in young individuals.7–9
In view of these considerations, we investigated, in a
population-based cohort of young adults from Northern
Ireland, the associations between cardiorespiratory fitness,
physical activity, and arterial stiffness. Associations with
stiffness (as estimated by pulse wave velocity [PWV]) of 2
arterial segments (the elastic aortoiliac and the muscular
aortodorsalis pedis segments) were investigated.
Methods
Study Population
This study was conducted as part of an ongoing longitudinal study,
The Young Hearts (YH) Project, which initially examined the
Received May 19, 2004; first decision June 16, 2004; revision accepted August 27, 2004.
From the School of Applied Medical Sciences and Sports Studies (C.A.B.), University of Ulster, Jordanstown, Northern Ireland; Institute for Research
in Extramural Medicine (I.F., J.W.T.), VU University Medical Center, Amsterdam, the Netherlands; Department of Public Health (I.F.), Erasmus
MC-University Medical Center, Rotterdam, the Netherlands; Northern Ireland Centre for Diet and Health (A.M.G.), University of Ulster, Jordanstown,
Northern Ireland; Department of Child Health (M.J.S.), The Queen’s University of Belfast, Belfast, Northern Ireland; and the Department of
Epidemiology and Community Health (L.J.M.), The Queen’s University of Belfast, Belfast, Northern Ireland.
Correspondence to Professor Colin Boreham, School of Applied Medical Sciences and Sports Studies, University of Ulster, Jordanstown, Northern
Ireland, BT37 0QB United Kingdom. E-mail [email protected]
© 2004 American Heart Association, Inc.
Hypertension is available at http://www.hypertensionaha.org
DOI: 10.1161/01.HYP.0000144293.40699.9a
721
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Hypertension
November 2004
prevalence of coronary risk factors in a random sample of young
people (n⫽1015; aged either 12 years or 15 years) in Northern
Ireland. Sampling procedures, study design, and response rates of the
first 2 screening phases (YH1 and YH2) are described in detail
elsewhere.26,27 All subjects in the original cohort were invited to
participate in a third screening phase (YH3: October 1997–October
1999) when aged 20 to 25 years. Two hundred and fifty-one men
(48.7% of the original male cohort) and 238 women (51.3% of the
original female cohort) attended the third phase of the study.28 The
present analyses involved 405 subjects (203 women) for whom
complete data on arterial stiffness, cardiorespiratory fitness, and
physical activity were available at this time point. Table 1 shows the
main characteristics of the study population. Each subject provided
written informed consent, and the study was approved by the
Medical Ethical Committee of the Queen’s University of Belfast.
Cardiorespiratory Fitness and Physical Activity
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Cardiorespiratory fitness was measured using a submaximal cycle
ergometer test described in detail elsewhere.27 In brief, subjects were
required to pedal at a steady pace (50 to 70 pedal revolutions/min)
for the duration of the test, which normally lasted 15 minutes. The
workload was increased after each 3-minute period until a heart rate
of approximately 170 bpm was achieved. Heart rate was averaged
over the last 15 sec of each workload (Polar Vantage heart rate
monitor, Polar, Finland). Oxygen uptake was monitored throughout
the test using an on-line respiratory gas analyzer (Quinton QMC) and
maximal oxygen uptake (VO2max) predicted by extrapolation of VO2
at 170 bpm to the age-adjusted estimated maximal heart rate, and
expressed in mL/kg per minute.
Data on frequency, duration, and type of physical activities
habitually undertaken were obtained using a modification of the
Baecke questionnaire of habitual physical activity which was designed to quantify work, sports, and nonsports leisure activity.29
Work, sports, and nonsports leisure activity scores were calculated
based on 5-point Likert scales; these 3 scores were then added to
provide a total physical activity score.
Arterial Stiffness
We used a noninvasive optical method to estimate PWV, by
determining the transit time (TT) that the wave of dilatation,
propagating in the arterial wall as a result of the pressure wave
generated by contraction of the left ventricle, took to arrive at a distal
site over a known distance.30,31 TT measurements were performed
with a photoplethysmographic probe and were triggered by the
R-wave of the ECG (in milliseconds). The distance between the
sternal notch to the femoral artery and between the sternal notch to
the dorsalis-pedis artery (in 0.1 centimeters) was then divided by the
TT of the pulse wave to arrive at each of these arterial sites to
determine PWV (expressed in m/s) of the aortoiliac and the aortodosalis pedis segments, respectively. A single trained technician
performed all measures on the study subjects who had previously
rested in a supine position for 15 minutes in a quiet temperaturecontrolled room. All measures were taken on the left side of the
body. Estimations of TT based on ⬍10 cycles, or those in which the
coefficient of variance was ⬎20%, were rejected. All subjects had
refrained from smoking and caffeine containing beverages on the day
the measurements were performed.
