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. Author manuscript; available in PMC: 2013 Dec 10.
Published in final edited form as: J Affect Disord. 2012 May 11;141(0):484–487. doi: 10.1016/j.jad.2012.01.046

Sleep duration is associated with dyslipidemia in patients with bipolar disorder in clinical remission

I Soreca 1, ML Wallace 2, E Frank 1, BP Hasler 1, JC Levenson 1,3, DJ Kupfer 1
PMCID: PMC3612347  NIHMSID: NIHMS377325  PMID: 22578889

Abstract

Background

The pathways to increased cardiovascular risk in bipolar disorder include health behaviors, psychosocial stress and long-term medication exposure. However, the evidence that the association between cardiovascular risk factors and bipolar disorder remains significant after controlling for these co-factors suggests that additional important risk factors have yet to be identified. Our hypothesis is that disturbances in the sleep-wake cycle are an important and under-recognized pathway through which affective disorders lead to increased cardiovascular risk.

Methods

In patients with bipolar disorder type 1 in clinical remission, we: 1) explored whether sleep disturbance predicted the endorsement of NCEP ATP-III criteria for dyslipidemia, independent of other lifestyle factors and 2) tested the association between low HDL (NCEP-ATP III) and sleep duration measured with actigraphy over an eight-day period.

Results

Median sleep duration is significantly associated with low HDL. The risk of having low HDL increases by 1.23 with every 30 minutes of reduced sleep time.

Limitations

Since sleep patterns in patients with bipolar disorder are variable and irregular, it is possible that other sleep characteristics, not present during the span of our study, or the variability itself may be what drives the increased cardiovascular risk

Conclusions

Sleep characteristics of patients with bipolar disorder in clinical remission are associated with cardiovascular risk. More specifically, sleep duration was associated with low HDL. Clinicians should pay special attention to sleep hygiene in treating individuals with bipolar disorder, even when they are in clinical remission.

Keywords: bipolar disorder, sleep, cardiovascular risk, HDL

Introduction

The pathways through which bipolar disorder is thought to increase CV risk include health behaviors (e.g., smoking, physical inactivity, poor diet, obesity), psychosocial stress (e.g., low occupational status, low income, poor educational attainment) and long-term medication exposure. However, the evidence that the association between cardiovascular risk factors and bipolar disorder remains significant after controlling for these co-factors (Murray et al., 2009, Goldstein et al., 2009, Fiedorowicz et al., 2009) suggests that additional important risk factors have yet to be identified.

Our hypothesis is that disturbances in the sleep-wake cycle are an important and under-recognized pathway through which affective disorders lead to increased CV risk. Bipolar disorder is characterized by a high frequency of subsyndromal inter-episode symptom excursions (Sachs, 2003), including sleep disturbances. While a limited number of studies have described PSG sleep staging in euthymic patients with conflicting results (Knowles et al., 1986, Sitaram et al., 1982), recent findings from sleep diaries and actigraphy indicate that the remitted patients with bipolar disorder have a substantial degree of sleep disturbance(Millar et al., 2004, Jones et al., 2005, Harvey et al., 2005).

A wealth of research over the past decade has linked sleep disturbances and short sleep duration with an increased risk of metabolic syndrome (Hall et al., 2008, Arora et al., 2011) and, more specifically, to altered serum lipid profile (Gangwisch et al., 2010, Kaneita et al., 2008). Even though patients with bipolar disorder are especially vulnerable to cardiovascular morbidity and mortality, to the best of our knowledge no study has explored sleep as a potential link to cardiovascular risk. We therefore sought to explore whether sleep duration would predict the emdorsement of NCEP ATP-III (Grundy et al., 2005) criteria for dyslipidemia, independent of other lifestyle factors, in a sample of patients with bipolar disorder type 1 in clinical remission.

Methods

General Procedures

The Institutional Review Board at the University of Pittsburgh reviewed and approved all of the study procedures. Participants in this study were taking part in a larger NIMH funded treatment study (MH081003) comparing standard of care with an integrated model of care for patients with bipolar 1 disorder in maintenance treatment. As part of the inclusion criteria for the parent study, participants were required to meet lifetime criteria for bipolar disorder, type I (ascertained with the SCID-IV), be free of unstable or untreated medical conditions, have a BMI 25 and be in remission, defined as an HAM-D and YMRS scores 10 and 8, respectively, for at least two weeks and have not been hospitalized in the previous year. At study entry participants were also asked to complete fasting blood work to measure lipid profile and wear an actigraphy on their non-dominant wrist for eight consecutive days in their naturalistic environment. The baseline assessments were used for the current analysis. All the participants were on standard of care medications for bipolar disorder.

Dyslipidemia was defined, according to the NCEP ATP-III criteria, as having HDL-C < 40 mg/dL (male), < 50 mg/dL (female) or being on medications to correct dyslipidemia (Grundy et al., 2005).

Statistical analyses

To determine the best way to calculate the central tendency of sleep duration over one week of actigraphy, we first created a histogram of the week of sleep duration observations. Because the sleep duration data were skewed, we chose to use the median to summarize the week of observed sleep durations for each individual.

Non-parametric tests were used to compare patients with and without low HDL and the other components of the metabolic syndrome on age, HAMD, YMRS, psychotropic medications, sleep duration, and fragmentation index due to their skewed distributions. Since there was no differences in these parameters based on other components of metabolic syndrome than low HDL, a logistic regression model was then built to evaluate the contribution of median sleep duration to the likelihood of having low HDL after controlling for age, sex, BMI, and current smoking (yes/no). These covariates were selected based on univariate association with the outcome variable in this sample and also based on a priori knowledge of risk factors for low HDL.

Results

Patients that met the low HDL criterion had significantly shorter median and mean sleep duration, but did not differ on any of the other measures (including HAM-D and YMRS) (Table 1). No differences in sleep parameters or symptom severity were found when patient were compared according to the other components of the metabolic syndrome (results not shown, available upon request)

Table 1.

Subjects characteristics

Low HDL N Median (Variance)
Age No 35 43.11(95.1)
Yes 51 47.59(84.17)
BMI No 33 31.04(34.69)
Yes 48 34.49(40.23)
HRS-25 No 42 7.00(26.26)
Yes 60 7.00(11.46)
YMRS No 42 1.00(4.7)
Yes 60 1.00(5.28)
Nicotine use No 34 N/A
Yes 50
Sleep duration (hours) No 29 8.63 (101.53)
Yes 39 7.40(123.7)
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Median sleep duration is significantly associated with the low HDL. As shown in Table 2, individuals with one minute shorter median sleep duration are 1/exp(−.007*1) = 1.007 times more likely to have low HDL. In other words, the risk of having low HDL increases by 1/exp(− .007*30) = 1.23 with every 30 minutes of reduced median sleep time (Table 2).

Table 2.

Logistic regression model testing the association between median sleep duration and low HDL rate.

B SE Wald Sig Exp(B)
Age .027 .030 .804 .370 1.027
Sex −.072 .596 .014 .904 .931
BMI .028 .045 .385 .535 1.029
Nicotine use .825 .707 1.362 .243 2.283
Sleep duration −.007 .003 4.368 .037 .993
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Discussion

Sleep characteristics during the inter-episode interval in bipolar disorder are an important and yet under-recognized feature of this phase of the illness and are associated with impaired functioning and quality of life (Gruber et al., 2009) (Ehlers et al., 1988, Harvey et al., 2005). Moreover, ongoing sleep disturbances are a risk factor for syndromal recurrence (Jackson et al., 2003, Colombo et al., 1999, Kasper and Wehr, 1992, Wu and Bunney, 1990). In this study, we show that sleep characteristics of patients with bipolar disorder in clinical remission are associated with cardiovascular risk. More specifically, sleep duration was associated with increased risk of having low HDL according to the ATP III definition. Of note, while the median sleep duration of patients with low HDL and normal HDL differed by roughly one hour, overall sleep duration was comparable to normative values for the healthy subjects in both groups (Monk et al., 2000).

The association between sleep duration and dyslipidemia in the general population has been shown to have a bimodal distribution, with both shortest and longest reported sleep duration being associated with CVD risk (van den Berg et al., 2008, Bjorvatn et al., 2007). Mechanisms linking short sleep duration (roughly 4 hours per night) with increased cardiovascular risk involve increased markers of inflammation and autonomic dysregulation (van Leeuwen et al., 2009, Novati et al., 2008, Meier-Ewert et al., 2004). Animal models of sleep restriction suggest that insufficient sleep, by acting on stress systems, may predispose individuals to further mood and neuroendocrine dysregulation (van Leeuwen et al., 2009). This is consistent with epidemiological evidence that sleep restriction is an important risk factor for stress-related conditions, including cardiovascular diseases and mood disorders (Hoevenaar-Blom et al., 2011, Murray and Harvey, 2010).

Longer reported sleep, on the other hand, may simply represent longer time in bed (versus longer time of actual consolidated sleep) and thus reflect worse general health or simply lower level of daily activity. In our sample, the overall median sleep duration was roughly 8 hours, with approximately 1 hour difference in sleep duration between the low and the normal HDL group, suggesting that the parameters for “healthy” sleep duration in patients with bipolar disorder may be different than those for the general adult population. Alternatively, one could argue that mechanisms linking sleep duration to cardiovascular risk may be different in patients with mood disorders, making them more vulnerable to changes in sleep duration even within values that are considered normal for adult individuals.

The present study is not free of limitations: the cross-sectional design prevents us from inferring causal relationships; since sleep patterns in patients with bipolar disorder are variable and irregular, it is possible that other sleep characteristics or mood symptoms, not present during the span of our study, or the variability itself may be what drives the increased cardiovascular risk. We tried to minimize uncaptured variability by recruiting patients who had been in clinical remission for at least 2 weeks and by assessing their sleep over an eight-day period. Even though current medications did not have an effect on the results, we can’t rule out that prior medications used may still confound the association between sleep parameters and HDL.

This is the first study to show that in patients with bipolar disorder in clinical remission, sleep duration is associated with a worse cardiovascular profile. Further studies to elucidate mechanisms for sleep-related cardiovascular risk in mood disorder are needed. At the same time, this report suggest that clinicians should pay special attention to sleep hygiene in treating individuals with bipolar disorder, even when they are in clinical remission.

Acknowledgement

We thank Victoria J. Grochocinski and David E. Curet for data management, Joan Buttenfield and the DMDPP clinicians for completing the assessments. We finally thank all our study participants.

Funding This work was funded by MH081003 (DJK) and DA027508-03 (IS)

Footnotes

Contributors Author I.S. designed the study managed the literature searches and wrote the first draft of the manuscript. Author M.L.W. managed the analyses. Author EF and DJK designed the study and wrote the protocol. Authors J.C.L. and B.P.H. managed the literature searches and contributed to writing the first draft of the manuscript. All authors contributed to and have approved the final manuscript.

Conflict of Interest Drs I.S., M.L.W., B.P.H., J.C.L. and D.J.K. have no potential conflict of interest to disclose. Dr EF is in the Servier International Advisory Board and owns Guilford Press and American Psychological Association Press Royalties.

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