Genetics
High Lp(a) triples peripheral artery disease and doubles abdominal aortic aneurysm risk, confirmed genetically, in 108,146 Danes (J Am Coll Cardiol 2023)
Original title: Lipoprotein(a) and Risks of Peripheral Artery Disease, Abdominal Aortic Aneurysm, and Major Adverse Limb Events
In 108,146 individuals from the Copenhagen General Population Study, 2,450 developed peripheral artery disease (PAD) and 1,251 developed abdominal aortic aneurysm (AAA) during follow-up. Individuals with Lp(a) at or above the 99th percentile (>=143 mg/dL, >=307 nmol/L) had multivariable-adjusted hazard ratios of 2.99 (95% CI 2.09-4.30) for PAD and 2.22 (95% CI 1.21-4.07) for AAA compared with those below the 50th percentile (<=9 mg/dL, <=17 nmol/L), and those with PAD had a 3.04-fold (95% CI 1.55-5.98) higher incidence of major adverse limb events. Genetically higher Lp(a) (per 50 mg/dL) predicted similar risk increases (risk ratio 1.39 for PAD, 1.21 for AAA), consistent with the observational estimates. In women smokers aged 70-79, absolute 10-year PAD risk rose from 8% to 21% across the Lp(a) range, and in men from 11% to 29%. The findings support Lp(a) as a causal risk factor for peripheral vascular disease, relevant as Lp(a)-lowering therapies enter phase 3 trials.
Original 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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.