Relevance of circadian changes in blood pressure

Hypertension is one of the most important challenges for public health systems to manage. This relevance is determined by its high prevalence and its association with the risk of cardiovascular and renal disease (1-3). In 2000, approximately a quarter of
worldwide adult population had hypertension, and this proportion is expected to rise to 29% of the adult population in 2025, which would amount to 1560 million individuals (4).

Biological rhythms

Current management of hypertensive patients does not often consider or at least gives little importance to the biological rhythms inherent to the disease process. The development of techniques for ambulatory blood pressure monitoring and home-blood pressure measurements has generated a series of questions directly related to the chronobiology of the cardiovascular system (5). In recent years, research evidence highlights the influence of nocturnal blood pressure (BP) values and, more specifically, the absence of a nocturnal dipping and an increased morning surge of blood pressure, on the development of target organ damage and an increased cardiovascular risk (5).

Nocturnal dip

Ambulatory blood pressure monitoring techniques have expanded our knowledge regarding the circadian rhythms of blood pressure. Several studies suggest a relationship between cardiovascular complications such as acute myocardial infarction and cerebrovascular disease with circadian BP changes (6). In fact, many studies suggest that patients who do not show an appropriate nocturnal dip in blood pressure may develop a variety of disorders associated with increased rates of cardiovascular morbidity and mortality (7-9). Ohkubo et al demonstrated that a diminished nocturnal decline in BP is a risk factor for cardiovascular mortality in the general population (10).
 
"Non-dipper" individuals

In this regard, Cuspidi et al have shown that the persistence of non-dipper patterns is associated with increased left ventricular mass index, a thicker interventricular septum, and a larger diameter of the left atrium and aortic root in a group of 375 previously untreated hypertensive patients (7). Similarly, non-dipper hypertensive patients show a greater degree of insulin resistance and lower levels of adiponectin, compared to dipper hypertensives (8). These non-dipper hypertensive patients had a more severe impairment of endothelial function as manifested by a reduced ability of endothelium-dependent vasodilation and mediated by a decrease in nitric oxide release (9). In fact, reverse dipper hypertensive patients showed wider pulse pressure at night than any other group, suggesting the potential role of arterial stiffness as an underlying mechanism of impaired cardiovascular risk (11).

Long-term prognosis

All these changes determine a worsened long-term prognosis for non-dipper. In a meta-analysis including data of 3468 patients from four prospective studies, the dipping pattern and the night-day BP ratio significantly and independently predicted mortality and cardiovascular events in hypertensive patients without a history of major cardiovascular disease (12). In diabetic patients, the loss of the physiological circadian pattern is associated with increased mortality in both type 1 and type 2 diabetes (13).

Early morning surge

Moreover, there is growing evidence linking an early morning rise in blood pressure with increased cardiovascular risk (14). Although the mechanisms responsible for this relationship are not well known, several factors contribute to hemodynamic and neurohumoral blood pressure (6,14,15). It has been described in patients with coronary disease in which myocardial ischemia may appear transiently in the first two hours after waking (16). Similarly, in reviewing a group of 1167 patients with ischemic stroke, early morning stroke onset as opposed to strokes at any other times of day, have been observed more frequently (17) and the incidence of stroke is directly related to the magnitude of the morning rise in blood pressure (18). Similarly, several meta-analyses have confirmed the relationship between cardiovascular complications (myocardial infarction (19) or stroke (20)) and strokes occuring at highest incidence in the early hours of the morning.