Study Questions Need for Repeat Lipoprotein(a) Testing

Richard Mark Kirkner

February 16, 2022

Repeat testing of lipoprotein(a) to assess a patient's cardiovascular risk doesn't seem to yield any additional helpful information, and a one-time baseline measure of Lp(a) molar concentration could be sufficient to help define lifetime risk, suggests a large analysis of a national database in the United Kingdom.

The study examined the correlation between baseline and first follow-up measures of Lp(a) molar concentration and incident coronary artery disease among 16,017 individuals in a cohort of the UK Biobank, a prospective observational study of about 500,000 middle-aged people recruited between 2006 and 2010 with ongoing follow-up.

Results showed found little change in Lp(a) molar concentration measures from baseline to an average of 4.4 years afterward, but did find an association between statin usage and significant increases in Lp(a) in people with high baseline levels. The study was published online on Feb. 14 in the Journal of the American College of Cardiology.

The baseline and follow-up Lp(a) molar concentration measures "are highly correlated with 85% of the repeat values being within 25 nmol/L of each other," senior author Pradeep Natarajan, MD, MMSc, of Massachusetts General Hospital, Boston, said in an interview. "When predicting events, the follow-up Lp(a) concentration did not yield additional information beyond the baseline Lp(a)."

Additionally, the study found that statin therapy didn't lead to meaningful changes in Lp(a) molar concentration levels. Patients on statins who had baseline Lp(a) above 70 nmol/L "had modest follow-up concentrations, but this did not appreciably change atherosclerotic cardiovascular disease risks," Natarajan said. "For patients without clinical cardiovascular disease who are not on medicines that markedly change Lp(a), additional Lp(a) assessments are unlikely to provide additional prognostic information beyond the baseline Lp(a) measurement."

Added lead author Mark Trinder, MSc: "These findings suggest that, in the absence of therapies substantially altering Lp(a), a single accurate measurement of Lp(a) molar concentration is an efficient method to inform atherosclerotic cardiovascular disease risk." Mr. Trinder is an MD/PhD candidate at the Centre for Heart Lung Innovation at the University of British Columbia, Vancouver, and a visiting scholar in medical and population genetics and the Cardiovascular Disease Initiative at the Broad Institute of MIT and Harvard in Cambridge, Mass.

This study claims to be unique for two reasons: It reported on repeat Lp(a) measurements among the general population rather than a clinical trial, and it assessed the influence of statins on Lp(a) molar concentration rather than Lp(a) mass.

"Lp(a) molar concentration aims to mitigate challenges with mass assays, which are influenced by assay size," Natarajan said. However, he noted that major clinical trials of investigative drugs for lowering Lp(a), specifically the ongoing HORIZON trial (NCT04023552), are using Lp(a) mass rather than molar concentration.

"There is an imperfect correlation between the two," Natarajan said. "Depending on the results of this trial and others, and evaluation of both mass and molar concentration assays, we will then be able to better understand the path forward. These issues and the multiple assays have been challenging for both the clinical and scientific community."

Santica Marcovina, ScD, PhD, coauthor of the invited commentary (J Am Coll Cardiol. 2022 Feb 14. doi: 10.1016/j.jacc.2021.11.053), said in an interview that the study's major contribution to the literature is the finding that the molar concentration of Lp(a) appears to be stable regardless of statin use.

"This important finding provides evidence that no longitudinal measurements of Lp(a) are needed in the primary prevention of atherosclerotic CVD and that once-in-a-lifetime measurement may reliably allow clinicians to assess whether or not Lp(a)-related risk is present in their patients," she said. Marcovina is senior director of clinical laboratory sciences at Medpace Reference Laboratories, Cincinnati.

She noted that this study provides an actionable strategy for cardiologists. "Considering the clinical benefits, the relative low cost for measuring Lp(a), the fact that measurements need to be performed only once in the vast majority of individuals, all point to the implementation of Lp(a) general screening as soon as possible."

Natarajan has financial relationships with Amgen, Apple, AstraZeneca, Boston Scientific, Blackstone Life Sciences, Genentech and Novartis. Marcovina has provided consulting for Roche, Denka, and Novartis, and has received research support from Amgen through Medpace.

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