Morning surge and nocturnal dipping pattern: Two different entities or statistical gymnastics?

Under physiological conditions, blood pressure (BP) dips at night during sleep to rise again in the morning after awakening.1 Although the normal morning BP rise can be considered physiological, an exaggerated morning BP surge (defined by a predetermined threshold of >25–55 mm Hg) has been associated with incident cardiovascular disease and all-cause mortality in many2-4 but not all studies.5-7 In fact, findings of two Italian studies have suggested that blunted, instead of excessive, morning BP surge is related to adverse cardiovascular outcomes.5, 7 In this issue of the Journal of Clinical Hypertension, Fujiwara and colleagues8 provide insight into these prior contradictory findings by investigating the relationship of the morning BP surge with 24-hour BP patterns. The authors hypothesize that the increased cardiovascular risk in patients with blunted morning BP surge observed in some prior studies might be explained by a high prevalence of nocturnal BP rise (the riser pattern) among these patients.5, 7 In their study, Fujiwara and colleagues use data from an observational study that evaluated the effects of clinidipine on ambulatory BP and heart rate in 501 patients with hypertension. For each participant, the authors calculated the nocturnal systolic BP reduction rate (100×[1−sleep systolic BP/wake systolic BP]) and then categorized the participants into extreme dippers (nocturnal reduction rate of ≥20%), dippers (nocturnal reduction rate between 10% and <20%), nondippers (0%–10% reduction in nocturnal BP), and risers (nocturnal reduction rate of <0%). The authors also estimated for each patient the systolic sleep-trough morning BP surge (defined as the difference between the lowest 1-hour moving average of nocturnal BP and morning BP) and systolic prewaking surge (defined as the difference between BP measured 2 hours before awakening and morning BP). The researchers found that a blunted morning BP surge (being in the lowest decile of morning BP surge) was associated with a greater prevalence of the riser pattern. Conversely, exaggerated morning BP surge (being in the highest decile of morning BP surge) was related to high prevalence rates of extreme nocturnal dipping. More specifically, the prevalence of patients with a riser pattern was significantly higher in the lowest sleep-trough morning surge decile and in the prewaking surge decile than in the remaining deciles (56.0% vs 10.4% and 59.2% vs 10.2%, respectively; P<.0001 for both). Although the study by Fujiwara and coworkers has several strengths, such as a relatively large study sample with objective 24-hour BP measurements, several limitations of the study also merit consideration. Most importantly, the authors were unable to assess the interrelationships between blunted morning BP surge, the riser pattern, and cardiovascular outcomes because of the cross-sectional nature of the study. In addition, the authors did not attempt to elucidate the possible underlying causes of the blunted morning BP surge or the riser pattern. Doing so might have facilitated the interpretation of the study findings because diurnal BP variation is also associated with several clinical entities (eg, obstructive sleep apnea, chronic kidney disease, and diabetes mellitus) that are independently associated with cardiovascular outcomes.1 Furthermore, the generalizability of the results to other populations remains unknown. The study sample consisted solely of patients with hypertension living in Japan, who, on average, have a slightly different diurnal BP profile than Europeans.9 Other potential limitations include the nonstandardized drug regimen, the use of several different ambulatory monitors, and the previously observed poor reproducibility of the morning BP surge.10, 11 The findings from Fujiwara and coworkers complement several previous studies that have examined the association between the morning surge and cardiovascular disease with mixed results.1-5 Fujiwara adds evidence to support that the strong intrinsic relationship between morning surge and nocturnal BP patterns is most likely the main reason for the prior contradictory findings. Studies by Kario2 and Verdecchia and colleagues4 have already previously demonstrated that morning BP surge and nocturnal BP dipping are positively correlated.2, 4 That is, individuals with a greater morning BP surge also tend to have a greater nocturnal BP dip. The authors of the current study provide further insight on this matter by showing that the majority of persons with a blunted BP surge also have a nocturnal riser pattern. These findings strongly suggest that the previously observed positive association between blunted morning BP surge and adverse cardiovascular outcomes could be a result of the statistical and methodological challenges related to defining morning BP surge, ie, if a person exhibits a nocturnal rising pattern in his or her BP, it is understandably unlikely that the same person would at the same time demonstrate a significant BP surge in the morning. Because the nocturnal riser pattern has been previously associated with a 1.89-fold risk of cardiovascular events relative to normal dipping, its adverse effects most likely override the potential beneficial effects of the blunted morning surge.12 Despite the interesting findings by Fujiwara and colleagues, the authors do not comment about any clinical or policy implications their study might have. Clearly, the practicing physician may get confused when trying to interpret an ambulatory BP profile. Should he or she be more worried about a patient having an exaggerated morning BP surge, or just be content that the patient is showing an appropriate nocturnal dipping pattern? Although the determinants and prognosis of the morning BP surge are still being investigated, the authors of the European position paper on the use of ambulatory BP monitoring seem to have already made their mind up on the clinical importance of the morning BP surge.13 These guidelines currently state: “Given the methodological problems in determining the morning surge that include its association with the degree of night-time BP fall, different methods for its quantification, poor reproducibility, and the variety of definitions used in different studies, its relevance to clinical practice is limited.” Until prospective, well-analyzed studies on the relative impact of BP surge and nocturnal dipping status on cardiovascular outcomes are published, it seems to make the most sense to follow the recommendations of the current guidelines for the time being.13 Current evidence suggests that morning BP surge is a complicated phenomenon with a somewhat unclear prognostic significance. The article by Fujiwara and colleagues demonstrates that the morning BP surge can be blunted or even negative in many individuals with a rising nocturnal BP pattern. Researchers studying the morning BP surge should therefore consider excluding individuals with a blunted or negative morning surge from the analyses, or otherwise risk having perplexing results. Clinicians, on the other hand, need to bear in mind that a strong interrelationship between the morning BP surge and the nocturnal BP pattern exists. Until contradictory evidence appears, physicians should concentrate mainly on the BP level, nighttime dipping patterns, and BP variability when interpreting patient's ambulatory BP profile. These BP phenotypes are relatively easy to interpret and are associated with a less ambiguous cardiovascular prognosis compared with morning BP surge.12-14 None.