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Association Between Peak Expiratory Flow and the Development of Carotid Atherosclerotic Plaques
Mahmoud Zureik, MD, PhD;
Francine Kauffmann, MD;
Pierre-Jean Touboul, MD;
Dominique Courbon, BS;
Pierre Ducimetière, PhD
Arch Intern Med. 2001;161:1669-1676.
ABSTRACT
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Background Numerous population-based studies have suggested that impaired lung
function is associated with subsequent coronary heart diseasesrelated
mortality and cardiovascular diseaserelated mortality. The relative
contribution of atherosclerosis in these associations is unknown.
Objective To examine the association of peak expiratory flow (PEF) with the occurrence
during 4 years of atherosclerotic plaques in the extracranial carotid arteries
in a sample of 656 subjects (aged 59-71 years) free of coronary heart disease
and stroke at baseline.
Methods Peak expiratory flow was measured at the baseline examination. Peak
expiratory flow values relative to the predicted values (relative PEF values)
were calculated, predicted values being obtained from previously published
sex-specific regression equations of PEF on age and height. A carotid B-mode
ultrasonographic examination was performed at baseline and 2 and 4 years later.
The occurrence of carotid plaques during follow-up
was defined as the appearance of 1 plaque (or more) in previously normal carotid
segments and/or the appearance of new plaques in the carotid segments that
previously had plaques.
Results The proportion of subjects who experienced an occurrence of carotid
atherosclerotic plaques during follow-up was 16.8% (110/656). The unadjusted
odds ratios from the highest to the lowest quintiles of relative PEF values
were 1.00, 1.07 (95% confidence interval [CI], 0.69-2.79), 1.08 (95% CI, 0.52-2.24),
1.38 (95% CI, 0.69-2.79), and 3.07 (95% CI, 1.62-5.85) (P<.001 for trend). Adjustment for major known cardiovascular risk
factors did not markedly change the results, and the multivariate-adjusted
odds ratio of carotid plaque occurrence in subjects with the lowest quintile
of PEF compared with those with the highest quintile remained highly significant
(odds ratio, 2.84; 95% CI, 1.45-5.71) (P = .002).
Particularly in all smoking categories, carotid plaque occurrence was higher
in subjects with the lowest relative PEF values. In never smokers, the multivariate-adjusted
odds ratio of carotid plaque occurrence in subjects with the lowest quintile
of PEF compared with those with the highest quintile was 2.80 (95% CI, 1.14-6.88).
Conclusions Reduced lung function predicts the development of carotid atherosclerosis
in elderly subjects. The nature of these associations remains largely unknown
and merits further investigations. Nevertheless, assessment of lung function,
which is simple and inexpensive, could help identify a population at high
risk of atherosclerosis development and coronary heart disease.
INTRODUCTION
ESTABLISHED cardiovascular risk factors, such as advancing age, male
sex, smoking, hypertension, and hypercholesterolemia, do not fully explain
the risk of coronary heart diseases (CHDs) in the population. Other unrecognized
factors could also contribute to the risk. Numerous prospective studies1-12
have suggested that impaired lung function is independently associated with
subsequent myocardial infarction, cardiovascular disease and CHD-related
mortality, and all-cause mortality. However, the physiopathological mechanisms
underlying these associations are not known and the relative contribution
of atherosclerosis to the subsequent CHD events in subjects with reduced lung
function remains speculative.
Atherosclerosis is obviously the main underlying pathologic feature
of ischemic cardiovascular diseases. Until recently, direct assessment of
atherosclerosis was principally restricted to autopsy and angiographic studies
that were conducted in highly selected populations and in subjects with advanced
atherosclerosis. These facts could explain, at least in part, the lack of
population-based studies investigating possibly more-specific relationships
of lung function with atherosclerosis development.
