Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension (IRE-HT)

The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension: A Study of Randomized Controlled Trial

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 Clinic and Ambulatory BP (AMBP) in Hong Kong Chinese.

(ii) To evaluate the impact of IRE on atherogeneisis surrogates (brachial flow-mediated dilation, FMD and carotid intima-media thickness IMT).

(iii) To evaluate the impact of IRE on mechanisms of BP reduction, including endothelial function FMD, carotid IMT, inflammatory parameters and arterial wall stiffness (cfPWV).

Setting:

Randomized samples of 200 HT patients, aged 18-75 years 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 (yoga) 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. BP - Clinic BP and Ambulatory BP parameters at baseline, 12 weeks and 24 weeks. (primary outcome)
2. Brachial FMD and carotid IMT at baseline, 24 weeks and 1 year. (primary outcome)
3. Carotid-femoral pulse wave velocity (cf-PWV) at baseline and 24 weeks.
4. 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).
5. 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.

Study Overview

• Status: Recruiting
• Conditions: Atherosclerosis Cardiovascular Disease
• Intervention / Treatment: Other: Squatting Exercise; Other: Stretching (Yoga) Exercise

Detailed Description

1. Introduction

   Hypertension (HT) is the most common condition worldwide predisposing to atherosclerotic diseases (stroke, heart attack and peripheral vascular disease), apart from other traditional risk factors [1-3]. However, most HT patients have suboptimal BP control despite anti-HT medications [4]. On this issue, aerobic and dynamic exercise are effective in BP-reduction, but HT-patients often have poor compliance with exercise, mainly because of requirement of additional time, skill training, venue and equipments [5-6]. Isometric resistance exercised (IRE) (e.g. wall squat) may improve BP control, characterized by sustained muscle contractions with minimal change in muscle length and joint angle. However, most randomized trials of IRE have short duration and their long-term effect on BP-reduction, mechanisms and atherosclerosis complications, particularly in the Chinese, remain unknown [7-11].

   Much advance in noninvasive vessel-imaging has been witnessed in past few decades. Brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT), have been advocated as surrogate markers for the documentation of early atherosclerosis and evaluation of preventive measures (12-20). Both brachial FMD and carotid IMT can now be measured accurately with high reproducibility, and have been related to cardiovascular outcomes. In clinical context, a 0.1mm increase in carotid IMT has been associated with 41% increase in stroke and 43% increase in acute myocardial infarction over a follow-up period of 2-7 years. [17] An 8% difference in carotid IMT was approximately similar to the kind of difference seen between diabetes and non-diabetes Chinese adults [21).

2. Aims and Hypotheses to be Tested

   Systemic hypertension has been proven accelerating atherosclerotic process. To further test this initial hypothesis, this interventional substudy aims:

   (i) To evaluate the impact of IRE on Clinic and Ambulatory BP (AMBP) in Hong Kong.

   (ii) To evaluate the impact of IRE on atherosclerotic surrogates (brachial FMD and carotid IMT).

   (iii) To evaluate the impact of IRE on mechanisms of BP and atherogenesis reductions, including endothelial function FMD, carotid IMT and arterial wall stiffness (cfPWV), and inflammatory parameters.

3. Plan of Investigation The brachial FMD and carotid IMT before and after IRE intervention will be compared between the wall-squat and control intervention groups.

3.1 The impact of Isometric resistance exercise (IRE) Intervention on brachial FMD and carotid IMT.

Subjects:

200 HT adults, aged 18-75yr with SBP 135-160mmHg on AMBP will be recruited. Those with incapacitating osteoarthritis of knee and secondary HT will be excluded.

3.2 Methods: These HT participants will be randomized to practise IRE (100 adults) 14 mins per session, (2 mins IRE x 4sets, 2 mins rest in between), 3 sessions per week, or usual standard care & stretching (yoga) exercise (100 adults).

