Environmental tobacco smoke exposure and heart disease: A systematic review

Table 1 Studies providing evidence on heart disease and environmental tobacco smoke exposure in never smokers

Study No.	Ref.1	Year2	Location	Type3	Sexes included4	Disease fatality5	Disease definition6	No. of cases7
1	Hirayama[29]	1984	Japan	P16	F	F	IHD	494
2	Garland et al[30]	1985	United States/California	P10	F	F	IHD	19
3	Lee et al[31]	1986	England	CC	M, F	NF	IHD	118
4	Martin et al[32]	1986	United States/Utah	CS	F	NF	PHA	23
5	Svendsen et al[33]	1987	United States	P9	M	F + NF	IHD	69
6	Butler[34]	1988	United States/California	P6	F	F	IHD	808
7	Palmer et al[35]	1988	United States/Not known	CC	F	NF	MI	336
8	Hole et al[36]	1989	Scotland	P12	M, F	F, NF	IHD, A/E	120
9	Jackson[37]	1989	New Zealand	CC	M, F	F + NF	IHD + MI	303
10	Sandler et al[38]	1989	United States/Maryland	P12	M, F	F	AHD	1358
11	Humble et al[39]	1990	United States/Georgia	P20	F	F	CVD	76
12	Dobson et al[40]	1991	Australia	CC	M, F	F + NF	IHD + MI	343
13	Gardiner et al[41]	1992	Scotland	CC	M + F	F + NF	IHD	12
14	La Vecchia et al[42]	1993	Italy	CC	M, F	NF	FMI	113
15	Layard[25]	1995	United States	CC	M, F	F	IHD	1389
169	Le Vois et al[26] (CPS I)	1995	United States	P13	M, F	F	AHD	14891
17	Mannino et al[43]	1995	United States	CS	M + F	NF	CVD	?
18	Muscat et al[44]	1995	United States/4 cities	CC	M, F	NF	NMI	114
19	Tunstall-Pedoe et al[45]	1995	Scotland	CS	M + F	NF	IHD	428
20	Steenland et al[46]	1996	United States	P7	M, F	F	IHD	3819
21	Janghorbani et al[47]	1997	Iran	CC	F	NF	IHD	200
22	Kawachi et al[48]	1997	United States	P10	F	F + NF	IHD + MI	152
23	Ciruzzi et al[49]	1998	Argentina	CC	M, F	NF	FMI	336
24	McElduff et al[50]	1998	Australia	CC	M, F	F + NF	MI	283
25	Spencer et al[51]	1999	Australia	CC	M	NF	FMIS	91
26	He et al[52]	2000	China/Xi’an	CC	F	NF	MI/CS	115
27	Iribarren et al[53]	2001	United States	CS	M, F	NF	HD	4801
28	Rosenlund et al[54]	2001	Sweden	CC	M, F	NF	FMI	334
29	Pitsavos et al[55]	2002	Greece	CC	M + F	NF	FMI/UA	279
309	Enstrom et al[27]	2003	United States/California	P39	M, F	F	IHD	5932
31	Chen et al[56]	2004	Scotland	CS	M + F	NF	IHD	385
32	Nishtar et al5710	2004	Pakistan	CC	M + F	NF	CAD	?
3311	Whincup et al[58]	2004	Great Britain	P21	M	F + NF	IHD	111
34	McGhee et al[59]	2005	Hong Kong	CC	M, F	F	IHD	584
35	Qureshi et al[60]	2005	United States	P11	F	F + NF	CVD	328
							CVD-Stroke	219
36	Hedblad et al[61]	2006	Sweden	P19	M	F + NF	IHD + MI, FMI	91
37	Stranges et al[62]	2006	United States	CC	M, F	NF	FMI	284
38	Teo et al[63]	2006	52 countries	CC	M + F	NF	FMI	6280
39	Wen et al[64]	2006	China/Not known	P6	F	F	CVD	272
							CVD-Stroke	115
40	Eisner et al[65]	2007	United States	P8	M, F	F	CVD	1057
41	Hill et al[66]	2007	New Zealand	P3	M, F	F	IHD	2571
42	Hill et al[66]	2007	New Zealand	P3	M, F	F	IHD	1680
43	He et al[67]	2008	China/Beijing	CS	F	NF	IHD	431
44	Sulo et al[68]	2008	Albania	CC	M + F	NF	ACS	169
45	Vozoris et al[69]	2008	Canada	CS	M + F	NF	HD	1773
46	Ding et al[70]	2009	Hong Kong	CC	F	NF	IHD	314
47	Gallo et al[71]	2010	Europe	P?	M, F	F	CVD12	399
					M + F		IHD	81
48	Hamer et al[72]	2010	England, Scotland	P7	M + F	F	CVD	96
4911	Jefferis et al[73]	2010	Great Britain	P11	M + F	F + NF	FMI	74
50	Peineman et al[74]	2011	Germany	CS	M + F	NF	IHD	128
51	Chen[75]	2012	China/4 provinces	CS	M + F	NF	IHD	405
							MI	171
52	He et al[76]	2012	China/Xi’an	P26	M, F	F	IHD	41
53	Clark et al[77]	2013	Singapore	P16	M, F	F	IHD	311
54	Iversen et al[78]	2013	Norway	P11	M, F	F + NF	FMI	326
55	Kastorini et al[79]	2013	Greece	CC	M + F	NF	ACS	52
56	Rostron[80]	2013	United States	P11	M + F	F	IHD	?
57	Batty et al[81]13	2014	United Kingdom	P17	M, F	F	CVD	98
58	Shiue[82]	2014	Scotland	CS	M + F	NF	MI	255

¹First author of paper, followed by a number to distinguish multiple studies with the same author;

²Year of publication;

³Study types are CC: Case-control, CS: Cross-sectional, P: Prospective. Number after P is estimated mean years of follow-up; ?: Indicates length of follow-up not stated;

⁴M + F indicates only results for combined sexes available; M, F indicates separate sex results available;

⁵F: Fatal; NF: Non-fatal; F + NF indicates only combined results available; F, NF indicates separate results available;

⁶A/E: Angina or ECG abnormality; ACS: Acute coronary syndrome; AHD: Arteriosclerotic heart disease; CAD: Coronary artery disease; CVD: Cardiovascular disease; FMI: First myocardial infarction; FMI/UA: First myocardial infarction or unstable angina; FMIS: First myocardial infarction surviving 28 d, HD: Heart disease; IHD: Ischaemic (coronary) heart disease; MI: Myocardial infarction; MI/CS: Myocardial infarction or coronary stenosis; NMI: Newly diagnosed myocardial infarction; PHA: Previous heart attack. “+” indicates inclusion of cases with either disease, indicates different outcome definitions for fatal and non-fatal analyses respectively;

⁷Number of heart disease cases in never smokers are totals in the study. For analyses relating to some exposure indices, numbers may be lower than this. ? indicates numbers not available;

⁸For study 6 numbers relate only to the spouse-pairs cohort, the AHSMOG cohort including ex-smokers;

⁹Studies 16 and 30 were both part of CPS I. Study 30 covered a smaller geographic area but a longer follow-up period;

¹⁰For study 32, although the source paper does not state that the analyses were restricted to never smokers, this has been confirmed to us by the authors;

¹¹Study 49 included the same male participants as study 33, but started at the end of the follow-up period of that study, so there was no overlap of cases between the two studies;

¹²For study 47, CVD was defined as any circulatory disease excluding cerebrovascular causes;

¹³For study 57, results in never smokers were taken from Supplementary tables supplied by the authors.

