Epidemiological evidence associating secondhand smoke exposure with cardiovascular disease.

Abstract

The objective of this paper was to review the epidemiological literature examining the association between secondhand smoke (SHS) and cardiovascular disease (CVD). Specifically, we examined the various screening methods available in assessing smoking behaviour and quantifying nicotine absorption. Further, we considered the natural history of those exposed to SHS and the associated risk of CVD. We reviewed routine methods used to assess exposure to SHS; evaluated the utility of subjective screening questions regarding smoking behaviour and examined the efficacy of nicotine and cotinine biomarkers used to quantify SHS exposure in epidemiological and clinical-based research. Self-reporting is practical and cost-effective in identifying smoking behaviour patterns, but is subject to recall bias and underestimation of exposure, especially in the presence of children. Nicotine and cotinine biomarkers have proven valuable in quantifying tobacco smoke absorption and establishing biological plausibility. A combination of SHS self-reported and biomarker evaluation provide the most stringent method of establishing exposure. Sufficient evidence is reported in epidemiological research to support a causal association between SHS exposure and increased risks of CVD morbidity and mortality among both men and women. The risk of developing an acute cardiac syndrome or chronic lifetime coronary events is at least 30%. Similarly, reduction in the incidence of a myocardial infarction decreases by nearly 50% in the absence of SHS. Considering the biological plausibility and dose-response relationship between SHS and CVD, effective interventions that incorporate a comprehensive screening method of behavioral and biological measures of exposure coupled with efficacious treatment should elicit favorable change for at-risk populations.

Full text

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Inflammation & Allergy - Drug Targets, 2009, 8, 321-327 321

1871-5281/09 $55.00+.00 © 2009 Bentham Science Publishers Ltd.
Epidemiological Evidence Associating Secondhand Smoke Exposure with
Cardiovascular Disease
Brent E. Faught*,1, Andreas D. Flouris2 and John Cairney3
1Faculty of Applied Health Sciences, Brock University, Canada
2Institute of Human Performance and Rehabilitation, Centre for Research and Technology Thessaly, Greece
3Departments of Family Medicine, Psychiatry and Behavioural Neurosciences & Clinical Epidemiology and
Biostatistics, McMaster University, Canada
Abstract: The objective of this paper was to review the epidemiological literature examining the association between
secondhand smoke (SHS) and cardiovascular disease (CVD). Specifically, we examined the various screening methods
available in assessing smoking behaviour and quantifying nicotine absorption. Further, we considered the natural history
of those exposed to SHS and the associated risk of CVD. We reviewed routine methods used to assess exposure to SHS;
evaluated the utility of subjective screening questions regarding smoking behaviour and examined the efficacy of nicotine
and cotinine biomarkers used to quantify SHS exposure in epidemiological and clinical-based research. Self-reporting is
practical and cost-effective in identifying smoking behaviour patterns, but is subject to recall bias and underestimation of
exposure, especially in the presence of children. Nicotine and cotinine biomarkers have proven valuable in quantifying
tobacco smoke absorption and establishing biological plausibility. A combination of SHS self-reported and biomarker
evaluation provide the most stringent method of establishing exposure. Sufficient evidence is reported in epidemiological
research to support a causal association between SHS exposure and increased risks of CVD morbidity and mortality
among both men and women. The risk of developing an acute cardiac syndrome or chronic lifetime coronary events is at
least 30%. Similarly, reduction in the incidence of a myocardial infarction decreases by nearly 50% in the absence of
SHS. Considering the biological plausibility and dose-response relationship between SHS and CVD, effective
interventions that incorporate a comprehensive screening method of behavioral and biological measures of exposure
coupled with efficacious treatment should elicit favorable change for at-risk populations.
Keywords: Secondhand smoke, cardiovascular disease, epidemiology, screening, exposure, biomarkers, self-reporting,
morbidity, mortality.
1. INTRODUCTION