Week-0 ~ Health Examination, Randomization (IRE vs Yoga), Vascular Study (FMD & IMT), Blood Test, and Arterial wall stiffness (cfPWV)

Week-13 ~ Compliance (adhenence) checking

Week-24 ~ Health Examination, vascular study (FMD & IMT), blood tests, and arterial wall stiffness (cfPWV)

One Year ~ Compliance (adherence) checking, vascular study (FMD & IMT), vessel wall stiffness, and blood Tests

• Collection of health data:

  1. Questionnaire - All adult subjects will be interviewed and required to complete a detailed questionnaire regarding their individual and family history of cardiovascular diseases, hypertension, diabetes and current use of medications. Information on socio-economic status, tobacco use and lifestyle will be collected.
  2. Health examination - Each participant will receive a health examination and their weight and height, blood pressures, body mass index (BMI) and wait-hip circumference ratio (WHR) will be measured (light clothing and no shoes).
  3. Blood tests: 10ml of fasting blood will be taken for WBC platelet, fasting glucose, HgbA1C, low density lipoprotein cholesterol, hsC-reactive protein, fibrinogen and IL-6.
• Vascular Studies:

Endothelial function, flow-mediated dilation (FMD) of the brachial artery and carotid IMT will be studied by using high resolution ultrasound.

(i) Endothelial function, (brachial flow-mediated dilation, FMD) will be studied by using high resolution ultrasound, as described previously. [12,22-24] In brief, the diameter of the brachial artery will be measured on B-mode ultrasound images, using a linear array transducer (HF L38) with a median frequency of 13-6MHz and a standard Sonosite (MicroMaxx) system. Forearm tourniquet cuff placement will be applied to induce reactive hyperemia on deflation. Scans of brachial artery 10cm proximal to elbow will be acquired at rest, during reactive hyperemia (to induce flow-mediated endothelium-dependent dilation, FMD). FMD will be expressed as % of dilation from baseline vessel diameter normalized with vessel strain. Hyperemia is calculated as the % increase in blood flow after cuff deflation compared with baseline.

(ii) Carotid intima-media thickness (CIMT) measurement - B-mode ultrasound examinations will be performed using a 10-5 probe, with a 7.5 MHz scanning frequency linear array transducer. All carotid scans will be performed by a single operator after a predetermined, standardized scanning protocol for the right and left carotid arteries as described by Salonen and Salonen [16] and Touboul et al [19], using images of the far wall of the distal 10 mm of the common carotid arteries. All scans will be recorded on super-VHS videotape for subsequent off-line analysis for intima-media thickness (IMT), using a verified automatic edge-detecting and measurement software package as described previously. [19-24] The intra-observer variability of mean IMT is 0.003 to 0.011mm (CV 0.998%).

3.3 Outcomes

3.3.1 Primary outcomes: (i) Daytime ambulatory SBP and DBP (mean and BP variability) (mmHg) at baseline, 24 weeks and 1 year (ii) Vascular Parameters: Brachial FMD (%) and Carotid IMT (mm) at baseline, 24 weeks and 1 year.

3.3.2 Secondary outcomes: (i) Clinic BP and Ambulatory BP parameters (mmHg) at baseline, 24 weeks and 1 year.

(ii) Carotid femoral pulse wave velocity, cfPWV (mm/sec) at baseline and 24 weeks.

(iii) Other important traditional atherosclerosis risk factors: BMI (weight kg/ height m^2), glucose (mmol/l), lipid profiles (mmol/l), HgbA1-C (%), creatinine (umol/L), haemoglobin (g/dl), hsCRP (mg/l), Fibrinogen (mg/dl) and IL-6 (pg/ml) at baseline, 24 weeks and 1 year.

3.3.3 Safety profiles (if any) including CVS event and hospitalization at 1 year,

4. Compliance with Declaration of Helsinki. The design, methodology and conduction of project are in compliance with Declaration of Helsinki.

5. Data processing and analysis:

(5.1) Power Calculation: The Proc Power in the STS 9.2 statistical packages (SAS Institute Inc. Cary. NC, US) was used to calculate the sample size for FMD and carotid IMT. Data from our previous studies on Chinese adults in Hong Kong reported FMD was in 6-8% +/- 1.3%, and carotid IMT was 0.55-0.68mm +/- 0.1mm. On the assumption of post IRE brachial FMD will improve to 6.7-8.7 +/- 1.4%, and carotid IMT will reduce to 0.51-0.61mm +/- 0.11mm, recruitment of 200 Chinese adults (100 in each group) will be adequately powered (85%) to detect a group difference in brachial FMD of 1.2% and in carotid IMT of 0.06mm (12%), at 1 year between the two treatment groups.

