Acute Passive Heating in Healthy Older Adults

The Time Course of Cardiovascular Function, Cognitive Function and Heat Shock Proteins in Response to Acute Passive Heating in Older Adults

Aging is associated with a decline in cardiovascular health, cognitive function and losses in muscle strength, with half or more of those over age 65 suffering from two or more comorbidities (e.g., heart disease, type 2 diabetes). The worldwide population of older adults is growing rapidly, with one in six people expected to be over age 65 by 2050. This will place further financial burden from chronic diseases on already stressed healthcare systems. While studies show that frequent exercise is an effective way for older adults to maintain or improve cardiovascular and metabolic health, older individuals are less physically active and do not adhere well to exercise programs, often due to physical or medical limitations. Therefore, alternative methods for older adults to get the same health benefits as exercise require further exploration. Recent work has shown a single session of passive heat therapy could be an alternative way to improve cardiovascular health and cognitive function in various populations, however, the length of time that these benefits last is yet to be explored.

Study Overview

• Status: Completed
• Conditions: Aging
• Intervention / Treatment: Other: Passive heating

Detailed Description

Aging is associated with declines in cardiovascular health and cognitive function as well as chronic inflammation and the development of neurodegenerative conditions such as Alzheimer's and Parkinson's disease. Additionally, ageing results in a loss of muscle size and strength, commonly referred to as sarcopenia, leading to increased risk of falls or adverse exercise-related events. It is well understood that frequent exercise improves cardiovascular and metabolic health whilst lowering the risk of disease and all-cause mortality, acting as a treatment for many different health conditions. Despite the evidence of its efficacy, many individuals struggle with adherence to exercise programmes, particularly older adults and clinical populations, with many individuals within these populations unable to perform exercise due to physical limitations or medical contraindications. With one in six people expected to be over the age of 65 years by 2050 and corresponding increases in non-communicable diseases (e.g., cancer, diabetes, cardiovascular disease) anticipated from this aging population, the development of adjunct treatments or alternatives to exercise to improve general health in older populations is needed.

Recent work has shown one such potential solution could be the use of passive heat therapy (PHT) (e.g., hot water immersion, sauna), which can achieve health benefits comparable to exercise. Acute PHT induces vascular improvements including increased blood flow, reduced blood pressure. and macro- and microvascular dilator function in various populations. Acute PHT has also been shown to increase reaction time, while mixed results have been seen in its effect on executive function in both young and older populations. The mechanisms for these improvements, however, are currently unclear, and may be related to increases in nitric oxide activity or reductions in biomarkers of inflammation.

One potential mechanism for the physiological benefits obtained from PHT is the increase of cytoprotective heat shock proteins (HSP) (specifically HSP27, HSP60, HSP70 and HSP90) intracellularly (i) and extracellularly (e) in response to increases in deep body temperature. Increases in the expression of these HSPs have been shown to play a role in reducing inflammation and protecting the vasculature via increases in endothelial nitric oxide synthase activity. Increased HSP concentrations may also prevent the accumulation of harmful biomarkers in the brain that play a role in cognitive decline and development of neurodegenerative diseases. There is also evidence that increased preoperative levels of both iHSP70 and eHSP70 are correlated with improved postoperative outcomes following cardiac surgery. Aging, however, is associated with a reduction in HSP transcription activity in various tissues, resulting in an impaired heat shock response and development of a pro-inflammatory state.

Previous work using acute hot water immersion has shown mixed results, with various studies showing increases in eHSP70, iHSP70 and iHSP90, while others have reported no change in expression. Heating stimuli applied in these studies has varied in magnitude, duration and whole body or not, and measurements of HSPs have taken place at various time points before, during and after PHT. Therefore, it is possible that upregulation of HSPs may have been missed, as no time course relationship exists between a single bout of PHT and upregulation of HSPs. Additionally, the duration for acute vascular and cognitive benefits from PHT and when function is returned to baseline is yet to be determined. A time course relationship study to determine the peak HSP response to acute passive heat therapy in older adults would provide insight into the relationship between acute changes in vascular or cognitive function and concurrent upregulation of both intracellular and extracellular HSPs, as well as its potential implications for improved surgical outcomes.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Hampshire
    • Portsmouth, Hampshire, United Kingdom, PO4 0SU
      • Spinnaker Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 51 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female age ≥ 55
• Free from cardiometabolic disease
• Body mass index of 18-35 kg/m2
• Receipt of a normal 12-lead ECG approved by the School Independent Medical Officer
• Capacity to understand and provide their written, informed consent to participate in the study protocol

Exclusion Criteria:

• Unable to understand or cooperate with the study protocol due to learning difficulties or otherwise
• Any current, or past medical (last five years), history of any cardiovascular, respiratory, cancer, renal, hepatic, gastrointestinal, haematological, lymphatic, neurological, psychiatric, or any other disease or diseases.
• Any regular medication for the last five years (not including acute courses of treatment of less than one month for discrete, resolved conditions).
• Medications that may influence physiological responses to the passive heating intervention Uncontrolled hypertension (≥ 150 mmHg systolic and/or ≥ 90 mmHg diastolic)
• Body mass index of > 35 kg/m2
• Recent long-term exposure to a hot climate (within the previous three months)
• Current smoker (or have stopped smoking within the previous three months)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Passive heating intervention; 1 h hot water immersion (to the clavicle, @40°C, rectal temperature ~38.5°C and <39°C)	Other: Passive heating; 1 h hot water immersion (to the clavicle, @40°C, rectal temperature ~38.5°C and <39°C)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brachial artery flow-mediated dilation	Percentage change in brachial artery diameter and return to baseline as assessed by ultrasound.	Pre hot water immersion, then 1 hour, 3 hours, 24 hours and 48 hours post

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microvascular function	Change in microvascular function and return to baseline as assessed via iontophoresis on the forearm with acetylcholine (Ach) and Insulin, Area under the curve is the unit.	Pre hot water immersion, then 1 hour, 3 hours, 24 hours and 48 hours post
Stroke volume	Change in stroke volume and return to baseline measured noninvasively via thoracic impedance. mL/m^2 is the unit	Pre hot water immersion, then 1 hour, 3 hours, 24 hours and 48 hours post
Total peripheral resistance	Change in total peripheral resistance and return to baseline measured noninvasively via thoracic impedance	Pre hot water immersion, then 1 hour, 3 hours, 24 hours and 48 hours post
Cardiac output	Change in cardiac output and return to baseline measured noninvasively via thoracic impedance. L/min is the unit.	Pre hot water immersion, then 1 hour, 3 hours, 24 hours and 48 hours post
Intracellular HSP27 concentration	Change in iHSP27 concentration and return to baseline. Measured via immunoblotting in peripheral blood mononuclear cells (PBMCs).	Pre hot water immersion, then immediately post, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours and 48 hours post
Intracellular HSP60 concentration	Change in iHSP60 concentration and return to baseline. Measured via immunoblotting in peripheral blood mononuclear cells (PBMCs).	Pre hot water immersion, then immediately post, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours and 48 hours post
Intracellular HSP70 concentration	Change in iHSP70 concentration and return to baseline. Measured via immunoblotting in peripheral blood mononuclear cells (PBMCs).	Pre hot water immersion, then immediately post, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours and 48 hours post
Intracellular HSP90 concentration	Change in iHSP90 concentration and return to baseline. Measured via immunoblotting in peripheral blood mononuclear cells (PBMCs).	Pre hot water immersion, then immediately post, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours and 48 hours post
Plasma eHSP27 concentration	Change in plasma eHSP27 concentration and return to baseline. Measured via ELISA.	Pre hot water immersion, then immediately post, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours and 48 hours post
Plasma eHSP60 concentration	Change in plasma eHSP60 concentration and return to baseline. Measured via ELISA.	Pre hot water immersion, then immediately post, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours and 48 hours post
Plasma eHSP70 concentration	Change in plasma eHSP70 concentration and return to baseline. Measured via ELISA.	Pre hot water immersion, then immediately post, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours and 48 hours post
Plasma eHSP90 concentration	Change in plasma eHSP90 concentration and return to baseline. Measured via ELISA.	Pre hot water immersion, then immediately post, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours and 48 hours post
Reaction time	Change in reaction time and return to baseline as assessed using ANAM: Automated Neurophysiological Assessment Metrics.	Pre hot water immersion, then immediately post, 3 hours, 24 hours and 48 hours post
Logical reasoning	Change in logical reasoning and return to baseline as assessed using ANAM: Automated Neurophysiological Assessment Metrics.	Pre hot water immersion, then immediately post, 3 hours, 24 hours and 48 hours post
Memory	Change in memory function and return to baseline as assessed using ANAM: Automated Neurophysiological Assessment Metrics.	Pre hot water immersion, then immediately post, 3 hours, 24 hours and 48 hours post
Cerebral oxygenation	Change in cerebral oxygenation and return to baseline. Assessed using Near-infrared spectroscopy (NIRS) attached to the forehead	Pre hot water immersion, then immediately post, 3 hours, 24 hours and 48 hours post
Brachial and carotid artery blood flow velocity	Change from baseline in blood flow velocity of the brachial artery and right common carotid artery as assessed via ultrasound. cm/s is the unit.	Pre hot water immersion, then 1 hour, 3 hours, 24 hours and 48 hours post
Carotid vessel diameter	Change in vessel diameter of the right common carotid artery and return to baseline as assessed via ultrasound. mm is the unit.	Pre hot water immersion, then 1 hour, 3 hours, 24 hours and 48 hours post
Carotid intima-media thickness	Change in intima-media thickness of the right common carotid artery and return to baseline as assessed via ultrasound. mm is the unit.	Pre hot water immersion, then 1 hour, 3 hours, 24 hours and 48 hours post
Carotid compliance	Change in compliance of the right common carotid artery and return to baseline as assessed via ultrasound. µm^2 per kilopascal is the unit.	Pre hot water immersion, then 1 hour, 3 hours, 24 hours and 48 hours post
Carotid distensibility	Change in distensibility of the right common carotid artery and return to baseline as assessed via ultrasound. 10^-3/kPa is the unit.	Pre hot water immersion, then 1 hour, 3 hours, 24 hours and 48 hours post
Carotid stiffness	Change in stiffness of the right common carotid artery and return to baseline as assessed via ultrasound. Meters per second is the unit.	Pre hot water immersion, then 1 hour, 3 hours, 24 hours and 48 hours post

Collaborators and Investigators

• Sponsor: University of Portsmouth

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2023
• Primary Completion (Actual): July 24, 2025
• Study Completion (Actual): July 24, 2025

Study Registration Dates

• First Submitted: November 8, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 21, 2022

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Endothelial function; Cognitive function; Passive heating; Heat shock proteins
• Other Study ID Numbers: UoPAPHHOA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data will be anonymized and raw data uploaded to the University of Portsmouth repository.
• IPD Sharing Time Frame: After data has been collected and analyzed it will be available indefinitely.
• IPD Sharing Access Criteria: Available to public at repository website
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No