Children of parents who smoke have increased risk of developing carotid atherosclerotic plaque in adulthood. However, parents who exercise good smoking hygiene can lessen their child’s risk of developing plaque.

Participants were from the Cardiovascular Risk in Young Finns Study (n=2448). Information on childhood exposure to parental smoking was collected in 1980 and 1983. Carotid ultrasound data were collected in adulthood in 2001 or 2007. Childhood serum cotinine levels from 1980 were measured from frozen samples in 2014 (n=1578). The proportion of children with nondetectable cotinine levels was highest among households in which neither parent smoked (84%), was decreased in households in which 1 parent smoked (62%), and was lowest among households in which both parents smoked (43%). Regardless of adjustment for potential confounding and mediating variables, the relative risk of developing carotid plaque in adulthood increased among those children with 1 or both parents who smoked (relative risk, 1.7; 95% confidence interval, 1.0–2.8; P =0.04). Although children whose parents exercised good “smoking hygiene” (smoking parents whose children had nondetectable cotinine levels) had increased risk of carotid plaque compared with children with nonsmoking parents (relative risk, 1.6; 95% confidence interval, 0.6–4.0; P =0.34), children of smoking parents with poor smoking hygiene (smoking parents whose children had detectable serum cotinine levels) had substantially increased risk of plaque as adults (relative risk, 4.0; 95% confidence interval, 1.7–9.8; P =0.002).

The association between passive smoking exposure in childhood and adverse cardiovascular health in adulthood is not well understood. Using a 26-year follow-up study, we examined whether childhood exposure to passive smoking was associated with carotid atherosclerotic plaque in young adults.

Introduction

Children exposed to environmental tobacco smoke (passive smoke) have a poorer cardiovascular health profile.1 Recently, we demonstrated that exposure to parental smoking in childhood was associated with lower endothelium-dependent flow-mediated dilatation2 and higher carotid intima-media thickness3 in adulthood. Although these data indicate a detrimental effect of passive smoking in childhood persisting to adult markers of atherosclerosis, it has not been quantified whether parents who smoke can nevertheless reduce any associated increased risk by exercising good “smoking hygiene” (ie, not smoking in the vicinity of the child). To gain more insight into the long-term harms of passive smoke exposure in early life, we undertook the first investigation of whether parental smoking and smoking hygiene in childhood are related to the presence of carotid atherosclerotic plaque in adulthood. We report results using data from the Cardiovascular Risk in Young Finns Study and thus exploit its design as a long-standing cohort of >20 years, the availability of parental self-reports, extensive data available on potential confounding and mediating factors that have been collected since childhood, and our recent measurement of an objective biomarker of exposure, serum cotinine, from frozen serum samples stored since childhood.

Editorial see p 1231

Clinical Perspective on p 1246

Methods

Participants

The Cardiovascular Risk in Young Finns Study, conducted across 5 university cities with medical schools in Finland (Helsinki, Kuopio, Oulu, Tampere, and Turku), is a prospective study beginning in childhood initiated to examine the early-life risk factors of cardiovascular disease.4 Baseline measurements in 1980 were collected on 3596 participants 3, 6, 9, 12, 15, or 18 years of age, and of these, 2991 attended the 3-year follow-up performed in 1983. As part of a comprehensive battery of measurements, questionnaires on exposure to parental smoking were collected at both the 1980 and 1983 surveys, and B-mode ultrasound of the carotid artery was collected at the 21- and 27-year follow-ups performed in 2001 and 2007. For this study, analyses of the association between exposure to parental smoking in childhood from the 1980 and 1983 data and adult carotid plaque collected in either 2001 or 2007 included up to 2448 participants (68% of those eligible from baseline). Of these, serum cotinine levels in 1980 were available for a subset of 1578 participants. Informed consent was provided by participants or their parents. The study was conducted according to the guidelines of the Declaration of Helsinki and received local ethics committee approval.

