Lipoprotein(a) and Major Adverse Cardiovascular Events in Patients With or Without Baseline Atherosclerotic Cardiovascular Disease

Adam N Berman; David W Biery; Stephanie A Besser; Avinainder Singh; Arthur Shiyovich; Brittany N Weber; Daniel M Huck; Sanjay Divakaran; Jon Hainer; Gurleen Kaur; Michael J Blaha; Christopher P Cannon; Jorge Plutzky; James L Januzzi; John N Booth 3rd; J Antonio G López; Shia T Kent; Khurram Nasir; Marcelo F Di Carli; Deepak L Bhatt; Ron Blankstein

doi:10.1016/j.jacc.2023.12.031

Lipoprotein(a) and Major Adverse Cardiovascular Events in Patients With or Without Baseline Atherosclerotic Cardiovascular Disease

J Am Coll Cardiol. 2024 Mar 5;83(9):873-886. doi: 10.1016/j.jacc.2023.12.031.

Authors

Adam N Berman¹, David W Biery², Stephanie A Besser², Avinainder Singh², Arthur Shiyovich², Brittany N Weber², Daniel M Huck², Sanjay Divakaran², Jon Hainer³, Gurleen Kaur⁴, Michael J Blaha⁵, Christopher P Cannon², Jorge Plutzky², James L Januzzi⁶, John N Booth 3rd⁷, J Antonio G López⁸, Shia T Kent⁷, Khurram Nasir⁹, Marcelo F Di Carli¹⁰, Deepak L Bhatt¹¹, Ron Blankstein¹²

Affiliations

¹ Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: https://twitter.com/adambermanMD.
² Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁵ Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland, USA.
⁶ Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Baim Institute for Clinical Research, Boston, Massachusetts, USA.
⁷ Center for Observational Research, Amgen Inc, Thousand Oaks, California, USA.
⁸ Global Development, Amgen Inc, Thousand Oaks, California, USA.
⁹ Department of Cardiovascular Medicine, Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas, USA.
¹⁰ Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹¹ Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai Health System, New York, New York, USA. Electronic address: https://twitter.com/DLBHATTMD.
¹² Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: rblankstein@bwh.harvard.edu.

PMID: 38418000
DOI: 10.1016/j.jacc.2023.12.031

Abstract

Background: Lipoprotein(a) [Lp(a)] is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). However, whether the optimal Lp(a) threshold for risk assessment should differ based on baseline ASCVD status is unknown.

Objectives: The purpose of this study was to assess the association between Lp(a) and major adverse cardiovascular events (MACE) among patients with and without baseline ASCVD.

Methods: We studied a retrospective cohort of patients with Lp(a) measured at 2 medical centers in Boston, Massachusetts, from 2000 to 2019. To assess the association of Lp(a) with incident MACE (nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or cardiovascular mortality), Lp(a) percentile groups were generated with the reference group set at the first to 50th Lp(a) percentiles. Cox proportional hazards modeling was used to assess the association of Lp(a) percentile group with MACE.

Results: Overall, 16,419 individuals were analyzed with a median follow-up of 11.9 years. Among the 10,181 (62%) patients with baseline ASCVD, individuals in the 71st to 90th percentile group had a 21% increased hazard of MACE (adjusted HR: 1.21; P < 0.001), which was similar to that of individuals in the 91st to 100th group (adjusted HR: 1.26; P < 0.001). Among the 6,238 individuals without established ASCVD, there was a continuously higher hazard of MACE with increasing Lp(a), and individuals in the 91st to 100th Lp(a) percentile group had the highest relative risk with an adjusted HR of 1.93 (P < 0.001).

Conclusions: In a large, contemporary U.S. cohort, elevated Lp(a) is independently associated with long-term MACE among individuals with and without baseline ASCVD. Our results suggest that the threshold for risk assessment may be different in primary vs secondary prevention cohorts.

Keywords: lipoprotein(a) cohort; lipoprotein(a) therapies.

MeSH terms

Atherosclerosis* / complications
Atherosclerosis* / epidemiology
Cardiovascular Diseases* / etiology
Humans
Lipoprotein(a)
Retrospective Studies
Risk Assessment
Risk Factors

Substances

Lipoprotein(a)