Clinical trial NCT00741585: Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Multiple Risk Assessment
Official title: Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Multiple Risk Assessment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Essential Hypertension
Cardiovascular Disease
Stroke
Chronic Kidney Disease
Keywords: Ambulatory blood pressure monitoring
Chronotherapy
Circadian
Non-dipper
Type 2 diabetes
Resistant hypertension
Total mortality
Lead sponsor: University of Vigo
Sponsor class: OTHER
Collaborators: name: Servicio Gallego de Salud
First posted: 2008-08-26
Enrollment: 21983
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate the impact of circadian time of treatment in cardiovascular, cerebrovascular, metabolic, and renal risk assessment.
timeFrame: Yearly evaluation for at least ten years
Secondary outcomes:
measure: To evaluate the influence of circadian time of treatment in BP control of hypertensive patients.
timeFrame: Yearly evaluation for at least ten years
measure: 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.
timeFrame: Yearly evaluation for at least ten years
measure: To evaluate the influence of diabetes and circadian time of treatment in the prevalence of an altered (non-dipper) BP profile.
timeFrame: Yearly evaluation for at least ten years
measure: To evaluate the influence of age and circadian time of treatment in the prevalence of an altered (non-dipper) BP profile.
timeFrame: Yearly evaluation for at least ten years
measure: To evaluate, for all groups of interest, the prevalence and vascular, metabolic, and renal risk profile of white-coat hypertension.
timeFrame: Yearly evaluation for at least ten years
measure: To evaluate, for all groups of interest, the prevalence and vascular, metabolic, and renal risk profile of masked hypertension.
timeFrame: Yearly evaluation for at least ten years
measure: To evaluate, for all previous objectives, potential differences between men and women.
timeFrame: Yearly evaluation for at least ten years
measure: To evaluate the impact of changes in ambulatory BP in vascular, metabolic, and renal risk assessment.
timeFrame: Yearly evaluation for at least ten years
Other outcomes:
Locations:
city: Friol
country: Spain
facility: CS Friol
state: Lugo
city: Baiona
country: Spain
facility: CS Baiona
state: Pontevedra
city: Bueu
country: Spain
facility: CS Bueu
state: Pontevedra
city: La Estrada
country: Spain
facility: CS A Estrada
state: Pontevedra
city: La Guardia
country: Spain
facility: CS A Guarda
state: Pontevedra
city: Nigran
country: Spain
facility: CS Valmiñor
state: Pontevedra
city: Nigrán
country: Spain
facility: CS Panxón
state: Pontevedra
city: Tomiño
country: Spain
facility: CS Tomiño
state: Pontevedra
city: Vigo
country: Spain
facility: Bioengineering & Chronobilogy Labs., University of Vigo
state: Pontevedra
city: Vigo
country: Spain
facility: Hospital do Meixoeiro
state: Pontevedra
city: Vigo
country: Spain
facility: CS Calle Cuba
state: Pontevedra
city: Vigo
country: Spain
facility: CS A Doblada
state: Pontevedra
city: Vigo
country: Spain
facility: CS Coia
state: Pontevedra
city: Vigo
country: Spain
facility: CS Sardoma
state: Pontevedra
city: Vigo
country: Spain
facility: CS Teis
state: Pontevedra
city: Vilaboa
country: Spain
facility: CS Vilaboa
state: Pontevedra
city: Vilagarcía De Arousa
country: Spain
facility: CS San Roque
state: Pontevedra
city: Lugo
country: Spain
facility: CS Fingoi
city: Orense
country: Spain
facility: Complexo Hospitalario Universitario de Ourense
city: Pontevedra
country: Spain
facility: CS Lerez
Study officials:
affiliation: University of Vigo
name: Ramon C Hermida, PhD
role: STUDY_DIRECTOR
References:
citation: Hermida RC, Crespo JJ, Dominguez-Sardina M, Otero A, Moya A, Rios MT, Sineiro E, Castineira MC, Callejas PA, Pousa L, Salgado JL, Duran C, Sanchez JJ, Fernandez JR, Mojon A, Ayala DE; Hygia Project Investigators. Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial. Eur Heart J. 2020 Dec 21;41(48):4565-4576. doi: 10.1093/eurheartj/ehz754.
citation: Hermida RC. Sleep-time ambulatory blood pressure as a prognostic marker of vascular and other risks and therapeutic target for prevention by hypertension chronotherapy: Rationale and design of the Hygia Project. Chronobiol Int. 2016;33(7):906-36. doi: 10.1080/07420528.2016.1181078. Epub 2016 May 24.