Clinical trial NCT05474079: Exercise Training & Statins for Cardiovascular Health
Official title: The Effects of Supervised Exercise Training in the Primary Prevention of Cardiovascular Disease in Stain-Users and Non Statin-Users
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Risk Reduction
Cardiovascular Diseases
Lead sponsor: Cardiff Metropolitan University
Sponsor class: OTHER
Collaborators: name: Health and Care Research Wales
First posted: 2022-07-26
Enrollment: 80
Sex: ALL
Minimum age (years): 50
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Cardiovascular disease (CVD) refers to any condition that affects the heart and/or blood vessels (e.g. heart attack, stroke) and is the leading cause of death and disability worldwide. Regular exercise and statin therapy are widely recommended as frontline prevention strategies to reduce CVD risk. Recent changes to National Health Service (NHS) healthcare guidelines state that even individuals with a relatively low risk of CVD (≥10% risk score) should take a statin. When prescribed after a heart attack or stroke, both exercise and statins reduce the risk of a CVD-related death by \~25%, with some evidence to suggest that the combination of these therapies may offer additive cardiovascular protection. However, far less is known about the combined effects of exercise and statin therapy in primary CVD prevention (i.e. before a CVD event). Poor blood vessel function represents the earliest stage of CVD, which can be measured with ultrasound at different regions of the body (limbs, brain, heart) to sensitively detect early CVD risk. Regular exercise provides a variety of cardiovascular benefits and has a direct therapeutic effect on blood vessel function. In contrast, statin therapy primarily reduces CVD risk by lowering cholesterol, which may also improve blood vessel function. Although both therapies can separately reduce CVD risk, the interaction between exercise training and statin therapy on blood vessel function has never been directly compared in the setting of primary prevention, and it's currently unknown whether a combination of both therapies offers additional cardiovascular benefit. Therefore, the main aims of this study are to (i) investigate the effect of supervised exercise training on blood vessel function (limbs, brain, heart) in individuals with a CVD-risk score of ≥10% and (ii) examine whether these exercise effects differ in individuals taking a statin compared to those not taking a statin.

Detailed description: Over 340,000 people in Wales live with cardiovascular disease (CVD). It causes 28% of all annual deaths and costs the Welsh NHS £469 million per year (British Heart Foundation, 2019). Physical inactivity causes a third of all CVD cases and only 53% of Welsh adults currently meet the recommended minimum physical activity guidelines (Statistics for Wales, 2019). Accordingly, Wales is the most physically inactive nation in the UK with one of the highest rates of CVD. Regular exercise is widely recommended by GPs as a frontline prevention strategy to reduce CVD-risk. Similarly, statins are also routinely prescribed as part of primary healthcare across the UK to lower cholesterol levels and reduce CVD-risk. Recent changes to NHS primary healthcare guidelines state that even individuals with a relatively low risk of CVD (10-year CVD-risk score ≥10%; QRISK3) should take a statin. When prescribed after a heart attack or stroke, both exercise and statins reduce the risk of a CVD-related death by \~25%; some evidence suggests that the combination of these therapies may offer additive cardiovascular protection. However, far less is known about the combined effects of exercise and statin therapy in primary CVD prevention.

Sensitive ultrasound techniques can be used to examine vascular, cerebrovascular and cardiac structure and function to provide a comprehensive overview of cardiovascular health. Poor vascular function represents the earliest stage of CVD and is more sensitive at detecting CVD risk than traditional risk factors. Regular exercise provides a variety of cardiovascular benefits and has a direct therapeutic effect on vascular function. In contrast, statin therapy primarily reduces CVD-risk by lowering cholesterol, which may also improve vascular function. Although both therapies can separately reduce CVD risk, the interaction between exercise training and statin therapy on vascular function has never been directly compared in the setting of primary prevention; and it is currently unknown whether a combination of both therapies offers additional cardiovascular benefit.

This study will utilise a comprehensive series of cutting-edge vascular, cerebrovascular and cardiac ultrasound techniques to examine the effectiveness of exercise and statin therapy as primary CVD prevention strategies. If results demonstrate that exercise training provides similar cardiovascular benefits to statin therapy, and/or the combination of these preventive strategies offer additive benefit, this could have considerable implications on primary prevention healthcare recommendations.