Measures

Exposure: Parental Smoking, Serum Cotinine, and Smoking Hygiene

Parental Smoking

Parents of participants self-reported their smoking habits in 1980 and 1983. At both time points, 1 parent responding on behalf of both parents was asked to indicate the smoking status of the mother and father separately in the household from 2 questions. The first question asked whether the mother/father had ever smoked daily for at least 1 year (responses could be “yes” or “no”), and the second question asked whether the mother/father was currently smoking (responses could be “does not smoke,” “occasionally,” or “daily”). Mothers or fathers who indicated they had ever smoked daily for at least 1 year in either 1980 or 1983 were designated as ever smokers. Mothers or fathers who indicated they currently occasionally or daily smoked in either 1980 or 1983 were designated as current smokers. For both current and ever smoking variables, families were then classified into “none” or “1 or 2 parents smoking.”

Serum Cotinine

Child fasting serum samples were collected in 1980 and stored at −20°C until they were analyzed in 2014. During storage, samples were not thawed or refrozen. Serum cotinine measures were made using standardized methods that we have previously detailed.5 Briefly, serum cotinine was extracted into dichloroethane by the method of Feyerabend and Russell6 with the concentrated extract measured by means of gas-liquid chromatography, with levels as low as 0.16 ng/mL detectable.

Parental Smoking Hygiene

A variable to indicate parental smoking hygiene was generated for those participants with both serum cotinine and parental reports of current or ever smoking in 1980 (n=1578). A 3-level categorical variable was constructed: 1=no parental smoking; 2=children with a zero (nondetectable) cotinine level but whose parents smoked (hygienic parental smoking); and 3=children with a detectable serum cotinine level >0 and <3 ng/mL and whose parents smoked (nonhygienic parental smoking). We used the cut point for serum cotinine of <3 ng/mL to indicate passive smoke exposure, given that values above this level among children are indicative of active smoking.7 Thus, those with a serum cotinine level ≥3 ng/mL were not included (n=248). Approximately 10% of those with nonsmoking parents had detectable serum cotinine levels; removal of these participants did not substantially change the results shown.

Potential Confounders

Potential confounders included child and adult body mass index (BMI), own smoking status, and markers of socioeconomic status (parental education and occupation, family income), as well as childhood measures of physical activity and fruit and vegetable consumption.

Anthropometric Measures

At both baseline and follow-up, weight was measured in light clothes without shoes with a digital Seca weighing scale to the nearest 0.1 kg. Height was measured by a wall-mounted Seca stadiometer to the nearest 0.5 cm. BMI was calculated as weight in kilograms divided by height in meters squared.

Questionnaire Measures

At baseline and the 1983 follow-up, parents of participants self-reported their own total years of schooling, family income, and occupation, as well as total fruit and vegetable consumption of their children. Participants ≥12 years of age at baseline and the 1983 follow-up reported their own smoking status without their parents present. To maximize the sample size for our analyses with available data, those 3 to 9 years of age were presumed to be nonsmokers. At baseline and the 1983 follow-up, an index of physical activity was calculated using inputs of duration, intensity, and frequency of self-reported physical activity from 9 to 18 years of age, as previously detailed in full.8 At the 2001 and 2007 follow-ups, participants reported their total years of schooling and their current smoking status.

Potential Mediators

Potential mediators included child and adult blood pressures, fasting lipids, and high-sensitivity C-reactive protein (hs-CRP).

Blood Pressure

Brachial artery blood pressure was measured at baseline and the 1983 follow-up with the use of a standard mercury sphygmomanometer in those ≥6 years of age. For those 3 years of age in 1980, blood pressure was measured with an ultrasound device (Arteriosonde 1020, Roche). For the adult follow-ups, blood pressure was measured with a random-zero sphygmomanometer. All measurements were taken on the right arm after the participant had been seated for 5 minutes. Readings to the nearest even number of millimeters of mercury were performed at least 3 times on each participant, with the mean of these 3 measurements used to denote blood pressure values.

Blood Biochemistry

At baseline and each follow-up, measurements of lipid levels were performed in duplicate in the same laboratory. Standard enzymatic methods were used for measuring levels of serum total cholesterol, triglycerides, and high-density lipoprotein cholesterol. If determination methods and kits changed during the course of the study, values were corrected to 2001 levels.9,10 Low-density lipoprotein cholesterol was estimated with the Friedewald equation.11 Childhood hs-CRP levels in 1980 were assayed from stored serum samples that were analyzed in 2005, with values shown to be stable despite storage.12 The 1980, 2001, and 2007 hs-CRP levels were determined on an automated Olympus AU400 analyzer using a turbidimetric immunoassay kit (1980 and 2001, CRP-UL reagent; 2007, CRP Latex reagent).

