Determinants of Vascular Function in

Healthy Young Adults

1,2
1,2
1,2
Leanna"Tu ,"Siddhartha"Angadi" ","Chris.an"Roberts "

1UCLA/"USC"Center"for"Popula.on"Health"and"Health"Dispari.es,"2"Exercise"and"Metabolic"Disease"Laboratory,"School"

of"Nursing,"University"of"California,"Los"Angeles"

Abstract0
Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the US.
Arterial stiffness, measured by augmentation index (AIx) and pulse wave velocity (PWV), is a marker
of future atherosclerosis and cardiovascular risk. The anthropometric, biochemical, physical activity,
and fitness determinants of AIx and PWV are not well defined.
Purpose: To investigate whether anthropometric, biochemical, physical activity, and fitness indices
are significant predictors of AIx and PWV variation.
Methods: Data from existing cohorts from the Exercise and Metabolic Disease Research Laboratory at
UCLA were used in this analysis. The merged population consisted of 62 healthy young men with
normal, overweight, and obese body mass indices (BMI). Data collected included anthropometric
measures, physical activity and fitness levels, vascular measures, blood lipids, serum glucose and
insulin, hormones, inflammation markers, and adipokines. Forward stepwise regression was used for
this analysis (SPSS ver. 20, IBM, NY).
Results: The principal predictors of AIx in our cohort were low-density lipoprotein (LDL) and
plasminogen activator inhibitor-1 (PAI1) (adj. R2 = 0.206, p = 0.026), and the predictor of PWV was
bDBP (brachial diastolic blood pressure) (adj. R2 = 0.065, p = 0.027).
Conclusion: LDL, PAI1, and bDBP are significant predictors of vascular health. Traditional
anthropometric measures were not the greatest predictors in arterial stiffness. Further research on
the relationships between these novel markers and other determinants of vascular health is necessary.

Objec5ves0
Examine anthropometric, biochemical, physical activity and fitness determinants of AIx and PWV
Examine whether anthropometric measures are significantly correlated with vascular health
markers in this population

Background0
Cardiovascular disease (CVD) is the leading cause of mortality. Based on 2008 data, CVD accounted for
32.8% of all deaths in the US.1
Arterial stiffness has been shown as an independent predictor of CVD and vascular health in
general in healthy subjects.2
Augmentation index (AIx) and pulse wave velocity (PWV) are markers of arterial stiffness;
although they measure different arterial properties, they have been shown to be related.3
According to 2008 data, 33.7% of US adults are obese (BMI 30 kg/m2) and 67.3% of US adults are
overweight (BMI 25 kg/m2)
BMI, waist circumference, total body fat, and percent body fat are commonly used indices of
obesity.

Methods
Subject Population:
The study population was comprised of 62 healthy young adult males between the ages of 18-35 from existing cohorts
at the Exercise and Metabolic Disease Research Laboratory at UCLA. All participants abstained from food, caffeine,
alcohol, medications, and vitamin supplementation 10 hours prior to the start of the test.
Anthropometry and Fitness:
A DXA scan was used to determine regional fat and lean mass distribution. The BMI was calculated using the total
mass. Percent trunk fat (%TF) was calculated. Waist circumference (WC) was measured twice and the average was
recorded.
Certified trainers guided subjects through a 1-repetition maximum (1-RM) test for bench press, leg press, and
machine row.
Subjects completed the International Physical Activity Questionnaire from which moderate, moderate-vigorous, and
vigorous activity levels were calculated in MET-minutes/week.
Applanation Tonometry:
After 15 minutes of rest in the supine position, brachial systolic and diastolic blood pressures (bSBP and bDBP) were
obtained. Radial artery waveforms using applanation tonometry (Sphygmocor, AtCor Medical, IL) were recorded.
Heart rate, central/aortic systolic and diastolic blood pressures (cSBP and cDBP), aortic pulse pressure (APP), and
augmented pressure (AP) were obtained from the radial waveform using previously validated methodology.4
Augmentation index (AIx) was calculated as the AP expressed as a percentage of the APP and normalized to a HR of
75 beats per minute.
To determine carotid-femoral pulse wave velocity (PWV), transit distances from the carotid artery, suprasternal
notch, and femoral artery were measured as straight lines with a tape measure. Sequential recordings of pulse
pressure changes at the carotid and femoral artery sites were recorded. The generated pulse waves were compared
to a timing reference generated by an electrocardiogram (EKG). The PWV was then calculated as the distance
between measurement sites divided by the transit time.

