FOCUS: Controversy reigns over the effects on the heart of passive smoking. Until this has been resolved, the results of important studies on heart disease will be fogged by uncertainty
Even second-hand cigarette smoke is bad for your heart, a major study in The New England Journal of Medicine concluded earlier this year. No surprises there. But in addition to publishing the authors' estimate of how dangerous passive smoking is, the journal took the unusual step of running an editorial in the same issue that appeared to rubbish the research findings.
According to the researchers, from Tulane University in New Orleans, nonsmokers exposed to environmental tobacco smoke (ETS) face a 25 per cent increased risk of coronary heart disease. The dissenting editorial writer, John Bailar from the University of Chicago, said an increased risk of such magnitude was not plausible given how dilute second-hand smoke becomes in air.
The stark disagreement in the very same issue of the journal illustrates how contentious the subject is. Tobacco companies are keen to downplay the risks, antismoking campaigners are keen to talk them up. And even respected scientists are in serious disagreement or are undecided on how much passive smoking contributes to the population's burden of heart disease.
Researchers such as Richard Doll at the University of Oxford, one of the world's leading authorities on smoking and health, admits the jury is still out. In the face of this, many doctors say it would be prudent for people to minimise their exposure to cigarette smoke-especially if they already have symptoms of coronary disease.
But for researchers investigating other causes of heart disease, the uncertainty surrounding passive smoking is a real problem. How can you measure how significant other factors, such as diet, genetics and exercise, are in causing heart disease, when you don't know how much allowance to make for passive smoking?
The controversial 25 per cent figure, reported in the NEJM by Jiang He and his colleagues at the Tulane University School of Public Health and Tropical Medicine (vol 340, p 920), was achieved by pooling many different statistical results -a "meta-analysis". It included the results of 18 international studies and has a strong claim to be the most reliable yet on heart disease risks due to passive smoking.
So why was Bailar, a respected expert on the analysis of medical studies, so sceptical?
A back-of-the-envelope calculation explains his concern. People who smoke 20 cigarettes a day face a 75 to 80 per cent higher risk of developing heart disease than nonsmokers, and studies suggest that passive smokers breathe in about 1 per cent of the amount inhaled by direct smokers. As such, they should also face about 1 per cent of the extra heart disease risk faced by smokers. In other words, just 0á75 per cent-more than 30 times lower than the figure found by Jiang He and his colleagues.
This huge discrepancy is dividing medical scientists into two camps. On one side are those who believe it reveals the existence of a highly non-linear effect of tobacco smoke on the body, where just a whiff can trigger a dramatic increase in risk.
On the other side are those who, like Bailar, suspect the discrepancy highlights fundamental flaws in the methods used to assess the risks from passive smoking. Some go further, arguing that in the drive to discourage smoking, implausible results are not being questioned as rigorously as they should.
No one is accusing Jiang He and his colleagues of shoddy research. Even Bailar concedes that their meta-analysis of 18 studies is up to scratch. What worries him is whether even the best meta-analysis is capable of reliably detecting small risks. In his editorial, Bailar argues that there are many ways in which a meta-analysis of passive smoking studies can give spuriously high risk figures. They range from publication bias, in which the meta-analysis is affected by a tendency of researchers only to publish studies finding significant extra risk, to outright lying by smokers or ex-smokers, who tell researchers they have never smoked.
But it is the sheer size of the figure found by He and his colleagues that most worries Bailar: "I find it hard to understand how environmental tobacco smoke, which is far more dilute than actively inhaled smoke, could have an effect that is such a large fraction of the added risk of coronary heart disease among active smokers," he says.
Malcolm Law of the Wolfson Institute of Preventive Medicine in London backs Jiang He's results, having reached similar conclusions in the British Medical Journal six months earlier (vol 315, p 973). Law notes that if you compare people who actively smoke just five cigarettes a day with people who smoke 20 a day, the increased risk is also non-linear (see Graph). The lighter smokers increase their risk of heart disease by 40 per cent. The people who smoke four times as many cigarettes only double their risk. "So we shouldn't be surprised by the passive smoking finding," he says.
Jiang He told New Scientist that he was "very surprised and disappointed" by Bailar's criticisms. "Our study is a very complete meta-analysis," he insists. "We have searched for all studies on a relationship between passive smoking and coronary heart disease-including unpublished studies." He also rejects the charge of implausibility: "There are many potential mechanisms by which passive cigarette smoking results in coronary heart disease."
But to make sense of the results, these mechanisms must explain how just a little cigarette smoke can trigger the bulk of the heart disease risk caused by exposure to tobacco. And one such, says Doll, is platelet aggregation.
Clumping together whenever blood vessels are damaged, platelets are part of the body's repair mechanisms. But even relatively small increases in platelet aggregation have been implicated in a substantially higher risk of heart disease. Some research also suggests that passive smoking may boost platelet aggregation enough to create the extra heart disease risks found by the meta-analysis (Circulation, vol 83, p 38).
It is a line of argument that fails to convince Robert Nilsson, an expert on cellular toxicology at the University of Stockholm. "Although it seems that platelet aggregation is affected by active smoking, adequate evidence showing that it may account for the large effect from ETS is lacking," he says. Doll agrees: "It makes a plausible story, but not a wholly convincing one."
A host of other mechanisms has also been suggested, from cell damage to increases in cholesterol, yet no obvious smoking gun has emerged. "It is puzzling," says Doll. "I don't wholly agree with Bailar. On balance, I think there is something in it-but nobody can say for sure at the moment." He says the current state of knowledge suggests that the best that can be said is that passive smoking may increase the risk of heart disease. Finding out for certain will be "an intriguing and difficult problem".
However, Nilsson remains concerned: "Because all tobacco smoke is seen as a major health risk, some scientists and physicians seem to have shelved their efforts to analyse the possible effects of passive smoking rigorously."
And one unfortunate consequence, he says, is that the heart disease risk figure of 25 per cent might be erroneously set in stone-and therefore skew other heart disease research. If the 25 per cent figure is an exaggeration, it would provide a smoke screen behind which other sources of heart disease could slip past researchers, undetected.
Pinning down the correct risk figure has nothing to do with "letting the tobacco companies off the hook", says Nilsson. "Exposure to tobacco smoke is a major confounder in many investigations," he says. "It is therefore extremely important to be able to define correctly the levels of risk involved."
Author: Robert Matthews
New Scientist magazine issue 29th May 1999
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