Outcome: Carotid Atherosclerotic Lesion

In 2001 and 2007, B-mode ultrasound studies of the left carotid artery were performed with Sequoia 512 ultrasound mainframes (Acuson) with 13.0-MHz linear-array transducers according to a standardized protocol.13 Digitally stored scans from both time points were analyzed by a single reader blinded to participant details. The best-quality end-diastolic frame was selected, and ultrasonic calipers were used to measure carotid intima-media thickness from the far wall of the common carotid artery ≈10 mm proximal to the bifurcation that included the carotid bulb. Evidence for carotid plaque in these images was scanned by the reader, with the presence of atherosclerotic plaque defined as a distinct area of the carotid vessel wall protruding into the lumen >50% of the adjacent intima-media layer.14 All plaques were observed in the carotid bulb.

Statistical Analyses

Statistical analyses were performed with STATA version 10 (StataCorp, College Station, TX). Baseline characteristics are displayed by plaque status in adulthood, with continuous variables presented as mean (SD) or, if skewed distributions, as median (25th and 75th percentiles) and categorical variables as proportions.

Assessment of the Relation Between Parental and Own Self-Reports of Smoking Status With Serum Cotinine Levels

To provide biological validation of the questionnaire data on parental smoking as a proxy for passive smoke exposure, we compared parental responses of current and ever smoking status in 1980 with the offspring’s serum cotinine level from 1980. We display basic descriptive statistics for cotinine levels according to self-reports of the mother, father, and parental ever and current smoking status, as well as the child’s own smoking status. Because serum cotinine levels were substantially right skewed with ≈70% of our cohort having a nondetectable or zero cotinine level, we used zero-inflated Poisson regression to examine the association between the self-report data with offspring serum cotinine. For all analyses of the parental smoking variables, we restricted our sample to those participants whose serum cotinine was <3 ng/mL, given that values above this level among children are indicative of active smoking.7 Finally, we report the diagnostic statistics of sensitivity, specificity, positive predictive value, and negative predictive value to assess the ability of the self-report data to predict offspring with cotinine levels >0 to <3 ng/mL in the case of parental smoking and cotinine levels ≥3 ng/mL in the case of active smoking. Sensitivity was calculated as follows: true positives/(true positives+false negatives); specificity, true negatives/(true negatives+false positives); positive predictive value, true positives/(true positives+false positives); and negative predictive value, true negatives/(true negatives+false negatives).

Risk of Adult Carotid Plaque in Offspring According to Parental Smoking

Poisson regression with robust standard errors was used to estimate the relative risk and 95% confidence intervals (CIs) of having a carotid atherosclerotic lesion in adulthood (treated as a dichotomy where 0=no lesion present and 1=lesion present) as a factor of exposure to ≥1 parents ever smoking (no versus yes) and to ≥1 parents currently smoking (no versus occasional or daily). A series of multivariable models were examined that progressed from the inclusion of potential confounding variables (models 1–3) through to possible intermediates (models 4 and 5). Multivariable models are presented adjusted for age, sex, and duration of follow-up (model 1); model 1 plus childhood covariates of parental education, BMI, smoking, and fruit and vegetable intake (model 2); model 2 plus adult covariates of education and smoking status (model 3); model 3 plus child cardiovascular risk factors of systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides (model 4); and model 4 plus adult cardiovascular risk factors of systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides (model 5). We also report these associations for mother and father, ever and current smoking separately. We found no evidence of interaction between exposure to parental smoking and sex or age of children in these analyses.

Risk of Adult Plaque In Offspring According to Parental Smoking Hygiene

To estimate the relative risk and 95% CIs of having a carotid atherosclerotic lesion in adulthood as a factor of parental smoking hygiene, we again used Poisson regression with robust standard errors. Effects were estimated for mother, father, and parental smoking hygiene. For these analyses, we used the multivariable model equivalent to model 3 for the above analyses that adjusted for what we considered to be the major potential confounding factors (age, sex, duration of follow-up, childhood covariates of parental education, BMI, smoking, fruit and vegetable intake, and adult covariates of education and smoking status). A test of linear trend was performed by including the 3-level parental smoking variable to the model unexpanded but ordered according to increasing exposure. We found no evidence of significant interaction between exposure to parental smoking and sex or age in these analyses.

