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AJH 2006; 19:701–707

Sedentary Lifestyle and Antecedents


of Cardiovascular Disease in Young Adults

Jonathan M. McGavock, Todd J. Anderson, and Richard Z. Lewanczuk

Background: The aim of this study was to determine mL/mmHg 䡠 100; P ⬍ .01) artery compliance were sig-
whether sedentary young individuals are characterized by nificantly lower in sedentary subjects than in physically
reductions in determinants of vascular health and insulin active or endurance-trained subjects, whereas flow-medi-
sensitivity relative to their physically active, age-matched ated dilation was not different between the groups. The
peers. HOMAIR was 2.5-fold higher in the sedentary group than
Methods: A total of 135 otherwise healthy young men in the endurance-trained group (P ⬍ .05).
(n ⫽ 68) and women (n ⫽ 67) ⬍40 years of age (28 ⫾ 5 Conclusions: Sedentary individuals are character-
years) were studied in this investigation and stratified into ized by reductions in both arterial compliance and in-
three groups based on physical activity status: 1) sedentary sulin sensitivity relative to their endurance-trained peers,
(n ⫽ 73); 2) physically active (n ⫽ 24); and 3) endurance- independent of changes in conventional risk factors for
trained (n ⫽ 38). Arterial compliance and flow-mediated cardiovascular disease. These findings lend further support
dilation were determined by diastolic pulse contour wave for the need for regular physical activity in the prevention
analysis and echocardiographic imaging of the brachial of cardiovascular disease in individuals of all ages. Am J
artery respectively. Insulin sensitivity was estimated from Hypertens 2006;19:701–707 © 2006 American Journal of
the homeostasis model for insulin resistance and the 13C- Hypertension, Ltd.
glucose breath test.
Results: Both conduit (16.4 ⫾ 0.5 v 19.5 ⫾ 0.7 mL/ Key Words: Arterial compliance, cardiorespiratory fit-
mmHg 䡠 10; P ⬍ .01) and resistant (8.5 ⫾ 0.3 v 10.7 ⫾ 0.5 ness, insulin resistance.

S
edentary lifestyle and physical inactivity predis- The underlying mechanisms through which physical
pose individuals to as many as 25 different chronic inactivity accelerates disease progression are not com-
diseases,1 including cardiovascular disease (CVD) pletely understood, but appear to be related in part to
and type 2 diabetes mellitus (DM-2).2,3 Moreover, low arterial stiffening6,7 and insulin resistance.8 Although the
cardiorespiratory fitness exacerbates the risk for all-cause vascular and metabolic maladaptations associated with a
mortality in individuals with and without underlying chronic sedentary lifestyle in aged individiuals are fairly well
disease.4 Conversely, studies in older adults reveal that described, the natural history of this “sedentary death
life-long daily aerobic exercise effectively attenuates the syndrome9” is currently unresolved. Specifically it is un-
risk for CVD and DM-2 in men and women, secondary to clear whether the negative influence of sedentary lifestyle
favorable changes in conventional and novel risk factor on determinants of cardiovascular risk emerge only in later
profiles.5– 8 In fact, the differences in certain determinants life or whether they are present in younger persons. In that
of cardiovascular risk (ie, left ventricular and arterial com- regard, the primary aim of this investigation was to deter-
pliance) between exercising and sedentary older adults are mine whether sedentary, young, otherwise healthy men
so profound that some speculate that excessive morbidity and women display differences in antecedents of CVD (ie,
and mortality associated with aging may be more related arterial stiffness, endothelium-dependent dilation, and in-
to sedentary lifestyle than senescence.5,8 sulin sensitivity) relative to their physically active peers.

