Lipoprotein(a) and Risks of Peripheral Artery Disease, Abdominal Aortic Aneurysm, and Major Adverse Limb Events

Peter E Thomas; Signe Vedel-Krogh; Sune F Nielsen; Børge G Nordestgaard; Pia R Kamstrup

doi:10.1016/j.jacc.2023.10.009

Lipoprotein(a) and Risks of Peripheral Artery Disease, Abdominal Aortic Aneurysm, and Major Adverse Limb Events

J Am Coll Cardiol. 2023 Dec 12;82(24):2265-2276. doi: 10.1016/j.jacc.2023.10.009.

Authors

Peter E Thomas¹, Signe Vedel-Krogh¹, Sune F Nielsen², Børge G Nordestgaard¹, Pia R Kamstrup³

Affiliations

¹ Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Denmark; The Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
² Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Denmark; The Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Denmark.
³ Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Denmark; The Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Denmark. Electronic address: Pia.roerbaek.kamstrup@regionh.dk.

PMID: 38057068
DOI: 10.1016/j.jacc.2023.10.009

Abstract

Background: Lp(a) (lipoprotein[a])-lowering therapy to reduce cardiovascular disease is under investigation in phase 3 clinical trials. High Lp(a) may be implicated in peripheral artery disease (PAD), abdominal aortic aneurysms (AAAs), and major adverse limb events (MALE).

Objectives: The authors investigated the association of high Lp(a) levels and corresponding LPA genotypes with risk of PAD, AAA, and MALE.

Methods: The authors included 108,146 individuals from the Copenhagen General Population Study. During follow-up, 2,450 developed PAD, and 1,251 AAAs. Risk of MALE was assessed in individuals with PAD at baseline and replicated in the Copenhagen City Heart Study.

Results: Higher Lp(a) was associated with a stepwise increase in risk of PAD and AAA (P for trend <0.001). For individuals with Lp(a) levels ≥99th (≥143 mg/dL, ≥307 nmol/L) vs <50th percentile (≤9 mg/dL, ≤17 nmol/L), multivariable-adjusted HRs were 2.99 (95% CI: 2.09-4.30) for PAD and 2.22 (95% CI: 1.21-4.07) for AAA. For individuals with PAD, the corresponding incidence rate ratio for MALE was 3.04 (95% CI: 1.55-5.98). Per 50 mg/dL (105 nmol/L) genetically higher Lp(a) risk ratios were 1.39 (95% CI: 1.24-1.56) for PAD and 1.21 (95% CI: 1.01-1.44) for AAA, consistent with observational risk ratios of 1.33 (95% CI: 1.24-1.43) and 1.27 (95% CI: 1.15-1.41), respectively. In women smokers aged 70 to 79 years with Lp(a) <50th and ≥99th percentile, absolute 10-year risks of PAD were 8% and 21%, and equivalent risks in men 11% and 29%, respectively. For AAA, corresponding risks were 2% and 4% in women, and 5% and 12% in men.

Conclusions: High Lp(a) levels increased risk of PAD, AAA, and MALE by 2- to 3-fold in the general population, opening opportunities for prevention given future Lp(a)-lowering therapies.

Keywords: abdominal aortic aneurysm; lipoprotein(a); lower-extremity amputation; major adverse limb event; peripheral artery disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aortic Aneurysm*
Aortic Aneurysm, Abdominal* / epidemiology
Aortic Aneurysm, Abdominal* / genetics
Female
Humans
Lipoprotein(a)
Male
Peripheral Arterial Disease* / epidemiology
Risk Factors

Substances

Lipoprotein(a)
LPA protein, human