High-resolution B-mode ultrasonography is a noninvasive, valid, and
reproducible method of directly visualizing and assessing carotid atherosclerosis,13 and it is used in many population-based studies.14-19
Angiographic and ultrasonographic studies20-21
have found that carotid atherosclerotic plaques are associated with the presence
of other localizations of atherosclerosis and can be used as a marker of general
atherosclerosis.
In the present report, based on the longitudinal data of the Etude sur
le Vieillissement Artériel study, we assessed the associations of peak
expiratory flow (PEF) measured at the first examination and carotid plaque
occurrence during the 4-year follow-up of a population of 656 subjects aged
between 59 and 71 years.
SUBJECTS AND METHODS
Details of the Etude sur le Vieillissement Artériel study have
been reported previously.22-24
The initial study population was composed of 1389 volunteers, aged between
59 and 71 years, who were recruited from the electoral rolls of Nantes, France.
The study protocol was approved by the Comité d'Ethique du Centre Hospitalier
Universitaire du Kremlin-Bicêtre, and written informed consent was obtained
from all participants. After the baseline visit, which took place in the morning
between June 3, 1991, and July 2, 1993, subjects were invited to participate
in 2- and 4-year follow-up examinations.
MEDICAL HISTORY AND STANDARD BIOLOGICAL PROCEDURES
Medical information, obtained at the baseline examination by a standardized
questionnaire, included demographic background, education, occupation, medical
history, drug use, and personal habits, such as cigarette and alcohol consumption.
In addition to the 6 specified common diseases (myocardial infarction, angina,
stroke, hypercholesterolemia, hypertension, and diabetes), each subject was
asked whether he or she had ever had an asthma attack or had experienced other
chronic medical conditions such as chronic bronchitis. "Respiratory diseases"
used in the analysis regrouped subjects with a self-reported asthma attack
or a history of chronic bronchitis.
The smoking habits' questionnaire included detailed information on whether
the subject had ever smoked cigarettes, the duration of cigarette smoking,
the average daily number of cigarettes smoked, and the age at which smoking
ceased (if applicable). Subjects were classified as never, former, or current
smokers. For ever smokers, cigarette pack-years were also calculated by multiplying
the number of years of smoking by the average number of cigarettes smoked
per day, divided by 20. Two independent measurements of systolic and diastolic
blood pressure were made with a digital electronic tensiometer (model SP9;
Spengler, Frankfurt, Germany) after a 10-minute rest, and the mean value was
used in the analysis. Subjects with a systolic blood pressure of 160 mm Hg
or higher, those with a diastolic blood pressure of 95 mm Hg or higher, and/or
those who were using antihypertensive drugs were considered to have hypertension. Hypercholesterolemia was defined as a total cholesterol
level of 6.2 mmol/L or higher ( 240 mg/dL) or use of lipid-lowering drugs.
Subjects who reported a medical history of diabetes, use of antidiabetic drugs,
or a fasting plasma glucose level of 7.0 mmol/L or higher ( 126 mg/dL)
were considered to have diabetes. The body mass index was computed as weight
in kilograms divided by the square of height in meters.
PEF TEST
The PEF test was performed only at the baseline visit. Measurements
of PEF were taken between 9 AM and 11 AM, before the ultrasonographic examination,
by trained research assistants using the Mini Wright peak flowmeter. Subjects
were asked to take a deep breath and blow as hard and as fast as they could
into the instrument while they were standing. The cooperation of subjects
in performing the PEF test was recorded (good or bad). Three measurements
of PEF were taken. The coefficient of variation for PEF measurements was 8.9%.
The maximum of the 3 measurements was used for analysis. The highest measurement
was within 10% of the second highest for 95.1% of the subjects and within
15% for 98.4% of them.
The same device was used during the entire study period (14 months).
This device might have lost accuracy after repeated use. Peak expiratory flow
values were thus split according to examination periods (each 1 month), and
no measurement drift was detected over time.
