Published online Apr 26, 2017. doi: 10.13105/wjma.v5.i2.14
Peer-review started: October 9, 2016
First decision: December 29, 2016
Revised: January 10, 2017
Accepted: February 28, 2017
Article in press: March 2, 2017
Published online: April 26, 2017
Processing time: 201 Days and 12.8 Hours
To review evidence relating passive smoking to heart disease risk in never smokers.
Epidemiological studies were identified providing estimates of relative risk (RR) of ischaemic heart disease and 95%CI for never smokers for various indices of exposure to environmental tobacco smoke (ETS). “Never smokers” could include those with a minimal smoking experience. The database set up included the RRs and other study details. Unadjusted and confounder-adjusted RRs were entered, derived where necessary using standard methods. The fixed-effect and random-effects meta-analyses conducted for each exposure index included tests for heterogeneity and publication bias. For the main index (ever smoking by the spouse or nearest equivalent, and preferring adjusted to unadjusted data), analyses investigated variation in the RR by sex, continent, period of publication, number of cases, study design, extent of confounder adjustment, availability of dose-response results and biomarker data, use of proxy respondents, definitions of exposure and of never smoker, and aspects of disease definition. Sensitivity analyses were also run, preferring current to ever smoking, or unadjusted to adjusted estimates, or excluding certain studies.
Fifty-eight studies were identified, 20 in North America, 19 in Europe, 11 in Asia, seven in other countries, and one in 52 countries. Twenty-six were prospective, 22 case-control and 10 cross-sectional. Thirteen included 100 cases or fewer, and 11 more than 1000. For the main index, 75 heterogeneous (P < 0.001) RR estimates gave a combined random-effects RR of 1.18 (95%CI: 1.12-1.24), which was little affected by preferring unadjusted to adjusted RRs, or RRs for current ETS exposure to those for ever exposure. Estimates for each level of each factor considered consistently exceeded 1.00. However, univariate analyses revealed significant (P < 0.001) variation for some factors. Thus RRs were lower for males, and in North American, larger and prospective studies, and also where the RR was for spousal smoking, fatal cases, or specifically for IHD. For case-control studies RRs were lower if hospital/diseased controls were used. RRs were higher when diagnosis was based on medical data rather than death certificates or self-report, and where the never smoker definition allowed subjects to smoke products other than cigarettes or have a limited smoking history. The association with spousal smoking specifically (1.06, 1.01-1.12, n = 34) was less clear in analyses restricted to married subjects (1.03, 0.99-1.07, n = 23). In stepwise regression analyses only those associations with source of diagnosis, study size, and whether the spouse was the index, were independently predictive (at P < 0.05) of heart disease risk. A significant association was also evident with household exposure (1.19, 1.13-1.25, n = 37). For those 23 studies providing dose-response results for spouse or household exposure, 11 showed a significant (P < 0.05) positive trend including the unexposed group, and two excluding it. Based on fewer studies, a positive, but non-significant (P > 0.05) association was found for workplace exposure (RR = 1.08, 95%CI: 0.99-1.19), childhood exposure (1.12, 0.95-1.31), and biomarker based exposure indices (1.15, 0.94-1.40). However, there was a significant association with total exposure (1.23, 1.12-1.35). Some significant positive dose-response trends were also seen for these exposure indices, particularly total exposure, with no significant negative trends seen. The evidence suffers from various weaknesses and biases. Publication bias may explain the large RR (1.66, 1.30-2.11) for the main exposure index for smaller studies (1-99 cases), while recall bias may explain the higher RRs seen in case-control and cross-sectional than in prospective studies. Some bias may also derive from including occasional smokers among the “never smokers”, and from misreporting smoking status. Errors in determining ETS exposure, and failing to update exposure data in long term prospective studies, also contribute to the uncertainty. The tendency for RRs to increase as more factors are adjusted for, argues against the association being due to uncontrolled confounding.
The increased risk and dose-response for various exposure indices suggests ETS slightly increases heart disease risk. However heterogeneity, study limitations and possible biases preclude definitive conclusions.
Core tip: We present an up-to-date meta-analysis of the evidence relating environmental tobacco smoke (ETS) exposure to heart disease risk in never smokers. An association is evident for smoking by the spouse (or nearest equivalent) with the relative risk estimated as 1.18 (95%CI: 1.12-1.24), and also with some other indices of ETS exposure. Though the findings suggest a causal relationship, data limitations and bias limit interpretation.