Table 2 Potential confounding variables adjusted for and definition of never smoker

Study No.	Ref.1	Variables adjusted for2	Definition of never smokers3
1	Hirayama[29]	Sex, age, marital status	Never cigarettes
2	Garland et al[30]	Sex, age, marital status, blood pressure, cholesterol, obesity	Never cigarettes
3	Lee et al[31]	Sex, age, marital status	Never NOS
4	Martin et al[32]	Sex, marital status, blood pressure, obesity, alcohol, diabetes, family history of heart disease, exercise	Never NOS
5	Svendsen et al[33]	Sex, age, marital status, blood pressure, cholesterol, social class, obesity, alcohol	Never any product
6	Butler[34]	Sex, age, marital status	Never cigarettes
7	Palmer et al[35]	Sex, marital status	Never NOS
8	Hole et al[36]	Sex, age, blood pressure, cholesterol, social class, obesity	Never NOS
9	Jackson[37]	Sex, age, social class, obesity, family history of heart disease	Never NOS
10	Sandler et al[38]	Sex, age, social class, personal history of heart disease	Never any product
11	Humble et al[39]	Sex, age, marital status, blood pressure, cholesterol, obesity	Never NOS
12	Dobson et al[40]	Sex, age, social class, obesity, personal history of heart disease	Never cigarettes
13	Gardiner et al[41]	Sex, age, hospital admission date	Never any product
14	La Vecchia et al[42]	Sex, age, marital status, blood pressure, cholesterol, social class, obesity, diabetes, family history of heart disease, coffee	Never NOS
15	Layard[25]	Sex, age, marital status, race	Never 100 cigarettes in lifetime
16	Le Vois et al[26] (CPS I)	Sex, age, marital status, race	Never NOS
17	Mannino et al[43]	Sex, age, social class, race, housing	Never NOS
18	Muscat et al[44]	Sex, age, blood pressure, social class, race	Never one cigarette, pipe or cigar per day for more than a year
19	Tunstall-Pedoe et al[45]	Age, blood pressure, cholesterol, housing	Never any product and cotinine < 17.5 mg/mL
20	Steenland et al[46]	Sex, age, marital status, blood pressure, social class, obesity, alcohol, diabetes, exercise, personal history of heart disease, occupation, oestrogen use, aspirin use, diuretic use and personal history of arthritis	Never any product daily for as long as a year (men), never cigarettes (women)
21	Janghorbani et al[47]	Sex, age, marital status	Never any product
22	Kawachi et al[48]	Sex, age, blood pressure, cholesterol, obesity, alcohol, diabetes, family history of heart disease, exercise, occupation, oestrogen use, oral contraceptive use, saturated fat intake, vitamin E intake, menopausal status and use of postmenopausal hormones	Never NOS
23	Ciruzzi et al[49]	Sex, age, blood pressure, cholesterol, social class, obesity, diabetes, family history of heart disease, exercise	Never NOS
24	McElduff et al[50]	Sex, age, social class, obesity, family history of heart disease	Never cigarettes or quit at least 10 yr ago, and not current other products
25	Spencer et al[51]	Sex, age	Never NOS
26	He et al[52]	Sex, age, blood pressure, cholesterol, family history of heart disease, personality type	Never NOS
27	Iribarren et al[53]	Sex, age, marital status, cholesterol, social class, obesity, alcohol, diabetes, race, exercise, personality type	Never any product
28	Rosenlund et al[54]	Sex, age, blood pressure, cholesterol, social class, obesity, diabetes, occupation	Never any product regularly for at least a year
29	Pitsavos et al[55]	Sex, age, blood pressure, cholesterol, obesity, alcohol, diabetes, exercise and family history of heart disease	Never cigarettes
30	Enstrom et al[27]	Sex, age, marital status, social class, obesity, race, exercise, housing, fruit or fruit juice intake and health status	Never any product4
31	Chen et al[56]	Sex, age, blood pressure, cholesterol, social class, obesity, alcohol, family history of heart disease, employment status, dietary vitamin C and fibre	Never NOS and cotinine < 17.5 mg/mL
32	Nishtar et al[57]	Sex, age, matched pair (conditional logistic regression was used)	Never NOS
33	Whincup et al[58]	Sex, age, blood pressure, cholesterol, social class, obesity, alcohol, diabetes, exercise, personal history of heart disease, town of residence, FEV1, height, triglycerides and white cell count	Never any product and cotinine < 14.1 mg/mL
34	McGhee et al[59]	Sex, age, marital status, social class	Never NOS
35	Qureshi et al[60]	Sex, age, marital status, blood pressure, cholesterol, obesity, alcohol, diabetes, race	Never NOS
36	Hedblad et al[61]	Sex, blood pressure, cholesterol, obesity, alcohol, diabetes, exercise, personal history of heart disease, triglycerides and FEV1	Never one cigarette per day
37	Stranges et al[62]	Sex, blood pressure, cholesterol, social class, obesity, alcohol, diabetes, race, exercise	Never 100 cigarettes in lifetime
38	Teo et al[63]	Sex, age, alcohol, exercise, region, consumption of fruits and vegetables	Never any product regularly
39	Wen et al[64]	Sex, age, social class, obesity, exercise, occupation, intake of meats, vegetables and fruit	Never NOS
40	Eisner et al[65]	Sex, age, marital status, social class	Never cigarettes or quit at least 20 yr ago, and < 10 pack-years
41, 42	Hill et al[66]	Sex, age, marital status, social class, race, occupation	Never NOS
43	He et al[67]	Sex, age, marital status, blood pressure, cholesterol, social class, obesity, alcohol, diabetes, family history of heart disease, exercise, triglycerides, family history of stroke	Never 100 cigarettes in lifetime
44	Sulo et al[68]	Sex, age, blood pressure, social class, obesity, diabetes, family history of heart disease, race, exercise, occupation, financial loss in pyramid schemes, emigration of spouse and/or offspring, religious observance	Never cigarettes
45	Vozoris et al[69]	Sex, age, social class, province, immigration status, presence of children younger than 12 yr in household	Never cigarettes
46	Ding et al[70]	Sex, age, blood pressure, cholesterol, social class, alcohol, diabetes, family history of heart disease, exercise, oestrogen use, history of stroke, history of gout	Never NOS
47	Gallo et al[71]	Sex, age, social class, obesity, exercise, study centre	Never NOS
48	Hamer et al[72]	Sex, age, blood pressure, cholesterol, social class, exercise, personality type, survey location, log C-reactive protein, fibrinogen	Never NOS
49	Jefferis et al[73]	Sex, age, blood pressure, cholesterol, social class, obesity, alcohol, diabetes, exercise, region, triglycerides, FEV1, C-reactive protein, interleukin 6, white cell count	Never any product or quit at least 5 yr ago, and cotinine < 15 mg/mL
50	Peinemann et al[74]	None	Never NOS
51	Chen[75]	None	Never cigarettes
52	He et al[76]	Sex, age, marital status, blood pressure, cholesterol, social class, obesity, alcohol, occupation, triglycerides	Never 100 cigarettes in lifetime
53	Clark et al[77]	Sex, age, social class, obesity, dialect, dietary fibre intake	Never NOS
54	Iversen et al[78]	Sex, age, blood pressure, cholesterol, obesity, exercise, living with a smoker (for analysis of hours spent in smoke-filled rooms), hours spent in smoke-filled rooms (for analysis of living with a smoker)	Never cigarettes
55	Kastorini et al[79]	Sex, age, blood pressure, cholesterol, obesity, diabetes, family history of heart disease, exercise, personality type, Mediterranean Diet Score	Never one cigarette a day
56	Rostron[80]	Sex, age, race, social class, alcohol, blood pressure, obesity, personal history of heart disease	Never 100 cigarettes in lifetime
57	Batty et al[81]	Sex, age, social class, alcohol, diabetes, exercise, personal history of heart disease, personal history of cancer	Never NOS
58	Shiue[82]	Sex, age, race, social class, alcohol, survey weighting, exercise, blood pressure, obesity	Never any product

