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Identification and treatment of individuals with nocturnal non-dipper blood pressure pattern

Identificación y tratamiento de los individuos con patrón nocturno de presión arterial non-dipper

 

 

Roberto Manfredini,¹ Fabio Fabbian,¹ interviewer Ricardo Cárdenas²

 

1 Universita degli Studi di Ferrara, Ferrara, Italia

2 Sociedad Iberoamericana de Información Científica, Ciudad de Buenos Aires, Argentina

 

The interviewees declares no conflict of interest.

 

SIIC: Considering the fact that even normotensives with a non-dipping blood pressure (BP) pattern are at a higher risk of cardiovascular complications, which preventive measurements, if any, could be implemented in this group of subjects?

RM: It is estimated that approximately 20% of normotensive adults have a non-dipper BP profile and, thus, are at relatively high cardiovascular disease (CVD) risk. It is important to define whether these “normotensive” individuals are otherwise healthy or present comorbidities, e. g., diabetes, chronic kidney disease (CKD), and/or past CVD events. In the first case, there is no indication to pharmacological treatment. Characteristics of sleep should be investigated (many of these patients have higher night BP values due to sleeping problems) and a supervising clinical and careful ambulatory blood pressure monitoring (ABPM) check schedule could be suggested.

 

Which specific factors represent the highest risk for cardiovascular complications in the presence of a non-dipper pattern in BP rhythm?

Reverse or inverted dipping (i. e., the condition characterized by unchanged or even increased nighttime BP compared with daytime values) represents an extreme, not rare, alteration in circadian BP rhythm. It is usually considered a harmful BP phenotype, although available literature on its clinical and prognostic implications is still under investigation. A meta-analysis by Salles et al. involving more than of 17 000 hypertensives examined the systolic night-to-day ratio and different dipping patterns (extreme, reduced, and reverse dippers) relative to normal dippers. Adjusted hazard ratios (HRs) were calculated for total cardiovascular events (CVEs), coronary events, strokes, cardiovascular mortality, and total mortality. Reverse dipping also predicted all end-points: HRs were 1.57 to 1.89, moreover reduced dippers, relative to normal dippers, had a significant 27% higher risk for total CVEs. Asymptomatic target organ damage (such as increased QRS voltage/duration, left ventricular mass index, carotid intima‐media thickening, pulse wave velocity, urinary albumin excretion, and reduced glomerular filtration rate) is considered an intermediate step in the continuum of cardiovascular disease and an important predictor of cardiovascular morbidity and mortality and all‐cause mortality. A growing amount of evidence indicates that non-dippers have more marked cardiac and extracardiac organ damage compared with patients with preserved nocturnal BP fall.

 

Besides angiotensin converting enzyme inhibitors and angiotensin receptor blockers, which other drugs could potentially be included as part of a tailored chronotherapy for an optimized cardiovascular treatment?

It has been shown that CVD risk was markedly lower in patients ingesting ≥1 medications at bedtime compared with those ingesting all medications upon awakening, independent of class. Although greater benefits have been reported for angiotensin converting enzimes (ACEs) and angiotensin II receptor-blockers (ARBs), also calcium channel blockers show benefit for bedtime compared with awakening treatment. Finally, it can be remembered that for alpha-blockers (e. g., doxazosine) only bedtime ingestion is effective, to contrast the early morning alpha hypertone.

 

Which follow-up regime is the most effective one to determine whether or not the bedtime treatment is working on a given patient?

This is a very difficult question. Guidelines do not help, since there is not an optimal timetable for performing ABPM. ABPM should be performed in difficult cases such as identification of masked normotension, masked hypertension, sleep-time hypertension, and reduced decline of sleep-time BP, in order to deliver clinically useful information for making a correct diagnosis, or for tailoring the anti-hypertensive treatment regimen for each individual patient. Evaluation of ABPM in more than 11 000 adults, higher 24-hour and nighttime BP were significantly associated with greater risks of death and a cardiovascular outcome, consisting of cardiovascular mortality combined with nonfatal coronary events, heart failure, and stroke. However, clinical judgment in difficult cases is essential, probably repeating ABPM after 4-6 weeks from a change of treatment could be considered a good decision. An algorithm to triage patients with suspected high blood pressure has been suggested for ABPM in routine clinical practice (Sheppard et al., BMJ 2018).

 

What change in the profile of side effects, if any, should the patient be aware of when switching from daytime to bedtime drug administration, in non-dipper subjects?

Although treatment of nocturnal hypertension does not create problems in adult population, such this approach in multimorbid older adults with frailty is still matter of debate. It is not possible to exclude the onset of serious adverse effects, such as hypotension orthostatic hypotension, and falls. The association between hypertension, elderly and frailty may show various aspects. In older subjects, nocturnal dipping of lesser magnitude was associated with greater brain atrophy, and they both were also associated with slower gait speed and worse functional outcome after stroke. Particular attention should be given to older patients with dementia and mild cognitive impairment. In these patients, in fact, excessive SBP lowering could be harmful, since low daytime SBP was independently associated with a greater progression of cognitive decline. An altered circadian BP pattern in frail subjects is not surprising, and nocturnal hypertension seems to represent frequent diagnosis. However management of hypertension in this population appears to be very complex. In frail hypertensive patients, extreme dipper pattern, orthostatic hypotension, post-prandial hypotension, target organ hypoperfusion, target organ damage and major clinical events could represent a vicious and harmful circle. Thus, therapy should be personalized.

 

Which sleeping habits and other lifestyle modifications, besides bedtime treatment, could be implemented in order to diminish the risk of CVE, in subjects with a non-dipping BP pattern?

A good sleep hygiene may be very important. Some easy suggestions could be (i) respect a regular time of rest (not later than 11 PM), (ii) avoiding late dinner time, (iii) avoiding physical exercise prior to go to bed, (iv) avoiding the use of blue-light emitting devices (smartphones, tablets, PCs, e-books), and (v) avoiding evening coffee or cola drinks or alcohol assumption.

 

Alzheimer´s disease and vascular dementia have been associated with a non-dipper pattern of BP rhythm. Which other psychiatric disorders have been associated with the phenomenon?

Depressive symptoms in older subjects are accompanied by lower nocturnal BP fall and are significant independent determinants of SBP variability. However, higher BV values during sleep are also reported in depressed females, even at the adolescent age. Overall, the great majority of poor sleep quality individuals are more prone to nocturnal elevation of BP levels. Again, patients with restless leg syndrome (RLS), that is an uncomfortable feeling in which the patient wants to budge the legs with ache in the legs, may be associated with a non-dipper patterns of BP. In particular, RLS symptom score may be higher in patients with non-dipping blood pressure patterns, and non-dipping patients often report more severe RLS.

 

According to recent literature, which other diseases could be approached from a chronobiological perspective, therapeutically speaking?

As for my expertise in the topic of internal medicine, a chronobiologic perspective should be considered for metabolic, rheumatologic, gastroenterologic, and respiratory diseases (De Giorgi et al., Eur Rev Int Med 2013). For example, adequate evidence seems to support simvastatin, corticosteroids (slow-release formulation) for arthritic patients, and ranitidine should preferably be administered in the evening. Moreover, studies on chronotherapy with low-dose aspirin are promising, showing a decrease in early morning platelet activity with evening intake compared with morning intake. Morning dosing could be better for proton pump inhibitors, whereas time of administration is not crucial for asthma inhalation drugs. As for other fields, certainly oncology and chronotherapy of cancer are the most promising and amazing topic of application.