Association of Secondhand Smoke With Stroke Outcomes

Michelle P. Lin, MD, MPH; Bruce Ovbiagele, MD, MSc, MAS; Daniela Markovic, MS;
Amytis Towfighi, MD

Background and Purpose—Approximately half of never smokers are exposed to secondhand smoke (SHS). Smoking is a
well-established stroke risk factor, yet associations between SHS, stroke, and poststroke mortality remain uncertain. We
aimed to determine the prevalence of exposure to SHS among those with and without stroke and its impact on mortality.
Methods—Data were obtained from the US National Health and Nutrition Examination Surveys for 27 836 never smokers
with/without self-reported stroke aged ≥18 years, sampled from 1988 to 1994 and 1999 to 2012, with linked mortality
through 2010. Household exposure to SHS was determined by self-report; exposure severity was quantified by serum
cotinine level. Independent relationships between SHS and all-cause mortality were assessed using Cox regression
models, before and after adjusting for sociodemographics and comorbidities.
Results—From 1988 to 1994 to 1999 to 2012, age-adjusted prevalence of exposure to SHS declined from 11.5% to 6.6%
among survivors of stroke (P=0.08), and 14.6% to 5.9% among persons without stroke (P<0.01). Factors associated with
high exposure to SHS were male sex, black race, ≤12th-grade education, poverty income ratio ≤200%, high alcohol
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intake, and history of myocardial infarction (all P<0.05). High exposure to SHS was associated with higher odds of
previous stroke (odds ratio, 1.46; P=0.026). There was a dose-dependent relationship between exposure to SHS and all-
cause mortality after stroke.
Conclusions—Individuals with previous stroke have 50% greater odds to have been exposed to SHS; SHS is associated with
a 2-fold increase in mortality after stroke. This study highlights the importance of obtaining exposure to SHS history and
counseling patients and their families on the potential impact of SHS on poststroke outcomes.   (Stroke. 2016;47:2828-
2835. DOI: 10.1161/STROKEAHA.116.014099.)
Key Words: cardiovascular disease ◼ prevalence ◼ risk factor ◼ secondhand smoke ◼ stroke

C igarette smoking, an independent modifiable risk factor

for cardiovascular disease, doubles the risk of stroke.1 Up
to 1 in 4 cardiovascular disease deaths in the United States
and (3) to explore the dose effect of household exposure to
SHS on all-cause mortality after stroke.

each year are attributable to smoking2; the risk is strongly dose
related.3 Although smoking is a well-established stroke risk
factor, the associations between secondhand smoking, stroke,
and mortality after stroke remain uncertain.
The Centers for Disease Control and Prevention found that
nearly half of US nonsmokers are exposed to secondhand
smoke (SHS),4 and no risk-free level of exposure to SHS
exists.5,6 Despite a quarter century of multipronged efforts to
reduce active smoking, exposure to SHS continues to cause
>41 000 deaths among nonsmoking adults and 400 deaths in
infants each year, and ≈$5.6 billion annually in terms of lost
productivity.7
The aims of the current study were (1) to describe trends
in the prevalence of household exposure to SHS among never
smokers over the past two and half decades, (2) to examine the
association between household exposure to SHS and stroke,
Methods
Study Population
Data were obtained from the US National Health and Nutrition
Examination Surveys (NHANES), which are a series of cross-sectional,
national, stratified, multistage probability surveys constituting represen-
tative samples of the civilian, noninstitutionalized US population. Each
survey participant completed a household interview and underwent a
physical examination. Detailed descriptions of the plan and operation of
each survey have been published.8 The study received approval from the
National Center for Health Statistics Research Ethics Review Board, and
participants were asked to sign an informed consent form. Our sample
included adult (≥18 years) never smokers from survey participation in
1988 to 1994 and 1999 to 2012 to mortality assessment in 2010.
Definition of SHS
Household exposure to SHS was measured in 2 ways: self-report
and serum cotinine levels. NHANES provides data on exposure to

Received May 16, 2016; final revision received August 18, 2016; accepted September 12, 2016.
From the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD (M.P.L.); Department of Neurology, Medical
University of South Carolina, Charleston (B.O.); Department of Biomathematics, University of California at Los Angeles (D.M.); Department of Neurology,
University of Southern California (A.T.); and Department of Neurology, Rancho Los Amigos National Rehabilitation Center, Downey, CA (A.T.).
Guest Editor for this article was Stephen M. Davis, MD, FRACP.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.
116.014099/-/DC1.
Correspondence to Michelle P. Lin, MD, MPH, Department of Neurology, Johns Hopkins School of Medicine, 600 N Wolfe St Phipps Bldg, Suite 486,
Baltimore, MD 21287. E-mail michelle.py.lin@gmail.com
© 2016 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.116.014099

