Predictors of Carotid Intima-Media Thickness Progression in Young Adults: The Bogalusa Heart Study

Article (PDF Available)inStroke 38(3):900-5 · April 2007with22 Reads
DOI: 10.1161/01.STR.0000258003.31194.0a · Source: PubMed
Abstract
We sought to evaluate the predictors of carotid intima-media thickness (CIMT) progression in young adults and to determine whether they differed between the sexes. Although risk factors for the progression of atherosclerosis in middle-aged and elderly adults are well known, they are less well understood in young adults. CIMT is a validated measure of subclinical atherosclerosis. B-mode ultrasound images of the far walls of both carotid arteries were obtained in 336 young adults in the Bogalusa Heart Study, whose mean+/-SD age was 32.3+/-3.0 years. CIMT and risk factors were measured at baseline (1995-1996) and after 5.8+/-0.6 years. Multivariable regression was used to determine the predictors of CIMT progression. CIMT progression rates in women (0.015+/-0.024 mm/y) and men (0.020+/-0.027 mm/y) were not statistically different after controlling for body mass index (P=0.155). Smoking was a statistically significant predictor of common and composite CIMT progression in both sexes. In men, systolic blood pressure was an independent predictor of internal carotid and composite CIMT progression, fasting glucose predicted common CIMT progression, and family history predicted composite CIMT progression. In young adults, smoking was a consistent predictor of short-term CIMT progression in men and women. Traditional risk factors also predicted CIMT progression in men.

Figures

Shengxu Li, Wei Chen, Gerald S. Berenson and James H. Stein
Heather M. Johnson, Pamela S. Douglas, Sathanur R. Srinivasan, M. Gene Bond, Rong Tang,
Bogalusa Heart Study
Predictors of Carotid Intima-Media Thickness Progression in Young Adults : The
Print ISSN: 0039-2499. Online ISSN: 1524-4628
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Predictors of Carotid Intima-Media Thickness Progression
in Young Adults
The Bogalusa Heart Study
Heather M. Johnson, MD; Pamela S. Douglas, MD; Sathanur R. Srinivasan, PhD;
M. Gene Bond, PhD; Rong Tang, MD, MS; Shengxu Li, MD, MPH; Wei Chen, MD, PhD;
Gerald S. Berenson, MD; James H. Stein, MD
Background and Purpose—We sought to evaluate the predictors of carotid intima-media thickness (CIMT) progression
in young adults and to determine whether they differed between the sexes. Although risk factors for the progression of
atherosclerosis in middle-aged and elderly adults are well known, they are less well understood in young adults. CIMT
is a validated measure of subclinical atherosclerosis.
Methods—B-mode ultrasound images of the far walls of both carotid arteries were obtained in 336 young adults in the
Bogalusa Heart Study, whose meanSD age was 32.33.0 years. CIMT and risk factors were measured at baseline
(1995–1996) and after 5.80.6 years. Multivariable regression was used to determine the predictors of CIMT
progression.
Results—CIMT progression rates in women (0.0150.024 mm/y) and men (0.0200.027 mm/y) were not statistically
different after controlling for body mass index (P0.155). Smoking was a statistically significant predictor of common
and composite CIMT progression in both sexes. In men, systolic blood pressure was an independent predictor of internal
carotid and composite CIMT progression, fasting glucose predicted common CIMT progression, and family history
predicted composite CIMT progression.
Conclusions—In young adults, smoking was a consistent predictor of short-term CIMT progression in men and women.
Traditional risk factors also predicted CIMT progression in men. (Stroke. 2007;38:900-905.)
Key Words: aging
atherosclerosis
cardiovascular diseases
carotid arteries
smoking
A
ssociations between cardiovascular risk factors and
carotid intima-media thickness (CIMT), a marker of
subclinical atherosclerosis, have been established across a
wide spectrum of ages, including children and adults. The
focus of these studies, however, has been on absolute CIMT
rather than on changes in wall thickness over time. Longitu-
dinal changes provide pathophysiological insight into athero-
genesis and may predict future cardiovascular events.
1,2
Indeed, in the Bogalusa Heart Study, childhood risk factors
were associated with CIMT in young adulthood, and an
increasing risk factor burden was associated with increased
aortic and coronary atherosclerosis found at autopsy in young
adults.
1,3
Although the risk factors for atherosclerosis progression
are well known, their differential effect between the sexes
is less well understood, especially in young adults and
children.
1,4
In middle-aged and older women, serum tri-
glycerides, presence of the metabolic syndrome, and pulse
pressure predict CIMT progression compared with men,
whereas physical activity and fibrinogen levels indepen-
dently predict CIMT in middle-aged and older men but not
in women.
5–9
Age, systolic blood pressure (SBP), fasting
glucose, and smoking predict CIMT progression in both
middle-aged and older men and women.
