Study finds loss of Y chromosome in blood cells of ageing men may raise heart disease risk
Credit: Peopleimages.com - YuriArcurs
A new study by Monash researchers has found that age-related loss of the Y chromosome from circulating blood cells may represent an under-recognised biological signal associated with myocardial infarction risk in older men. The study was published in the prestigious Journal of the American College of Cardiology (JACC).
Led by Dr Monira Hussain and Professor Paul Lacaze from the School of Public Health and Preventive Medicine, the study measured the loss of Y chromosome in circulating blood cells of thousands of initially healthy older men from the ASPREE study. The analysis then examined whether older men who had higher levels of Y chromosome loss were more likely to develop future major cardiovascular events over long-term follow-up.
As men age, some of their cells gradually lose the Y chromosome. While this phenomenon can occur in different tissues, it is most often measured in circulating blood cells. This age-related change is called “loss of Y” (LOY).
LOY is common in older men and becomes more frequent with increasing age, affecting approximately 20-30 per cent of men aged over 70. LOY is not inherited or present at birth; but develops gradually over time during the ageing process.
Previous research had linked LOY to pre-existing heart failure and other chronic conditions. However, it was not known whether LOY in otherwise healthy men predicted future risk of myocardial infarction, commonly known as a heart attack, which remains one of the leading causes of death in older men worldwide.
The study followed more than 5,000 older men participating in the ASPREE study. All participants at enrolment were free from cardiovascular disease and were then followed for several years, with heart attacks and strokes carefully identified using clinical records.
Over time, men with higher levels of Y chromosome loss in their blood were found to have a significantly increased risk of myocardial infarction. Men with LOY experienced around a 70 per cent higher risk compared with men whose blood cells retained the Y chromosome. This association remained even after accounting for established cardiovascular risk factors such as smoking, blood pressure, cholesterol levels, diabetes, and kidney function.
Importantly, the association appeared specific to myocardial infarctions rather than stroke, suggesting that the biological processes underlying different types of cardiovascular disease may not be identical.
To strengthen the findings, the association was also examined in a large independent population of men from the UK Biobank, where a similar pattern was observed.
Dr Hussain said that together, these findings are the first to suggest that age-related loss of the Y chromosome may represent a biological signal associated with myocardial infarction risk in older men. “They also broaden understanding of LOY beyond heart failure, highlighting its potential relevance to ischemic heart disease, the form of cardiovascular disease responsible for most fatal events,” she said. “The results may also help shed light on biological factors that contribute to sex differences in cardiovascular disease risk.
“Further research will be needed to determine whether measuring LOY could eventually contribute to improved assessment of cardiovascular risk in ageing men, and to understand how these findings extend across diverse populations,” she said.
About Monash University
Monash University is Australia’s largest university with more than 80,000 students. In the 60 years since its foundation, it has developed a reputation for world-leading high-impact research, quality teaching, and inspiring innovation.
With four campuses in Australia and a presence in Malaysia, China, India, Indonesia and Italy, it is one of the most internationalised Australian universities.
As a leading international medical research university with the largest medical faculty in Australia and integration with leading Australian teaching hospitals, we consistently rank in the top 50 universities worldwide for clinical, pre-clinical and health sciences.
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