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ApoA-1 versus HDL-C as markers of cardiovascular risk
Selin Bilgic1, Karol Pencina2, Michael Pencina3
1Mike and Valeria Rosenbloom Centre for Cardiovascular Prevention, Department of Medicine, McGill University Health Centre, 1001 Decarie Blvd, Montreal, Quebec H4A 3J1, Canada (Bilgic, K. Pencina, M. Pencina, Dufresne, Thanassoulis, and Sniderman).
Insights
Apolipoprotein A-1 (apoA-1) and high-density lipoprotein cholesterol (HDL-C) show similar associations with atherosclerotic cardiovascular disease (ASCVD) risk. Upon analysis, apoA-1 explained more of the risk than triglycerides, suggesting HDL-C
Area of Science:
- Cardiovascular Research
- Biomarker Analysis
- Lipid Metabolism
Background:
- Conflicting data exists on the relative importance of apolipoprotein A-1 (apoA-1) versus high-density lipoprotein cholesterol (HDL-C) in predicting atherosclerotic cardiovascular disease (ASCVD) risk.
- Understanding the precise role of these markers is crucial for accurate risk assessment.
Purpose of the Study:
- To directly compare the predictive capabilities of apoA-1 and HDL-C for cardiovascular risk.
- To investigate the interaction between apoA-1 and HDL-C in ASCVD risk prediction.
Main Methods:
- Utilized residual discordance analysis with Cox proportional hazard models.
- Analyzed data from 291,995 UK Biobank participants with a median follow-up of 11 years.
- Performed interaction tests and decomposed HDL-C into apoA-1, log-triglyceride, and residual components.
Main Results:
- Both apoA-1 and HDL-C demonstrated similar associations with ASCVD risk (HR=0.85 for both).
- Significant interaction was observed between apoA-1 and HDL-C, modifying their individual effects.
- Upon decomposition, apoA-1 accounted for the largest portion of HDL-C's effect, more so than log-triglycerides.
Conclusions:
- HDL-C and apoA-1 exhibit equivalent strength in association with ASCVD risk, with their effects being mutually modifying.
- Decomposition analysis indicates apoA-1 is a stronger determinant of HDL-C's risk-predictive capacity compared to triglycerides.
- These observational findings suggest that triglyceride levels may not solely determine the relationship between HDL and cardiovascular risk.
Background:
Conflicting results have been reported as to the relative importance of apolipoprotein A-1 (apoA-1) vs high-density lipoprotein cholesterol (HDL-C) as markers of atherosclerotic cardiovascular disease (ASCVD) risk.
Objective:
To compare the apoA-1 and HDL-C as predictors of cardiovascular risk.
Methods:
Residual 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 participants, followed for a median of 11 years. Interaction tests for the 2 markers and estimation of the effects of partitioning HDL-C into apoA-1, log-triglyceride, and the remaining residual were also performed.
Results:
ApoA-1 and HDL-C had similar associations with ASCVD risk (hazard ratios [HRs] of 0.85, P value <.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-1 and HDL-C (HR = 1.05, 95% CI: (1.04-1.06); P < .001). Decomposing HDL-C into the 3 components, apoA-1 accounted for the largest portion of the effect, with an HR of 0.85 (95% CI: 0.83-0.86), with smaller effects for ln triglycerides: 1.04 (95% CI: 1.02-1.06) and the residual of HDL-C: 0.98 (95% CI: 0.96-0.995).
Conclusion:
HDL-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-1 retained more of the effect of HDL-C as compared with 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.
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