Lipoprotein(a)-associated atherogenesis may increase Coronary Heart Disease Risk: Study

In a recent genetic analysis published in the Journal of the American College of Cardiology uncovered a compelling evidence that lipoprotein(a) (Lp(a)), a risk factor for coronary heart disease (CHD), holds a significant atherogenicity that is six times greater than low-density lipoprotein (LDL) on a per-particle basis.

After utilizing the genome-wide association studies within the UK Biobank population Elias Björnson and team identified two clusters of single nucleotide polymorphisms related to Lp(a) and LDL concentrations. Both Lp(a) and LDL were found to contain one apolipoprotein B (apoB) per particle which formed the basis for a comparative analysis.

The Mendelian randomization-derived odds ratio (OR) for CHD associated with a 50 nmol/L increase in Lp(a)-apoB was 1.28 (95% CI: 1.24-1.33) which was significantly higher than the corresponding increase in LDL-apoB (1.04; 95% CI: 1.03-1.05). Also, the polygenic scores were used to rank subjects based on the difference in Lp(a)-apoB versus LDL-apoB and this demonstrated a greater hazard ratio (HR) for CHD per 50 nmol/L apoB in the Lp(a) cluster (1.47; 95% CI: 1.36-1.58) when compared to the LDL cluster (1.04; 95% CI: 1.02-1.05).

The findings of this study suggest that the atherogenicity of Lp(a) is approximately six times greater than that of LDL on a per-particle basis, with a point estimate of 6.6 (95% CI: 5.1-8.8). Understanding the heightened risk posed by Lp(a) at the genetic level paves opportunities for drug-based interventions and helped it to emerge as the critical target for therapeutic strategies to reduce CHD risk in a significant proportion of the at-risk population.

The implications of this study could potentially help in reshaping how clinicians approach cardiovascular risk management. As this study delve deeper into the molecular underpinnings of heart disease, this sheds light firmly on Lp(a) by offering hope for more effective and targeted interventions in the treatment against CHD.

Reference:

Björnson, E., Adiels, M., Taskinen, M.-R., Burgess, S., Chapman, M. J., Packard, C. J., & Borén, J. (2024). Lipoprotein(a) is markedly more atherogenic than LDL. Journal of the American College of Cardiology, 83(3), 385–395. https://doi.org/10.1016/j.jacc.2023.10.039