¹First author of paper;

²In some cases similar adjustment variables have been considered under one name. Thus blood pressure includes hypertension; social class includes education and income; obesity includes weight; family history of heart disease includes family history of hypertension; and housing includes urban-rural;

³Never any product: Never smoked cigarettes, pipes or cigars; Never NOS: Never smoked, product unspecified;

⁴Questions on pipe and cigar smoking were asked at baseline, but not at the follow-up interviews.

Table 3 Heart disease relative risk estimates used in the main analysis for spouse ever smoked (or nearest equivalent) and in sensitivity analyses for spouse a current smoker, as well as additional results for household exposure

			Exposure index
Study No.1	Author2	Sex	Source3	Timing4	Fatality5	Relative risk (95%CI)6
Results used in the main analysis7
1	Hirayama[29]	F	S	E	F	1.16 (0.94-1.43)8
2	Garland et al[30]	F	S	E	F	2.70 (0.63-11.58)
3	Lee et al[31]	M	S	M	NF	1.24 (0.58-2.67)
		F	S	M	NF	0.93 (0.53-1.64)
4	Martin et al[32]	F	S	E	NF	2.60 (1.20-5.70)9
5	Svendsen et al[33]	M	S	C	F + NF	1.61 (0.96-2.71)
6	Butler[34]	F	S	E	F	1.07 (0.65-1.75)
7	Palmer et al[35]	F	S	E	NF	1.20
8	Hole et al[36]	M	H10	E	F	1.73 (1.01-2.96)11
		F	H10	E	F	1.65 (0.79-3.46)11
9	Jackson[37]	M	H	C	F + NF	1.06 (0.39-2.91)
		F	H	C	F + NF	3.74 (1.15-12.19)
10	Sandler et al[38]	M	H	C	F	1.31 (1.05-1.64)
		F	H	C	F	1.19 (1.04-1.36)
11	Humble et al[39]	F	S	C(N)	F	1.59 (0.99-2.57)
12	Dobson et al[40]	M	H	C	F + NF	0.97 (0.50-1.86)
		F	H	C	F + NF	2.46 (1.47-4.13)
13	Gardiner et al[41]	M + F	S	M	F + NF	0.57 (0.19-1.74)
14	La Vecchia et al[42]	M	S	E	NF	1.09 (0.47-2.53)
		F	S	E	NF	1.27 (0.52-3.09)
15	Layard[25]	M	S	E	F	0.97 (0.73-1.28)
		F	S	E	F	0.99 (0.84-1.16)
16	Le Vois et al[26] (CPS I)	M	S	E	F	0.97 (0.90-1.05)
		F	S	E	F	1.03 (0.98-1.08)
17	Mannino et al[43]	M + F	H	C	NF	1.12
18	Muscat et al[44]	M	S	E	NF	1.38 (0.70-2.75)
		F	S	E	NF	1.33 (0.59-2.99)
19	Tunstall-Pedoe et al[45]	M + F	T	C	NF	1.34 (1.07-1.67)
20	Steenland et al[46]	M	S	E	F	1.09 (0.98-1.21)
		F	S	E	F	1.04 (0.93-1.16)
21	Janghorbani et al[47]	F	S	E	NF	1.38 (0.95-2.01)
22	Kawachi et al[48]	F	H	C	F + NF	1.53 (0.81-2.90)9
23	Ciruzzi et al[49]	M	S	C	NF	1.18 (0.55-2.52)
		F	S	C	NF	1.73 (0.89-3.36)
24	McElduff et al[50]	M	T	C	F + NF	0.82 (0.55-1.22)
		F	T	C	F + NF	2.15 (1.18-3.92)
25	Spencer et al[51]	M	H	E	NF	No significant association
26	He et al[52]	F	S	E	NF	1.60 (0.94-2.90)
27	Iribarren et al[53]	M	H	C	NF	1.13 (1.00-1.27)
		F	H	C	NF	1.20 (1.09-1.30)
28	Rosenlund et al[54]	M	S	E	NF	0.96 (0.64-1.44)
		F	S	E	NF	1.53 (0.95-2.44)
29	Pitsavos et al[55]	M + F	H	C	NF	1.33 (0.89-1.99)
30	Enstrom et al[27]	M	S	E	F	0.93 (0.83-1.04)
		F	S	E	F	0.99 (0.92-1.08)
31	Chen et al[56]	M + F	H	C	NF	1.20 (0.70-2.20)
32	Nishtar et al[57]	M + F	S	E	NF	2.38 (1.04-5.42)
34	McGhee et al[59]	M	H	P	F	1.30 (0.88-1.93)
		F	H	P	F	1.39 (0.95-2.04)
35	Qureshi et al[60]	F	S	E	F + NF	1.05 (0.81-1.38)12
37	Stranges et al[62]	M	H	E	NF	0.98 (0.65-1.50)
		F	H	E	NF	1.30 (0.67-2.51)
38	Teo et al[63]	M + F	T	C	NF	1.37 (1.27-1.48)
39	Wen et al[64]	F	S	M	F	0.99 (0.72-1.37)13
41	Hill et al[66]	M	H	C	F	1.04 (0.88-1.23)
		F	H	C	F	0.98 (0.83-1.17)
42	Hill et al[66]	M	H	C	F	1.18 (0.96-1.44)
		F	H	C	F	1.27 (0.98-1.66)
43	He et al[67]	F	T	T	NF	1.69 (1.31-2.18)
44	Sulo et al[68]	M	S	C	NF	1.68 (0.81-3.47)
		F	S	C	NF	1.19 (0.25-5.64)
45	Vozoris et al[69]	M + F	T	C	NF	1.00 (0.80-1.20)
46	Ding et al[70]	F	H	E	NF	1.52 (1.01-2.27)
47	Gallo et al[71]	M + F	S	C	F	1.99 (0.92-4.29)14
49	Jefferis et al[73]	M + F	S	C	F + NF	2.41 (1.04-5.59)
50	Peinemann et al[74]	M + F	T	C	NF	1.27 (0.84-1.92)
51	Chen[75]	M + F	T	E	NF	1.16 (0.93-1.45)15
52	He et al[76]	M	T	E	F	2.24 (0.76-6.59)
		F	T	E	F	2.10 (0.69-6.33)
53	Clark et al[77]	M	H	C	F	1.98 (1.00-3.93)
		F	H	C	F	0.94 (0.67-1.32)
54	Iversen et al[78]	M	H	A	F + NF	0.91 (0.61-1.35)
		F	H	A	F + NF	1.42 (1.06-1.90)
55	Kastorini et al[79]	M + F	T	E	NF	4.33 (1.52-12.38)
56	Rostron[80]	M + F	H	C	F	0.82 (0.39-1.70)
57	Batty et al[81]	M	H	C	F	1.26 (0.37-4.31)
		F	H	C	F	1.12 (0.55-2.28)
58	Shiue[82]	M + F	T	C	NF	1.47 (0.96-2.24)
Alternative result used in the analysis of spouse a current smoker
2	Garland et al[30]	F	S	C(N)	F	2.25 (0.32-15.74)
4	Martin et al[32]	F	S	C	NF	3.40
6	Butler[34]	F	S	C(N)	F	1.40 (0.51-3.84)
14	La Vecchia et al[42]	M	S	C(N)	NF	1.09 (0.39-3.01)
		F	S	C(N)	NF	1.36 (0.46-4.05)
16	Le Vois et al[26] (CPS I)	M	S	C(N)	F	0.98 (0.91-1.06)
		F	S	C(N)	F	1.04 (0.99-1.09)
20	Steenland et al[46]	M	S	C(N)	F	1.22 (1.07-1.40)
		F	S	C(N)	F	1.10 (0.96-1.27)
28	Rosenlund et al[54]	M	S	C(N)	NF	0.98 (0.57-1.69)
		F	S	C(N)	NF	2.59 (1.27-5.29)
30	Enstrom et al[27]	M	S	C(N)	F	0.92 (0.80-1.05)
		F	S	C(N)	F	0.97 (0.89-1.06)
37	Stranges et al[62]	M	H	C	NF	0.71 (0.40-1.23)
		F	H	C	NF	0.94 (0.48-1.82)
39	Wen et al[64]	F	S	C	F	1.19 (0.84-1.67)16
Additional household exposure results
18	Muscat et al[44]	M	H	E	NF	1.40 (0.70-2.81)
		F	H	E	NF	1.55 (0.55-4.37)
20	Steenland et al[46]	M	H	C(N)	F	1.15 (1.01-1.32)
		F	H	C(N)	F	1.07 (0.98-1.17)
21	Janghorbani et al[47]	F	H	E	NF	1.34 (0.94-1.91)
23	Ciruzzi et al[49]	M	H17	C	NF	1.89 (1.13-3.18)
		F	H17	C	NF	1.54 (0.95-2.51)
47	Gallo et al[71]	M + F	H	C	F	1.31 (0.83-2.08)18

¹Study 40 omitted as results only available per 10 years of living with a smoker. Studies 33, 36 and 48 omitted as they only provide results for a biochemical index of ETS exposure;

²First author of paper;

³S: Spouse (or partner), H: Household member (or exposure at home), T: Total;

⁴E: Ever exposed (compared to never exposed) or unspecified; M: During marriage; C(N): Current exposure (compared to never exposed); C: Current exposure (compared to non-current exposure), P: In the past, T: In the last 10 years, A: In adulthood;

⁵F: Fatal; NF: Non-fatal; F + NF indicates combined results were analysed;

⁶Relative risks are adjusted for covariates if adjusted data are available. Those without 95%CI are not used in the meta-analyses;

⁷Except where lacking a 95%CI, as in studies 7, 17 and 25;

⁸Adjusted for the age of the husband. Alternative estimates[115] were very similar;

⁹Estimates given by Wells[1];

¹⁰Cohabitant(s) age 45-64 also attending screening;

¹¹Estimates given by Wells[116];

¹²Result for CVD - Stroke. Result also available for CVD: 1.00 (0.81-1.24);

¹³Result for CVD - Stroke. Result also available for CVD: 1.18 (0.92-1.51);

¹⁴Result for CVD. Result for IHD shown in the “household” section of this table;

¹⁵Result for IHD. Result also available for myocardial infarction: 0.93 (0.66-1.31);

¹⁶Result for CVD - Stroke. Results also available for CVD: 1.37 (1.06-1.78);

¹⁷Smoking by close relatives (although not necessarily living in same home);

¹⁸Result for IHD. Result also available for CVD: 1.82 (1.06-3.12). ETS: Environmental tobacco smoke; CVD: Cardiovascular disease; IHD: Ischaemic heart disease; CPS: Cancer Prevention Studies.

Table 4 Meta-analyses of heart disease¹ risk among never smokers in relation to ever smoking by the spouse (or nearest equivalent)

