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Lp(a) (Lipoprotein[a]) Concentrations and Incident Atherosclerotic Cardiovascular Disease: New Insights From a Large National Biobank
Open accessAbstract
Objective: Lp(a) (lipoprotein[a]) concentrations are associated with atherosclerotic cardiovascular disease (ASCVD), and new therapies that enable potent and specific reduction are in development. In the largest study conducted to date, we address 3 areas of uncertainty: (1) the magnitude and shape of ASCVD risk conferred across the distribution of lipoprotein(a) concentrations; (2) variation of risk across racial and clinical subgroups; (3) clinical importance of a high lipoprotein(a) threshold to guide therapy. Approach and Results: Relationship of lipoprotein(a) to incident ASCVD was studied in 460 506 middle-aged UK Biobank participants. Over a median follow-up of 11.2 years, incident ASCVD occurred in 22 401 (4.9%) participants. Median lipoprotein(a) concentration was 19.6 nmol/L (25th–75th percentile 7.6–74.8). The relationship between lipoprotein(a) and ASCVD appeared linear across the distribution, with a hazard ratio of 1.11 (95% CI, 1.10–1.12) per 50 nmol/L increment. Substantial differences in concentrations were noted according to race—median values for white, South Asian, black, and Chinese individuals were 19, 31, 75, and 16 nmol/L, respectively. However, risk per 50 nmol/L appeared similar—hazard ratios of 1.11, 1.10, and 1.07 for white, South Asian, and black individuals, respectively. A high lipoprotein(a) concentration defined as ≥150 nmol/L was present in 12.2% of those without and 20.3% of those with preexisting ASCVD and associated with hazard ratios of 1.50 (95% CI, 1.44–1.56) and 1.16 (95% CI, 1.05–1.27), respectively. Conclusions: Lipoprotein(a) concentrations predict incident ASCVD among middle-aged adults within primary and secondary prevention contexts, with a linear risk gradient across the distribution. Concentrations are variable across racial subgroups, but the associated risk appears similar.
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“Consequently, genetic studies found a causal link between elevated Lp(a) levels and a higher risk for CVD diseases,[184–189] and vice versa [190].”
From Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention (2023) · cites this paper as [189]
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Metadata
- Authors
- Patel, A. P., Wang, M., Pirruccello, J. P., Ellinor, P. T., Ng, K., Kathiresan, S., & Khera, A. V.
- Affiliations
- Broad Institute (US)
- IBM Research - Cambridge (United States) (US)
- Corresponding author
- Khera, Amit V.
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2021-01
- Volume
- 41
- Issue
- 1
- Pages
- 465-474
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC7769893
- OpenAlex
- W3097307979
- Cited by
- 567
- References
- 50
- Citations by year
- 2026: 135 · 2025: 147 · 2024: 110 · 2023: 89 · 2022: 60 · 2021: 25
- FWCI
- 39.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion, other-oa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association (R01 HL128914, 18SFRN34110082)
- Massachusetts General Hospital
- Broad Institute
- Fondation Leducq (K24HL105780, 18SFRN34110082, 1RO1HL092577, T32HL007208, 14CVD01, R01HL128914)
- Medical Research Council (MC_PC_17228)
- National Heart, Lung, and Blood Institute (1RO1HL092577, R01HL128914, K24HL105780, R01HL092577, T32HL007208)
- National Human Genome Research Institute (K08HG010155, 18SFRN34110082)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- lipoprotein(a), atherosclerotic cardiovascular disease, incident cardiovascular events, racial differences, risk gradient, primary prevention, secondary prevention, middle-aged adults, UK Biobank
- MeSH terms
- Race Factors, Heart Disease Risk Factors, Adult, Aged, Female, United Kingdom, Humans, Male, Middle Aged, Primary Prevention, Prognosis, Time Factors, Biomarkers, Incidence, Lipoprotein(a), Biological Specimen Banks, Risk Assessment, Atherosclerosis, Secondary Prevention
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