ApoA-1 versus HDL-C as Markers of Cardiovascular Risk

BackgroundConflicting results have been reported as to the relative importance of apoA-1 versus HDL-C as markers of ASCVD risk. MethodsResidual discordance analysis with Cox proportional hazard models comparing apoA-1 and HDL-C as markers of ASCVD risk was applied to a sample of 291,995 UK Biobank, followed for a median of 11 years. Interaction test for the two markers and estimation of the effects of partitioning HDL-C into apoA-I, log-triglyceride and the remaining residual were also performed. ResultsApoA-1 and HDL-C had similar associations with ASCVD risk (HRs of 0.85, p-value < 0.001 for both). The residual of HDL-C added significantly to the risk associated with apoA-1 as did the residual of apoA-1 to HDL-C. There was a statistically significant interaction between apoA-I and HDL-C (HR=1.05, 95% CI: (1.04, 1.06); p < 0.001). Decomposing HDL-C into the 3 components, apoA-I accounted for the largest portion of the effect with a HR of 0.85 95%CI: (0.83, 0.86) with smaller effects for lnTG: 1.04 (1.02, 1.06) and residual of HDL-C: 0.98 95%CI: (0.96, 0.995). ConclusionsHDL-C and apoA-1 have associations of equivalent strength with ASCVD risk with significant interaction modifying the effect of one by the other. Upon decomposition, ApoA-I retained more of the effect of HDL-C as compared to log-triglycerides. While only observational, the results are consistent with the relation of HDL to risk not being determined by the concurrent level of triglyceride. Clinical PerspectiveThe plasma levels of HDL-C and apoA-I are potent predictors of cardiovascular risk. However, there are few data comparing the relative precision of HDL-C and apoA-I for this purpose. Moreover, the risk of low HDL-C has been attributed to concurrent hypertriglyceridemia, consequently downgrading the potential importance of HDL in predicting or explaining risk. Novel FindingsBased on residual discordance analysis, HDL-C and apoA-I have similar predictive precision for ASCVD risk. However, each adds significantly to the other and. Moreover, triglycerides account for only a small portion of the risk attributable to HDL with apoA-I accounting for the principal portion. Clinical SignificanceHDL, whether measured as HDL-C or apoA-I, is a potent predictor of ASCVD risk. It remains essential to search for the biological basis or bases for these relationships.