ULTRASONOGRAPHY
Ultrasonographic examinations at baseline and at the 2- and 4-year follow-up
visits were performed using an ultrasonograph (model SSD-650; Aloka, Tokyo,
Japan), with a transducer frequency of 7.5 MHz. Acquisition, processing, and
storage of B-mode images were computer-assisted, with software specially designed
for longitudinal studies (EUREQUA; TSI, Meudon, France).25
Details of the protocol have been described elsewhere.22-24
At each examination, it involved scanning of the common carotid arteries (CCAs),
of the carotid bifurcations, and of the origin (first 2 cm) of the internal
carotid arteries. At the examination, the intima-media thickness (IMT) was
measured on the far wall of the middle and distal CCA as the distance between
the lumen-intima interface and the media-adventitia interface26
using an automated edge detection algorithm. One transversal and 2 longitudinal
measurements of IMT (at a site free of any discrete plaques) were completed
on the right and left CCAs; the mean of the 4 right and left longitudinal
CCA IMT measurements was used in the analysis.
The near and far walls of all arterial segments (ie, CCA or bifurcation-origin
of the internal carotid artery) were scanned longitudinally and transversally
to assess the presence of plaques. The presence of plaques was defined as localized echo structures encroaching into the vessel
lumen for which the distance between the media-adventitia interface and the
internal side of the lesion was 1 mm or greater.
The same 4 ultrasonographers performed the ultrasonographic examinations
at baseline and at the 2- and 4-year follow-up visits. For each subject, we
attempted to have the 2- and 4-year follow-up examinations performed by the
ultrasonographer who had performed the baseline examination. This was the
case for 76% of the subjects. The reproducibility of the scanning and reading
procedures has been reported elsewhere.24 Briefly,
to study the reproducibility of plaque detection, 75 baseline examination
images of carotid bifurcationinternal carotid artery (52 longitudinal
and 23 transversal images) with plaques, as defined by the ultrasonographers,
and 80 images of carotid bifurcationinternal carotid artery (44 longitudinal
and 36 transversal images) without plaques were randomly chosen and sent to
a single expert ultrasonographer (P-.J.T.) to assess blindly the presence
or absence of plaques. The coefficients for agreement between the
2 readings were 0.86 for longitudinal views and 0.91 for transverse views.
To study the reproducibility of CCA IMT measurements, a rereading study was
made on a random subsamples of images of CCAs (n = 81). The mean absolute
difference and the correlation coefficient between repeated readings of CCA
IMT were 0.06 mm and 0.82, respectively.24
DATA ANALYSIS
The occurrence of carotid plaques during follow-up (at the 2- and/or the 4-year examination) was defined as the occurrence
of 1 plaque (or more) in previously normal segments and/or the occurrence
of new plaques in segments that previously had plaques.
For each subject, the PEF relative to the predicted value (relative
PEF value) was calculated, predicted values being obtained from previously
published sex-specific regression equations of PEF on age and height.27 The means of PEF in the whole population, in men,
and in women were 410 mL/min (SD, 100 mL/min), 496 mL/min (SD, 92 mL/min),
and 357 mL/min (SD, 62 mL/min), respectively. The means of relative PEF values
in the whole population, in men, and in women were 86.6% (SD, 14.9%), 88.9%
(SD, 15.9%), and 85.1% (SD, 14.1%), respectively. The relative PEF values
were divided into 5 categories according to quintiles of sex-specific values.
The cutoff points of the 20th, 40th, 60th, and 80th percentiles were 78.1%,
88.2%, 93.0%, and 100.0%, respectively, for men and 76.0%, 83.1%, 89.6%, and
96.4%, respectively, for women.
Standard procedures from SAS statistical software (SAS Institute Inc,
Cary, NC) were used for univariate and multivariate analyses. Associations
of the 5 categories (quintiles) of relative PEF values with 4-year carotid
plaque occurrence and baseline cardiovascular risk factors were assessed by 2 tests and analysis of variance. Baseline cardiovascular risk factors
considered in the analysis were age, sex, smoking habits, alcohol consumption,
body mass index, hypertension, hypercholesterolemia, diabetes, CCA IMT, and
the presence of carotid plaques at baseline. For multivariate analyses, we
used dichotomic multiple logistic regression models with plaque occurrence
(yes or no) as the dependent variable and categories of PEF and baseline cardiovascular
risk factors as independent variables. Multivariate-adjusted odds ratios (ORs)
and 95% confidence intervals (CIs) of plaque occurrence according to quintiles
of relative PEF values, independent of baseline cardiovascular risk factors,
were estimated by a multivariate logistic regression model, using the group
of subjects with the highest relative PEF values (quintile 5) as the reference.
The PEF protocol was implemented in the Etude sur le Vieillissement
Artériel study from the 11th month on (up to the end of the baseline
examination, 14 months). For this reason, the PEF test was not performed in
the first 604 subjects. The subjects who underwent the PEF test were slightly
older than those who were recruited before implementation of the PEF protocol
(65.2 vs 64.8 years; P = .02). No statistically significant
differences were observed for the other baseline cardiovascular risk factors,
the presence of carotid plaques at baseline, or 4-year carotid plaque occurrence.
Furthermore, 57 subjects who reported at the baseline examination a history
of angina, myocardial infarction, or stroke were excluded from the analysis.
Of the 728 remaining subjects, 656 (90.1%) had complete data on baseline PEF
and cardiovascular risk factors and underwent at least 1 follow-up B-mode
ultrasonographic examination (589 underwent 2 and 67 underwent only 1). At
baseline, there were no statistically significant differences between subjects
who participated and those who did not in the 4-year follow-up survey for
PEF, cardiovascular risk factors, and ultrasonographic examination findings.
RESULTS
The associations of baseline population characteristics and baseline
ultrasonographic examination findings with quintiles of relative PEF values
are shown in Table 1. Subjects
with the lowest relative PEF values (quintile 1) had a higher mean CCA IMT.
They also tended to be older and to have a higher prevalence of carotid plaques,
but the differences did not reach statistical significance. Alcohol consumption,
body mass index, hypertension, hypercholesterolemia, and diabetes were not
significantly related to PEF categories. As expected, smoking habits and a
history of respiratory diseases were strongly associated with PEF categories.
The cigarette pack-years among ever smokers from the highest to the lowest
PEF quintiles were 15.2, 19.9, 23.0, 22.3, and 27.5 (P
= .02 for difference).
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Table 1. Baseline Population Characteristics and Ultrasonographic Examination
Findings According to Categories of Relative Peak Expiratory Flow Values*
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The proportion of subjects who had an occurrence of carotid atherosclerotic
plaques during follow-up was 16.8% (110/656). The distribution and ORs of
carotid plaque occurrence associated with quintiles of relative PEF values
are shown in Figure 1 and in Table 2. After adjustment for age, sex,
body mass index, hypertension, hypercholesterolemia, diabetes, smoking habits,
alcohol consumption, CCA IMT, and presence of carotid plaques at baseline,
the ORs did not markedly change and the multivariate-adjusted OR of carotid
plaque occurrence in subjects with the lowest quintile of PEF compared with
those with the highest quintile remained highly significant (P<.001). In the multivariate analyses, the substitution of cigarette
pack-years (as a continuous variable, with never smokers assigned the value
of 0) for smoking habits categories did not alter the results. In this model,
the multivariate-adjusted OR of carotid plaque occurrence in subjects with
the lowest quintile of relative PEF values compared with those with the highest
quintile was 2.92 (95% CI, 1.51-5.86).
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Percentage of subjects with 4-year carotid plaque occurrence according
to quintiles of relative peak expiratory flow values. Quintile 1 indicates
the lowest relative peak expiratory flow values; 5, the highest values.
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Table 2. Association of Categories of Relative Peak Expiratory Flow
With 4-Year Carotid Plaque Occurrence*
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SUBGROUP ANALYSES
Analyses stratified according to baseline cardiovascular risk factors
are presented in Table 3. In all
categories of smoking habits, carotid plaque occurrence was higher in subjects
with the lowest relative PEF values. In all other subgroups, carotid plaque
occurrence was also higher in subjects with the lowest relative PEF values,
although the association was weaker among hypertensive subjects.
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Table 3. Distribution of 4-Year Cartotid Plaque Occurrence According
to Categories of Relative Peak Expiratory Flow Values Within Categories of
Baseline Cardiovascular Risk Factors*
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A further multivariate analysis was performed in the group of never
smokers (n = 406) (Table 4). The
multivariate-adjusted OR of carotid plaque occurrence in subjects with the
lowest quintile of PEF compared with those with the highest quintile was 2.80.
In never smokers without carotid plaques at baseline, this association was
even slightly stronger (Table 4).
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Table 4. Distribution of 4-Year Carotid Plaque Occurrence According
to Categories of Relative Peak Expiratory Flow Values in Never Smokers*
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The exclusion of subjects who reported respiratory diseases at baseline
(n = 50) did not alter the results. The multivariate-adjusted ORs from the
highest to the lowest PEF quintiles were 1.00, 1.09 (95% CI, 0.50-2.38), 1.21
(95% CI, 0.56-2.67), 1.39 (95% CI, 0.64-3.02), and 2.73 (95% CI, 1.32-5.63)
(P<.001 for trend). The association of PEF categories
with carotid plaque occurrence was also observed after the exclusion of subjects
who had respiratory diseases, hypertension, hypercholesterolemia, and/or diabetes
(data not shown).
When subjects with nonrepeatable measurements of PEF (>10% difference
between the 2 highest values [n = 32]) were excluded, the multivariate-adjusted
ORs from the highest to the lowest PEF quintiles were 1.00, 1.14 (95% CI,
0.52-2.50), 1.40 (95% CI, 0.64-3.07), 1.56 (95% CI, 0.71-3.42), and 3.11 (95%
CI, 1.42-6.81) (P<.001 for trend). The exclusion
of subjects with apparent poor cooperation in performing the PEF test (n =
25) did not modify the results (data not shown). We also divided our population
into 3 groups according to examination periods (0-5, 6-10, and >10 months);
the amplitude and mean of PEF measurements were not different in the 3 groups
and the association of PEF with carotid occurrence was observed within each
of them (data not shown).
FURTHER ANALYSES
Instead of quintiles, the relative PEF values were also divided into
2 categories usually used in asthma management and prevention28:
greater than 80% (n = 474) and 80% or less (n = 182). The unadjusted ORs of
plaque occurrence in the 2 groups were 1.00 and 2.50 (95% CI, 1.64-3.82),
respectively. The respective multivariate-adjusted ORs were 1.00 and 2.32
(95% CI, 1.47-3.70).
When we defined, a posteriori, the carotid plaques as localized protrusions of the vessel wall into the lumen with a
thickness of 1.5 mm or greater instead of 1 mm or greater (102 subjects had
a plaque thickness of 1.5 mm), the multivariate-adjusted OR of carotid
plaque occurrence in subjects with the lowest quintile of PEF compared with
those with the highest quintile was 2.98 (95% CI, 1.48-5.47).
COMMENT
In this 4-year longitudinal observational study performed in a large
sample of relatively older subjects, low values of PEF relative to the predicted
ones were associated with increased carotid plaque occurrence, even after
adjustments for conventional cardiovascular risk factors. In a recent article
on the Etude sur le Vieillissement Artériel study,24
it was reported that age, sex, smoking habits, hypertension, hypercholesterolemia,
CCA IMT, and the presence of carotid plaques at baseline were also related
to carotid plaque occurrence.
The association of PEF with carotid plaque occurrence was observed in
several important subgroups, including men, women, and never smokers. The
magnitude of the associations and the consistency of the results are noteworthy
and, to our knowledge, this is the first study that reports the relationship
between reduced lung function and the subsequent development of carotid atherosclerosis.
