Severe, yet lesser-known heart condition far more common than doctors thought

LONDON — An alarming new study has revealed that a potentially fatal heart condition may be lurking in the genes of far more people than previously thought. Researchers in the United Kingdom have discovered that about one in every 1,000 individuals carries genetic variants that could lead to transthyretin amyloidosis (ATTR), a severe and often overlooked form of heart disease.

This startling finding comes from an analysis of the UK Biobank, a massive database containing genetic and health information from nearly half a million British adults. The study, published in JAMA Cardiology, suggests that the prevalence of these risky genetic variants is much higher than current estimates of diagnosed ATTR cases.

ATTR occurs when a protein called transthyretin, which normally helps transport vitamins and hormones in the blood, begins to misfold and clump together. These protein clumps, called amyloid fibrils, can accumulate in various organs, particularly the heart, leading to life-threatening complications.

The disease can be inherited (hereditary ATTR), meaning it is passed down from the genes of your parents. It can also develop spontaneously later in life (wild-type ATTR). This study focused on hereditary ATTR, which is caused by mutations in the TTR gene. Until now, it was thought to be a rare condition, affecting only a small number of families. However, this new research paints a very different picture.

The team identified 473 individuals carrying genetic variants classified as “likely pathogenic” or “pathogenic” – meaning they have a high chance of causing disease. This represents about 0.1% of the study population — or one in 1,000 people. Even more striking, among participants of African ancestry, the prevalence shot up to 4.3% — or about one in 23 individuals.

Despite carrying these high-risk genetic variants, only a small fraction of individuals (2.8%) had actually been diagnosed with amyloidosis based on their medical records. This suggests that many people may be living with undiagnosed ATTR or are at risk of developing it in the future.

“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,” says senior author Dr. Luis Lopes from University College London’s Institute of Cardiovascular Science in a media release.

“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,” adds first author Dr. Nay Aung from the William Harvey Research Institute at Queen Mary University of London.

The study also found that individuals carrying these risky TTR variants were more likely to have thicker heart muscles – a telltale sign of ATTR. These findings have significant implications for public health and clinical practice.

With the recent development of effective treatments for ATTR, early identification of at-risk individuals could be life-saving. The study’s authors suggest that increased vigilance and potentially genetic screening could help catch cases earlier before irreversible damage occurs.

As our understanding of genetic risks continues to evolve, studies like this highlight the power of large-scale genetic databases in uncovering hidden health threats. It also underscores the complexity of genetic diseases, where carrying a risky gene doesn’t always mean developing the disease – a phenomenon known as variable penetrance.

For now, the message is clear: ATTR may be far more common than we thought, and awareness among both doctors and the public needs to increase. As one researcher put it, this study is a wake-up call to the medical community to be on high alert for this sneaky but serious condition.