User login
TOPLINE:
While low-density lipoprotein (LDL) particles are much more abundant than lipoprotein(a) [Lp(a)] particles and carry the greatest overall risk for coronary heart disease (CHD), .
METHODOLOGY:
- To compare the atherogenicity of Lp(a) relative to LDL on a per-particle basis, researchers used a genetic analysis because Lp(a) and LDL both contain one apolipoprotein B (apoB) per particle.
- In a genome-wide association study of 502,413 UK Biobank participants, they identified genetic variants uniquely affecting plasma levels of either Lp(a) or LDL particles.
- For these two genetic clusters, they related the change in apoB to the respective change in CHD risk, which allowed them to directly compare the atherogenicity of LDL and Lp(a), particle to particle.
TAKEAWAY:
- The odds ratio 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.
- Additional supporting evidence was provided by using polygenic scores to rank participants according to the difference in Lp(a)-apoB vs LDL-apoB, which revealed a greater risk for CHD per 50 nmol/L apoB for the Lp(a) cluster (hazard ratio [HR], 1.47; 95% CI, 1.36-1.58) than the LDL cluster (HR, 1.04; 95% CI, 1.02-1.05).
- Based on the data, the researchers estimate that the atherogenicity of Lp(a) is roughly sixfold greater (point estimate of 6.6; 95% CI, 5.1-8.8) than that of LDL on a per-particle basis.
IN PRACTICE:
“There are two clinical implications. First, to completely characterize atherosclerotic cardiovascular disease risk, it is imperative to measure Lp(a) in all adult patients at least once. Second, these studies provide a rationale that targeting Lp(a) with potent and specific drugs may lead to clinically meaningful benefit,” wrote the authors of an accompanying commentary on the study.
SOURCE:
The study, with first author Elias Björnson, PhD, University of Gothenburg, Gothenburg, Sweden, and an editorial by Sotirios Tsimikas, MD, University of California, San Diego, and Vera Bittner, MD, University of Alabama at Birmingham, was published in the Journal of the American College of Cardiology.
LIMITATIONS:
The UK Biobank consists primarily of a Caucasian population, and confirmatory studies in more diverse samples are needed. The working range for the Lp(a) assay used in the study did not cover the full range of Lp(a) values seen in the population. Variations in Lp(a)-apoB and LDL-apoB were estimated from genetic analysis and not measured specifically in biochemical assays.
DISCLOSURES:
The study had no commercial funding. Some authors received honoraria from the pharmaceutical industry. A complete list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
TOPLINE:
While low-density lipoprotein (LDL) particles are much more abundant than lipoprotein(a) [Lp(a)] particles and carry the greatest overall risk for coronary heart disease (CHD), .
METHODOLOGY:
- To compare the atherogenicity of Lp(a) relative to LDL on a per-particle basis, researchers used a genetic analysis because Lp(a) and LDL both contain one apolipoprotein B (apoB) per particle.
- In a genome-wide association study of 502,413 UK Biobank participants, they identified genetic variants uniquely affecting plasma levels of either Lp(a) or LDL particles.
- For these two genetic clusters, they related the change in apoB to the respective change in CHD risk, which allowed them to directly compare the atherogenicity of LDL and Lp(a), particle to particle.
TAKEAWAY:
- The odds ratio 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.
- Additional supporting evidence was provided by using polygenic scores to rank participants according to the difference in Lp(a)-apoB vs LDL-apoB, which revealed a greater risk for CHD per 50 nmol/L apoB for the Lp(a) cluster (hazard ratio [HR], 1.47; 95% CI, 1.36-1.58) than the LDL cluster (HR, 1.04; 95% CI, 1.02-1.05).
- Based on the data, the researchers estimate that the atherogenicity of Lp(a) is roughly sixfold greater (point estimate of 6.6; 95% CI, 5.1-8.8) than that of LDL on a per-particle basis.
IN PRACTICE:
“There are two clinical implications. First, to completely characterize atherosclerotic cardiovascular disease risk, it is imperative to measure Lp(a) in all adult patients at least once. Second, these studies provide a rationale that targeting Lp(a) with potent and specific drugs may lead to clinically meaningful benefit,” wrote the authors of an accompanying commentary on the study.
SOURCE:
The study, with first author Elias Björnson, PhD, University of Gothenburg, Gothenburg, Sweden, and an editorial by Sotirios Tsimikas, MD, University of California, San Diego, and Vera Bittner, MD, University of Alabama at Birmingham, was published in the Journal of the American College of Cardiology.
LIMITATIONS:
The UK Biobank consists primarily of a Caucasian population, and confirmatory studies in more diverse samples are needed. The working range for the Lp(a) assay used in the study did not cover the full range of Lp(a) values seen in the population. Variations in Lp(a)-apoB and LDL-apoB were estimated from genetic analysis and not measured specifically in biochemical assays.
DISCLOSURES:
The study had no commercial funding. Some authors received honoraria from the pharmaceutical industry. A complete list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
TOPLINE:
While low-density lipoprotein (LDL) particles are much more abundant than lipoprotein(a) [Lp(a)] particles and carry the greatest overall risk for coronary heart disease (CHD), .
METHODOLOGY:
- To compare the atherogenicity of Lp(a) relative to LDL on a per-particle basis, researchers used a genetic analysis because Lp(a) and LDL both contain one apolipoprotein B (apoB) per particle.
- In a genome-wide association study of 502,413 UK Biobank participants, they identified genetic variants uniquely affecting plasma levels of either Lp(a) or LDL particles.
- For these two genetic clusters, they related the change in apoB to the respective change in CHD risk, which allowed them to directly compare the atherogenicity of LDL and Lp(a), particle to particle.
TAKEAWAY:
- The odds ratio 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.
- Additional supporting evidence was provided by using polygenic scores to rank participants according to the difference in Lp(a)-apoB vs LDL-apoB, which revealed a greater risk for CHD per 50 nmol/L apoB for the Lp(a) cluster (hazard ratio [HR], 1.47; 95% CI, 1.36-1.58) than the LDL cluster (HR, 1.04; 95% CI, 1.02-1.05).
- Based on the data, the researchers estimate that the atherogenicity of Lp(a) is roughly sixfold greater (point estimate of 6.6; 95% CI, 5.1-8.8) than that of LDL on a per-particle basis.
IN PRACTICE:
“There are two clinical implications. First, to completely characterize atherosclerotic cardiovascular disease risk, it is imperative to measure Lp(a) in all adult patients at least once. Second, these studies provide a rationale that targeting Lp(a) with potent and specific drugs may lead to clinically meaningful benefit,” wrote the authors of an accompanying commentary on the study.
SOURCE:
The study, with first author Elias Björnson, PhD, University of Gothenburg, Gothenburg, Sweden, and an editorial by Sotirios Tsimikas, MD, University of California, San Diego, and Vera Bittner, MD, University of Alabama at Birmingham, was published in the Journal of the American College of Cardiology.
LIMITATIONS:
The UK Biobank consists primarily of a Caucasian population, and confirmatory studies in more diverse samples are needed. The working range for the Lp(a) assay used in the study did not cover the full range of Lp(a) values seen in the population. Variations in Lp(a)-apoB and LDL-apoB were estimated from genetic analysis and not measured specifically in biochemical assays.
DISCLOSURES:
The study had no commercial funding. Some authors received honoraria from the pharmaceutical industry. A complete list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.