• To evaluate the impact of circadian time of treatment in cardiovascular, cerebrovascular and renal risk assessment. [ Time Frame: Yearly evaluation for at least ten years ] [ Designated as safety issue: Yes ]
  

• To evaluate the influence of circadian time of treatment in BP control of hypertensive patients. [ Time Frame: Yearly evaluation for at least ten years ] [ Designated as safety issue: Yes ]
  
• 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 ] [ Designated as safety issue: Yes ]
  
• 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 ] [ Designated as safety issue: Yes ]
  
• 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 ] [ Designated as safety issue: Yes ]
  
• To evaluate, for all groups of interest, the prevalence and cardiovascular risk profile of white-coat hypertension. [ Time Frame: Yearly evaluation for at least ten years ] [ Designated as safety issue: Yes ]
  
• To evaluate, for all groups of interest, the prevalence and cardiovascular risk profile of masked hypertension. [ Time Frame: Yearly evaluation for at least ten years ] [ Designated as safety issue: Yes ]
  
• To evaluate, for all previous objectives, potential differences between men and women. [ Time Frame: Yearly evaluation for at least ten years ] [ Designated as safety issue: Yes ]
  
• To evaluate the impact of changes in ambulatory BP in cardiovascular, cerebrovascular and renal risk assessment. [ Time Frame: Yearly evaluation for at least ten years ] [ Designated as safety issue: Yes ]
  

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.