Insights into nocturnal blood pressure

Blood pressure (BP) is the leading risk factor for cardiovascular disease1 and is a major cause of morbidity and mortality worldwide.2 Successful control remains suboptimal in many jurisdictions and most guidelines now recommend moving away from BP measured in the office setting when deciding on treatment.3 Accordingly out‐of‐office BP monitoring is becoming increasingly important in the diagnosis and management of hypertension. Home BP monitoring (HBPM) is easy to perform, inexpensive, and engages patients in the care of their hypertension. Currently, approximately 65% of the American population with hypertension own a HBPM.4 Although 24‐hour ambulatory blood pressure monitoring (ABPM) is not always widely available, it remains the gold standard for diagnosing hypertension and indeed the only method of evaluating nighttime BP.5, 6 The greater use of ABPM highlights those with suboptimal BP and the need to use medications which offer effective 24‐hour BP control.7

There has been a tendency in clinical practice to concentrate on ABPM daytime pressures. However, the association of nighttime hypertension with the cardiovascular consequences of hypertension, such as stroke, has focused the scientific literature on nocturnal hypertensive patterns, such as isolated nocturnal hypertension, and a non‐dipping pattern of BP.8, 9 The Dublin outcome study showed that for every 10 mm Hg rise in nighttime systolic BP there was a 21% increase in cardiovascular mortality after adjustment for covariates including clinic BP.11 Furthermore when compared to those with a normal nighttime BP profile, in patients with a rise in nighttime BP, so called “reverse dippers”, the adjusted association with stroke mortality was increased by 169%.11 The definition of the so‐called “dipping status” of a patient is traditionally based on the behavior of BP going from wakefulness to sleep, depending on whether BP falls, rises, or remains constant. Sleep is associated with a 10%‐20% reduction in systolic and diastolic BP compared to wakefulness.12 Referred to as “BP dipping", this reduction coincides with the sympathetic withdrawal and subsequent parasympathetic predominance that occurs when going from wake to non‐rapid eye movement sleep.

In this issue of Journal of clinical hypertension, there is an interesting article by Booth and colleagues focusing on nocturnal hypertension and the contribution of gender and race.13 In a cohort of just 800 subjects from the larger coronary artery risk development in young adults study who went on to have an ABPM showed an increased incidence of nocturnal hypertension and non‐dipping pattern amongst black males. Black people had higher mean ambulatory BPs at baseline and this was coupled with increased prevalence of known cardiovascular risk factors and antihypertensive medication usage. After adjustment for these potential confounders coupled with mean clinic and daytime ambulatory BP, the prevalence of nocturnal hypertension was greatest amongst black males. In multivariate analysis, the prevalence ratio for nocturnal hypertension was 1.65 (1.18‐2.32) for black women, 1.63 (1.14‐2.33) for white men, and 2.01 (1.43‐2.82) for black men when compared to white females. Nocturnal systolic BP dipping patterns followed a similar theme. Compared with white women, the multivariable‐adjusted prevalence ratio for non‐dipping systolic BP was 1.66 (1.18‐2.32), 0.91 (0.58‐1.42), and 1.66 (1.15‐2.39) amongst black women, white men, and black men, respectively.

A significant proportion of patients were already on BP lowering medication and this research highlights the need for periodic ABPM coupled with HBPM in the management of sometimes complex patients. However, some potential limitations need to be considered. Given that the combination of both diaries and actigraphy were used to define the nighttime period rather than fixed time windows, it is not clear whether we get a true measure of nighttime BP as used in other studies.11 More information on the classes of antihypertensive usage would be helpful as short‐acting BP lowering medications taken early in the day can alter the normal circadian pattern. This is particularly relevant in a black population where drug class resistance exists more commonly. Perhaps the greatest challenge for research of this nature is the confounding aspect of undiagnosed obstructive sleep apnea (OSA). With the availability of the activity monitors, the authors may be in a position to discuss sleep quality in future publications. It is likely that the presence of sleep disturbance contributed somewhat to the elevated nighttime BPs observed in this study.

OSA is characterized by recurrent periods of complete or partial collapse of the upper airway during sleep causing sleep fragmentation and frequent awakenings which often result in excessive daytime sleepiness. In more severe forms of the disease, periods of obstructed breathing result in profound intermittent hypoxia with resultant bursts in sympathetic nerve activity and dramatic increases in heart rate and BP. The severity of OSA is determined by the apnea‐hypopnea index14 which is a measure of the number of periods of obstructed breathing per hour of sleep. The prevalence of OSA with associated daytime sleepiness has been estimated at between 2% and 7% in diverse middle‐aged adult populations.15 Adults with OSA are typically centrally obese, and although this obesity is strongly causally linked to the condition, there is an increased prevalence of cardiovascular morbidity and mortality amongst OSA sufferers above what would be expected from their weight alone. In addition to OSA, patients often present with one or more co‐morbidities including dyslipidemia, early diabetes, and hypertension. In studies which have examined the prevalence of OSA amongst hypertensive populations, 20%‐40% of individuals have been subsequently diagnosed with co‐morbid OSA with levels as high as 71% amongst drug‐resistant hypertensives.16 In a small ABPM sub‐study of the Wisconsin sleep cohort study those with OSA observed a 10 mm Hg increase in nocturnal  systolic BP compared to their Non‐OSA counterparts.17

Studies with ABPM in OSA patients demonstrate a higher prevalence of diminished nocturnal BP dipping compared with those without OSA.17 A study revealed an 84% prevalence of non‐dipping in a sample of untreated patients with mild to severe OSA.18 Gender appears to influence the prevalence of OSA, and affects males up to 10 times more commonly than females.19, 20 Blacks have a higher prevalence of OSA after controlling for confounding variables.22 In the Cleveland Family Study, blacks presented with OSA at a younger age than their white counterparts.23 In addition, black people are twice as likely to have severe OSA.24

Finally, our understanding of what targets to treat our patients to has changed following the publication of the SPRINT study.25 This landmark trial has shown that a more intensive BP lowering regime seems to improve outcome. Regrettably managing hypertension and attaining lower targets is not always that straightforward in sometimes complex patients. We must individualize our therapies and use out‐of‐office measurements to assist us. The use of ABPM, as reflected in the accompanying study, identifies those with abnormal circadian profiles at higher risk of future cardiovascular events.