Sensitivity Analyses

Sensitivity analyses were conducted by including additional covariates that resulted in reduced sample sizes: childhood physical activity index (available only for those 9–18 years of age), child (1980) and adult hs-CRP (hs-CRP was not measured in 1983, and approximately one fifth of the sample had missing values from 1980), and other markers of childhood socioeconomic status (family income and highest parental occupation), in addition to parental years of education.

Results

Baseline characteristics of participants are shown in Table 1. Carotid plaque was present in 65 participants (2.6%) and always occurred in the carotid bulb. The mean (SD) age of participants at follow-up was 36.6 years (5.5 years), and the length of follow-up was 26.0 years (2.2 years).

Table 1. Baseline Characteristics of Participants in the Cardiovascular Risk in Young Finns Study According to Presence of Carotid Artery Plaque in Adulthood Presence of Carotid Plaque No Yes n 2,384 64 Male sex, % 45 65 Age, y 10.4 (5.0) 13.6 (4.0) Parental school years* 10 (8,13) 9 (8,10) Family income (below average/average/above average), % 26/51/23 33/51/16 Parental occupation (nonmanual/manual/farmer), %* 60/27/13 52/41/8 Smoking prevalence (n=1155), %† 12 18 BMI, kg/m2 17.8 (3.1) 19.1 (2.8) Systolic blood pressure, mm Hg 112 (12) 118 (12) Diastolic blood pressure, mm Hg 73 (11) 76 (10) HDL cholesterol, mmol/L 1.56 (0.30) 1.52 (0.31) LDL cholesterol, mmol/L 3.44 (0.81) 3.52 (0.84) Triglycerides, mmol/L 0.59 (0.45, 0.79) 0.66 (0.53, 0.93) hs-CRP, mg/L 0.22 (0.11, 0.56) 0.24 (0.11, 0.74) Fruit consumption, frequency/wk 6.3 (6.3, 9.5) 6.3 (3.0, 9.5) Vegetable consumption, frequency/wk 6.3 (3.0, 9.5) 6.3 (3.0, 6.3) Physical activity index (n=2008)‡ 9 (8, 10) 9 (8, 10)

Assessment of the Relation Between Parental and Own Self-Reports of Smoking Status With Serum Cotinine Levels

The association between reports of parental smoking and the participant’s own smoking status with serum cotinine levels in participant offspring is presented in Table I in the online-only Data Supplement. As the level of reported parental smoking increased, the mean and 90th percentile for cotinine levels in the child offspring also increased. Moreover, the proportion of children with nondetectable (zero) cotinine levels was highest among households in which no parent smoked and lowest among households in which both parents smoked. Our modeling showed that participants were significantly less likely to have a serum cotinine level of 0 ng/mL as the level of reported parental smoking increased. Similar findings were observed for participant self-reports of their own smoking status. Sensitivity, specificity, positive predictive value, and negative predictive value of parental self-reports of smoking and participant’s own smoking status for the prediction of serum cotinine levels in child offspring are shown in Table II in the online-only Data Supplement. The best predictive utility of cotinine levels >0 and <3 ng/mL (indicative of passive smoke exposure) was observed for parental current smoking (≥1 parent). The specificity, positive predictive value, and negative predictive value for predicting serum cotinine levels ≥3 ng/mL from self-report of the participant’s own smoking status was high, but the sensitivity was somewhat lower.

