Non-linear Association of Alkaline Phosphatase-to-Albumin Ratio with All-Cause and Cancer Mortality: Evidence from NHANES 2005-2016

Abstract Background The relationship between the alkaline phosphatase-to-albumin ratio (APAR) and mortality remains unclear. This research looked into the association between APAR levels and cause-specific mortality in US adults. Methods A cohort of 7561 participants from NHANES (2005-2016) was analyzed, with mortality outcomes collected from National Death Index (NDI) records. Cox proportional hazards models and restricted cubic spline (RCS) analysis were utilized to determine hazard ratio (HR) and reveal the non-linear relationship between APAR levels and mortality. Inflection points were calculated using a recursive algorithm. Results Followed for an average 99.41 months, a total of 1048 deaths occurred, including 200 cancer deaths and 348 cardiovascular disease (CVD)-related deaths. Following multivariate adjustment, significant associations were observed between APAR levels and increased all-cause and CVD mortality. Furthermore, non-linear correlations between APAR levels and all-cause and cancer mortality were revealed, characterized by an L-shaped pattern, with mortality rates stabilizing at 1.289 and 2.167, respectively. Participants with APAR levels above the inflection point exhibited a 29.2% increase in all-cause mortality risk per unit increase in APAR levels (HR 1.292, 95% CI 1.217-1.372), and a 38.3% increase in cancer mortality risk (HR 1.383, 95% CI 1.199-1.596). Conclusion This study demonstrated non-linear associations between APAR levels and all-cause and cancer mortality. Thresholds of 1.289 and 2.167 might serve as potential targets for APAR to reduce all-cause and cancer mortality, respectively. Nevertheless, these findings necessitate validation through large-scale clinical trials for further substantiation.