Levels of Lipoprotein(a) Reduction Needed to Reduce Heart Disease May Have Been Overestimated

CAD, coronary artery disease, stent, atherosclerosis, angiogram, angiography
CAD, coronary artery disease, stent, atherosclerosis, angiogram, angiography
Investigators used Mendelian randomization analysis to determine the amount of lipoprotein(a) reduction needed to match the effect on coronary heart disease outcomes that lowering low-density lipoprotein cholesterol has.

According to a Mendelian randomization analysis, lowering lipoprotein(a) (Lp[a]) by 65.7 mg/dL has the same effect on coronary heart disease (CHD) outcomes as lowering low-density lipoprotein cholesterol by 38.67 mg/dL, according to study results published in JAMA Cardiology.

The study included effects estimated for Lp(a) from a genome-wide association study (GWAS) and a meta-analysis on Lp(a) that included 5 different primarily population-based studies of European ancestry. The researchers used a Mendelian randomization analysis to estimate the required Lp(a)-lowering effect size needed to have a clinically meaningful effect.

The researchers performed all Lp(a) measurements in 1 laboratory and used genetic estimates for 27 single-nucleotide polymorphisms (SNPs) on Lp(a) concentrations. The retrieved odds ratios for these 27 SNPs associated with CHD risk were from a subsample of the CHD Exome Plus Consortium.

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The Lp(a)-GWAS Consortium included 13,781 participants from 5 studies, and the CHD Exome Plus Consortium included 20,793 CHD cases and 27,540 controls. Of these, 4  studies had a similar age distribution (means between 51 and 59 years), whereas 1 cohort had a mean age of 32 years.

To determine the required reduction in Lp(a), the researchers first confirmed the data from the other studies using the common 27 SNPs. They then used effect estimates from the same 27 SNPs for Lp(a), which allowed them to reach their estimate of 65.7 mg/dL.

“Estimations of the required lipoprotein(a)-lowering potential of a drug to be clinically effective might have been overestimated in the past; this might be explained by standardization issues of lipoprotein(a) assays,” the researchers wrote.


Lamina C, Kronenberg F; Lp(a)-GWAS-Consortium. Estimation of the required lipoprotein(a)-lowering therapeutic effect size for reduction in coronary heart disease outcomes: a mendelian randomization analysis [published online April 24, 2019]. JAMA Cardiol. doi:10.1001/jamacardio.2019.1041