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Dietary fiber intake and atherosclerosis progression: The Los Angeles Atherosclerosis Study
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Dietary fiber intake and atherosclerosis progression: The Los Angeles Atherosclerosis Study
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DIETARY FIBER INTAKE AND ATHEROSCLEROSIS PROGRESSION:
THE LOS ANGELES ATHEROSCLEROSIS STUDY
By
Huiyun Wu
A thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(Applied Biostatistics and Epidemiology)
December 2003
Copyright 2003 Huiyun Wu
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UMI Number: 1420408
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UNIVERSITY OF SOUTHERN CALIFORNIA
THE GRADUATE SCHOOL
UNIVERSITY PARK
LOS ANGELES, CALIFORNIA 90089-1695
This thesis, written by
H u iy u n Wu __________________________
under the direction o f M s thesis committee, and
approved by all its members, has been presented to and
accepted by the Director o f Graduate and Professional
Programs, in partial fulfillment o f the requirements fo r the
degree of
M a s te r o f S c ie n c e
Director
Date Decem ber 1 7 , 2003
Thesis Committei
Chair
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ACKNOWLEDGMENTS
I would like to thank the members of my Master’s Thesis Committee, Drs,
James H. Dwyer (Chair), Mimi C. Yu, and Jian-min Yuan, for their advice and
suggestions throughout the course of my research and preparation of this thesis.
Thanks also go to Dr. Kathleen M. Dwyer for her constructive comments and helpful
editing on earlier drafts of this thesis.
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TABLE OF CONTENTS
ACKNOWLEDGMENTS ....... li
TABLE OF C O N TEN TS...................... ill
LIST OF TABLES. ....... iv
ABSTRACT............ ...... v
INTRODUCTION ...... 1
SUBJECTS AND METHODS................... 2
Study population. ...................... 2
Carotid IMT measurement.. ......................................... ..3
Dietary intake assessment ...................... 4
Serum lipid determination............... .4
Other measures............................. 5
Statistical analysis. ........... .5
RESULTS ....... 7
Baseline characteristics ................................................ .7
Dietary fiber intake and IMT progression. ........ 10
Correction of measurement errors... ..................... .14
Effect of serum lipid ..................... 15
DISCUSSION ....................................... .......17
Dietary fiber intake and atherosclerosis progression. ......17
Correction of measurement error. ................. 19
Involvement of serum lipid. ......... 20
Conclusion ..........................21
REFERENCE ...... 23
iii
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LIST OF TABLES
Table 1. Characteristics of participants at baseline by quintile of energy-adjusted
total fiber intake. The Los Angeles Atherosclerosis Study (1995-1999)......8
Table 2. IMT progression by quintile of energy-adjusted dietary fiber intake.
The Los Angeles Atherosclerosis Study (1995-999).......................... 12
Table 3. Influence of measurement error on estimates of regression slope relating
IMT progression to dietary fiber. The Los Angeles Atherosclerosis Study
(1995-1999)...................................... ...15
Table 4. Correlation of dietary fiber with serum lipids. The Los Angeles
Atherosclerosis Study (1995-1999).................... 16
iv
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ABSTRACT
Background: Few epidemiologic studies have addressed mechanisms of association
between dietary fiber intake and cardiovascular events.
Objective: To estimate relations between atherosclerosis progression and dietary
fiber intake.
Design: 573 adults free of heart disease were recruited. Data of intima-media
thickness of common carotid, dietary intake, and serum lipids were obtained at
baseline and follow-ups.
Results: Significant inverse associations were observed between IMT progression
and intake of viscous fiber and pectin. Correction for measurement error increased
the magnitude of these estimates. The TC/HDL-C was significantly inversely related
to intake total fiber, viscous fiber and pectin. The magnitude of associations between
IMT progression and intake of viscous fiber and pectin was attenuated by adjustment
for serum lipids.
Conclusion: Viscous fiber appeared to be protective while serum lipids may play a
role in the observed association.
