Restless Legs Syndrome as a Prognostic Tool for Cardiovascular Disease
Year: 2015
Type: editorial
Abstract: The authors have indicated no financial conflicts of interest. Restless legs syndrome (RLS), clinically characterized by urges to move the legs that worsen with rest or at night and are relieved with movement,1 is a common condition that affects an estimated 5% to 10% of the population.2–4 Past epidemiological studies have investigated the relationship between RLS and associated downstream impacts on the cardiovascular system, but results from both cross-sectional and prospective studies have been mixed. In the Sleep Heart Health Study cross-sectional cohort study, RLS was associated with coronary artery disease and cardiovascular disease.5 However, in the cross-sectional Women's Health Study, RLS was not associated with major cardiovascular disease.6 Results from prospective studies were similarly mixed. In the prospective analyses based on the Women's Health Study6 and the Physician's Health Study,7 RLS was not associated with increased risk of developing cardiovascular disease. In contrast, in the prospective Nurses' Health Study, women with RLS duration of 3 or more years had approximately 70% increased risk of developing coronary heart disease, after adjusting for other well-known risk factors for coronary heart disease.8 In this issue of SLEEP, Van Den Eeden and colleagues9 provide important information about the relationship between RLS and cardiovascular disease that may help explain these past conflicting results. Their study differentiated between diagnoses of primary RLS and secondary RLS. The latter category included RLS secondary to another diagnosis, including anemia, pregnancy and chronic renal failure. Primary RLS was not associated with increased risk of cardiovascular disease, but had a 20% increased risk of hypertension. Secondary RLS, however, was significantly associated with increased risk of cardiovascular disease, coronary artery disease, and hypertension. The only outcome that was consistently associated with both primary and secondary RLS was hypertension; this is consistent with our previous finding that women with RLS had a higher prevalence of hypertension.10 As previous epidemiological studies generally did not distinguish between primary and secondary RLS, it is possible that studies that were negative for an association between RLS and cardiovascular disease were enriched in primary RLS cases, while positive studies were enriched in secondary RLS cases. The study of Van Den Eeden et al.9 also provides further support for primary and secondary RLS as distinct clinicopathological entities. Primary and secondary RLS have similar clinical presentations, and differentiation between the two requires knowledge of the patient's family history and comorbidities.11 Studies have shown that primary and secondary RLS cases have different characteristics. Cases of primary or idiopathic RLS are usually familial, though exact inherited genetic abnormalities are still under investigation.11,12 Patients with idiopathic RLS are typically younger at age of onset,11 which was also confirmed by Van Den Eeden et al.9 In comparing patients with idiopathic RLS and uremic RLS, patients with uremic RLS had faster and more severe clinical deterioration than idiopathic RLS with less response to dopaminergic agents.13 Consistently, Van Den Eeden et al. found that secondary RLS—including RLS secondary to renal failure—portended more concerning prognoses.9 We hypothesize that secondary RLS is a useful marker of increased risk of future development of cardiovascular disease, but the mechanism is likely through the underlying medical conditions that gave rise to the RLS. Indeed, Van Den Eeden et al. found that individuals with secondary RLS had ∼30% to 40% increased risks of developing coronary artery disease and cardiovascular disease, respectively.9 The association between primary/secondary RLS and cardiovascular disease and/or hypertension highlights the importance of screening RLS to identify individuals with increased risk of cardiovascular disease. Future studies can seek to distinguish medical etiologies underlying RLS that are associated with the highest risk of cardiovascular disease. In turn, early lifestyle modifications and medical interventions of coexisting risk factors, such as better control of hyperlipidemia and obesity,14 can potentially decrease risk of RLS and cardiovascular disease.
Source: SLEEP
DOI: 10.5665/sleep.4790
Authors: Janice C. Wong, Weijuan Li, Xiang Gao
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W969564897