Autonomic Regulation of Blood Pressure and Heart Rate During Orthostasis and Exercise in Healthy and Hypertensive Individuals

Assessment of Autonomic Regulation of Blood Pressure and Heart Rate in Healthy and Hypertensive Individuals During Orthostasis and Physical Exercise

The goal of this observational study is to assess arterial stiffness and autonomic regulation of blood pressure and heart rate in healthy adults and people with arterial hypertension during orthostatic stress and graded physical exercise. The main objective is to analyze cardiovascular responses to exercise on a cycle ergometer in different subgroups of participants with hypertension.

The study includes healthy young adults and older adults with hypertension. Participants undergo standardized assessments including orthostatic testing, graded exercise testing on a cycle ergometer, electrocardiography, and measurement of arterial stiffness parameters such as pulse wave velocity, as well as other vascular and hemodynamic parameters.

The results of this study are expected to improve understanding of cardiovascular physiology and autonomic regulation in people with hypertension and may contribute to earlier recognition of autonomic dysfunction and improved clinical management.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Orthostatic Hypotension; Autonomic Dysfunction

Detailed Description

The autonomic nervous system plays an important role in the regulation of cardiovascular responses to orthostatic stress and physical exercise. Alterations in autonomic regulation may contribute to abnormal blood pressure responses, orthostatic hypotension, or exaggerated blood pressure responses during exercise, particularly in individuals with arterial hypertension.

The aim of this study is to assess arterial stiffness and autonomic regulation of blood pressure and heart rate in healthy individuals and people with arterial hypertension. The study includes healthy young adults and older adults with hypertension who are followed at the Department of Hypertension. Older participants are further categorized into subgroups including hypertension, hypertension with orthostatic hypotension, hypertension with orthostatic hypertension, and hypertension with diabetes mellitus.

All participants undergo standardized cardiovascular evaluation including orthostatic testing, graded exercise testing on a cycle ergometer, electrocardiography, and measurement of arterial stiffness parameters such as pulse wave velocity. During these procedures, blood pressure responses, heart rate variability, and heart rate recovery after exercise are assessed. Additional vascular and hemodynamic parameters are also recorded.

Additional clinical data, including laboratory test results and ambulatory blood pressure monitoring (ABPM) obtained as part of routine outpatient care prior to study participation, are collected from medical records for participants with hypertension with their written informed consent.

The study aims to improve understanding of cardiovascular autonomic regulation and vascular function in both healthy individuals and people with hypertension and related conditions.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Amela Kabaklić, MD, PhD; Phone Number: +386 1 522 43 05; Email: amela.kabaklic@kclj.si

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Recruiting
    • University Medical Centre Ljubljana
    • Contact: Amela Kabaklić, MD, PhD; Phone Number: +386 1 522 43 05; Email: amela.kabaklic@kclj.si
    • Sub-Investigator: Timur Mušić, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population includes healthy young adults and older adults with arterial hypertension who are followed at the Department of Hypertension, University Medical Centre Ljubljana. Participants with hypertension are categorized into subgroups including hypertension without orthostatic blood pressure abnormalities, hypertension with orthostatic hypotension, hypertension with orthostatic hypertension, and hypertension with diabetes.

Description

Inclusion Criteria:

• Healthy volunteers aged 18-35 years without known acute or chronic disease, non-smokers, body mass index (BMI) 20-24.9 kg/m², and negative orthostatic test
• Participants aged ≥60 years with arterial hypertension followed at the Department of Hypertension
• Hypertension group: controlled arterial hypertension, negative orthostatic test, without diabetes mellitus
• Hypertension with orthostatic hypotension group: controlled arterial hypertension and positive orthostatic test indicating orthostatic hypotension
• Hypertension with orthostatic hypertension group: controlled arterial hypertension and positive orthostatic test indicating a rise in blood pressure during orthostatic testing
• Hypertension with diabetes mellitus group: controlled arterial hypertension and diabetes mellitus without previously diagnosed autonomic dysfunction
• Ability to provide written informed consent

Exclusion Criteria:

