Key result
Genetically predicted Lp(a) was estimated to be approximately 6.6 times (95% CI 5.1-8.8) more atherogenic for CHD risk than LDL on a per-particle basis.
Why the study?
The relative atherogenicity of lipoprotein(a) compared with low-density lipoprotein on a per-particle basis was indeterminate.
Is genetically predicted Lp(a) more atherogenic than LDL on a per-particle basis for coronary heart disease risk in the UK Biobank population?
Observational
Is genetically predicted Lp(a) more atherogenic than LDL on a per-particle basis for coronary heart disease risk in the UK Biobank population?
Lp(a) is approximately 6-fold more atherogenic than LDL on a per-particle basis, highlighting it as a key target for drug-based intervention to reduce CHD risk.
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.
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Björnson et al. (2024) conducted an observational in Coronary heart disease (CHD). Higher Lp(a)-apoB (50 nmol/L increment) vs. Higher LDL-apoB (50 nmol/L increment) was evaluated on Coronary heart disease (CHD) (OR 1.28, 95% CI 1.24-1.33). Genetically predicted Lp(a) was estimated to be approximately 6.6 times (95% CI 5.1-8.8) more atherogenic for CHD risk than LDL on a per-particle basis.
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