Publications

OBJECTIVE

To determine whether greater frequency and severity of hot flashes are independently associated with insomnia symptoms and objective measures of disrupted sleep among healthy postmenopausal women with hot flashes.

METHODS

A baseline cross-sectional analysis of a multicenter, randomized trial in 217 healthy postmenopausal women aged 40 to 60 years with hot flashes was conducted. Hot flash frequency and severity were recorded in a daily diary; frequency of moderate to severe hot flashes was the primary measure. Insomnia symptoms were assessed with the Insomnia Severity Index (ISI). Hot flash frequency and severity and objective parameters of sleep-wake patterns (using a wrist actigraph) were concurrently measured over an average of seven consecutive 24-hour periods in a subcohort of 112 women.

RESULTS

The mean age of participants was 54 years, and 80% were white; 33% had an ISI score greater than 14, consistent with at least moderate insomnia. In multivariable analysis, the mean ISI score showed a stepwise increase in magnitude with higher frequency of moderate to severe hot flashes (adjusted mean ISI score, 9.5, 11.4, 11.9, and 13.0 for quartiles 1-4, respectively; P for trend = 0.002). Higher frequency of moderate to severe hot flashes was also independently associated in a graded manner with greater nighttime wakefulness (P for trend = 0.028) and a higher number of long wake episodes (P for trend = 0.008) but was not related to sleep efficiency, total sleep time, or sleep latency.

CONCLUSIONS

Among healthy postmenopausal women with hot flashes, frequency of moderate to severe hot flashes was independently associated in a graded manner with severity of insomnia symptoms and objective measures of nighttime wakefulness and sleep fragmentation.

Activation of sphingosine kinase/sphingosine 1-phosphate-mediated signaling has emerged as a critical cardioprotective pathway in response to acute ischemia/reperfusion injury. Application of exogenous sphingosine 1-phosphate (S1P) in cultured cardiac myocytes subjected to hypoxia or treatment of isolated hearts either before ischemia or at the onset of reperfusion (pharmacologic preconditioning or postconditioning) exerts prosurvival effects. Synthetic congeners of S1P mimic these responses. Gene-targeted mice null for the sphingosine kinase 1 isoform whose hearts are subjected to ischemia/reperfusion injury exhibit increased infarct size and respond poorly either to ischemic preconditioning or to ischemic postconditioning. Measurements of cardiac sphingosine kinase activity and S1P parallel these observations. High-density lipoprotein is a major carrier of S1P, and studies of hearts in which selected S1P receptors have been deleted implicate the S1P cargo of high-density lipoprotein in cardioprotection. These observations have considerable relevance for future therapeutic approaches to acute and chronic myocardial injury.