SIRT6 may influence the development of CVDs in several ways: (1) impact glycolipid homeostasis by controlling the expression of multiple related metabolic genes [21,34,35]; (2) Negatively regulate cardiac hypertrophy by attenuating insulin-like growth factor (IGF)-Akt signaling and, thus, impacting the development of heart failure [20]; (3) SIRT6 is a critical regulator of vascular smooth muscle cell differentiation, which contributes to atherosclerosis [36]. Here, SIRT6 is linked to heart failure.