The association of hypnotics with incident cardiovascular disease and mortality in older women with sleep disturbances

Abstract

Background/objective: Insomnia is common in older women and is associated with higher cardiovascular disease (CVD) risk. Nonbenzodiazepine GABA agonists (Z-drugs) are the most commonly prescribed sleep aids. The study objective was to determine whether the use of Z-drugs is associated with the risk of developing CVD and mortality in older women with sleep disturbances.

Patients/methods: The study cohort included post-menopausal women who, at baseline, scored ≥9 with the Women's Health Initiative Insomnia Rating Scale (N = 40,728). Members of the cohort were categorized as users of Z-drugs, users of other prescription hypnotics, or non-users. Outcomes were composite CVD (congestive heart failure, stroke, and fatal/non-fatal myocardial infarction) and mortality. Hazard ratios were estimated from Cox proportional hazards regression models adjusted for demographics, medical history, and sleep measures. To address potential confounding by indication, we also adjusted for propensity to be prescribed hypnotics.

Results: The mean age of our cohort was 63.57 years (SD = 7.23) and mean follow-up time after the initial follow-up visit was 14.0 years (SD = 6.3). Z-drug use was significantly associated with an increased risk of composite CVD (HR = 1.35, 95%CI: 1.02-1.79) and all-cause mortality (HR = 1.38, 95%CI: 1.13-1.69). When groups were divided by heavy and casual use, only heavy users (≥3 times per week) had an increased risk of mortality.

Conclusions: Z-drugs use was associated with an increased risk for death and CVD in post-menopausal women being treated for sleep disturbances. Additional research is needed to evaluate both frequency and duration of Z-drug use.

Keywords: Cardiovascular disease; Hypnotics; Insomnia; Older women; Sleep disturbances.