Environmental tobacco smoke exposure and heart disease: A systematic review

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.