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INTRODUCTION
Cardiovascular disease (CVD) due to advanced atherosclerosis is the leading
cause of death and disability in the US (National Heart, Lung, and Blood Institute,
1994). Numerous risk factors, including dietary pattern, physical inactivity, serum
lipids, diabetes, cigarette smoking, obesity and psychological stress, have been
proposed as contributing to the initiation and development of atherosclerosis and its
clinical manifestations (Hopkins and Williams, 1989). The possible health benefits
of dietary fiber in reducing the risk of CVD were hypothesized in the 1970’s
(Trowell, 1972). Evidence of associations between dietary fiber and atherosclerosis
has accumulated from epidemiologic observations (Fehily et al., 1993; Humble et al.
1993; Khaw and Barrett-Connor, 1987; Kromhout et al., 1982; Kromhout and de
Lezenne Coulander, 1984; Kushi et al., 1985; Morris et ah, 1977; Pietinen et ah,
1996), and a limited number of clinical trials (Amtzenius et ah, 1985; Burr et ah,
1989; Hjermann et ah, 1981; Omish et ah, 1990; Rimm et ah, 1996; Wolk et ah,
1999). Experimental data from both animals and humans suggest that an association
between increased dietary fiber intake and improved plasma lipids profile including
reduced low-density lipoprotein cholesterol (LDL_C) concentration. These
observations indicated a regulation pathway among fiber, plasma lipid and
atherosclerosis (Anderson, 1995; Fernandez, 2001).
Dietary fiber constitutes a group of dietary components. Fruit, vegetables,
whole grains and cereals are the major sources. Total dietary fiber can be divided
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into two groups: viscous fiber (pectin, gums, and mucilage which were previously
classified as water-soluble fiber) and non-viscous fiber (cellulose, hemicellulose, and
lignin which were previously classified as water-insoluble fiber). Increased intake of
viscous fiber lowers blood levels of LDL-C in animal models (Anderson, 1995) and
in clinical intervention studies (Glore et al., 1994). Several properties of viscous fiber
have been proposed as mediating this cholesterol-lowering effect, including
viscosity, bile acid binding capacity and, perhaps, cholesterol synthesis inhibiting
capacity after fermentation in the colon (Glore et al., 1994; Tillotson et al., 1997).
The present cohort study addressed the association of intake of different types
of dietary fiber with progression of carotid atherosclerosis among middle-age women
and men. Possible mediation of this association by serum, lipids also was examined.
SUBJECTS AND METHODS
Study population
The Los Angeles Atherosclerosis Study is a prospective study designed to
investigate the relationship between potential etiologic factors and atherosclerosis
progression. The cohort has been described previously (Dwyer et al., 2001; Dwyer et
al., 1998). In brief, 269 women aged 45 to 60 years and 304 men aged 40 to 60 years
with no history of heart attack, angina, revascularization, or stroke at entry were
randomly sampled from strata in a large utility company. The strata were age,
ethnicity (Hispanic, non-Hispanic) and smoking status. Hispanics and smokers were
2
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over-sampled. Participation rate among sampled eligible employees was 85%,
resulting in a cohort of 573 subjects in the baseline examination. The baseline
examination took place in 1995-96. Two follow-up examinations were conducted at
1.5 and 3 years after the baseline examination. Seventy-three subjects were excluded
due to loss of follow-up, resulting in a longitudinal study sample of 500 participants.
There were no significant differences in baseline characteristics between
participants with and without follow-ups. In the modeling of serum lipid data, 53
subjects were excluded from the present analysis due to non-fasting blood draw (<8
hours since the last meal) or serum triacylglycerol concentration >3.95 mmol/L, 2
subjects were excluded from the present study due to missing values of serum lipids,
and 5 subjects were excluded because of large discrepancies between repeated
measurements of total cholesterol (TC) concentration difference (>3.36mmol/L).
The protocol for this study was approved by the Institutional Review Board
for the Keck School of Medicine of the University of Southern California. Informed
consent was obtained from all the participants.
