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Lipoprotein(a) as a Causal Risk Factor for Cardiovascular Disease
Sean Doherty1, Sebastian Hernandez1, Rishi Rikhi2
1Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 USA.
Current Cardiovascular Risk Reports
|February 21, 2025
Summary
Lipoprotein(a) [Lp(a)] is a significant, genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS). Guidelines now recommend Lp(a) testing for primary prevention in all adults.
Area of Science:
- Cardiology
- Genetics
- Lipidology
Background:
- Lipoprotein(a) [Lp(a)] is an atherogenic molecule similar to LDL-C.
- Approximately 20% of the global population has elevated Lp(a) levels, primarily due to genetic factors (~90%).
- Lp(a) possesses proatherogenic, proinflammatory, and antifibrinolytic properties.
Purpose of the Study:
- To review the evidence supporting Lipoprotein(a) [Lp(a)] as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD).
- To summarize the role of Lp(a) in the development of calcific aortic valve stenosis (CAVS).
Main Methods:
- Review of epidemiological data.
- Analysis of genome-wide association studies.
- Examination of Mendelian randomization studies and meta-analyses.
Main Results:
- Strong associations exist between Lp(a) levels and ASCVD and CAVS.
- Emerging data suggest links between Lp(a) and ischemic stroke, peripheral arterial disease, and heart failure, though less robust.
- Multiple lines of evidence confirm Lp(a) as a causal risk factor for ASCVD and CAVS.
Conclusions:
- Current guidelines from major cardiology and lipid associations recommend universal Lp(a) testing for primary ASCVD prevention.
- Further research into Lp(a)-targeted therapies is crucial for understanding its causal role in cardiovascular disease.
- Lp(a) is a validated, genetically influenced risk factor for ASCVD and CAVS.
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