By William C. Haas III, MD, MBA

Integrative Medicine Fellow, Department of Family and Community Medicine, University of Arizona, Tucson

Dr. Haas reports no financial relationships relevant to this field of study.

SUMMARY POINTS

  • Hypertensive patients taking estazolam achieved greater improvements in sleep scores compared to patients taking placebo.
  • The use of estazolam was associated with a 10.5 mmHg and 8.1 mmHg reduction in systolic and diastolic blood pressure, respectively, after three weeks of treatment.

SYNOPSIS: The use of a benzodiazepine hypnotic among hypertensive patients was associated with improvements in both sleep scores and blood pressure.

SOURCE: Li Y, Yang Y, Li Q, et al. The impact of the improvement of insomnia on blood pressure in hypertension. J Sleep Res 2016; [Epub ahead of print].

The relationship between disordered sleep patterns and increased cardiovascular morbidity and mortality is widely underappreciated, especially in the primary care setting. Several studies have documented an increased risk for developing hypertension among those with poor sleep patterns.1,2 Moreover, insomnia has been associated with substantial elevations in blood pressure among those already diagnosed with hypertension.3 Unfortunately, despite these negative correlations, few studies have evaluated the effect of improving sleep on blood pressure control.

Through a conventional pharmacological intervention, a group of Chinese researchers recently attempted to evaluate whether treating insomnia could effectively lower blood pressure in a group of hypertensive patients. Using standard diagnostic criteria established by the World Health Organization for hypertension and insomnia, 566 patients with both disorders were recruited from either an outpatient sleep center or an inpatient geriatric ward. Patients were permitted to participate in the study if currently treated with antihypertensive medications; however, they were excluded if currently taking hypnotics, antipsychotics, or antidepressants. Additional exclusion criteria included diagnosis of sleep apnea, drug/alcohol addiction, chronic renal failure, or a Hamilton Depression score > 16. A total of 403 patients met criteria for participation and 402 completed the study.

As a part of the intervention, patients were randomized in a double-blind fashion to receive either Prosom (estazolam) or placebo for 28 days. Estazolam was started at a dose of 1 mg nightly and adjusted upward to 2 mg on day four based on patient-perceived efficacy — only 21 patients increased to 2 mg per night. The antihypertensive medications used by the patients during the study were long-acting drugs dosed once-daily in the morning and were not changed throughout the study. Blood pressure was measured every seven days for four weeks according to measurement guidelines issued by the World Health Organization.4 Sleep patterns were assessed along the same time line using the Pittsburgh Sleep Quality Index (PSQI). Patients were also interviewed weekly to follow the use of approved medication (estazolam, placebo, antihypertensives) and restricted medication (antipsychotics, antidepressants, non-issued hypnotics, caffeine).

With regard to sleep outcomes, the global PSQI scores for patients receiving estazolam improved within seven days of treatment and reached nearly 50% improvement by day 28 (18.2 ± 4.9 to 9.3 ± 3.3; P < 0.001). Moreover, scores for all the individual PSQI components, including sleep latency, sleep efficiency, and sleep duration, improved in the treatment group after four weeks (P < 0.001), while the control group only noted improvements in sleep latency. Overall efficacy of insomnia treatment, as determined by 50% reduction in PSQI global score, occurred in 63.7% of patients in the estazolam group and only 14% of patients in the control group (P < 0.001).

Blood pressure demonstrated a similar pattern of improvement. After the third week, the Estazolam group noted significant reductions in blood pressure, and achieved a 10.5 ± 3.9 mmHg and 8.1 ± 3.6 mmHg reduction in systolic and diastolic blood pressure, respectively (P < 0.001). The control group did not achieve significant reductions in either systolic or diastolic blood pressure during the intervention.

COMMENTARY

Li and colleagues have conducted one of the few studies pertaining to the effect of sleep enhancement on blood pressure control among hypertensive patients. The researchers found that treatment with a benzodiazepine hypnotic (estazolam) resulted in improved sleep patterns, while effectively reducing daytime blood pressure. The study was generally well designed with only minor limitations. The setting of patient recruitment, particularly the inpatient geriatric unit, may have enhanced results due to artificial disturbances in sleep patterns that commonly occur in the inpatient setting and in that age group. Furthermore, recruiting patients from different settings also may have limited the external validity of the study without specifically analyzing the effect of treatment setting. Regardless of these shortcomings, the present study highlights the importance of addressing sleep disorders among hypertensive patients.

From an integrative medicine perspective, the present study was not chosen in an attempt to promote hypnotics in hypertensive patients with insomnia. Rather, the study was reviewed to draw attention to the importance of sleep in patients with comorbid conditions such as hypertension. Sleep disorders are highly prevalent in the United States, with an estimated 30-40% of the population experiencing inadequate sleep.5 Unfortunately, primary care providers routinely forget to screen for sleep disorders when conducting a health history.6 Before sleep disorders can be addressed, they must first be identified.

In addition to raising awareness, hopefully, this study will spur new research regarding integrative treatments for sleep disorders among hypertensive patients. The current body of literature supporting integrative approaches for improving blood pressure through sleep enhancement is generally lacking. One study evaluating prolonged-release melatonin failed to note improvements in blood pressure compared to placebo.7 On the other hand, another small study implementing twice daily acupressure for four weeks found in significant improvements in PSQI scores as well as systolic and diastolic blood pressure.8 Additional research demonstrating a connection between integrative treatment modalities and concurrent improvements in sleep and blood pressure are needed.

Until additional research emerges, practitioners should continue to screen for sleep disorders and review strategies to promote adequate sleep. Safe and effective sleep hygiene recommendations should start with enhancing the sleep environment to ensure the bedroom is cool, quiet, and dark. Encourage patients to reduce excessive “mind noise” through a meditative or journaling practice before bed. Recommend eliminating disrupters of the body’s natural circadian rhythm, such as television and/or computers, within the hour before bedtime. These strategies may or may not improve blood pressure as a result of improved sleep, but they will certainly help disordered sleep patterns in a non-habit forming manner. Ultimately, the present study should not be viewed as a nod for benzodiazepines use; rather it should generate a renewed focus on integrative sleep modalities.

REFERENCES

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  3. Verdecchia P, Schillaci G, Borgioni C, et al. Gender, day-night blood pressure changes and left ventricular mass in essential hypertension: Dippers and peakers. Am J Hypertens 1995;8:193-196.
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  7. Lemoine P, Wade A, Katz A, et al. Efficacy and safety of prolonged-release melatonin for insomnia in middle-aged and elderly patients with hypertension: A combined analysis of controlled clinical trials. Integr Blood Press Control 2012;5:9-17.
  8. Zheng L, Chen Y, Chen F, et al. Effect of acupressure on sleep quality of middle-aged and elderly patients with hypertension. IJNSS 2014;1:334-338.