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

Recruiting

Phase 4 Results N/A

Trial Description

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 (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 as a function of the circadian time of administration.

Conditions

Interventions

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

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary To evaluate the impact of circadian time of treatment in cardiovascular, cerebrovascular and renal risk assessment. Yearly evaluation for at least ten years Yes
Secondary To evaluate the influence of circadian time of treatment in BP control of hypertensive patients. Yearly evaluation for at least ten years Yes
Secondary 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. Yearly evaluation for at least ten years Yes
Secondary To evaluate the influence of diabetes and circadian time of treatment in the prevalence of an altered (non-dipper) BP profile. Yearly evaluation for at least ten years Yes
Secondary To evaluate the influence of age and circadian time of treatment in the prevalence of an altered (non-dipper) BP profile. Yearly evaluation for at least ten years Yes
Secondary To evaluate, for all groups of interest, the prevalence and cardiovascular risk profile of white-coat hypertension. Yearly evaluation for at least ten years Yes
Secondary To evaluate, for all groups of interest, the prevalence and cardiovascular risk profile of masked hypertension. Yearly evaluation for at least ten years Yes
Secondary To evaluate, for all previous objectives, potential differences between men and women. Yearly evaluation for at least ten years Yes
Secondary To evaluate the impact of changes in ambulatory BP in cardiovascular, cerebrovascular and renal risk assessment. Yearly evaluation for at least ten years Yes
Primary To evaluate the impact of circadian time of treatment in cardiovascular, cerebrovascular, metabolic, and renal risk assessment. Yearly evaluation for at least ten years Yes
Secondary To evaluate, for all groups of interest, the prevalence and vascular, metabolic, and renal risk profile of white-coat hypertension. Yearly evaluation for at least ten years Yes
Secondary To evaluate, for all groups of interest, the prevalence and vascular, metabolic, and renal risk profile of masked hypertension. Yearly evaluation for at least ten years Yes
Secondary To evaluate the impact of changes in ambulatory BP in vascular, metabolic, and renal risk assessment. Yearly evaluation for at least ten years Yes

Sponsors