Nocturia and night-time blood pressure

Nocturia (defined as waking at night one or more times in order to void before returning to sleep) [1], represents a widespread condition that can negatively impact on the quality of sleep and overall health [2]. Nocturia may originate from factors that differ according to the three categories of nocturia: diurnal polyuria, nocturnal polyuria, and low nocturnal bladder capacity [3]. The prevalence of nocturia ranges from 11 to 93% when adopting the definition of one or more void per night, and from 2 to 61.5% according to the definition of two or more voids per night [4]. The prevalence increases with age. Moreover, although being often attributed to prostatic hypertrophy, nocturia is reported not only in men but also in women [4]. In younger populations, higher rates of nocturia were observed in women than in men, whereas in subjects older than 60 years, the reversed is the case [3]. Among the most obvious consequences of nocturia is sleep interruption, associated with lower sleep quality, which in turn reduces well being, vitality, productivity, and mental health [5]. More severe consequences of nocturia have also been reported. Data from the National Health and Nutrition Examination Survey III have shown that nocturia is a predictor of mortality. A metanalysis including about 30 000 subjects has shown that nocturia was associated with a 28% excess mortality risk per year [6].The increased mortality risk may be explained not only by the association of nocturia with several diseases, such as chronic kidney disease, heart failure, ischemic heart disease, and stroke but also diabetes and/or hypertension [7]. In hypertensive patients the prevalence of nocturia is higher than in normotensive individuals (34 vs. 24%) [8]. Although longitudinal evidence is limited, the relationship between nocturia and hypertension has been confirmed in several cross-sectional studies on general population samples [9] .One of them is the Multi-Ethnic Study of Atherosclerosis (MESA) study on community-living adults aged 60 years and older, which showed an independent association between nocturia and hypertension, older age, and use of diuretics. Interestingly, hypertension was not related to the development of nocturia over a 2-year follow-up [10] and, conversely, nocturia was not predictive of hypertension in a retrospective analysis of male adults during a 17-year follow-up [11]. Some evidence supports the relationship between the nondipping behavior of blood pressure (BP) and an increased prevalence of nocturia. The mechanisms by which nocturia may impair BP dipping are multifold. Using a patient-completed questionnaire for sleep-quality assessment, Manning et al.[12] have shown that nocturia alters the perceived quality of sleep and increases the perception of sleep disturbances; it has been suggested that the timing of the first night urine void, after few hours of sleep, may have an especially profound effect on sleep quality because it interrupts the restorative slow-wave sleep that occurs earlier at night. Finally, in patients with chronic kidney disease, the number of voids per night was associated with progressively higher night-time SBP, and thus a reduced night-time dipping [13]; in these patients the effect of nocturia on dipping was mediated by an increased nocturnal activity, as treatment with diuretics and the degree of renal dysfunction, were not associated with the nondipping status. In their cross-sectional study on a large-scale general Japanese population, published in the current issue of the Journal of Hypertension[14], Matsumoto et al. have explored the relationship between nocturia and night-time BP by evaluating simultaneously sleep BP and sleep fragmentation. The results of this study provide further evidence on the clinical relevance of nocturia in hypertension, as the overall prevalence of hypertension was increased according to the number of night-time voids. A previous important contribution is also the HEIJO-KYO cohort in old individuals with a relatively low prevalence of hypertension (about 40%), in which a frequency of nocturnal voiding greater than two was significantly and progressively associated with a higher night-time SBP and a lower dipping, independently of potential confounding factors including daytime and night-time physical activity, endogenous melatonin levels, and bedroom light levels [15].To be also mentioned is the Nagahama study [14], which enrolled younger individuals with no physical impairment or dysfunction. The prevalence of nocturia was 71% according to the definition of one or more voids per night and 21% considering only those with two or more voids per night, in line with previous reports in individuals with similar characteristics. Prevalence of women was quite high (69%), which makes the results confirmatory of the association between nondipping and nocturia in both sexes, and in both premenopausal and postmenopausal state women, limiting the possible role of prostatic hyperthrophy as a cause for this condition. The changes in nocturnal activity, and therefore nocturia, may be also influenced by sleep apnea, which accounts for the observation that nocturia is a common symptom of the sleep apnea syndrome [16]. In the Sleep Heart Health Study, middle-aged to elderly individuals underwent polysomnograph showing that nocturia is independently associated with the prevalence and severity of sleep-disordered breathing, although, a cause–effect relationship between the two variables could not be assessed [17]. We may speculate that in sleep apnea patients, nocturia is stimulated by an increase in natriuretic peptides caused by intermittent hypoxia, sympathetic nervous system hyperactivity, and variations in intrathoracic pressure, leading to a sleep disturbance and daytime fatigue. In a large (n = 22 674) French cohort of obstructive sleep apnea patients, nocturia was associated with the prevalence of hypertension after adjustment for confounders [18]. Available data also include a metanalysis of five studies examining the effect of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea and nocturia, and treatment was reported to reduce the frequency of nocturia and night-time urine volume [19]. Another more recent study [20] investigated the effect of CPAP on nocturnal urine volume in a small number of patients with obstructive sleep apnea and showed that the night-time void frequency was significantly decreased from 2.1 to 1.2 after CPAP treatment. The work by Matsumoto et al.[14] also provides additional relevant information on the role of sleep breathing disorders. As Matsumoto et al.[14] have measured sleep duration by an actigraphy device, oxygen desaturation index by pulse oximetry, and sleeping and awake periods based on the actigraphy data (approximating the polysomnography-calculated apnea hypoxia index), their article also provides information on the impact of sleep breathing disorders on sleep, short of the less reliable patients’ self-reported sleep diaries. The results confirm that oxygen desaturation attenuates the nocturnal hypotension, although the relationship lost statistical significance when sleep fragmentation was included in the analysis. In this study, authors have also addressed the possible effect of seasonal variations [21], showing that total sleep duration is shorter in summer, with an increased frequency and duration of arousals. Despite the evidence that nocturia is increased in summer while the voiding frequency is lower in winter, the positive association between nondipping and nocturia remained significant in all seasons confirming that nocturia may affect night-time BP independently of sleep quality. Finally, Matsumoto et al.[14] report on the effect of antihypertensive treatment on the presence and frequency of nocturia showing a parallel increase in the prevalence of patients treated with antihypertensive drugs and the number of nocturnal voids. However, the authors were not able to assess the specific effects of different classes of drugs on nocturia, an issue on which contrasting data are reported. In the Syst-Eur trial, the prevalence of nocturia and the frequency of voids was increased in treated hypertensive patients [22]. Burgio et al.[23] reported that use of diuretics was associated with nocturia only in women, whereas other studies have found no association between any type of diuretics and nocturia in individuals older than 60 years [24–27]. In the Boston Area Community Health (BACH) survey, the use of calcium channel blockers was associated with nocturia in women treated with loop diuretics, whereas loop diuretic treatment alone was associated with nocturia in men, independently of the use of other antihypertensive drugs [27]. Beta-blockers may decrease bladder capacity and cause nocturia, especially with an evening administration whereas alpha-blockers may reduce bladder outflow obstruction in men with prostatic hypertrophy, although no consistent data are available to support these considerations with actual data. Overall, the results of the study by Matsumoto et al.[14], underscore the close independent relationship that exists between nocturia and nocturnal BP, emphasizing the importance of devoting more attention to nocturia, a frequent and often forgotten clinical symptom. Clinicians should ask more carefully about the presence and/or the number of nocturnal voids in all patients and not only in elderly, especially male, individuals. The epidemiological evidence that in patients with nocturia, a nondipping pattern of BP may increase morbidity and mortality risks should reinforce the need for a prospective longitudinal assessment of the incidence and interaction of these two conditions in patients at increased cardiovascular risk. ACKNOWLEDGEMENT Conflicts of interest There are no conflicts of interest.