Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Cardiovascular Risk Assessment

Condition(s) targeted: Essential Hypertension; Total Mortality; Cardiovascular Disease; Stroke; Chronic Kidney Disease

Intervention: Any antihypertensive medication alone or in combination (Drug); Any antihypertensive medication alone or in combination (Drug); Ambulatory blood pressure monitoring (Device)

Phase: Phase 4

Status: Recruiting

Sponsored by: University of Vigo

Official(s) and/or principal investigator(s):
Ramon C Hermida, PhD, Study Director, Affiliation: University of Vigo

Overall contact:
Ramon C Hermida, PhD, Phone: 34986812148, Email: rhermida@uvigo.es

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 and renal risk in hypertensive patients

3. the influence of circadian time of treatment in cardiovascular, cerebrovascular 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.

Official title: Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Cardiovascular Risk Assessment

Study design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Primary outcome: To evaluate the prognostic value of ABPM, the impact of changes in ambulatory BP and the impact of circadian time of treatment in cardiovascular, cerebrovascular and renal risk assessment.

Secondary outcome:

To evaluate the influence of circadian time of treatment in BP control and the remodeling of the circadian BP pattern of hypertensive patients.

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.

To evaluate the influence of diabetes, presence of treatment, and the circadian time of treatment in the prevalence of an altered (non-dipper) BP profile.

To evaluate the influence of age, presence of treatment, and the circadian time of treatment in the prevalence of an altered (non-dipper) BP profile.

To evaluate, for all groups of interest, the prevalence and cardiovascular risk profile of white-coat hypertension.

To evaluate, for all groups of interest, the prevalence and cardiovascular risk profile of masked hypertension.

To evaluate, for all previous objectives, potential differences between men and women.

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, microalbuminuria, 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 (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 cardiovascular morbidity and mortality; second, whether potential changes in the circadian BP pattern after treatment with antihypertensive medications may be associated to changes in the risk of cardiovascular events, stroke, 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 antihypertensive medication, used either alone or in combination, to modulate the circadian BP pattern as a function of the circadian time of administration.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Ramon C Hermida, PhD, Phone: 34986812148, Email: rhermida@uvigo.es

CS Fingoi, Lugo 27002, Spain; Recruiting
Carmen Castiñeira, MD, Phone: 34982251035, Email: Carmen.Castineira.Perez@sergas.es
Carmen Castiñeira, MD, Principal Investigator
Maria C Aguado, Sub-Investigator
Carmen Costa, Sub-Investigator
Domingo D Garcia, MD, Sub-Investigator
Bernardino Pardo, MD, Sub-Investigator
Enrique J Vazquez, MD, Sub-Investigator

Complexo Hospitalario Universitario de Ourense, Orense 32005, Spain; Recruiting
Alfonso Otero, MD, PhD, Phone: 34988385625, Email: Alfonso.Santiago.Otero.Gonzalez@sergas.es
Alfonso Otero, MD, PhD, Principal Investigator

CS Lerez, Pontevedra 36156, Spain; Recruiting
Ana Moya, MD, Phone: 34986871496, Email: ana.moya.alvarez@sergas.es
Ana Moya, MD, Principal Investigator
Andres Ruiz, MD, Sub-Investigator
Aurelia Constenla, Sub-Investigator
Maria I Franco, Sub-Investigator

CS Friol, Friol, Lugo 27220, Spain; Recruiting
Esther Gomez, MD, Phone: 34639512093, Email: Esther.Gomez.Sal@sergas.es
Esther Gomez, MD, Principal Investigator

Bioengineering & Chronobilogy Labs., University of Vigo, Vigo, Pontevedra 36200, Spain; Recruiting
Ramon C Hermida, PhD, Phone: 34986812148, Email: rhermida@uvigo.es
Diana E Ayala, MD, PhD, Phone: 34986812148, Email: dianaelva@uvigo.es
Ramon C Hermida, PhD, Principal Investigator
Diana E Ayala, MD, PhD, Principal Investigator
Artemio Mojon, PhD, Sub-Investigator
Jose R Fernandez, PhD, Sub-Investigator
Ignacio Alonso, PhD, Sub-Investigator
Maria J Fontao, Sub-Investigator
Rita Soler, Sub-Investigator
Susana Serrano, Sub-Investigator

CS A Estrada, La Estrada, Pontevedra 26680, Spain; Recruiting
Luis Meijide, MD, Phone: 34986573459, Email: Luis.Meijide.Calvo@sergas.es
Luis Meijide, MD, Principal Investigator
Mariana Carbon, MD, Sub-Investigator
Maria C Garcia, MD, Sub-Investigator
Francisco Romero, MD, Sub-Investigator
Maria P Brea, Sub-Investigator

