HaemoDYNAMICs in Primary and Secondary Hypertension

NCT01742702 | Unknown

• 9 other identifiers: R06086M2006-002065-392009-014542-29R07110MR07053MR08012R09103MR10056R21094
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (2)

• Change in haemodynamic variables during the follow-up

  Haemodynamic measurements are performed at baseline, and after approximately 10 years of follow-up

  baseline, ten years

• Cardiovascular events

  All cardiovascular events during follow-up

  ten years of follow-up

Secondary Outcomes (3)

• Haemodynamic response to head-up tilt and research drugs

  0, 5, 10, 15, 20, 25 and 30 minutes

• Haemodynamic response to bisoprolol or dietary supplements (liquorice, milk casein-derived polypeptides)

  baseline and after 2 weeks (liquorice); 3 weeks (bisoprolol), or 12 weeks (polypeptides)

• Haemodynamic changes induced by Ironman competition

  Recordings within 2 hours after completion Ironman competition, 12-18 hours later, and within 1-4 before or 4-8 weeks after the competition

Study Arms (8)

DYNAMIC (ongoing)

Subjects with primary or secondary hypertension and normotensive control subjects. In addition haemodynamic recordings to 50 subjects suffering from chronic fatigue syndrome will be performed.

AERO-DYNAMIC (recordings completed)

Subjects who had voluntarily decided to participate in a professionally coached marathon school (Varala Sports Institute, Tampere) were given the chance for haemodynamic recordings before, during and after the training protocol.

Drug: Nitroglycerin 0.25 mg (single dose, no longer given since January 2017); Drug: Salbutamol 400 µg (single dose, no longer given since January 2017)

Liquorice (recordings completed)

Normotensive subjects, daily liquorice ingestion (daily glycyrrhizin dose 290-370 mg) for 2 weeks, haemodynamic measurements before and after the intervention.

Drug: Nitroglycerin 0.25 mg (single dose, no longer given since January 2017); Drug: Salbutamol 400 µg (single dose, no longer given since January 2017); Dietary Supplement: Liquorice (2 weeks, glycyrrhizin 290-370 mg daily, no longer given since 2012)

Milk polypeptides (recordings completed)

Daily ingestion of yoghurt containing small milk casein-derived polypeptides for 12 weeks versus placebo yoghurt.

Dietary Supplement: Small milk casein-derived polypeptides (12 weeks daily, recordings completed 2011)

Bisoprolol (recordings completed)

Hypertensive subjects, bisoprolol 5 mg once daily versus placebo in a double-blind, cross-over protocol.

Drug: Nitroglycerin 0.25 mg (single dose, no longer given since January 2017); Drug: Salbutamol 400 µg (single dose, no longer given since January 2017); Drug: Bisoprolol (5 mg daily for 3 weeks, recordings completed 2011)

Aortic stenosis (ongoing)

Subjects with aortic stenosis confirmed by echocardiography

Methodological (recordings completed)

35 normotensive subjects who received research drugs (nitroglycerin, salbutamol, placebo resoriblet, placebo inhalation, L-arginine infusion, saline infusion) in a placebo-controlled, double-blinded manner

Drug: Nitroglycerin 0.25 mg (single dose, no longer given since January 2017); Drug: Salbutamol 400 µg (single dose, no longer given since January 2017); Drug: L-arginine (10 min infusion, no longer given since January 2017)

Participants of Ironman Triathlon

Altogether 80 athletes participating in a full length Ironman competition. Non-invasive recordingds are performed under normal conditions during the training period and after completion of a full-length Ironman competition.

Interventions

Nitroglycerin 0.25 mg (single dose, no longer given since January 2017) DRUG

From the beginning of the study until the end of year 2016 a single dose of sublingual nitroglycerin was given to examine the associated acute haemodynamic effects (recordings completed).

Also known as: Nitro resoriblet, Orion Pharma, Espoo, Finland

AERO-DYNAMIC (recordings completed); Bisoprolol (recordings completed); Liquorice (recordings completed); Methodological (recordings completed)

Salbutamol 400 µg (single dose, no longer given since January 2017) DRUG

From the beginning of the study until the end of year 2016 a 400 µg dose of inhaled salbutamol was given to examine the associated acute haemodynamic effects (recordings completed).

