Clinical trial NCT01742702: HaemoDYNAMICs in Primary and Secondary Hypertension
Official title: Non-Invasive HaemoDYNAMICs in Primary and Secondary Hypertension: the DYNAMIC-study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Primary Hypertension
Secondary Hypertension
Aortic Stenosis
Renal Insufficiency
Keywords: Blood pressure
Hypertension
Arterial stiffness
Cardiac output
Vascular resistance
Pulse wave reflection
Head-up tilt
Lead sponsor: Tampere University
Sponsor class: OTHER
Collaborators: name: Finnish Foundation for Cardiovascular Research
name: Paavo Nurmi Foundation
name: Sigrid Jusélius Foundation
name: Finnish Cultural Foundation
name: Tampere Tuberculosis Foundation
name: Medical Research Fund of the Tampere University Hospital, Finland
name: Aarne Koskelo Foundation
name: Finnish Medical Foundation
name: Finnish Kidney Foundation
name: Päivikki and Sakari Sohlberg Foundation, Finland
First posted: 2012-12-05
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult hypertensive and normotensive subjects who were treated in Tampere University Hospital clinics of internal medicine or cardiology, or visited medical doctors as outpatients at occupational health care providers in the Pirkanmaa Hospital District.

Patients with primary aldosteronism from all University clinics (Helsinki, Turku, Kuopio, Oulu) in Finland, who were referred to Tampere University Hospital for adrenal vein sampling.

Patients with acromegalia from all University clinics (Helsinki, Turku, Kuopio, Oulu) in Finland.

Participants of Ironman Triathlon competition.

Brief summary: The primary aim of the present study was to examine the haemodynamic changes in primary hypertension and secondary hypertension (renal diseases, endocrine diseases, obesity-associated hypertension) with a non-invasive haemodynamic measurement protocol utilizing radial pulse wave analysis and whole-body impedance cardiography in both supine position and during head-up tilt. For comparison, haemodynamics of subjects with chronic fatigue syndrome will also be recorded.

Detailed description: Elevated blood pressure (BP) and related cardiovascular complications are the leading causes of morbidity and mortality in the modern world. In routine clinical practice, the haemodynamic status is commonly assessed by measuring heart rate and blood pressure at rest, which provides only limited information about functional haemodynamic status. In addition, the haemodynamic changes resulting in similar elevations of BP may differ substantially between patients and disorders.

Therefore, we investigated the haemodynamic changes in primary and secondary hypertension and in the control subjects with non-invasive radial pulse wave analysis and whole-body impedance cardiography. The method includes the determination of volume status using bioimpedance spectroscopy, determination of peripheral and central BP, cardiac function, vascular resistance, arterial compliance and indices of pulse wave reflection. Besides the measurements performed in the supine position, passive orthostatic challenge is included in the protocol to assess the upright functional haemodynamic status.

The repeatability and reproducibility of the protocol was first examined with a double-blind, randomized protocol in 35 subjects (methodological study group), and after that the administration of research drugs has been open-label. The effects of single doses of two largely endothelium-dependent agents, inhaled salbutamol and intravenous L-arginine, and one endothelium-independent agent, sublingual nitroglycerin, were investigated. However, challenges with the acute dosing of all medical compounds was terminated at the end of December 2016. Thereafter, the measurement protocol has included supine and upright recordings on the tilt-table, followed by supine measurements during paced breathing (15 breaths per minute for 5 minutes, 6 breaths per minute for 5 minutes) that modulate the autonomic nervous tone.

The study population has consisted of subgroups described below. The study protocol of each subgroup has been approved by the ethics committee of the Pirkanmaa Hospital District (Ethics committee ID's above), and the administration of research drugs has also been approved by the Finnish Agency for Medicines (EudraCT-numbers above).

Eligibility criteria: Inclusion Criteria:

* Independent, community-dwelling adults
* Hypertensive subjects (primary or secondary hypertension)
* Normotensive control subjects
* Subjects with aortic stenosis (subgroup "aortic stenosis")
* Participants of Ironman Triathlon competition

Exclusion Criteria:

