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(Circulation. 1997;96:1403-1407.)
© 1997 American Heart Association, Inc.
Articles |
Passive Cigarette Smoking and Reduced HDL Cholesterol Levels in Children With High-Risk Lipid Profiles
From the Division of Hematology (E.J.N.) and the Department of Cardiology (M.M.-S., A.L.B., J.W.N.), Children's Hospital, and the Department of Pediatrics, Harvard Medical School, Boston, Mass, and the Department of Epidemiology and Biostatistics, Boston (Mass) University School of Public Health (A.S.B.). Dr Mietus-Snyder is currently at the Gladstone Institute of Cardiovascular Disease, University of California, San Francisco.
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Abstract |
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Background HDL cholesterol levels are known to be lower in smokers than in nonsmokers. Previous studies have demonstrated an association of decreased HDL cholesterol with passive smoking in children but have not adjusted for potential confounding factors.
Methods and Results In a cross-sectional, pilot-scale study, we examined the relationship of HDL cholesterol levels to passive smoking in children and adolescents referred to a tertiary hyperlipidemia clinic. Eligibility criteria included (1) first visit to a lipid clinic, (2) LDL cholesterol >95th percentile for age or HDL cholesterol <5th percentile, (3) age between 2 and 18 years, and (4) absence of secondary causes of hyperlipidemia. Sociodemographic information, diet record, medical history, and fasting lipid profiles were obtained. Of 109 eligible patients, 103 (94%) were studied. Twenty-seven percent came from households with cigarette smokers. HDL cholesterol levels were 38.7±1.2 mg/dL (mean±SEM) in passive smokers versus 43.6±1.2 mg/dL in children without smoke exposure (P=.005). Smoking exposure was not significantly associated with other lipid values. The effect of smoking on HDL cholesterol was minimally affected by potential confounders. In multivariate regression adjusting for body mass index, age, sex, exercise, and dietary fat intake, passive smoking remained a significant risk factor for decreased HDL cholesterol (P=.012).
Conclusions Mean HDL cholesterol levels are lower in dyslipidemic children from households with smokers than in those without household smoke exposure. Passive smoking may worsen the risk profile for later atherosclerosis among high-risk young persons.
Key Words: cholesterol • hyperlipoproteinemia • smoking
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Introduction |
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Exposure to environmental tobacco smoke, or "passive smoking," has been shown to have important medical consequences in adults and children, including increased risk of cancer and respiratory disease.1 2 3 Active smoking is associated with reduced HDL cholesterol levels in adults4 5 and young persons.6 In adults, passive smoking has been reported to have a similar effect.7 Previous studies in children and adolescents have documented a relationship between lower HDL cholesterol levels and passive smoking8 9 but have not adjusted for potential confounding factors, such as diet, obesity, or sociodemographic factors. No studies of passive smoking in childhood have examined subjects at high risk for future cardiovascular disease.
The purpose of our cross-sectional study was to examine the relationship of HDL cholesterol levels to passive smoking in children with abnormal lipid profiles. Our study population was composed of children and adolescents newly referred to a tertiary hyperlipidemia clinic. Most patients had a positive family history of early heart disease, and approximately one third came from households with smokers. We recorded factors that were potentially associated with low HDL cholesterol levels, including sociodemographic variables, dietary intake, exercise, and fasting lipid profiles.
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Methods |
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Subjects
Subjects were drawn from among 161 new patients referred to the lipid program at Children's Hospital, Boston, over an 18-month period. Entry criteria for the study included (1) first visit to a lipid clinic, (2) dyslipidemia (LDL cholesterol >95th percentile for age or HDL cholesterol <5th percentile for age), (3) age between 2 and 18 years, (4) absence of secondary causes of hyperlipidemia or medications that might affect the lipid profile, and (5) informed consent of parents. The study was approved by the Committee on Clinical Investigation at Children's Hospital.
Study Design
This was a cross-sectional study of children and
adolescents referred for hyperlipidemia. Before the
first lipid clinic visit, we mailed a survey of demographic information
and 3-day diet record to families of referred patients. Upon
arrival at the clinic, a fund-of-knowledge questionnaire and a survey
of attitudes about lipid disorders and therapy were administered. A
nutritionist reviewed dietary records with families, and the
physician's evaluation included a medical history and physical
examination. Subjects and their families were asked to estimate the
number of hours of television that the child watched daily and the
number of hours of aerobic exercise performed weekly (giving examples
of sports, cycling, walking, running around, etc).
