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. 2022 Dec 1;5(12):e2245720.
doi: 10.1001/jamanetworkopen.2022.45720.

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

Alexis F Guédon  1 , Jean-Baptiste De Freminville  1 , Tristan Mirault  1   2 , Nassim Mohamedi  1 , Bastien Rance  3 , Natalie Fournier  4   5 , Jean-Louis Paul  4   5 , Emmanuel Messas  1   2 , Guillaume Goudot  1   2
Affiliations

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

Alexis F Guédon et al. JAMA Netw Open. .

Abstract

Importance: High 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.

Objective: To assess the association between Lp(a) levels and incidence of major adverse limb events in unselected hospitalized patients.

Design, setting, and participants: This 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 measures: The 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.

Results: A 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 relevance: Results 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mirault reported receiving grants from Genzyme and personal fees from Novartis during the conduct of the study; personal fees from Bayer Healthcare and Incyte outside the submitted work; and nonfinancial support from Bayer Healthcare, Merck Sharp & Dohme, Amgen, Bristol-Myers Squibb–Pfizer, and Alexion outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Study Population
HEGP indicates Hôpital Européen Georges-Pompidou; Lp(a), lipoprotein(a).
Figure 2.
Figure 2.. Kaplan-Meier Survival Curves of the Cumulative Incidence of Major Adverse Limb Event (MALE) by Lipoprotein(a) (Lp[a]) Level Categories
The inset shows the detail on an enlarged y-axis.
See this image and copyright information in PMC

References

    1. Criqui MH, Matsushita K, Aboyans V, et al. ; American Heart Association Council on Epidemiology and Prevention; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; Council on Lifestyle and Cardiometabolic Health; Council on Peripheral Vascular Disease; and Stroke Council . Lower extremity peripheral artery disease: contemporary epidemiology, management gaps, and future directions: a scientific statement from the American Heart Association. Circulation. 2021;144(9):e171-e191. doi:10.1161/CIR.0000000000001005 - DOI - PMC - PubMed
    1. Fowkes FGR, Aboyans V, Fowkes FJI, McDermott MM, Sampson UKA, Criqui MH. Peripheral artery disease: epidemiology and global perspectives. Nat Rev Cardiol. 2017;14(3):156-170. doi:10.1038/nrcardio.2016.179 - DOI - PubMed
    1. Nehler MR, Duval S, Diao L, et al. . Epidemiology of peripheral arterial disease and critical limb ischemia in an insured national population. J Vasc Surg. 2014;60(3):686-95.e2. doi:10.1016/j.jvs.2014.03.290 - DOI - PubMed
    1. Aboyans V, Ricco JB, Bartelink MEL, et al. ; ESC Scientific Document Group . 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO) The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39(9):763-816. doi:10.1093/eurheartj/ehx095 - DOI - PubMed
    1. Gerhard-Herman MD, Gornik HL, Barrett C, et al. . 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135(12):e686-e725. doi:10.1161/CIR.0000000000000470 - DOI - PMC - PubMed