		Fixed-effect	Random-effects	Publication bias	Heterogeneity2
Subgroup	n3	Relative risk (95%CI)	Relative risk (95%CI)	P4 value	χ2	DF5	P6 value
Main analyses7
All	75	1.10 (1.08-1.13)	1.18 (1.12-1.24)	< 0.001	176.45	74	< 0.001
By sex
Combined	14	1.32 (1.24-1.40)	1.30 (1.14-1.47)	NS	23.54	13	< 0.05
Males	25	1.04 (1.00-1.09)	1.07 (1.01-1.15)	< 0.05	32.90	24	NS
Females	36	1.09 (1.06-1.12)	1.20 (1.12-1.29)	< 0.001	81.04	35	< 0.001
			Between sexes		38.98	2	< 0.001
By continent
North America	25	1.05 (1.02-1.08)	1.07 (1.02-1.12)	< 0.05	45.67	24	< 0.01
Europe	23	1.31 (1.18-1.46)	1.31 (1.18-1.46)	NS	20.63	22	NS
Asia	14	1.29 (1.17-1.42)	1.32 (1.16-1.49)	< 0.05	18.94	13	NS
Other	13	1.26 (1.19-1.33)	1.24 (1.07-1.44)	NS	37.12	12	< 0.001
			Between continents		54.09	3	< 0.001
By publication period
1984-1991	16	1.28 (1.17-1.39)	1.35 (1.18-1.54)	< 0.05	21.29	15	NS
1992-1998	18	1.04 (1.00-1.07)	1.06 (1.00-1.12)	< 0.1	24.86	17	< 0.1
1999-2005	13	1.08 (1.03-1.13)	1.13 (1.02-1.24)	< 0.1	28.86	12	< 0.01
2006-2009	13	1.24 (1.17-1.31)	1.19 (1.06-1.34)	NS	32.96	12	< 0.001
2010-2016	15	1.26 (1.11-1.41)	1.31 (1.11-1.55)	< 0.05	21.07	14	< 0.1
			Between periods		47.42	4	< 0.001
By number of heart disease cases8
1-99	13	1.62 (1.32-1.99)	1.66 (1.30-2.11)	NS	14.83	12	NS
100-199	14	1.33 (1.11-1.58)	1.33 (1.11-1.58)	NS	5.78	13	NS
200-999	30	1.26 (1.17-1.35)	1.27 (1.16-1.39)	NS	44.09	29	< 0.05
1000+	18	1.08 (1.05-1.10)	1.08 (1.02-1.15)	NS	76.70	17	< 0.001
			Between numbers		35.06	3	< 0.001
By study design
Case-control	32	1.29 (1.21-1.36)	1.28 (1.15-1.42)	NS	52.18	31	< 0.05
Prospective	33	1.04 (1.01-1.07)	1.09 (1.03-1.14)	< 0.001	55.43	32	< 0.01
Cross-sectional	10	1.20 (1.14-1.28)	1.24 (1.12-1.37)	NS	16.78	9	< 0.1
			Between types		52.06	2	< 0.001
By number of confounders considered in the study
0-2	15	1.03 (0.99-1.07)	1.05 (0.92-1.12)	< 0.1	17.51	14	NS
3-4	10	1.27 (1.16-1.39)	1.32 (1.13-1.55)	NS	16.65	9	< 0.1
5-9	38	1.13 (1.09-1.18)	1.19 (1.09-1.30)	< 0.05	94.55	37	< 0.001
10+	12	1.16 (1.10-1.22)	1.21 (1.10-1.32)	< 0.05	21.01	11	< 0.05
			Between groups		26.72	3	< 0.01
By results available in the study on dose-response
No	24	1.15 (1.08-1.22)	1.19 (1.08-1.32)	< 0.05	44.81	23	< 0.01
Yes	51	1.10 (1.07-1.12)	1.18 (1.11-1.25)	< 0.01	129.74	50	< 0.001
			Between groups		1.90	1	NS
By spouse the index
Yes	34	1.03 (1.00-1.06)	1.06 (1.01-1.12)	< 0.001	47.62	33	< 0.05
No	41	1.23 (1.19-1.28)	1.24 (1.16-1.32)	NS	72.59	40	< 0.01
			Between groups		56.24	1	< 0.001
Spouse the index, by whether unmarried subjects were excluded
Yes	23	1.02 (0.99-1.05)	1.03 (0.99-1.07)	< 0.05	27.88	22	NS
No	11	1.30 (1.10-1.54)	1.35 (1.11-1.63)	< 0.01	12.00	10	NS
			Between groups		7.74	1	< 0.01
By heart disease fatality considered
Fatal	31	1.04 (1.01-1.07)	1.07 (1.02-1.12)	< 0.001	46.74	30	< 0.05
Non-fatal	31	1.27 (1.22-1.33)	1.27 (1.19-1.36)	NS	39.58	30	NS
Both	13	1.25 (1.10-1.43)	1.34 (1.06-1.68)	NS	28.43	12	< 0.01
			Between groups		61.70	2	< 0.001
By heart disease definition
IHD	32	1.06 (1.03-1.11)	1.12 (1.05-1.19)	< 0.001	56.92	31	< 0.01
MI	18	1.34 (1.25-1.43)	1.29 (1.14-1.46)	NS	23.10	17	NS
Other/Mixed	25	1.08 (1.05-1.12)	1.20 (1.10-1.30)	< 0.001	58.29	24	< 0.001
			Between definitions		38.14	2	< 0.001
By use of biomarker data to exclude smokers
Yes	6	1.30 (1.08-1.57)	1.30 (1.08-1.57)	NS	3.89	5	NS
No	69	1.10 (1.08-1.13)	1.18 (1.12-1.24)	< 0.001	169.45	68	< 0.001
			Between groups		3.12	1	< 0.1
By any use of proxy respondents
Yes	11	1.10 (0.99-1.23)	1.23 (0.98-1.53)	NS	26.38	10	< 0.01
No	64	1.10 (1.08-1.13)	1.18 (1.12-1.24)	< 0.001	150.07	63	< 0.001
			Between groups		0.00	1	NS
By type of control
Healthy	15	1.30 (1.13-1.50)	1.38 (1.12-1.70)	< 0.1	27.67	14	< 0.05
Diseased/hospital	15	1.12 (1.01-1.24)	1.14 (1.01-1.28)	< 0.1	14.72	14	NS
Both	2	1.37 (1.27-1.48)	1.37 (1.27-1.48)	NC	0.29	1	NS
Prospective/cross-sectional	43	1.07 (1.05-1.10)	1.13 (1.08-1.19)	< 0.001	91.01	42	< 0.001
			Between types		42.78	3	< 0.001
			Between types, excluding prospective/cross-sectional		9.51	2	< 0.01
By source of diagnosis
Death certificate only	27	1.04 (1.01-1.07)	1.06 (1.02-1.11)	< 0.01	41.57	26	< 0.05
Medical data used	41	1.35 (1.28-1.43)	1.34 (1.23-1.46)	NS	51.49	40	NS
Self-report only	7	1.17 (1.10-1.24)	1.17 (1.07-1.27)	NS	8.11	6	NS
			Between sources		75.29	2	< 0.001
By definition of never smoker
Never any product	11	1.10 (1.05-1.15)	1.15 (1.05-1.27)	NS	32.42	10	< 0.001
Never, product unstated	33	1.05 (1.02-1.09)	1.15 (1.07-1.24)	< 0.001	49.99	32	< 0.05
Never cigarettes	12	1.17 (1.06-1.30)	1.21 (1.05-1.38)	NS	16.54	11	NS
Other	19	1.20 (1.14-1.25)	1.21 (1.07-1.37)	NS	57.89	18	< 0.001
			Between definitions		19.62	3	< 0.001
Sensitivity analyses
Preferring unadjusted to adjusted estimates	75	1.06 (1.04-1.08)	1.16 (1.09-1.24)	< 0.01	321.31	74	< 0.001
Preferring current to ever exposure	75	1.12 (1.09-1.14)	1.19 (1.13-1.26)	< 0.001	176.96	74	< 0.001
Excluding studies 15 and 16	71	1.16 (1.12-1.19)	1.21 (1.15-1.28)	< 0.01	144.97	70	< 0.001
Excluding study 30	73	1.12 (1.10-1.15)	1.20 (1.14-1.26)	< 0.001	158.21	72	< 0.001
Excluding studies 15, 16 and 30	69	1.20 (1.17-1.24)	1.23 (1.17-1.29)	< 0.05	109.86	68	< 0.001

¹Nearest equivalent to IHD as shown in Tables 1 and 3;

²Heterogeneity relates to variation between studies within subgroup, except for results given in italics which relate to heterogeneity between subgroups;

³N: Number of estimates in meta-analysis;

⁴Egger test P expressed as < 0.001, < 0.01, < 0.05, < 0.1 or NS (P ≥ 0.1). NC indicates not calculable as too few data points;

⁵DF: Degrees of freedom;

⁶Expressed as < 0.001, < 0.01, < 0.05, < 0.1 or NS (P ≥ 0.1);

⁷Relative risks are adjusted for covariates if adjusted data are available, with estimates for ever exposure preferred to those for current exposure where there is choice;

⁸Number of cases was estimated for Nishtar[57] (as category 1-99) and for Rostron[80] (as category 100-199). MI: Myocardial infarction.