smoking is the involuntary breathing of other people's
tobacco smoke, Approximately 5000 chemicals are produced
from cigarette smoke; many poisonous [1]. Secondhand
smoke increases the risk of cardiovascular disease (CVD) by
30%, based on epidemiological and biological evidence [2].
A 30-minute SHS exposure was found to affect coronary
flow velocity reserve in non-smokers, suggesting endothelial
dysfunction in coronary circulation [3]. Evidence from
cohort [4, 5], case-control [6] designs and meta-analysis [7]
have all suggested a longitudinal association between CVD
and SHS exposure. Further, clinical-based and animal model
research has supported this association by suggested a
biological plausibility for prolonged exposure to SHS [8-10].
Nevertheless, controversial evidence also exists with regards
to the natural history of SHS exposure and risk of CVD in
non-smokers.
Secondhand smoke (SHS), previously known as passive

has been suggested as a probable reason for the
inconsistency in the literature. Exposure misclassification
appears to be attributed to proxy measures of exposure that

Lack of an accurate method of assessing SHS exposure

*Address correspondence to this author at the Faculty of Applied Health
Sciences, Brock University, St. Catharines, Ontario, L2S 3A1, Canada;
E-mail: bfaught@brocku.ca
do not account for spousal smoking status [11, 12], exposure
source including home and workplace [5, 11] and lack of
SHS normative data and/or recognition of quantifying
intolerable levels of nicotine differences in pediatric and
adult populations [13]. Valid and efficient means of
objectifying secondhand smoke exposure would lead to more
thorough surveillance techniques of estimating the risk of
cardiovascular disease. This epidemiological review will
address the current literature as it applies to quantifying SHS
exposure and the natural history of cardiovascular disease
among those exposed to secondhand smoke.
2. MEASURING SECONDHAND SMOKE EXPOSURE

health, particularly since laws governing the right to smoke
in community environments are felt to infringe the rights of
those who smoke, while protecting the health of non-
smokers. Public policy is, at times, established based on
epidemiological research. However, observational studies,
the mainstay of most epidemiological research, pose
significant methodological challenges, which in turn often
threaten both the internal and external validity of the results.
Specifically, validity of studies in cardiovascular disease and
SHS is the ability to accurately estimate tobacco smoke
exposure and absorption. Secondhand smoke exposure lacks
a true screening or reference standard and is an area of
research that requires specific attention when interpreting
Secondhand smoke is a controversial issue in public

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322 Inflammation & Allergy - Drug Targets, 2009, Vol. 8, No. 5 Faught et al.
exposure and relative risk [14]. The inability to accurately
classify smokers and non-smokers makes establishing risk
challenging. Misclassification of smokers as non-smokers,
which is more likely due to recall bias and systematic error,
presents the opportunity for underestimating the causal
association between SHS exposure and cardiovascular
disease. An accurate assessment of the risks associated with
tobacco smoke exposure depends on a generalizable and
valid measurement. Self-reporting in conjunction with an
objective (biomarker) method of screening for SHS exposure
is well documented [15-19].
Subjective Measures

attractive approach to establishing a measure of SHS
exposure and non-smokers because they are non-invasive
and demonstrate strong face validity [13]. Further, self-
report information provides important details regarding
source, duration of exposure and proximity of SHS exposure.
Matt and colleagues [20, 21] demonstrated that well
designed interviews can illicit information from parents
regarding SHS exposure in children, explaining 20-40% of
the variance from corresponding biomarker information.
Questionnaires are considered advantageous because of the
low costs and practicality of administering [22]. Nevertheless,
subjective measures are prone to recall bias in retrospective
epidemiologic studies. Further, self-report is always open to
question in specific populations such as pregnant mothers
and parents of young children to divulge their smoking status
or child’s exposure to SHS due to the social stigma of
smoking [14]. For example, Al-Delaimy and colleagues
(2001) showed that parents reported smoking outside the
home and never near their children to avoid SHS exposure
[23]. However, the results indicated higher levels of tobacco
smoke among the children of these parents compared to the
children of non-smoking parents. Nevertheless, subjective
measures including interview and questionnaire methods
provide necessary information on smoking patterns and
nicotine contamination.
Self-administered questionnaires and interviews are an
Objective Measures

