Loss of the Y chromosome (LOY) in blood cells has been linked to a significantly heightened risk of myocardial infarction, or heart attack, in older men without a history of cardiovascular disease. This emerging evidence underscores the connection between clonal hematopoiesis-a condition marked by age-related genetic changes-and heart issues.
Researchers examined genetic and clinical data from over 5,000 healthy males aged 65 and older who participated in a large prevention trial and were tracked for an average of 8.4 years. Their study concluded that LOY, a prevalent age-associated genetic modification, independently raises the risk of major cardiovascular events, particularly heart attacks.
LOY occurs when a portion of a man’s circulating white blood cells loses the Y chromosome over time. While previous studies have linked LOY to aging, cancer, smoking, and increased mortality, comprehensive evidence in healthy populations has been sparse. During the study’s follow-up, nearly 10% of participants suffered major cardiovascular events, including heart attacks or ischemic strokes. After controlling for established cardiovascular risk factors, each standard deviation increase in LOY was associated with a 14% rise in heart attack risk. Men exhibiting the highest levels of LOY had a staggering 68% greater risk compared to those without detectable LOY.
Interestingly, no significant link was found between LOY and ischemic strokes, suggesting a more direct relationship with coronary disease than with vascular events in general. To bolster their findings, researchers also analyzed data from over 190,000 middle-aged men in a major population biobank. This additional analysis revealed a consistent, albeit less pronounced, connection between LOY and heart attacks.
The implications of this finding are profound. As cardiovascular disease continues to be the leading global cause of death, identifying new biological risk markers is critical. LOY is viewed as a distinct form of clonal hematopoiesis, which can lead to inflammatory responses and atherosclerosis through age-related genetic alterations.
The authors of the study caution that the observational nature of their work prevents definitive conclusions about causality. LOY was assessed at a single time point, and the study’s predominantly older White male population may limit wider applicability. Nonetheless, the results raise intriguing possibilities that genetic mosaicism in blood cells might one day enhance cardiovascular risk assessment for aging males. Further investigation is essential to determine whether the loss of the Y chromosome is a modifiable risk factor or simply a marker of biological aging.
For those interested in the cutting-edge intersection of genetics and cardiovascular health, this study highlights the potential of LOY as an early indicator of heart risk in older men and the importance of ongoing research in this crucial area of public health. The study sheds new light on how genetic changes can influence the heart’s health and paves the way for future investigations into mitigating risks associated with age-related genetic alterations.
Reference: Hussain SM et al. Loss of Y chromosome and major cardiovascular events in a prospective study of older men. JACC. 2026; DOI:10.1016/j.jacc.2025.10.069.
Original Source: https://www.emjreviews.com/cardiology/news/loss-of-y-chromosome-linked-to-cardiovascular-risk/
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Publish Date: 2026-01-15 21:32:00
