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

U

University of Vigo

Status and phase

Completed
Phase 4

Conditions

Chronic Kidney Disease
Stroke
Essential Hypertension
Cardiovascular Disease

Treatments

Drug: Any antihypertensive medication alone or in combination
Device: Ambulatory blood pressure monitoring

Study type

Interventional

Funder types

Other

Identifiers

NCT00741585
HYGIA
Hygia-2007-440

Details and patient eligibility

About

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.

Full 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.

Enrollment

21,983 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

21,983 participants in 2 patient groups

1
Active Comparator group
Description:
Treatment with all prescribed hypertension medications on awakening
Treatment:
Device: Ambulatory blood pressure monitoring
Drug: Any antihypertensive medication alone or in combination
Drug: Any antihypertensive medication alone or in combination
2
Active Comparator group
Description:
Treatment with at least one prescribed hypertension medication at bedtime
Treatment:
Device: Ambulatory blood pressure monitoring
Drug: Any antihypertensive medication alone or in combination
Drug: Any antihypertensive medication alone or in combination

Trial contacts and locations

20

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Data sourced from clinicaltrials.gov

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