More people may be at risk of a potentially fatal heart condition than previously thought, according to a new study led by researchers at UCL (University College London) and Queen Mary University of London. The study was published in the journal JAMA Cardiology.
The team analysed the genes of 469,789 people in the UK (from the database UK Biobank) and found that one in 1,000 had genetic variants linked to cardiac transthyretin (ATTR) amyloidosis, a potentially fatal condition. The authors also found that participants with African ancestry had a much higher, with one in 23 (4.3%) having genes thought to be linked to the disease.
Patients with cardiac amyloidosis have an abnormal protein called amyloid buildup in the heart tissue. This stiffens the heart, making it less able to pump blood. If left untreated, it is likely to be fatal within four to six years. “We found a higher than expected number of people in the UK with potentially harmful genetic variants linked to cardiac ATTR amyloidosis, an often fatal condition,” said Dr Luis Lopes from the UCL Institute of Cardiovascular Science. “Many people with these variants will not go on to develop disease. However, it is important to try to identify those who do as early as we can, as there are promising new medicines that can effectively treat the condition, and acting earlier with these medicines is likely to help patients more.”
“Our study showed that people carrying these potentially harmful variants have a two-to-three-fold increase in the risk of heart failure and cardiac rhythm issues. This again highlights the need for early detection and monitoring for disease progression,” added Dr Nay Aung, from the William Harvey Research Institute, Queen Mary University of London.
Up till now, cardiac amyloidosis has been considered rare, affecting between one in 120,000 and one in 830,000 people globally. In recent years, however, the number of patients with this condition has increased, partly due to improvements in imaging pioneered at the UCL Centre for Amyloidosis. Cardiac amyloidosis can be hereditary, caused by a mutation in a gene called transthyretin, but it can also occur in elderly patients without a genetic basis. The hereditary form is more common in certain geographic clusters of populations in Portugal, Japan, and Sweden, as well as among individuals with Black African ancestry.
Instead of looking at just one gene, the new study estimated the prevalence of 62 variants identified as having a link to the disease. Using data from the UK Biobank, the research team found that people with these variants had a higher risk of heart failure, thickening of the heart muscle, and heart rhythm problems. Despite this, less than 3% of patients were diagnosed with cardiac amyloidosis. The authors believe that the risk is high for many more patients, and the disease may develop later in life or still be in its earliest stages during the time of the study. For this reason, they called for greater vigilance for possible hereditary cardiac amyloidosis among people with cardiovascular symptoms, such as unexplained thickened heart muscle.
The next step is assessing how many patients with these variants actually develop the disease. This could help to develop possible screening strategies to detect the condition early. At the moment, genetic tests are only offered to patients with symptoms or people whose family members have the disease. One promising new treatment for cardiac amyloidosis is a gene-editing therapy developed at the UCL Centre for Amyloidosis. The aim is to prevent the buildup of amyloid in the heart. Current treatments can only relieve the symptoms of heart failure but cannot address the underlying cause.
Aung N, Nicholls HL, Chahal CAA, et al. Prevalence, Cardiac Phenotype, and Outcomes of Transthyretin Variants in the UK Biobank Population. JAMA Cardiol. doi:10.1001/jamacardio.2024.2190