8,10
Although these
conventional cardiovascular risk factors have been associ-
ated with increased CIMT in young adults, sex-related
differences in the predictors of CIMT progression in young
adults have not been described.
4,11
The purpose of this
study was to evaluate the predictors of CIMT progression
in young adults and to determine whether they differed
between the sexes. Because the Bogalusa Heart Study is a
longitudinal study of the natural history of atherosclerosis
in children and young adults, it allows serial measurements
of CIMT over time.
Received June 15, 2006; final revision received September 14, 2006; accepted October 6, 2006.
From the Division of Cardiovascular Medicine (H.M.J., J.H.S.), University of Wisconsin Medical School, Madison; the Division of Cardiovascular
Medicine (P.S.D.), Duke University Medical Center, Durham, NC; the Tulane Center for Cardiovascular Health and the Department of Epidemiology
(S.R.S., S.L., W.C., G.S.B.), Tulane University Health Sciences Center, New Orleans, La; and the Division of Vascular Ultrasound Research (M.G.B.,
R.T.), Wake Forest University School of Medicine, Winston-Salem, NC.
Correspondence and reprint requests to James H. Stein, MD, Department of Medicine, Division of Cardiovascular Medicine, University of Wisconsin
Medical School, 600 Highland Ave, G7/341 CSC (MC 3248), Madison, WI 53792. E-mail jhs@medicine.wisc.edu
© 2007 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000258003.31194.0a
900
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Subjects and Methods
Study Participants and Design
The institutional review boards at Tulane University Health Sciences
Center and the University of Wisconsin Medical School approved
this study. The Bogalusa Heart Study is a biracial, longitudinal study
of the natural history of atherosclerosis in the rural community of
Bogalusa, La.
1,3,11
A detailed description of the study methods has
been previously reported.
3,11
In the 1995 to 1996 survey, 519
participants (meanSD age, 323 years; 71% white; 39% men)
underwent B-mode ultrasonography of the carotid arteries with
measurement of CIMT. In the 2000 to 2001 survey, CIMT was
measured in 1204 participants (364 years old; 70% white; 43%
men). This report includes a cohort of 336 subjects who were
scanned in both surveys. This subgroup was not statistically different
from the total study population in regard to sex, total cholesterol,
age, SBP, body mass index (BMI), family history of coronary artery
disease, tobacco use, fasting glucose, insulin, total cholesterol/HDL
cholesterol, alcohol use, common CIMT, bulb CIMT, and internal
CIMT.
12
Family history was defined in the Bogalusa Heart Study as
a mother or father having a myocardial infarction, percutaneous
coronary angioplasty, coronary artery bypass surgery, or angina
pectoris at any age.
One white male participant reported that he experienced a myo-
cardial infarction at the time of the 1995 to 1996 survey.
12
In
addition, 10 subjects self-reported cardiovascular disease on a
questionnaire at the 2000 to 2001 survey. Data from these 11
subjects were included in this study. The remaining study partici-
pants were free of clinical cardiovascular disease.
Study Procedures
Study-related protocols have been reported previously.
1,11
Images of
the right and left common carotid arteries, carotid bulbs, and internal
carotid arteries were acquired with a Toshiba SonoLayer SSH 160A
ultrasound system (Toshiba Medical, Tokyo, Japan) and a 7.5-MHz
linear-array transducer. Images were imaged and measured accord-
ing to previously described protocols developed for the Atheroscle-
rosis Risk in Communities Study.
11,13
A single reader conducted
measurements with use of a semiautomated border-detection pro-
gram.
11
At the 1995 to 1996 visit, 75 subjects underwent repeat
assessments after 10 to 12 days, with a mean absolute difference of
0.050.03 mm for all CIMT segments, which is comparable to that
in other CIMT studies.
14,15
Statistical Analysis
Analyses were performed with SAS software (SAS Systems, Cary,
NC). For each carotid segment, the average of the right- and
left-sided far wall measurements was used to define the segmental
maximum CIMT. “Composite” CIMT was defined as the average of
the segmental maximum CIMT measurements (“mean max”). Miss-
ing data were handled conservatively by listwise deletion, such that
both right- and left-sided measurements were required to determine
common carotid, carotid bulb, and internal carotid artery values.
12
Cardiovascular risk factors and CIMT at each survey were described
by meanSD values and contrasted by paired t tests with Bonfer-
roni’s adjustment for multiple comparisons or Fisher exact test.
Triglyceride values were corrected for outliers. The
2
test was used
for between-group comparisons of categorical data. CIMT progres-
sion rates were estimated by determining the paired difference in
CIMT values between surveys, annualized on the basis of the time
between measurements. CIMT progression rates were contrasted
between sexes and races according to a general linear model with
adjustment for BMI and the Benjamini and Hochberg adjustment for
multiple comparisons.