Risk of Adult Plaque in Offspring According to Parental Smoking

Table 2 shows the association between ever and current parental smoking and risk of plaque in adulthood. Exposure to parental smoking in childhood was associated with increased risk of carotid plaque in adulthood, regardless of adjustment for potential confounding or mediating factors. Tables III and IV in the online-only Data Supplement display the equivalent models for maternal and paternal smoking status separately. In the fully adjusted model (model 5, Table III in the online-only Data Supplement), exposure to ever maternal smoking in childhood led to a relative risk of developing carotid plaque of 1.7 (95% CI, 1.0–2.8), whereas ever paternal smoking exposure led to a relative risk of developing carotid plaque of 1.8 (95% CI, 0.9–3.5). In the fully adjusted model (model 5, Table IV in the online-only Data Supplement), exposure to current maternal smoking in childhood led to a relative risk of developing carotid plaque of 1.7 (95% CI, 1.0–3.0), whereas current paternal smoking exposure led to a relative risk of developing carotid plaque of 1.3 (95% CI, 0.7–2.2). When serum cotinine was examined as a dichotomy (nondetectable versus detectable) in the subset with this and all covariates available (n=1330), the relative risk of developing carotid plaque was 2.0 (95% CI, 0.9–4.2; P=0.08).

Table 2. Relative Risk and 95% CI of Carotid Plaque Among Adult Offspring by Parental Reports of Ever and Current Smoking in the Offspring’s Childhood* Ever Parental Smoking(None vs 1 or Both) Current† Parental Smoking(None vs 1 or Both) Model RR 95% CI P Value RR 95% CI P Value 1, Age, sex, duration of follow-up 2.4 1.2–4.9 0.01 1.7 1.1–2.9 0.03 2, Model 1 plus childhood parental school years, childhood smoking,‡ child BMI, child fruit and vegetable consumption 2.4 1.2–4.8 0.01 1.7 1.0–2.8 0.04 3, Model 2 plus own adult study years, own adult smoking 2.3 1.2–4.7 0.02 1.6 1.0–2.7 0.05 4, Model 3 plus child systolic BP, child HDL-C, child LDL-C, child triglycerides 2.5 1.2–5.1 0.01 1.7 1.0–2.8 0.04 5, Model 4 plus adult BMI, adult systolic BP, adult HDL-C, adult LDL-C, adult triglycerides 2.6 1.3–5.3 0.007 1.7 1.0–2.8 0.04

Risk of Adult Plaque in Offspring According to Parental Smoking Hygiene

Table 3 shows the association between parental smoking hygiene and risk of plaque in adulthood. Children whose parents smoked nonhygienically had a significantly increased risk of developing carotid plaque in adulthood compared with those whose parents did not smoke. Children with parents who had good smoking hygiene had a 60% to 90% increased risk of developing carotid plaque in adulthood, but CIs were wide and included 1. Although we found no evidence of a statistically significant interaction by age, we note that the effect of unhygienic smoking among those 3 to 9 years of age was stronger than the effect observed for those 12 to 18 years of age (relative risk, 6.3 [95% CI, 0.8–47.7] versus 3.5 [95% CI, 1.3–9.6]). The numbers with carotid plaque for these age-stratified analyses were low, with 7 and 22 cases for the younger and older age groups. When maternal smoking was separated from paternal smoking, children whose mothers or fathers smoked hygienically had a higher risk of a carotid plaque in adulthood compared with those with nonsmoking parents, but the increased risk was not statistically significant. However, exposure to nonhygienic maternal smoking in childhood showed a significantly increased risk of developing carotid plaque in adulthood. The effect for paternal smoking tended to be weaker than for maternal smoking but remained marginally significant.

Table 3. Relative Risk and 95% CI of Carotid Plaque Among Adult Offspring by Parental Smoking Hygiene in the Offspring’s Childhood* Mother Smoking Father Smoking Parental Smoking Exposure RR 95% CI P Value RR 95% CI P Value RR 95% CI P Value Ever smoking Never a smoker 1.0 Referent Referent 1.0 Referent Referent 1.0 Referent Referent Hygienic parental smoking† 1.3 0.5–3.5 0.56 1.6 0.6–4.5 0.36 1.9 0.6–5.7 0.25 Nonhygienic parental smoking‡ 3.4 1.3–8.8 0.01 2.9 0.9–9.3 0.07 4.1 1.3–12.9 0.02 P for trend 0.03 0.07 0.01 Current smoking Not a smoker 1.0 Referent Referent 1.0 Referent Referent 1.0 Referent Referent Hygienic parental smoking† 1.4 0.4–4.4 0.59 1.6 0.6–4.2 0.29 1.6 0.6–4.0 0.34 Nonhygienic parental smoking‡ 5.2 2.2–12.1 <0.001 2.7 1.0–7.7 0.06 4.0 1.7–9.8 0.002 P for trend 0.009 0.09 0.03

