Genetic test for heart disease

A new genetic test to diagnose individuals at risk of coronary heart disease at a much earlier stage has been unveiled. An international team of scientists married up over 49,000 inherited genetic markers called "snips" - single nucleotide polymorphisms - with whether or not 15,000 individuals carrying those markers had developed heart disease. This has enabled them to identify a pattern of markers that together can spell out the likelihood of a person going on to have heart disease later in life. And this means that it might be possible to intervene and ward off a heart attack before it even happens. Nilesh Samani is one of the study authors and he took Chris Smith throughtthe details.

Nilesh - Heart disease is the commonest cause of early death in this country and in many countries round the world. There are many reasons - important lifestyle factors: smoking, lack of physical activity, having certain conditions such as high blood pressure and diabetes, high cholesterol, but there is also a very important genetic component to this. Perhaps about fifty per cent of the risk of getting heart disease is related to an inherited component.

Chris - And so is that what you're probing with this present piece of research - trying to get a handle on how those genes play a role in the development of the disease and finding out who's got them?

Nelesh - In the last few years we spent a lot of time trying to identify genetic differences between people which affect the risk of getting coronary heart disease - we've found quite a few of these now. But this particular research takes us beyond that point and asks the question, if we had this genetic information on individuals, how well does it predict them getting heart disease?

Chris - If we know we already have these risk factors, are we not already pretty good at identifying who the people are who are likely to suffer a heart attack?

Nilesh - No because of two reasons: the risk factors like high blood pressure or cholesterol only explains part of the risk of getting heart disease and, to a large extent, the genetic factors that we have identified are independent of those. Some of them work through these risk factors but the majority of them don't so they provide independent information. What we know is that coronary heart disease, the underlying process, starts in people in their twenties and at that stage the risk factors we currently use are not particularly discriminatory between individuals. Whereas your genetic risk factors - you're born with them and so we can look at them at any stage in one's life and, therefore, put people into different categories of what their genetic risk is.

Chris - And how did you do that?

Nilesh - So we created from the studies we've done  where we've identified the genetic variations, we've created a genetic risk score. And then, on the basis of that risk score, we look to see whether those individuals who had the highest burden of genetic risk (top 20 per cent), versus those who had the lowest burden, what their lifetime risk of getting coronary heart disease was in a number of populations that we had access to around the world. And what you see is that if you are unlucky as an individual to have the top twenty per cent of genetic risk, then over the lifetime your risk of getting coronary heart disease was at least fivefold higher.

Chris - Armed with that information, how do you propose that we use it?

Nilesh - Obviously more work needs to be done to show that this finding can be applied to different populations under different situations. But if we confirm that then I think that one of the things that we can do is to identify those individuals who are at highest risk much earlier, at a time when the process is developing silently and to try and prevent it progressing by giving them advice about lifestyle. Perhaps giving them some treatments, such as statins, at that very early stage in the disease process rather than waiting for the condition to develop.

Chris - Although the study doesn't tell you whether that intervention will work, does it? Because what it does say is you can identify people who carry these high risk genes but it doesn't tell you if we intervene in those people whether we can affect the outcome?

Nilesh - You're absolutely right. We have some evidence that they probably do because in some other studies investigators have shown that if you carry a high genetic risk burden and you give statins to those individuals, versus people who carry a low genetic risk burden, then the absolute benefit from the statins is much higher in those who had high genetic risk. So we know that if you can identify those people even some of the treatments we have now are likely to be of benefit. But you are absolutely right that we need to do more studies to both demonstrate that having this knowledge will be be beneficial. And secondly that this is something that the public will accept in terms of screening and finally that it is cost effective for health to be able to supply it.