Kwok Leung Ong1, Nicholas Hui2, Andrzej S Januszewski3, Nadeem O Kaakoush2, Aimin Xu4, Rana Fayyad5, David A DeMicco5, Alicia J Jenkins3, Anthony C Keech3, David D Waters6, Philip J Barter2, Kerry-Anne Rye2. 1. Lipid Research Group, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. Electronic address: oklws@yahoo.com.hk. 2. Lipid Research Group, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. 3. National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia. 4. Department of Medicine, University of Hong Kong, Hong Kong, China; State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, China. 5. Pfizer, Inc., New York, NY, United States. 6. Division of Cardiology, San Francisco General Hospital, the University of California at San Francisco, San Francisco, CA, United States.
Abstract
BACKGROUND: Higher plasma fibroblast growth factor 21 (FGF21) levels predict incident cardiovascular events in type 2 diabetes patients. However, whether FGF21 levels predict cardiovascular events in statin-treated patients in the general population is unknown. We investigated whether FGF21 levels predict major cardiovascular event (MCVE) in the Treating to New Targets (TNT) trial participants. METHODS: After 8-week run-in on atorvastatin 10 mg/day, 10,001 patients with stable coronary disease in the TNT trial were randomized to 10 mg or 80 mg/day of atorvastatin for a median of 4.9 years. We analyzed data from 1996 patients with plasma FGF21 levels measured at randomization. Among them, 1835 patients had FGF21 measured one-year post-randomization. RESULTS:Higher ln-transformed FGF21 levels at randomization were associated with higher risk of incident MCVE (adjusted hazards ratio per SD increase = 1.18, P = 0.019). At 1-year post-randomization, FGF21 levels were lower in patients randomized to receive 80 mg versus 10 mg atorvastatin (186.9 versus 207.5 pg/mL respectively, P = 0.006). Higher ln-transformed FGF21 levels at 1-year post-randomization were also associated with higher subsequent risk of MCVEs (adjusted hazards ratio per SD increase = 1.24, P = 0.009). However, changes in FGF21 levels over 1-year were not related to subsequent MCVE risk. FGF21 levels had significant incremental value in net reclassification improvement in MCVE risk prediction. CONCLUSIONS:Higher plasma FGF21 levels are associated with higher CVD risk in statin-treated high-risk patients. Higher dose atorvastatin is associated with a reduction in FGF21 levels. FGF21 provides incremental value in CVD risk prediction in statin-treated patients.
RCT Entities:
BACKGROUND: Higher plasma fibroblast growth factor 21 (FGF21) levels predict incident cardiovascular events in type 2 diabetespatients. However, whether FGF21 levels predict cardiovascular events in statin-treated patients in the general population is unknown. We investigated whether FGF21 levels predict major cardiovascular event (MCVE) in the Treating to New Targets (TNT) trial participants. METHODS: After 8-week run-in on atorvastatin 10 mg/day, 10,001 patients with stable coronary disease in the TNT trial were randomized to 10 mg or 80 mg/day of atorvastatin for a median of 4.9 years. We analyzed data from 1996 patients with plasma FGF21 levels measured at randomization. Among them, 1835 patients had FGF21 measured one-year post-randomization. RESULTS: Higher ln-transformed FGF21 levels at randomization were associated with higher risk of incident MCVE (adjusted hazards ratio per SD increase = 1.18, P = 0.019). At 1-year post-randomization, FGF21 levels were lower in patients randomized to receive 80 mg versus 10 mg atorvastatin (186.9 versus 207.5 pg/mL respectively, P = 0.006). Higher ln-transformed FGF21 levels at 1-year post-randomization were also associated with higher subsequent risk of MCVEs (adjusted hazards ratio per SD increase = 1.24, P = 0.009). However, changes in FGF21 levels over 1-year were not related to subsequent MCVE risk. FGF21 levels had significant incremental value in net reclassification improvement in MCVE risk prediction. CONCLUSIONS: Higher plasma FGF21 levels are associated with higher CVD risk in statin-treated high-risk patients. Higher dose atorvastatin is associated with a reduction in FGF21 levels. FGF21 provides incremental value in CVD risk prediction in statin-treated patients.
Authors: Pirkka T Pekkarinen; Markus B Skrifvars; Ville Lievonen; Pekka Jakkula; Laura Albrecht; Pekka Loisa; Marjaana Tiainen; Ville Pettilä; Matti Reinikainen; Johanna Hästbacka Journal: Sci Rep Date: 2021-01-12 Impact factor: 4.379