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Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol-Mediated Cardiovascular Risk: A
Harpreet S Bhatia1, Simon Wandel2, Peter Willeit3
1Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (H.S.B., S.T.).
Circulation
|November 4, 2024
Summary
High lipoprotein(a) [Lp(a)] levels significantly increase atherosclerotic cardiovascular disease (ASCVD) risk, independent of low-density lipoprotein cholesterol (LDL-C). Lowering LDL-C does not eliminate the elevated ASCVD risk associated with high Lp(a) levels.
Area of Science:
- Cardiology
- Genetics
- Preventive Medicine
Background:
- Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] are independently linked to atherosclerotic cardiovascular disease (ASCVD).
- The combined impact of Lp(a) and LDL-C levels on ASCVD risk requires further elucidation.
Purpose of the Study:
- To investigate the association between Lp(a) and LDL-C levels and ASCVD risk.
- To determine if LDL-C lowering mitigates Lp(a)-associated ASCVD risk.
Main Methods:
- A meta-analysis of 27,658 participants from 6 placebo-controlled statin trials.
- Assessed the association of baseline Lp(a) and LDL-C levels with ASCVD events using multivariable models.
- Evaluated the joint association of Lp(a) and achieved LDL-C levels with ASCVD risk.
Main Results:
- Elevated Lp(a) levels showed a log-linear association with increased ASCVD risk.
- Individuals with Lp(a) >50 mg/dL had higher ASCVD risk across all LDL-C levels.
- The highest ASCVD risk was observed with Lp(a) >50 mg/dL and high LDL-C levels.
Conclusions:
- Lp(a) and LDL-C levels independently and additively contribute to ASCVD risk.
- LDL-C reduction alone may not fully counteract the risk posed by elevated Lp(a).
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