ApoM and Major Adverse Cardiovascular Events in Chronic Kidney Disease: A Prospective Cohort Study

BACKGROUND: Cardiovascular disease is the leading cause of mortality in patients with chronic kidney disease (CKD). APOM plays a critical role in reverse cholesterol transport by facilitating the formation of pre-β-HDL (high-density lipoprotein) and enabling the binding of S1P (sphingosine-1-phosphate) to HDL, a complex involved in several antiatherogenic processes. In this study, we sought to investigate the potential association between plasma APOM levels and the risk of adverse cardiovascular outcomes in individuals with CKD. METHODS: Plasma APOM levels were quantified using a sandwich ELISA-based assay. Plasma S1P levels were measured by high-performance liquid chromatography. The primary end point was a composite of major adverse cardiovascular events (MACE) and all-cause mortality. RESULTS: In this secondary analysis of the CARE FOR HOMe study (Cardiovascular and Renal Outcome in CKD 2-4 Patients-The Fourth Homburg Evaluation), 463 nondialysis patients with CKD stages G2 to G4 were included. Plasma APOM levels exhibited a significant inverse association with the risk of MACE (standardized hazard ratio, 0.60 [95% CI, 0.49-0.75]; P<0.001) and all-cause mortality (standardized hazard ratio, 0.63 [95% CI, 0.48-0.83]; P<0.001). This inverse association with MACE remained robust after adjusting for established cardiovascular and renal risk factors. These findings were further corroborated in an independent cohort of 822 patients with CKD from the Copenhagen CKD study. Plasma S1P levels showed an inverse association with MACE in univariable analyses; however, this relationship lost statistical significance after multivariable adjustments. CONCLUSIONS: Our findings demonstrate a significant association between low plasma APOM levels and an increased risk of MACE in patients with CKD. These results suggest that APOM may play a role in cardiovascular protection in this vulnerable population.