Relating Lipoprotein(a) Concentrations to Cardiovascular Event Risk After Acute Coronary Syndrome: A Comparison of 3 Tests-Reference-Cited by-全球学者库

Relating Lipoprotein(a) Concentrations to Cardiovascular Event Risk After Acute Coronary Syndrome: A Comparison of 3 Tests

Published:2024-01-16 Issue:3 Volume:149 Page:192-203
ISSN:0009-7322
Container-title:Circulation
language:en
Short-container-title:Circulation

Author:

Szarek Michael¹²³^ORCID,Reijnders Esther⁴^ORCID,Jukema J. Wouter⁵⁶^ORCID,Bhatt Deepak L.⁷^ORCID,Bittner Vera A.⁸^ORCID,Diaz Rafael⁹^ORCID,Fazio Sergio¹⁰^ORCID,Garon Genevieve¹¹,Goodman Shaun G.¹²¹³^ORCID,Harrington Robert A.¹⁴^ORCID,Ruhaak L. Renee⁴^ORCID,Schwertfeger Markus¹⁵,Tsimikas Sotirios¹⁶^ORCID,White Harvey D.¹⁷^ORCID,Steg P. Gabriel¹⁸^ORCID,Cobbaert Christa⁴^ORCID,Schwartz Gregory G.¹^ORCID,

Affiliation:

1. Division of Cardiology, University of Colorado School of Medicine, Aurora (M. Szarek, G.G.S.).

2. CPC Clinical Research, Aurora, CO (M. Szarek).

3. State University of New York, Downstate Health Sciences University, Brooklyn (M. Szarek).

4. Departments of Clinical Chemistry and Laboratory Medicine (E.R., L.R.R., C.C.), Leiden University Medical Center, the Netherlands.

5. Cardiology (J.W.J.), Leiden University Medical Center, the Netherlands.

6. Netherlands Heart Institute, Utrecht (J.W.J.).

7. Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York, NY (D.L.B.).

8. Division of Cardiovascular Disease, University of Alabama at Birmingham (V.A.B.).

9. Estudios Cardiológicos Latino América, Instituto Cardiovascular de Rosario, Argentina (R.D.).

10. Regeneron Pharmaceuticals Inc, Tarrytown, NY (S.F.).

11. Sanofi, Ontario, Canada (G.G.).

12. Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada (S.G.G.).

13. St Michael’s Hospital, University of Toronto, Ontario, Canada (S.G.G.).

14. Stanford Center for Clinical Research, Department of Medicine, Stanford University, CA (R.A.H.).

15. Roche Diagnostics International AG, Zug, Switzerland (M. Schwertfeger).

16. Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine, University of California San Diego, La Jolla (S.T.).

17. Green Lane Cardiovascular Research Unit, Te Whatu Ora–Health New Zealand, Te Toka Tumai, and University of Auckland, New Zealand (H.D.W.).

18. Université Paris-Cité, INSERM-UMR1148, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, FACT (French Alliance for Cardiovascular Trials), and Institut Universitaire de France, Paris (P.G.S.).

Abstract

BACKGROUND: Lipoprotein(a) is a risk factor for cardiovascular events and modifies the benefit of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. Lipoprotein(a) concentration can be measured with immunoassays reporting mass or molar concentration or a reference measurement system using mass spectrometry. Whether the relationships between lipoprotein(a) concentrations and cardiovascular events in a high-risk cohort differ across lipoprotein(a) methods is unknown. We compared the prognostic and predictive value of these types of lipoprotein(a) tests for major adverse cardiovascular events (MACE). METHODS: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the PCSK9 inhibitor alirocumab with placebo in patients with recent acute coronary syndrome. We compared risk of a MACE in the placebo group and MACE risk reduction with alirocumab according to baseline lipoprotein(a) concentration measured by Siemens N-latex nephelometric immunoassay (IA-mass; mg/dL), Roche Tina-Quant turbidimetric immunoassay (IA-molar; nmol/L), and a noncommercial mass spectrometry–based test (MS; nmol/L). Lipoprotein(a) values were transformed into percentiles for comparative modeling. Natural cubic splines estimated continuous relationships between baseline lipoprotein(a) and outcomes in each treatment group. Event rates were also determined across baseline lipoprotein(a) quartiles defined by each assay. RESULTS: Among 11 970 trial participants with results from all 3 tests, baseline median (Q1, Q3) lipoprotein(a) concentrations were 21.8 (6.9, 60.0) mg/dL, 45.0 (13.2, 153.8) nmol/L, and 42.2 (14.3, 143.1) nmol/L for IA-mass, IA-molar, and MS, respectively. The strongest correlation was between IA-molar and MS (r=0.990), with nominally weaker correlations between IA-mass and MS (r=0.967) and IA-mass and IA-molar (r=0.972). Relationships of lipoprotein(a) with MACE risk in the placebo group were nearly identical with each test, with estimated cumulative incidences differing by ≤0.4% across lipoprotein(a) percentiles, and all were incrementally prognostic after accounting for low-density lipoprotein cholesterol levels (all spline P ≤0.0003). Predicted alirocumab treatment effects were also nearly identical for each of the 3 tests, with estimated treatment hazard ratios differing by ≤0.07 between tests across percentiles and nominally less relative risk reduction by alirocumab at lower percentiles for all 3 tests. Absolute risk reduction with alirocumab increased with increasing lipoprotein(a) measured by each test, with significant linear trends across quartiles. CONCLUSIONS: In patients with recent acute coronary syndrome, 3 lipoprotein(a) tests were similarly prognostic for MACE in the placebo group and predictive of MACE reductions with alirocumab at the cohort level. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01663402.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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