16
Predictors of CIMT progression were mod-
eled separately for men and women. Each multiple linear-regression
model of CIMT progression included the following independent
variables from the 1995 to 1996 survey: age, BMI, fasting glucose,
log insulin, SBP, total cholesterol/HDL cholesterol, race, alcohol use
(yes/no), family history of heart disease (yes/no), and smoking
status (yes/no) as previously reported.
11
Models also were ad-
justed for CIMT at the 1995 to 1996 survey because baseline
CIMT was strongly correlated with CIMT progression (r⫽⫺0.20
to 0.30) by segment. SBP was used in the models because it had
a stronger association with CIMT than did diastolic blood
pressure in the Bogalusa Heart Study, and these 2 values were
collinear.
11
The total-to-HDL cholesterol ratio was used instead
of individual lipid values because this ratio has demonstrated the
strongest associations with CIMT and is less sensitive to the
fasting status of the subjects.
Additional models that included sex and baseline CIMT were
created to evaluate whether the effects of smoking on CIMT
progression were related to differences in the number of cigarettes
smoked per day, years smoked, and smoking history (ie, current
smoker, former smoker, never smoker).
Results
Subject Characteristics
Subject characteristics and CIMT values at each visit are
provided in Table 1. At the time of the 1995 to 1996 survey,
the 336 subjects were 32.43.0 years old (range, 25 to 37),
73% were white, and 62% were women. A family history of
heart disease was reported by 64.1% of subjects. Use of
alcohol was reported by 72.4% of subjects. There were 123
participants (36.7%) who reported cigarette use (mean,
16.29.9 cigarettes per day) for an average of 13.35.6
years. Follow-up was 5.80.6 years (range, 4 to 8). At the
2000 to 2001 survey, subjects were 38.22.9 years old
(range, 31 to 43). Significant increases in BMI, fasting
glucose, SBP, and all CIMT measurements were observed
between the 2 visits.
CIMT Progression Rates
CIMT progression rates were as follows: common carot-
id0.0160.002 mm/y, carotid bulb0.0230.051 mm/y,
internal carotid0.0090.041 mm/y, and composite
CIMT0.0170.026 mm/y. CIMT progression rates did not
differ significantly in women versus men: common
CIMT0.0140.018 versus 0.0190.020 mm/y (P0.103),
bulb0.0210.047 versus 0.0250.055 mm/y (P0.513),
internal CIMT0.0070.038 versus 0.0110.044 mm/y
(P0.490), and composite CIMT0.0150.024 versus
0.0200.027 mm/y (P0.155). Significant differences in
CIMT progression between white and black participants
also were not seen (data not shown). Progression rates by
sex and race are in displayed in Table 2. Common CIMT
progressed more slowly in white women than in black
women, black men, and white men (P0.05); however,
after adjustment for multiple comparisons, theses differ-
ences were not statistically significant (P0.066 to 0.096).
Similarly, bulb CIMT progressed more rapidly in black
men than in white women (P0.021); however, after
adjustment, this difference was not statistically significant
(P0.126).
Predictors of CIMT Progression
Predictors of segmental and composite CIMT progression
for all participants are listed in Table 3. Although sex did
not predict the progression of CIMT, there were differ-
ences between the sexes in predictors of CIMT progres-
sion. In women, smoking was a significant predictor of
Johnson et al Carotid IMT in Young Adults 901
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common carotid and composite CIMT progression. Predic-
tors with borderline statistical significance in women
included smoking and SBP for the carotid bulb and age for
common and composite CIMT. No independent predictors
of internal CIMT were identified for women.
In men, smoking also predicted common and composite
CIMT progression. SBP was an independent predictor of
internal carotid and composite CIMT progression. Family
history predicted composite CIMT progression, and fasting
glucose predicted common CIMT progression. Predictors of
borderline statistical significance in men included alcohol use
for common CIMT, family history for bulb and internal
CIMT progression, and BMI for internal carotid CIMT
progression.
The percentage of smokers did not change between surveys
and was similar among men and women at each survey
(Table 1). Similarly, the number of cigarettes smoked per
day, years of smoking, and smoking history were similar
between the sexes. The association between the number of
cigarettes smoked per day and CIMT progression was of
borderline significance (P0.052).
Discussion
Cross-sectional studies have established CIMT as a marker
of atherosclerosis and have determined predictors for
absolute CIMT and its progression.
1,2,8,10,11,17,18
In this
study, we identified the predictors of CIMT progression in
young (25- to 37-year-old) adults. The major finding was
that smoking was the most consistent predictor of CIMT
progression in both sexes and the only statistically signif-
icant predictor of composite CIMT progression in young
women during an average follow-up of 5.8 years. In
previous studies, smoking predicted CIMT in young women.
11,18
An earlier report from the Bogalusa Heart Study demon-
strated that LDL cholesterol and BMI predicted absolute
CIMT in young adults; however, smoking status was not
incorporated in that analysis.
