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The purpose of this study is to assess whether remote ischaemic conditioning, applied chronically, improves vascular health in older adults
Hypertension and stroke remain leading causes of mortality across the world (1). Hypertension affects more than 1 in 4 adults and is the 3rd biggest risk factor for premature death and disability in the UK (2). Cerebrovascular disease is ranked 4th in the list of leading causes of death in the UK (3). At present, the treatment of these conditions largely involves chronic pharmacotherapy. In parallel, it is increasingly appreciated that polypharmacy poses a significant challenge to our older adult population. Guthrie et al showed that the number of people prescribed >5 medications in an area of the UK doubled between 1995 and 2010 (from 11.4% to 20.8%) (4). Age is significantly associated with polypharmacy, with an odds ratio of 118.3 when those aged 20-29 are compared to those >80. What's more, it has been estimated that adverse drug reactions account for 6.5% of hospital admissions (5), with age correlating significantly with admissions for this reason. Therefore, discovering a non-pharmacological intervention for hypertension and cerebrovascular disease could greatly benefit the population, particularly the elderly, both in terms of treating the diseases themselves and reducing the harmful effects of polypharmacy.
Remote ischaemic preconditioning (RIPC) is the induction of non-lethal ischaemia in one organ or tissue, with the aim of conditioning a distant organ or tissue against ischaemic events. It is achieved via inflation of a blood pressure cuff to supra-systolic pressures for a short period of time. A recent meta-analysis showed that chronic RIC, but not acute RIC, significantly lowered diastolic and mean arterial blood pressure (6). The studies included in this review were small and performed in a younger population, hence larger studies are needed to clarify the effect of RIC in the field of hypertension and, importantly, the elderly.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Remote Ischaemic Preconditioning | Active Comparator | RIPC is induced by 4 cycles of 5 minutes of healthy upper limb ischaemia followed by 5 minutes reperfusion. Ischaemia is induced by inflation of a blood pressure cuff to 20mmHg above systolic blood pressure. RIPC is conducted 3 times weekly for 6-weeks. |
|
| Sham remote ischaemic preconditioning | Sham Comparator | Sham RIPC is induced by 4 cycles of 5 minutes of healthy upper limb ischaemia followed by 5 minutes reperfusion. Ischaemia is induced by inflation of a blood pressure cuff to 20mmHg. RIPC is conducted 3 times weekly for 6-weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Remote Ischaemic Preconditioning | Device | RIPC is induced by 4 cycles of 5 minutes of healthy upper limb ischaemia followed by 5 minutes reperfusion. Ischaemia is induced by inflation of a blood pressure cuff to 20mmHg above systolic blood pressure. RIPC is conducted 3 times weekly for 6-weeks. Clinic blood pressure is measured at weeks 0, 3 and 6. 24-hour blood pressure is measured at weeks 0 and 6. |
| Measure | Description | Time Frame |
|---|---|---|
| Clinic systolic blood pressure | Changes in blood pressure measured by automated sphygmomanometer over 6 weeks. Measured after participants have rested for 10 minutes in a temperature controlled room. | Measured at baseline, week 3 and week 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Clinic diastolic blood pressure | Changes in blood pressure measured by automated sphygmomanometer over 6 weeks. Measured after participants have rested for 10 minutes in a temperature controlled room. | Measured at baseline, week 3 and week 6 |
| Clinic Mean arterial pressure |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Timothy England, MB ChB PhD | University of Nottingham | Principal Investigator |
| Bethan Phillips, PhD | University of Nottingham | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| School of Medicine, Royal Derby Hospital Site, University of Nottingham | Derby | Derbyshire | DE22 3DT | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33501848 | Background | Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Cheng S, Delling FN, Elkind MSV, Evenson KR, Ferguson JF, Gupta DK, Khan SS, Kissela BM, Knutson KL, Lee CD, Lewis TT, Liu J, Loop MS, Lutsey PL, Ma J, Mackey J, Martin SS, Matchar DB, Mussolino ME, Navaneethan SD, Perak AM, Roth GA, Samad Z, Satou GM, Schroeder EB, Shah SH, Shay CM, Stokes A, VanWagner LB, Wang NY, Tsao CW; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association. Circulation. 2021 Feb 23;143(8):e254-e743. doi: 10.1161/CIR.0000000000000950. Epub 2021 Jan 27. | |
| Background | Health matters: combating high blood pressure: Public Health England; 2017 | ||
| Background | https://www.stroke.org.uk/what-is-stroke/stroke-statistics | ||
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
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Participants complete a 6-week intervention period during which the participants receive either RIPC or sham. There is then a 6-week washout period, after which participants complete the other intervention
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Participants are blinded to intervention. Assessors measuring outcomes are blinded to participant identity and intervention.
|
| Sham Remote Ischaemic Preconditioning | Device | Sham RIPC is induced by 4 cycles of 5 minutes of healthy upper limb ischaemia followed by 5 minutes reperfusion. Ischaemia is induced by inflation of a blood pressure cuff to 20mmHg. RIPC is conducted 3 times weekly for 6-weeks. Clinic blood pressure is measured at weeks 0, 3 and 6. 24-hour blood pressure is measured at weeks 0 and 6. |
|
Changes in blood pressure measured by automated sphygmomanometer over 6 weeks. Measured after participants have rested for 10 minutes in a temperature controlled room. |
| Measured at baseline, week 3 and week 6 |
| 24-hour systolic blood pressure | Changes in blood pressure measured by 24-hour blood pressure monitor. | Measured at baseline and week 6 |
| 24-hour diastolic blood pressure | Changes in blood pressure measured by 24-hour blood pressure monitor. | Measured at baseline and week 6 |
| 24-hour mean arterial pressure | Changes in blood pressure measured by 24-hour blood pressure monitor. | Measured at baseline and week 6 |
| Flow mediated dilatation (FMD) | Flow mediated dilatation is measured by continuous ultrasound imaging of the brachial artery. Brachial artery diameter is measured using edge tracking software for one minute before distal occlusion is applied to the brachial artery for 5 minutes at 230mmHg using and automated vascular assessment pressure cuff. Following release of the distal occlusion, flow mediated dilatation is measured for 4 minutes using edge tracking software | Measured at baseline, week 3 and week 6 |
| Pulsewave velocity (PWV) | Pulsewave velocity is measured using carotid and femoral artery transducers. Pulse transit time and the distance between transducers is then used to calculate PWV. | Measured at baseline, week 3 and week 6 |
| Serum biomarkers | Biomarkers of RIC mechanism will be quantified by ELISA from plasma samples collected before and after intervention. | Measured at baseline and week 6. |
| 25889849 |
| Background |
| Guthrie B, Makubate B, Hernandez-Santiago V, Dreischulte T. The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995-2010. BMC Med. 2015 Apr 7;13:74. doi: 10.1186/s12916-015-0322-7. |
| 15231615 | Background | Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, Farrar K, Park BK, Breckenridge AM. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ. 2004 Jul 3;329(7456):15-9. doi: 10.1136/bmj.329.7456.15. |
| 33748739 | Background | Baffour-Awuah B, Dieberg G, Pearson MJ, Smart NA. The effect of remote ischaemic conditioning on blood pressure response: A systematic review and meta-analysis. Int J Cardiol Hypertens. 2021 Feb 23;8:100081. doi: 10.1016/j.ijchy.2021.100081. eCollection 2021 Mar. |