Systematic Reviews
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Apr 26, 2017; 5(2): 14-40
Published online Apr 26, 2017. doi: 10.13105/wjma.v5.i2.14
Environmental tobacco smoke exposure and heart disease: A systematic review
Peter N Lee, Barbara A Forey, Jan S Hamling, Alison J Thornton
Peter N Lee, Barbara A Forey, Jan S Hamling, P.N. Lee Statistics and Computing Ltd., Sutton, Surrey SM2 5DA, United Kingdom
Alison J Thornton, Independent Consultant in Statistics, Okehampton, Devon EX20 1SG, United Kingdom
Author contributions: Lee PN and Forey BA planned the study; Thornton AJ and Hamling JS carried out the literature searches, assisted by Lee PN and Forey BA; Forey BA, Hamling JS and Thornton AJ carried out the data entry which was independently checked by one of these or Lee PN; Lee PN and Forey BA discussed any difficulties in interpreting published data or in the appropriate methods for derivation of RRs; Forey BA and Hamling JS conducted the main statistical analyses along lines discussed and agreed with Lee PN; Lee PN drafted the paper which was critically reviewed by the other authors.
Conflict-of-interest statement: Lee PN, Director of P.N. Lee Statistics and Computing Ltd., is an independent consultant in statistics and an advisor in the fields of epidemiology and toxicology to a number of tobacco, pharmaceutical and chemical companies including the sponsors of this study; Forey BA and Hamling JS are employees of, and Thornton AJ, a consultant to, P.N. Lee Statistics and Computing Ltd.
Data sharing statement: Supplementary File 1 provides a description of the reasons for rejection of some papers. Supplementary File 2 gives full details of the meta-analyses conducted. Supplementary File 3 gives full details of the stepwise multiple regression analysis. Supplementary File 4 gives some results for less commonly used indices of ETS exposure. Copies of the database files are available on request from the corresponding author at peterLee@pnlee.co.uk.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Peter N Lee, MA, Director, P. N. Lee Statistics and Computing Ltd., 17 Cedar Road, Sutton, Surrey SM2 5DA, United Kingdom. peterlee@pnlee.co.uk
Telephone: +44-20-86428265 Fax: +44-20-86422135
Received: October 7, 2016
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
Abstract
AIM

To review evidence relating passive smoking to heart disease risk in never smokers.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Passive smoking; Heart disease; Dose-response; Meta-Analysis; Review

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.