Received August 12, 2005. First decision January 9, 2006. Accepted Support for this project was obtained from the Canadian Institutes for
January 14, 2006. Health Research; the Alberta Heritage Foundation for Medical Research;
From the Division of Endocrinology (JMMcG, RZL), Faculty of and Pfizer Canada. Support was also provded by a Strategic Training
Medicine, University of Alberta, Edmonton, Alberta, Canada; Depart- Fellowship from the Canadian Institutes of Health Research (to J.M.M).
ment of Cardiovascular Sciences and the Libin Cardiovascular Institute Address correspondence and reprint requests to Dr. Jonathan McGav-
(TJA), University of Calgary, Calgary, Alberta, Canada; and Division of ock, Manitoba Institute for Child Health, 715 McDermott Avenue, Win-
Hypertension (JMMcG), University of Texas Southwestern Medical nipeg, MB R3E3P4, Canada. e-mail: jon.mcgavock@utsouthwestern.
Centre at Dallas, Dallas, Texas. edu

© 2006 by the American Journal of Hypertension, Ltd. 0895-7061/06/$32.00


Published by Elsevier Inc. doi:10.1016/j.amjhyper.2006.01.013
702 SEDENTARY LIFESTYLE AND DISEASE RISK AJH–July 2006 –VOL. 19, NO. 7

Table 1. Characteristics of study subjects

Variable Sedentary Physically active Endurance trained


Men/women 37/37 12/14 19/16
Age (y) 28 ⫾ 5 27 ⫾ 2 26 ⫾ 6
Weight (kg) 73 ⫾ 17 71 ⫾ 8 67 ⫾ 8*
BMI (kg/m2) 24.6 ⫾ 4.8 23.8 ⫾ 2.4 22.1 ⫾ 2.1*
VO2max (mL/kg/min) 35 ⫾ 6 45 ⫾ 6* 59 ⫾ 10*
% Predicted 95 ⫾ 12 127 ⫾ 9* 156 ⫾ 14*
Metabolic variables
Cholesterol 4.7 ⫾ 1.0 4.4 ⫾ 0.8 4.1 ⫾ 0.7
LDL (mmol/L) 2.8 ⫾ 0.9 2.4 ⫾ 0.5 2.2 ⫾ 0.5
HDL (mmol/L) 1.1 ⫾ 0.2 1.2 ⫾ 0.1 1.2 ⫾ 0.2
TG (mmol/L) 1.4 ⫾ 1.0 1.0 ⫾ 0.4 1.0 ⫾ 0.6*
Insulin (␮U/L) 8.8 ⫾ 9 5.9 ⫾ 2.2 4.6 ⫾ 2.0*
Glucose (mmol/L) 5.1 ⫾ 1.4 4.8 ⫾ 0.4 4.8 ⫾ 0.3
HOMA 2.2 ⫾ 3.9 1.1 ⫾ 0.5 1.0 ⫾ 0.4*
Hemodynamic variables
SBP (mmHg) 119 ⫾ 13 122 ⫾ 9 117 ⫾ 9
DBP (mmHg) 69 ⫾ 9 67 ⫾ 7 65 ⫾ 7
HR (bpm) 68 ⫾ 12 63 ⫾ 6 55 ⫾ 6*
SVR (dynes 䡠 sec 䡠 cm⫺5) 1164 ⫾ 28 1169 ⫾ 47 1374 ⫾ 40
FMD (%) 3.6 ⫾ 1.0 2.0 ⫾ 1.2 2.9 ⫾ 1.2

% Predicted ⫽ cardiorespiratory fitness expressed as a percentage of age and gender predicted values obtained from previously published
regression equations (refs. 10, 11); BMI ⫽ body mass index; DBP ⫽ diastolic blood pressure; FMD ⫽ flow-mediated dilation; HOMA ⫽
homeostasis mode assessment; HR ⫽ heart Rate; SBP ⫽ Systolic blood pressure; SVR ⫽ systemic vascular resistance.
All data presented as mean ⫾ SE.
* P ⬍ 0.01 v sedentary group.