Also known as: Ventoline, GlaxoSmithKline, Uxbridge, Middlesex, UK

AERO-DYNAMIC (recordings completed); Bisoprolol (recordings completed); Liquorice (recordings completed); Methodological (recordings completed)

L-arginine (10 min infusion, no longer given since January 2017) DRUG

From the beginning of the study until the end of year 2016 L-arginine infusion 10 mg/kg/min could be given for 10 minutes to examine acute haemodynamic effects (recordings completed).

Also known as: L-arginine HCl 20 mg ml/l, B. Braun Ag, Melsungen, Germany

Methodological (recordings completed)

Liquorice (2 weeks, glycyrrhizin 290-370 mg daily, no longer given since 2012) DIETARY_SUPPLEMENT

Daily liquorice intake (daily glycyrrhizin dose 290-370 mg) for two weeks, measurements before and after intervention (recordings completed).

Also known as: Halva liquorice (TM), Kouvola liquorice (TM)

Liquorice (recordings completed)

Small milk casein-derived polypeptides (12 weeks daily, recordings completed 2011) DIETARY_SUPPLEMENT

Daily intake of yoghurt containing small milk casein-derived polypeptides (12 weeks) and placebo yoghurt (12 weeks), measurements before and after intervention (recordings completed 2011).

Also known as: Valio (TM) evolus yoghurt

Milk polypeptides (recordings completed)

Bisoprolol (5 mg daily for 3 weeks, recordings completed 2011) DRUG

Bisoprolol 5 mg daily for 3 weeks and placebo tablet daily for 3 weeks, double-blind, randomized, placebo-controlled cross-over protocol. Measurements before and after interventions (recordings completed 2011).

Also known as: Emconcor 5 mg, Merck KGaA, Darmstadt, Germany

Bisoprolol (recordings completed)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Tampere University: lead
• Finnish Foundation for Cardiovascular Research: collaborator
• Paavo Nurmi Foundation: collaborator
• Sigrid Jusélius Foundation: collaborator
• Finnish Cultural Foundation: collaborator
• Tampere Tuberculosis Foundation: collaborator
• Medical Research Fund of the Tampere University Hospital, Finland: collaborator
• Aarne Koskelo Foundation: collaborator
• Finnish Medical Foundation: collaborator
• Finnish Kidney Foundation: collaborator
• Päivikki and Sakari Sohlberg Foundation, Finland: collaborator

Study Sites (2)

Tampere University

Tampere, Southern Finland, 33014, Finland

RECRUITING

Tampere University Hospital

Tampere, Southern Finland, 33521, Finland

RECRUITING

Related Publications (10)

• Taurio J, Hautaniemi EJ, Koskela JK, Eraranta A, Hamalainen M, Tikkakoski A, Kettunen JA, Kahonen M, Niemela O, Moilanen E, Mustonen J, Porsti I. The characteristics of elevated blood pressure in abdominal obesity correspond to primary hypertension: a cross-sectional study. BMC Cardiovasc Disord. 2023 Mar 27;23(1):161. doi: 10.1186/s12872-023-03150-w.

  PMID: 36973671 DERIVED

• 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.

  PMID: 35652524 DERIVED

• 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.

  PMID: 34039285 DERIVED

• 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.

  PMID: 33188272 DERIVED

• 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.

  PMID: 31626649 DERIVED

• 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.

  PMID: 27329447 DERIVED

• 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.

  PMID: 27266507 DERIVED

• 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.

  PMID: 27216309 DERIVED

• 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.

  PMID: 25153328 DERIVED

• 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.

  PMID: 24237764 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma, serum, urine

MeSH Terms

Conditions

Essential Hypertension; Aortic Valve Stenosis; Renal Insufficiency; Hypertension

Interventions

Nitroglycerin; Albuterol; halofantrine; Arginine; Glycyrrhiza glabra extract; Glycyrrhizic Acid; Bisoprolol

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Ventricular Outflow Obstruction; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Nitro Compounds; Organic Chemicals; Ethanolamines; Amino Alcohols; Alcohols; Amines; Phenethylamines; Ethylamines; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Pentacyclic Triterpenes; Triterpenes; Terpenes; Hydrocarbons; Phenoxypropanolamines; Propanolamines; Propanols

Study Officials

• Ilkka Pörsti, MD, PhD

  Tampere University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Professor of Internal Medicine

Study Record Dates

• First Submitted: November 29, 2012
• First Posted: December 5, 2012
• Study Start: May 25, 2006
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: August 19, 2021

Record last verified: 2021-08

Locations

FI (2)