Plaque rupture is a major cause of heart attack. Mechanical factors including blood pressure and shear stress have been found to be related to the rupture risk. The blood vessel is naturally under a periodical and low-level pressure stress state, therefore, the plaque rupture can be treated as a fatigue problem. By simplifying the blood vessel as a cylinder, the crack propagation and the fatigue rupture are investigated. The theoretical solution for an edge crack in a classical cylinder is used to calculate the Stress Intensity Factor (SIF) with the Paris Law being utilized to determine the crack growth rate. The fatigue crack growth is numerically simulated. The various factors that may influence the fatigue life are studied. The results show that when the ratio of the external radius to the internal radius is fixed, the effect of the internal radius on the fatigue crack growth can be neglected; the thrombus with an increase of the wall thickness will reduce the stress concentration, this single factor may have a positive effect to the vascular life from the point view of fatigue; the blood pressure has a great effect on the fatigue life, in an exponential manner.