measures of SHS exposure, objective methods are necessary.
Biomarkers comprise the most recognizable objective means
of determining SHS exposure [24]. Furthermore, biomarkers
are critical in understanding the mechanisms responsible for
adverse health effects associated with SHS exposure.
Finally, biomarkers are necessary in establishing biological
plausibility in epidemiological research [25]. Nicotine and
cotinine measured in bodily fluids (blood, saliva and urine)
and hair are identified as the most recognized biomarkers of
tobacco smoke exposure. A recent investigation of men and
women of African-American and Caucasian ethnicity were
monitored for exposure to aged, diluted sidestream smoke
generated in a controlled environmental chamber with a
standard rate of air nicotine for 4 hours [26]. The results
indicated a consistent response from nicotine and cotinine
biomarkers in non-smokers, regardless of gender and race.
Considering the biases associated with subjective

smoke exposure [27]. Ishiyama et al. (1983) first reported
nicotine in hair samples of humans [28]. Hair nicotine
Nicotine is the main constituent of tobacco and secondhand
concentration determined by gas chromatography/mass
spectrometry is traditionally considered superior in assessing
secondhand smoke exposure [29]. Nicotine assessed in
biological fluids has a short half-life of 2-3 hours, therefore
making these forms less discriminative in detecting absorption
[24]. Sorenson and colleagues (2007) reported a strong
association between nicotine in hair of one year old infants
exposed to low levels (10-99 days per year) of parental reported
secondhand smoke [17]. Further, nicotine extraction positively
correlates with the number of cigarettes smoked per day in the
household [15] and workplace [30]. The optimum method of
extracting nicotine in hair from children is using an isotope
dilution with spiked samples (3.3 ng/mg) with a 60 minute
shaking time. Man and colleagues (2009) reported that in order
to attain a high screening sensitivity, the amount of hair required
for nicotine extraction is minimal (5 mg) [15]. Despite the
proven validity and reliability of hair nicotine as a viable
biomarker for SHS exposure [29], controversial issues such as
hair treatment [31, 32], hair colour [29, 33] and ethnicity [34-
36] on nicotine levels in hair need to be examined in
epidemiological studies [22].

biomarker of tobacco smoke exposure [37-39]. As a nicotine
metabolite, cotinine can be detected in bodily fluids (i.e.,
blood, urine, saliva) and hair. Cotinine is metabolized to 3’-
hydroxycotinine primarily through enzymatic activity of
CYP2A6, principally in the liver [13]. Renal excretion is the
main contributor to eliminating
accounting for 38% of all urinary nicotine metabolites in
humans [40] and has been shown to be present in urine 72
hours post-exposure [41]. Very little is known as to the value
of 3’-hydroxycotinine as a biomarker for SHS exposure,
suggesting more clinical-based research is required.
Nevertheless, urinalysis screening of nicotine and its’
metabolic constituents for SHS exposure has demonstrated
high utility. A recent comparative investigation of urinary
nicotine, cotinine and 3'-hydroxycotinine indicated a
consistently (90%) high detection rate suggesting these
chemicals can be used interchangeably as biomarkers of SHS
exposure [41].
Cotinine concentrations in urine have also been
positively correlated with blood cotinine levels [42]. Total
plasma cotinine is the principal assay used to quantify
smoking and exposure to
epidemiological research. However, cotinine is also
characterized into secondary
including cotinine glucuronide, 3-hydroxycotinine, and 3-
hydroxycotinine glucuronide. De Leon and colleagues
(2002) investigated the stability of cotinine plasma and sub-
components as biomarkers for tobacco in smokers and non-
smokers [43]. Plasma total cotinine concentration was most
accurate in quantifying tobacco smoke followed by 3-
hydroxycotinine glucuronide and 3-hydroxycotinine plasma
concentrations. Cotinine glucuronide and its components of
glucuronidation were not
misclassifying 27% of non-smokers. Overall, the results
indicated that at least two plasma samples of total cotinine
are needed to accurately quantify SHS exposure in
epidemiological studies. Finally, urinary cotinine assessment
has demonstrated high utility in the surveillance of smoking
cessation programs after a clinical event or of smoking in
Cotinine is considered by some to be the most valid
3’-hydroxycotinine
secondhand smoke in
biological metabolites,
effective biomarkers,

