Prospective study of restless legs syndrome and total and cardiovascular mortality among women

Objective We prospectively examined whether women with physician-diagnosed restless legs syndrome (RLS) had a higher risk of total and cardiovascular disease (CVD) mortality relative to those without RLS. Methods The current study included 57,417 women (mean age 67 years) from the Nurses' Health Study without cancer, renal failure, and CVD at baseline (2002). Main outcomes were total and CVD mortality. We used the Cox proportional hazards model to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and CVD-specific mortality based on RLS status, adjusting for age, presence of major chronic diseases, and other potential confounders. Results We documented 6,448 deaths during 10 years of follow-up. We did not observe a significant association between presence of physician-diagnosed RLS and high risk of total mortality (adjusted HR 1.15, 95% CI 0.98-1.34). When cause-specific mortality was studied, participants with RLS had a significantly higher risk of CVD mortality (adjusted HR 1.43, 95% CI 1.02-2.00) relative to those without RLS after adjustment for potential confounders. Longer duration of RLS diagnosis was significantly associated with a higher risk of CVD mortality (p for trend = 0.04). Excluding participants with common RLS comorbidities strengthened the association between RLS and total (adjusted HR 1.43, 95% CI 1.03-1.97) and CVD mortality (adjusted HR 2.27, 95% CI 1.21-4.28). However, we did not find a significant association between RLS and mortality due to cancer and other causes. Conclusions Women with RLS had a higher CVD mortality rate, which may not be fully explained by common co-occurring disorders of RLS.