Carotid intima-media thickness (IMT) measurement
The protocol for the common carotid IMT measurement used in this study
has been described previously (Dwyer et al., 1998). Briefly, a 1-cm segment of the
far wall adjacent to the carotid bulb was analyzed using automated software with an
edge-detection algorithm developed at the Jet Propulsion Laboratory (Pasadena, CA)
(Selzer et al., 1994). Measurements were averaged over the left and right carotid
3
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artery in the supine and lateral positions. A reproducibility study of this protocol
detected a mean absolute difference of 0.022 mm (coefficient of variation 2.8 %)
between repeated scans by 2 sonographers. Scan readers were blinded to dietary fiber
intake. All measurements were conducted in a mobile unit located at the
participant's work site.
Dietary intake assessment
Dietary intake was assessed with 24-hour diet recalls. Briefly, at visit 1, a 24-
hour dietary recall from the participant was obtained by in-person interview by a
trained nurse. Use of vitamin in the previous day was also asked. The second and
third 24-hour diet recalls were obtained by telephone interview within two months of
the initial recalls. Two 24-hour recalls were collected on weekdays and one on
weekend day. Three 24-hour diet recalls were performed again with the same
procedure at the follow-up examination that began 18 months after the initial
examination, resulting in a total of up to 6 records per participant during the study.
The recalls were collected using the protocol and software provided by Nutrient Data
System (Nutrition Coordinating Center, University of Minnesota, Minneapolis, MN
55454) (Feskanich et al., 1989; Schakel et al., 1988).
Seram lipid determination
Blood samples were processed immediately after collection and stored at -
80°C. Serum TC, high-density-lipoprotein cholesterol (HDL-C) and triacylglycerol
4
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were determined using an automated clinical chemistry analyzer by enzymatic
method in a laboratory of University of Southern California. LDL-C was estimated
using the formula of Delong based on serum TC, HDL-C and triacylglycerol
concentration (DeLong et al., 1986).
Other measures
Ethnicity, alcohol intake, cigarette use, physical activity, medication use and
medical history were measured through in-person interview. Anthropometric
measurements and blood pressures also were collected by the study nurse or
sonographer during the baseline and follow-up examinations.
Statistical analysis
The characteristics of the participants at baseline were analyzed for linear
trend across the quintiles of total dietary fiber intake with logistic regression for
categorical variables and general linear regression for continuous variables.
Relations between progression of IMT and other factors were modeled with
two repeated measures regression models. Quintiles of components of dietary fiber
intake (total dietary fiber, non-viscous fiber, viscous fiber and pectin) were used to
assess the relation between fiber and IMT progression. Tests of trend across
quintiles were derived from models using dietary intake as continuous variables.
Model 1 was adjusted for age, sex, and total energy intake. Model 2 was further
adjusted for ethnicity, smoking status, alcohol intake, vigorous physical activity
5
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times/week), work-related psychological stress (ordinal variable), treatment with
cholesterol-lowering or anti-hypertension medication (yes, no), diabetes (yes, no),
use of vitamin C or E supplements (yes, no), systolic blood pressure (continuous),
body mass index (weight in kg divided by height in squared meter, continuous
variable)(BMI), intake of vegetables, fruit, saturated fat, magnesium and potassium,
and the interaction of dietary fiber and sex as covariates. Model 3 was further
adjusted for serum lipids (continuous variable). Dietary fiber intake was adjusted for
total energy intake by including total energy in the model as a covariate.
We used measurement model to correct measurement error in diet
assessment. In the measurement model, the intake of viscous fiber and the intake of
pectin were expressed as unobserved variables indicated by the intake from the two
observed measurements (baseline and 18-month follow-up). The influence of the
measurement error in diet assessment on atherosclerosis progression was then
investigated by incorporating the measurement model into a structural model. The
attenuation of slopes that occurs when predictor variables are measured with error is
sometimes referred to as "regression dilution bias (MacMahon et al, 1990). The
model estimates the slope of the dependent variable regressed on the long-term
average intake, which is unobserved, by assuming that the errors of measurement at
each examination are random (Dwyer, 1983). The estimates of slope were adjusted
for the same confounders as in Model 2 above. Relations between dietary fiber
intake and serum lipids were analyzed with Pearson correlation coefficients.
