Atherosclerosis Clinical Trials

Background: Hypertension (HT) is the most common condition worldwide, predisposing to atherosclerotic disease. However, most HT patients have suboptimal BP control despite anti-HT medications. Isometric resistance exercise (IRE) (e.g. wall squat) may improve BP control, characterized by sustained muscle contraction with minimal change in muscle length and joint angle. Most randomized trials of IRE are short duration and their long-term effects on BP and atherosclerotic complications, particularly in the Chinese, remain unknown. Study objectives: (i) To evaluate the impact of IRE on atherogenesis surrogates (brachial flow-mediated dilation, FMD and carotid intima-media thickness IMT). (ii) To evaluate the impact of IRE on mechanisms of atherogenesis improvement, inflammatory parameters, arterial wall stiffness (cfPWV) and biochemical profiles. Setting: Randomized samples of 200 HT patients, aged \>18years with systolic BP 135-160mHg while on no or stable anti-HT medications.

Design: Randomized controlled IRE trial - stratified randomization with randomization block size of 4. 1. 100 patients for wall squat exercise of 14 mins each session (2 mins IRE x 4 sets, 2 mins rest in between), 3 sessions per week, for 1 year, plus advice on healthy diet and lifestyle. 2. 100 control patients (usual care) with advice on diet and healthy lifestyles and simple stretching exercise programme for 1 year. All patients will be invited to continue their exercise programme and return for follow up FMD and carotid IMT at 24 weeks and 1 year, and PWV at 24 weeks. Main outcome measures: 1. Brachial FMD and carotid IMT at baseline, 24 weeks and 1 year. (primary outcome) 2. Carotid-femoral pulse wave velocity (cf-PWV) at baseline and 24 weeks. (secondary outcome) 3. Important atherosclerosis risk factor parameters at baseline, 24 weeks and 1 year - including fasting serum glucose, lipid profiles, HgbA1-C, creatinine, hs-CRP, CBP, fibrinogen, and interleukin 6 (IL-6). (secondary outcome) 4. Safety profiles (if any) including CVS event and hospitalization at 1 year. Expected results: IRE Intervention versus control group, (i) 3mHg more reduction in SBP (Clinic and AMBP). (ii) A group absolute difference in FMD of 1%, and in carotid IMT of 0.06mm between the 2 treatment groups. Implications: IRE as suggested will be beneficial to management of HT, and will be of great importance in health care of this common disorder in both primary and secondary preventions of atherosclerosis diseases.