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Poor Sleep and Hypertension

In Fitness/Health, Insomnia on Wednesday, 26 September 2012 at 07:36

Poor Sleep Relted to Resistant Hypertension

Sue Hughes

September 24, 2012 (Washington, DC) — Poor sleep quality is associated with a doubling in the risk of resistant hypertension in women, with the mechanism possibly mediated by depression, a new study shows [1].

The study was presented here at last week’s American Heart Association High Blood Pressure Research 2012 Scientific Sessions by Dr Rosa Maria Bruno (University of Pisa, Italy).

“I would say that treating insomnia may improve resistant hypertension, although we need further data before we make firm clinical recommendations on this,” Bruno told heartwire .

She commented: “There is lots of evidence that sleep disorders are related to cardiovascular events, but most relate to sleep-disordered breathing such as sleep apnea. Also, there have been many studies showing an association between short sleep duration and the incidence of cardiovascular events or hypertension. But we looked at whether insomnia was linked to the severity of hypertension, and we found poor sleep quality was significantly more prevalent in patients with resistant hypertension.”

Quality Rather Than Quantity

The researchers reported that it was the quality of sleep rather than the duration of sleep that seemed to be the important factor in the relationship with resistant hypertension. They also found a large difference between men and women.

Bruno noted: “In women, poor sleep quality was strongly related to anxiety and depression and resistant hypertension, but this was not the case for men. This difference remained after accounting for other confounding factors. In women, we found that poor sleep quality was associated with a fivefold increase in the probability of having resistant hypertension, even after adjustment.”

She cautioned that as this was only a cross-sectional study, they can conclude there is an independent association between poor sleep quality and resistant hypertension, but they cannot deduce that this is a causal effect. “This needs to be confirmed in a prospective study. It could also be that the hypertension is causing the insomnia, but we believe that the insomnia is making the hypertension worse.”

Experimental evidence supports this view. It is known that interrupted sleep stimulates the sympathetic nervous system and increases cortisol levels, both of which cause an increase in blood pressure.

For the study, data on sleep quality, anxiety/depression, and cardiovascular risk factors were collected for 270 patients from a hypertension outpatient unit. Sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI), and anxiety and depression with the Beck Depression Inventory (BDI). Poor sleep quality was defined as PSQI >5, mild to severe depressive symptoms as BDI score >10. Patients with obstructive sleep apnea were excluded. Resistant hypertension was defined as a failure to control hypertension with three or more drugs.

Complete data were available for 234 patients, half of whom were women. Mean sleep duration was 6.4 hours, and 49% of participants had short sleep duration (less than six hours), which was similar in both sexes.

However, women had higher PSQI scores and a higher prevalence of poor sleep quality. Women showed also higher depression scores and prevalence of depressive symptoms than men.

Sleep and Depression Scores in Women vs Men

Score Women Men p
PSQI score 5.2 3.6 0.03
Poor sleep quality (%) 46 30 0.01
Depression score 4.5 1.8 0.006
Prevalence of depressive symptoms (%) 20 7 0.003

Resistant hypertension was present in 15% of patients, and these individuals had higher PSQI scores than those without resistant hypertension, a difference shown in women but not in men. The association between depression score and resistant hypertension showed a similar trend.

Sleep Scores (PSQI) Related to Resistant Hypertension

Group Resistant hypertension No resistant hypertension p
Entire population 5.8 4.1 0.03
Women 6.8 4.8 0.04
Men 4.7 3.5 0.37

Depression Scores (BDI) Related to Resistant Hypertension

Group Resistant hypertension No resistant hypertension p
Entire population 3.6 2.8 0.02
Women 5.1 3.7 0.03
Men 2.0 1.9 0.53

In a multiple logistic regression analysis (including age, sex, obesity, diabetes, previous CV events, sleep duration, use of hypnotic drugs) poor sleep quality was independently associated with resistant hypertension (OR 2.2). But this relationship lost significance when depressive symptoms were included in the model.

References

  1. Bruno RM, Palagini L, Di Giulio A, et al. Relation between poor sleep quality and resistant hypertension. American Heart Association High Blood Pressure Research Scientific Sessions; September 21, 2012; Washington, DC. Abstract 63.