Table 5 Dose-response evidence for heart disease among never smokers in relation to smoking by the spouse or household members in adulthood

Study No.	Ref.1	Sex	Exposure grouping	Relative risks by grouping2	Significance (trend)3
Smoking by the spouse
1	Hirayama[29]	F	0, 1-19, 20+ (cigs/d)	1.00, 1.10, 1.314	+
5	Svendsen et al[33]	M	0, 1-19, 20+ (cigs/d)	1.00, 1.20, 1.75
14	La Vecchia et al[42]	M + F	0, 1-14, 15+ (cigs/d)	1.00, 1.13, 1.30
15	Layard[25]	M	0, 1-14, 15-34, 35+ (cigs/d)	1.00, 0.76, 1.07, 0.92
		F	0, 1-14, 15-34, 35+ (cigs/d)	1.00, 0.85, 1.15, 1.06
16	Le Vois et al[26] (CPS I)	M	0, 1-19, 20-39, 40+ (cigs/d)	1.00, 0.99, 0.98, 0.72
		F	0, 1-19, 20-39, 40+ (cigs/d)	1.00, 1.04, 1.06, 0.95
20	Steenland et al[46]	M	0, 1-19, 20, 21+ (cigs/d)	1.00, 1.33, 1.17, 1.09
		F	0, 1-19, 20, 21-39, 40+ (cigs/d)	1.00, 1.15, 1.07, 0.99, 1.04
		M	0, 1-12, 13-21, 22-29, 30+ (year)	1.00, 1.14, 1.13, 1.14, 1.25
		F	0, 1-14, 15-25, 26-33, 34+ (year)	1.00, 0.84, 0.99, 1.20, 1.20
		M	0, 1-5, 6-14, 15-27, 28+ (pack year)	1.00, 1.25, 1.33, 1.13, 1.00
		F	0, 1-12, 13-25, 26-33, 34+ (pack year)	1.00, 0.83, 1.12, 1.09, 1.26
21	Janghorbani et al[47]	F	0, 1-30, 31+ (year)	1.00, 1.74, 0.85
		F	0, 1-19, 20+ (cigs/d)	1.00, 1.76, 1.11
		F	0, 1-10, 11+ (pack year)	1.00, 1.95, 1.17
23	Ciruzzi et al[49]	F	0, 1-20, 21+ (cigs/d)	1.00, 0.82, 3.00
26	He et al[52]	F	0, 1-10, 11-20, 21+ (cigs/d)	1.00, 0.93, 1.40, 3.20	+
			0-5, 6-15, 16-30, 31+ (year)	1.00, 0.80, 2.10, 2.30	+
			0, 1-399, 400-799, 800+ (cigs/day × year)	1.00, 1.20, 1.90, 3.60	+
28	Rosenlund et al[54]	M + F	0, 1-19, 20+ (cigs/d)	1.00, 1.02, 1.58
		M + F	0, 1-32, 33+ (year)	1.00, 1.11, 1.25
		M + F	0, 1-20, 21+ (pack-year)	1.00, 1.09, 1.33
30	Enstrom et al[27]	M	0, 1-9, 10-19, 20, 21-39, 40+ (cigs/d)	1.00, 0.98, 0.82, 0.89, 1.13, 1.24
		F	0, 1-9, 10-19, 20, 21-39, 40+ (cigs/d)	1.00, 1.03, 0.99, 1.02, 0.88, 0.80
39	Wen et al[64]	F	0, < 8.8, 8.8-17.9, 18.0+ (pack-year)	1.00, 1.10, 1.12, 1.225
47	Gallo et al[71]	M + F	0, 0.5, 1.0, 1.5+ (packs/d)	1.00, 1.87, 1.89, 2.466
Smoking by household members
8	Hole et al[36]	F	0, 1-14, 15+ (cigs/d)	1.00, 2.09, 4.12	+
9	Jackson[37]	M	None, low, high (exposure)	1.00, 1.30, 0.90
		F	None, low, high (exposure)	1.00, 2.10, 7.50	+
18	Muscat et al[44]	M	None, 1-20, 21-30, 31+ (year)	1.0, 1.7, 1.5, 1.1
		F	None, 1-20, 21-30, 31+ (year)	1.0, 2.0, 0.9, 1.7
22	Kawachi et al[48]	F	None, occasional, regular	1.00, 1.19, 2.11	+
		F	< 1, 1-9, 10-19, 20-29, 30+ (year)	1.00, 1.19, 1.54, 1.11, 1.50
27	Iribarren et al[53]	M	0, 1-9, 10-39, 40+ (h/wk)	1.00, 1.12, 1.26, 1.20	+
		F	0, 1-9, 10-39, 40+ (h/wk)	1.00, 1.21, 1.31, 1.36	+
29	Pitsavos et al[55]	M + F	0, 1-4, 5-9, 10-19, 20-29, 30-39, 40+ (years living with a regular smoker)	1.00, 1.07, 1.16, 1.39, 1.75, 2.20, 3.09	+
34	McGhee et al[59]	M + F	0, 1, 2+ (smokers in the home)	1.00, 1.26, 1.68	+
40	Eisner et al[65]	M + F	Per 10 years exposure	1.10
46	Ding et al[70]	F	0, < 1, 1+ (packs/d)	1.00, 1.14, 1.69	+
			0, < 5, 5+, (year)	1.00, 1.26, 1.52	+
			0, < 4, 4+, (h/d)	1.00, 1.28, 1.82	+
			0, < 5, 5+, (pack-year)	1.00, 1.44, 1.53	+
			0, < 20, 20+ (h-year)	1.00, 1.22, 1.61	+
47	Gallo et al[71]	M + F	0, < 1, 1-2, 3+ (h/d)	1.00, 1.39, 2.08, 1.946	+
54	Iversen et al[78]	M	0, < 10, 10-19, 20-29, 30+ (year)	1.00, 0.70, 1.20, 0.70, 1.10
		F	0, < 10, 10-19, 20-29, 30+ (year)	1.00, 1.00, 1.40, 1.30, 1.60	+

¹First author of paper;

²Relative risks are adjusted for covariates if adjusted data are available;

³Significant (P < 0.05) positive (negative) trends are indicated by + (or -). Blank entries indicate non-significance. The trend test includes the unexposed group. Significant trends excluding the unexposed group are only evident for study 26 (all exposed indices);

⁴The 1-19 cigs/d group includes ex-smokers. Estimates are adjusted for the age of the husband. Alternative estimates, adjusted for the age of the subject are also given by Hirayama[115];

⁵Results for CVD. Not available for CVD - Stroke;

⁶Results for CVD. Not available for IHD. M: Male; F: Female; CVD: Cardiovascular disease; IHD: Ischaemic (coronary) heart disease.

Table 6 Relative risk of heart disease among never smokers in relation to four other indices of environmental tobacco smoke exposure

