Fig. 3

Directed acyclic graph highlighting potential mechanism underpinning the association between APOE ε4 and MCF. APOE ε4 carriers had a better strain profile characterized by higher absolute (i.e., better) longitudinal and radial PDSRs using CMR in the UK Biobank. In addition, ε4 carriers had a slightly lower E/e’ (in ALSPAC and NSHD) and LVmass (in SABRE and UK Biobank) albeit not statistically significant. In the literature, ε4 has been linked to a higher level of androgens which can increase myocardial calcium and ε4 has also been linked to pro-catabolic glucose and ketone metabolism. Thus, we postulate that enhanced myocardial dynamics, contractility, and energetics rather than pathological hypertrophy mediate this association