6
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Regression equations with measurement models were estimated by maximum
likelihood using the software AMOS, Version 4 (SmallWaters Corporation, Chicago,
B L 60615). Only continuous variable models were estimated with correction for
measurement error. Other repeated measures models, including those with quintiles,
were estimated by maximum likelihood using the Mixed procedure in SAS, Version
8.2. (SAS Institute, Cary, NC 21550).
RESULTS
Baseline characteristics
Total dietary fiber intake was averaged with baseline and the 18-month
follow-up assessments. The median total fiber intake in the highest quintile was two
fold greater than the lowest (25.3 g/d vs 12.7 g/d). Subjects were grouped into
quintiles of total dietary fiber intake. Total fiber intake differed significantly across
the five categories of race/ethnicity (p=0.04 by chi-square, df =16). There were more
Asians (p=0.04) and African-Americans (p=0.02) in low fiber intake categories.
Fiber intake also differed significantly across the categories of smoking status
(p<0.01 by chi-square, df =8). Subjects with low fiber intake tended to be current
smokers (p<0.01) while subjects with higher intake tended to be never smokers
(p<0.01) (Table 1). Subjects with higher fiber intake also had lower intake of total
fat (p<0.01), saturated fat (p<0.01) and cholesterol (p<0.01). Serum TC/HDL-C was
inversely associated with level total fiber intake (p=G.03) (Table 1).
7
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Table 1. Characteristics of participants at baseline by quintile of energy-adjusted total fiber intake.
The Los Angeles Atherosclerosis Study (1995-1999)
Characteristics
Quintile of dietary fiber intake P for
trend 1
1st (lowest)
^ jn d ^rd
4th
5th (highest)
Median fiber intake (g/day) 12.7 15.3 17.6 19.9 25.3
Sample size 100 100 100 100 100
Sex (% women) 39.0 46.0 53.0 54.0 40.0 0.53
Race/Ethnicity (%)
Non-Hispanic White 59.0 49.0 53.0 53.0 65.0 0.31
Hispanic 20.0 33.0 33.0 37.0 24.0 0.41
Asian 10.0 11.0 6.0 6.0 3.0 0.04
Afric an - Ameri c an 10.0 6.0 4.0 3.0 3.0 0.02
Other 1.0 1.0 4.0 1.0 5.0 0.20
Smoking status (%) <0.01
Current 41.1 29.0 21.0 16.0 14.0 <0.01
Former 21.0 29.0 31.0 27.0 27.0 0.48
Never 38.0 42.0 48.0 57.0 59.0 <0.01
Diabetes (%) 1.0 2.0 2.0 4.0 5.0 0.06
Age (yr, mean±SEM) 49.9±0.4 49.210.5 50.110.5 50.210.5 50.310.5 0.22
IMT (pm, mean+SEM)2 693.0111.0 659.5110.0 643.7118.2 663.6110.3 667.718.9 0.13
BMI (kg/m2 ,mean±SEM) 3 28.310.5 27.910.6 27.510.4 28.110.6 27.910.5
0.68
Physical activity (times/week) 4 1.710.2 1.610.2 1.810.2 2.110.2 2.510.2 <0.01
Dietary intake (mean+SEM)
Total energy (KJ/day) 89061254 87511269 77281234 80081254 86401259
0.12
Total fat (% energy) 35.110.7 33.6 10.6 31.610.7 31.610.8 28.410.7
<0.01
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Table 1 (cont.)