Study No.	Ref.1	Sex	Exposure index2	Relative risk (95%CI)3	Exposure description
3	Lee et al[31]	M	Workplace	0.66 (0.26-1.66)
		F	Workplace	0.69 (0.26-1.87)
		M	Total	0.39 (0.17-0.90)	Home, work, travel, leisure
		F	Total	0.52 (0.24-1.09)	Home, work, travel, leisure
5	Svendsen et al[33]	M	Workplace	1.40 (0.80-2.50)
		M	Total	1.17 (0.62-1.19)	Spouse, work
9	Jackson et al[37]	M	Workplace	1.80 (0.94-3.46)
		F	Workplace	1.55 (0.48-5.03)
		M	Total	1.14 (0.76-1.70)	Home, work
		F	Total	1.56 (0.76-3.20)	Home, work
12	Dobson et al[40]	M	Workplace	0.95 (0.51-1.78)
		F	Workplace	0.66 (0.17-2.62)
		M	Total	1.09 (0.72-1.63)	Home, work
		F	Total	2.24 (1.28-3.91)	Home, work
18	Muscat et al[44]	M	Workplace	1.20 (0.60-2.20)
		F	Workplace	1.00 (0.40-2.50)
		M	Childhood	0.79 (0.39-1.63)	Mother, father, other relatives
		F	Childhood	0.72 (0.30-1.72)	Mother, father, other relatives
19	Tunstall-Pedoe et al[45]	M + F	Total	1.34 (1.07-1.67)	Exposure to tobacco smoke from someone else in the previous three days
		M + F	Biomarker	1.13 (0.93-1.38)	Serum cotinine
20	Steenland et al[46]	M	Workplace	1.03 (0.89-1.19)
		F	Workplace	1.06 (0.84-1.34)
22	Kawachi et al[48]	F	Workplace	1.68 (0.81-3.47)
		F	Total	1.71 (1.03-2.84)	Home, work
24	McElduff et al[50]	M	Total	0.82 (0.55-1.22)	Daily at home, work
		F	Total	2.15 (1.18-3.92)	Daily at home, work
26	He et al[52]	F	Workplace	1.85 (0.86-4.00)4
		F	Total	2.87 (1.36-6.05)	Spouse, work
27	Iribarren et al[53]	M	Total	1.07 (0.96-1.19)	Home, small spaces, large indoor areas
		F	Total	1.10 (1.01-1.20)	Home, small spaces, large indoor areas
28	Rosenlund et al[54]	M	Workplace	1.14 (0.78-1.67)
		F	Workplace	0.94 (0.59-1.50)
		M + F	Total	1.18 (0.87-1.60)	Spouse, work
29	Pitsavos et al[55]	M + F	Workplace	1.97 (1.16-3.34)
		M	Total	1.33 (0.94-1.88)	Home, work
		F	Total	1.39 (0.87-2.23)	Home, work
31	Chen et al[56]	M + F	Workplace	1.70 (0.90-3.20)
		M + F	Total	1.50 (1.03-2.20)	Other people’s tobacco smoke in the previous three days
		M + F	Biomarker	0.86 (0.64-1.16)	Serum cotinine
32	Nishtar et al[57]	M + F	Total	2.87 (1.28-6.42)	Unspecified, but includes spouse and others
33	Whincup et al[58]	M	Biomarker	1.67 (1.03-2.72)	Serum cotinine
36	Hedblad et al[61]	M	Biomarker	2.22 (1.21-4.09)	Blood carboxyhaemoglobin
37	Stranges et al[62]	M	Workplace	0.97 (0.64-1.48)
		F	Workplace	0.96 (0.60-1.55)
		M	Childhood	1.04 (0.72-1.52)	Unspecified
		F	Childhood	0.93 (0.57-1.51)	Unspecified
		M	Total	1.11 (0.69-1.77)	Lifetime; home, work, public places; RR is compared to lower tertile of exposure
		F	Total	0.58 (0.33-1.03)	Lifetime; home, work, public places; RR is compared to lower tertile of exposure
38	Teo et al[63]	M + F	Total	1.37 (1.27-1.48)	Family, friends, co-workers
39	Wen et al[64]	F	Workplace	1.21 (0.74-2.01)5
		F	Childhood	1.49 (1.01-2.22)5	In early life from family members
		F	Total	1.25 (0.69-2.25) 5	Spouse, work, early life
43	He et al[67]	F	Total	1.69 (1.31-2.18)	Home, work
45	Vozoris et al[69]	M + F	Total	1.00 (0.80-1.20)	Exposed on most days in the previous month
47	Gallo et al[71] (EPIC)	M	Workplace	0.93 (0.46-1.90)6
		F	Workplace	0.76 (0.47-1.24)6
		M	Childhood	1.11 (0.72-1.69)6	Parents
		F	Childhood	1.18 (0.88-1.57)6	Parents
48	Hamer et al[72]	M	Biomarker	1.50 (0.85-2.64)	Salivary cotinine
49	Jefferis et al[73]	M + F	Biomarker	0.94 (0.59-1.51)	Serum cotinine
50	Peinemann et al[74]	M + F	Total	1.27 (0.84-1.92)	Home, work, other
51	Chen[75]	M + F	Total	1.16 (0.93-1.45)7	Home, work, other
52	He et al[76]	M	Total	2.24 (0.76-6.59)	Lifetime; home, work
		F	Total	2.10 (0.69-6.33)	Lifetime; home, work
54	Iversen et al[78]	M	Total	0.97 (0.61-1.55)	Time spent in smoke-filled rooms
		F	Total	0.70 (0.44-1.12)	Time spent in smoke-filled rooms
55	Kastorini et al[79]	M + F	Total	4.33 (1.52-12.38)	Partner, parents, children, roommates, colleagues; 30+ min/d
56	Rostron[80]	M + F	Biomarker	1.02 (0.70-1.47)	Serum cotinine
57	Batty et al[81]	M	Biomarker	0.49 (0.19-1.25)	Salivary cotinine
		F	Biomarker	1.26 (0.70-2.24)	Salivary cotinine
58	Shiue[82]	M + F	Total	1.47 (0.96-2.24)	Home, work, other

¹First author of paper;

²Biomarker RRs are all based on cotinine measurement except for study 36 which is based on COHb;

³Relative risks are adjusted for covariates if adjusted data are available. Some of the RRs are repeats of those given in Table 3;

⁴Estimate given by an earlier report of the same study[117];

⁵Results for CVD-Stroke. Results also available for CVD: workplace 0.92 (0.64-1.32), childhood 1.26 (0.94-1.69), total 1.45 (0.95-2.22);

⁶Results for CVD-Stroke. Not available for IHD;

⁷Result for IHD. Result for MI also available: 0.93 (0.66-1.31). M: Male; F: Female; CVD: Cardiovascular disease; IHD: Ischaemic (coronary) heart disease; MI: Myocardial infarction.

Table 7 Meta-analyses of heart disease¹ risk among never smokers in relation to four other indices of environmental tobacco smoke exposure

		Fixed-effect	Random-effects	Publication bias	Heterogeneity
Index of exposure	n2	Relative risk (95%CI)	Relative risk (95%CI)	P3	χ2	DF4	P5 value
Workplace	22	1.08 (0.99-1.19)	1.08 (0.99-1.19)	NS	20.12	21	NS
Childhood	7	1.12 (0.95-1.31)	1.12 (0.95-1.31)	< 0.1	4.77	6	NS
Total	33	1.21 (1.16-1.26)	1.23 (1.12-1.35)	NS	90.21	32	P < 0.001
Biomarker	9	1.11 (0.98-1.26)	1.15 (0.94-1.40)	NS	15.40	8	P < 0.1

¹Nearest equivalent to IHD as shown in Tables 1 and 6;

²n: Number of estimates in meta-analysis;

³Egger test P expressed as < 0.001, < 0.01, < 0.05, < 0.1 or NS (P ≥ 0.1);

⁴DF: Degrees of freedom;

⁵Expressed as < 0.001, < 0.01, < 0.05, < 0.1 or NS (P ≥ 0.1).