2828
 Lin et al   Secondhand Smoke and Stroke Outcomes    2829
SHS at home in family smoking questionnaires. The specific question
that provided data on exposure to SHS at home was: “Does anyone
who lives here smoke cigarettes, cigars, or pipes anywhere inside this
home?” If the answer to this question was yes, the respondent was
considered to be exposed to SHS at home.
Exposure to SHS severity was quantified by serum cotinine level,
a metabolite of nicotine that has been validated in previous human
studies with a sensitivity of 91% and specificity of 87% to differenti-
ate active smokers from nonsmokers not exposed to SHS and those
exposed to SHS (area under the curve 0.902).9–11 Cotinine levels
were categorize by undetectable (<0.05 ng/mL), median, and across
quartiles.
Outcome Measures: SHS Prevalence,
Stroke, and Mortality
Prevalence of exposure to SHS and the geometric mean of serum coti-
nine levels were computed and compared across time (1988–1994
and 1999–2012) in people with and without stroke. History of stroke
was obtained by self-report (“Has a doctor or other health profes-
sional ever told you that you had a stroke”). Mortality was reported
as 10-year cumulative mortality and as mortality rates per 1000
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person-years.
Demographic and comorbid covariates included age, sex, race/
ethnicity, poverty income ratio (PIR; which represents the ratio of
family income to their appropriate poverty threshold. Ratios <100%
indicate that the income for the respective family below the official
definition of poverty. PIR >200% is a commonly used threshold in
NHANES studies, indicates that income was 200% above the appro-
priate poverty threshold), education level (≤12th grade versus >12th
grade), hypertension (blood pressure >140/90 mm Hg, on antihyper-
tensive medications, or self-report), diabetes mellitus (hemoglobin
A1C ≥6.5%, on diabetes mellitus medications, or self-report), hyper-
cholesterolemia (total serum cholesterol ≥240 mg/dL or on choles-
terol-lowering medications), history of myocardial infarction (MI,
by self-report), chronic kidney disease (CKD, urine albumin to urine
creatinine ratio >30 mg/g), chronic obstructive pulmonary disease
(forced expiratory volume 1/forced vital capacity ratio <0.7, or self-
report), and alcohol intake in the past 12 months. Time was catego-
rized as early (1988–1994) and late (1999–2012).
Statistical Analysis
We estimated the survey-weighted prevalence of the baseline sociode-
mographic and comorbidities by self-reported history of stroke. We
compared the crude and age-adjusted prevalence of self-reported
household exposure to SHS for a given time interval according to
the level of each baseline covariate in people with and without stroke
using logistic regression analyses taking into account the NHANES
survey design. Crude and age-adjusted geometric means of serum
cotinine levels were compared by level of each covariate over time
in people with and without stroke using linear regression analyses
taking into account the NHANES survey design. Mean serum coti-
nine–level comparisons were determined on the log scale to reduce
skewness and remove the impact of outliers. Age adjustment was per-
formed using the direct method based on 2 age groups (<65 years and
≥65 years) to the overall age distribution in the early time interval
under the regression models.
To evaluate the relationship between exposure to SHS and the odds
of previous stroke, multivariable logistic regression analyses before
and after adjusting for covariates were performed. Model 1 adjusted
for sociodemographic factors (age, sex, race/ethnicity, PIR, and edu-
cation level). Model 2 adjusted for sociodemographic factors (as
above) and comorbidities (hypertension, diabetes, hypercholesterol-
emia, MI, CKD, chronic obstructive pulmonary disease, and alcohol
intake).
For mortality, we computed the crude and the age-adjusted mor-
tality rates per 1000 person-years by each cotinine category using
the Poisson regression model adjusting for the survey design after
stratifying by previous stroke. In addition, we computed the hazard
ratios and the corresponding 10-year adjusted mortality risks by each
cotinine category using the Cox regression model taking into account
the survey design after stratifying by previous stroke (adjusted mod-
els 1 and 2).
To examine the association between exposure to SHS and all-cause
mortality, univariable and multivariable analyses were performed
using Cox regression models after adjusting for the survey design
variables. Age-adjusted hazard ratios of all-cause mortality compar-
ing highest quartile of serum cotinine versus undetectable serum
cotinine were computed in people with previous stroke versus those
without previous stroke. Data were analyzed using STATA software
version 11.2 (StataCorp, Inc, College Station, TX) and R (version
3.0.2).
Results
Study Population
A total of 27 836 never smokers aged ≥18 years were included
in the study. Survivors of stroke were more likely to be
women, age ≥65 years, have ≤12th-grade education, have PIR
≤200%, and have hypertension, diabetes mellitus, hypercho-
lesterolemia, MI, and CKD (Table 1).
Prevalence of Exposure to SHS
From 1988 to 1994 to 1999 to 2012, age-adjusted prevalence
of household exposure to SHS declined from 11.5% (95%
confidence interval [CI], 5.6%–17.4%) to 6.6% (95% CI,
4.4%–8.8%) among survivors of stroke (P=0.08) and from
14.6% (95% CI, 13.0%–16.2%) to 5.9% (95% CI, 5.3%–6.5%)
among people without stroke (P<0.01; Table 2). Although
SHS prevalence among all subgroups without previous stroke
declined over time, SHS prevalence among survivors of stroke
who were aged <45 years, ≥80 years, men, were associated
with PIR >200% and with CKD, or had reported high alcohol
intake increased without achieving statistical significance.
The geometric mean of serum cotinine levels decreased
over time from 0.26 to 0.06 ng/mL (P<0.01) among survi-
vors of stroke and from 0.24 to 0.05 ng/mL (P<0.01) among
people without previous stroke. Similar trends were observed
after adjusting for age. There was a temporal shift toward
more individuals having undetectable serum cotinine levels,
from 21.84% in 1988 to 1994 to 64.78% in 1999 to 2012
(inversely, prevalence of exposure to SHS declined from
78.16% to 35.22% over time; Table I in the online-only Data
Supplement).
Characteristics associated with high exposure to SHS
(higher mean serum cotinine level) were younger age, male
sex, black race, ≤12th-grade education, PIR ≤200%, high
alcohol intake (>12 drinks per year), and history of MI (all
P<0.05 in 1999–2012 survey; Table II in the online-only Data
Supplement).
Association Between SHS and Stroke History
Stroke prevalence was higher among participants with self-
reported household SHS (2.69±0.48%) compared with those
without exposure to SHS (2.24±0.14%) in 1999 to 2012. High
exposure to SHS (cotinine level above median) was associated
with higher odds of stroke (odds ratio, 1.46; 95% confidence
interval [CI], 1.05–2.3; P=0.026) in the NHANES 1999 to
2012 cohort (Table 3). This relationship was not observed in
the 1988 to 1994 cohort.
 2830  Stroke  November 2016

