Elsevier

The Lancet

Volume 378, Issue 9799, 8–14 October 2011, Pages 1297-1305
The Lancet

Articles
Cigarette smoking as a risk factor for coronary heart disease in women compared with men: a systematic review and meta-analysis of prospective cohort studies

https://doi.org/10.1016/S0140-6736(11)60781-2Get rights and content

Summary

Background

Prevalence of smoking is increasing in women in some populations and is a risk factor for coronary heart disease. Whether smoking confers the same excess risk of coronary heart disease for women as it does for men is unknown. Therefore, we aimed to estimate the effect of smoking on coronary heart disease in women compared with men after accounting for sex differences in other major risk factors.

Methods

We undertook a systematic review and meta-analysis of prospective cohort studies published between Jan 1, 1966, and Dec 31, 2010, from four online databases. We selected cohort studies that were stratified by sex with measures of relative risk (RR), and associated variability, for coronary heart disease and current smoking compared with not smoking. We pooled data with a random effects model with inverse variance weighting, and estimated RR ratios (RRRs) between men and women.

Findings

We reviewed 8005 abstracts and included 26 articles with data for 3 912 809 individuals and 67 075 coronary heart disease events from 86 prospective trials. In 75 cohorts (2·4 million participants) that adjusted for cardiovascular risk factors other than coronary heart disease, the pooled adjusted female-to-male RRR of smoking compared with not smoking for coronary heart disease was 1·25 (95% CI 1·12–1·39, p<0·0001). This outcome was unchanged after adjustment for potential publication bias and there was no evidence of important between-study heterogeneity (p=0·21). The RRR increased by 2% for every additional year of study follow-up (p=0·03). In pooled data from 53 studies, there was no evidence of a sex difference in the RR between participants who had previously smoked compared with those who never had (RRR 0·96, 95% CI 0·86–1·08, p=0·53).

Interpretation

Whether mechanisms underlying the sex difference in risk of coronary heart disease are biological or related to differences in smoking behaviour between men and women is unclear. Tobacco-control programmes should consider women, particularly in those countries where smoking among young women is increasing in prevalence.

Funding

None.

Introduction

Worldwide, there are 1·1 billion smokers, of whom a fifth are women.1 Every year, more than 5 million deaths occur that are directly attributed to tobacco, with 1·5 million of these deaths occurring in women.2 These figures are projected to increase to 8 million female smokers and 2·5 million deaths in women by 2030 if present patterns of smoking persist.2 However, these estimates are based on two assumptions: first, that the male-to-female smoking ratio persists, which is an unlikely scenario because of the reported increased uptake of smoking in young women compared with young men in some countries;3, 4 and second, that smoking affects men and women equally, which might not be true for all diseases. For example, women who smoke have a significantly greater relative risk (RR) of lung cancer than do male smokers,5, 6, 7, 8 and there is some debate about whether this sex difference is also true for smoking and coronary heart disease.9

In 1998, Prescott and colleagues9 reported that women who smoked had a 50% greater coronary risk than did their male counterparts, leading them to conclude that “women may be more sensitive than men to some of the harmful effects of smoking”. Estimates of the sex-specific associations between smoking and subsequent coronary heart disease from large prospective studies such as the Nurses Health Studies (all women),10 and the British Doctors Study (separate studies for men11 and women12) vary, possibly because of differences in study design, classification of smoking status, and amount of adjustment for confounders. Therefore, whether any reported sex difference between these studies is real or an artifact of methodological differences cannot be established. Direct comparisons of the relation between smoking and coronary heart disease in men and women can be made through internal, within-study comparisons in studies with male and female participants, thereby reducing the role of extraneous, between-study factors. The largest meta-analysis to date to do this comparison is the Asia Pacific Cohort Studies Collaboration (APCSC),13 which reported evidence of a sex difference in the effect of smoking on risk of coronary heart disease (smoking was more hazardous in women than it was in men) but only for the heaviest smokers. However, this study was restricted in geographical scope, and thus did not take account of all the available data, and did not directly estimate the relative effects of smoking between the sexes.

To establish whether women who smoke are at greater risk of coronary heart disease than are men who smoke, irrespective of smoking intensity and independent of other risk factors, we undertook a meta-analysis of prospective cohort studies (including APCSC) that reported sex-specific effects of smoking on subsequent risk of coronary heart disease.

Section snippets

Search strategy and selection criteria

We undertook a systematic review of the published work without language restrictions according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines.14 We selected relevant studies published between Jan 1, 1966, and Dec 31, 2010, from CINAHL, Embase, PubMed, and Cochrane Library databases with the following combined text and MeSH heading search strategy: “smoking” OR “cigarettes” OR “tobacco” AND “coronary heart disease” OR “ischaemic heart disease” AND “cohort” AND

Results

We identified 8005 articles, of which 56 (1%) included data for the association between smoking and coronary heart disease. 30 (54%) of these 56 studies were excluded, mainly because they did not provide sex-stratified estimates of RR (figure 1). 26 articles with information from 86 cohort studies were eligible for inclusion.13, 15, 16, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44 Two of these articles contained information about 60 cohort studies;

Discussion

Cigarette smoking is one of the main causes of coronary heart disease worldwide and will remain so as populations that have so far been relatively unscathed by the smoking epidemic begin to smoke to a degree previously noted only in high-income countries. This expectation is especially true for young women in whom the popularity of smoking, particularly in some low-income and middle-income countries, might be on the rise.3, 4 The effects of this rise are particularly concerning as evidence from

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