Abstract
BACKGROUND: There is evidence indicating that both lipoprotein(a) [Lp(a)] and fibrinogen (FIB) are associated with mortality, However, the impact of their combination on mortality has not been determined. Thus, the aim of this study was to examine the association between the combination of Lp(a) and FIB with all-cause and cause-specific mortality. METHODS: This prospective cohort study enrolled 4,730 participants from the third National Health and Nutrition Examination Survey. The exposure variables included Lp(a), FIB and their combination, while the outcome variables consisted of all-cause, cardiovascular disease (CVD) and cancer-related mortality. Multivariate COX regression, subgroup analysis, sensitivity analysis and restricted cubic spline (RCS) were used to investigate the association between Lp(a), FIB and their combination with all-cause, CVD and cancer-related mortality. RESULTS: Over a median follow-up period of 235 months, 2,668 individuals died, including 1,051 deaths attributed to CVD and 549 deaths due to cancer. Multivariate Cox regression analyses revealed independent associations between both Lp(a) and FIB with all-cause, CVD, and cancer-related mortality. Compared to participants in the 1st to 50th percentiles of both Lp(a) and FIB, those in the 90th to 100th percentiles exhibited multivariable adjusted HRs of 1.813 (95% CI: 1.419-2.317, P < 0.001), 2.147 (95% CI: 1.483-3.109, P < 0.001) and 2.355 (95% CI: 1.396, 3.973, P = 0.001) for all-cause, CVD and cancer-related mortality, respectively. Subgroup and sensitivity analyses did not substantially attenuate the association between the combination of high Lp(a) and high FIB with the risk of all-cause and CVD-related mortality. Additionally, the RCS analysis showed that the relationship between Lp(a) and the risk of all-cause and cancer-related mortality, as well as the relationship between FIB and the risk of cancer-related mortality, were linear (P for nonlinearity > 0.05). Conversely, the relationship between Lp(a) and the risk of CVD-related mortality, as well as the relationship between FIB and the risk of all-cause and CVD-related mortality, were nonlinear (P for nonlinearity < 0.05). CONCLUSIONS: High levels of Lp(a) and FIB together conferred a greater risk of mortality from all-cause, CVD and cancer.