Eligibility criteria: Inclusion Criteria:

Statin Users:

* Sedentary
* Non-smokers
* 50-65 years old
* A 10-year CVD-risk score \> 10% (estimated via QRISK3)
* Weight stable (\<5% weight change over the last 3 months)
* Prescription of an 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitor (statin) in stable dose for a minimum of 3 months and maximum of 3 years

Non-Statin Users:

* Sedentary
* Non-smokers
* 50-65 years old
* A 10-year CVD-risk score \> 10% (estimated via QRISK3)
* Weight stable (\<5% weight change over the last 3 months)

Exclusion Criteria (Statin Users and Non-Statin Users):

* History or signs/symptoms of established cardiovascular, metabolic, renal or musculoskeletal disease
* Diagnosed with familial hyperlipidaemia and/or diabetes mellitus
* Stage 2 hypertension (≥160/100 mmHg)
* Any contraindications to exercise (e.g. unstable angina, severe orthopaedic conditions) and/or advised by GP not to undertake exercise
* BMI \>40kg/m2
* Current smoker or within 6 months of cessation
* Use of any medication other than statins (e.g., fibrates, metformin, thiazolidinediones, orlistat, anti-hypertensives) that could independently alter lipid metabolism and/or vascular function
* Post-menopausal female and using hormone replacement therapy, or pre-menopausal using oral contraceptives that independently alter lipid metabolism and/or vascular function

Primary outcomes:
measure: Change in Flow Mediated Dilatation (FMD)
timeFrame: Pre and post intervention (12 weeks)
Secondary outcomes:
measure: Change in sublingual glyceryl trinitrate (GTN) induced dilatation
timeFrame: Pre and post intervention (12 weeks)
measure: Change in cold pressor induced dilatation
timeFrame: Pre and post intervention (12 weeks)
measure: Change in arterial stiffness
timeFrame: Pre and post intervention (12 weeks)
measure: Change in ultrasound assessment of cerebrovascular function- Assessment of cerebrovascular reactivity
timeFrame: Pre and post intervention (12 weeks)
measure: Change in ultrasound assessment of cerebrovascular function -Dynamic cerebral autoregulation
timeFrame: Pre and post intervention (12 weeks)
measure: Change in ultrasound assessment of cerebrovascular function - Cerebrovascular reactivity to an acute bout of exercise
timeFrame: Pre and post intervention (12 weeks)
measure: Change in ultrasound assessment of cerebrovascular function - Assessment of neurovascular coupling
timeFrame: Pre and post intervention (12 weeks)
measure: Change in Cognitive Function Assessment
timeFrame: Pre and post intervention (12 weeks)
measure: Change in blood lipid profile
timeFrame: Pre and post intervention (12 weeks)
measure: Change in blood glucose and insulin profile
timeFrame: Pre and post intervention (12 weeks)
measure: Changes in blood pro-inflammatory cytokines
timeFrame: Pre and post intervention (12 weeks)
Other outcomes:
measure: Change in 7-day physical activity monitoring: Intensity of activity
timeFrame: Pre and post intervention (12 weeks)
measure: Change in 7-day physical activity monitoring: Frequency of activity
timeFrame: Pre and post intervention (12 weeks)
measure: Change in 7-day physical activity monitoring: Duration of activity
timeFrame: Pre and post intervention (12 weeks)
measure: Change in 7-day physical activity monitoring: Frequency of sedentary periods
timeFrame: Pre and post intervention (12 weeks)
measure: Change in 7-day physical activity monitoring: Duration of sedentary periods
timeFrame: Pre and post intervention (12 weeks)
measure: Change in 24-hour ambulatory blood pressure
timeFrame: Pre and post intervention (12 weeks)
measure: Change in VO2peak cardiopulmonary max test
timeFrame: Pre and post intervention (12 weeks)
Locations:
city: Cardiff
country: United Kingdom
facility: Cardiff Metropolitan University
Study officials:
affiliation: Cardiff Metropolitan University
name: Chris Pugh
role: PRINCIPAL_INVESTIGATOR
References: