Telomere biology in atherosclerotic cardiovascular disease (aCVD) is shown for both leukocyte/systemic telomere length (TL) (left) and vascular lesion TL (right). Note that leukocyte telomeres are typically shorter than vascular tissue telomeres (20). (A) Hypothesis 1: Inheritance of shorter telomeres leads to atherosclerosis. (B) Hypothesis 2: Accelerated telomere attrition leads to aCVD. (C) Hypothesis 3: Telomere attrition is an epiphenomenon arising from atherosclerosis/aCVD-associated oxidative stress and inflammation. (D) Hypothesis 4: The local telomere attrition rate in atherosclerotic lesions determines aCVD onset, but is not reflected in systemic TL (either in leukocytes or healthy vascular tissue). Alarm clock represents mitotic clock (reflecting critical telomere attrition).