Recently, cross-sectional results of the British Regional Heart Study29 showed that reduced forced expiratory volume in 1
second, in subjects aged between 56 and 77 years, was associated with an increased
CCA IMT and a higher prevalence of carotid plaques; the latter difference
was not statistically significant. Our cross-sectional findings corroborated
with these results (Table 1).
Several explanations could be formulated to explain the observed association
of PEF with carotid plaque occurrence. The association could be due to the
relation of confounding factors, especially smoking habits, with lung function
and atherosclerosis. To test this hypothesis, analyses were conducted adjusting
and stratifying for major conventional cardiovascular risk factors. The main
findings were the apparent independent association of PEF with carotid atherosclerosis
in the overall group and the observation in all subgroups of a higher plaque
occurrence in subjects with reduced lung function. Furthermore, more than
60% of the subjects were never smokers and results were similar for all smoking
categories. Despite our efforts to take into account the major conventional
cardiovascular risk factors in the statistical analyses, residual effects
of them and the effects of unknown or, to a lesser extent, unmeasured factors
could not be entirely ruled out. However, the strength of the observed association
of PEF with carotid plaque occurrence would make unlikely that these factors
could account for more than a small part of the association between PEF and
carotid atherosclerosis.
Ventilatory lung function, especially in elderly subjects, could be
regarded as a measurement of the overall health status.30
Assessment of pulmonary function could be also dependent on the participant's
effort, willingness, and ability to give maximal performance.31
Reduced lung function may then be a sign or a symptom of other disease processes
that could ultimately lead to atherosclerosis. However, our results were based
on subjects free of CHD and stroke, and when we further excluded in the analysis
subjects with chronic cardiovascular and respiratory conditions and those
with apparent poor cooperation in performing the PEF test, the results were
not altered and were similar to those observed in the whole population.
Another explanation of the observed association in our study is that
reduced lung function and atherosclerosis are dependent, at least in part,
on the same physiopathological processes, and decreased lung function might
be then an earlier response to these processes than plaque formation. In regard
to this hypothesis, inflammatory mechanisms may be of particular interest.
On the one hand, poor lung function could result from increased airway responsiveness
and allergy32; both of them are prototypes
of inflammatory diseases. On the other hand, an increasing body of evidence
supports the hypothesis that atherosclerosis may be an inflammatory disease
that shares many similarities with other inflammatory or autoimmune diseases,
such as rheumatoid arthritis and idiopathic pulmonary fibrosis.33-34
However, the study of the inflammatory and immunological components of atherosclerosis
is still at its beginning and is raising more questions than answers.34 Other mechanisms might also be important in the development
of respiratory and cardiovascular disease, such as oxidative stress.35-37
Another explanation of our results is that impaired pulmonary function
itself may contribute to the causation of atherosclerosis. However, the mechanisms
by which a low value of PEF confers an increased risk of plaque occurrence
are not clear. Reduced lung function may result in chronic hypoxemia,2 and the imbalance between the demand and the supply
of oxygen in the arterial wall has been suggested to be a key factor for the
development of atherosclerotic lesions.38-39
Our population consisted of volunteers with a relatively low prevalence
of CHD who agreed to undergo follow-up examinations. Taking into account the
high rate of participation in the follow-up survey (90%), the potential effects,
on the observed associations, of selective survival and self-selection biases
are probably small but could not be ruled out. The weaker association of PEF
with carotid atherosclerosis observed in hypertensive subjects should be interpreted
with caution since we performed, in this part of the analysis, multiple statistical
comparisons and a chance finding could not be excluded.
Most of the studies that have suggested that lung function predicted
overall mortality and mortality from cardiovascular diseases used forced vital
capacity or forced expiratory volume in 1 second as the measure of lung function.