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Epidemiological Evidence Associating Secondhand Smoke Exposure Inflammation & Allergy - Drug Targets, 2009, Vol. 8, No. 5 323
pregnant women. It also offers useful detection of SHS
exposure in children hospitalized for persistent respiratory
illnesses [44].

attention because of its non-invasive approach [39, 45].
Those exposed to low doses of secondhand smoke usually
have cotinine concentrations in saliva <5 ng/ml, while heavy
exposure to SHS in adults can result in levels >10 ng/ml
[37]. Murray and colleagues (1993) reported a higher cut-off
(?20 ng/ml) for salivary cotinine in classifying smokers from
non-smokers [46]. Sensitivity and specificity were 99.0%
and 91.5%, respectively and were somewhat better than
carbon monoxide (sensitivity=93.7%; specificity=87.2%).
These results are also consistent with a lower saliva cotinine
cut-off of ?13 ng/ml (sensitivity=86.5%; specificity=95.9%)
[47]. Saliva samples were also consistent with self-report
questionnaire, suggesting evidence of strong construct
validity for the screening of active and passive exposure to
tobacco smoke. Non-invasive saliva and urinary cotinine
sampling were superior to plasma cotinine in non-smoking
Italian females exposed and unexposed to SHS [48]. Finally,
commercial brand saliva cotinine test strips (i.e., NicAlert)
for smoking classification (10mg/ml) was found to be as
effective (sensitivity=93%; specificity=95%) and more time
and cost-effective than gas chromatography–nitrogen
phosphorous [49].
Cotinine measurements in saliva are receiving much

sources has proven effective, but has also posed unique
challenges. Specifically, cotinine in body fluids reflect SHS
exposure only a couple days preceding the study and do not
capture exposure in individuals that purposely abstain from
tobacco smoke several days prior to being assessed. As a
result, valid estimates of biomarkers are not time sensitive and
provoke the search for a more consistent and accurate
biomedical estimate of SHS exposure [24]. Cotinine hair
analysis is a noninvasive technique used to detect the presence
of nicotine metabolites in the hair shaft. Since cotinine collects
in the hair shaft during growth, it has the ability to measure
long-term and cumulative SHS exposure. Although cotinine
hair analysis addresses the issue of SHS duration of exposure,
a complete understanding of its’ overall utility is
undetermined at this point. Few studies have been published
that address this issue. Cotinine in the body is dependent on
nicotine metabolism, which in turn is influenced by factors
such as age and pregnancy. As a result, characterization of hair
cotinine should be population specific. A study by Groner and
colleagues (2004) examined cotinine hair levels in mother and
their children (<3 years old) exposed to active and passive
tobacco smoke. Both child and maternal hair cotinine levels
correlated with self-reported maternal smokers and self-
reported maternal non-smokers [50]. Overall, child hair
cotinine levels (1.18 ng/mg) were significantly higher than
maternal levels (.78 ng/mg). This was consistent among
children of non-smokers (.77 ng/mg) and their mothers (.35
ng/mg), while no difference was found in hair cotinine levels
of maternal smokers (1.91 ng/mg) and their children (1.92
ng/mg). Finally, child age, gender or race did not influence the
relationship between child and maternal hair cotinine. Further
research is necessary in understanding the utility of hair
cotinine in quantifying SHS exposure in young children and
adults.
Cotinine fluid analysis from invasive and non-invasive
3. SECONDHAND SMOKE AND CARDIOVASCULAR
DISEASE MORBIDITY AND MORTALITY