We hypothesized that sedentary individuals would be gation, and the Research Ethics Review Board within the
characterized by lower levels of insulin sensitivity, in- Faculty of Medicine at the University of Alberta approved
creased arterial stiffness, and reduced flow-mediated dila- the study protocol.
tion relative to their physically active peers.
Arterial Compliance
and Resting Hemodynamics
Methods Resting measurements of vascular function were per-
Study Population and Design formed in the morning after a 10-h fast, lying supine in a
dimly lit room, with participants having refrained from
A total of 135 otherwise healthy young men (n ⫽ 68, age
vigorous exercise for a period of 48 h before testing.
20 to 40 years) and women (n ⫽ 67, age 20 to 40 years)
Arterial compliance was calculated from diastolic pulse
were studied. Individuals were excluded from the investi-
contour wave analysis obtained from the radial artery as
gation if they presented with or were currently taking
previously described.12 This technique involves 30-sec
medication for type 2 diabetes or cardiovascular disease
recordings of signal-averaged arterial pulse waves by ap-
(such as statins or antihypertensive medications) (Table 1).
planation tonometry using a surface residing pressure
Subjects were stratified into one of three groups based on
transducer (HDI CR-2000, Hypertension Diagnostics, Ea-
self-reported physical activity status: 1) sedentary (⬍30
gan, MN).
min/day of aerobic exercise, ⬍3 days/week); 2) physically
active (30 to 45 min/day of moderate aerobic exercise, 3 to
Brachial Artery
5 days/week); and 3) endurance-trained (⬎45 min/day of
Ultrasonography for Assessment
moderate-to-intense aerobic exercise ⱖ5 days/week). Verifi-
of Flow-Mediated Vasodilation
cation of self-report was done by comparing cardiorespira-
tory fitness 䡠 (O2max, mL 䡠 kg⫺1 䡠 min⫺1) of each individual Brachial artery flow-mediated dilation was performed in
with age-predicted values obtained from previously pub- male subjects only according to the methods initially de-
lished regression formulas.10,11 scribed by Celermajer, which have recently been described
Participants were studied on 3 separate days for deter- in detail elsewhere.13 Briefly, a 7.5-MHz linear phased
mination of the following: 1) arterial compliance, endo- array ultrasound transducer attached to an ultrasound ma-
thelium-dependent dilation and phlebotomy; 2) insulin chine (Sonos 5500, Hewlett-Packard, Avondale, PA) was
sensitivity; and 3) maximal exercise capacity. Informed used to image the brachial artery longitudinally just above
consent was obtained from all subjects before the investi- the antecubital fossa. Brachial artery dilation in response
AJH–July 2006 –VOL. 19, NO. 7 SEDENTARY LIFESTYLE AND DISEASE RISK 703

to 5 min of forearm ischemia and after sublinguinal nitro- 90-min breath samples reflect insulin-mediated glucose
glycerin (⬃0.4 mg) were used to assess endothelium- disposal and incorporation into CO2. The 13CO2 was mea-
dependent and independent dilation respectively. A period sured in breath samples using an AP2003 isotope ratio mass
of 5 min separated the two experiments and M-mode spectrometer (Analytical Precision Limited, Cheshire, En-
images were recorded over a period of 2 to 3 min after gland) by a technician blinded to the status of the study
each experiment. Images were analyzed by two techni- subject. This method has been validated in our laboratory and
cians with extensive experience in ultrasound analysis correlates well with glucose disposal rate during a hyperin-
using computer-assisted edge detection brachial artery sulinemic-euglycemic clamp (r ⫽ 0.69, P ⬍ .001).14
analysis software (DEA, Montreal, PQ, Canada) to calcu-
late brachial artery diameters. Using this software, the
intra- and inter-observer variability is essentially zero. Blood Collection and Analysis
Blood was drawn in the fasted state after ultrasonographic
Insulin Sensitivity imaging. Fasting hematologic measurements included glu-
Insulin sensitivity was assessed using [13C]glucose breath cose, insulin, HbA1c, total cholesterol, HDL, triglycerides,
test method (Diatest, Isodiagnostika, Edmonton AB, Can- and LDL and the homeostasis model of insulin resistance
ada) as previously described.14 The [13C] glucose breath (HOMAIR) as previously described.12
test is a noninvasive estimate of insulin sensitivity that
determines the rate of absorption and metabolism of [13C]-
Graded Maximal Exercise Test
labeled glucose by measuring exhaled 13CO2 in a fasted
state and 90 minutes after ingestion of 25 mg of [13C]glu- Expired gas analysis (TrueOne, ParvoMedics, Salt Lake
cose mixed with 15 g dextrose. Differences in baseline and City, UT) was performed at rest and during graded exer-