Although PEF is widely considered and used as an indirect index of airway
caliber,40 it might be a less sensitive measure
of lung function than are spirometric measures.40
However, the strong correlation between PEF and forced vital capacity and
forced expiratory volume in 1 second is well-known1, 40
and, as expected, reduced PEF in our study was associated with respiratory
manifestations and smoking habits. Recent international guidelines31, 41 support the use of PEF measurements
for clinical and epidemiological purposes. Furthermore, several studies1, 7 have reported an independent association
of PEF with cardiovascular disease and death.
Peak expiratory flow measurements were obtained by the Mini Wright peak
flowmeter, which is simple and easy to use in a population survey. We do not
think that the device used lost accuracy during the study period. No PEF measurement
drift was detected over time, and similar patterns of association of PEF with
carotid occurrence were observed according to examination periods. Most established
designs of portable PEF meters hold their calibration for longer than 3 years,42 and the Mini Wright PEF meters aged up to 14 years
can give readings that are as good as new meters.43
The reproducibility of the instantaneous measures of PEF was in agreement
with the results of other studies,40 and the
number of subjects with nonrepeatable measurements was low. Although the exclusion
of these subjects yielded similar findings to those reported in this article,
we preferred to present the results obtained from the whole population. In
fact, several studies44-45 have
shown that the application of rigid repeatability criteria for lung function
tests may bias epidemiological findings by the exclusion of subjects with
high risks of accelerated loss of lung function and mortality.
In accordance with other investigations,46-47
a definition of plaque as a localized protrusion
of the vessel wall into the lumen with a thickness of 1 mm or greater was
used in our protocol. One could argue that this value is relatively low and
that a minor wall irregularity may be mistakenly considered as a plaque. However,
the results of the reproducibility study, for the presence (or the absence)
of plaque, were satisfactory, and a reanalysis of our data using a more restrictive
definition of plaque thickness ( 1.5 mm) also showed a strong association
between baseline PEF and the occurrence of carotid plaques.
In conclusion, our results suggest that reduced lung function predicts
the 4-year occurrence of carotid atherosclerotic plaques in elderly subjects.
The nature of these associations remains unknown and merits further investigations.
The increasing prevalence of asthma and chronic obstructive pulmonary disease
worldwide48-49 should push further
attention of the possible relationship between the respiratory and cardiovascular
diseases. If lung function or its determinants were causally related to atherosclerosis,
our findings would provide new insight on the determinism of cardiovascular
risk in the population. Nevertheless, from a practical viewpoint, assessment
of lung function, which is simple and inexpensive, could help identify a population
at high risk of atherosclerosis development and CHD.
AUTHOR INFORMATION
Accepted for publication December 11, 2000.
The Etude sur le Vieillissement Artériel study is organized under
an agreement between the National Institute of Health and Medical Research,
Paris, France, and the Merck, Sharp and Dohme-Chibret Company, Paris, and
is supported by EISAI Company, Paris la Défense, France.
We thank C. Frette, PhD, for setting up the respiratory part of the
Etude sur le Vieillissement Artériel study; J. M. Fève, MD,
C. Leroux, MD, C. Magne, MD, and I. Ruelland, MD, for performing ultrasonography;
and F. Neukirch, MD, for critical reading and constructive comments during
preparation of the manuscript.
Corresponding author and reprints: Mahmoud Zureik, MD, PhD, Unit
of Cardiovascular and Metabolic Epidemiology, National Institute of Health
and Medical Research, Hôpital Paul Brousse, 16 av Paul Vaillant Couturier,
94807 Villejuif CEDEX, France (e-mail: zureik{at}vjf.inserm.fr).
From the Units of Cardiovascular and Metabolic Epidemiology (Drs Zureik
and Ducimetière and Ms Courbon) and Epidemiology and Biostatistics
(Dr Kauffmann), the National Institute of Health and Medical Research, Villejuif,
and the Centre de Diagnostic et de Prévention Neurovasculaire Paris
(Dr Touboul), France.
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