public health due to its acknowledged adverse health effects
[51-55]. Exposure to SHS is related to the ever increasing
frequency of diseases among children and adults, such as
respiratory illness, asthma, otitis media, sudden infant death
syndrome, vascular dysfunction, and predisposition towards
cardiovascular disease and cancer [56]. The response of the
cardiovascular system in adults to secondhand smoke has been
well documented [51-55]. In the United States only, among
30,000 to 60,000 deaths from cardiovascular disease per year in
nonsmokers have been attributed to secondhand smoke [57].
The 2006 Surgeon General’s Report stated that evidence is
sufficient to infer a “causal relationship between exposure to
secondhand smoke and increased risks of coronary heart disease
morbidity and mortality among both men and women”, adding
that there is no risk-free level of exposure to secondhand smoke
[58]. Moreover, there is a confirmed link between chronic SHS
(lifestyle incorporating frequent SHS exposures) and various
types of cancer including lung cancer [59], leukemia [60, 61],
breast cancer [62], upper aero digestive tract carcinomas [63],
and nasal cancer [64].
A recent study demonstrated that the relative risk of
developing acute cardiac syndrome was found to be
increased by 50% among tobacco smoke exposed
nonsmokers [65]. Specifically, it was estimated that 34
coronary events per 134 subjects would occur as a result of
secondhand smoke exposure during their lifetime [65]. This
notion is in line with evidence showing a reduction in the
incidence of respiratory symptoms among hospitality
workers following the implementation of smoke-free laws in
different countries [66-68]. The latter is further supported in
a study where hospital admissions for myocardial infarctions
decreased by nearly 50% when a total smoking ban was
enforced and returned to baseline when the ban was repealed
[69]. Furthermore, a recent case control study [70]
examining the relationship of all types of tobacco exposure
(active smoking, past smoking, secondhand smoke exposure,
and chewing tobacco) and acute non-fatal myocardial
infarction demonstrated that secondhand smoke exposure
was associated with a graded increase in risk related to
exposure. In the same study, the odds ratio of acute
myocardial infarction was 1.24 in those exposed the least (1-
7 hours per week) and increased to 1.62 in those who were
most exposed (>21 hours per week) [70]. Epidemiological
evidence associating secondhand smoke with cardiovascular
disease morbidity and mortality based on evidence from the
2006 Report of the U.S. Surgeon General [58] are
summarized in Table 1. Based on the presented evidence, it
can be postulated that chronic exposures to secondhand
smoke generate significant adverse effects on several
systems of the human body and are associated with increased
morbidity and mortality.
It is well known that secondhand smoke is a major threat to

effects of secondhand smoke have evaluated longitudinal
epidemiological data, while exposure studies assessing the
acute and short-term secondhand smoke effects are limited.
Yet, this knowledge is essential and of the utmost
importance for elucidating the underlying physiological
The vast majority of published studies regarding the

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324 Inflammation & Allergy - Drug Targets, 2009, Vol. 8, No. 5 Faught et al.
mechanisms involved in the secondhand smoke-induced
system disruption [53]. The limited experimental studies that
assess the acute and short-term effects of exposure to
secondhand smoke include cellular, animal, and human
studies that indicate a number of pathophysiological
mechanisms through which the deleterious effects of
secondhand smoke may arise and have been recently
reviewed elsewhere [5]. In brief, data thus far have shown
that even brief exposures to secondhand smoke disrupt the
normal physiological functioning of the respiratory, the
cardiovascular, the immune and the endocrine systems
generating significant adverse effects [53].
4. SUMMARY

smoke exposure increases the risk of cardiovascular disease
Numerous epidemiological studies indicate secondhand
by an estimated 30%. The risk is substantially comparable to
mainstream smoking. Non-smokers appear to be more
sensitive to SHS than do smokers, possibly due to a hyper-
sensitive physiological system to small doses of SHS
compounds, as well as the physical adaptation typically
associated with smokers with years of prolonged tobacco
exposure. Nicotine and cotinine, the main metabolite of
nicotine, are the most useful biomarkers for quantifying
exposure to secondhand smoke. However, distinguishing
classification of smoking behaviour cannot be confirmed
using biomarkers alone. Despite biases reported with self-
report and interview questions; these subjective assessment
tools are valuable in establishing the source, frequency and
duration of secondhand smoke exposure. Combined self-
reporting and biomarker assessment is the most effective
means of establishing an accurate estimation of SHS
exposure in epidemiological research. In the presence of
Table 1. Epidemiological Evidence Associating Secondhand Smoke with Cardiovascular Disease Morbidity and Mortality Based
on Evidence from the 2006 Report of the U.S. Surgeon General [58]

