Combined Effects of Statins and Exercise on Training Sensitive Health Markers

Summary

Around the world, about 4 in 10 adults have abnormal blood fat levels-known as dyslipidaemia-which raises their chances of getting heart disease. Many people with this condition are prescribed statins, medications that help lower the "bad" Low-density lipoprotein cholesterol (LDL-C) in the blood and, in doing so, help prevent serious heart-related problems. While statins do lower these harmful cholesterol levels, recent research suggests that statins might interfere with some of the positive effects that exercise typically has on muscle cells' energy centers (the mitochondria) and on a person's aerobic capacity. It is not yet fully understood how statins might influence these exercise benefits at the molecular level. To address this gap, the present study will look closely at how taking statins combined with a structured exercise program affects both the muscle cells and the whole-body fitness of people with dyslipidaemia. By using a wide-ranging protein analysis, the research aims to identify changes in muscle proteins and other metabolism-related factors that could explain why statins might alter the expected improvements from exercise.

Methods and Analysis In this 12-week study, we aim to enrol between 100 and 125 adults (aged 40-65 years, with dyslipidaemia without established heart disease); the trial is powered for the first 100, and recruitment will stay open up to 125 to offset potential drop-outs. Participants will be randomly split into one of four groups: (1) exercise plus a placebo (an inactive pill), (2) exercise plus a daily high-dose statin (atorvastatin, 80 mg), (3) a daily high-dose statin without exercise, or (4) a placebo without exercise. More participants will be placed in the exercise groups to better understand the combined effects of exercise and statins. The main measurement will be how well the muscle's mitochondria work, assessed by changes in an enzyme called citrate synthase (CS) from before the program to after. Other important measures will include overall fitness (using a peak oxygen uptake (VO2peak) test) and detailed protein analyses. The study will also look at genetic variations to see if they influence how each participant responds to the treatment.

Ethics and Sharing of Results The study has received approval from the Faroe Islands Ethical Committee (2024-10) and follows international guidelines to protect participants' rights and data. Once the research is complete, the findings will be shared in leading scientific journals for the broader public and medical community to learn from.

Conditions

• Dyslipidemias

Interventions

DRUG

Atorvastatin 80mg

Daily intake of 80 mg of the approved drug Atorvastatin. Starting at dose 40 mg with 40 mg weekly increment reaching the maintenance dosage of 80 mg on week two, which is the approved maximum dosage of Atorvastatin. Participants who don't tolerate this fast up-titration may have prolonged tritation protocol (up to four weeks). Under special circumstances, participants with intolerable side-effects may stay at a lower dose (40 mg/day). The dosage and applied up-tritation is based on recommendations from trained cardiologists at the National Hospital of the Faroe Islands.

BEHAVIORAL

Exercise

Exercise will be performed as aerobic interval training sessions on cycling ergometers lasting \~45 min, four times weekly for 12 weeks. All exercise sessions will be supervised. Participants will wear HR monitor system during all sessions (Polar Electro Oy, Kempele, Finland) and the Borg 6-to-20 scale will also be used to assess the rate of perceived exertion during exercise sessions. A 4-week ramp-up phase will be applied, consisting of two sessions in weeks 1 and 2, three sessions in weeks 3 and 4 after which participants will complete 4 sessions a week from weeks 5 to 12.

Sponsors & Collaborators

• University of Copenhagen

  collaborator OTHER

• Research council Faroe Islands

  collaborator UNKNOWN

• National Hospital of the Faroe Islands

  collaborator OTHER_GOV

• Betri Stuðul

  collaborator UNKNOWN

• University of the Faroe Islands

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

40 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-05-01

Primary Completion

2025-12-16

Completion

2026-01-30

Countries

• Faroe Islands

Study Locations