Association Between Lp(a) and Cardiovascular Events in Individuals with Peripheral Artery Disease in the Mass General Brigham Lp(a) Registry
Abstract Body (Do not enter title and authors here): Background:
Both lipoprotein(a) [Lp(a)] and peripheral artery disease (PAD) are independently associated with atherosclerotic cardiovascular disease (ASCVD) events. Whether elevated Lp(a) provides additional risk stratification among individuals with PAD is less well-established.
Methods:
The Mass General Brigham (MGB) Lp(a) registry includes all individuals with Lp(a) measured at two tertiary care centers from 2000-2019. Those with a history of PAD were grouped into quartiles according to Lp(a) percentile: 1st-25th (Q1, Lp(a) ≤ 14nmol/L), 26th-50th (Q2, 14 - 42nmol/L), 51st-75th, (Q3, 42-132nmol/L), and 76th-100th (Q4, 132-855nmol/L). Outcomes were major adverse cardiovascular events (MACE: composite of cardiovascular death, myocardial infarction, ischemic stroke, or coronary revascularization) and major adverse limb events (MALE: composite of peripheral revascularization [endovascular or surgical], acute limb ischemia, or major lower extremity amputation). Cox proportional hazard modeling was used to assess the association between Lp(a) and the outcomes of interest. Analyses were adjusted for traditional risk factors.
Results:
Among 3,791 individuals with PAD, (39% female, median age 68 [IQR: 59-77]), 79% had hypertension, 81% had dyslipidemia, and 37% had diabetes. Relative to Q1, those in Q3 and Q4 had a 19% and 26% increased risk of MACE, respectively (adj. HR: 1.19, 95% CI 1.03-1.37, p=0.018; adj. HR: 1.26, 95% CI: 1.09-1.45, p=0.001, Fig, A). Individuals in Q4 had a 23% higher risk of MALE (adj. HR: 1.23, 1.03-1.48, p=0.022, Fig, B) relative to those in Q1. The overall event rate (per 1000 patient years) for MACE increased monotonically across all four subgroups while for MALE was increased only for those in the highest Lp(a) group.
Conclusions:
In individuals with PAD, Lp(a) levels provide additional prognostic information beyond traditional risk factors. Lp(a) above the 50th percentile was associated with higher risk of MACE, while levels greater than 75th percentile were associated with an increased risk of both MACE and MALE.
Mcclintick, Daniel
( Brigham and Womens Hospital
, Boston
, Massachusetts
, United States
)
Gerhard, Marie
( BRIGHAM AND WOMEN S HOSPITAL
, Boston
, Massachusetts
, United States
)
Januzzi, James
( Massachusetts General Hospital
, Wellesley Hills
, Massachusetts
, United States
)
Di Carli, Marcelo
( BRIGHAM AND WOMENS HOSPITAL
, Boston
, Massachusetts
, United States
)
Secemsky, Eric
( Beth Israel Deaconess Medical Cente
, Boston
, Massachusetts
, United States
)
Bhatt, Deepak
( Mount Sinai Fuster Heart Hospital
, Scarsdale
, New York
, United States
)
Blankstein, Ron
( BRIGHAM AND WOMENS HOSPITAL
, Boston
, Massachusetts
, United States
)
Divakaran, Sanjay
( Brigham and Womens Hospital
, Boston
, Massachusetts
, United States
)
Biery, David
( BRIGHAM AND WOMENS HOSPITAL
, Boston
, Massachusetts
, United States
)
Berman, Adam
( Brigham and Womens Hospital
, Brookline
, Massachusetts
, United States
)
Besser, Stephanie
( Brigham and Women's Hospital
, Champaign
, Illinois
, United States
)
Shiyovich, Arthur
( Brigham and Womens hospital
, Boston
, Massachusetts
, United States
)
Singh, Avinainder
( Brigham and Womens Hospital
, Boston
, Massachusetts
, United States
)
Huck, Daniel
( Brigham and Womens Hospital
, Boston
, Massachusetts
, United States
)
Weber, Brittany
( BRIGHAM AND WOMENS HOSPITAL
, Boston
, Massachusetts
, United States
)
Bonaca, Marc
( CPC Clinical Research
, Aurora
, Colorado
, United States
)
Author Disclosures:
Daniel McClintick:DO NOT have relevant financial relationships
| Marie Gerhard:DO NOT have relevant financial relationships
| James Januzzi:DO have relevant financial relationships
;
Researcher:Abbott:Active (exists now)
; Consultant:Prevencio:Active (exists now)
; Consultant:Quidel:Active (exists now)
; Consultant:Roche Diagnostics:Active (exists now)
; Consultant:AstraZeneca:Active (exists now)
; Consultant:Boehringer Ingelheim:Active (exists now)
; Consultant:Beckman:Active (exists now)
; Consultant:Abbott:Active (exists now)
; Individual Stocks/Stock Options:Jana Care:Active (exists now)
; Individual Stocks/Stock Options:Imbria:Active (exists now)
; Researcher:Novartis:Active (exists now)
; Researcher:Applied Therapeutics:Active (exists now)
; Researcher:BMS:Active (exists now)
; Researcher:AstraZeneca:Active (exists now)
| Marcelo Di Carli:DO have relevant financial relationships
;
Research Funding (PI or named investigator):Sun Pharma:Active (exists now)
; Research Funding (PI or named investigator):Alnylam:Past (completed)
; Research Funding (PI or named investigator):Xylocor:Past (completed)
; Consultant:Valo Health:Past (completed)
; Consultant:Sanofi:Past (completed)
; Consultant:MedTrace:Active (exists now)
; Research Funding (PI or named investigator):Gilead Sciences:Past (completed)
; Research Funding (PI or named investigator):Amgen:Active (exists now)
| Eric Secemsky:No Answer
| 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)
| Ron Blankstein:No Answer
| Sanjay Divakaran:DO have relevant financial relationships
;
Consultant:Kinevant Sciences:Past (completed)
| David Biery:No Answer
| Adam Berman:DO NOT have relevant financial relationships
| Stephanie Besser:DO NOT have relevant financial relationships
| Arthur Shiyovich:No Answer
| Avinainder Singh:DO NOT have relevant financial relationships
| Daniel Huck:DO NOT have relevant financial relationships
| Brittany Weber:DO have relevant financial relationships
;
Advisor:Novo Nordisk:Active (exists now)
; Advisor:Aegpha:Past (completed)
; Advisor:BMS:Past (completed)
; Advisor:Kiniksa:Active (exists now)
; Advisor:Horizon Therapeutics:Past (completed)
| Marc Bonaca:DO have relevant financial relationships
;
Research Funding (PI or named investigator):Dr. Bonaca is the Executive Director of CPC:Active (exists now)
; Research Funding (PI or named investigator):Dr. Bonaca is the Executive Director of CPC:Active (exists now)
