Association of Lipoprotein(a) Levels With Incidence of Major Adverse Limb Events

Abstract

ImportanceHigh lipoprotein(a) (Lp[a]) levels are involved in the development of cardiovascular events, particularly in myocardial infarction, stroke, and peripheral artery disease. Studies assessing the Lp(a) levels associated with adverse lower-limb events are lacking.ObjectiveTo assess the association between Lp(a) levels and incidence of major adverse limb events in unselected hospitalized patients.Design, Setting, and ParticipantsThis large retrospective monocentric cohort study was conducted from January 1, 2000, to December 31, 2020. Data were derived from the clinical information system of the Hôpital Européen Georges-Pompidou, a Paris-based university hospital. Patients who underwent at least 1 Lp(a) measurement at the center during the study period were included. Patients who had no follow-up data or who had the first Lp(a) measurement after the study outcome had occurred were excluded. Data analyses were performed from May 2021 to January 2022.Main Outcomes and MeasuresThe primary outcome was the first inpatient major adverse limb event, defined as a major amputation, peripheral endovascular revascularization, or peripheral surgical revascularization, during follow-up. Secondary outcomes included individual components of the primary outcome. Lipoprotein(a) levels were categorized as follows: normal (<50 mg/dL), high (50 to <134 mg/dL), and very high (≥134 mg/dL); to convert Lp(a) values to milligrams per liter, multiply by 0.1.ResultsA total of 16 513 patients (median [IQR] age, 58.2 [49.0-66.7] years; 9774 men [59.2%]) were included in the cohort. The median (IQR) Lp(a) level was 24 (10.0-60.0) mg/dL. The 1-year incidence of major adverse limb event was 2.44% in the overall population and 4.54% among patients with very high Lp(a) levels. High (adjusted accelerated failure time [AFT] exponential estimate: 0.43; 95% CI, 0.24-0.78; Benjamini-Hochberg–corrected P = .01) and very high (adjusted AFT exponential estimate: 0.17; 95% CI, 0.07-0.40; Benjamini-Hochberg–corrected P < .001) Lp(a) levels were independently associated with an increased risk of major adverse limb event.Conclusions and RelevanceResults of this study showed that higher Lp(a) levels were independently associated with an increased risk of a major adverse limb event in hospitalized patients. The Lp(a) measurement needs to be taken into account to improve lower-limb vascular risk assessment.

Lipoprotein(a): Emerging insights and therapeutics

“…Studies in patients with established PAD have demonstrated that high Lp(a), particularly ≥30 mg/dL, is associated with higher rates of lower limb peripheral revascularizations (HR 1.33; 95 % CI 1.06–1.66) though no differences were seen in risk of major adverse cardiovascular outcomes or mortality in this particular analysis [60] . Similarly, in a large retrospective study utilizing administrative data from a center in Paris, the 1-year incidence of major adverse limb events was 4.5 % in those with Lp(a) ≥134 mg/dL vs. 2.4 % in overall population [61] . Further large prospective randomized controlled clinical trials will hopefully continue to explore the impact of Lp(a) on both the incidence and the progression of PAD.…”

Small apolipoprotein(a) isoforms may predict primary patency following peripheral arterial revascularization

“…High Lp(a) levels are associated with adverse limb events in patients with symptomatic PAD undergoing lower extremity revascularization 25 26 2 . International guidelines (Canadian 27 and ECC 28 ) advocate for all individuals to have Lp(a) measured once in a lifetime.…”

Preventive Therapies in Peripheral Arterial Disease

“…The one-year incidence of MALE outcomes was higher in those with higher Lp(a) (lipoprotein a) levels compared to the overall population (HR 4.54% vs. 2.44%, p = 0.01). The authors also reported that the high and very high Lp(a) levels were independent risk factors for MALE [83].…”