Table 1.  Patient Characteristics of Never Smokers, by Stroke Status NHANES 1988 to 1994 and 1999 to 2012
NHANES 1988–1994 NHANES 1999–2012
No Stroke Stroke Survivor No Stroke Stroke Survivor
n=8528 (Weighted %) n=196 (Weighted %) n=18 546 (Weighted %) n=566 (Weighted %)
Age, n (%)
 18–44 y 5056 (63.7) 11 (10.2) 9374 (53.7) 36 (10.4)
 45–64 y 1623 (20.9) 28 (15.6) 5234 (31.4) 137 (27.2)
 65–79 y 1202 (11.4) 82 (43.9) 2686 (10.7) 224 (35.9)
≥80 y
  647 (4) 75 (30.3) 1252 (4.2) 169 (26.5)
Sex, n (%)
 Women 5560 (61.7) 139 (71.1) 11 306 (58.4) 361 (68.2)
 Men 2968 (38.3) 57 (29.9) 7240 (41.6) 205 (31.8)
Race/ethnicity, n (%)
 Non-Hispanic white 3012 (70.7) 108 (72.9) 7607 (65.1) 289 (70.3)
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 Non-Hispanic black 2469 (12.4) 53 (16.0) 4052 (12.5) 146 (15.7)

 Mexican American 2621 (6.5) 27 (2.1) 3963 (9.2) 72 (4.2)
 Other 426 (10.4) 8 (9.0) 2924 (13.2) 59 (9.8)
Education level, n (%)
≤12 grade
  5847 (52.5) 164 (77.3) 8918 (37.4) 362 (57.4)
 >12 grade 2621 (47.0) 29 (22) 9600 (62.5) 202 (42.4)
 Missing 60 (0.5) 3 (0.7) 28 (0.1) 2 (0.2)
Poverty income ratio, n (%)
≤200%
  4019 (29.9) 114 (55.9) 7488 (30.0) 282 (43.2)
 >200% 3639 (62.8) 54 (34.2) 9442 (63.1) 235 (49.4)
 Missing 870 (7.3) 28 (9.9) 1616 (6.9) 49 (7.3)
Comorbidities, n (%)
 Hypertension* 2843 (28.7) 154 (75.6) 6903 (32.6) 461 (78.8)
 Diabetes† 1145 (9.3) 69 (33.7) 2247 (8.7) 197 (31.7)
 Hypercholesterolemia‡ 2623 (31.5) 107 (56.4) 6313 (33.1) 310 (54.4)
 Myocardial infarction 235 (1.9) 44 (18.4) 426 (1.8) 89 (14.0)
 Chronic kidney disease§ 894 (7.5) 47 (19.6) 1981 (8.0) 163 (27.4)
 COPD/emphysema‖ 1526 (15.7) 75 (31.0) 1245 (7.1) 60 (11.4)
 Alcohol intake in past year 2949 (44.8) 22 (12.3) 9772 (59.1) 228 (39.2)
Self-report household secondhand smoking, n (%)
 Yes 1576 (15.0) 27 (11.7) 1136 (5.9) 46 (7.0)
 No 6942 (84.9) 169 (88.3) 17 256 (93.4) 516 (92.1)
 Missing 10 (0.1) … 154 (0.7) 4 (0.9)
Serum cotinine, median (IQR), ng/mL 0.168 (0.069–0.482) 0.126 (0.035–0.726) 0.035 (0.011–0.103) 0.034 (0.011–0.090)
Myocardial infarction, secondhand smoking, alcohol intake in past year are assessed only by self-report. BP indicates blood pressure; COPD, chronic obstructive
pulmonary disease; IQR, interquartile range; and NHANES, US National Health and Nutrition Examination Surveys.
*BP >140/90 mm Hg or on antihypertensive medications or self-report.
†Hemoglobin A1C ≥6.5% or on diabetes medications or self-report.
‡Total serum cholesterol ≥240 mg/dL or on anticholesterol medications.
§Urine albumin to urine creatinine ratio >30 mg/g.
‖Forced expiratory volume 1/forced vital capacity ratio <0.7 or self-report.
 Lin et al   Secondhand Smoke and Stroke Outcomes    2831

