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

Nathan D Wong; Wenjun Fan; Xingdi Hu; Christie Ballantyne; Ron C Hoodgeveen; Michael Y Tsai; Auris Browne; Matthew J Budoff

doi:10.1016/j.jacc.2024.02.031

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

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

Authors

Nathan D Wong¹, Wenjun Fan², Xingdi Hu³, Christie Ballantyne⁴, Ron C Hoodgeveen⁵, Michael Y Tsai⁶, Auris Browne³, Matthew J Budoff⁷

Affiliations

¹ Division of Cardiology, University of California-Irvine, Irvine, California, USA; Department of Epidemiology and Biostatistics, University of California-Irvine, Irvine, California, USA. Electronic address: ndwong@uci.edu.
² Division of Cardiology, University of California-Irvine, Irvine, California, USA; Department of Epidemiology and Biostatistics, University of California-Irvine, Irvine, California, USA.
³ Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
⁴ Division of Cardiology, Baylor College of Medicine and the Texas Heart Institute, Houston, Texas, USA.
⁵ Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
⁶ Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
⁷ Division of Cardiology, Lundquist Institute, Harbor-UCLA Medical Center, Torrance, California, USA.

PMID: 38631771
DOI: 10.1016/j.jacc.2024.02.031

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).

MeSH terms

Atherosclerosis* / epidemiology
Cardiovascular Diseases* / epidemiology
Diabetes Mellitus*
Female
Heart Disease Risk Factors
Humans
Lipoprotein(a)
Male
Prospective Studies
Risk Assessment
Risk Factors

Substances

Lipoprotein(a)