Potential Confounders/Intermediate Variables
Assessment of body height, weight and skinfolds, blood pressure,
lipids and glucose levels, smoking behavior, alcohol consumption,
and nutrient intake have been described in detail previously.23,26 –28,30
Statistical Analysis
We used multiple linear regression models to investigate the relationship between VO2max and physical activity scores on the one
hand (determinants) and PWV of 2 different arterial segments on the
other (outcomes). The analyses were performed in several steps
based on an initial model which included adjustments for age, sex,
mean arterial pressure, and body height and weight (model 1);
further adjustments for potential confounders such as smoking status
(non-, light-, and heavy-smoker, as determined by the sex-specific
median number of cigarettes smoked per day among smokers),
alcohol consumption (non-, moderate-, and heavy-drinker, as determined by the sex-specific median number of grams of alcohol
consumed per day among drinkers), and intake of fat (as % of total
energy intake), and/or intermediate (ie, in the pathway between the
determinants and the outcome) variables, such as body fatness (as
expressed by the sum of 4 skinfolds) were investigated. Mutual
adjustments between VO2max and physical activity were also performed to assess not only the strength of the relationships with
arterial stiffness independently of one another, but also their potential confounding/intermediate role in the associations investigated.
After we assessed the main effects, we added interaction terms
between our main determinants and sex to the linear regression
models. When the probability value of the interaction term was
significant (ie, ⬍0.05), stratified analyses were performed and
results presented separately for men and women. All analyses were
performed with the Statistical Package of Social Sciences, 10.1 for
Windows (SPSS Inc).
Results
Cardiorespiratory Fitness and Arterial Stiffness
VO2max was inversely and significantly associated with PWV
of both the elastic aortoiliac segment and the muscular
aortodorsalis pedis segment. These associations were only
slightly stronger with the muscular segment and were independent of (ie, not confounded nor mediated by) lifestyle
variables, body fatness, and physical activity (Table 2).
Physical Activity and Arterial Stiffness
Sports-related physical activity score was inversely and
significantly associated with PWV of the aortodorsalis pedis
segment only (Table 3). Adjustment for other lifestyle variables and body fatness did not attenuate the strength of the
latter association, which, however, decreased considerably
(⬇40%) after further adjustment for VO2max.
Conversely, and in the men only, positive associations
were found between (nonsports) leisure-related physical activity and PWV of both arterial segments, though more
strongly and significantly with the PWV of the aortoiliac
segment only (P⫽0.001 and P⫽0.021 for interaction with sex
in the associations between leisure-related physical activity
and PWV of the aortoiliac and the aortodorsalis pedis
segments, respectively). Again, these associations were not
attenuated after adjustment for other lifestyle variables and
body fatness. Further adjustment for VO2max, however,
strengthened the associations so that the association between
leisure physical activity and PWV of the aortodorsalis pedis
segment was now significant. No significant associations
were found between work-related activity and PWV of both
segments.
Discussion
The main findings of our study were that cardiorespiratory
fitness was inversely associated with arterial stiffness (as
measured by PWV). With regard to physical activity levels,
only sports-related physical activities were favorably (ie,
inversely) associated with arterial stiffness (a phenomenon
that was mediated by cardiorespiratory fitness), whereas
leisure physical activities, in men only, were adversely (ie,
positively) associated with arterial stiffness. All these asso-
Boreham et al
TABLE 1.
