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临床试验/NCT05474079
NCT05474079招募中不适用

The Effects of Supervised Exercise Training in the Primary Prevention of Cardiovascular Disease in Stain-Users and Non Statin-Users

Cardiff Metropolitan University1 个研究点 分布在 1 个国家目标入组 80 人开始时间: 2022年7月20日最近更新:
适应症
干预措施

试验速览

阶段
不适用
状态
招募中
入组人数
80
试验地点
1
主要终点
Change in Flow Mediated Dilatation (FMD)

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Prevention
盲法
Triple (Participant, Care Provider, Investigator)

入排标准

年龄范围
50 Years 至 65 Years(Adult, Older Adult)
性别
All
接受健康志愿者
是

入选标准

  • •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)

排除标准

  • •(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

研究组 & 干预措施

Statin users exercise intervention

Experimental

The exercise training program will consist of individually tailored, progressive moderate-intensity aerobic exercise. Exercise training will comprise of a combination of treadmill, cross-trainer and cycle ergometer-based exercise. Exercise will progressively increase in both intensity and duration throughout the course of the intervention. Participants will begin the intervention with 30 minutes of moderate-intensity aerobic exercise at 40% heart rate reserve (HRR) three times per week for the initial 4 weeks. From week 4, exercise intensity will increase to 50% HRR, and at week 6 the duration of each session will increase to 45 minutes. From week 8, participants will exercise at an intensity of 60% HRR for 45 minutes, and from week 10, this will increase to five sessions per week.

干预措施: Moderate intensity exercise training (Other)

Statin users conventional care control

No Intervention

Participants randomized to the conventional primary care control group will not receive any supervision or guidance throughout the 12-week intervention beyond the initial standard healthcare advice provided by their general practitioner (GP).

Non-statin users exercise intervention

Experimental

The exercise training program will consist of individually tailored, progressive moderate-intensity aerobic exercise. Exercise training will comprise of a combination of treadmill, cross-trainer and cycle ergometer-based exercise. Exercise will progressively increase in both intensity and duration throughout the course of the intervention. Participants will begin the intervention with 30 minutes of moderate-intensity aerobic exercise at 40% HRR three times per week for the initial 4 weeks. From week 4, exercise intensity will increase to 50% HRR, and at week 6 the duration of each session will increase to 45 minutes. From week 8, participants will exercise at an intensity of 60% HRR for 45 minutes, and from week 10, this will increase to five sessions per week.

干预措施: Moderate intensity exercise training (Other)

Non-statin users conventional care control

No Intervention

Participants randomized to the conventional primary care control group will not receive any supervision or guidance throughout the 12-week intervention beyond the initial standard healthcare advice provided by their GP.

结局指标

主要结局

Change in Flow Mediated Dilatation (FMD)

时间窗: Pre and post intervention (12 weeks)

Brachial artery FMD, as a non-invasive measure of endothelial nitric oxide function, will be assessed using high resolution Duplex vascular ultrasonography in accordance with published guidelines.

次要结局

  • Change in cold pressor induced dilatation(Pre and post intervention (12 weeks))
  • Change in sublingual glyceryl trinitrate (GTN) induced dilatation(Pre and post intervention (12 weeks))
  • Change in arterial stiffness(Pre and post intervention (12 weeks))
  • Change in ultrasound assessment of cerebrovascular function- Assessment of cerebrovascular reactivity(Pre and post intervention (12 weeks))
  • Change in ultrasound assessment of cerebrovascular function -Dynamic cerebral autoregulation(Pre and post intervention (12 weeks))
  • Change in ultrasound assessment of cerebrovascular function - Cerebrovascular reactivity to an acute bout of exercise(Pre and post intervention (12 weeks))
  • Change in ultrasound assessment of cerebrovascular function - Assessment of neurovascular coupling(Pre and post intervention (12 weeks))
  • Change in Cognitive Function Assessment(Pre and post intervention (12 weeks))
  • Change in blood lipid profile(Pre and post intervention (12 weeks))
  • Change in blood glucose and insulin profile(Pre and post intervention (12 weeks))
  • Changes in blood pro-inflammatory cytokines(Pre and post intervention (12 weeks))

研究者

申办方类型
Other
责任方
Sponsor

研究点 (1)

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