Scientific Sessions 2024  /  Novel Roles for Lipids and Lipoproteins in Cardiovascular Diseases  /  Lipoprotein(a) [Lp(a)]-Enriched Plasma Undergoes More Rapid Oxidation than Small Dense LDL-Enriched Plasma that is Inhibited by Eicosapentaenoic Acid (EPA)
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American Heart Association

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Final ID: Su1016

Lipoprotein(a) [Lp(a)]-Enriched Plasma Undergoes More Rapid Oxidation than Small Dense LDL-Enriched Plasma that is Inhibited by Eicosapentaenoic Acid (EPA)

Abstract Body (Do not enter title and authors here): Background: Elevated Lp(a) levels are associated with increased cardiovascular (CV) risk, along with small dense LDL (sdLDL). Lp(a) contains oxidized phospholipid that may “seed” lipid oxidation reactions compared to other lipoproteins. The omega-3 fatty acid EPA delivered as icosapent ethyl (4 g/d) reduced CV events in high-risk patients, including those with elevated Lp(a) (REDUCE-IT). EPA has conjugated double bonds that trap lipid free radicals. We compared rates of oxidation for Lp(a)-enriched and sdLDL-enriched LDL with potential inhibition by EPA at a pharmacologic concentration.
Methods: Lp(a) and sdLDL were enriched to 66% of total ApoB-containing particles from patients with elevated levels following isopycnic centrifugation. Lp(a), sdLDL and LDL were matched for total protein (50 µg/mL) and incubated at 37°C for 30 min with EPA (50 µM). Samples then underwent copper sulfate-induced oxidation (20 µM) monitored by formation of malondialdehyde (MDA) for 3 h. We normalized rates of oxidation to total available lipid in the samples.
Results: After 0.5 h, Lp(a)-enriched plasma underwent the most rapid oxidation – 60% of total lipid oxidation (p<0.001 vs other fractions) – followed by sdLDL-enriched plasma (30% of total oxidation) then pure LDL (17% of total oxidation). All samples underwent complete oxidation by 2 h. Initially (t = 0 h), Lp(a) enriched plasma contained more oxidized lipid than all other fractions (p<0.05). The relative antioxidant activity of EPA was greatest in the Lp(a) enriched samples; EPA inhibited oxidation of Lp(a)-enriched, sdLDL-enriched, and pure LDL by 50%, 46% and 47% (p<0.001), respectively, at 2 h. The antioxidant activity of EPA in samples persisted at all time points.
Conclusions: Lp(a)-enriched plasma underwent rapid oxidation attributed to oxidized phospholipid content and followed by sdLDL and LDL. Oxidation was disproportionately inhibited by EPA in Lp(a) enriched plasma due to free radical scavenging mechanism associated with its multiple conjugated double bonds. The high lipid oxidation rates for Lp(a) inhibited by EPA may contribute to the benefit observed in REDUCE-IT, including in subjects with elevated Lp(a) levels.
  • Sherratt, Samuel  ( Mount Sinai Fuster Heart Hospital , New York , New York , United States )
  • Libby, Peter  ( BRIGHAM AND WOMENS HOSPITAL , Boston , Massachusetts , United States )
  • Bhatt, Deepak  ( Mount Sinai Fuster Heart Hospital , Scarsdale , New York , United States )
  • Mason, Preston  ( Brigham and Womens Hospital , Beverly , Massachusetts , United States )
    • Author Disclosures:
    Samuel Sherratt: DO have relevant financial relationships ; Employee:Elucida Research:Active (exists now) | Peter Libby: DO have relevant financial relationships ; Consultant:Amgen, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Novo Nordisk, Novartis, and Sanofi-Regeneron:Active (exists now) ; Other (please indicate in the box next to the company name):Dr. Libby is on the Board of Directors of XBiotech, Inc. Dr. Libby has a financial interest in Xbiotech, a company developing therapeutic human antibodies, in TenSixteen Bio, a company targeting somatic mosaicism and clonal hematopoiesis of indeterminate potential (CHIP) to discover and develop novel therapeutics to treat age-related diseases, and in Soley Therapeutics, a biotechnology company that is combining artificial intelligence with molecular and cellular response detection for discovering and developing new drugs, currently focusing on cancer therapeutics. Dr. Libby’s interests were reviewed and are managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of-interest policies.:Active (exists now) ; Other (please indicate in the box next to the company name):Dr. Libby’s laboratory has received research funding in the last 2 years from Novartis, Novo Nordisk and Genentech:Active (exists now) ; Advisor:AmAmgen, Caristo Diagnostics, CSL Behring, Elucid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Novartis, PlaqueTec, Polygon Therapeutics, TenSixteen Bio, Soley Thereapeutics, and XBiotech, Inc.:Active (exists now) | Deepak Bhatt: DO have relevant financial relationships ; Advisor:Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys:Active (exists now) ; Other (please indicate in the box next to the company name):Trustee: American College of Cardiology; Unfunded Research: FlowCo:Active (exists now) ; Other (please indicate in the box next to the company name):Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions;:Active (exists now) ; Royalties/Patent Beneficiary:Royalties: Elsevier (Editor, Braunwald’s Heart Disease):Active (exists now) ; Researcher:Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio;:Active (exists now) ; Royalties/Patent Beneficiary:Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent);:Active (exists now) ; Other (please indicate in the box next to the company name):Honoraria: Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee);:Active (exists now) ; Other (please indicate in the box next to the company name):Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum):Active (exists now) ; Other (please indicate in the box next to the company name):Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial);:Active (exists now) ; Consultant:Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene:Active (exists now) ; Other (please indicate in the box next to the company name):Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock);:Active (exists now) | Preston Mason: DO have relevant financial relationships ; Research Funding (PI or named investigator):Amarin:Active (exists now) ; Consultant:Esperion:Past (completed) ; Consultant:Boehringer Ingelheim:Active (exists now) ; Research Funding (PI or named investigator):Lexicon:Past (completed) ; Research Funding (PI or named investigator):Viatris:Active (exists now)
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Novel Roles for Lipids and Lipoproteins in Cardiovascular Diseases

Sunday, 11/17/2024 , 03:15PM - 04:15PM

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