Loss of Y Chromosome and Major Cardiovascular Events in a Prospective Study of Older Men

Loss of the Y chromosome (LOY) from a percentage of circulating leukocytes is common in older men and is associated with cardiovascular risk. However, most studies have involved men with preexisting disease, not healthy men followed prospectively.

This study sought to investigate the association between LOY and risk of incident major adverse cardiovascular events (MACEs), including myocardial infarction (MI) and ischemic stroke.

This study included 5,131 men aged ≥ 65 years from the ASPREE (ASPirin in Reducing Events in the Elderly) trial with no prior cardiovascular disease at baseline. LOY percentage was measured in peripheral blood using microarrays and the log-R-ratio method. MACEs, including MI and ischemic stroke, were collected during the trial and subsequent observational follow-up. Cox regression assessed associations of LOY as a continuous (per SD) and categorical (decile-based) variable. Deciles 1 through 6 (reference) represented no LOY, deciles 7 through 9 moderate, and decile 10 substantial.

Over a median of 8.4 years of follow-up, 9.8% men (n = 505) experienced MACEs, with 5% (n = 256) MI and 4% (n = 207) ischemic stroke. In the fully adjusted model, each SD increase in LOY was associated with 14% higher MI risk (HR per SD: 1.14; 95% CI: 1.02-1.28). Men with substantial LOY (decile 10) had 68% higher MI risk vs men without LOY (HR: 1.68; 95% CI: 1.16-2.54). No associations were observed for ischemic stroke. Results were robust to sensitivity analyses. In 191,340 men aged 40 to 70 years from the UK Biobank, LOY was also associated with MI (HR per SD: 1.03; 95% CI: 1.01-1.06).

LOY is associated with increased MI risk, but not stroke, in older men.