Fitness, Physical Activity, and Arterial Stiffness
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Characteristics of the Study Population (The Young Hearts Study, Phase 3)
Study Variable
Age, y
Height, cm
Men
(n⫽202)
Women
(n⫽203)
P Value
22.4 (1.6)
22.8 (1.7)
0.034
178.2 (6.6)
164.5 (6.2)
⬍0.001
Weight, kg
75.6 (11.8)
64.6 (12.0)
⬍0.001
Body mass index, kg/m2
23.8 (3.2)
23.9 (4.3)
NS
⬍0.001
Sum of 4 skinfolds,* mm
44.5 (18.8)
58.8 (20.4)
Systolic pressure, mm Hg
118.7 (11.5)
106.7 (10.6)
⬍0.001
Diastolic pressure, mm Hg
76.6 (9.2)
71.1 (9.5)
⬍0.001
Mean arterial pressure, mm Hg
90.6 (8.7)
83.0 (9.0)
⬍0.001
Total cholesterol, mmol/L†
4.49 (0.88)
4.75 (0.88)
LDL-cholesterol, mmol/L†
2.85 (0.82)
2.92 (0.79)
NS
HDL-cholesterol, mmol/L†
1.28 (0.29)
1.47 (0.40)
⬍0.001
Triglycerides, mmol/L†
0.82 (0.43)
0.77 (0.42)
NS
⬍0.001
0.006
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Fasting plasma glucose, mmol/L‡
4.47 (0.54)
4.31 (0.35)
Heart-rate, bpm
71.1 (11.4)
73.8 (10.6)
0.016
Total energy intake, kcal
3146 (824)
1985 (581)
⬍0.001
Fat intake, % total energy intake
32.7 (5.8)
33.1 (6.1)
0.526
Alcohol drinkers, %
Alcohol consumption among drinkers, g/day
Smokers, %
Tobacco consumption among smokers, cigarettes/day
85.6
43 (28–72)
36.1
10 (10–20)
76.4
16 (8–26)
36.0
10 (5–13.5)
0.017
⬍0.001
NS
0.002
VO2max, mL/kg per minute
38.3 (8.3)
26.9 (5.3)
⬍0.001
Sports physical activity score
2.73 (0.81)
2.44 (0.65)
⬍0.001
Works physical activity score
2.81 (0.63)
2.57 (0.53)
⬍0.001
Leisure physical activity score
2.37 (0.67)
2.38 (0.55)
NS
Total physical activity score
7.90 (1.34)
7.40 (1.21)
⬍0.001
PWV aortoiliac segment, m/s
3.26 (0.49)
2.91 (0.35)
⬍0.001
PWV aortodorsalis pedis, m/s
5.19 (0.53)
4.74 (0.47)
⬍0.001
Data are means (standard deviations) or medians (interquartile ranges). PWV indicates pulse wave velocity; VO2max,
predicted maximal oxygen uptake.
*The 4 skinfolds are biceps, triceps, suprailiac and subscapular.
†Data available on 189 men and 166 women and ‡159 men and 155 women only. Differences between males and
females were determined by Student t test for independent samples or ␹2 tests.
ciations were independent of other lifestyle variables and
body fatness. This is the first population-based study to report
the associations of cardiorespiratory fitness and physical
activity (investigating the confounding and/or mediating role
of each other in the relationships) with arterial stiffness in the
same population. This has eliminated the possibility that
differences in results thus obtained, as compared with previous reports, could be attributed to different study design
and/or methodologies for measuring arterial properties.
The strong associations between cardiorespiratory fitness
and arterial stiffness largely mirror those reported in other
population-based studies relating VO2max levels and arterial
stiffness in younger32 and older adults17 as well as in smaller
scale studies.15,18,19 In addition, several exercise-training
studies have shown that improvements in cardiorespiratory
fitness are accompanied by beneficial changes in arterial
stiffness, both in healthy individuals15,18,33 and in heart
patients.34 However, such exercise needs to be cardiovascular
in nature (ie, aerobic, involving large muscle groups) because
compelling evidence exists showing that strength (or resistance) training is associated with greater arterial stiffness.35–37
Whether aerobic physical activity has to lead to increases in
VO2max to be favorably associated with arterial adaptations
is, however, not clear.15,18,21,33 Two recent intervention studies have indicated that a 3-month aerobic exercise training
program significantly decreased arterial stiffness, arguing that
this decrease in arterial stiffness was independent of concomitant increases in VO2max (and beneficial changes in other
risk factors).15,18 These increases were indeed present in both
and were even significant in one of the studies,15 but the data
to sustain such an argument (ie, the role of increases in
physical activity independently of VO2max) were, unfortunately, not shown. In the present study, our statistical analyses models specifically addressed this question. We found
that only sports-related activities (eg, jogging, swimming,
tennis), which by definition are of higher intensity than those
performed in leisure-time (eg, walking, bicycling), were favorably associated with arterial stiffness, an association that
724
Hypertension
November 2004
TABLE 2. Associations Between Cardiorespiratory Fitness and
Pulse Wave Velocity in 2 Arterial Segments
Pulse Wave Velocity
Main Determinant
Model
Aortoiliac
Segment
Aortodorsalis Pedis
Segment
1
⫺0.14 (0.018)
⫺0.20 (⬍0.001)
2*
⫺0.19 (0.003)
⫺0.21 (⬍0.001)
3
⫺0.18 (0.004)
⫺0.21 (0.001)
4
⫺0.18 (0.008)
⫺0.20 (0.002)
VO2max
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Data are standardized regression coefficients (P values). VO2max indicates
cardiorespiratory fitness.