1
Autopsy studies of young
adults in the Bogalusa Heart Study and the Pathobiological
Determinants of Atherosclerosis in Youth Study demon-
strated an association between coronary atherosclerosis and
cigarette smoking.
3,19
In middle-aged and older populations,
total years of cigarette smoking was the most significant
independent predictor of severe carotid atherosclerosis.
20
In
middle-aged adults in the Atherosclerosis Risk in Communi-
ties study, there was a linear relation between total pack-years
of smoking and increased CIMT that persisted with adjust-
ment for age and sex.
17
TABLE 1. Participant Characteristics From the 1995–1996 and 2000 –2001 Surveys
Survey 1
1995–1996
Survey 2
2000 –2001
Survey 1 vs
Survey 2
Men Women P
adj
Men Women P
adj
P
adj
Age 32.4 (2.8) 32.2 (3.0) 0.609 38.3 (2.9) 38.0 (2.9) 0.389 0.001
BMI 28.1 (5.9) 27.6 (7.3) 0.574 29.9 (6.6) 29.1 (7.6) 0.410 0.001
Glucose 81.4 (9.4) 78.8 (13.1) 0.073 87.6 (15.6) 84.9 (21.2) 0.289 0.001
Insulin 12.8 (8.9) 12.2 (10.8) 0.629 15.0 (11.4) 12.1 (9.4) 0.021 0.174
Current smoker, % 36.4 36.7 0.999 32.8 33.5 0.800 0.445
SBP 117.1 (12.7) 110.5 (13.3) 0.001 121.7 (14.0) 116.1 (14.5) 0.001 0.001
Total/HDL
cholesterol ratio
4.9 (1.7) 3.9 (1.3) 0.001 4.9 (1.6) 3.8 (1.0) 0.001 0.553
HDL cholesterol 43.6 (14.7) 52.3 (13.4) 0.001 43.1 (13.6) 53.2 (12.4) 0.001 0.603
Triglycerides 127.9 (70.4) 101.3 (53.0) 0.585 122.4 (68.8) 95.9 (52.0) 0.373 0.327
LDL cholesterol 133.6 (39.9) 120.2 (29.8) 0.001 131.6 (38.9) 121.6 (31.8) 0.017 0.964
Common CIMT 0.683 (0.102) 0.658 (0.085) 0.037 0.797 (0.130) 0.746 (0.122) 0.001 0.001
Bulb CIMT 0.910 (0.179) 0.834 (0.151) 0.001 1.103 (0.386) 0.964 (0.277) 0.001 0.001
Internal CIMT 0.705 (0.105) 0.670 (0.107) 0.030 0.793 (0.197) 0.707 (0.170) 0.002 0.001
Composite CIMT 0.761 (0.094) 0.718 (0.087) 0.001 0.884 (0.191) 0.800 (0.157) 0.001 0.001
All values mean (SD) unless otherwise noted.
TABLE 2. CIMT Progression Rates
Site Race and Sex N
Mean
CIMT, mm/y 95% CI, mm/y
Common carotid White men 93 0.019 0.015–0.023
Black men 31 0.021 0.013–0.028
White women 148 0.013 0.010–0.015
Black women 57 0.018 0.013–0.024
Carotid bulb White men 90 0.021 0.011–0.032
Black men 30 0.034 0.009–0.060
White women 145 0.022 0.015–0.028
Black women 52 0.020 0.003–0.037
Internal carotid White men 83 0.011 0.001–0.021
Black men 26 0.014 0.001–0.026
White women 136 0.009 0.001–0.016
Black women 53 0.004 0.002–0.010
Composite White men 81 0.019 0.013–0.025
Black men 26 0.027 0.016–0.030
White women 138 0.014 0.010–0.019
Black women 50 0.015 0.008–0.020
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TABLE 3. Predictors of CIMT Progression
a. Common Carotid Artery
Variable
Men Women
95% CI P
adj
95% CI P
adj
Intercept 0.0242 0.0833 0.0348 0.417 0.0424 0.0825 0.0023 0.038
Age 0.0001 0.0013 0.0015 0.874 0.0009 0.0001 0.0018 0.065
BMI 0.0006 0.0004 0.0017 0.221 0.0001 0.0004 0.0007 0.640
Current drinker 0.0089 0.0181 0.0004 0.059 0.0009 0.0070 0.0053 0.777
Current smoker 0.0092 0.0007 0.0177 0.035 0.0064 0.0003 0.0125 0.039
Family history 0.0016 0.0062 0.0094 0.687 0.0013 0.0048 0.0073 0.682
Glucose 0.0005 0.0001 0.0010 0.025 0.0000 0.0003 0.0003 0.979
Log insulin 0.0021 0.0247 0.0205 0.854 0.0034 0.0140