Supplementary Material for: Myocardial Ageing Among a Population-Based Cohort Is Associated with Adverse Cardiovascular Outcomes and Sex-Specific Differences Among Older Adults

Introduction
Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit.

Methods
Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included.

Results
956 participants [mean age 63±12.9 years, n=424 males (44%)] were categorized based on mitral peak early to late diastolic filling velocity (E/A) ratios: E/A <0.8 (28%), E/A 0.8-1.2 (39%), E/A (29%), E/A >2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI 2.24-3.56), and 0.45 per 100 person-years (95% CI 0.26-0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes were significantly different among E/A categories (log-rank p=0.0269). E/A<0.8 (HR 1.80, 95%CI 1.031, 3.14, p=0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI 2.62-4.84), and 0.75 per 100 person-years (95% CI 0.39-1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI 1.56-3.16), and 0.21 per 100 person-years (95% CI 0.067-0.64) for all-cause death. For E/A<0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8-1.2 category (HR 2.49, 95%CI 1.18, 5.23, p=0.017).

Conclusion: Myocardial ageing was an independent predictor of cardiovascular outcomes in community-dwelling older adults prior to clinical CVD. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.