(5.2). Data Analysis: Statistical Analysis System SPSS version 28 (SAS Institute Inc., Cary, NC, US) will be used for all statistical analyses. Descriptive methods will be used to describe characteristics of cardiovascular risks. The primary endpoints are AMBP, brachial FMD and carotid IMT; serological inflammatory biomarkers (Neutrophil/ monocyte ratio and Platelet), hsCRP, fibrinogen and IL-6 are secondary endpoints. Students' T-tests will be used to detect the group differences in brachial FMD and carotid IMT. Multivariable linear and logistic regressions will be used to calculate the risk magnitude by IRE vs usual care and stretching exercise interventions, and to control potential confounders such as traditional cardiovascular risk factors.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: KS Woo, MBBS, MD, FACC; Phone Number: +852 26474966; Email: kamsangwoo@cuhk.edu.hk

Study Locations

• Hong Kong
  • Shatin, Hong Kong
    • Recruiting
    • The Chinese University of Hong Kong, Department of Medicine & Therapeutics
    • Contact: Kam Sang Woo, MBBS, MD, FACC; Phone Number: +852 26474966; Email: kamsangwoo@cuhk.edu.hk
    • Contact: Daphne Chu; Email: daphne.chu@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. asymptomatic clinically stable adults
2. aged 18-75 years
3. Both genders
4. Suboptimal BP (on stable medication) with SBP 135-160mmHG on ambulatory BP monitoring (AMBP)
5. Agreeable to no drug changes in coming 1 year 24 weeks
6. Agreeable to provide informed written consent form
7. Agreeable to have AMBP and ultrasonic (FMD & IMT) scan third (baseline, 24 weeks and preferably 1 year)

Exclusion Criteria:

1. relative contraindications to AMBP (e.g. atrial fibrillation)
2. severe osteoarthritis of knee
3. known secondary HT
4. pregnancy/breastfeeding
5. active malignancy
6. Serious coronary profiles, (unstable angina), renal or hepatic derangement
7. Need to change medications for control BP at 24 weeks ( SBP>160 mmHg)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Anti HT + Isometric Resistance Squatting Exercise (100 Adults); A more linear thigh-leg squatting angle is allowed in initial 2 weeks, but aiming at 90 degree thigh-leg angle after 4 weeks.	Other: Squatting Exercise; 14 minutes per session (2 mins x 4 sets, 2 mins rest in between, 3 session per week)
Active Comparator: Anti HT + Stretching (Yoga) Exercise (100 Adults); A liberal leg stretching excerise will be practised	Other: Stretching (Yoga) Exercise; 2 mins x 4 sets, 2 mins rest in between, 3 sessions per week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	Changes in Daytime BP monitoring (mmHg)	Baseline, 24 weeks and 1 year
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	Changes in Brachial FMD (%)	Baseline, 24 weeks and 1 year
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	Changes in Carotid IMT (mm)	Baseline, 24 weeks and 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	Changes in Clinic BP and Ambulatory BP parameters (mmHg)	Baseline, 24 weeks and 1 year
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	Changes in Carotid femoral pulse wave velocity, cfPWV (mm/sec)	Baseline and 24 weeks
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	Other important traditional atherosclerosis risk factors: Changes in BMI (weight kg/ height m^2)	Baseline, 24 weeks and 1 year
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	Changes in Fasting Glucose (mmol/l)	Baseline, 24 weeks and 1 year
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	Changes in Fasting Lipid profiles (mmol/l); Changes in high density lipoprotein cholesterol (HDL-C) (mmol/l); Changes in low density lipoprotein cholesterol (LDL-C) (mmol/l); Changes in Triglyceride (TG) (mmol/l)	Baseline, 24 weeks and 1 year
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	HgbA1-C (%)	Baseline, 24 weeks and 1 year
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	Creatinine (umol/L)	Baseline, 24 weeks and 1 year
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	Haemoglobin (g/dl)	Baseline, 24 weeks and 1 year
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	hsCRP (mg/l)	Baseline, 24 weeks and 1 year
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	Fibrinogen (mg/dl)	Baseline, 24 weeks and 1 year
The Impact of Isometric Resistance Exercise on Accelerated Atherosclerosis in Hypertension	IL-6 (pg/ml)	Baseline, 24 weeks and 1 year

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Kam Sang Woo, Chinese University of Hong Kong