Assessment of Smoking Status
Each subject was asked if he or she smoked cigarettes; all
denied active smoking. Adolescent patients (
13 years old) were
questioned about smoking in confidence, with their parents out of the
room. We classified subjects as passive smokers if they lived in a
household in which at least one individual smoked. This information was
obtained at the initial visit. To further quantify passive smoke
exposure, we conducted a telephone survey after the initial clinic
visit. We asked parents to describe the number of smokers in the
household, the number of packs per day smoked by each smoker, and the
approximate number of hours per week that each smoker was in the
household with the patient. From these data, we estimated the total
number of packs per day to which each patient was exposed. These
estimates were inexact because of variation in such factors as the
percentage of time children spent in the homes of divorced parents, the
packs per day smoked by household members, and the time the child spent
outside the home. As a result, we dichotomized the passive smoking
group into children whose passive smoke exposure was 1 pack/d and
those exposed to <1 pack/d.
During this retrospective follow-up, we discovered one subject, classified as coming from a nonsmoking home, whose mother was a smoker. She never smoked in the home, did not want her children to know she smoked, and so deliberately misanswered the question regarding smokers in the household. Because she did not smoke at home, we continued to classify this child as coming from a nonsmoking household, although the relationship between passive smoking and HDL cholesterol was significant whether he was included or excluded.
Diet Assessment
The Minnesota Nutrition Evaluation System (Nutrition
Coordinating Center, University of Minnesota, Minneapolis) was used to
quantify fat and cholesterol intake. Diet record review
and diet histories were obtained from the parents and children together
(regardless of patient age) by the lipid clinic nutritionist. The RISCC
score10 11 (ratio of ingested saturated fat and
cholesterol to ingested calories) was calculated by the
formula [1.01xsaturated fat intake (g)±0.05xcholesterol
intake (mg)]/ingested kcal/1000.
Assessment of Obesity
Weight and height were measured with shoes removed, with a
single clinical balance and scale. Body mass index was calculated as
weight (kg)/[height (m)]2.
Quantification of Exercise and Television Viewing
Families were asked by the physician to estimate the number of
hours of aerobic exercise per week and the amount of television viewing
per day. This information was gained in the examination room with
parents present.
Survey of Attitudes and Fund-of-Knowledge Questionnaire
Three questions were used to probe attitudes about therapy for
lipid disorders (Table 1
). The score on each question
ranged from 1 to 5, with 5 being the most positive. Analyses
involving attitude were performed on the summary score of these three
questions. Similarly, seven true-false questions (Table 1) were used to
explore fund of knowledge, with a score range of zero to seven
questions correct. Questionnaires were self-administered to parents,
regardless of the age of the subjects. The questions were designed in
our clinic for use in this study and were not validated in other
settings.
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Lipid Measurement
Serum samples were obtained on the morning of the clinic visit
after a 12-hour fast. Triglyceride and total
cholesterol levels were determined with an Ektachem
analyzer by slide enzymatic methods. HDL
cholesterol was measured after precipitation of LDL
cholesterol and VLDL cholesterol with dextran
sulfate. LDL cholesterol was estimated by the method of
Friedewald et al.12 The instrument was calibrated daily
with Kodak standards. Our institution's laboratory participates in the
Centers for Disease Control/National Heart, Lung, and Blood
Institute lipid certification program.
Statistical Methods
We used two-sided t tests to compare continuous
variables. 
2 tests were used to compare
categorical variables. We used ANCOVA to compare mean HDL levels in
nonsmokers and passive smokers, adjusting for potential confounders
including demographic characteristics, dietary intake, and other lipid
variables. We estimated the effect of passive smoking on HDL,
adjusting for each potential confounder separately and then adjusting
simultaneously for those potential confounders known to
affect HDL levels. ANCOVA with interaction terms was used to
investigate effect modification by potential confounders. None of the
variables examined were statistically significant effect modifiers,
but the small number of patients limited our power to detect
significant effects. Results were considered statistically significant
at a value of P<.05.
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Results |
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Among 161 patients referred to our lipid clinic, 109 met the entry criteria and 103 (94%) were enrolled. Of the remaining 6 children, 1 was excluded post hoc because he had homozygous familial hypercholesterolemia and extreme outlying lipid values. Families of the other 5 eligible children declined participation. Twenty-eight of the ineligible patients had normal LDL cholesterol (<95th percentile) at the time of evaluation. None of the patients evaluated during this period had HDL <5th percentile and normal LDL cholesterol. Patient characteristics are shown in Table 2
. Twenty-eight
subjects (27%) came from households with smokers, constituting the
passive smoking group. Children classified as nonsmokers and those
classified as passive smokers did not differ significantly in mean age,
race, proportion of boys (Table 2), or proportion of adolescents (19%
versus 24%, respectively, were >12 years old). More than 70% of
patients in each group had a family history of premature heart disease,
and nearly all patients had a family history of
hypercholesterolemia, reflecting the initial
reasons for evaluation of cholesterol in childhood and
referral to a lipid clinic in particular.
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Mothers of children in the nonsmoking households, compared with those
in smoking households, had more education, with a greater percentage
achieving a graduate degree (24% versus 4%, respectively) and fewer
having only a high-school education (12% versus 36%, respectively;
Table 2
). Although these difference did not achieve statistical
significance in our small sample, this trend is consistent with
the greater preponderance of smokers among persons of lower
socioeconomic and education status.
Children in the nonsmoking and passive smoking groups did not differ
significantly in dietary fat intake, degree of obesity, self-reported
hours of exercise and television, maternal education, or fund of
knowledge/attitudes (Table 2). The groups ingested a similar number of
calories for body weight. Subjects in both nonsmoking and passive
smoking groups were generally on low-fat diets at the time of their
presentation to the lipid clinic. Mean fat intake in each
group was <28% of total calories, and mean saturated fat intake,
<10% of total calories. The ratio of ingested saturated fat and
cholesterol to calories was also similar in nonsmokers and
passive smokers (14.9±0.5 versus 14.6±1.0, respectively). The
majority of subjects in each group reported >7 hours of aerobic
exercise weekly and <3 hours of television daily.
Lipid Profiles
Mean serum HDL cholesterol levels were significantly
lower among passive smokers than among children without smoke exposure
(38.7±1.2 versus 43.6±1.2 mg/dL, P=.005) (Table 3). For both groups, these values were lower than the
expected population mean for age (ranging from 54 to 57 mg/dL
before puberty, with values in boys dropping to a mean of 47
mg/dL during adolescence). In contrast, mean levels of LDL
cholesterol and triglycerides were similar in
the two groups. Mean LDL cholesterol levels were >160
mg/dL in each group, with the expected population 95th
percentile during childhood and adolescence ranging from 133 to 136
mg/dL in boys and 140 to 144 mg/dL in
girls.13 Mean triglyceride levels were
borderline elevated, without significant difference between the
nonsmoking and passive smoking groups.
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We explored whether HDL cholesterol was related to the estimated intensity of smoke exposure ascertained in a retrospective telephone survey. Estimates were possible in 24 of the 28 patients who reported exposure. When patients were classified into groups exposed to at least 1 pack/d (n=10), exposed to <1 pack/d (n=14), or not exposed (n=75), the relationship between smoking dose and HDL cholesterol did not reach statistical significance (ANOVA, P=.07). However, the small number of patients in the smoking subgroups and the inexact quantification of smoke exposure that could be obtained from a retrospective survey provided insufficient statistical power to exclude such a relationship.
Relation of HDL Cholesterol to Other Variables
We explored the correlation of HDL cholesterol level
to variables other than smoking status. As expected, levels were
inversely related to body mass index (r=-.21,
P=.034) and plasma triglyceride level
(r=-.46, P<.001). Higher HDL
cholesterol levels also were associated with greater
dietary fat intake, assessed either as RISCC score (r=.19,
P=.055), total fat intake as a fraction of total calories
(r=.21, P=.032), or percentage of calories as
saturated fat (r=.21, P=.037). The HDL
cholesterol levels of the subjects were not significantly
associated with sex, race, level of parental education, self-reported
amount of exercise and time spent watching television, or measures of
fund of knowledge or attitude. There was not sufficient statistical
power to determine the effect of smoking according to the sex of the
member of the household who smoked.
Exclusion of Confounding
We explored whether the effect of passive smoking on HDL
cholesterol could be explained by potential confounders,
including other lipid values (eg, triglyceride levels),
dietary factors, fund of knowledge, hours of aerobic exercise, measures
of obesity, or sociodemographic variables, including maternal
education. Household cigarette smoking was not significantly associated
with any of these variables. Passive smoking remained a
statistically significant predictor of HDL cholesterol
level when we adjusted individually for each potential confounding
variable. Furthermore, the effect estimates for difference in HDL
cholesterol levels between nonsmoking and passive smoking
children were minimally affected by adjustment for confounders (Table 4). Children in nonsmoking versus smoking households had
a mean difference in serum HDL cholesterol levels of 4.9
mg/dL when unadjusted, of 4.7 mg/dL when adjusted for
dietary fat expressed as percent of calories, and of 4.1 mg/dL
when adjusted for serum triglyceride level. In
multivariate regression adjusting
simultaneously for body mass index, age, sex, RISCC score,
triglyceride level, hours of self-reported exercise, and
percent dietary fat, passive smoking remained a significant factor for
decreased HDL cholesterol (adjusted mean difference in HDL
cholesterol, 3.7 mg/dL, P=.012).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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We have found that mean HDL cholesterol levels were significantly lower in hyperlipidemic children who came from households with smokers compared with those from nonsmoking households. The effect of passive smoking in the present study was not attributable to demographic characteristics of the smoking households, the knowledge about lipids or attitudes of the parents, or physiological factors including age, body mass index, exercise, diet, or serum triglyceride levels. To the best of our knowledge, this is the first report of the effect of passive smoking in children with significant dyslipidemia and family history of early heart disease. Such children constitute a group of particular importance, because currently available data suggest that their long-term risk will be greater than that of the general population.