CS A Guarda, La Guardia, Pontevedra 36780, Spain; Recruiting
Juan J Crespo, MD, Phone: 34986614450, Email: JuanJose.Crespo.Sabaris@sergas.es
Juan J Crespo, MD, Principal Investigator
Raquel Fernandez, MD, Sub-Investigator
Carmen M Fernandez, MD, Sub-Investigator
Amelia Ferreras, MD, Sub-Investigator
Manuel Quintans, MD, Sub-Investigator
Javier Rodriguez, MD, Sub-Investigator
Pilar Rua, MD, Sub-Investigator
Aurelio Alvarez, Sub-Investigator
Asuncion Cadilla, Sub-Investigator
Carmen Outeiro, Sub-Investigator
Carmen Soto-Davila, Sub-Investigator

CS Bayona, Bayona, Pontevedra 36300, Spain; Recruiting
Francisco J Iglesias, MD, Phone: 34986357239, Email: FranciscoJavier.Iglesias.Mato@sergas.es
Francisco J Iglesias, MD, Principal Investigator

CS Bueu, Bueu, Pontevedra 36930, Spain; Recruiting
Miguel A Aboal, MD, Phone: 34986323313, Email: miguel.angel.aboal.beato@sergas.es
Miguel A Aboal, MD, Principal Investigator

CS Calle Cuba, Vigo, Pontevedra 36202, Spain; Recruiting
Felisa Dominguez, MD, Phone: 34986416226, Email: fdominguez@meditex.es
Felisa Dominguez, MD, Principal Investigator

CS Coia, Vigo, Pontevedra 36209, Spain; Recruiting
Peregrina Eiroa, MD, Phone: 34986209282, Email: pereeiroa@telefonica.net
Peregrina Eiroa, MD, PhD, Principal Investigator
Jesus C Nieto, MD, Sub-Investigator

CS Panxón, Nigrán, Pontevedra 36340, Spain; Recruiting
Jose L Salgado, MD, Phone: 34986368615, Email: joseluis.salgado.conde@sergas.es
Jose L Salgado, MD, Principal Investigator
Esperanza Parrado, Sub-Investigator
Alfredo Pereira, Sub-Investigator

CS San Roque, Villagarcia de Arosa, Pontevedra 36600, Spain; Recruiting
Envira Sineiro, MD, Phone: 34986507448, Email: Elvira.Sineiro.Galinanes@sergas.es
Elvira Sineiro, MD, Principal Investigator
Margarita Alvariño, Sub-Investigator
Luis M Fontenla, Sub-Investigator
Margarita Fraga, MD, Sub-Investigator
Barbara Llovo, Sub-Investigator
Rita Martinez, Sub-Investigator
Santiago Santidrian, MD, Sub-Investigator

CS Sardoma, Vigo, Pontevedra 36214, Spain; Recruiting
Manuel Dominguez, MD, PhD, Phone: 34986416324, Email: Manuel.Dominguez.Sardina@sergas.es
Manuel Dominguez, MD, PhD, Principal Investigator

CS Teis, Vigo, Pontevedra 36216, Spain; Recruiting
Pedro A Callejas, MD, Phone: 34986374229, Email: PedroAntonio.Callejas.Cabanillas@sergas.es
Pedro A Callejas, MD, Principal Investigator

CS Valmiñor, Nigran, Pontevedra 36250, Spain; Recruiting
Susana Hernaiz, MD, Phone: 34655391498, Email: Susana.Hernaiz.Valero@sergas.es
Susana Hernaiz, MD, Principal Investigator

CS Vilaboa, Vilaboa, Pontevedra 36141, Spain; Recruiting
Sonia M Gomara, MD, Phone: 34986679229, Email: SoniaMaria.Gomara.Villabona@sergas.es
Sonia M Gomara, MD, Principal Investigator
Julio J Alvarez, MD, Sub-Investigator
Margarita Estevez, Sub-Investigator
Maria C Ferreira, Sub-Investigator

Hospital do Meixoeiro, Vigo, Pontevedra 36200, Spain; Recruiting
Roberto Perez, MD, Phone: 34627517077, Email: roberto.perez.alvarez@sergas.es
Roberto Perez, MD, Principal Investigator

CS A Doblada, Vigo, Pontevedra 36205, Spain; Recruiting
Teresa Rios, MD, Phone: 34986275121, Email: teresa.rios.rey@sergas.es
Teresa Rios, MD, Principal Investigator

CS Tomiño, Tomiño, Pontevedra 36200, Spain; Recruiting
Evangelina Filloy, MD, Phone: 34-986-623411, Email: evangelina.filloy.miguez@sergas.es
Evangelina Filloy, MD, Principal Investigator
Adolfo T Perez, MD, Sub-Investigator
Nieves Turienzo, MD, Sub-Investigator
Dolores Cardalda, Sub-Investigator
Jose C Varela, Sub-Investigator
Francisca Vazquez, Sub-Investigator

Official web site for the study

Starting date: January 2008
Ending date: December 2020
Last updated: August 31, 2009