Researcher Dr Dirk Paul said: “We previously discovered that certain gene variants are more common in people with heart disease. Now the challenge is to find out how exactly these gene variants contribute to the risk of heart disease.”

Using stem cells from 200 healthy volunteers, the team grew them in the laboratory into macrophages, which are specialist cells responsible for sweeping up harmful particles, such as cholesterol in the arteries.

Dr Paul said: “Macrophages are part of the biological machinery that clears away fatty material inside the arteries – but in individuals who carry these gene variants, the machinery doesn’t work properly leading to a build-up of cholesterol.

“This in turn leads to atherosclerosis, the condition that causes most heart attacks and strokes.

“We fed the macrophages with cholesterol and then studied them in minute molecular detail to see what happened. This will improve our understanding of how atherosclerosis develops.

“This new approach will help us see how the gene variants affect disease risk and translate this knowledge into new treatments.”

• This study was funded by the NIHR Cambridge BRC and the BHF Cambridge Centre of Research Excellence.
• For more information visit the Cardiovascular Epidemiology Unit – Integrative Human Genomics research web pages.

Researchers in Cambridge carried out the largest ever genetic study of the disease by analysing the genomes – the DNA – of more than 1,000 people with PAH.

They discovered that mutations in several genes were responsible for causing the illness, including four genes that were not previously known to be connected to the disease. The mutations cause some proteins to stop working well, contributing to the arterial stiffness.

Understanding the causes of the disease will help researchers to better target new treatments to help people with PAH.​

It usually results when the heart beats with rapid erratic electrical impulses (known as ventricular fibrillation) and arises in a person with underlying heart disease. Those at risk of sudden cardiac arrest can be given an Implantable Cardiac Defibrillator (ICD), which sends shocks to the heart to restore normal cardiac rhythm. The ICD is placed under the skin and leads are passed through a vein into the heart.

ICDs can cause problems when the device for example deteriorates or breaks down and then there is a risk for the patient. Researchers in Cambridge developed a subcutaneous ICD (S-ICD) which can be placed under the skin, removing the need for surgery or having the device wired up to the heart.

The device successfully completed clinical trials which resulted in European approval (2009) and FDA approval in the United States (2012) and is routine treatment in most UK Specialist Centres.

Over 50,000 people have now benefited from the S-ICD worldwide. In October 2013 the S-ICD was awarded the Prix Galien (‘regarded as equivalent Nobel Prize in biopharmaceutical research’) in New York as the ‘Best Medical Technology’.

Most guidelines now regard the S-ICD as an option of choice for most patients for both the primary and secondary prevention of sudden cardiac death.

More information about this research can be heard by Nick Morrell, in the video above.