Contemporary patterns of lipoprotein(a) testing and associated clinical care and outcomes

Michelle D Kelsey^{1

2}, Hillary Mulder², Karen Chiswell², Zachary M Lampron², Ester Nilles², Jacquelyn P Kulinski³, Parag H Joshi⁴, W Schuyler Jones^{1

2}, Alanna M Chamberlain^{5

6}, Thorsten M Leucker⁷, Wenke Hwang⁸, M Wesley Milks⁹, Anuradha Paranjape¹⁰, Jihad S Obeid¹¹, MacRae F Linton¹², Shia T Kent¹³, Eric D Peterson⁴, Emily C O'Brien², Neha J Pagidipati^{1

2}

Affiliations

¹ Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
² Duke Clinical Research Institute, Durham, NC, USA.
³ Department of Medicine, Division of Cardiology, Medical College of Wisconsin, Milwaukee, USA.
⁴ Department of Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁵ Department of Quantitative Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
⁶ Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.
⁷ Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD, USA.
⁸ Department of Public Health Sciences, Penn State Hershey Medical Center, The Pennsylvania State University, PA, USA.
⁹ Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹⁰ Department of Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA.
¹¹ Division of Biomedical Informatics, Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
¹² Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹³ Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA.

PMID: 37025553
PMCID: PMC10070377
DOI: 10.1016/j.ajpc.2023.100478

Contemporary patterns of lipoprotein(a) testing and associated clinical care and outcomes

Michelle D Kelsey et al. Am J Prev Cardiol. 2023.

. 2023 Mar 1:14:100478.

doi: 10.1016/j.ajpc.2023.100478. eCollection 2023 Jun.

Authors

Affiliations

¹ Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
² Duke Clinical Research Institute, Durham, NC, USA.
³ Department of Medicine, Division of Cardiology, Medical College of Wisconsin, Milwaukee, USA.
⁴ Department of Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁵ Department of Quantitative Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
⁶ Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.
⁷ Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Baltimore, MD, USA.
⁸ Department of Public Health Sciences, Penn State Hershey Medical Center, The Pennsylvania State University, PA, USA.
⁹ Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹⁰ Department of Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA.
¹¹ Division of Biomedical Informatics, Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
¹² Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹³ Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA.

PMID: 37025553
PMCID: PMC10070377
DOI: 10.1016/j.ajpc.2023.100478

Abstract

Objective: Elevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease, yet little is known about Lp(a) testing patterns in real-world practice. The objective of this analysis was to determine how Lp(a) testing is used in clinical practice in comparison with low density lipoprotein cholesterol (LDL-C) testing alone, and to determine whether elevated Lp(a) level is associated with subsequent initiation of lipid-lowering therapy (LLT) and incident cardiovascular (CV) events.

Methods: This is an observational cohort study, based on lab tests administered between Jan 1, 2015 and Dec 31, 2019. We used electronic health record (EHR) data from 11 United States health systems participating in the National Patient-Centered Clinical Research Network (PCORnet). We created two cohorts for comparison: 1) the Lp(a) cohort, of adults with an Lp(a) test and 2) the LDL-C cohort, of 4:1 date- and site-matched adults with an LDL-C test, but no Lp(a) test. The primary exposure was the presence of an Lp(a) or LDL-C test result. In the Lp(a) cohort, we used logistic regression to assess the relationship between Lp(a) results in mass units (< 50, 50-100, and > 100mg/dL) and molar units (<125, 125-250, > 250nmol/L) and initiation of LLT within 3 months. We used multivariable adjusted Cox proportional hazards regression to evaluate these Lp(a) levels and time to composite CV hospitalization, including hospitalization for myocardial infarction, revascularization and ischemic stroke.

Results: Overall, 20,551 patients had Lp(a) test results and 2,584,773 patients had LDL-C test results (82,204 included in the matched LDL-C cohort). Compared with the LDL-C cohort, the Lp(a) cohort more frequently had prevalent ASCVD (24.3% vs. 8.5%) and multiple prior CV events (8.6% vs. 2.6%). Elevated Lp(a) was associated with greater odds of subsequent LLT initiation. Elevated Lp(a) reported in mass units was also associated with subsequent composite CV hospitalization [aHR (95% CI): Lp(a) 50-100mg/dL 1.25 (1.02-1.53), p<0.03, Lp(a) > 100mg/dL 1.23 (1.08-1.40), p<0.01].

Conclusion: Lp(a) testing is relatively infrequent in health systems across the U.S. As new therapies for Lp(a) emerge, improved patient and provider education is needed to increase awareness of the utility of this risk marker.

Keywords: Cardiovascular prevention; Lipoprotein(a).

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Michelle D Kelsey reports financial support was provided by Amgen Inc. Disclosures: PHJ reports grant support from the Make Well Known Foundation through an unrestricted grant from Amgen; grant support from Novartis and Novo Nordisk. MFL has received research funding from the NIH (HL116263), Amgen, Regeneron, Ionis, Merck, REGENXBIO, Sanofi and Novartis and has served as a consultant for Esperion, Alexion Pharmaceuticals and REGENXBIO. EDP reports research support from: Amgen Inc., Janssen Pharmaceutical Products, Bristol Myers Squibb, Esperion; and consulting fees from: Jansen Pharmaceutical Products, Boehringer Ingelheim, Novartis, Cerner. NJP reports research grants from: Amgen, Inc.; AstraZeneca; Baseline Study LLC; Boehringer Ingleheim; Duke Clinical Research Institute; Eli Lilly & Company; Novartis Pharmaceuticals, Novo Nordisk Pharmaceutical Company; Regeneron Pharmaceuticals, Inc.; Sanofi-S.A.; Verily Sciences Research Company; Consulting fees from AstraZeneca; Boehringer Ingleheim; Esperion Therapeutics, Eli Lilly & Company, Novo Nordisk Pharmaceutical Company. The remaining authors have nothing to disclose.

Figures

Fig 1a — **Fig. 1**
a: Consort Diagram of Lp(a) Cohort, 1b: Consort Diagram of LDL-C Cohort.

Fig 2 — **Fig. 2**
a: Histogram of Lp(a) values in Lp(a) cohort with results in mass units. b: Histogram of Lp(a) values in Lp(a) cohort with results in molar units.

Fig 3 — **Fig. 3**
Lipid lowering therapy initiation by Lp(a) level in Lp(a) Outcomes Cohort for Mass Units Results.

Fig 4 — **Fig. 4**
Lp(a) Level and CV hospitalization outcome in Lp(a) outcomes cohort for mass units results.

See this image and copyright information in PMC

References

1. Wilson DP, Jacobson TA, Jones PH, Koschinsky ML, McNeal CJ, Nordestgaard BG, et al. Use of Lipoprotein(a) in clinical practice: a biomarker whose time has come. A scientific statement from the National Lipid Association. J Clin Lipidol. 2019;13(3):374–392. - PubMed
1. Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69(6):692–711. - PubMed
1. Welsh P, Welsh C, Celis-Morales CA, Brown R, Ho FK, Ferguson LD, et al. Lipoprotein(a) and cardiovascular disease: prediction, attributable risk fraction, and estimating benefits from novel interventions. Eur J Prevent Cardiol. 2020 - PubMed
1. Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, White IR, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302(4):412–423. - PMC - PubMed
1. Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, Heath SC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009;361(26):2518–2528. - PubMed

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P01 HL116263/HL/NHLBI NIH HHS/United States

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Contemporary patterns of lipoprotein(a) testing and associated clinical care and outcomes

Affiliations

Contemporary patterns of lipoprotein(a) testing and associated clinical care and outcomes

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous