Public Release:  Shorter height is directly associated with increased risk of coronary heart disease

University of Leicester-led study uses genetic approach to show link between height and disease

University of Leicester

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  • "We have shown that the association between shorter height and higher risk of coronary heart disease is a primary relationship and is not due to confounding factors such as nutrition or poor socioeconomic conditions."- Professor Sir Nilesh Samani, BHF Professor of Cardiology at the University of Leicester.

  • Coronary heart disease is the most common cause of death worldwide and is the UK's single biggest killer.

  • Nearly one in six men and one in ten women die from coronary heart disease.

  • Coronary heart disease is responsible for around 73,000 deaths in the UK each year, an average of 200 people each day, or one every seven minutes.

  • 2.3 million people are living with coronary heart disease in the UK - over 1.4 million men and 850,000 women.

The shorter you are- the more your risk of coronary heart disease.

That's the key finding of a new study led by the University of Leicester which discovered that every 2.5 inches change in your height affected your risk of coronary heart disease by 13.5%. For example, compared to a 5ft 6inch tall person, a 5 foot tall person on average has a 32% higher risk of coronary heart disease because of their relatively shorter stature.

The research, led by Professor Sir Nilesh Samani, British Heart Foundation Professor of Cardiology at the University of Leicester, is published online in the New England Journal of Medicine. The research was supported by the British Heart Foundation, The National Institute for Health Research (NIHR) and others.

Professor Samani said: "For more than 60 years it has been known that there is an inverse relationship between height and risk of coronary heart disease.

"It is not clear whether this relationship is due to confounding factors such as poor socioeconomic environment, or nutrition, during childhood that on the one hand determine achieved height and on the other the risk of coronary heart disease, or whether it represents a primary relationship between shorter height and more coronary heart disease.

"Now, using a genetic approach, researchers at the University of Leicester undertaking the study on behalf of an international consortium of scientists (the CADIoGRAM+C4D consortium) have shown that the association between shorter height and higher risk of coronary heart disease is a primary relationship and is not due to confounding factors."

Coronary heart disease is the commonest cause of premature death worldwide. It is the condition where the arteries that supply blood to the heart muscle (coronary arteries) become narrowed due to a deposition of fatty material (plaque) in the walls of the arteries. If a blood clot forms over the plaque then the artery can become completely blocked suddenly giving rise to a heart attack.

Professor Samani, who is also Head of the Department of Cardiovascular Sciences at the University of Leicester and a Consultant Cardiologist at Leicester's Hospitals, added: "Height has a strong genetic determination and in the last few years a large number of genetic variants have been identified in our DNA that determines one's height.

"The beauty about DNA is that it cannot be modified by one's lifestyle or socio-economic conditions. Therefore if shorter height is directly connected with increased risk of coronary heart disease one would expect that these variants would also be associated with coronary heart disease and this is precisely what we found."

Dr Christopher Nelson, British Heart Foundation-funded lecturer who undertook the analysis said: "We had genetic data through the CARDIoGRAM+C4D consortium on almost 200,000 persons with or without coronary heart disease. We examined whether 180 genetic variants that affect height also associated with coronary heart disease. In aggregate, we found that for every change in height of 6.5 cm (approx. 2.5 inches) caused by these variants the risk of coronary heart disease changed on average by 13.5%.

"The more height increasing genetic variants that you carry the lower your risk of coronary heart disease and conversely if you were genetically shorter the higher your risk."

Dr Nelson added: "We also examined whether the association we found between shorter height and higher risk of coronary heart disease could be explained by an effect of height on known risk factors for coronary heart disease like cholesterol, high blood pressure, diabetes etc. We only observed an association with cholesterol and fat levels which could explain a small proportion (less than a third) of the relationship between shorter height and coronary heart disease. The rest is probably explained by shared biological processes that determine achieved height and the development of coronary heart disease at the same time".

Professor Jeremy Pearson, Associate Medical Director at the BHF, which part-funded the study, said: "By using the power of very large scale genetic studies, this research is the first to show that the known association between increased height and a lower risk of coronary heart disease is at least in part due to genetics, rather than purely down to nutrition or lifestyle factors. The team has identified several ways that naturally occurring gene variations can control both a person's height and their risk of coronary heart disease. Further exploration of these genes may suggest new ways to reduce the risk of heart and circulatory disease."

Professor Samani concluded: "While we know about many lifestyle factors such as smoking that affect risk of coronary heart disease, our findings underscore the fact that the causes of this common disease are very complex and other things that we understand much more poorly have a significant impact.

"While our findings do not have any immediate clinical implications, better and fuller understanding of the biological mechanisms that underlie the relationship between shorter height and higher risk of coronary heart disease may open up new ways for its prevention and treatment."

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Research supported by the British Heart Foundation, the United Kingdom National Institute for Health Research, the European Union project CVgenes@target, and a grant from the Leducq Foundation.

Notes for Editors

CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics) consortium) represents a collaborative international effort to combine data from multiple large scale genetic studies to identify risk loci for coronary artery disease and myocardial infarction. Members and institutions participating in the consortium can be found at http://www.cardiogramplusc4d.org/

Professor Samani can be contacted via e-mail on njs@le.ac.uk or by telephone on (+44) 116 204 4758

This article was published on April 8, 2015, at NEJM.org.

DOI: 10.1056/NEJMoa1404881

British Heart Foundation

Coronary heart disease is the UK's single biggest killer. For over 50 years we've pioneered research that's transformed the lives of people living with heart and circulatory conditions. Our work has been central to the discoveries of vital treatments that are changing the fight against heart disease. But so many people still need our help. From babies born with life-threatening heart problems to the many Mums, Dads and Grandparents who survive a heart attack and endure the daily battles of heart failure. Every pound raised, minute of your time and donation to our shops will help make a difference to people's lives. For more information, visit bhf.org.uk

The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website.

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