• Dementia, neurodegenerative disease, or cognitive impairment preventing understanding of study procedures
• Known cardiovascular disease including heart failure (NYHA II-IV), myocardial infarction within the previous 6 months, clinically significant arrhythmias, or peripheral arterial occlusive disease
• Uncontrolled arterial hypertension
• Change in antihypertensive therapy within the previous 4 weeks
• Presence of a cardiac pacemaker
• Treatment with antiarrhythmic drugs (class I, III, or IV), digoxin, alpha-receptor blockers, or other medications known to significantly affect heart rate variability or autonomic function
• Advanced renal failure (eGFR <30 mL/min/1.73 m²) or advanced liver failure
• Active malignancy
• Body mass index ≥35 kg/m²
• Acute illness within the previous 4 weeks
• Current smoking
• Inability to safely perform exercise testing on a cycle ergometer
• Severe psychiatric disorders without stable treatment
• Pregnancy or breastfeeding
• Participation in another clinical study
• Refusal or inability to provide written informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
Healthy Young Adults; Healthy volunteers aged 18-35 years without known cardiovascular disease.
Hypertension; Participants with arterial hypertension without orthostatic blood pressure abnormalities during orthostatic testing and without diabetes.
Hypertension With Orthostatic Hypotension; Participants with arterial hypertension and orthostatic hypotension identified during orthostatic testing.
Hypertension With Diabetes; Participants with arterial hypertension and coexisting diabetes.
Hypertension With Orthostatic Hypertension; Participants with arterial hypertension and orthostatic hypertension identified during orthostatic testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate Variability	Assessment of heart rate variability parameters during orthostatic testing and graded exercise testing as indicators of autonomic cardiovascular regulation.	Baseline (Day 1 study visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure Response to Exercise	Assessment of systolic and diastolic blood pressure response during graded exercise testing on a cycle ergometer.	During graded exercise testing at the study visit (Day 1)
Pulse Wave Velocity	Measurement of arterial stiffness using pulse wave velocity.	Baseline (Day 1 study visit)
Heart Rate Recovery	Rate of decrease in heart rate following completion of graded exercise testing on a cycle ergometer.	Immediately after graded exercise testing at the study visit (Day 1)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Orthostatic Blood Pressure Response	Assessment of changes in systolic and diastolic blood pressure during standardized orthostatic testing.	During orthostatic testing at the study visit (Day 1)
Orthostatic Heart Rate Response	Change in heart rate during standardized orthostatic testing.	During orthostatic testing at the study visit (Day 1)

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana
• Investigators: Principal Investigator: Amela Kabaklić, MD, PhD, University Medical Centre Ljubljana

Publications and helpful links

General Publications

• Shaffer F, Ginsberg JP. An Overview of Heart Rate Variability Metrics and Norms. Front Public Health. 2017 Sep 28;5:258. doi: 10.3389/fpubh.2017.00258. eCollection 2017.
• Freeman R, Abuzinadah AR, Gibbons C, Jones P, Miglis MG, Sinn DI. Orthostatic Hypotension: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018 Sep 11;72(11):1294-1309. doi: 10.1016/j.jacc.2018.05.079.
• Mancia G, Kreutz R, Brunstrom M, Burnier M, Grassi G, Januszewicz A, Muiesan ML, Tsioufis K, Agabiti-Rosei E, Algharably EAE, Azizi M, Benetos A, Borghi C, Hitij JB, Cifkova R, Coca A, Cornelissen V, Cruickshank JK, Cunha PG, Danser AHJ, Pinho RM, Delles C, Dominiczak AF, Dorobantu M, Doumas M, Fernandez-Alfonso MS, Halimi JM, Jarai Z, Jelakovic B, Jordan J, Kuznetsova T, Laurent S, Lovic D, Lurbe E, Mahfoud F, Manolis A, Miglinas M, Narkiewicz K, Niiranen T, Palatini P, Parati G, Pathak A, Persu A, Polonia J, Redon J, Sarafidis P, Schmieder R, Spronck B, Stabouli S, Stergiou G, Taddei S, Thomopoulos C, Tomaszewski M, Van de Borne P, Wanner C, Weber T, Williams B, Zhang ZY, Kjeldsen SE. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023 Dec 1;41(12):1874-2071. doi: 10.1097/HJH.0000000000003480. Epub 2023 Sep 26.
• Pecanha T, Silva-Junior ND, Forjaz CL. Heart rate recovery: autonomic determinants, methods of assessment and association with mortality and cardiovascular diseases. Clin Physiol Funct Imaging. 2014 Sep;34(5):327-39. doi: 10.1111/cpf.12102. Epub 2013 Nov 17.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 14, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 14, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Heart Rate Variability; Arterial Stiffness; Pulse Wave Velocity; Exercise Testing; Orthostatic Test
• Additional Relevant MeSH Terms: Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Autonomic Nervous System Diseases; Orthostatic Intolerance; Hypotension; Hypertension; Hypotension, Orthostatic; Primary Dysautonomias
• Other Study ID Numbers: OHHR-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared due to privacy and confidentiality considerations related to clinical data collected in this study.

Drug and device information, study documents

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