Two previous reports examined the relation between passive cigarette
smoke exposure and HDL cholesterol levels in children and
adolescents. Moskowitz et al8 studied 216 pairs of twins
as part of the Medical College of Virginia twin study. One hundred five
pairs of twins had at least one smoking parent. In these
normocholesterolemic children, HDL
cholesterol and the HDL2 subfraction were
significantly lower in children exposed to passive cigarette smoke. The
effect of passive smoking on HDL2 was significant only in
boys and was related to thiocyanate levels. Feldman et al9
studied 391 teenagers. They found that HDL cholesterol
levels were a mean of 6.8% lower in teens with plasma cotinine levels
2.5 mg/mL compared with those with lower cotinine levels. Our
study differs from these previous reports in several important regards.
First, the population studied is at greater risk of early heart
disease, on the basis of family history of premature
atherosclerosis and lipid profile abnormalities.
Second, the subjects in our study are younger by several years than the
high school students studied by Feldman et al; the great majority were
too young to have been smokers themselves. Children of smokers are more
likely to smoke themselves, and false denial of personal cigarette use
by adolescents during a physician visit would greatly confuse
interpretation of the role of passive smoke. Most importantly, the
design of the present study allowed us to exclude confounding
factors such as dietary fat intake, reported exercise, obesity, and
triglyceride levels in the effect of smoking on HDL
cholesterol. The present study extends those of
Moskowitz8 and Feldman9 and suggests that a
trial of active smoking cessation counseling for lipid clinic family
members could be an important therapeutic intervention. Smoking
cessation is an effective means of increasing HDL
cholesterol in adults.14 15 16 It is interesting
to compare the present results with those of a large study of
passive smoking exposure in Chinese adults, in which passive smokers
had lipid abnormalities approximating those of light
smokers.7
Interpretation of these data is constrained by a few limitations. We did not use pharmacological tests of smoking exposure such as thiocyanate or cotinine levels or perform HDL subclass analyses. The small number of patients analyzed precludes potentially interesting analyses of subgroups, including analysis of the relationship of passive smoking dose (assessed by parental reports of smoking) to HDL cholesterol levels. We studied a restricted population with abnormal lipid profiles, and no subjects had pure low HDL phenotypes. Therefore, one cannot necessarily generalize these conclusions to the population at large. Nevertheless, there are nearly 3 million American children and adolescents in the age range studied with LDL cholesterol levels >95th percentile for age and who would be expected to be at the highest risk from lowered levels of HDL cholesterol. Finally, it should be noted that our study design did not permit us to prove that cessation of smoke exposure in our passive smokers would increase HDL cholesterol to levels in controls.
In summary, the present data demonstrate that HDL cholesterol levels are lower in dyslipidemic children with a history of exposure to cigarette smoke in the household than in children not exposed to cigarette smoke at home. The magnitude of the potential improvement (11.2%) for HDL cholesterol with cessation of smoke exposure is as great as that observed for almost any other intervention. Whereas intensive individual dietary intervention has been shown in the multisite DISC Study to lower LDL cholesterol in moderately hyperlipidemic school-age children,17 this type of intervention did not improve the HDL cholesterol.17 Adjustment for potential confounders, including dietary fat intake, serum triglyceride level, and exercise, only minimally changed the magnitude of difference in HDL cholesterol between passive smokers and nonsmokers. The results of this small-scale study suggest that interventions resulting in decreased cigarette exposure may substantially increase HDL cholesterol levels in this group of patients at higher risk for premature cardiovascular disease. This hypothesis should be the focus of future investigations.
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Acknowledgments |
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This work was supported in part by Grant-in-Aid 13-515-901 from the American Heart Association, Massachusetts Affiliate (Dr Mietus-Snyder) and by the Kobren Fund. Dr Neufeld is a fellow of the Lucille P. Markey Foundation. We gratefully acknowledge the assistance of Isabel Vasquez, RD, in performing the diet analyses.
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Footnotes |
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Reprint requests to Dr Ellis J. Neufeld, Division of Hematology, Children's Hospital, 300 Longwood Ave, Boston, MA 02115.
Received March 5, 1997; revision received April 24, 1997; accepted April 27, 1997.
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