Investigating the genetic markers of atherosclerosis

Terho Lehtimäki directs a research group that specialises in cardiovascular research. The group was a partner in an international research project last year that found a connection between foetal growth and adulthood diseases.

A research project at the University of Tampere is probing how insidious atherosclerosis – the stiffening of the cardiac arteries – could be diagnosed earlier, in order to prevent sudden deaths from coronary heart disease.

Atherosclerosis forms plaques in the lining of the arteries. The plaque structures can distend outwards from the arteries and make the blockages invisible even in a coronary angiogram. In the worst cases, the plaque disrupts and creates a blockage in the artery. Death can follow in just a few minutes.

“Two people can have coronary heart disease and one dies suddenly but the other one does not. The likelihood of death cannot be predicted with the current means, and in the worst cases the patient has no idea that she or he is ill in the first place,” says Terho Lehtimäki, Professor of Clinical Chemistry at the University of Tampere.

A sudden death from coronary heart disease can be the fate of a person at peak working condition. However, usually atherosclerosis occurs in older patients.

The treatment of the disease has taken great leaps forward in past decades, but diagnosis has not. Lehtimäki’s research group hopes to find a solution in patient genes. The group is involved in the international AtheroRemo research consortium. The research received an EUR 18 million grant from the European Union, which is the largest grant ever awarded by the EU for research on cardiovascular diseases.

Genetic link explains adulthood disease

Professor Terho Lehtimäki is excited about the modern technology which makes it possible for large international research communities to work together.

“The power of science makes me believe that these findings will soon benefit the whole world”, he says.

Terho Lehtimäki, Professor of Clinical Chemistry at the University of Tampere

Quite surprisingly, the same genes that cause low birth weight are related to the risk factors of chronic illnesses in adulthood, such as coronary heart disease and atherosclerosis.

One gene that affects birth weight has been discovered to be related to high blood pressure.

“There is now evidence for why low birth weight babies have more chronic illnesses in adulthood”, Lehtimäki says.

This genetic cluster was discovered to affect metabolism, i.e. blood sugar levels, which is one of the most significant risks of coronary heart disease. High blood pressure also predisposes to coronary heart disease.

If a low birth weight baby has certain genes that have caused the low weight, he or she has a higher risk of developing diabetes or coronary heart disease in adulthood.

15,000 deaths by coronary heart disease occur in Finland every year. According to the statistics of the Social Insurance Institution of Finland, 300,000 Finns are on some kind of medication for cardiovascular conditions. It is a major problem.

Genetic testing instead of measuring lipids

Terho Lehtimäki hopes that at some point genetic testing will replace the current measuring of lipids or fats in the bloodstream, or that genetic testing will be used together with lipids testing.

According to Lehtimäki, genetic testing has more diagnostic significance than lipids.

The whole arsenal of genetic testing could be applied in health care, but at this point it is still too expensive.

“It will take years before we can convince the average doctor about the benefits of the new test. However, after the markets have been formed, we can quickly take the test to routine production and get the full benefit of these observations from basic research.”

The tests could be used to screen the likelihood of coronary heart disease.

“The great thing about genetic testing is that for example all the hundred genes that contribute to coronary heart disease can be tested with just one test.”

What use is knowing the risks? Do people want to know that they are at risk of sudden death from heart disease?

As Lehtimäki sees it, the information is valuable in awakening patient awareness and emphasising the need for lifestyle change. Genes have an outstanding effect but the combined effect of genes and the environment are not fully known. Lifestyle plays a crucial role in people’s health.

“Of course, in the end people decide for themselves what they eat or drink. But after hearing about the risks, sensible people can seize the opportunity and change their habits.”

AtheroRemo project:

Researchers benefit from cooperation

Terho Lehtimäki’s group is one of the most active authors of scientific publications in medicine at the University of Tampere and also in Finland. Lehtimäki leads a 12-strong research group which specialises in cardiovascular diseases.

The first week of December 2012 was ‘a super week’ for Lehtimäki’s research group: In one week, three articles that were co-authored by Lehtimäki’s group were published in the most prestigious scientific journals: two in Nature Genetics and one in Nature.

In the Scholar chart updated by the medical library TERKKO at the University of Helsinki, Lehtimäki and his group have been in the number one position for a long time. His colleague Mika Kähönen has held the second place. Lehtimäki calls the Scholar chart a gossip column but thinks that the first place is important because the list ranks not only the numbers of articles, but first and foremost their quality.

“I sometimes wonder how an ordinary person like myself can top the chart. I guess we are super ordinary people,” Professor Lehtimäki jokes.

Despite the super talk, Lehtimäki does not want to take all the credit. Without a skilled group, one researcher alone cannot make the charts. The research group has a thirty-year concerted history of working with genes.

“It is a pleasure to work together with future professors – people who are more skilled than I am.”

Networking pays

Modern technology enables wide international research consortiums where research groups from different countries and universities bring their data together. This is especially important in genetic research because the research can be conducted with significantly wider genetic data than a single research group could ever be able to gather.

Lehtimäki’s and Professor Mika Kähönen’s research groups became involved in the big research consortiums in 2006, and in 2009 they ‘hit the jackpot’.

Lehtimäki’s research group is currently involved in 28 international research consortiums. “Networking is the most important thing in the current research. My aim is that the research communities that have now been created would expand further and benefit the research communities in Tampere and the whole country,” Lehtimäki says.

Scholar chart:

Terho Lehtimäki
  • Professor of Clinical Chemistry at the University of Tampere. He has studied at UTA since 1986 and worked in different positions at the School of Medicine since 1988.
  • Chief physician of Fimlab and the director of Fimlab research and education.
  • Main area of interest cardiovascular diseases and their risks.
  • Together with his research group and cooperation partners he has been able to join international research consortiums with the help of the YoungFinns and FINCAVAS data sets.
  • His closest collaboration on the Kauppi campus is with Professor Mika Kähönen and his research team.

Text: Tiina Lankinen
Photographs: Teemu Launis
Translation: Laura Tohka

This story was originally published in Finnish in Aikalainen 2/2013