Cardiovascular disease: It's personal

Cardiologist David Celermajer has a party-trick. He poses this quick quiz for his audience: showing them a slide of a person with a big lump of cholesterol in their heart, he asks how old the person is.
Image of David Celermajer

The answer is 94, and he died of prostate cancer. Then I show them a slide of a person with a very small but bleeding plaque. That person was 37 and died of heart disease,” says Celermajer, Scandrett Professor of Cardiology at the University of Sydney. “So it’s not just the big plaque that is dangerous and the little one is OK. It’s not enough to know the size of the plaque, you have to know a lot more, such as what type of plaque it is. Is it vulnerable, or is it impervious? And it’s very hard to tell.”

The slides in the quiz were taken after the two people had died. But, as Celermajer says: “You can’t do autopsies to find out if living people have got plaque. Our holy grail is noninvasive detection, especially of vulnerable plaque in vulnerable people.”

One of the non-invasive methods, which he pioneered over 20 years ago, is flow-mediated dilation (FMD), done with an ultrasound on the arm. It forms the story of Celermajer’s discovery of how to detect heart disease in its earliest stages.

“Twenty-one years ago, in the Lancet, we described the FMD test conducted on children with an average age of eight. We found that the children with very high cholesterol already had impaired blood vessel function in their first decade of life. This was the first ever demonstration that you could detect the earliest stages of heart disease in children without having to cut them open.”

So significant were the findings that the study remains one of the most highly cited papers in the world of heart disease . . . ever. For the children in that study, the prognosis seems unlikely to be good. About half of them had cholesterols of around eight - normal is less than four - making them seriously predisposed to cardiovascular disease.

Celermajer also conducted the same type of research into blood vessel function for teenage ‘passive smokers’, the results of which were published in the New England Journal of Medicine in 1996. He compared teenage smokers with teenagers who were not smokers but lived at home with parents who were. What he found was that the teenagers exposed to cigarette smoke in the home had sick blood vessels, as sick as the kids who smoked themselves.

He’s quick to point out that there is a duration effect. The teenagers whose parents smoked were exposed to the smoke all through childhood, while the 16-year-old smokers had only taken up cigarettes in the past year or two. However, the results in both groups was just as bad, no matter how long it had taken each to arrive there.

“Passive smoking all your life might be worse than active smoking for a couple of years. If parents smoke then their children are exposed to smoking for extended periods and perhaps at a time when their blood vessels are very prone to environmental influences.”

This study was one of the major pieces of scientific data that brought about the mandating of passive smoking protection. In the late 1990s, the Californian Congress placed a ban on smoking in public places and similar legislation followed around the world. The research can be credited with contributing to the saving of tens of thousands of lives.

Risk of heart disease can be seen in children even younger than those in adolescence or early childhood. In 1999, a team working in California showed that unborn babies of mothers with really high cholesterol had deposits of cholesterol in the aorta, the main blood vessel of the body. In 2005, Celermajer conducted similar research showing that babies who were very small, from growth restriction in utero, had blood vessel damage noticeable on the day they were born. Such babies are also at high risk of heart disease later on in life.

The good news for the babies of mothers with high cholesterol is that, after birth, if they are out of the high cholesterol environment, their arteries go back to normal. “We can see the changes, but in a child they are quite easily reversible. Some risk factors are worse than others. The damage caused by high cholesterol in childhood can be relatively transient but the damage caused by smoking is particularly stubborn.”

The advantage of non-invasive and repeatable procedures that allow us to look at heart and vessel health is that they give us the opportunity to see early signs of heart disease, as well as the efficacy of interventions to avoid the disease. “The availability of a non-invasive way to study blood vessel health opens the door to all these questions: what are the predisposing factors?; how much of each one do you need; how reversible is it with withdrawal of the risk factor or some other clever intervention?” says Celermajer.

At the moment, the imaging technique used in his research is not being done clinically because it is technically a very demanding test to undertake. About 300 or 400 research groups around the world use it. But he does envisage a time when this imaging moves into the clinical realm.

“I would love there to be a test that can be done on teenagers and young adults to stratify their risk and I think it will happen. It personalises the risk. We’ve shown people in their 20s the plaques in their blood vessels when they smoke, and they’ve said: ‘I had no idea. Man, is that really me?!’ Looking at the warning on a cigarette packet has far less of an effect. When it’s demonstrable in them and their blood vessels, and they know that’s what most Australians die of, they’re frightened.”

Celermajer has found that there’s nothing like being confronted with the visual evidence of your own damaged blood vessels and seeing normal healthy vessels to get a smoker to quit. So what are the ‘after’ pictures like?

“There has been follow-up to see what changes there are to the blood vessels after smoking cessation and there has definitely been improvement, but it is hard to study because not many people are successful with quitting in the long term. We have done reversibility studies with obesity. One nice study in adolescents who were obese showed that you can reverse all that damage with sustained diet and exercise.”

Research into the earliest stages of cardiovascular disease is extremely important because the disease is the number one killer in the western world, responsible for 30-40% of all deaths and commoner than all cancers put together.

“What is really devastating is that it is now the number one cause of death and suffering worldwide, even in developing countries. We’ve done a lot of work in the developing world - in China, India, sub-Saharan Africa - to look at the emergence of cardiovascular disease here. When I started in 1996 with the CATHAY (Chinese ATHerosclerosis in Aged and Youth) study it was right at the beginning of the atherosclerosis epidemic in China. In rural India, we’ve done a risk factor survey, looking at how much heart and blood vessel disease they had. We expected, for example, an incidence of diabetes of 1% and we found an incidence of over 10%.”

Because cardiovascular disease is largely environmentally cast, lifestyle changes promise great hope of reducing risk. “Most people think it is about 90% of what we stick in our system and about 10% genetic. In about 10% of people with heart attacks, they’re pristine, never smoked, never got fat, exercise regularly . . . but they’ve likely inherited a bad gene from a parent.”

Celermajer refers to Chris Anderson, one of the many famous Australians who has gone public after his experience of early heart disease. “He’s an Australian rugby league player and he had coronary artery surgery at 48 - one of the fittest guys around.”