In this cohort study, we presented novel findings showing that, in comparison to categorizing Lp(a), FIB, or any other combined metrics individually, extremely high levels of both Lp(a) and FIB concurrently were associated with a significantly increased risk of mortality from all-cause, CVD, and cancer, indicating that individuals exhibiting elevated levels of both Lp(a) and FIB warrant more vigilant monitoring and the implementation of more intensive risk management strategies. The gene discussed is LPA; the disease is cancer.