Cardiovascular disease risk associated with elevated lipoprotein(a) attenuates at low low-density lipoprotein cholesterol levels in a primary prevention setting.
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Authors
Verbeek, Rutger
Hoogeveen, Renate M
Langsted, Anne
Stiekema, Lotte CA
Verweij, Simone L
Hovingh, G Kees
Wareham, Nicholas J
Boekholdt, S Matthijs
Nordestgaard, Børge G
Stroes, Erik SG
Publication Date
2018-07-14Journal Title
Eur Heart J
ISSN
0195-668X
Publisher
Oxford University Press (OUP)
Volume
39
Issue
27
Pages
2589-2596
Language
eng
Type
Article
This Version
AM
Physical Medium
Print
Metadata
Show full item recordCitation
Verbeek, R., Hoogeveen, R. M., Langsted, A., Stiekema, L. C., Verweij, S. L., Hovingh, G. K., Wareham, N. J., et al. (2018). Cardiovascular disease risk associated with elevated lipoprotein(a) attenuates at low low-density lipoprotein cholesterol levels in a primary prevention setting.. Eur Heart J, 39 (27), 2589-2596. https://doi.org/10.1093/eurheartj/ehy334
Abstract
AIMS: Lipoprotein(a) (Lp(a)) elevation is a causal risk factor for cardiovascular disease (CVD). It has however been suggested that elevated Lp(a) causes CVD mainly in individuals with high low-density lipoprotein cholesterol (LDL-C) levels. We hypothesized that the risk associated with high Lp(a) levels would largely be attenuated at low LDL-C levels. METHODS AND RESULTS: In 16 654 individuals from the EPIC-Norfolk prospective population study, and in 9448 individuals from the Copenhagen City Heart Study (CCHS) parallel statistical analyses were performed. Individuals were categorized according to their Lp(a) and LDL-C levels. Cut-offs were set at the 80th cohort percentile for Lp(a). Low-density lipoprotein cholesterol cut-offs were set at 2.5, 3.5, 4.5, and 5.5 mmol/L. Low-density lipoprotein cholesterol levels in the primary analyses were corrected for Lp(a)-derived LDL-C (LDL-Ccorr). Multivariable-adjusted hazard ratios were calculated for each category. The category with LDL-Ccorr <2.5 mmol/L and Lp(a) <80th cohort percentile was used as reference category. In the EPIC-Norfolk and CCHS cohorts, individuals with an Lp(a) ≥80th percentile were at increased CVD risk compared with those with Lp(a) <80th percentile for any LDL-Ccorr levels ≥2.5 mmol/L. In contrast, for LDL-Ccorr <2.5 mmol/L, the risk associated with elevated Lp(a) attenuated. However, there was no interaction between LDL-Ccorr and Lp(a) levels on CVD risk in either cohort. CONCLUSION: Lipoprotein(a) and LDL-C are independently associated with CVD risk. At LDL-C levels below <2.5 mmol/L, the risk associated with elevated Lp(a) attenuates in a primary prevention setting.
Keywords
Humans, Cardiovascular Diseases, Lipoprotein(a), Risk Assessment, Prospective Studies, Primary Prevention, Middle Aged, Female, Male, Cholesterol, LDL
Sponsorship
Medical Research Council (MC_UU_12015/1)
Medical Research Council (G1000143)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
Identifiers
External DOI: https://doi.org/10.1093/eurheartj/ehy334
This record's URL: https://www.repository.cam.ac.uk/handle/1810/291163
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