Saturated fat (% energy) 12.4±0.3 11.310.3 10.610.3 10.20.3 9.010.3
<0.01
Cholesterol (mg/day) 317.3± 15.5 294.2114.3 224.6110.6 254.0112.8 220.9113.6
<0.01
Alcohol (g/day)
6.1±I.l 11.711.8 7.511.3 6.411.1 6.311.0
0.26
Serum lipids (mean±SEM)
TC (mmol/L)5 5 .5 8 1 0 .1 0 5.6510.10 5.6610.09 5.4610.09 5.5010.10
0.22
HDL-C (mmol/L) 6 1.3910.03 1.4810.02 1.5010.04 1.5310.04 1.4610.03
0.09
LDL-C (mmol/L) 7 3.4610.09 3.5410.10 3.5010.09 3.3610.10 3.4010.10 0.33
Triacylglycerol (mmol/L) 2.1810.15 1.7810.11 2.0510.15 1.7410.12 1.8010.11
0.06
TC/HDL-C 5 4.2510.12 4.0210.11 4.0210.11 3.77+0.10 3.9810.12
0.03
Logistic Regression and General Linear Models were used to test for trend across quintiles of fiber intake for categorical
and continuous variables, respectively.
2 IMT = intima-media thickness of the common carotid arteries.
3 BMI = body mass index.
4 Physical (aerobic) activity (such as running or brisk walking) sufficient to induce sweating.
5 TC = Serum total cholesterol.
6 HDL-C = high density lipoprotein cholesterol.
7 LDL-C=low density lipoprotein cholesterol.
8 TC/HDL-C = total cholesterol divided by high density lipoprotein cholesterol.
Mean IMT was 667 jiim (SD = 98) at baseline examination. The
largest IMT was observed in the lowest quintile of intake. But there was no
significant trend of IMT across the quintiles of intake (Table 1). The annual IMT
progression rate was 10.0 jim/yr (SD=15.9). This progression rate represents an
increase of 1.5% per year and 4.5% over three years. There was no significant
difference (p=0.61) in mean progression rates (mean ±SD) between women
(9.2±15.1pm/yr) and men (10.7116.5 fim/yr). Since no significant interaction was
observed between sexes and dietary fiber intake, data from men and women were
pooled for analyses.
Dietary fiber intake and IMT progression
IMT progression tended to decline across quintiles of dietary fiber intake
(Table 2). This inverse association reached statistically significant level for viscous
fiber (p for trend = 0.05) and pectin (p = 0.01), and marginally significant for total
fiber (p=0.06), but not significant for non-viscous fiber (p=0.26) after multivariate
adjustment. Since vegetables and fruits are the major two food groups rich in dietary
fiber in general and viscous fiber in particular, and also contain many other anti
atherogenic constituents, the multivariate-adjusted model was further adjusted for
vegetable and fruit intake. The results indicated that controlling for vegetable and
fruit intake did not produce much attenuation of the magnitude of the inverse
association between IMT progression and viscous fiber or pectin intake with p value
still significant (10 % and 8 % for soluble and pectin respectively). However, the
10
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association magnitude was attenuated after adjusting for serum lipids, with the slope
decreased by 32% for viscous fiber and 15% for pectin (Table 2).
