British Heart Foundation petition against cigarette machines

The British Heart Foundation has launched a petition to ban the sale of cigarettes from vending machines in the UK. The charity hopes that banishing cigarette vending machines will reduce the number of under 18s who take up smoking.

In the UK you need to be at least 18 years old to buy cigarettes from a shop and, technically, this old to get cigarettes from a vending machine. Vending machines aren't manned, however, making it easier for under 18s to circumvent this rule and get their hands on cigarettes. 66% of adult smokers started when they were under age, so stopping people from taking up smoking as teenagers is crucial to prevent a livelong addition to cigarettes.

According to the BHF, 6% of children aged 11-15 are regular smokers and as many as one in six of these teenagers buy their cigarettes from cigarette vending machines. A 2007 study reporting on test purchases by young people found that teenagers were able to buy cigarettes from vending machines on more than four in ten occasions, with a number of councils reporting a 100% successful purchase rate. Using vending machines was the most successful way for young people to get hold of cigarettes - almost twice as successful as other ways tested such as purchasing cigarettes from a newsagent, off licence or petrol station kiosk.

Smoking is a leading risk factor for heart disease - of the 114,000 smokers who die as a result of smoking each year in the UK, one in four die from cardiovascular disease. Measures to help people quit smoking, or stop them from smoking in the first place, are thus a key part of the BHF's strategy.

• You can help put cigarette vending machines out of order for good by signing the BHF petition here.

Cardiologists circumspect on stellar JUPITER results

The publication this week in New England Journal of Medicine of the JUPITER trial - which found that the statin rosuvastatin reduces the risk of heart attack and other cardiovascular events in people with normal cholesterol levels - has cause quite a stir. The likes of the BBC and the Daily Mail squealed that statins should be prescribed to all healthy adults, but what did the study actually look at, and what do doctors think of the findings?

In patients with raised cholesterol levels, treatment with statins reduces the risk of cardiovascular events such as heart attack and stroke; however, nearly half of all first cardiovascular events occur in people whose cholesterol levels are below current thresholds for pharmacological therapy. The JUPITER trial investigated the benefits of treatment with rosuvastatin (also known as crestor) in 17,802 patients over 50 years of age who had normal blood levels of low density lipoprotein (LDL) cholesterol ('bad' cholesterol), but elevated levels of another marker of heart disease called C-reactive protein (CRP).

Compared with a placebo, statin treatment reduced the levels of both LDL cholesterol and CRP by considerable amounts (50% and 37%, respectively), and also almost halved the likelihood of a major cardiovascular event such as a heart attack or stroke. When the results were broken down, it was found that the risk specifically of heart attack was reduced by 54% and the risk of fatal or nonfatal stroke decreased by 48%.

CRP levels are not usually measured in people at risk of heart disease, yet statin treatment had a remarkable effect in people who were otherwise apparently healthy but had elevated levels of this marker. Doctors are now been asking whether measurement of CRP levels should be undertaken in all people at risk of heart disease, and whether statins should be prescribed as a preventative measure to a wider range of people, regardless of whether their cholesterol levels indicate that they should receive such treatment.

In an editorial in the same issue of New England Journal of Medicine, Mark A Hlatky from Stanford University School of Medicine in California goes through the trial with a fine tooth comb to decide whether or not doctors should change how they prescribe statins.

He notes that "JUPITER was a trial of statin therapy, not high-sensitivity CRP testing", and opines that "the evidence still favors [a] selective strategy for measuring high-sensitivity C-reactive protein, not routine measurement". Dr Hlatky also points out that the trial was only 2 years long, so could not assess the effects of long-term statin treatment, and that the cost of rosuvastatin is much higher than that of generic statins, so the benefits of broader prescription of rosuvastatin treatment need to be weighed up against these factors.

You don't have to just take Dr Hlatky's word though. New England Journal of Medicine are hosting an online Clinical Directions poll to find out directly from doctors whether they are likely to change how they practice on the basis of the JUPITER results.

So far over 1,500 doctors and medical professionals have voted in the poll, and only 53% believe that the approach to laboratory screening and therapeutic use of statins in apparently healthy adults should be changed. The comments on the poll are just as cautious - Greg Rice of Libby, Montana says "Certainly what this study clearly shows most is that there is a large cohort of high risk patients we are missing. However, simply giving them a statin is not a very cost effective way to reduce the risk of coronary disease", whereas Timur Timurkaynak of Ankara, Turkey states "I really wonder what have we learned from jupiter trial that we don't know before".

So it seems that the jury is going to being deliberating for some time as to whether apparently healthy people should have their CRP levels measured and should receive statins. The JUPITER trial seems to have thrown up more questions than it has answered, and it is clear that more research is needed before statins start getting dished out willy nilly.

• Nature News has a good run down of the JUPITER study and whether you should be heading straight to your doctor for preventative statin treatment
  

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Ridker PM et al. (2008). Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein New England Journal of Medicine DOI: 10.1056/NEJMoa0807646

Would you like a defibrillator with your coke sir?

Authorities in Japan have taken an interesting approach to improving the dire survival rates after out-of-hospital sudden cardiac arrest (SCA), i.e. heart attack in the home or in a public place rather than in a ward on a hospital.

Nature Clinical Practice Cardiovascular Medicine reports that automated external defibrillator devices (AEDs) are being placed in vending machines and advertising hoardings in public spaces in Japan. Members of the public can then use these devices to provide defibrillation at the scene of a SCA, saving precious minutes before emergency services arrive.

The American Heart Association estimates that 166,200 people die in the United States each year from out-of-hospital SCA and only 6.4% of patients who are admitted to hospital for SCA survive until discharge.

