Neeltje A E Allard1, Tom J J Schirris2,3, Rebecca J Verheggen1, Frans G M Russel2,3, Richard J Rodenburg3,4, Jan A M Smeitink3,4, Paul D Thompson5, Maria T E Hopman1, Silvie Timmers1. 1. Department of Physiology, Radboud University Medical Center, Nijmegen, Netherlands. 2. Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, Netherlands. 3. Centre for Systems Biology and Bioenergetics, Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, Netherlands. 4. Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, Radboud University Medical Center, Nijmegen, Netherlands. 5. Division of Cardiology, Hartford Hospital, Hartford, Connecticut.
Abstract
Context: Statin myopathy is linked to disturbances in mitochondrial function and exercise intolerance. Objectives: To determine whether differences exist in exercise performance, muscle function, and muscle mitochondrial oxidative capacity and content between symptomatic and asymptomatic statin users, and control subjects. Design: Cross-sectional study. Setting: Department of Physiology, Radboud University Medical Center. Participants: Long-term symptomatic and asymptomatic statin users, and control subjects (n = 10 per group). Interventions: Maximal incremental cycling tests, involuntary electrically stimulated isometric quadriceps-muscle contractions, and biopsy of vastus lateralis muscle. Main Outcomes Measured: Maximal exercise capacity, substrate use during exercise, muscle function, and mitochondrial energy metabolism. Results: Peak oxygen uptake, maximal work load, and ventilatory efficiency were comparable between groups, but both statin groups had a depressed anaerobic threshold compared with the control group (P = 0.01). Muscle relaxation time was prolonged in both statin groups compared with the control group and rate of maximal force rise was decreased (Ptime×group < 0.001 for both measures). Mitochondrial activity of complexes II and IV was lower in symptomatic statin users than control subjects and tended to be lower for complex (C) III (CII: P = 0.03; CIII: P = 0.05; CIV: P = 0.04). Mitochondrial content tended to be lower in both statin groups than in control subjects. Conclusion: Statin use attenuated substrate use during maximal exercise performance, induced muscle fatigue during repeated muscle contractions, and decreased muscle mitochondrial oxidative capacity. This suggests disturbances in mitochondrial oxidative capacity occur with statin use even in patients without statin-induced muscle complaints.
Context: Statin myopathy is linked to disturbances in mitochondrial function and exercise intolerance. Objectives: To determine whether differences exist in exercise performance, muscle function, and muscle mitochondrial oxidative capacity and content between symptomatic and asymptomatic statin users, and control subjects. Design: Cross-sectional study. Setting: Department of Physiology, Radboud University Medical Center. Participants: Long-term symptomatic and asymptomatic statin users, and control subjects (n = 10 per group). Interventions: Maximal incremental cycling tests, involuntary electrically stimulated isometric quadriceps-muscle contractions, and biopsy of vastus lateralis muscle. Main Outcomes Measured: Maximal exercise capacity, substrate use during exercise, muscle function, and mitochondrial energy metabolism. Results: Peak oxygen uptake, maximal work load, and ventilatory efficiency were comparable between groups, but both statin groups had a depressed anaerobic threshold compared with the control group (P = 0.01). Muscle relaxation time was prolonged in both statin groups compared with the control group and rate of maximal force rise was decreased (Ptime×group < 0.001 for both measures). Mitochondrial activity of complexes II and IV was lower in symptomatic statin users than control subjects and tended to be lower for complex (C) III (CII: P = 0.03; CIII: P = 0.05; CIV: P = 0.04). Mitochondrial content tended to be lower in both statin groups than in control subjects. Conclusion: Statin use attenuated substrate use during maximal exercise performance, induced muscle fatigue during repeated muscle contractions, and decreased muscle mitochondrial oxidative capacity. This suggests disturbances in mitochondrial oxidative capacity occur with statin use even in patients without statin-induced muscle complaints.
Authors: L Janssen; S J C M Frambach; N A E Allard; M T E Hopman; T J J Schirris; N C Voermans; R J Rodenburg; N M A Blijlevens; S Timmers Journal: Leukemia Date: 2019-03-14 Impact factor: 11.528
Authors: Vlad F Avram; Imen Chamkha; Eleonor Åsander-Frostner; Johannes K Ehinger; Romulus Z Timar; Magnus J Hansson; Danina M Muntean; Eskil Elmér Journal: Int J Mol Sci Date: 2021-01-03 Impact factor: 5.923
Authors: Jill M Slade; George S Abela; Mitchell Rozman; Robert J McClowry; David Hurley; Sean C Forbes; Ronald A Meyer Journal: Am Heart J Plus Date: 2021-06-24
Authors: Ben Henderson; Guilherme Lopes Batista; Carlo G Bertinetto; Joris Meurs; Dušan Materić; Coen C W G Bongers; Neeltje A E Allard; Thijs M H Eijsvogels; Rupert Holzinger; Frans J M Harren; Jeroen J Jansen; Maria T E Hopman; Simona M Cristescu Journal: Metabolites Date: 2021-03-24