Retrieved from: http://www.medscape.com/viewarticle/771457?src=nl_topic

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friendship is like a box of chocolates…

In Humor, Insomnia on Monday, 24 September 2012 at 07:30

Hypnotic use and side effects

In Insomnia, Medication, Neuropsychology, Psychiatry on Tuesday, 18 September 2012 at 05:25

chronic insomnia and sleep deprivation are major issues affecting over 30% of  the u.s population.  approximately 10 million people are prescribed hypnotics to treat insomnia.  while the concurrent effects from untreated insomnia are vast, and hypnotic use may be the only viable option, it is suggested that one educate themselves on the effects related to untreated insomnia (see previous post titled “the state of sleep in the u.s.”) and options for treatment as well as recent research regarding the side-effects of some treatments.  

Hypnotic Use Linked With Increased Risk for Early Death

Megan Brooks & Laurie Barclay, MD

http://www.medscape.org/viewarticle/759730

Clinical Context

In 2010, approximately 6% to 10% of US adults used a hypnotic drug for sleep problems. Earlier studies have suggested an association between hypnotic use and excess mortality rates.

The objectives of this study by Kripke and colleagues were to estimate the mortality risks and cancer risks associated with specific, currently popular hypnotics, using a matched cohort design and proportional hazards regression models. In addition, the investigators examined what degree of risk associated with hypnotic use could be explained by confounders and comorbid conditions.

Study Synopsis and Perspective

Adults who use hypnotics to help them sleep have a greater than 3-fold increased risk for early death, according to results of a large matched cohort survival analysis.

Hazard ratios were elevated in separate analyses for several commonly prescribed hypnotics and for newer shorter-acting drugs, the researchers say. The drugs included benzodiazepines, such as temazepam; nonbenzodiazepines, such as zolpidem, eszopiclone, and zaleplon; barbiturates; and sedative antihistamines.

“The take-home from the article is that the risks associated with hypnotics are very high, and certainly these possible risks outweigh any benefits of hypnotics,” first author Daniel F. Kripke, MD, co-director of research at the Scripps Clinic Viterbi Family Sleep Center in La Jolla, California, told Medscape Medical News.

“Our study is the 19th epidemiological study showing that hypnotics are significantly associated with excess mortality,” Dr. Kripke added, noting it is also the first to specify the drugs and the first to show dose-response. “Even considering that the epidemiologic studies show association and do not prove causality, the risks look much larger than the benefits,” Dr. Kripke added.

Their analysis also showed a 35% overall increased risk for cancer in hypnotics users. “The risks of hypnotics are similar to the risks of cigarettes,” Dr. Kripke said.

The associations were evident in every age but were greatest among those aged 18 to 55 years, the investigators note. “Rough order-of-magnitude estimates…suggest that in 2010, hypnotics may have been associated with 320,000 to 507,000 excess deaths in the USA alone,” they report.

The new report is published February 28 in BMJ Open.

Dr. Kripke, a long-time critic of hypnotics, emphasized that the data “apply only to the particular hypnotics studied when used as sleeping pills. They do not apply to drugs which were not tested.” Moreover, he said, they may not apply when the drugs are used other purposes, “in which they might be life-saving. Oddly enough, the data for use of benzodiazepines for anxiety may not be similar,” Dr. Kripke noted.

“Risks Outweigh Any Benefits”

In 2010, an estimated 6% to 10% of adults in the United States took a hypnotic drug to help them sleep, with the percentages probably higher in Europe, Dr. Kripke and colleagues note in their report.

Data for their analysis were derived from the electronic medical records of the Geisinger Health System, the largest rural integrated health system in the United States, serving a 41-county area of Pennsylvania with roughly 2.5 million people.

Study participants included 10,529 adults (mean age, 54 years) who received hypnotic prescriptions and 23,676 matched controls with no hypnotic prescriptions, followed for an average of 2.5 years between 2002 and 2007.

“As predicted,” report the researchers, patients prescribed any hypnotic, even fewer than 18 pills per year, were significantly more likely to die during follow-up compared with those prescribed no hypnotics. A dose-response effect was evident, and the findings “were robust with adjustment for multiple potential confounders and consistent using multiple strategies to address confounding by health status,” they report.

