The loss of the Y chromosome represents the most frequent genetic mutation occurring after conception in males, predominantly affecting white blood cells—key components of the immune system responsible for combating pathogens.
This chromosomal loss accumulates with age as stem cells rapidly divide to replenish white blood cells. Approximately 40% of men aged 70 exhibit detectable levels of cells lacking the Y chromosome.
Interest in this phenomenon surged in 2014 when Lars Forsberg of Uppsala University, Sweden, and his team discovered that older men with significant Y chromosome loss in their blood had a life expectancy reduced by an average of five and a half years compared to men without this loss. Subsequent studies, including those by Walsh, have connected this mutation specifically to heightened heart disease risk.
Building on these findings, Forsberg and colleagues have recently explored the relationship between Y chromosome loss and cardiovascular conditions.
Utilizing data from the Swedish Cardiopulmonary Bioimage Study—which includes detailed vascular imaging of over 30,150 volunteers aged 50 to 64, about half male—they assessed early signs of atherosclerosis, or blood vessel narrowing, in participants without diagnosed cardiovascular disease.
Among nearly 12,400 male participants with available genetic data, researchers categorized men into three groups based on the extent of Y chromosome loss in their white blood cells: no detectable loss, loss in 10% or fewer cells, and loss in more than 10%. Their atherosclerosis levels were compared against each other and against female participants.
The results revealed that nearly 75% of men with over 10% Y chromosome loss showed narrowed blood vessels, compared to about 60% in men with 10% or less loss. Men with undetectable Y loss still showed atherosclerosis in approximately 55% of cases, while about 30% of women exhibited the condition. Forsberg emphasizes that “loss of Y is not the sole explanation for sex differences in heart disease—other factors contribute.”
This study follows research led by Thimoteus Speer at Goethe University Frankfurt, which examined men undergoing angiography for suspected cardiovascular disease.
Speer’s team found that men with Y chromosome loss in more than 17% of immune cells had over twice the risk of dying from a heart attack within ten years compared to those with fewer affected cells.
“The findings from Forsberg’s and our studies align closely,” Speer notes. “Forsberg reports increased coronary atherosclerosis, and we observe a significantly higher risk of heart attack-related death, which is the ultimate consequence of coronary atherosclerosis.”
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