* Pregnancy
* Systolic blood pressure \<90 mmHg
* Allergies to test compounds

Primary outcomes:
measure: Change in haemodynamic variables during the follow-up
timeFrame: baseline, ten years
measure: Cardiovascular events
timeFrame: ten years of follow-up
Secondary outcomes:
measure: Haemodynamic response to head-up tilt and research drugs
timeFrame: 0, 5, 10, 15, 20, 25 and 30 minutes
measure: Haemodynamic response to bisoprolol or dietary supplements (liquorice, milk casein-derived polypeptides)
timeFrame: baseline and after 2 weeks (liquorice); 3 weeks (bisoprolol), or 12 weeks (polypeptides)
measure: Haemodynamic changes induced by Ironman competition
timeFrame: Recordings within 2 hours after completion Ironman competition, 12-18 hours later, and within 1-4 before or 4-8 weeks after the competition
Other outcomes:
Locations:
city: Tampere
country: Finland
facility: Tampere University
state: Southern Finland
city: Tampere
country: Finland
facility: Tampere University Hospital
state: Southern Finland
Study officials:
affiliation: Tampere University
name: Ilkka Pörsti, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koskela JK, Tahvanainen A, Tikkakoski AJ, Kangas P, Uitto M, Viik J, Kahonen M, Mustonen J, Porsti I. Resting heart rate predicts cardiac autonomic modulation during passive head-up tilt in subjects without cardiovascular diseases. Scand Cardiovasc J. 2022 Dec;56(1):138-147. doi: 10.1080/14017431.2022.2079713.
citation: Hamid H, Kurra V, Choudhary MK, Bouquin H, Niemela O, Kahonen MAP, Mustonen JT, Porsti IH, Koskela JK. Plasma uric acid is related to large arterial stiffness but not to other hemodynamic variables: a study in 606 normotensive and never-medicated hypertensive subjects. BMC Cardiovasc Disord. 2021 May 26;21(1):257. doi: 10.1186/s12872-021-02072-9.
citation: Kokko E, Nevalainen PI, Choudhary MK, Koskela J, Tikkakoski A, Huhtala H, Niemela O, Viukari M, Mustonen J, Matikainen N, Porsti I. Aldosterone-to-renin ratio is related to arterial stiffness when the screening criteria of primary aldosteronism are not met. Sci Rep. 2020 Nov 13;10(1):19804. doi: 10.1038/s41598-020-76718-7.
citation: Hautaniemi EJ, Tikkakoski AJ, Eraranta A, Kahonen M, Hamalainen E, Turpeinen U, Huhtala H, Mustonen J, Porsti IH. Liquorice ingestion attenuates vasodilatation via exogenous nitric oxide donor but not via beta2-adrenoceptor stimulation. PLoS One. 2019 Oct 18;14(10):e0223654. doi: 10.1371/journal.pone.0223654. eCollection 2019.
citation: Kangas P, Tahvanainen A, Tikkakoski A, Koskela J, Uitto M, Viik J, Kahonen M, Koobi T, Mustonen J, Porsti I. Increased Cardiac Workload in the Upright Posture in Men: Noninvasive Hemodynamics in Men Versus Women. J Am Heart Assoc. 2016 Jun 21;5(6):e002883. doi: 10.1161/JAHA.115.002883.
citation: Wilenius M, Tikkakoski AJ, Tahvanainen AM, Haring A, Koskela J, Huhtala H, Kahonen M, Koobi T, Mustonen JT, Porsti IH. Central wave reflection is associated with peripheral arterial resistance in addition to arterial stiffness in subjects without antihypertensive medication. BMC Cardiovasc Disord. 2016 Jun 7;16:131. doi: 10.1186/s12872-016-0303-6.
citation: Tahvanainen AM, Tikkakoski AJ, Koskela JK, Nordhausen K, Viitala JM, Leskinen MH, Kahonen MA, Koobi T, Uitto MT, Viik J, Mustonen JT, Porsti IH. The type of the functional cardiovascular response to upright posture is associated with arterial stiffness: a cross-sectional study in 470 volunteers. BMC Cardiovasc Disord. 2016 May 23;16:101. doi: 10.1186/s12872-016-0281-8.
citation: Leskinen MH, Hautaniemi EJ, Tahvanainen AM, Koskela JK, Paallysaho M, Tikkakoski AJ, Kahonen M, Koobi T, Niemela O, Mustonen J, Porsti IH. Daily liquorice consumption for two weeks increases augmentation index and central systolic and diastolic blood pressure. PLoS One. 2014 Aug 25;9(8):e105607. doi: 10.1371/journal.pone.0105607. eCollection 2014.
citation: Koskela JK, Tahvanainen A, Haring A, Tikkakoski AJ, Ilveskoski E, Viitala J, Leskinen MH, Lehtimaki T, Kahonen MA, Koobi T, Niemela O, Mustonen JT, Porsti IH. Association of resting heart rate with cardiovascular function: a cross-sectional study in 522 Finnish subjects. BMC Cardiovasc Disord. 2013 Nov 15;13:102. doi: 10.1186/1471-2261-13-102.