Early medical response is crucial for people who suffer an out-of-hospital SCA. For every minute that passes between collapse and defibrillation, survival from witnessed SCA falls by 7-10%. In most cases it is the emergency services who provide defibrillation, but time is lost waiting for paramedics to arrive at the scene.

An obvious way to shorten the time between SCA and defibrillation is for lay witnesses to perform the procedure. In fact, studies have found that defibrillation by members of the public considerably improves survival after SCA.

The Japanese government authorized the lay use of AEDs in July 2004. Subsequently, a study by the Japanese Fire and Disaster Management Agency in 2006 found that 32.1% of the 140 SCA victims who were defibrillated by a member of the public were still alive at 1 month, compared with 8.3% of the 18,180 people who did not receive defibrillation from a lay person.

In most countries public-access AEDs can only be used by trained individuals, be they members of the public, first aiders, paramedics and so on; however, what is interesting in Japan is that no training is necessary in order to use these devices. In addition, the Japanese government has formally declared that the liability of an individual who uses an AED is limited, irrespective of the outcome of resuscitative efforts.

Another interesting point about public-access AEDs in Japan is that rather than being directed by the government, the positioning of AEDs in public places is being spearheaded by commercial companies. As Nature Clinical Practice Cardiovascular Medicine reports:

"The cost of keeping an AED in a vending machine is primarily covered by the revenue from drink purchases and is shared by the manufacturer of the drink, the provider of the machine, the distributor of the AED, and the proprietor who provides the space and electricity. Allowing paid advertising on a display panel above a box housing an AED is another method of funding public access AEDs. Again, the proprietor has only to provide the space and electricity. These creative efforts are surely effective in keeping down AED dissemination costs."

Although Japan was a little behind other countries when it came to introducing public-access AEDs, the creative approaches to accessibility undertaken by the Japanese are in a class of their own.

Hadrian's heart trouble

Today I went to see the Hadrian: Empire and Conflict exhibition at the British Museum, which "explores the life, love and legacy of Rome’s most enigmatic emperor". The exhibition was fascinating, providing all sorts of detail about how the Roman empire was run and some fascinating perspectives on ancient culture.

One particularly interesting poster noted that the detailed and naturalistic statues of Hadrian in the exhibition always feature a diagonal crease in both earlobes - a tell-tale sign that the great emperor might have suffered from coronary artery disease.


For over 20 years, researchers have noted an association between bilateral diagonal earlobe creases and coronary artery disease. There is controversy, however, as to whether the presence of these creases genuinely reflects a higher risk of heart disease.

A recent study in the journal Atherosclerosis found that the presence of diagonal earlobe creases correlated with the thickness of the intimal and medial layers that line blood vessels. Intima-media thickness reflects the build up of plaques in arteries, which causes 'furring' and narrowing of vessels and increases the risk of heart attack. In addition, a 2006 study that examined 520 cadavers undergoing forensic autopsy and a 2004 study of 415 patients both found that diagonal earlobe creases correlated with coronary artery disease.

On the other hand, Jorde et al. found that the prevalence of various risk factors associated with heart disease was the same in individuals with earlobe creases and in those without, although the authors noted that the creases were more common in older individuals. Similarly, Brady et al. concluded that the association between earlobe creases and coronary artery disease was down to the fact that the prevalence of both conditions increases with age.

Despite these studies, the majority of the literature on this subject does seem to agree that earlobe creases are a sign of heart disease.

Thanks to modern research, this otherwise innocuous detail recorded by the dedicated sculptors of ancient Rome is able to give us fascinating insight into the physical health of Hadrian, and also suggests that humans living thousands of years ago suffered the same illnesses as we do now. As the poster in the British Museum points out, we may never know whether Hadrian had coronary artery disease, but the intricate craftsmanship in the statues of this great emperor provide a tantalizing hint of what might have finally seen him off.

Randomized control freakery

Nature Clinical Practice Cardiovascular Medicine has recently published an interesting review article on clinical trial design - 'From randomized trials to registry studies: translating data into clinical information'.

This isn't a guide on how to read a clinical paper - you should have a look at Prof Trisha Greenhalgh's book 'How to read a paper' or the extracts published in the BMJ way back in 1997 in you need tips on that front. Rather, the NCP Cardiovascular Medicine review examines different study designs, and interestingly puts forward a case for observational trials, as compared with randomized controlled trials.

Randomization - in which patients are allocated to treatment or no treatment (or placebo) in an entirely indiscriminate manner, thus distributing both known and unknown confounders between groups - and control or placebo groups - which comprise patients who do not receive the intervention - are the benchmarks of a good clinical study, allowing an investigator to isolate the effect of a treatment from various confounding factors.

However, the NCP review argues:

"The results of observational studies are often dismissed in favor of prospective randomized studies because of the widely recognized biases inherent in observational studies. Yet such studies form the basis of much of the medical knowledge we have today. Accordingly, rather than dismiss information gained from observational studies, it is more appropriate to recognize these biases and their effect on results, and to modify interpretation appropriately. Indeed, from a practical standpoint, all studies sustain some form of bias, either implicitly or explicitly."

In addition, the authors state:

"Strict inclusion and exclusion criteria mean that the results of randomized studies might not be as applicable to general populations as are findings from observational studies, including both clinical registries and retrospective reviews"

The take-home message of the article is that practicing clinicans should analyze the patient population of a trial carefully before applying the findings to a patients of theirs.

This paper also discusses statistical power and the use of surrogate and composite end points, the validity (or not) of post hoc analysis, and the utility of peer review for spotting trial-design pitfalls. But obviously I'm more interested in the iconoclastic view of randomized controlled trials...