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Methods
Blood lipids, hormones, inflammatory markers, and adipokines:
Total cholesterol, LDL, HDL, oxldl, triglycerides, adiponectin, amylin, CRP, fasting glucose and insulin, IL-8, leptin,
MCP1, MMP-9, MPO, sE-selectin, sICAM, sVCAM, PAI1, TNF-, and VEGF were measured. All the biochemical
measurements were calculated using commercially available, previously validated assay kits.
Statistical Analyses:
Data analyses were performed with SPSS ver. 20 (IBM, NY).
Correlations were assessed between the anthropometric measures and AIx / PWV.
Data were obtained on independent determinants of AIx and PWV using forward stepwise regression analysis. P values
of <0.05 were considered significant. P-entry = 0.05 and P-removal = 0.1.

Results
Baseline characteristics
Variable

Mean00SD

Age"(yrs)

22.1""2.6

BMI"(kg/m2)

AIx Model Summary

Model

Adjusted R
Square

Std.
Error

R Square
Change F Change

27.88""3.61

LDL

0.405

0.150

9.75598

0.164

11.802

0.001

WC"(cm)

91.3""11.1

LDL, PAI1

0.482

0.206

9.43149

0.068

5.200

0.026

%"TF

9.1""4.3

bSBP"(mmHg)

125.1""11.6

bDBP"(mmHg)

76.1""9"

cSBP"(mmHg)

107""10

Std.
Error

cDBP"(mmHg)

76.7""9.3

0.88814"

AIx"(%)

^9.8""10.5

PWV"(m/s)

6.59""0.84

LDL"(mg/dL)

83.7""26.9

PAI1"(ng/mL)

136.9""57.6

MPO"(unit/mL)

264.4""195.3

MMP^9"(g/mL)

239.9""121.4

PWV Model Summary

Model

Adjusted R
Square

bDBP

0.283

0.065"

R Square
Change F Change
0.080"

5.149"

p
0.027"

Correlations
BMI *
0.101
(0.34)
0.11
(0.29)

AIx
PWV

WC*
0.05
(0.64)
0.11
(0.31)

% TF*
0.15
(0.16)
0.19
(0.07)

* R, (p value)

LDL and PAI1 were the main determinants of augmentation index.

In young men it appears that brachial diastolic blood pressure was the only significant determinant of PWV.

Conclusions and Implications

The models indicate that in young healthy normal-weight, overweight and obese men:
LDL and PAI1 were the significant determinants of AIx.
bDBP was the only determinant of PWV.
However, it explains very little (6.5%) of the variance in PWV.
This suggests that in young healthy men, neither the traditional nor novel markers of vascular health do a
good job of explaining the variability observed in this measure.
It was bDBP not bSBP that predicted PWV; this is consistent with the Framingham Heart Studys finding
that in patients <50 years, DBP is a stronger predictor than SBP.5

BMI, waist circumference, and percent trunk fat were not statistically significant in either model.
It is interesting to note that the correlations between the above anthropometric measures and AIx / PWV
are not statistically significant.
It is plausible that anthropometric measures are not prominent determinants of vascular health.

There is a need for additional research to further investigate anthropometric, biochemical, and physical
determinants of vascular health and any interactions between the same.

References
1.Roger VL, Go AS, Lloyd-Jones DM et al. Heart Disease and Stroke Statistics2012 Update : A Report from the American Heart Association. Circulation.
2012;125:e12-e230.
2. Mattace-Raso FU, Van der Cammen TJ, Hofman A, et al. Arterial Stiffness and Risk of Coronary Heart Disease and Stroke : The Rotterdam Study.
Circulation. 2006;113:657-663.
3. Brown MJ, Brown, Y. Similarities and differences between augmentation index and pulse wave velocity in the assessment of arterial stiffness. Q J Med.
1999; 92:595-600.
4. ORourke MF, Pauca AL. Augmentation of the aortic and central arterial pressure waveform. Blood Press Monit. 2004; 9(4):179-85.
5. Franklin SS, Larson MG, Khan A. Does the Relation of Blood Pressure to Coronary Heart Disease Risk Change With Aging? Circulation. 2001;
103:1245-1249.

Acknowledgements
Funding for this work provided through the Summer Research Training Program, NHLBI Grant No. 1R25HL-108854-01 and the UCLA/ USC Center for
Population Health and Health Disparities, NHLBIGrant No 1P50-105188-01.
UCLA Exercise & Metabolic Disease studies funded by American Heart Association BGIA #0765139Y.