In a study published in the Journal of the American College of Cardiology (JACC), Dr Elias Björnson and his colleagues demonstrated that lipoprotein(a) (Lp(a)) is approximately six times more atherogenic than low-density lipoprotein (LDL) per particle.

Lp(a) is a lipoprotein particle that has long been recognised as a causal factor for coronary heart disease (CHD). However, until recently, its relative atherogenicity compared to low-density lipoprotein (LDL) on a per-particle basis has been undetermined.

This genetic study delved into this question by utilizing Mendelian randomization, a statistical method that employs genetic variants to uncover causal connections between risk factors and disease.

Analysing data from a cohort of the UK Biobank (502,413 participants), the researchers identified two distinct clusters of single-nucleotide polymorphisms (SNPs), one linked to Lp(a) mass concentration and the other associated with LDL concentration. By evaluating the association of these SNPs with CHD risk, they were able to draw a meaningful comparison of the atherogenicity of Lp(a) and LDL particles.

The study's findings indicates that an increase of 50 nmol/L in Lp(a)-apoB was associated with a 1.28-fold elevation in CHD risk compared to a 1.04-fold increase with the same increment in LDL-apoB. 

The researchers further demonstrated that the hazard ratio (HR) for CHD per 50 nmol/L apoB was 1.47 for the Lp(a) cluster compared to 1.04 for the LDL cluster, further solidifying the notion that Lp(a) is a more potent atherogenic lipoprotein than LDL.

In the conclusion of the analysis the researchers emphasised the potential of Lp(a) as a therapeutic target, stating: “Lp(a) represents a key target for drug-based intervention in a significant proportion of the at-risk population.”

Currently the 2022 European Atherosclerosis Society consensus statement further endorses the importance of Lp(a) measurement, recommending that it should be performed at least once in all adults.

References

Björnson E, et al. Lipoprotein(a) Is Markedly More Atherogenic Than LDL: An Apolipoprotein B-Based Genetic Analysis. JACC 2024;83(3):385–395.

Kalra A, et al. Parallax by Radcliffe Cardiology. EP 78: Your Guide to Lipoprotein(a) with Dr. Salim S Virani.