Conduit Artery Compliance Resistant Artery Compliance


12
A * B *
20
(mL/mmHg*100)

10
(mL/mmHg*10)

8
15

10 4
0 0
E.T. P.A. Sedentary E.T. P.A. Sedentary
12 Insulin 14 Expired 13CO2
C D
10 12

8 10
( U/L)

(δ ‰)

8
6 *
6
4
4
2
2
0 0
E.T. P.A. Sedentary E.T. P.A. Sedentary
FIG. 1. Physical activity status, arterial compliance and insulin sensitivity in young men and women. Cross-sectional comparisons of conduit
(A) and resistance (B) artery compliance as well as (C) fasting insulin and (D) expired 13CO2 (a marker of insulin sensitivity) between
sedentary (S.E.D.), physically active (PA) and endurance-trained (ET) young adults. *P ⬍ .01 v sedentary group. Differences remained
significant after adjustment for age, body mass index, and serum triglycerides.
704 SEDENTARY LIFESTYLE AND DISEASE RISK AJH–July 2006 –VOL. 19, NO. 7

30
50
Conduit Artery Compliance

A C
25 40
(ml/mmHg*10)

Insulin ( /L)
20 30
r = -0.31, p < 0.01
20
15
10
10
r = 0.27, p < 0.01 0

5
10 20 30 40 50 60 70 80 10 20 30 40 50 60 70 80
VO2peak (mL/kg/min) VO2peak (mL/kg/min)
Resistant Artery Compliance

18
16
B
(mL/mmHg*100)

14
12
10
8
6
r = 0.25, p < 0.01
4
2
10 20 30 40 50 60 70 80
VO2peak (mL/kg/min)
FIG. 2. Inter-relationships with cardiorespiratory fitness. Differences remained significant after adjusting for age and body mass index.

cise to exhaustion on a cycle ergometer as previously Results


described.12 Demographic Characteristics
Subject characteristics are presented in Table 1. No dif-
Statistical Analyses ferences in age or BMI were observed between the seden-
tary and physical active women; however sedentary men
Data are presented as means ⫾ SE unless otherwise stated.
were slightly heavier than the physically active and endur-
Differences in insulin sensitivity and hemodynamic vari-
ance-trained groups (27 ⫾ 5 v 23 ⫾ 2 kg/m2; P ⬍ .05).
ables across cardiorespiratory fitness stratifications were
According to the study design, 䡠 O2max, expressed as
assessed using linear regression analysis and analysis of
oxygen uptake relative to body mass and as a percentage
covariance (ANCOVA) where appropriate. Between-group of age-predicted normal, was significantly higher in both
comparisons were adjusted for age and body mass index the physically active and endurance-trained groups relative
(BMI) as covariates. Data were evenly distributed within to the sedentary group (P ⬍ .01) (Table 1). Furthermore the
the sample. Associations between insulin sensitivity, BMI, endurance-trained group had significantly higher VO2max
fitness, and systolic blood pressure (BP) were examined values than the physically active group (P ⬍ .05). Women
using stepwise linear regression analyses and bivariate displayed significantly lower 䡠 O2max values within each
correlations. To evaluate the association between insulin category, relative to their male peers (P ⬍ .05).
sensitivity and arterial compliance, all subjects were strat-
ified into three groups based on their HOMAIR. Differences
between the groups were determined using ANCOVA with Arterial Compliance
age and BMI included as covariates. All data was analyzed Conduit and resistant artery compliance were both signif-
using SPSS for windows, version 12.0 (SPSS Inc., Chi- icantly higher in the endurance-trained group, relative to
cago, IL). The ␣ level for all analysis was set a priori at the physically active and sedentary groups (P ⬍ .01) (Figs.
0.05. 1A, 1B). These differences remained significant after ad-
AJH–July 2006 –VOL. 19, NO. 7 SEDENTARY LIFESTYLE AND DISEASE RISK 705

