Rosangela A Hoshi1,2, Yanyan Liu1,2, Mohit Jain3, Daniel I Chasman2, Olga V Demler1,2,4, Samia Mora1,2, Heike Luttmann-Gibson1,2,3, Saumya Tiwari5, Franco Giulianini2, Allen M Andres5, Jeramie D Watrous5, Nancy R Cook2, Karen H Costenbader6, Olivia I Okereke3,7, Paul M Ridker1,2, JoAnn E Manson2,3, I-Min Lee2,3, Manickavasagar Vinayagamoorthy2, Susan Cheng8, Trisha Copeland2. 1. Center for Lipid Metabolomics, Division of Preventive Medicine, Division of Cardiovascular Medicine (R.A.H., Y.L., H.L.-G., P.M.R., O.V.D., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 2. Division of Preventive Medicine (R.A.H., Y.L., H.L.-G., F.G., N.R.C., P.M.R., J.E.M., I.-M.L., M.V., T.C., D.I.C., O.V.D., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 3. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (H.L.-G., O.I.O., J.E.M., I.-M.L., M.J.). 4. Department of Computer Science, ETH Zurich, Switzerland (O.V.D.). 5. Department of Pharmacology, University of California San Diego, La Jolla (S.T., A.M.A., J.D.W.). 6. Division of Rheumatology, Inflammation and Immunity (K.H.C.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 7. Department of Psychiatry, Massachusetts General Hospital, Boston (O.I.O.). 8. Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (S.C.).
Abstract
BACKGROUND: To clarify the mechanisms underlying physical activity (PA)-related cardioprotection, we examined the association of PA with plasma bioactive lipids (BALs) and cardiovascular disease (CVD) events. We additionally performed genome-wide associations. METHODS: PA-bioactive lipid associations were examined in VITAL (VITamin D and OmegA-3 TriaL)-clinical translational science center (REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01169259; N=1032) and validated in JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin)-NC (REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00239681; N=589), using linear models adjusted for age, sex, race, low-density lipoprotein-cholesterol, total-C, and smoking. Significant BALs were carried over to examine associations with incident CVD in 2 nested CVD case-control studies: VITAL-CVD (741 case-control pairs) and JUPITER-CVD (415 case-control pairs; validation). RESULTS: We detected 145 PA-bioactive lipid validated associations (false discovery rate <0.1). Annotations were found for 6 of these BALs: 12,13-diHOME, 9,10-diHOME, lysoPC(15:0), oxymorphone-3b-D-glucuronide, cortisone, and oleoyl-glycerol. Genetic analysis within JUPITER-NC showed associations of 32 PA-related BALs with 22 single-nucleotide polymorphisms. From PA-related BALs, 12 are associated with CVD. CONCLUSIONS: We identified a PA-related bioactive lipidome profile out of which 12 BALs also had opposite associations with incident CVD events.
BACKGROUND: To clarify the mechanisms underlying physical activity (PA)-related cardioprotection, we examined the association of PA with plasma bioactive lipids (BALs) and cardiovascular disease (CVD) events. We additionally performed genome-wide associations. METHODS: PA-bioactive lipid associations were examined in VITAL (VITamin D and OmegA-3 TriaL)-clinical translational science center (REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01169259; N=1032) and validated in JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin)-NC (REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00239681; N=589), using linear models adjusted for age, sex, race, low-density lipoprotein-cholesterol, total-C, and smoking. Significant BALs were carried over to examine associations with incident CVD in 2 nested CVD case-control studies: VITAL-CVD (741 case-control pairs) and JUPITER-CVD (415 case-control pairs; validation). RESULTS: We detected 145 PA-bioactive lipid validated associations (false discovery rate <0.1). Annotations were found for 6 of these BALs: 12,13-diHOME, 9,10-diHOME, lysoPC(15:0), oxymorphone-3b-D-glucuronide, cortisone, and oleoyl-glycerol. Genetic analysis within JUPITER-NC showed associations of 32 PA-related BALs with 22 single-nucleotide polymorphisms. From PA-related BALs, 12 are associated with CVD. CONCLUSIONS: We identified a PA-related bioactive lipidome profile out of which 12 BALs also had opposite associations with incident CVD events.
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