Sensitivity Analyses

Inclusion of child physical activity for those with physical activity data in childhood (those ≥9 years of age) did not appreciably modify the results, with the effect estimates for parental smoking changing by no more than 1% for model 5 shown in Table 2 and for the smoking hygiene analyses. With adjustment for other markers of childhood socioeconomic status (family income and highest parental occupation), the coefficients were reduced by up to 4%, with current parental smoking becoming marginal (P=0.07) in model 5 in Table 2, but ever smoking and smoking hygiene remained statistically significant. Adjustment for hs-CRP in childhood and adulthood increased the coefficient for parental smoking and smoking hygiene by up to 4% and remained statistically significant.

Because approximately one third of our sample had missing cotinine values, we undertook a sensitivity analysis that imputed serum cotinine for those with missing values using age, sex, parental smoking status, parental education, child smoking status, and child BMI as informing variables. Using the imputed cotinine values in models equivalent to those shown in Table 3, we found the estimates to be similar but the CIs somewhat narrower. For example, the relative risks using the imputed data were 1.6 (95% CI, 0.6–4.0) for hygienic and 3.1 (95% CI, 1.1–8.5) for nonhygienic ever parental smoking, 1.5 (95% CI, 0.7–3.2) for hygienic current smoking, and 3.4 (95% CI, 1.5–7.8) for nonhygienic current smoking.

Discussion

Offspring exposed to parental smoking in childhood had approximately twice the risk of having a carotid atherosclerotic plaque in adulthood than did those with nonsmoking parents. However, among offspring of parents who smoked and had a detectable serum cotinine level, which was indicative of poor parental smoking hygiene (eg, smoking in the presence of the child), the risk of plaque was more than doubled compared with those with no detectable cotinine. These data add to the growing body of evidence proposing that exposure to parental smoking early in life has an irreversible effect on arterial health in adulthood by demonstrating that parents who are unable to give up smoking can nonetheless lessen their child’s risk of future cardiovascular burden by exercising good smoking hygiene.2,3,15,16

Our analysis of adult development of carotid plaque extends our previous work linking parental smoking in childhood with increased adult carotid intima-media thickness and decreased brachial flow-mediated dilatation.2,4 Carotid intima-media thickness and plaque are separate phenotypes with different causative factors and predictive utilities for cardiovascular disease.17 The inclusion of serum cotinine levels, measured from stored serum samples as a result of our earlier findings with parental questionnaire data, within a large subgroup of the cohort provides validity of the long-term risks associated with pediatric exposure to parental cigarette smoking. Our data suggest that to provide the best long-term cardiovascular health for their offspring, parents should not smoke. However, parents who are unable to quit smoking may be able to reduce potential long-term risk for their children by smoking in a hygienic manner (ie, away from their children). These data also show that only 1 parent is required to be smoking in a nonhygienic manner for a child to be at significantly increased risk of developing carotid plaque in adulthood. Although both poor maternal and paternal smoking hygiene conveyed an increased risk to offspring, a stronger effect was observed for maternal smoking hygiene. We hypothesize that the stronger effect for maternal smoking hygiene may be due to increased time spent around the child on a daily basis compared with fathers, thereby increasing the offspring’s chances of exposure. We also tended to observe that the effect estimates for current parental smoking were weaker than those effect estimates for ever parental smoking. We hypothesize that ever smoking may more accurately capture the long-term exposure of the child during the child’s entire time living with the parent/parents, whereas current parental smoking provides only a snapshot of a single point in time that may be more informative of recent exposure to parental smoking.