justing for differences in age, BMI, and serum triglycer- Table 2. Determinants of insulin sensitivity in
ides between the groups. The differences in arterial healthy young men and women
compliance were observed despite their being no differ-
13
ences in BP or endothelium-dependent (flow-mediated) or Expired CO2 HOMA
-independent (nitroglycerine-mediated) dilation between Cumulative Cumulative
the groups. As expected, heart rate was significantly lower Variable r2 ␤ r2 ␤
in the physically active and endurance-trained men and BMI 0.32 ⫺0.56 0.33 0.57
women (P ⬍ .01). However no differences were observed Age 0.37 ⫺0.63 0.33 0.59
between the sedentary and PA groups. VO2max 0.44 ⫺0.66 0.34 0.57
Sex 0.50 ⫺0.49 0.35 0.55
Metabolic Variables Abbreviations as in Table 1.
Fasting insulin was nearly twofold higher in sedentary
subjects relative to their endurance-trained peers (P ⬍ .01,
Fig. 1C.). Similarly the HOMAIR was significantly higher systolic BP (r ⫽ 0.36) but was unrelated to large or small
in the sedentary group relative to the endurance-trained artery compliance. Sex, BMI, age, and 䡠O2max explained
group (2.1 ⫾ 0.4 v 1.0 ⫾ 0.5, P ⬍ .05). No differences in 44% of the variability in insulin sensitivity within the
expired 13CO2 were observed between men and women or cohort studied (P ⬍ .01) (Table 2). These same variables
among the physical activity groups (Fig. 1D). The trend explained 11% and 20% of variation in conduit and resis-
toward reduced insulin sensitivity in the sedentary group tant artery compliance respectively (Table 3).
was driven primarily by significant differences in the men,
as the differences in women were modest. Finally, serum
triglyceride was ⬃40% greater (P ⬍ .05) in sedentary Discussion
individuals, relative to their endurance-trained peers. The primary novel findings of this investigation are that,
When individuals were stratified into groups based on first, large and small artery compliance are lower in sed-
their HOMAIR, conduit artery compliance was signifi- entary individuals when compared with those of their
cantly lower in individuals with HOMAIR ⬎2.5 than in- endurance-trained peers, independent of conventional risk
dividuals with HOMAIR ⬍1.0 (Fig. 3). Resistant artery factors for cardiovascular disease, including BP. Second,
compliance was not different between the groups. sedentary individuals are also characterized by elevated
fasting insulin and HOMAIR relative to their endurance-
Relationships Between Vascular trained peers. Finally, arterial compliance and insulin sen-
Function, Insulin Sensitivity, and 䡠O2max sitivity, were indistinguishable between physically active
䡠O2max was positively associated with conduit and resis- individuals and their sedentary peers despite a large dif-
tant artery compliance (Figs. 2A, 2B) and was negatively ference in fitness.
associated with fasting insulin (Fig. 2C). These relation- Under the general concept of Neel’s Thrifty Genotype
ships remained significant after adjustment for age and Hypothesis, Lees and Booth suggest that successful human
BMI. The BMI was significantly (P ⬍ .01) associated with evolution has depended upon “a sub-group of genes [that
expired 13CO2(r ⫽ ⫺0.56), HOMAIR (r ⫽ 0.51), and function] to support physical activity for survival through
most of humankind’s existence, [and] require daily exer-
cise to maintain long-term health and vitality.”9 Within
20
this paradigm, Lees and Booth suggest that in cross-
Compliance (mL/mmHg)

* HOMA >2.5
sectional studies, physically active individuals must be
considered as reflecting the control condition, whereas
HOMA 1-2.5
-2.5
sedentary individuals represent the experimental condi-
HOMA < 1.0
15