Table 2.  Prevalence of Self-Reported Household Exposure to SHS by Level of Covariate in Never Smokers With and Without Self-
Reported History of Stroke
NHANES 1988–1994 NHANES 1999–2012 Temporal Change*
No
No Stroke Stroke No Stroke Stroke Stroke Stroke
Weighted P Weighted P Weighted P Weighted P
Count % Value Count % Value Count % Value Count % Value % %
Observed prevalence 14.6±0.8 … 11.5±3.0 … 5.9±0.3 … 6.6±1.2 … −8.7 −4.9
Age
 18–44 y 5052 16.8±1.1 <0.0001 11 2.1±1.7 0.03 9285 6.5±0.4 0.00 36 6.5±4.9 0.64 −10.3 4.4
 45–64 y 1620 15.2±1.2 28 25.1±10.9 5196 5.8±0.4 136 9.9±3.2 −9.3 −15.2
 65–79 y 1201 8.1±0.9 82 13.5±4.6 2666 4.6±0.5 222 6.0±1.7 −3.5 −7.5
≥80 y
  645 5.5±1.3 75 5.3±3.1 1245 3.0±0.5 168 5.8±1.8 −2.4 0.5
Sex
 Women 5553 14.8±0.9 139 14.9±3.9 0.01 11 210 5.7±0.3 358 6.8±1.5 −9.1 −8.1
 Men 2965 15.3±1.3 0.71 57 3.8±2.4 7182 6.3±0.4 0.24 204 7.7±2.3 0.74 −9.0 3.9
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Race
 Non-Hispanic white 3010 12.2±0.9 <0.0001 108 8.0±3.3 0.08 7563 5.6±0.4 <0.0001 287 6.0±1.6 0.03 −6.6 −1.9
 Non-Hispanic black 2465 22.4±1.2 53 22.1±4.8 4026 10.4±0.6 145 14.9±2.9 −12.0 −7.2
 Mexican American 2618 18.5±1.5 27 14.2±6.2 3915 4.6±0.4 72 0.4±0.4 −13.8 −13.8
 Other 425 23.3±3.7 8 22.9±15.2 2888 4.4±0.7 58 5.1±4.7 −18.8 −17.8
Education
≤12 grade
  5844 19.4±1.3 <0.0001 164 13.3±3.5 0.37 8813 8.6±0.5 <0.0001 358 7.7±1.7 0.50 −11.3 −5.6
 >12 grade 2619 9.5±0.9 29 6.6±5.2 9551 4.3±0.3 202 5.9±1.8 −5.2 −0.7
Poverty income ratio
≤200%
  4019 20.8±1.5 <0.0001 114 16.3±5.0 0.07 7485 8.3±0.6 <0.0001 282 6.7±1.4 0.93 −12.5 −9.6
 >200% 3638 11.6±0.8 54 4.4±2.7 9440 4.7±0.3 235 7.3±2.3 −6.8 2.9
Comorbidities
 Hypertension† Yes 2839 13.9±0.4 0.35 154 13.1±3.7 0.41 6861 6.4±0.4 0.12 458 6.8±1.3 0.53 −7.6 −6.3
No 5596 15.3±1.0 42 7.5±4.7 10 746 5.6±0.3 90 4.8±2.5 −9.6 −2.7
 Diabetes mellitus‡ Yes 1142 15.0±1.9 0.98 69 12.8±5.2 0.78 2228 7.1±0.7 0.06 195 7.2±2.2 0.68 −7.9 −5.6
No 7362 15.0±0.09 127 11.1±3.5 15 241 5.7±0.3 341 6.2±1.2 −9.3 −4.9
 Hypercholesterolemia§ Yes 2619 13.3±1.2 <0.0001 107 12.0±3.6 0.89 6266 4.9±0.3 <0.0001 307 4.2±1.1 0.01 −8.4 −7.9
No 2322 10.4±0.09 54 10.0±5.3 7221 5.1±0.4 183 9.1±2.6 −5.2 −0.9
 Myocardial infarction Yes 235 17.2±3.0 0.42 44 21.0±9.1 0.11 422 5.0±1.2 0.48 88 9.6±4.7 0.50 −12.2 −11.4
No 8151 14.8±0.8 150 9.7±2.8 17 970 6.0±0.3 474 6.7±1.2 −8.9 −3.0
 Chronic kidney disease‖ Yes 891 15.0±2.5 1.00 47 3.0±2.0 0.00 1959 6.2±0.8 0.64 161 4.9±1.4 0.07 −8.8 1.9
No 7377 15.0±0.9 116 9.5±3.0 15 976 6.0±0.3 342 6.9±1.6 −9.1 −2.6
 COPD/emphysema¶ Yes 1523 13.7±1.3 0.24 75 12.5±4.9 0.84 1236 7.4±0.9 0.06 60 8.3±0.8 0.80 −6.2 −4.2
No 6993 15.3±0.9 121 11.3±3.5 17 130 5.8±0.3 499 7.0±1.3 −9.4 −4.4
  Alcohol intake in past year Yes 2946 15.0±1.4 0.97 22 5.5±5.5 0.40 9695 6.4±0.4 0.05 227 8.2±2.4 0.53 −8.6 2.6
No 5572 15.0±0.9 174 12.5±3.3 8697 5.3±0.4 335 6.4±1.5 −9.7 −6.2
Myocardial infarction, SHS, alcohol intake in past year are assessed only by self-report. BP indicates blood pressure; COPD, chronic obstructive pulmonary disease; NHANES,
US National Health and Nutrition Examination Surveys; and SHS, secondhand smoking.
*Temporal change in the prevalence of self-reported household SHS was calculate by subtracting NHANES 1988–1994 value from NHANES 1999–2012 value.
†BP >140/90 mm Hg or on antihypertensive medications or self-report.
‡Hemoglobin A1C ≥6.5% or on diabetes mellitus medications or self-report.
§Total serum cholesterol ≥240 mg/dL or on anticholesterol medications.
‖Urine albumin to urine creatinine ratio >30 mg/g.
¶Forced expiratory volume 1/forced vital capacity ratio <0.7 or self-report.
 2832  Stroke  November 2016

Table 3.  Prevalence and Odds Ratio of Stroke by SHS Status and Across Serum Cotinine Level; NHANES 1988 to 1994 and
1999 to 2012
Stroke Prevalence Crude Model 1* Model 2†
1988–1994 Weighted % OR P Value OR P Value OR P Value
SHS
 Yes 1.20±0.33 0.75 (0.42–1.34) 0.33 1.01 (0.57–1.78) 0.97 0.91 (0.54–1.54) 0.72
 No 1.60±0.16 1.00 … 1.00 … 1.00 …
Serum cotinine
 Undetectable 2.31±0.53 1.00 … 1.00 … 1.00 …
 Below median 1.30±0.22 0.56 (0.30–1.05) 0.07 0.75 (0.39–1.45) 0.39 0.69 (0.35–1.37) 0.29
 Above median 1.47±0.26 0.63 (0.33–1.21) 0.17 0.98 (0.47–2.03) 0.96 0.95 (0.46–1.94) 0.88
Stroke prevalence Crude Model 1* Model 2†
1999–2012 Weighted % OR P Value OR P Value OR P Value
SHS
 Yes 2.69±0.48 1.21 (0.82–1.78) 0.34 1.33 (0.89–1.99) 0.17 1.31 (0.87–1.98) 0.19
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 No 2.24±0.14 1.00 … 1.00 … 1.00 …