Table 8 Other indices of environmental tobacco smoke exposure - dose response results among never smokers

Study No.	Author1	Sex	Exposure grouping	Relative risk by grouping (95%CI)2	Significance3
Workplace exposure
22	Kawachi et al[48]	F	No, occasional, regular	1.00, 1.49, 1.92
26	He et al[52]	F	0-5, 6-10, 11-20, 21+ cigs/d	1.00, 0.87, 2.95, 3.56	+
		F	0-5, 6-15, 16+ year	1.00, 3.08, 1.56
		F	0, 1-2, 3, 4+ smokers	1.00, 1.16, 5.06, 4.11	+
		F	0, 1-2, 3-4, 5+ h/d	1.00, 0.62, 4.03, 21.32	+
		F	0, 1-2000, 2001-4000, 4000+, cigs/d × year × smokers × h	1.00, 1.00, 2.05, 9.23	+
28	Rosenlund et al[54]	M + F	0, 1-31, 32+ yr	1.00, 1.04, 1.30
		M + F	0, 1-68, 69+ h-year (= h/d × year)	1.00, 0.99, 1.48
39	Wen et al[64]	F	0, < 10, 10-24, > 24 yr	1.00, 0.86, 0.96, 0.934
40	Eisner et al[65]	M + F	Per 10 yr exposure	1.04
Childhood exposure
18	Muscat et al[44]		Exposure to mother, father, other relatives
		M	None, 1-17, > 17 yr	1.0, 0.9, 0.7
		F	None, 1-17, > 17 yr	1.0, 0.6, 0.8
39	Wen et al[64]	F	In early life from family members5
			0, < 20, 20+, year	1.00, 1.21, 1.364	+
Total exposure
3	Lee et al[31]		Home, work, travel, leisure combined index
		M	Score: 0-1, 2-4, 5-12	1.00, 0.43, 0.43
		F	Score: 0-1, 2-4, 5-12	1.00, 0.59, 0.81
5	Svendsen et al[33]		Spousal and/or workplace exposure
		M	Neither, spouse, work, both	1.0, 1.2, 1.0, 1.7
9	Jackson[37]		Exposure at home and/or work6
		M	No, yes	1.00, 1.14 (0.76-1.70)
		F	No, yes	1.00, 1.56 (0.76-3.20)
12	Dobson et al[40]		Exposure at home and/or work
		M	No, yes	1.00, 1.09 (0.72-1.63)
		F	No, yes	1.00, 2.24 (1.28-3.91)	+
19	Tunstall-Pedoe et al[45]		Exposure to tobacco smoke from someone else in the previous three days
		M + F	None, little, some, a lot, (self-classified)	1.00, 1.2, 1.5, 1.6	+
22	Kawachi et al[48]		Exposure at home and/or work
		F	None, occasional, regular	1.00, 1.58, 1.91	+
26	He et al[117]		ETS exposure from spouse and/or work
		F	Neither, spouse, work, both	1.00, 2.07, 2.53, 4.18	+
27	Iribarren et al[53]		Exposure at home, in small spaces, in large indoor areas
		M	0, 1-9, 10-39, 40+ total h/wk	1.00, 0.90, 1.08, 1.13	+
		F	0, 1-9, 10-39, 40+ total h/wk	1.00, 0.86, 1.07, 1.17	+
28	Rosenlund et al[54]		Exposure from spouse and/or work
		M + F	0, > 16, 7-16, 1-6, < 1, year ago	1.00, 0.92, 1.11, 1.30, 1.39
		M + F	0, 1-12, 13-23, 24-34, 35+, year	1.00, 0.72, 0.97, 1.54, 1.48	+
		M + F	0, 1-17, 18-41, 42-89, 90+, h-year, (= year × h/d)	1.00, 0.70, 1.22, 1.27, 1.55	+
29	Pitsavos et al[55]		Exposure at home and/or work
		M	None, occasional, regular	1.00, 1.25, 1.47	+
		F	None, occasional, regular	1.00, 1.29, 1.56	+
31	Chen et al[56]		Exposure to tobacco smoke from someone else in the previous three days
		M + F	None, a little, some, a lot	1.00, 1.30, 1.50, 1.80	+
			Exposure to other people’s tobacco smoke
		M + F	0, > 0-2, 3-5, ≥ 6 h/d	1.00, 1.20, 1.60, 1.70
37	Stranges et al[62]		Cumulative lifetime ETS exposure at home, work and in public settings
		M	Tertile: 1, 2, 3	1.00, 0.93, 1.40
		F	Tertile: 1, 2, 3	1.00, 0.50, 0.67
38	Teo et al[63]		Exposure from family, friends, co-workers
		M + F	< 1, 1-7, 8-14, 15-21, 22+ h/wk	1.00, 1.32, 1.52, 1.73, 1.49	+
43	He et al[67]		Exposed at home and/or work
		F	0, 1-9, 10-19, 20+, cigs/d	1.00, 1.41, 1.85, 1.77	+
			0, 1-20, 21-40, 41+, min/d	1.00, 1.46, 1.78, 1.86	+
52	He et al[76]		Exposed at home and/or work7
		M + F	None Low Moderate High	1.00, 1.74, 2.25, 3.79	+
54	Iversen et al[78]		Time spent in a smoke-filled rooms
		M	0, 1-6, > 6, h/d	1.00, 1.00, 0.80
		F	0, 1-6, > 6, h/d	1.00, 0.70, 0.70
58	Shiue[82]		Exposed at home, work, other people’s home
		M + F	0, 1, 2+ of these places	1.00, 1.37, 2.64	+
Biomarker
19	Tunstall-Pedoe et al[45]		Serum cotinine (ng/mL)
		M + F	0, > 0-1.05, 1.06-3.97, 3.98-17.49	1.00, 1.00, 1.30, 1.20
31	Chen et al[56]		Serum cotinine (ng/mL)
		M + F	0, > 0-1.05, 1.06-3.97, 3.98-17.49	1.00, 0.70, 1.00, 1.10
33	Whincup et al[58]		Serum cotinine (ng/mL)
		M	≤ 0.7, 0.8-1.4, 1.5-2.7, 2.8-14.0	1.00, 1.54, 1.89, 1.67	+
36	Hedblad et al[61]		Blood carboxyhaemoglobin (%)
		M	0.13-0.49, 0.50-0.57, 0.58-0.66, 0.67-5.47 (quartiles)	1.00, 1.26, 1.77, 3.71	+
48	Hamer et al[72]		Salivary cotinine (ng/mL)
		M + F	≤ 0.05, 0.06-0.70, 0.71-14.99	1.00, 1.33, 2.00	+
			Per unit increase in log cotinine	1.60 (1.11-2.31)
49	Jefferis et al[73]		Serum cotinine (ng/mL)
		M + F	≤ 0.05, 0.06-0.19, 0.20-0.70, 0.71-15	1.00, 0.91, 0.99, 0.94
			Per doubling of cotinine	1.00 (0.86-1.16)
56	Rostron[80]		Serum cotinine (ng/mL)
		M + F	< 0.1, 0.1- < 1, 1- < 15	1.00, 0.97, 1.41
57	Batty et al[81]		Salivary cotinine (ng/mL)
		M	≤ 0.3, 0.4-1.2, 1.3-15.0	1.00, 0.41, 0.62
		F	≤ 0.3, 0.4-1.2, 1.3-15.0	1.00, 0.99, 1.70

¹First author;

²Relative risks presented are adjusted for covariates if adjusted data are available. When two groups only are being compared (or results for log cotinine are given), the relative risk and 95%CI limits for the exposed group (per unit increase) are shown; when more than two exposure groups are being compared, only the set of relative risks is shown;

³Significant (P < 0.05) positive (or negative) differences or trends are indicated by + (or -). ? indicates not known whether significant or not. Blank entries indicate non-significance. The trend test includes the unexposed group;

⁴Results for CVD. Not available for CVD - Stroke;

⁵For study 39 the results for any childhood exposure (yes/no) shown in Table 4 relate to CVD minus stroke but the results by years exposed shown here relate to CVD as a whole;

⁶The data shown here for study 9 come from the publication describing study 24;

⁷The index of exposure was a combination of exposure at home (four categories of pack-years) and exposure at work (four categories of pack-years × h/d). M: Male; F: Female; CVD: Cardiovascular disease.