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. 2024 Jul 18;23(1):257.
doi: 10.1186/s12933-024-02348-2.

Lipoprotein(a) as a cardiovascular risk factor among patients with and without diabetes Mellitus: the Mass General Brigham Lp(a) Registry

Arthur Shiyovich  1   2 , Adam N Berman  1 , Stephanie A Besser  1 , David W Biery  1 , Rhanderson Cardoso  1 , Sanjay Divakaran  1 , Avinainder Singh  1 , Daniel M Huck  1   2 , Brittany Weber  1 , Jorge Plutzky  1 , Christopher Cannon  1 , Khurram Nasir  3 , Marcelo F Di Carli  1   2 , James L Januzzi  4 , Deepak L Bhatt  5 , Ron Blankstein  6   7
Affiliations

Lipoprotein(a) as a cardiovascular risk factor among patients with and without diabetes Mellitus: the Mass General Brigham Lp(a) Registry

Arthur Shiyovich et al. Cardiovasc Diabetol. .

Abstract

Background: Diabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood.

Objective: To investigate the relationship between elevated Lp(a) and DM with CAD outcomes.

Methods: Retrospective analysis of the MGB Lp(a) Registry involving patients ≥ 18 years who underwent Lp(a) measurements between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasms, and prior atherosclerotic cardiovascular disease (ASCVD). The primary outcome was a combination of cardiovascular death or myocardial infarction (MI). Elevated Lp(a) was defined as > 90th percentile (≥ 216 nmol/L).

Results: Among 6,238 patients who met the eligibility criteria, the median age was 54, 45% were women, and 12% had DM. Patients with DM were older, more frequently male, and had a higher prevalence of additional cardiovascular risk factors. Over a median follow-up of 12.9 years, patients with either DM or elevated Lp(a) experienced higher rates of the primary outcome. Notably, those with elevated Lp(a) had a higher incidence of the primary outcome regardless of their DM status. The annual event rates were as follows: No-DM and Lp(a) < 90th% - 0.6%; No-DM and Lp(a) > 90th% - 1.3%; DM and Lp(a) < 90th% - 1.9%; DM and Lp(a) > 90th% - 4.7% (p < 0.001). After adjusting for confounders, elevated Lp(a) remained independently associated with the primary outcome among both patients with DM (HR = 2.66 [95%CI: 1.55-4.58], p < 0.001) and those without DM (HR = 2.01 [95%CI: 1.48-2.74], p < 0.001).

Conclusions: Elevated Lp(a) constitutes an independent and incremental risk factor for CAD outcomes in patients with and without DM.

Keywords: Coronary artery disease outcomes; Diabetes mellitus; Lipoprotein (a).

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Conflict of interest statement

AS, ANB, SB, DWB, RC, SD, AvS, DH, KN, JP: noneBW: Scientific advisory board: Kiniksa, Horizon Therapuetics, and Novo NordiskCC: Dr. Cannon reports in calendar years 2021 to 2023: Research Grants from: Amgen, Better Therapeutics, Boehringer-Ingelheim (BI), Daiichi Sankyo, Merck, Novo Nordisk, Pfizer. Consulting fees from Amryt/Chiesi, Alnylam, Amarin, Amgen, Applied Therapeutics, Ascendia, Biogen, BI, BMS, CSL Behring, Eli Lilly, Janssen, Lexicon, Merck, Milestone, Pfizer, Rhoshan, SanofiI serve on Data and Safety Monitoring Boards for the Applied Therapeutics, Areteia and Novo Nordisk. JJ: Dr. Januzzi is a Trustee of the American College of Cardiology, is a Board Member of Imbria Pharmaceuticals, is a director at Jana Care, has received research support from Abbott, Applied Therapeutics, HeartFlow Inc, Innolife and Roche Diagnostics, consulting income from Abbott, AstraZeneca, Bayer, Beckman, Boehringer-Ingelheim, Janssen, Novartis, Merck, and Roche Diagnostics, and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Bayer, CVRx, Intercept, Pfizer and Takeda; MDC: Grant support from AmgenDLB: Dr. Bhatt discloses the following relationships - Advisory Board: 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; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); Consultant: Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene; 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); 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), 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); Other: Clinical Cardiology (Deputy Editor); 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); Research Funding: 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; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo.RB: Dr. Blankstein has received research support from Amgen Inc, Novartis Inc, and Beren Therapeutics, and has served as a consultant/advisory board for Caristo Inc, Elucid Inc, Hearflow Inc, Nanox AI, and Beren Therapeutics.

Figures

Fig. 1
Fig. 1
Unadjusted (A) and adjusted (B) annual event rates stratified by Lp(a) and DM status. Lp(a): Lipoprotein (a); DM: Diabetes mellitus. Adjusted for age, sex, hyperlipidemia, hypertension, smoking
Fig. 2
Fig. 2
Cumulative incidence of the primary outcome (cardiovascular death or MI) among patients with (A) and without (B) diabetes mellitus stratified by Lp(a). Lp(a): Lipoprotein (a); MI: myocardial infarction
See this image and copyright information in PMC

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