Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Multiple Risk Assessment (HYGIA)

August 24, 2018 updated by: Ramon C. Hermida, University of Vigo

The HYGIA study was designed to investigate prospectively

  1. the prognostic value of ambulatory blood pressure (BP) monitoring among subjects primarily evaluated at primary care settings
  2. the impact of changes in ambulatory BP during follow-up in cardiovascular, cerebrovascular, metabolic, and renal risk in hypertensive patients
  3. the influence of circadian time of treatment in cardiovascular, cerebrovascular, metabolic, and renal risk in hypertensive patients
  4. the prevalence of an altered BP profile as a function of antihypertensive treatment, circadian time of treatment, age, and presence of diabetes, among other factors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Ambulatory blood pressure (BP) measurements (ABPM) correlate more closely with target organ damage and cardiovascular events than clinical cuff measurements. ABPM reveals the significant circadian variation in BP, which in most individuals presents a morning increase, small post-prandial decline, and more extensive lowering during nocturnal rest. However, under certain pathophysiological conditions, the nocturnal BP decline may be reduced (non-dipper pattern) or even reversed (riser pattern). This is clinically relevant since the non-dipper and riser circadian BP patterns constitute a risk factor for left ventricular hypertrophy, albuminuria, cerebrovascular disease, congestive heart failure, vascular dementia, and myocardial infarction. Hence, there is growing interest in how to best tailor and individualize the treatment of hypertension according to the specific circadian BP pattern of each patient.

The reduction of the normal 10-20% sleep-time BP decline that is characteristic of the non-dipper and riser patterns is indeed associated with elevated risk of target organ damage, particularly to the heart (left ventricular hypertrophy, congestive heart failure, and myocardial infarction), brain (stroke), and kidney (albuminuria and progression to end-stage renal failure). These results suggest that cardiovascular risk could be influenced not by BP elevation alone, but also by the magnitude of the circadian BP variability. However, the potential dimension of an altered BP profile is still under debate, as there is current discrepancy on the actual prevalence of a non-dipper BP profile among groups of interest, mainly the elderly, patients with diabetes and patients with resistant hypertension.

Moreover, several independent prospective studies have suggested that nighttime BP may be a better predictor of cardiovascular risk than daytime BP. Common to all previous trials is that prognostic significance of ABPM has relied on a single baseline profile from each participant, without accounting for possible changes in the BP pattern, mainly associated to antihypertensive therapy and aging during follow-up. Moreover, the potential benefit, i.e., reduction in cardiovascular risk, associated with the normalization of the circadian BP variability (e.g., conversion from non-dipper to dipper pattern) from appropriately envisioned treatment strategy is still a matter of debate.

The HYGIA study was designed to investigate, first, the comparative prognostic value of several BP parameters (including, among many others, BP variability, the diurnal/nocturnal ratio, diurnal and nocturnal means, hyperbaric index, slope of morning rise, etc) in the prediction of vascular, metabolic, and renal morbidity and mortality; second, whether potential changes in the circadian BP pattern after treatment with hypertension medications may be associated to changes in the risk of cardiovascular events, stroke, diabetes, and/or chronic kidney disease; and third, in keeping with the second major objective above, to further assess the potential changes in efficacy, safety profile, and/or capability of hypertension medications, used either alone or in combination, to modulate the circadian BP pattern and to reduce vascular, metabolic, and renal risks as a function of the circadian time of administration.

Study Type

Interventional

Enrollment (Actual)

21983

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Lugo, Spain, 27002
        • CS Fingoi
      • Orense, Spain, 32005
        • Complexo Hospitalario Universitario de Ourense
      • Pontevedra, Spain, 36156
        • CS Lerez
    • Lugo
      • Friol, Lugo, Spain, 27220
        • CS Friol
    • Pontevedra
      • Baiona, Pontevedra, Spain, 36300
        • CS Baiona
      • Bueu, Pontevedra, Spain, 36930
        • CS Bueu
      • La Estrada, Pontevedra, Spain, 26680
        • CS A Estrada
      • La Guardia, Pontevedra, Spain, 36780
        • CS A Guarda
      • Nigran, Pontevedra, Spain, 36250
        • CS Valmiñor
      • Nigrán, Pontevedra, Spain, 36340
        • CS Panxón
      • Tomiño, Pontevedra, Spain, 36200
        • CS Tomiño
      • Vigo, Pontevedra, Spain, 36200
        • Hospital Do Meixoeiro
      • Vigo, Pontevedra, Spain, 36200
        • Bioengineering & Chronobilogy Labs., University of Vigo
      • Vigo, Pontevedra, Spain, 36202
        • CS Calle Cuba
      • Vigo, Pontevedra, Spain, 36205
        • CS A Doblada
      • Vigo, Pontevedra, Spain, 36209
        • CS Coia
      • Vigo, Pontevedra, Spain, 36214
        • CS Sardoma
      • Vigo, Pontevedra, Spain, 36216
        • CS Teis
      • Vilaboa, Pontevedra, Spain, 36141
        • CS Vilaboa
      • Vilagarcía De Arousa, Pontevedra, Spain, 36600
        • CS San Roque

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female subjects ≥18 years of age.
  • High-normal BP or essential hypertension.
  • Any subject with recommendation for evaluation with ABPM according to the 2007 European Guidelines.
  • Informed consent to participate in the study prior to any study procedures.