11
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Table 2. Intima-media thickness progression by quintile of energy-adjusted dietary fiber intake. The Los Angeles
Atherosclerosis Study (1995-1999)7
Quintile of intake
Pfor
trend
Change
in slope
(%)3
Model2 1st 3rd 4th 5,h
Total dietary fiber
Age, sex, energy-adjusted 10.0011.89 11.0211.66 8.5111.64 10.7411.74 7.3611.87 0.32
Multivariate-adjusted
12.8612.73 12.2411.94 8.4111.88 9.9611.98 4.8512.91 0.06
Lipid-adjusted 10.2412.65 12.7411.93 7.6411.86 10.1711.93 4.5612.78 0.15 38
Non-viscous fiber
Age, sex, energy-adjusted 10.9811.87 7.6911.67 10.8711.64 10.3711.70 8.0911.84 0.63
Multivariate-adjusted 11.8712.60 9.7911.98 10.4811.91 10.8012.02 6.5912.67 0.26
Lipid-adjusted 10.0212.57 10.5911.93 9.8711.88 10.7111.97 8.6812.52 0.71 50
Viscous Fiber
Age, sex, energy-adjusted 9.5711.87 12.0511.63 7.9611.68 11.0511.64 6.5611.90 0.16
Multivariate-adjusted 11.1212.76 13.3911.97 8.5211.81 9.6811.92 5.8712.87 0.05
Lipid-adjusted 10.6412.70 13.7211.95 8.7811.78 10.3011.89 6.8612.80 0.10 32
Pectin
Age, sex, energy-adjusted 11.1211.71 11.2511.65 9.4411.70 7.6411.59 8.4811.76 0.46
Multivariate-adjusted 12.2712.12 12.2511.94 10.1811.90 7.1011.89 6.45+2.23 0.01
Lipid-adjusted 11.7312.09 12.2811.87 11.0211.87 6.9911.85 6.9812.18 0.05 15
1 Values are expressed as mean+SEM (in pm/yr).
~ Multivariate model added adjustments for ethnicity, smoking status, physical activity, stress, use of cholesterol-lowering
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Table 2 (cont.)
medication or use of anti-hypertensive medication, diabetes, supplementation of vitamin C and vitamin E, BMI, systolic
blood pressure, and intake of vegetable, fruit, saturated fat, magnesium and potassium; lipids-adjustcd model added
adjustment for HDL, LDL and triacylglycerol. See “Methods” for the coding in the model.
3 Percent change in slope between lipid-adjusted model and multivariate-adjusted model.
Correction of Measurement error
Correction for measurement error in dietary variables increased the
magnitude of regression coefficients relating IMT progression to dietary fiber intake
(Table 3). When only baseline measurement of dietary fiber intake was used, the
regression coefficient of fiber intake on IMT progression was -1,33 for viscous fiber
and -2.73 for pectin. Averaging the measures of dietary fiber intake from the
baseline and follow-up, but not correcting the measurement error, improved the
regression coefficient for viscous fiber (from -1.33 to -1.57), but not for pectin
(from -2.73 to -2.22). However, relative to the average of the six 24-hour recalls
from the two examinations, the modeling of measurement error more than doubled
the magnitude of the association.
14
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Table 3. Influence of measurement error on estimates of regression slope relating
IMT progression to dietary fiber. The Los Angeles Atherosclerosis Study (1995-
1999)
Model Regression slope7 P value
Viscous fiber
Baseline -1.33±0.60 0.03
Follow-up -0.9010.62
0.15
Average of baseline and follow-up -1.5710.62
0.03
Measurement error corrected 2 -2.5211.11 0.02
Pectin
Baseline
-2.7311.26
0.03
Follow-up
-1.9511.31
0.12
Average of baseline and follow-up -2.2211.05
0.04
Measurement error corrected 3 -5.8712.34 0.01
Regression slope is the regression coefficient in the structural model.
2 ,3 See details in “Methods”.
Effect of serum lipid
We further examined the relation between dietary fiber intake and serum
lipids using correlation statistics. Small but statistically significant inverse
correlations were observed between TC/HDL-C and total fiber and viscous fiber
(Table 4). Conversely, HDL-C was positively related to total fiber (p=0.03), viscous
fiber (p=0.01) and pectin (p=0.04) (Table 4). These associations were not corrected
for attenuation due to measurement error in the dietary and lipid variables.