Serum cotinine
 Undetectable 2.33±0.18 1.00 … 1.00 … 1.00 …
 Below median 1.68±0.28 0.72 (0.49–1.05) 0.08 0.81 (0.55–1.19) 0.28 0.82 (0.56–1.20) 0.28
 Above median 2.38±0.30 1.02 (0.76–1.38) 0.88 1.46 (1.06–2.02) 0.02 1.46 (1.05–2.03) 0.03
COPD indicates chronic obstructive pulmonary disease; NHANES, US National Health and Nutrition Examination Surveys; OR, odds ratio; and SHS,
secondhand smoking.
*Model 1: adjusted for age, sex, race, poverty index ratio, and education.
†Model 2: adjusted for age, sex, race, poverty index ratio, education, hypertension, diabetes mellitus, hypercholesterolemia, myocardial infarction, chronic
kidney disease, COPD/emphysema, lung cancer, and alcohol intake.

Dose-Dependent Relationship Between Exposure
to SHS and Mortality Among Survivors of Stroke
Survivors of stroke with self-reported exposure to SHS
had higher all-cause mortality compared with survivors of
stroke without exposure to SHS (age-adjusted mortality rate:
96.4±20.8 versus 56.7±4.8 per 1000 person-years; P=0.026;
Table 4). Survivors of stroke were at higher odds of dying
from exposure to SHS (adjusted hazard ratio=1.72; 95% CI,
1.02–2.91; P=0.041). This correlation was not observed in
participants in the 1988 to 1994 survey or among participants
without a history of stroke.
There was a dose-dependent relationship between the quan-
tity of exposure to SHS and all-cause mortality after stroke.
Age-standardized mortality rates per 1000 person-years were
48.4±4.9, 47.8±11.5, 75.9±23.6, 103.1±31.1 across increas-
ing cotinine quartiles (trend P=0.01; Figure [A]). Similarly,
adjusted 10-year cumulative mortality rates were 39.0±5.9%,
40.7±9.8%, 58.3±14.2%, 65.4±13.3% across increasing coti-
nine quartiles (trend P=0.019; Table 4). Adjusted mortality
rate ratios were 1.04, 1.74, and 2.11 across increasing cotinine
quartiles (trend P=0.019). This relationship was not observed
in people without stroke (Table II in the online-only Data
Supplement).
There was a differential effect of SHS on mortality by his-
tory of stroke (Figure [B]). Among individuals with previ-
ous stroke, people with serum cotinine levels in the highest
quartile had 2.3 times greater mortality rates compared with
those with undetectable cotinine levels (hazard ratio=2.34;
95% CI, 1.36–4.01; P<0.01). Among individuals without
a history of stroke, the corresponding age-standardized
hazard ratio was 1.28 (95% CI, 0.98–1.67; P=0.07). Mortality
rates associated with SHS were nearly 2 times greater for
people with stroke compared with those without stroke,
after adjusting for age (rate ratio=1.82; 95% CI, 0.95–3.50;
P=0.07).
Discussion
Over the past two and a half decades, the prevalence of house-
hold exposure to SHS among never smokers decreased con-
siderably from 12% to 7% in participants with previous stroke
and from 15% to 6% in participants without previous stroke.
Household exposure to SHS remained higher among younger
individuals, men, non-Hispanic blacks, and those living in
poverty. Individuals with previous stroke were more likely to
be exposed to SHS than those without previous stroke. There
was a dose-dependent relationship between exposure to SHS
and all-cause mortality after stroke. This dose–response rela-
tionship was not observed in people without previous history
of stroke.
Our finding of a temporal decline in SHS prevalence is
consistent with other population-based studies,11–13 meta-anal-
yses,14,15 and a recent CDC Mortality and Morbidity Weekly
Report.13 In an analysis of nonsmokers aged ≥3 years who
participated in NHANES 1999 to 2012, Homa et al13 found
 Lin et al   Secondhand Smoke and Stroke Outcomes    2833