Exclusion Criteria:

  • Known or suspected contraindications to any potential medication under investigation.
  • Shift-workers.
  • Inability to communicate and comply with all study requirements.
  • Persons directly involved in the execution of this protocol.
  • Intolerants to the use of the ABPM device.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
Treatment with all prescribed hypertension medications on awakening
Drug: Any antihypertensive medication alone or in combination
All drugs on awakening
Other Names:
  • Valsartan
  • Atenolol
  • Lisinopril
  • Candesartan
  • Irbesartan
  • Olmesartan
  • Telmisartan
  • Ramipril
  • Carvedilol
  • Amlodipine
  • Enalapril
  • Quinapril
  • Nevibolol
  • Doxazosine
  • Lercanidipine
  • Manidipine
Drug: Any antihypertensive medication alone or in combination
One or more drugs at bedtime
Other Names:
  • Valsartan
  • Atenolol
  • Lisinopril
  • Candesartan
  • Irbesartan
  • Olmesartan
  • Telmisartan
  • Ramipril
  • Carvedilol
  • Amlodipine
  • Enalapril
  • Quinapril
  • Nevibolol
  • Doxazosine
  • Lercanidipine
  • Manidipine
Device: Ambulatory blood pressure monitoring
Sampling at 20-min intervals from 07:00 to 23:00 and at 30-min intervals at night for 48 consecutive hours
Other Names:
  • ABPM
Active Comparator: 2
Treatment with at least one prescribed hypertension medication at bedtime
Drug: Any antihypertensive medication alone or in combination
All drugs on awakening
Other Names:
  • Valsartan
  • Atenolol
  • Lisinopril
  • Candesartan
  • Irbesartan
  • Olmesartan
  • Telmisartan
  • Ramipril
  • Carvedilol
  • Amlodipine
  • Enalapril
  • Quinapril
  • Nevibolol
  • Doxazosine
  • Lercanidipine
  • Manidipine
Drug: Any antihypertensive medication alone or in combination
One or more drugs at bedtime
Other Names:
  • Valsartan
  • Atenolol
  • Lisinopril
  • Candesartan
  • Irbesartan
  • Olmesartan
  • Telmisartan
  • Ramipril
  • Carvedilol
  • Amlodipine
  • Enalapril
  • Quinapril
  • Nevibolol
  • Doxazosine
  • Lercanidipine
  • Manidipine
Device: Ambulatory blood pressure monitoring
Sampling at 20-min intervals from 07:00 to 23:00 and at 30-min intervals at night for 48 consecutive hours
Other Names:
  • ABPM

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To evaluate the impact of circadian time of treatment in cardiovascular, cerebrovascular, metabolic, and renal risk assessment.
Time Frame: Yearly evaluation for at least ten years
Yearly evaluation for at least ten years

Secondary Outcome Measures

Outcome Measure
Time Frame
To evaluate the influence of circadian time of treatment in BP control of hypertensive patients.
Time Frame: Yearly evaluation for at least ten years
Yearly evaluation for at least ten years
To evaluate the prevalence of an altered (non-dipper) BP profile in patients with resistant hypertension as a function of the circadian time of treatment.
Time Frame: Yearly evaluation for at least ten years
Yearly evaluation for at least ten years
To evaluate the influence of diabetes and circadian time of treatment in the prevalence of an altered (non-dipper) BP profile.
Time Frame: Yearly evaluation for at least ten years
Yearly evaluation for at least ten years
To evaluate the influence of age and circadian time of treatment in the prevalence of an altered (non-dipper) BP profile.
Time Frame: Yearly evaluation for at least ten years
Yearly evaluation for at least ten years
To evaluate, for all groups of interest, the prevalence and vascular, metabolic, and renal risk profile of white-coat hypertension.
Time Frame: Yearly evaluation for at least ten years
Yearly evaluation for at least ten years
To evaluate, for all groups of interest, the prevalence and vascular, metabolic, and renal risk profile of masked hypertension.
Time Frame: Yearly evaluation for at least ten years
Yearly evaluation for at least ten years
To evaluate, for all previous objectives, potential differences between men and women.
Time Frame: Yearly evaluation for at least ten years
Yearly evaluation for at least ten years
To evaluate the impact of changes in ambulatory BP in vascular, metabolic, and renal risk assessment.
Time Frame: Yearly evaluation for at least ten years
Yearly evaluation for at least ten years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Vigo

Collaborators

Servicio Gallego de Salud

Investigators

  • Study Director: Ramon C Hermida, PhD, University of Vigo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2008

Primary Completion (Actual)

June 30, 2018

Study Completion (Actual)

June 30, 2018

Study Registration Dates

First Submitted

August 25, 2008

First Submitted That Met QC Criteria

August 25, 2008

First Posted (Estimate)

August 26, 2008

Study Record Updates

Last Update Posted (Actual)

August 28, 2018

Last Update Submitted That Met QC Criteria

August 24, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HYGIA
  • Hygia-2007-440

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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