High lipoprotein(a) is associated with major adverse limb events after femoral artery endarterectomy

Maarten C Verwer,Farahnaz Waissi,Joost M Mekke,Mirthe Dekker,Erik S.G Stroes,Gert J De Borst,Jeffrey Kroon,Constantijn E.V.B Hazenberg,Dominique P.V De Kleijn

doi:10.1016/j.atherosclerosis.2021.11.019

Maarten C Verwer, Farahnaz Waissi + Show 7 more

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https://doi.org/10.1016/j.atherosclerosis.2021.11.019

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Abstract

Backgrounds and aimsElevated lipoprotein(a) (Lp[a]) has been identified as a causal risk factor for cardiovascular disease including peripheral arterial disease (PAD). Although Lp(a) is associated with the diagnosis of PAD, it remains elusive whether there is an association of Lp(a) with cardiovascular and limb events in patients with severe PAD. MethodsPreoperative plasma Lp(a) levels were measured in 384 consecutive patients that underwent iliofemoral endarterectomy and were included in the Athero-Express biobank. Our primary objective was to assess the association of Lp(a) levels with Major Adverse Limb Events (MALE). Our secondary objective was to relate Lp(a) levels to Major Adverse Cardiovascular Events (MACE) and femoral plaque composition that was acquired from baseline surgery. ResultsDuring a median follow-up time of 5.6 years, a total of 225 MALE were recorded in 132 patients. Multivariable analysis, including history of peripheral intervention, age, diabetes mellitus, end stage renal disease and PAD disease stages, showed that Lp(a) was independently associated with first (HR of 1.36 (95% CI 1.02–1.82) p = .036) and recurrent MALE (HR 1.36 (95% CI 1.10–1.67) p = .004). A total of 99 MACE were recorded but Lp(a) levels were not associated with MACE.sLp(a) levels were significantly associated with a higher presence of smooth muscle cells in the femoral plaque, although this was not associated with MALE or MACE. ConclusionsPlasma Lp(a) is independently associated with first and consecutive MALE after iliofemoral endarterectomy. Hence, in patients who undergo iliofemoral endarterectomy, Lp(a) could be considered as a biomarker to enhance risk stratification for future MALE.

Highlights

Patients with peripheral artery disease (PAD) are treated with life style management and an appropriate medication regimen, such as antithrombotic or anticoagulant drugs in combination with lipidlowering therapies, in order to reduce the risk of future cardiovascular events (CVE)
We investigated the association of plasma Lp(a) levels with the risk of Major Adverse Limb Events (MALE) and Major Adverse Cardiovascular Events (MACE) in a cohort of patients undergoing iliofemoral endarterectomy
About 41% of the patients had a history of an infrainguinal peripheral intervention before baseline sur gery and 43% were previously diagnosed with coronary artery disease (CAD)

Summary

Introduction

Patients with peripheral artery disease (PAD) are treated with life style management and an appropriate medication regimen, such as antithrombotic or anticoagulant drugs in combination with lipidlowering therapies, in order to reduce the risk of future cardiovascular events (CVE). Patients with severe symptoms often require a vascular intervention to restore adequate perfusion. This will relieve most symptoms in the short term, the chronic nature of athero sclerosis will persist and the risk of future CVE remains extremely high [1]. Major Adverse Limb Events (MALE), a combination of lower limb amputation and peripheral vascular intervention, and Major Adverse Cardiovascular Events (MACE), a composite of non-fatal stroke/myo cardial infarction and cardiovascular death, are two important cate gories of CVE that reflect more localized and systemic disease progression and are used as objective performance goals after In order to determine which PAD patients are at elevated risk, biomarkers associated with future CVE are needed

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