Table 4.  All-Cause Mortality Across Serum Cotinine Quartiles and Self-Reported SHS Status Among Stroke Survivors
Self-Reported Exposure to SHS Serum Cotinine Quartiles
Detected, Detected, Detected,
1988–1994 No Yes P Value Undetectable <Median Quartile 3 Quartile 4 Trend P
No. of deaths/No. at risk 142/169 19/27 … 38/47 47/59 24/29 35/44 …
No. of person-years 1608 300 … 469 591 303 473 …
Crude mortality rate per
67.5±5.7 49.4±11.3 0.51 51.7±8.4 58.3±8.5 105.0±21.4 59.8±10.1 0.54
1000 person-years
Age-adjusted mortality
rate per 1000 person- 59.8±5.6 57.1±14.5 0.85 51.0±7.1 59.5±6.9 69.5±10.2 73.0±8.5 0.01
years
Adjusted 10-y cumulative
54.5±6.9% 43.4±16.8% 0.58 36.5±6.2% 50.1±6.9% 55.5±15.6% 52.7±10.0% 0.06
mortality risk (model 1)*
Adjusted 10-y cumulative
52.5±6.9% 46.5±18.6% 0.73 35.9±6.7% 43.9±6.6% 52.5±15.6% 60.3±12.8% 0.01
mortality risk (model 2)†
Adjusted (model 1)
Reference 0.72 (0.22–2.34) 0.58 Reference 1.53 (0.96–2.46) 1.79 (0.87–3.67) 1.65 (0.94–2.91) 0.06
hazard ratio*
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Adjusted (model 2)
Reference 0.84 (0.33–2.18) 0.73 Reference 1.30 (0.79–6.01) 1.67 (0.79–11.17) 2.08 (1.03–16.03) 0.01
hazard ratio†
Self-reported exposure to SHS Serum cotinine quartiles
Detected, Detected, Detected,
1999–2010 No Yes P Value Undetectable <median quartile 3 quartile 4 Trend P
No. of deaths/No. at risk 140/437 21/41 … 77/270 24/70 14/38 25/ 55 …
No. of person-years 2250 197 … 1374 429 164 267 …
Crude mortality rate per
57.0±4.8 83.9±18.3 0.15 53.7±6.1 45.6±9.3 57.0±15.2 95.7±19.1 0.06
1000 person-years
Age-adjusted mortality
rate per 1000 person- 56.7±5.5 96.4±20.8 0.03 48.4±8.9 47.8±11.5 75.9±23.6 103.1±31.1 0.00
years
Adjusted 10-y cumulative
45.5±5.1% 64.8±11.5% 0.04 39.5±5.8% 37.1±8.7% 50.3±14.2% 65.3±13.2% 0.02
mortality risk (model 1)*
Adjusted 10-y cumulative
43.8±5.6% 59.3±13.4% 0.17 39.0±5.9% 40.7±8.7% 58.3±14.2% 65.4±13.3% 0.02
mortality risk (model 2)†
Adjusted (model 1)
Reference 1.72 (1.02–2.91) 0.04 Reference 0.92 (0.50–1.70) 1.39 (0.65–2.99) 2.12 (1.15–3.85) 0.02
hazard ratio*
Adjusted (model 2)
ref 1.56 (0.83–2.93) 0.17 reference 1.04 (0.61–1.77) 1.74 (0.84–3.62) 2.11 (1.06–4.22) 0.02
hazard ratio†
NHANES 1988 to 1994 and 1999 to 2010 linked to mortality data 2010. COPD indicates chronic obstructive pulmonary disease; and SHS, secondhand smoke.
*Model 1 (demographic): adjusted for age, sex, race, poverty index ratio, and education.
†Model 2 (demographic+comorbidities): adjusted for age, sex, race, poverty index ratio, education, hypertension, diabetes mellitus, hypercholesterolemia, myocardial
infarction, chronic kidney disease, COPD/emphysema, and alcohol intake.

that exposure to SHS declined from 52.5% in 1999 to 2000 to
25.3% in 2011 to 2012. The 2011 to 2012 prevalence noted in
the study by Homa et al was similar to the prevalence observed
in the REGARDS study (Reasons for Geographic and Racial
Differences in Stroke) cohort (23%). Our design differed from
that of Homa et al in that we included a longer time frame,
only never smokers, adults ≥18 years, and reported outcomes
based on self-reported household exposure to SHS and coti-
nine levels.
We identified factors associated with higher household SHS
exposure: younger age, male sex, black race, lower education,
poverty, high alcohol intake, and history of MI. Similarly, a
US study demonstrated that during 2011 to 2012, SHS was
highest among children aged 3 to 11 years (40.6%), non-His-
panic blacks (46.8%), people living below the poverty level
(43.2%), and people living in rental housing (36.8%).13 Our
study also provides insights into temporal trends in household
SHS exposure. Although declines occurred in all age, sex, and
racial/ethnic categories among participants without previous
stroke, self-reported exposure to SHS increased among survi-
vors of stroke who were 18 to 44 years, ≥80 years, men, had
a PIR >200%, had a history of CKD, and had reported high
annual alcohol intake. These findings have not been reported
previously.
Since the 1980s, smoking bans have been implemented in a
variety of settings, likely contributing to the temporal decline
 2834  Stroke  November 2016
A B
Figure. A, Age-adjusted mortality rate per 1000 persons-year across serum cotinine level. B, Adjusted cumulative all-cause mortality
stratified by cotinine levels and stroke status. HR indicates hazard ratio.
in SHS.14 Comprehensive smoke-free legislation has been
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associated with lower rates of hospital admissions (and deaths)
for stroke (relative risk [RR], 0.84; 95% CI, 0.75–0.94), coro-
nary events (RR, 0.85; 95% CI, 0.82–0.88), and other heart
disease (RR, 0.61; 95% CI, 0.44–0.85).15 Numerous stud-
ies have shown a dose-dependent relationship between SHS
and stroke incidence.6,9,16,17 We further demonstrated a dose-
dependent relationship between household exposure to SHS
and all-cause mortality after stroke, a relationship that was not
observed in participants without stroke.
The lack of association between SHS and mortality among
those without stroke is hypothesis-generating and may imply
a differential physiological effect of exposure to SHS on
individuals with different comorbid conditions. Perhaps,
SHS can accelerate atherosclerosis in those with underlying
vascular risk factors but does not have an effect on those
without atherosclerosis. Indeed, SHS may act synergistically
with other vascular risk factors such as diabetes mellitus and
hypertension. Howard et al16 quantified the progression of
carotid artery atherosclerosis using 10 914 participants from
the ARIC study (Atherosclerosis Risk in Communities) and
found a greater impact of SHS smoking on atherosclerotic
progression in participants with diabetes mellitus than those
without diabetes mellitus (interaction P=0.004). Chronic
smoke exposure can lead to endothelial dysfunction,
impaired arterial wall elasticity leading to dysfunctional
cerebral autoregulation as have been demonstrated in animal
and human studies.18–21
The prevalence of stroke was greater in those who self-
reported exposure to SHS than those without this exposure
in the later cohort (1999–2012) but not in the earlier cohort
(1988–1994). A similar pattern was observed for those with
cotinine levels above the median when compared with people
with undetectable cotinine levels across time eras (Table 3).
The difference in findings between time eras may be attribut-
able to improved sensitivity of instruments used in cotinine
detection in 2001. The limit of detection for serum cotinine
was 0.05 ng/mL and changed to 0.015 mg/mL because of
improvements in the method. It is also plausible that the dif-
ference is because of chance as crude and adjusted odds ratios
for self-reported SHS were nonsignificant in either crude or
adjusted models. The observation that the odds ratios for those
with cotinine levels below the median (but not undetectable)
seem to have better outcomes than those with undetectable
levels of cotinine may provide some support that these are
chance findings.
This study has several strengths: we used a large nation-
wide sample of individuals in the United States, with both
survey- and laboratory-based measurements for exposure to
SHS and comorbid conditions. Use of serum cotinine lev-
els reduced recall bias intrinsic to self-reported SHS; nev-
ertheless, one cannot completely exclude miss-reporting or
laboratory errors. This study has several limitations. First,
because stroke was assessed by self-report, we lacked infor-
mation about stroke type, duration since stroke, stroke sever-
ity, and functional status, factors which may have had an
effect on mortality. Second, NHANES only captures nonin-
stitutionalized individuals and those who can comprehend
and respond to surveys, resulting in a possible bias toward
a healthier population. Third, we lacked detail on the dura-
tion and location of exposure to SHS. Serum cotinine levels
could be influenced by places outside of the household, such
as in the workplace, restaurants, and transportation system.
Although smoke-free laws may have contributed to decline in
total serum cotinine as exposure to smoking in public places
have declined, they may not necessarily have direct impact on
reducing household SHS.
In summary, the prevalence of exposure to SHS among
never smokers with and without history of stroke declined
between 1988 to 1994 and 1999 to 2012. High exposure to
SHS was associated with history of previous stroke. There
was a dose-dependent relationship between exposure to SHS
and all-cause mortality after stroke, but this relationship was
not observed in people without stroke. Although prospective
studies are needed to assess causality, this study highlighted
the importance of obtaining exposure to SHS history and
counseling patients and their families on the potential impact
of SHS on poststroke outcomes.
Sources of Funding
B. Ovbiagele is supported by award number U01 NS079179 from the
National Institute of Neurological Disorders and Stroke. A. Towfighi
 Lin et al   Secondhand Smoke and Stroke Outcomes    2835
is supported by 1U54NS081764-01 from the National Institute of
Neurological Disorders and Stroke and 11SDG7590160 from the
American Heart Association.
Disclosures
None.
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 Association of Secondhand Smoke With Stroke Outcomes
Michelle P. Lin, Bruce Ovbiagele, Daniela Markovic and Amytis Towfighi

