Lipoprotein(a) and cardiovascular disease
Key result
Emerging therapeutics lower high-risk Lp(a) levels by up to ~98%.
Why the study?
One in five people are at high risk for atherosclerotic cardiovascular disease and aortic valve stenosis due to high lipoprotein(a), yet there are currently no approved drugs to lower lipoprotein(a) concentrations.
Key Points
- To review the pathophysiology, genetics, epidemiology, clinical consequences, screening recommendations, and pipeline therapeutics for elevated lipoprotein(a).
- Literature synthesis examining the genetic epidemiology and causal cardiovascular risks linked to circulating lipoprotein(a) concentrations.
- Evaluation of clinical screening guidelines, diagnostic management strategies, and late-stage clinical trials targeting lipoprotein(a) reduction.
- Lipoprotein(a) concentrations are more than 90% genetically determined, affect one in five individuals at high risk for atherosclerotic cardiovascular disease and aortic valve stenosis, and are 17% higher in post-menopausal women.
- Concentrations vary globally, being lowest in east Asian, European, and southeast Asian populations, intermediate in south Asian, Middle Eastern, and Latin American populations, and highest in African populations.
- At least five investigational drugs reduce lipoprotein(a) concentrations by 65% to 98%, with three currently undergoing evaluation in large cardiovascular endpoint trials.
Structured PICO
P
Population
Individuals at high risk for atherosclerotic cardiovascular disease and aortic valve stenosis due to high lipoprotein(a) concentrations
E
Exposure
Lipoprotein(a) measurement, lifestyle adherence, medication to lower other cardiovascular risk factors, and future lipoprotein(a)-lowering drugs in development
Limitations
- No currently approved drugs to lower lipoprotein(a) concentrations
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
Børge Grønne NordestgaardClinical Professor, University of Copenhagen; Chief Physician, Herlev-Gentofte Hospital“By expanding testing, we can figure out who carries it and would benefit from lipoprotein(a)-lowering medication. And until the medication becomes available, we can use this knowledge to take better care of individuals with high concentrations of lipoprotein(a) in their blood. The main factors here are making sure to exercise, eating healthy, avoiding smoking and being overweight, and treating high cholesterol levels.”
Implication
This review summarizes the genetics, epidemiology, and clinical management of elevated lipoprotein(a), highlighting that while no specific lowering drugs are currently approved, five investigational agents reduce levels by 65-98%.
Abstract
One in five people are at high risk for atherosclerotic cardiovascular disease and aortic valve stenosis due to high lipoprotein(a). Lipoprotein(a) concentrations are lowest in people from east Asia, Europe, and southeast Asia, intermediate in people from south Asia, the Middle East, and Latin America, and highest in people from Africa. Concentrations are more than 90% genetically determined and 17% higher in post-menopausal women than in men. Individuals at a higher cardiovascular risk should have lipoprotein(a) concentrations measured once in their lifetime to inform those with high concentrations to adhere to a healthy lifestyle and receive medication to lower other cardiovascular risk factors. With no approved drugs to lower lipoprotein(a) concentrations, it is promising that at least five drugs in development lower concentrations by 65-98%, with three currently being tested in large cardiovascular endpoint trials. This Review covers historical perspectives, physiology and pathophysiology, genetic evidence of causality, epidemiology, role in familial hypercholesterolaemia and diabetes, management, screening, diagnosis, measurement, prevention, and future lipoprotein(a)-lowering drugs.
Discussion
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Cite This Study
Nordestgaard et al. (2024) conducted a review in Atherosclerotic cardiovascular disease and aortic valve stenosis associated with high lipoprotein(a). Lipoprotein(a) was evaluated. High lipoprotein(a) places 1 in 5 people at high cardiovascular risk, while at least 5 emerging drugs lower its concentrations by 65-98%.