Publications and helpful links

General Publications

• Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992 Nov 7;340(8828):1111-5. doi: 10.1016/0140-6736(92)93147-f.
• Chow CK, Teo KK, Rangarajan S, Islam S, Gupta R, Avezum A, Bahonar A, Chifamba J, Dagenais G, Diaz R, Kazmi K, Lanas F, Wei L, Lopez-Jaramillo P, Fanghong L, Ismail NH, Puoane T, Rosengren A, Szuba A, Temizhan A, Wielgosz A, Yusuf R, Yusufali A, McKee M, Liu L, Mony P, Yusuf S; PURE (Prospective Urban Rural Epidemiology) Study investigators. Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. JAMA. 2013 Sep 4;310(9):959-68. doi: 10.1001/jama.2013.184182.
• Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2002 Apr 2;136(7):493-503. doi: 10.7326/0003-4819-136-7-200204020-00006.
• Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation. 1997 Sep 2;96(5):1432-7. doi: 10.1161/01.cir.96.5.1432.
• Herrington DM, Fan L, Drum M, Riley WA, Pusser BE, Crouse JR, Burke GL, McBurnie MA, Morgan TM, Espeland MA. Brachial flow-mediated vasodilator responses in population-based research: methods, reproducibility and effects of age, gender and baseline diameter. J Cardiovasc Risk. 2001 Oct;8(5):319-28. doi: 10.1177/174182670100800512.
• Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO, Vita JA. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol. 2003 May 21;41(10):1769-75. doi: 10.1016/s0735-1097(03)00333-4.
• Brook RD, Rajagopalan S, Pope CA 3rd, Brook JR, Bhatnagar A, Diez-Roux AV, Holguin F, Hong Y, Luepker RV, Mittleman MA, Peters A, Siscovick D, Smith SC Jr, Whitsel L, Kaufman JD; American Heart Association Council on Epidemiology and Prevention, Council on the Kidney in Cardiovascular Disease, and Council on Nutrition, Physical Activity and Metabolism. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation. 2010 Jun 1;121(21):2331-78. doi: 10.1161/CIR.0b013e3181dbece1. Epub 2010 May 10.
• Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Desvarieux M, Ebrahim S, Fatar M, Hernandez Hernandez R, Kownator S, Prati P, Rundek T, Taylor A, Bornstein N, Csiba L, Vicaut E, Woo KS, Zannad F; Advisory Board of the 3rd Watching the Risk Symposium 2004, 13th European Stroke Conference. Mannheim intima-media thickness consensus. Cerebrovasc Dis. 2004;18(4):346-9. doi: 10.1159/000081812. Epub 2004 Nov 2.
• Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation. 2007 Jan 30;115(4):459-67. doi: 10.1161/CIRCULATIONAHA.106.628875. Epub 2007 Jan 22.
• Neunteufl T, Heher S, Katzenschlager R, Wolfl G, Kostner K, Maurer G, Weidinger F. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol. 2000 Jul 15;86(2):207-10. doi: 10.1016/s0002-9149(00)00857-2. No abstract available.
• O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med. 1999 Jan 7;340(1):14-22. doi: 10.1056/NEJM199901073400103.
• Woo KS, Chook P, Raitakari OT, McQuillan B, Feng JZ, Celermajer DS. Westernization of Chinese adults and increased subclinical atherosclerosis. Arterioscler Thromb Vasc Biol. 1999 Oct;19(10):2487-93. doi: 10.1161/01.atv.19.10.2487.
• Moncion K, Biasin L, Jagroop D, Bayley M, Danells C, Mansfield A, Salbach NM, Inness E, Tang A. Barriers and Facilitators to Aerobic Exercise Implementation in Stroke Rehabilitation: A Scoping Review. J Neurol Phys Ther. 2020 Jul;44(3):179-187. doi: 10.1097/NPT.0000000000000318.
• Smart NA, Way D, Carlson D, Millar P, McGowan C, Swaine I, Baross A, Howden R, Ritti-Dias R, Wiles J, Cornelissen V, Gordon B, Taylor R, Bleile B. Effects of isometric resistance training on resting blood pressure: individual participant data meta-analysis. J Hypertens. 2019 Oct;37(10):1927-1938. doi: 10.1097/HJH.0000000000002105.
• Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, Alexander L, Estep K, Hassen Abate K, Akinyemiju TF, Ali R, Alvis-Guzman N, Azzopardi P, Banerjee A, Barnighausen T, Basu A, Bekele T, Bennett DA, Biadgilign S, Catala-Lopez F, Feigin VL, Fernandes JC, Fischer F, Gebru AA, Gona P, Gupta R, Hankey GJ, Jonas JB, Judd SE, Khang YH, Khosravi A, Kim YJ, Kimokoti RW, Kokubo Y, Kolte D, Lopez A, Lotufo PA, Malekzadeh R, Melaku YA, Mensah GA, Misganaw A, Mokdad AH, Moran AE, Nawaz H, Neal B, Ngalesoni FN, Ohkubo T, Pourmalek F, Rafay A, Rai RK, Rojas-Rueda D, Sampson UK, Santos IS, Sawhney M, Schutte AE, Sepanlou SG, Shifa GT, Shiue I, Tedla BA, Thrift AG, Tonelli M, Truelsen T, Tsilimparis N, Ukwaja KN, Uthman OA, Vasankari T, Venketasubramanian N, Vlassov VV, Vos T, Westerman R, Yan LL, Yano Y, Yonemoto N, Zaki ME, Murray CJ. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015. JAMA. 2017 Jan 10;317(2):165-182. doi: 10.1001/jama.2016.19043.
• Lee EKP, Poon P, Yip BHK, Bo Y, Zhu MT, Yu CP, Ngai ACH, Wong MCS, Wong SYS. Global Burden, Regional Differences, Trends, and Health Consequences of Medication Nonadherence for Hypertension During 2010 to 2020: A Meta-Analysis Involving 27 Million Patients. J Am Heart Assoc. 2022 Sep 6;11(17):e026582. doi: 10.1161/JAHA.122.026582. Epub 2022 Sep 3.
• Smart NA, Gow J, Bleile B, Van der Touw T, Pearson MJ. An evidence-based analysis of managing hypertension with isometric resistance exercise-are the guidelines current? Hypertens Res. 2020 Apr;43(4):249-254. doi: 10.1038/s41440-019-0360-1. Epub 2019 Nov 22.
• Hansford HJ, Parmenter BJ, McLeod KA, Wewege MA, Smart NA, Schutte AE, Jones MD. The effectiveness and safety of isometric resistance training for adults with high blood pressure: a systematic review and meta-analysis. Hypertens Res. 2021 Nov;44(11):1373-1384. doi: 10.1038/s41440-021-00720-3. Epub 2021 Aug 12.
• Loaiza-Betancur AF, Chulvi-Medrano I. Is Low-Intensity Isometric Handgrip Exercise an Efficient Alternative in Lifestyle Blood Pressure Management? A Systematic Review. Sports Health. 2020 Sep/Oct;12(5):470-477. doi: 10.1177/1941738120943882. Epub 2020 Aug 10.
• Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb. 1991 Sep-Oct;11(5):1245-9. doi: 10.1161/01.atv.11.5.1245.
• Thomas GN, Chook P, Qiao M, Huang XS, Leong HC, Celermajer DS, Woo KS. Deleterious impact of "high normal" glucose levels and other metabolic syndrome components on arterial endothelial function and intima-media thickness in apparently healthy Chinese subjects: the CATHAY study. Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):739-43. doi: 10.1161/01.ATV.0000118015.26978.07. Epub 2004 Jan 22.
• Woo KS, Robinson JT, Chook P, Adams MR, Yip G, Mai ZJ, Lam CW, Sorensen KE, Deanfield JE, Celermajer DS. Differences in the effect of cigarette smoking on endothelial function in chinese and white adults. Ann Intern Med. 1997 Sep 1;127(5):372-5. doi: 10.7326/0003-4819-127-5-199709010-00006.
• (24) Woo KS, Chook P, Hu YJ, Wong MK, Yin YH, Li Albert Martin, Chan SW, Kwok CY Timothy and Celermajer DS. Age and Gender Specific Reference Values of Brachial Flow-mediated Dilation and Carotid Intima-media Thickness in CATHAY Study: Atherosclerosis Surrogate Markers in Chinese Adults. J Cardio and Vasc Med 2023;9:103.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: September 17, 2025
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Atherosclerosis; Essential Hypertension; Atherosclerosis Prevention; Carotid IMT; Isometric Resistance Exercise; Brachial FMD
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Hypertension; Essential Hypertension; Atherosclerosis; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Mind-Body Therapies; Complementary Therapies; Spiritual Therapies; Exercise Movement Techniques; Physical Therapy Modalities; Exercise; Yoga
• Other Study ID Numbers: 2022-618-T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: There is a plan to make IPD and related data dictionaries available. All IPD that underline results in a publication.
• IPD Sharing Time Frame: These materials will be available and shared on reasonable requests to Prof KS Woo from January 2025 till July 2027
• IPD Sharing Access Criteria: These materials will be available and shared on reasonable requests to Prof KS Woo from January 2025 till July 2027 (kamsangwoo@cuhk.edu.hk/ crec@cuhk.edu.hk)
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No