The Effect of Chronic Remote Ischaemic Preconditioning on Blood Pressure in Older Adults (RIPCo)

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.

Remote Ischaemic Preconditioning, Non-pharmacological, Remote Ischaemic Conditioning, Randomised Controlled Trial

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

Participants are blinded to intervention. Assessors measuring outcomes are blinded to participant identity and intervention.

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 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

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.

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.

Changes in blood pressure measured by automated sphygmomanometer over 6 weeks. Measured after participants have rested for 10 minutes in a temperature controlled room.

Changes in blood pressure measured by automated sphygmomanometer over 6 weeks. Measured after participants have rested for 10 minutes in a temperature controlled room.

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

Pulsewave velocity is measured using carotid and femoral artery transducers. Pulse transit time and the distance between transducers is then used to calculate PWV.

Biomarkers of RIC mechanism will be quantified by ELISA from plasma samples collected before and after intervention.

Inclusion Criteria: Participant is aged >65y and <85y. Participant is willing and able to give informed consent for participation in the study. Participant is physically able to perform RIPC. Exclusion Criteria: A BMI <18 or >35 kg/m2 Active cardiovascular, cerebrovascular or respiratory disease: e.g. uncontrolled hypertension (BP > 160/100), active angina, heart failure (class III/IV), arrhythmia, right to left cardiac shunt, recent cardiac event, COPD, pulmonary hypertension or recent (6 mo) stroke. If history of hypertension, no recent alteration to antihypertensive medication (3 months). A history of, or current neurological or musculoskeletal conditions (e.g. epilepsy) Having taken part in a research study in the last 3 months involving invasive procedures or an inconvenience allowance

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