Model 1: adjusted for age, sex, height, weight and mean arterial pressure;
Model 2, model 1 further adjusted for total physical activity score; Model 3,
model 2 further adjusted for smoking behavior, alcohol consumption, and total
intake of fat; Model 4, model 3 further adjusted for body fatness (as estimated
by the sum of 4 skinfolds).
*Adjustments for sports-related physical activity resulted in ␤⫽
⫺0.14 (P⫽0.031) and ␤ ⫽⫺0.18 (P⫽0.004) for aortoiliac and aortodorsalis
pedis pulse wave velocity, respectively.
was highly mediated by concomitant levels of VO2max. This
indicates that arterial stiffness-related benefits of exercise are
most likely to accrue if exercise prescription in young adults
targets improvements in VO2max.
In contrast, an adverse relationship between leisure-related
physical activities and arterial stiffness was found, and this
was, to a certain extent, sex-specific, in that the men, but not
the women, of our sample displayed consistently adverse
TABLE 3. Associations Between Physical Activity and Pulse
Wave Velocity in 2 Arterial Segments
Pulse Wave Velocity
Main Determinants
Sports physical activity
Work physical activity
Leisure physical activity
Model
Aortoiliac
Segment
Aortodorsalis Pedis
Segment
1
⫺0.05 (0.32)
⫺0.11 (0.015)
2
⫺0.03 (0.57)
⫺0.10 (0.023)
⫺0.10 (0.037)
3
⫺0.02 (0.66)
4
0.01 (0.83)
1
0.05 (0.31)
0.04 (0.33)
2
0.04 (0.44)
0.04 (0.32)
3
0.04 (0.41)
0.05 (0.26)
4
0.05 (0.33)
1
2
3
4
⫺0.06 (0.23)
0.06 (0.19)
M 0.26 (⬍0.001)
M 0.11 (0.097)
F ⫺0.05 (0.51)
F ⫺0.09 (0.16)
M 0.27 (⬍0.001)
M 0.12 (0.084)
F ⫺0.05 (0.50)
F ⫺0.08 (0.25)
M 0.27 (⬍0.001)
M 0.12 (0.075)
F ⫺0.04 (0.53)
F ⫺0.08 (0.26)
M 0.29 (⬍0.001)
M 0.15 (0.034)
F ⫺0.02 (0.75)
F ⫺0.06 (0.38)
Data are standardized regression coefficients (P values).
VO2max indicates cardiorespiratory fitness; M, men; and F, women. Model 1
is adjusted for age, sex, height, weight and mean arterial pressure; Model 2,
model 1 further adjusted for smoking behavior, alcohol consumption, and total
intake of fat; Model 3, model 2 further adjusted for body fatness (as estimated
by the sum of 4 skinfolds); Model 4, model 3 further adjusted for VO2max.
relationships between these types of activities and PWV.
Although an explanation of the mechanisms behind a sex
difference in the association between any determinant investigated, and arterial stiffness, could be an estrogen-dependent
phenomenon, such explanation in the present cohort is
unlikely (as no other sex interactions were found). We therefore hypothesized that a difference in the kind of physical
activities undertaken by men as compared with women in
their leisure time might explain this sex differentiation. With
this in mind, we examined further the 4 items that contribute
to the leisure physical activity score: television watching,
walking, bicycling, and bicycling to and from work or
shopping. We found that television watching contributed
significantly (P⫽0.006) more in men than in women to the
leisure activity score, whereas walking contributed significantly (P⬍0.001) more to the leisure activity score of women
than men, thus confirming our hypothesis.