15
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Table 4. Correlation between dietary fiber intake and serum lipids. The Los Angeles Atherosclerosis Study
(1995-1999) 12
Serum Lipid
Dietary fiber
LDL-C HDL-C LDL-C/HDL-C TC/HDL-C Triacylglycerol
Total fiber -0.032 (0.44) 0.091 (0.03) -0.078 (0.07) -0.094 (0.03) -0.077 (0.07)
Non-viscous fiber -0.024 (0.57) 0.075 (0.08) -0.065 (0.13) -0.079 (0.07) -0.076 (0.08)
Viscous fiber -0.038 (0.37) 0.114(0.01) -0.091(0.03) -0.105 (0.01) -0.062 (0.15)
Pectin -0.016(0.71) 0.089 (0.04) -0.082 (0.06) -0.074 (0.09) -0.083 (0.05)
The correlations are adjusted for age, sex, smoking status, diabetes, use of cholesterol-lowering medication,
use of anti-hypertension medication, systolic blood pressure, BMI, and intake of saturated fat and cholesterol.
See “Methods” for the coding in the model.
The values are expressed as Pearson correlation coefficients (P-value).
o \
DISCUSSION
Dietary fiber intake and atherosclerosis progression
Cohort studies of cardiovascular events have found inverse associations with
intake of fiber-rich foods, such as fruit, vegetables, whole grains, and cereals (Liu et
al., 1999; Pietinen et al., 1996; Rimm et al., 1996). However, these fiber-rich foods
also contain many anti-oxidants, minerals and other nutrients that may be associated
with CVD (Sacks, 1993). The present study observed a significant protective
association of viscous fiber and pectin intake with IMT progression after adjusting
for other known atherosclerosis risk factors and suspected dietary factors (Sacks,
1993). These findings are consistent with studies with clinical events as endpoints
(Kushi et al., 1985; Liu et al., 2002; Pietinen et al., 1996). For example, Pietinen et al
(Pietinen et al., 1996) observed that only viscous fiber remained significant after
adjustment for known risk factors and dietary variables similar to those included in
our analysis. Liu et al recently reported a weak inverse association between dietary
fiber intake and coronary events in a cohort with an 8.Ig difference in median total
dietary fiber intake between the highest and the lowest quintile (Liu et al., 2002). In
contrast, this value was 12.9 g in our cohort. This higher variation of dietary fiber
intake, or improved measurement of fiber intake, might have provided more power
17
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to detect an association. As a continuous variable measured during the pre-clinical
stage of atherosclerosis, IMT progression may provide more power to detect
associations than clinical events. For example, in a small study of volunteers with
established coronary disease (n=94), viscous fiber intake was found to be lower in
subjects with IMT progression, and higher in subjects with IMT regression (Markus
et al., 1997).
The present study demonstrated a significant inverse association of IMT
progression with increased pectin intake (Tables 2, 3). Pectin, as the major part of
viscous fiber, exists mainly in fruit and vegetables. It is known that the physiological
effects of dietary fiber depend on its properties. Water-holding capacity, for
example, an important property of viscous fiber, is much higher in vegetables and
fruit than in cereals or bran (Southgate, 1986). A number of mechanistic studies have
demonstrated that pectin has significant effects on lipid metabolism (Anderson and
Tietyen-Clark, 1986). However, epidemiological data on this issue are still lacking.
It has been suggested that dietary fiber might displace saturated fat intake,
and thus reduce CVD events (Swain et al., 1990). However, adjusting for saturated
fat intake in the present study did not diminish the association significantly,
supporting the previous conclusion that dietary fiber has beneficial cardiovascular
effects independent of saturated fat (Ascherio et al., 1996; Hu et al., 2000). It is also
plausible that fiber intake is confounded with other constituents of fruits and
vegetables, but we found the inverse association between pectin or pectin intake and
IMT progression to be independent of fruit and vegetable intake.
18
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The American Heart Association currently has no recommendation for a
specific fiber intake target for risk reduction in its Dietary Guideline due to
insufficient data (Krauss et al., 2000). Complexity of food composition is a natural
obstacle to causal inference from epidemiologic studies (Lampe, 1999; Willett,
1994), and lack of high quality measurement of intake probably leads to inconsistent
findings across studies of dietary intake (Khaw and Barrett-Connor, 1987; Liu et al.,
2002).