Table 3. Determinants of arterial compliance in


young men and women
10
Conduit Resistant
Cumulative Cumulative
Variable r2 ␤ r2 ␤
0
Conduit Resistant Age 0.05 ⫺0.21 0.02 ⫺0.09
BMI 0.05 0.07 0.12 0.34
Arterial Compliance VO2max 0.10 0.23 0.18 0.20
FIG. 3. Arterial compliance in young adults stratified by HOMAIR Sex 0.11 0.22 0.20 0.35
index. *P ⬍ .01 v sedentary group. Differences remained significant
after adjusting for age, body mass index, and serum triglycerides. Abbreviations as in Table 1.
706 SEDENTARY LIFESTYLE AND DISEASE RISK AJH–July 2006 –VOL. 19, NO. 7

tion.9 The current study was designed in this manner to we believe that, similar to previous studies,26,27 the data
determine the influence of sedentary lifestyle on cardio- suggest an interaction between insulin sensitivity and vas-
vascular and metabolic determinants of health in young cular health in young adults.
men and women. The most interesting clinical aspect of this study is that
Several authors have reported that age-related decre- dramatic reductions in novel biomarkers for cardiovascu-
ments in arterial compliance15 and endothelium-dependent lar and metabolic disease are evident in sedentary, young,
dilation16 are attenuated with vigorous life-long endurance otherwise healthy men and women despite a normal con-
exercise.6,7 To our knowledge no studies have assessed the ventional cardiovascular risk profile. These data support
influence of sedentary lifestyle on conduit and resistance the overwhelming amount of evidence demonstrating neg-
artery compliance in younger adults. We support and ative cardiovascular-related health outcomes in sedentary
extend the findings of previous studies6,7 in elderly indi- individuals and underscore the need for clinical recogni-
viduals by demonstrating that sedentary young men and tion of the positive health outcomes associated with daily
women are characterized by reductions in both conduit aerobic exercise, even in young, otherwise healthy indi-
and resistant artery compliance, relative to their endur- viduals. In the face of obesity and sedentary lifestyles occur-
ance-trained peers. Interestingly, in contrast to studies in ring at epidemic proportions among adults and children,
younger17 and older men,7 we did not observe differences early recognition of high-risk behavious and appropriate
in endothelium-dependent dilation between sedentary and intervention strategies are paramount in the prevention of
endurance-trained young men. This discrepancy is likely chronic disease. Finally, these data demonstrate that neg-
related to the different methods used (ie, venous occlusion ative cardiovascular and metabolic outcomes associated
plethysmography versus ultrasound imaging) or to the with physical inactivity are only marginally improved in
possibility that the methods used were not adequately individuals who perform aerobic exercise ⬍45 min at
sensitive to detect subtle differences between these groups moderate intensity, 3 to 4 days per week. These findings
of young, otherwise healthy men and women. support previous studies that have demonstrated more
In addition to CVD prevention, chronic daily aerobic favorable metabolic outcomes associated with vigorous
exercise is a cornerstone in the prevention of DM-218,19 physical activity.28
Conversely, prolonged20 and severe inactivity21,22 (ie, bed A common concern with this investigation and similar
rest) cause resistance to insulin-mediated glucose disposal, studies relates to the inability to determine whether the
which at least partly explains the increased risk for DM-2 differences in cardiovascular and metabolic parameters
in physically inactive older individuals.23,24 Similar to between the groups are related to physical inactivity per se
previous studies in aged individuals11 and women with or whether they are a function of differences in body
DM-2,15 we demonstrate that sedentary lifestyle/inactivity composition. Because BMI was a significant determinant
is associated with elevated fasting insulin and a concom- of insulin sensitivity within this group, it is possible that
itant increase in the HOMAIR in young men and women. differences in fasting insulin/HOMAIR are a function of
The negative influence of sedentary lifestyle on insulin greater adiposity in sedentary individuals. Although we
and HOMAIR were observed in a stepwise fashion to be have addressed this limitation by using BMI as a covariate
reduced marginally with moderate physical activity and in all group-wise comparisons, lean-ness is also a key
significantly with chronic endurance training (Fig. 1B). adaptation to vigorous exercise, and the two should not be
Furthermore, similar to our previous studies in women considered mutually exclusive.
with DM-2, a negative association was observed between A second possible concern, regarding the interpretation
䡠O2peak and HOMAIR in this population of young healthy of the data, relates to the methods used for determining
men and women (Fig. 2A), supporting the close link vascular health. We are aware that several methods are
between activity level and insulin sensitivity in human currently available to estimate vascular health noninva-
beings. sively in human beings and that the two methods used in
In general, the similarities between the cardiovascular this study have their own limitations and inherent weak-
and metabolic responses to chronic aerobic exercise and nesses.29 –31 Although flow-mediated dilation is a crude
prolonged deconditioning are quite remarkable. Ample estimate of endothelium-mediated dilation, it does not
evidence is available to demonstrate the close relationship reflect the other properties of the endothelium, nor does it
between metabolic dysregulation and cardiovascular dis- reflect the entire vasculature. Similarly, the use of diastolic
ease and dysfunction.25 We believe that one of the mech- pulse contour wave analysis has been criticized for its
anisms through which sedentary lifestyle leads to cardiac theoretical nature within a Windkessel model of the vas-
and vascular dysfunction is through a progressive decline culature.29 We are confident that using both methods si-
in insulin sensitivity.12 To evaluate the relationship be- multaneously adequately addresses these concerns.30
tween insulin resistance on vascular compliance, we strat- In conclusion, a sedentary lifestyle was found to be
ified the group into tertiles based on their HOMAIR (Fig. 3). characterized by a decrease in conduit and resistant arterial
Interestingly, large artery compliance was reduced in those compliance as well as by lower insulin sensitivity in young
with the highest HOMAIR, independent of age and BMI. men and women. These data suggest that the negative
Although these data are merely cross-sectional in nature, influence of sedentary lifestyle on vascular and metabolic
AJH–July 2006 –VOL. 19, NO. 7 SEDENTARY LIFESTYLE AND DISEASE RISK 707