Study/Location Design Exposure Population/Morbidity/Mortality Relative Risk (95% CI)
Ciruzzi [71]/ Argentina Case control SS & children smokers M: 336/ MI 1.68 (1.2-2.37)
Dobson [72]/ Australia Case control Work & home exposures
M: 180, W: 160/ MI
or death from CVD
M: 1.0 (0.5-1.8)
W: 2.5 (1.5-4.1)
Garland [73]/ U.S. Cohort SS W: 695/ death from CVD 2.7 (0.59-12.33)
He [74]/ China Case control
SS & >5 yrs
workplace exposure
W: 59/ CVD 2.36 (1.01-5.55)
He [75]/ China Case control SS W: 34/ death from CVD 1.5 (1.3-1.8)
Helsing [76]/ U.S. Cohort SS
M: 3488, W: 12348/
death from CVD
M: 1.31 (1.1-1.6)
W: 1.24 (1.1-1.4)
Humble [77]/ U.S. Cohort SS W: 513/ death from CVD 1.59 (0.99-2.57)
Kawachi [11]/ U.S. Cohort
Home or workplace
exposures
W: 32046/ MI or
death from CVD
1.73 (1.03-2.84)
La Vecchia [78]/ Italy Case control SS M: 69, W: 44 / MI 1.21 (0.57-2.52)
Layard [79]/ U.S. Case control SS
M: 475, W: 914/
death from CVD
M: 1.0 (0.7-1.3)
W: 1.0 (0.8-1.2)
Lee [80]/ UK Case control SS M: 41, W: 77/ CVD 1.03 (0.65-1.62)
LeVois [81]/ U.S. Cohort SS
M: 88455, W: 247412/
death from CVD
(0.97-1.04)
McElduff [82]/
Australia & New Zealand
Case control
Home & workplace
exposures combined
M: 686, W: 267/
MI or death from MI
1.41 (0.73-2.71)
Muscat [83]/ U.S. Case control
Home & workplace current
& childhood exposures
M: 68, W: 46/ MI 2.4 (1.1-4.8)
Rosenlund [5]/ Sweden Case control SS M: 199, W: 135/ MI 1.37 (0.9-2.09)
Sandler [84]/ U.S. Cohort SS
M: 4162, W: 14873/
death from CVD
1.22 (1.09-1.37)
Steenland [4]/ U.S Cohort
Home or workplace
exposures
M: 126500/ W: 353180/
death from CVD
1.21 (1.06-1.39)
Svendsen [85]/ U.S. Cohort SS M: 1245/ death from CVD 2.23 (0.72-6.92)
Teo [70]/ 52 countries Case control
SS, friends, co-worker
smokers
M & W: 12461/
acute non-fatal MI
1.24 (1.17 – 1.32)
1.62 (1.45-1.81)
Tunstall-Pedoe [86]/ Scotland Case control
Any exposure ?3 days
before survey
M & W: 70/ CVD 1.5 (0.9-2.6)
Note: SS = spouse smoker; M = men; W = women; CVD = cardiovascular disease; MI = myocardial infarction.

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error
(measurement error) and self-report (bias) measures,
epidemiological studies should assume conservative results.
The systematic error of biomarkers is quite possibly
distributed symmetrically across the normal distribution of
scores, while subjective human bias is more inclined to be
skewed toward a socially desirable response. Whenever
possible, epidemiological studies should be designed to
incorporate the most valid biomarkers available in an
environment whereby there exists’ little or no pressure to
give a socially desirable response by those exposed to both
active and passive tobacco smoke.
that is typically associated with biomarker

response relationship, with greater exposure to secondhand
smoke associated with increased risk of cardiovascular
disease mortality. These epidemiological studies suggest that
both physiological and biochemical data point to SHS
adversely affecting platelet function and damage to arterial
endothelium as contributors to increasing the risk of
cardiovascular disease. The effects of secondhand smoke are
substantial and aggressive, which explains the relatively
large risks that have been reported in epidemiological
studies. Nevertheless, secondhand smoking exposure and
cardiovascular disease are at least partially reversible.
Finally, appropriate assessment of secondhand smoke
exposure in home and work environments are warranted, as
well as recommendations to avoid such exposure. Consistent
public health initiatives to eliminate secondhand smoke in
these environments are encouraged.
Large scale studies have demonstrated a significant dose-
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Received: July 12, 2009

Revised: September 19, 2009 Accepted: September 30, 2009