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Targeted metabolomic profiling and prediction of cardiovascular events: a prospective study of patients with psoriatic arthritis and psoriasis
  1. Keith Colaco1,2,3,
  2. Ker-Ai Lee4,
  3. Shadi Akhtari5,6,
  4. Raz Winer7,
  5. Paul Welsh8,
  6. Naveed Sattar8,
  7. Iain B McInnes9,
  8. Vinod Chandran3,6,
  9. Paula Harvey5,6,
  10. Richard J Cook4,
  11. Dafna D Gladman3,6,
  12. Vincent Piguet1,6,
  13. Lihi Eder1,6
  1. 1 Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada
  2. 2 Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  3. 3 Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada
  4. 4 Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ontario, Canada
  5. 5 Department of Cardiology, Women's College Hospital, Toronto, Ontario, Canada
  6. 6 Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  7. 7 Department of Neurology, Rambam Health Care Campus, Haifa, Israel
  8. 8 BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
  9. 9 Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK
  1. Correspondence to Dr Lihi Eder, Women's College Research Institute, Women's College Hospital, Toronto, Canada; Lihi.EDER{at}wchospital.ca

Abstract

Objective In patients with psoriatic disease (PsD), we sought serum metabolites associated with cardiovascular (CV) events and investigated whether they could improve CV risk prediction beyond traditional risk factors and the Framingham Risk Score (FRS).

Methods Nuclear magnetic resonance metabolomics identified biomarkers for incident CV events in patients with PsD. The association of each metabolite with incident CV events was analysed using Cox proportional hazards regression models first adjusted for age and sex, and subsequently for traditional CV risk factors. Variable selection was performed using penalisation with boosting after adjusting for age and sex, and the FRS.

Results Among 977 patients with PsD, 70 patients had incident CV events. In Cox regression models adjusted for CV risk factors, alanine, tyrosine, degree of unsaturation of fatty acids and high-density lipoprotein particles were associated with decreased CV risk. Glycoprotein acetyls, apolipoprotein B and cholesterol remnants were associated with increased CV risk. The age-adjusted and sex-adjusted expanded model with 13 metabolites significantly improved prediction of CV events beyond the model with age and sex alone, with an area under the receiver operator characteristic curve (AUC) of 79.9 versus 72.6, respectively (p=0.02). Compared with the FRS alone (AUC=73.9), the FRS-adjusted expanded model with 11 metabolites (AUC=75.0, p=0.72) did not improve CV risk discrimination.

Conclusions We identify novel metabolites associated with the development of CV events in patients with PsD. Further study of their underlying causal role may clarify important pathways leading to CV events in this population.

  • arthritis
  • psoriatic
  • cardiovascular diseases
  • atherosclerosis

Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information. Not applicable.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information. Not applicable.

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Footnotes

  • Handling editor Josef S Smolen

  • Presented at This study reports work that was previously presented at the 2020 American College of Rheumatology Annual Meeting: Colaco K, Lee K, Akhtari S, et al. Targeted Metabolomic Profiling and Prediction of Cardiovascular Events: A Prospective Study of Patients with Psoriatic Arthritis and Psoriasis [(abstract]). Arthritis Rheumatol. 2020; 72 (suppl 10).

  • Contributors All authors were involved in study conception and design. KC, K-AL, RJC and LE analysed and interpreted the data. All authors were involved in interpretation of the results and drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. LE had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding KC is supported by the Enid Walker Estate, Women’s College Research Institute, Arthritis Society (TGP-19-0446), National Psoriasis Foundation (Early Career Grant) and the Edward Dunlop Foundation. LE is supported by a Young Investigator Award from the Arthritis Society and an Early Researcher Award from the Ontario Ministry of Science and Innovation. VC is supported by a Pfizer Chair Research Award, Rheumatology, University of Toronto, Canada. The study was supported in part by a discovery grant from the National Psoriasis Foundation and an operating grant from the Arthritis Society (YIO-16-394). The Psoriatic Disease Programme has been supported by a grant from the Krembil Foundation.

  • Competing interests KC reports grants from Arthritis Society, grants from National Psoriasis Foundation, during the conduct of the study. NS reports personal fees from Amgen, personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Eli Lilly, personal fees from Merck Sharpe & Dohme, personal fees from Novartis, personal fees from Novo Nordisk, personal fees from Pfizer, personal fees from Sanofi, outside the submitted work. IBM reports grants and personal fees from Abbvie, grants and personal fees from BMS, grants and personal fees from Janssen, grants and personal fees from Pfizer, grants and personal fees from Novartis, grants and personal fees from UCB, grants and personal fees from Eli Lilly, outside the submitted work. VC reports grants and personal fees from Amgen, grants and personal fees from Abbvie, grants, personal fees and other from Eli Lilly, personal fees from Janssen, personal fees from Novartis, personal fees from Pfizer, personal fees from UCB, personal fees from BMS, outside the submitted work. PH reports grants from Arthritis Society, during the conduct of the study. DDG reports grants and personal fees from Abbvie, grants and personal fees from Amgen, personal fees from BMS, grants and personal fees from Celgene, grants and personal fees from Eli Lilly, personal fees from Galapagos, personal fees from Gilead, grants and personal fees from Novartis, grants and personal fees from Pfizer, grants and personal fees from UCB, outside the submitted work. VP reports advisory work for Pfizer, AbbVie, Janssen, UCB, Novartis, Almirall and Celgene. VP has received honoraria from Kyowa Kirin Co. In his role as Department Division Director of Dermatology at the University of Toronto, VP has received departmental support from AbbVie, Bausch Health (formerly Valeant), Celgene, Janssen, LEO Pharma, Lilly, NAOS, Novartis, Pfizer, Pierre-Fabre and Sanofi in the past 3 years. LE reports grants from Arthritis Society, grants from National Psoriasis Foundation, grants from Ontario Ministry of Research Innovation and Science, during the conduct of the study. K-AL, SA, RW, RJC have no competing interests to declare.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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