Table 1. Risk for Death by Level of Hypnotic Use

Any Hypnotic

Hazard Ratio (95% Confidence Interval)

P Value

Up to 18 pills per year

3.60 (2.92 – 4.44)

<.001

18 – 132 pills per year

4.43 (3.67 – 5.36)

<.001

> 132 pills per year

5.32 (4.50 – 6.30)

<.001

Zolpidem was the most commonly prescribed hypnotic during the study interval, followed by temazepam; both were associated with significantly elevated risks for death, again in a dose-response fashion.

Table 2. Risk for Death with Zolpidem and Temazepam

Agent (mg/y)

Hazard Ratio (95% Confidence Interval)

P Value

Zolpidem

5 – 130

3.93 (2.98 – 5.17)

<.001

130 – 800

4.54 (3.46 – 5.95)

<.001

> 800

5.69 (4.58 – 7.07)

<.001

Temazepam

10 – 240

3.71 (2.55 – 5.38)

<.001

240 – 1640

4.15 (2.88 – 5.99)

<.001

> 1640

6.56 (5.03 – 8.55)

<.001

“The death [hazard ratios] HR associated with prescriptions for less commonly prescribed hypnotic drugs were likewise elevated and the confidence limits of death hazards for each other hypnotic overlapped that for zolpidem, with the exception of eszopiclone, which was associated with higher mortality,” the investigators report.

Any hypnotic use in the upper third (>132 pills per year) was also associated with a modest but statistically significant increased risk for incident cancer (HR, 1.35; 95% CI, 1.18 – 1.55). The cancer risk was nearly 2-fold higher with temazepam (>1640 mg per year; HR, 1.99; 95% CI, 1.57 – 2.52).

Study Raises “Important Concerns”

Prior studies have shown multiple causal pathways by which hypnotics might raise the risk for death. For example, controlled trials have shown that hypnotics impair motor and cognitive skills, such as driving. Use of hypnotics has been linked to an increase in automobile crashes and an increase in falls due to hangover sedation. In some patients, hypnotics may increase or prolong sleep apneas and suppress respiratory drive. They may also increase incident depression.

“The meagre benefits of hypnotics, as critically reviewed by groups without financial interest… would not justify substantial risks,” the investigators write. They say a “consensus is developing that cognitive-behavioural therapy of chronic insomnia may be more successful than hypnotics.”

In a prepared statement, Trish Groves, MBBS, MRCPsych, editor-in-chief of BMJ Open, comments: “Although the authors have not been able to prove that sleeping pills cause premature death, their analyses have ruled out a wide range of other possible causative factors. So these findings raise important concerns and questions about the safety of sedatives and sleeping pills.”

American Academy of Sleep Medicine Urges Caution

In a statement, Nancy Collop, MD, president of the American Academy of Sleep Medicine (AASM) urged caution in interpreting these data.

“Although the study found that the use of hypnotic medication, or sleeping pills, was associated with an increased risk of mortality, a cause-and-effect relationship could not be established because the study only analyzed an insurance database,” Dr. Collop notes in the statement. “The authors also noted several other limitations to their study. For example, it was impossible for them to control for psychiatric conditions and anxiety, which is an area of significant concern to this study population.” In addition, she adds, those taking hypnotics had a “markedly greater rate of several comorbid health problems than the control group, suggesting they were a sicker population.”

AASM guidelines say that hypnotic medication prescribed appropriately and monitored carefully is a “reasonably” safe therapy that provides some improvement in people with insomnia, Dr. Collop notes in the statement. When possible, behavioral and cognitive therapies should be used and if needed supplemented with short-term use of hypnotics, the guidelines recommend. “Patients taking hypnotics should schedule regular follow-up visits with their physician, and efforts should be made to prescribe the lowest effective dose of medication and to reduce the medication’s usage when conditions allow,” the statement adds.

Effective treatment of insomnia is important because it’s associated with a “host” of comorbid conditions, including major depression and other psychiatric disorders, as well as increased for suicide, motor vehicle accidents, and possibly cardiovascular disease, Dr. Collop points out. Other research has shown widespread changes in physiology and the central nervous system associated with insomnia, and the “marked dysfunction and diminished quality of life” reported by some of those with insomnia are similar to that seen with major psychiatric or medical illnesses.

“We commend Drs. Kripke, Langer and Kline for contributing new scientific information to the study of sleep medicine,” Dr. Collop notes in the AASM statement. “We believe it is important for patients and physicians to be aware of how sleep issues impact health. But we caution physicians and patients to consider the years of research in support of limited hypnotics use, under the clinical guidelines of the AASM, before making any drastic changes in therapy.”

The AASM recommends that individuals with ongoing sleep problems should seek help from a board-certified sleep physician, “at one of 2,400 AASM-accredited sleep centers across the US.” A sleep center listing is found at the AASM’s site, www.sleepcenters.org.

In a competing interests statement, Dr. Kripke reports long-term criticism of hypnotic drugs at his nonprofit Web site. He also discloses a family interest in an investment corporation that has a small percentage of its assets in stock of sanofi-aventis and Johnson & Johnson. His 2 coauthors have disclosed no relevant financial relationships. Dr. Collop has disclosed no relevant financial relationships.

BMJ Open. Published online February 28, 2012. Abstract

Study Highlights

  • This matched cohort study took place at a large, integrated US health system.
  • The investigators extracted longitudinal electronic medical records for a 1-to-2 matched cohort survival analysis.
  • Patients who received hypnotic prescriptions (n = 10,529) were matched with 23,676 control participants with no hypnotic prescriptions.
  • Mean age was 54 years, and average duration of follow-up (between January 2002 and January 2007) was 2.5 years.
  • Data were adjusted for age, sex, smoking, body mass index, ethnicity, marital status, alcohol use, and history of cancer.
  • Cox proportional hazards models allowed calculation of HRs for death.
  • The Cox models were controlled for risk factors and used up to 116 strata, which exactly matched case patients and control participants by 12 classes of comorbidity.
  • Compared with patients who were prescribed no hypnotics, those who were prescribed any hypnotic had markedly increased hazards of dying.
  • There was a dose-response association. The HR was 3.60 (95% CI, 2.92 – 4.44) for 0.4 – 18 doses per year, 4.43 (95% CI, 3.67 – 5.36) for 18 to 132 doses per year, and 5.32 (95% CI, 4.50 – 6.30) for more than 132 doses per year.
  • In separate analyses, HRs were increased for several widely used hypnotics and for newer shorter-acting drugs, including zolpidem, temazepam, eszopiclone, zaleplon, other benzodiazepines, barbiturates, and sedative antihistamines.
  • Among users in the highest tertiles of doses per year, the HRs for death were 5.3 for all hypnotics, 5.7 for zolpidem alone, and 6.6 for temazepam alone.
  • Patients in the highest tertile of hypnotic use had a significant (35%) increased risk for incident cancer (HR, 1.35; 95% CI, 1.18 – 1.55).
  • These findings were robust within groups having a comorbid condition, suggesting that the risks for death and cancer associated with hypnotic drugs were not explained by preexisting disease.
  • Hypnotic prescriptions were associated with increased diagnoses of esophageal regurgitation and peptic ulcer disease; the investigators note that increased regurgitation could cause esophageal damage and cancer.
  • On the basis of these findings, the investigators concluded that hypnotic prescriptions was associated with more than a 3-fold increased risk for death, even when the prescription was for less than 18 pills per year.
  • This association was also observed in separate analyses for several commonly used hypnotics and for newer, shorter-acting drugs. Control of selective prescription of hypnotics for patients in poor health did not explain the observed excess mortality rates.
  • Limitations of this study include possible residual confounding, lack of data on compliance with prescriptions, and inability to determine causality or to control for depression and other psychiatric symptoms.

Clinical Implications

  • Compared with control participants not receiving hypnotic prescriptions, patients receiving prescriptions for zolpidem, temazepam, and other commonly used hypnotics had a more than 3-fold risk for greater mortality in this matched cohort study. There appeared to be a dose-response relationship, but even patients prescribed less than 18 hypnotic doses per year had increased mortality rates.
  • Among patients prescribed hypnotics, the incidence of cancer was increased for several specific types of cancer, and those prescribed high doses had an increased overall rate of cancer of 35%.
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