LOSS of Y chromosome (LOY) in blood cells was linked to a significantly higher risk of myocardial infarction in older males without prior cardiovascular disease, according to new prospective data that added weight to growing evidence connecting clonal haematopoiesis with heart disease.
Researchers analysed genetic and clinical data from more than 5,000 healthy males aged 65 years and older who were enrolled in a large prevention trial and followed for a median of 8.4 years. The findings suggested that LOY, a common age-related genetic alteration, independently increased the risk of major cardiovascular events, particularly heart attack.
Loss of Y Chromosome and Cardiovascular Risk
The study focused on loss of Y chromosome, a phenomenon in which a proportion of circulating white blood cells in males lose the Y chromosome over time. LOY has previously been associated with ageing, smoking, cancer, and mortality, but evidence in healthy populations has been limited.
During follow-up, nearly 10% of participants experienced a major adverse cardiovascular event, including myocardial infarction or ischaemic stroke. After adjusting for established cardiovascular risk factors, each standard deviation increase in LOY was associated with a 14% higher risk of myocardial infarction. Males with the highest degree of LOY had a 68% higher heart attack risk compared with those without detectable LOY.
Notably, no significant association was observed between loss of Y chromosome and ischaemic stroke, suggesting a more specific link with coronary disease rather than vascular events overall.
To support the robustness of the findings, the investigators also examined data from more than 190,000 middle-aged males in a large population biobank. This independent analysis showed a consistent, though more modest, association between LOY and myocardial infarction.
Why This Finding Matters
Cardiovascular disease remains the leading cause of death globally, and identifying novel biological risk markers is a priority. Loss of Y chromosome is considered a subtype of clonal haematopoiesis, a condition in which blood cells acquire age-related genetic changes that may promote inflammation and atherosclerosis.
The authors noted that the study was observational and could not establish causality. LOY was measured at a single time point, and participants were predominantly older White males, which may limit generalisability.
However, the findings raised the possibility that genetic mosaicism in blood cells could one day help refine cardiovascular risk assessment in ageing males. Further research is needed to determine whether loss of Y chromosome is a modifiable risk factor or a marker of underlying biological ageing.
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.