The differentiation of the activity scores in work-, leisure-,
and sports-related activities was an important feature of our
study, which allowed us greater insight into the physical
activity-arterial stiffness relationships, which otherwise
would have been masked by the use of a general, total
habitual activity score (data not shown). The behavior of
physical activity is difficult to measure, and self-reported
physical activity is subject to recall bias and misclassification
(unlike cardiorespiratory fitness, which can be measured
objectively, using laboratory techniques, as in the present
study). This may explain the relatively weaker associations
found between arterial stiffness and (sports-related) physical
activity than with cardiorespiratory fitness. Despite this
limitation, our study clearly demonstrates that a detailed
characterization of physical activities performed by individuals (ie, not only their frequency, duration, and intensity, but
also the kind of activity) is essential and needs to be extracted
from questionnaires to better understand the relation between
physical activity and arterial stiffness.
The associations between cardiorespiratory fitness and
arterial stiffness were independent of lifestyle variables and
body fatness. Other mechanisms may thus explain the associations observed. Further adjustments for other traditional
cardiovascular risk factors (such as fasting LDL, HDL and
total cholesterol, tryglicerides and plasma glucose levels) did
not decrease the strength of the associations reported (data
not shown). The only other variable that did so to a considerable extent was resting heart rate (changes from ␤⫽⫺0.18,
[P⫽0.008] to ␤⫽⫺0.15, [P⫽0.028], in the aortoiliac segment and ␤⫽⫺0.20, [P⫽0.002] to ␤⫽⫺0.13, [P⫽0.047], in
the aortodorsalis pedis segment). Heart rate has been shown
to be an important factor in the intraindividual variation of
PWV, and therefore could have been an important confounder in the associations investigated.38,39 Alternatively, a
reduced resting heart rate is a known adaptation to endurance
training, and therefore could constitute, at least partially, one
mechanism that links high cardiorespiratory fitness to low
arterial stiffness. However, as the associations reported above
remained significant, other factors may also be involved.
Adaptation to shear stress forces can explain both the acute
and chronic adaptations to training-induced improvements of
cardiorespiratory fitness in humans.40 During exercise, blood
Boreham et al
flow increases leading to higher intraluminal forces, which
stimulates the release of vasodilating factors such as nitric
oxide (NO) and prostacyclin by the endothelium.41 For a
given exercise intensity, however, such increase in arterial
blood flow velocity is considerably higher at the distal than
proximal site of the abdominal aorta,42 which may thus
explain the stronger associations between the muscular as
compared with the more elastic segment, and cardiorespiratory fitness.20,32,43 In addition, changes in the relative proportions of collagen and elastin within the arterial wall as a
consequence of aerobic exercise training44,45 (in particular of
the arteries irrigating the limbs more involved in exercise)46
could constitute another mechanism explaining the observed
beneficial associations.
Fitness, Physical Activity, and Arterial Stiffness
10.
11.
12.
13.
14.
Perspectives
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Our study has relevant clinical and public health implications.
The clinical relevance of our findings lies in the important
role that cardiorespiratory fitness can play on the etiology of
arterial stiffness-related diseases such left-ventricular hypertrophy, heart-failure, and stroke. Indeed, cardiorespiratory
fitness is a strong, independent risk factor for cardiovascular
and all-cause mortality. The results of the present study,
obtained in a young and apparently healthy adult population,
suggest that these beneficial associations have their roots in
early life, and support the concept that arterial stiffness may
lie in the causal pathway between physical fitness and
stiffness-related morbidity. Therefore, and from a public
health perspective, the improvement of cardiorespiratory
fitness is an important tool for the primary prevention of
cardiovascular disease. This may be achieved by engaging in
sport activities on a regular basis.
15.
16.
17.
18.
19.
20.
21.
Acknowledgments
The British Heart Foundation and the Wellcome Trust supported
this study.
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Cardiorespiratory Fitness, Physical Activity, and Arterial Stiffness: The Northern Ireland
Young Hearts Project
Colin A. Boreham, Isabel Ferreira, Jos W. Twisk, Alison M. Gallagher, Maurice J. Savage and
Liam J. Murray
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Hypertension. 2004;44:721-726; originally published online September 27, 2004;
doi: 10.1161/01.HYP.0000144293.40699.9a
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