Stroke. 2016;47:2828-2835; originally published online October 11, 2016;

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doi: 10.1161/STROKEAHA.116.014099
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SUPPLEMENTAL MATERIAL
Supplemental Table I. Observed distribution of serum cotinine (weighted percent) among
never-smokers

NHANES 1999-2012 NHANES 1988-1994

Serum Cotinine
(ng/ml)
Overall Stroke Nonstroke Overall Stroke Nonstroke

undetectable, < 0.05 64.78 68.44 64.69 21.84 29.83 21.71

0.05 to <0.1 11.26 9.35 11.3 17.54 16.83 17.55
0.1 to < 0.5 12.58 12.46 12.58 37.45 25.46 37.64
0.5 to < 1.0 2.88 2.43 2.89 9.32 11.61 9.29
1.0 to < 10.0 4.12 3.89 4.13 9.49 9.75 9.49
≥ 10.0 4.38 3.43 4.4 4.35 6.52 4.32
Supplemental Table II. Mean serum cotinine levels among never-smokers by stroke status, NHANES 1988-1994, 1999-2012

NHANES 1988-1994 NHANES 1999-2012

No Stroke Stroke Survivor No Stroke Stroke Survivor

p- p- p-
N mean SE N mean SE N mean SE p-value N mean SE
value value value

Overall -- 0.240 0.013 -- -- 0.260 0.063 -- -- 0.062 0.002 -- -- 0.056 0.006 --

Age
18-44 yrs 4,718 0.27 0.02 0.00 11 0.19 0.20 0.36 8,693 0.080 0.004 <0.0001 30 0.075 0.030 0.52
45-64 yrs 1,549 0.21 0.01 27 0.25 0.16 4,928 0.051 0.002 125 0.064 0.016
65-79 yrs 1,107 0.17 0.01 76 0.38 0.12 2,508 0.040 0.002 207 0.055 0.009
≥ 80 yrs 594 0.17 0.03 65 0.17 0.06 1,130 0.036 0.002 145 0.044 0.009

Sex
Women 5,192 0.18 0.01 <.0001 126 0.23 0.06 0.50 10,496 0.045 0.001 <0.0001 322 0.044 0.005 0.01
Men 2,776 0.37 0.03 53 0.33 0.17 6,763 0.099 0.005 185 0.094 0.023

Race/Ethnicity
Non-Hispanic white 2,853 0.22 0.01 <.0001 102 0.19 0.05 <.0001 7,200 0.056 0.002 271 0.047 0.006
Non-Hispanic black 2,255 0.53 0.04 43 0.75 0.26 3,590 0.163 0.013 120 0.161 0.042
Mexican American 2,467 0.18 0.01 26 0.09 0.02 3,743 0.046 0.002 <0.0001 64 0.046 0.013 0.00
Other 393 0.24 0.03 8 0.83 1.03 2,726 0.056 0.004 52 0.051 0.016

