Author + information
- Received August 22, 2017
- Revision received September 29, 2017
- Accepted December 18, 2017
- Published online April 30, 2018.
- Leonardo P. de Carvalho, MD, PhDa,b,c,d,
- Sock Hwee Tan, PhDb,c,
- Ghim-Siong Ow, BSce,
- Zhiqun Tang, PhDe,f,
- Jianhong Ching, PhDg,
- Jean-Paul Kovalik, MD, PhDg,
- Sock Cheng Poh, BScb,
- Chee-Tang Chin, MBBSg,h,
- A. Mark Richards, MD, PhDb,i,
- Eliana C. Martinez, MD, PhDj,
- Richard W. Troughton, MD, PhDi,
- Alan Yean-Yip Fong, MBBSk,l,
- Bryan P. Yan, MBBSm,
- Aruni Seneviratna, MBBS, MPHb,
- Vitaly Sorokin, MD, PhDb,c,
- Scott A. Summers, PhDn,
- Vladimir A. Kuznetsov, PhD, SciDe,o,∗∗ ( and )
- Mark Y. Chan, MBBS, PhDb,c,∗ ()
- aFederal University of Sao Paulo State, Sao Paulo, Brazil
- bNational University Heart Center, Singapore, Singapore
- cCardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- dAlbert Einstein Hospital, São Paulo, Brazil
- eBioinformatics Institute, A*STAR, Singapore
- fInstitute of Molecular and Cell Biology, A*STAR, Singapore
- gProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore
- hNational Heart Centre Singapore, Singapore
- iChristchurch Heart Institute, University of Otago Christchurch, Christchurch Hospital, Christchurch, New Zealand
- jMiller School of Medicine, University of Miami, Miami, Florida
- kClinical Research Centre, Sarawak General Hospital, Kuching, Malaysia
- lDepartment of Cardiology, Sarawak General Hospital, Kuching, Malaysia
- mDepartment of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- nUniversity of Utah, Salt Lake City, Utah
- oNanyang Institute of Technology in Health & Medicine, Nanyang Technological University, Singapore
- ↵∗Address for correspondence:
Dr. Mark Y. Chan, Cardiac Department, Yong Loo-Lin School of Medicine, National University of Singapore, 1E, Kent Ridge Road, NUHS Tower Block, Level 9, Singapore 119228.
- ↵∗∗Dr. Vladimir A. Kuznetsov, Department of Urology, Department of Biochemistry and Molecular Biology, 750 East Adams Street, Weiskotten Hall, Room 1271, SUNY Upstate Medical University, Syracuse, New York 13210.
• Targeted profiling of ceramides identified a 12-ceramide plasma signature that predicted 12-month cardiovascular death, MI, and stroke in 2 prospective cohorts of AMI patients.
• Among coronary artery bypass grafting patients, plasma ceramides were higher in those with recent AMI compared with those without recent acute MI.
• Analysis of rat ischemic myocardium revealed a consistent increase in ceramide levels and overexpression of 3 enzymes in ceramide biosynthesis.
We identified a plasma signature of 11 C14 to C26 ceramides and 1 C16 dihydroceramide predictive of major adverse cardiovascular events in patients with acute myocardial infarction (AMI). Among patients undergoing coronary artery bypass surgery, those with recent AMI, compared with those without recent AMI, showed a significant increase in 5 of the signature’s 12 ceramides in plasma but not simultaneously-biopsied aortic tissue. In contrast, a rat AMI model, compared with sham control, showed a significant increase in myocardial concentrations of all 12 ceramides and up-regulation of 3 ceramide-producing enzymes, suggesting ischemic myocardium as a possible source of this ceramide signature.
- acute coronary syndrome
- major adverse cardiovascular and cerebrovascular events
- risk prediction
This work was supported by grants NMRC/CSA/028/2011 and NMRC/CG/014/2013 from the National Medical Research Council, Singapore. Dr. Richards has received salary support from NMRC/STaR/0022/2014. Drs. Ow, Tang, and Kuznetsov have received salary support from BII/A*STAR, Singapore. Dr. Summers has served as a consultant for and is a shareholder of Centaurus Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Kuznetsov and Chan contributed equally to this work and are joint senior authors.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received August 22, 2017.
- Revision received September 29, 2017.
- Accepted December 18, 2017.
- 2018 The Authors