Moderate Intensity Exercise Training Improves Skeletal Muscle Performance in Symptomatic and Asymptomatic Statin Users

J Am Coll Cardiol. 2021 Nov 23;78(21):2023-2037. doi: 10.1016/j.jacc.2021.08.075.


Background: The combination of statin therapy and physical activity reduces cardiovascular disease risk in patients with hyperlipidemia more than either treatment alone. However, mitochondrial dysfunction associated with statin treatment could attenuate training adaptations.

Objectives: This study determined whether moderate intensity exercise training improved muscle and exercise performance, muscle mitochondrial function, and fiber capillarization in symptomatic and asymptomatic statin users.

Methods: Symptomatic (n = 16; age 64 ± 4 years) and asymptomatic statin users (n = 16; age 64 ± 4 years) and nonstatin using control subjects (n = 20; age 63 ± 5 years) completed a 12-week endurance and resistance exercise training program. Maximal exercise performance (peak oxygen consumption), muscle performance and muscle symptoms were determined before and after training. Muscle biopsies were collected to assess citrate synthase activity, adenosine triphosphate (ATP) production capacity, muscle fiber type distribution, fiber size, and capillarization.

Results: Type I muscle fibers were less prevalent in symptomatic statin users than control subjects at baseline (P = 0.06). Exercise training improved muscle strength (P < 0.001), resistance to fatigue (P = 0.01), and muscle fiber capillarization (P < 0.01), with no differences between groups. Exercise training improved citrate synthase activity in the total group (P < 0.01), with asymptomatic statin users showing less improvement than control subjects (P = 0.02). Peak oxygen consumption, ATP production capacity, fiber size, and muscle symptoms remained unchanged in all groups following training. Quality-of-life scores improved only in symptomatic statin users following exercise training (P < 0.01).

Conclusions: A moderate intensity endurance and resistance exercise training program improves muscle performance, capillarization, and mitochondrial content in both asymptomatic and symptomatic statin users without exacerbating muscle complaints. Exercise training may even increase quality of life in symptomatic statin users. (The Effects of Cholesterol-Lowering Medication on Exercise Performance [STATEX]; NL5972/NTR6346).

Keywords: combined exercise training; exercise performance; mitochondrial dysfunction; muscle fiber type distribution; statin-associated muscle symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Endurance Training / methods
  • Exercise / physiology*
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Male
  • Middle Aged
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / physiology*
  • Muscular Diseases / chemically induced
  • Muscular Diseases / metabolism
  • Muscular Diseases / therapy*
  • Resistance Training / methods


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors

Associated data

  • NTR/NTR6346