health begins early in life and may contribute to the increased 14. Lewanczuk RZ, Paty BW, Toth EL: Comparison of the [13C]glucose
risk for type 2 diabetes and cardiovascular disease in those breath test to the hyperinsulinemic-euglycemic clamp when deter-
mining insulin resistance. Diabetes Care 2004;27:441– 447.
who are physically inactive. The findings also underscore 15. Smulyan H, Asmar RG, Rudnicki A, London GM, Safar ME:
the need for more regular and prolonged physical activity Comparative effects of aging in men and women on the properties of
in the primary prevention of chronic disease beginning the arterial tree. J Am Coll Cardiol 2001;37:1374 –1380.
early in life. 16. Celermajer DS, Sorensen KE, Spiegelhalter DJ, Georgakopoulos D,
Robinson J, Deanfield JE: Aging is associated with endothelial
dysfunction in healthy men years before the age-related decline in
Acknowledgments women. J Am Coll Cardiol 1994;24:471– 476.
17. Kingwell BA, Tran B, Cameron JD, Jennings GL, Dart AM: En-
The authors acknowledge the expert technical support pro- hanced vasodilation to acetylcholine in athletes is associated with
vided by Cameron McKnight and Ashlee McGuire. The lower plasma cholesterol. Am J Physiol 1996;270:H2008 –H2013.
authors also thank Dave Buchaski and the Hewlett Pack- 18. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin
ard Corporation for providing the ultrasonographic equip- JM, Walker EA, Nathan DM: Reduction in the incidence of type 2
ment used for this investigation. T.J.A. is a Senior Scholar diabetes with lifestyle intervention or metformin. N Engl J Med
2002;346:393– 403.
of the Alberta Heritage Foundation for Medical Research. 19. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H,
Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta
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