Correction of measurement error
Measurement error in dietary assessment has limited the evaluation of dietary
effects on disease processes because of the loss of statistical power and the bias of
both estimates of dietary effects and statistical significance in multivariate analyses
(Rosner and Gore, 2001). Correction of bias due to measurement error in the present
study increased the magnitude of the regression coefficient of IMT progression on
viscous fiber and pectin intake by over 100%. This provides support for a stronger
protective effect of dietary fiber against atherosclerosis than has been observed in
previous studies. With the exception of the Nurses’ Health Study (Wolk et al.,
1999), epidemiologic studies examining the possible effects of fiber intake on CVD
have estimated dietary intake from a single measurement. In a study of association
between dietary fiber and plasma lipids, Tillotson et al also found that four or five
measurements of dietary fiber intake produced larger regression coefficients than the
19
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single measurement at baseline, reflecting the greater reliability of multiple
measurements (Tillotson et al., 1997).
Involvement of serum lipid
It has been proposed that a protective effect of dietary fiber against CVD is
mediated through direct or indirect effects on serum lipids (Humble, 1997). The
significant associations of dietary fiber with plasma lipids, together with the
attenuation of the relation between dietary fiber intake and IMT progression when
serum lipids were included in the regression model, support the hypothesis.
However, LDL-C did not play an important mediating role in the current study.
Tillotson et al reported similar findings (Tillotson et al., 1997). The association
between dietary fiber and HDL-C observed in our study suggests a possible up-
regulation of HDL-C by dietary fiber. Results from other investigations support this
hypothesis (Tillotson et al., 1997).
Weight loss, physical exercise and smoking cessation have been linked to
elevation of HDL-C (Anderson, 1984; Nicolosi et al., 1999). However, the
mechanisms regulating the increase in HDL-C by these factors are still not clear. The
significantly lower concentrations of triacylglycerol in the highest intake of total
fiber, non-viscous fiber, and pectin in this study suggested a beneficial effect of
dietary fiber on CVD. However, a review of studies assessing the impact of dietary
fiber on triacylglycerol levels found inconsistency across studies (Brown et ah,
1999).
20
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The ratio TC/BDL-C showed the strongest association with dietary fiber
intake. Significant response of TC/HDL-C to diet manipulation has also been
observed in intervention studies. For example, one study using a low-fat diet
compared the impact on various lipid indicators and found the strongest effect on the
TC/HDL-C ratio. TC/HDL-C was proposed as the best metabolic predictor for the
effectiveness of intervention for CVD (Niebauer et ah, 1996). The TC/HDL-C ratio
has also been reported to be the strongest prospective predictor of CVD events in
numerous studies (Castelli et ah, 1983; Willett, 1994). Thus, the association of
TC/HDL-C with dietary fiber in the present study suggests a significant influence of
dietary fiber on lipid metabolism relevant to the pathogenesis of atherosclerosis and
thrombotic events.
Conclusion
Although increasing intake of dietary fiber has been recommended as a safe
and practical approach for cholesterol reduction (Trowell, 1981), several other
mechanisms may underlie the cardiovascular benefits of dietary fiber (Fukagawa et
ah, 1990; Ludwig et ah, 1999; Rouse et al., 1983). Small correlation coefficients (r
values) obtained in the present study also indicated that the regulation of serum lipids
by dietary fiber intake was not strong, which reflects the existence of multiple
pathways for serum lipid regulation. Thus, the current study suggests that increased
dietary fiber intake had significant cardiovascular benefit, and the regulation of
21
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serum lipids by dietary fiber may be partially involved in the process of slowing the
progression of atherosclerosis.
22
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Wu, Huiyun
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Dietary fiber intake and atherosclerosis progression: The Los Angeles Atherosclerosis Study
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Master of Science
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Applied Biostatistics and Epidemiology
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biology, biostatistics,health sciences, nutrition,health sciences, public health,OAI-PMH Harvest
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Dwyer, James (
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