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. 2024 Apr 23;83(16):1511-1525.
doi: 10.1016/j.jacc.2024.02.031.

Lipoprotein(a) and Long-Term Cardiovascular Risk in a Multi-Ethnic Pooled Prospective Cohort

Nathan D Wong  1 , Wenjun Fan  2 , Xingdi Hu  3 , Christie Ballantyne  4 , Ron C Hoodgeveen  5 , Michael Y Tsai  6 , Auris Browne  3 , Matthew J Budoff  7
Affiliations
Free article

Lipoprotein(a) and Long-Term Cardiovascular Risk in a Multi-Ethnic Pooled Prospective Cohort

Nathan D Wong et al. J Am Coll Cardiol. .
Free article

Abstract

Background: Lipoprotein(a) (Lp[a]) is a causal genetic risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited long-term follow-up data from large U.S. population cohorts.

Objectives: This study examined the relationship of Lp(a) with ASCVD outcomes in a large, pooled, multi-ethnic U.S.

Methods: The study included data on Lp(a) and ASCVD outcomes from 5 U.S.

Prospective studies: MESA (Multi-Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults), JHS (Jackson Heart Study), FHS-OS (Framingham Heart Study-Offspring), and ARIC (Atherosclerosis Risk In Communities). Lp(a) levels were classified on the basis of cohort-specific percentiles. Multivariable Cox regression related Lp(a) with composite incident ASCVD events by risk group and diabetes status.

Results: The study included 27,756 persons without previous ASCVD who were aged 20 to 79 years, including 55.0% women, 35.6% Black participants, and 7.6% patients with diabetes, with mean follow-up of 21.1 years. Compared with Lp(a) levels <50th percentile, Lp(a) levels in the 50th to <75th, 75th to <90th, and ≥90th percentiles had adjusted HRs of 1.06 (95% CI: 0.99-1.14), 1.18 (95% CI: 1.09-1.28), and 1.46 (95% CI: 1.33-1.59), respectively for ASCVD events. Elevated Lp(a) predicted incident ASCVD events similarly by risk group, sex, and race or ethnic groups, but more strongly in patients with vs without diabetes (interaction P = 0.0056), with HRs for Lp(a) levels ≥90th percentile of 1.92 (95% CI: 1.50-2.45) and 1.41 (95% CI: 1.28-1.55), respectively. Lp(a) also individually predicted myocardial infarction, revascularization, stroke, and coronary heart disease death, but not total mortality.

Conclusions: The study shows, in a large U.S. pooled cohort, that higher Lp(a) levels are associated with an increased ASCVD risk, including in patients with diabetes.

Keywords: cardiovascular disease; diabetes; epidemiology; lipids; lipoprotein(a).

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Conflict of interest statement

Funding Support and Author Disclosures This project has received funding from a research contract from Novartis to the University of California–Irvine. The ARIC study has received funding from the National Heart, Lung, and Blood Institute under current contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700006I. The CARDIA has received support from contracts HHSN268201800003I, HHSN268201800004I, HHSN268201800005I, HHSN268201800006I, and HHSN268201800007I from the National Heart, Lung, and Blood Institute (NHLBI). The FHS has received funding from the NNLBI under contract 75N92019D00031. The JHS has received support from and has been conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I/HHSN26800001), and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I) contracts from the NHLBI and the National Institute for Minority Health and Health Disparities (NIMHD). MESA has received support from contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the NHLBI and from grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). The results of this study were presented in part at the American Heart Association Scientific Sessions; November 2022; Chicago, Illinois. Dr Wong had received research support through the University of California—Irvine from Novartis, Novo Nordisk, and Regeneron; and has served as a consultant for Novartis and Ionis. Dr Ballantyne has received research support through Baylor College of Medicine from Novartis, Amgen, Eli Lilly, Merck, Ionis, Arrowhead, and Novo Nordisk; and has served as a consultant for Novartis, Amgen, Eli Lilly, Merck, Ionis, and Arrowhead. Dr Hoogeveen has received research support through Baylor College of Medicine from Denka Seiken; and has served as a consultant for Denka Seiken. Dr Hu is an employee of Novartis Pharmaceuticals Corporation. Dr Browne is an employee of Novartis Pharmaceuticals Corporation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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