Education Level
≤ 12 grade 5,453 0.32 0.02 <.0001 147 0.30 0.08 0.38 8,209 0.095 0.004 <0.0001 315 0.078 0.014 0.00
> 12 grade 2,470 0.18 0.01 29 0.17 0.10 9,029 0.048 0.002 191 0.036 0.004

Poverty Income Ratio

≤ 200% 3,741 0.34 0.02 <.0001 101 0.35 0.11 0.09 6,958 0.096 0.005 <0.0001 243 0.073 0.012 0.02
 > 200% 3,439 0.20 0.01 51 0.15 0.06 8,868 0.050 0.002 222 0.042 0.006

Comorbidities
Hypertension* yes 2,636 0.24 0.02 0.88 142 0.28 0.07 0.62 6,404 0.060 0.002 0.36 414 0.051 0.006 0.28
no 5,259 0.24 0.01 37 0.21 0.11 10,219 0.062 0.002 83 0.074 0.022

Diabetes† yes 802 0.22 0.02 0.42 57 0.30 0.14 0.66 2,089 0.060 0.004 0.57 174 0.064 0.013 0.33
no 7,161 0.24 0.01 122 0.24 0.06 0.66 15,135 0.062 0.002 331 0.052 0.006

Hypercholesterolemia‡ yes 2,163 0.18 0.01 0.99 94 0.23 0.05 0.31 5,984 0.048 0.002 0.00 287 0.047 0.007 0.36
no 2,285 0.18 0.01 52 0.41 0.23 7,236 0.056 0.002 183 0.060 0.011

Myocardial Infarction yes 213 0.28 0.05 0.33 40 0.48 0.36 0.29 394 0.063 0.009 0.93 78 0.116 0.046 0.04
no 7,633 0.24 0.01 137 0.22 0.05 16,865 0.062 0.002 429 0.050 0.005

chronic kidney disease § yes 821 0.20 0.02 0.04 43 0.14 0.05 0.13 1,833 0.062 0.004 0.99 156 0.050 0.009 0.65
no 6,960 0.24 0.01 112 0.26 0.08 15,204 0.062 0.002 312 0.055 0.008

COPD/emphysema ** yes 1,381 0.24 0.02 0.90 64 0.29 0.10 0.75 1,173 0.060 0.005 0.66 53 0.064 0.023 0.67
no 6,585 0.24 0.01 115 0.25 0.07 16,061 0.062 0.002 451 0.055 0.006

alcohol intake in past year yes 2,804 0.31 0.03 <.0001 21 0.44 0.33 0.46 9,297 0.071 0.003 <0.0001 209 0.081 0.017 0.02
no 5,164 0.20 0.01 158 0.24 0.06 7,962 0.051 0.002 298 0.044 0.006
* BP > 140/90 or on anti-hypertensive medications, or self-report
† Hemoglobin A1C ≥ 6.5% or on diabetes medications, or self report
‡ Totl serum cholesterol ≥ 240 mg/dl or on anti-cholesterol medications
§ urine albumin to urine creatinine ratio > 30 mg/g
# Alcohol consumption in past year
** FEV1/FVC < 0.7, or self report
myocardial infarction,second-hand smoking, alchol intake in past year: self-report
†† temporal change in the prevalence of self-reported household SHS was calculate by subtracting NHANES 1988-1994 value from NHANES 1999-2012 value
Supplemental Table III. Risk of death according to serum cotinine quartiles, and self-reported secondhand smoke (SHS) status among persons
without stroke, NHANES 1999-2010, 1988-1994 linked to mortality data 2010

Unadjusted Model 1 Model 2

1999-2010
HR lower upper p-value HR lower upper p-value HR lower upper p-value

self-reported household exposure to SHS

no 1.00 ref ref ref 1.00 ref ref ref 1.00 ref ref ref
yes 0.87 0.62 1.23 0.4390 1.29 0.91 1.83 0.1480 1.26 0.90 1.77 0.1770

serum cotinine levels

undetectable (<0.05ng/ml) 1.00 ref ref ref 1.00 ref ref ref 1.00 ref ref ref
exposed, < median 0.87 0.69 1.11 0.2630 1.00 0.79 1.27 0.9920 1.02 0.81 1.28 0.8940
exposed, quartile 3 0.71 0.49 1.02 0.0620 0.99 0.69 1.42 0.9610 0.93 0.65 1.34 0.7050
exposed, quartile 4 0.55 0.39 0.80 0.0010 1.03 0.72 1.49 0.8600 0.97 0.65 1.45 0.8890

Unadjusted Model 1 Model 2

1988-1994
HR lower upper p-value HR lower upper p-value HR lower upper p-value
self-reported household exposure to SHS
no 1.00 ref ref ref 1.00 ref ref ref 1.00 ref ref ref
yes 0.69 0.55 0.86 0.0010 1.04 0.85 1.26 0.7230 0.99 0.81 1.21 0.9120

serum cotinine levels

undetectable (<0.05ng/ml) 1.00 ref ref ref 1.00 ref ref ref 1.00 ref ref ref
exposed, < median 0.71 0.56 0.89 0.0040 0.96 0.82 1.12 0.6220 1.01 0.86 1.18 0.9040
exposed, quartile 3 0.53 0.41 0.68 0.0000 1.02 0.82 1.28 0.8610 1.02 0.81 1.29 0.8700
exposed, quartile 4 0.46 0.35 0.61 0.0000 0.96 0.76 1.21 0.7380 0.97 0.76 1.25 0.8230

* model 1 (demographic): adjusted for age, sex, race, poverty index ratio, education

** model 2 (demographic + comorbidities): adjusted for age, sex, race, poverty index ratio, education, hypertension, diabetes, hypercholesterolemia, myocardial infarction, chronic
kidney disease, COPD/emphysema, alcohol intake