ESC Congress 2026 Abstract · Oct 26, 2026

Loss of chromosome Y in elderly men is not associated with cardiovascular risk following acute myocardial infarction

By Opstad T, Palmero S, Rypdal KB et al.

Background: Genome instability is considered a hallmark of ageing, cellular senescence and age-related diseases, e.g., shortening of chromosome telomeres. Mosaic loss of chromosome Y (LOY) is relatively common in blood cells of ageing men, and LOY is increasingly being recognized as a male-specific genetic risk factor for disease. Purpose: To assess LOY frequency in elderly men with acute myocardial infarction (AMI) and evaluate associations with comorbidities and major adverse cardiovascular events (MACE). Methods: OMEMI was a multicenter randomized controlled trial of omega-3 supplements vs placebo, that included elderly patients with a recent (2-8 weeks) AMI between 2012 and 2020. The overall trial was neutral. This sub-study included all male participants (n=709, mean age 75, range 70-82). LOY frequency (%) was analyzed in blood leukocytes by digital PCR through absolute quantification of AMEL X and AMEL Y gene copy numbers using digital PCR at baseline (two-eight weeks post-MI), calculated by AMEL (X-Y)/X*100. LOY< 5% was interpreted as LOY absence according to previous studies. Leukocyte telomere length (LTL) was measured by qPCR (n=208). Cox proportional hazards regression was used to analyze time to event data for MACE, including stroke, AMI, heart failure (HF), unscheduled revascularization, and death during two years follow-up. Adjustment variables included age, sex, current smoking, body mass index (BMI), systolic blood pressure (SBP), hypertension, diabetes, heart failure, and creatinine at baseline. Results: Median leukocyte LOY was 7% (Q1, Q3; 1.3, 15.4) and 425 men (60%) presented with LOY≥5%. Higher LOY correlated with older age (r=0.078, p=0.038) and shorter LTL (r=-0.185, p=0.007). Cigarette smoking, lower SBP, lower triglycerides, and absence of diabetes were also associated with higher LOY quartile (Table). During two years of follow-up, 159 (22.5%) of men experienced a MACE. Men with LOY<5% had higher rates of MACE (26.1%) compared to those with LOY≥5% (20.0%). In multivariable Cox models, the risk of MACE decreased with increasing LOY (aHR 0.95 (0.90-0.99) per % increase, p=0.048), and patients in Q1 had the highest risk (aHR 1.44 (1.04-1.98), p=0.026, compared to Q2-4; Figure). Conclusion: Leukocyte LOY was relatively low (median 7%) in elderly male patients with a recent AMI, and higher LOY was associated with higher age and shorter telomeres. Unexpectedly, higher leukocyte LOY associated with a lower risk of MACE over the two following years. These findings warrant further exploration of LOY and genomic instability in elderly men with established cardiovascular disease.

doi.org/10.1093/eurheartj/ehag785.3801Open accessPopulations