The link between exposure to tobacco smoke and atherosclerosis is well established.18 It has been shown that the cardiovascular effects of passive smoking are nearly as substantial and rapid as those from long-term active smoking.19,20 Cigarette smoke promotes atherosclerosis progression by increasing lipid peroxidation and promoting accumulation of cholesterol esters in atherosclerotic plaque.1 Moreover, smoking is associated with decreased high-density lipoprotein cholesterol, increased platelet activation, inflammation, arterial stiffness, and endothelial dysfunction.21 Our adjustment for several potential mediating factors, including child and adult BMI, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and hs-CRP, did not substantially modify the effects observed for our parental smoking variables, suggesting that parental smoking might act on later risk of carotid plaque through other mechanisms.

Various channels exist to limit children’s exposure to environmental tobacco smoke, including restrictions to smoking in public places, in vehicles, and at home. Although benefit of smoking restrictions in public and work places has been shown to reduce serum cotinine levels and hospitalization for cardiovascular and respiratory disease among adults,22,23 there is some evidence that stricter public smoking regulations have increased passive smoke exposure to nonsmokers, especially children, by displacing smokers to private places such as the home,24,25 and despite the prevalence of tobacco smoking tending toward a decline in developed countries, exposure, particularly in the home, remains high.26 Home smoking bans may well have a substantial impact on children’s exposure but have inherent difficulties in regulation if implemented.27 What is probably as important is communicating to parents that their smoking has effects on their children’s health, both immediately and in the future. For example, many antitobacco mass-media campaigns and graphic pack warnings concentrate on the individual or are limited to the fetal and neonatal effects in offspring; however, our data provide some basis that these campaigns should be expanded to recognize the long-term cardiovascular effects of passive smoke exposure on children and adolescents.

The major strengths of this study include the availability of measurements beginning in childhood, follow-up of the cohort for >20 years, and validation of questionnaire measurements of parental smoking with the use of a biomarker. Limitations include the lack of data on intrauterine exposure to maternal and paternal tobacco smoke, an exposure that numerous studies have previously demonstrated to possess clear long-term adverse effects in relation to offspring general and cardiovascular health, specifically related to BMI,28 total cholesterol,29 and hypertension.30 Our results indicated that children 3 to 9 years of age had a greater adverse effect of unhygienic smoking than those 12 to 18 years of age, indicating a possible period of increased vulnerability, although this finding was statistically insignificant. Other limitations include the lack of availability of parental smoking hygiene behavior over time that may have helped us separate those families with an ongoing commitment to good smoking hygiene better than the use of a serum cotinine measurement at a single time point. A further limitation is the reliance on the surrogate end point of carotid plaque because this cohort does not currently have sufficient hard events to be analyzed. However, the relationship between carotid atherosclerosis and ischemic stroke is well established, and management via endarterectomy has been shown to reduce the risk of stroke in both symptomatic31 and asymptomatic32 individuals.

Differential loss to follow-up is a potential limitation in longitudinal studies; however, we have previously found participants in the adult follow-ups to align well with those who did not participate in terms of major risk factors except that participants tend to be older and more often female.4 Other limitations include imaging of only the left carotid artery; a lack of data on plaque size; and, because of the relatively young age of participants, a low number of cases with carotid plaque, resulting in our confidence limits for several comparisons being somewhat wide.

Conclusions

The risk of carotid plaque in adulthood was highest for the offspring of parents who reported smoking when their offspring were children. Not smoking at all was by far the safest option, but those parents who find it difficult not to smoke can at least lessen the deleterious effects of their smoking on the future cardiovascular health of their offspring by smoking more hygienically. These data, the first of their kind, provide quantitative evidence that reinforce the public health priority not only to reduce but also to stop children’s exposure to environmental tobacco smoke.

Acknowledgments

We thank the clinic and administrative staff for their contribution to data collection. Above all, we thank the participants of the Cardiovascular Risk in Young Finns Study.

Sources of Funding The Young Finns Study has been financially supported by The Academy of Finland : grants 134309 (Eye), 126925, 121584 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi) ; the Social Insurance Institution of Finland; Kuopio, Tampere , and Turku University Hospital Medical Funds; Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation of Cardiovascular Research and Finnish Cultural Foundations; Tampere Tuberculosis Foundation; and Emil Aaltonen Foundation . Dr Gall was supported by the National Heart Foundation of Australia ( PH 11H 6047 ). Dr Magnussen is supported through a National Health and Medical Research Council Early Career Fellowship ( APP1037559 ).

Disclosures None.

Footnotes