Björnson, E., Adiels, M., Taskinen, M.-R., Burgess, S., Chapman, M. J., Packard, C. J. and Borén, J. (2024) Lipoprotein(a) is markedly more atherogenic than LDL an apolipoprotein B-based genetic analysis. Journal of the American College of Cardiology, 83(3), pp. 385-395. (doi: 10.1016/j.jacc.2023.10.039) (PMID:38233012)
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Abstract
Background Lipoprotein(a) (Lp(a)) is recognized as a causal factor for coronary heart disease (CHD) but its atherogenicity relative to that of low-density lipoprotein (LDL) on a per-particle basis is indeterminate. Objectives The authors addressed this issue in a genetic analysis based on the fact that Lp(a) and LDL both contain 1 apolipoprotein B (apoB) per particle. Methods Genome-wide association studies using the UK Biobank population identified 2 clusters of single nucleotide polymorphisms: one comprising 107 variants linked to Lp(a) mass concentration, the other with 143 variants linked to LDL concentration. In these Lp(a) and LDL clusters, the relationship of genetically predicted variation in apoB with CHD risk was assessed. Results The Mendelian randomization-derived OR for CHD for a 50 nmol/L higher Lp(a)-apoB was 1.28 (95% CI: 1.24-1.33) compared with 1.04 (95% CI: 1.03-1.05) for the same increment in LDL-apoB. Likewise, use of polygenic scores to rank subjects according to difference in Lp(a)-apoB vs difference in LDL-apoB revealed a greater HR for CHD per 50 nmol/L apoB for the Lp(a) cluster (1.47; 95% CI: 1.36-1.58) compared with the LDL cluster (1.04; 95% CI: 1.02-1.05). From these data, we estimate that the atherogenicity of Lp(a) is approximately 6-fold (point estimate of 6.6; 95% CI: 5.1-8.8) greater than that of LDL on a per-particle basis. Conclusions We conclude that the atherogenicity of Lp(a) (CHD risk quotient per unit increase in particle number) is substantially greater than that of LDL. Therefore, Lp(a) represents a key target for drug-based intervention in a significant proportion of the at-risk population.
| Item Type: | Articles |
|---|---|
| Additional Information: | The work in this paper was supported by grants from Swedish Research Council, Swedish Heart Lung Foundation, from the Swedish state under the agreement between the Swedish government and the county councils; the ALF-agreement (ALFGBG-965404), Sigrid Juselius Foundation, Helsinki, Finland, and the Finnish Foundation for Cardiovascular Research. Dr Burgess is supported by the Wellcome Trust (225790/Z/22/Z). This research was funded by United Kingdom Research and Innovation Medical Research Council (MC_UU_00002/7) and supported by the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215-20014). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Packard, Professor Chris |
| Authors: | Björnson, E., Adiels, M., Taskinen, M.-R., Burgess, S., Chapman, M. J., Packard, C. J., and Borén, J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Journal of the American College of Cardiology |
| Publisher: | Elsevier |
| ISSN: | 0735-1097 |
| ISSN (Online): | 1558-3597 |
| Published Online: | 15 January 2024 |
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