The International Journal of Cardiovascular Imaging (2006) 22: 167–169 DOI 10.1007/s10554-005-9023-1
Ó Springer 2005
Editorial Comment
Failure to decrease blood pressure during sleep: non-dippers are among us Paul Steendijk Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
In response to the article by Erdogan et al., The influence of circadian blood pressure changes on aortic distensibility and left ventricular diastolic function in hypertensive individuals (DOI 10.1007/s10554-0059007-1). Blood pressure in healthy individuals follows a characteristic circadian pattern with a nocturnal decline of 10–20% followed by an increase early in the morning. The nocturnal pressure drop presumably is mainly caused by a reduction in sympathetic activity resulting in venous dilatation, translocation of blood to the periphery, and decreased venous return [1]. However, this normal pattern may be disturbed and identification of patients who do not show a normal fall in blood pressure during sleep (so called non-dippers, typically characterized as showing <10% nocturnal pressure drop) is of clinical and prognostic significance. This phenomenon has been investigated mainly in hypertensive patients and non-dipper status was identified as an independent predictor of prognosis in essential hypertension [2] and as a risk factor for mortality [3, 4]. In general, individuals with a non-dipper circadian blood pressure pattern are reported to be at higher risk of cerebrovascular and cardiovascular complications [3– 7]. Multiple studies concerning arterial hypertension have demonstrated more serious target-organ damage in non-dippers [8–10]. Most studies relate to increased left ventricular hypertrophy in nondippers [11], but also increased silent cerebrovascular damage was reported in elderly hypertensive patients [12]. In patients with renal insufficiency, the loss of nocturnal decrease of diastolic blood pressure may accelerate the rate of progression of the disease [13]. It should be noted that there is also a category of patients who, rather than
non-dippers, are extreme-dippers (>20% nocturnal pressure fall) and this group may be at risk for silent and clinical cerebral ischemia through hypoperfusion during sleep [6]. Early studies suggested that the circadian rhythm is mainly related to physical and mental activity [14]. Although more recent studies confirmed the relation between blood pressure variation and physical activity [15, 16], physical activity alone cannot explain the relatively high nocturnal blood pressure in non-dipper hypertension patients [17] and additional mechanisms must be present. Hemodynamic studies showed a smaller nocturnal decline in cardiac index in non-dippers, whereas total peripheral resistance and heart rate did not appear to show a different pattern between dippers and non-dippers [18]. Failure to decrease blood pressure at night was concluded to be most likely due to mal-suppression of sympathetic activity and/ or inadequate reduction of central blood volume during the night. Other studies specifically investigated the influence of the autonomic nervous system, generally using heart rate variability as a measure of autonomic activity, on the circadian rhythm of blood pressure [19, 20]. These studies indicate that non-dippers may indeed have an abnormal pattern of autonomic activity with lower circadian fluctuation. The latter is known to be a determinant of unfavourable prognosis in patients with coronary artery disease [19]. In addition, it was established that hypertension patients with non-dipper pattern have a greater impairment of
168 endothelial function than those with a dipper pattern. In particular, the non-dippers revealed a reduced NO release leading to a blunted endothelium-dependent vasodilatation [21]. Furthermore, a recent study showed that non-dipper hypertensive patients have significantly elevated plasma fibrogen levels compared with dippers [22], which may be directly related to the increased risk for vascular events in the non-dipper patients [23]. Currently, there appears to be no consensus regarding specific anti-hypertensive treatment for non-dipper hypertensive patients. Both sodium restriction and diuretics have been reported to shift the circadian rhythm of blood pressure from non-dipper to dipper pattern [24], whereas blockade of a1-adrenergic receptors might be effective to reduce nightly sympathetic hyperactivity [25]. Of importance is also the finding that the percentage of non-dippers is substantially higher in treated vs. untreated hypertensive patients (61 vs. 37%), which could be related to a lack of therapeutic coverage for the full 24-h of the day [17]. An important aspect of the identification of non-dippers is the use of continuous ambulatory blood pressure monitoring (ABPM). For this purpose automated non-invasive recording systems attached to an arm-cuff are generally used. The cuff may be inflated at programmed intervals, and systolic and diastolic blood pressures are determined from Korotkoff sounds during stepwise deflations [26]. Typically, blood pressure readings are obtained over a full 24-h period with normal activity, at 15-min intervals during the day and 30-min intervals at night. Unfortunately, the reproducibility of circadian blood pressure variation is limited [27, 28], particularly in older subjects [29]. Recent studies indicate that ABPM over multiple 24-h periods may be needed for an adequate diagnosis [30]. The study by Erdogan et al. [31] in this issue, investigated the influence of dipper vs. non-dipper status on aortic distensibility and left ventricular diastolic function in hypertensive patients. The authors concluded that left ventricular remodeling and diastolic function were similar in patients with non-dipper and dipper hypertension, but that aortic elastic properties showed a tendency to be more impaired in the non-dippers. The findings
with regard to diastolic function are consistent with an earlier study by Grandi et al. [32], but a very recent study by Aydin et al. [33] shows more impaired diastolic function in non-dippers in very similar patient groups. A comparison of aortic distensibility between dippers and non-dippers was previously only reported by Grandi et al. [32] and they did not find a difference. Strictly speaking, Erdogan et al. also did not find statistically significant differences, but their data suggest that statistical significances may be reached with a properly powered study. The small number of patients in the present study, in fact, is an important limitation. This limitation is even more evident in view of the fact that the definition of dipper or non-dipper was based on a single 24-h blood pressure recording, which was previously reported to have a very limited reproducibility. We conclude that the lack of a nocturnal pressure drop in some patients with hypertension is an interesting physiological phenomenon, which is not yet fully characterized. Moreover, non-dipper status may have important clinical and prognostic implications and may even require targeted therapy. In this respect, the findings by Erdogan et al. are interesting, but additional studies are required to settle the issues brought up in their article.
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Address for correspondence: P. Steendijk, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands E-mail: P.Steendijk@lumc.nl