The association between RLS and both CVRFs, such as hypertension and diabetes, and CVDs still remains elusive. Although several shared physiopathological causes could explain these possible relationships, the emerging body of literature focusing on these disorders remains controversial. The reasons for these inconsistent findings are mainly due to the different methodologies applied. First, considering that RLS, CVRFs and CVDs are influenced by age and sex, many clinical and population-based studies performed a selection bias by restricting the sample collection to these covariates. Second, assessments of covariates are often incomparable and the methods applied for diseases assessment are often affected by low sensitivity and specificity. Only few population-based studies collected data by means of face-to-face interview or physical examination in order to limit the false positive rate compared to questionnaires administered by mail or telephone. The assessment of RLS was not always performed according to IRLSSG criteria and anyway the four diagnostic criteria did not allow the exclusion of other disorders that may act as mimics (Hening et al., 2009; Allen et al., 2014). Disease assessment ranged from a self-reported diagnosis, information on the use of specific medications, or a direct measurement of BP and blood glucose levels. Moreover, some antihypertensive medications, such as beta-blockers and certain calcium channel blockers, could both ameliorate and aggravate RLS symptoms (Innes et al., 2012) and therefore it would be important to consider medications as confounding factors. In addition, the co-occurrence of several CVRFs is frequent and they may influence each other. Therefore, the cross-sectional nature of most studies cannot assess the causal relationship between them and the variables of interest (i.e., RLS and/ or CVDs). Finally, only few studies adjusted their analyses for other cardiovascular risk factors, such as diabetes mellitus, history of myocardial infarction, BMI, dyslipidemia, and smoking status, that might act as confounders or mediators. In summary, longitudinal population-based studies and meta-analyses will be necessary in order to build a sufficiently robust body of evidence on this topic.

中文翻译：

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不安腿综合征，心血管疾病和代谢疾病之间的关联：假设和文献证据。

RLS与两个CVRF（例如高血压和糖尿病）以及CVD之间的关联仍然难以捉摸。尽管几种共同的生理病理原因可以解释这些可能的关系，但针对这些疾病的新兴文献仍存在争议。这些发现不一致的原因主要是由于使用了不同的方法。首先，考虑到RLS，CVRF和CVD受年龄和性别的影响，许多临床和基于人群的研究通过将样本收集限制为这些协变量来进行选择偏倚。其次，对协变量的评估通常是无与伦比的，并且疾病评估所采用的方法通常受敏感性和特异性低的影响。与通过邮件或电话调查的问卷相比，只有少数基于人群的研究通过面对面访谈或体格检查来收集数据，以限制假阳性率。并非总是根据IRLSSG标准对RLS进行评估，并且无论如何，这四个诊断标准都不能排除可能起模仿作用的其他疾病（Hening等，2009； Allen等，2014）。疾病评估范围包括自我报告的诊断，有关使用特定药物的信息或直接测量BP和血糖水平。此外，某些降压药，例如β受体阻滞剂和某些钙通道阻滞剂，可以改善和加重RLS症状（Innes等，2012年），因此将药物视为混杂因素非常重要。此外，多个CVRF并存的情况很常见，并且它们可能会相互影响。因此，大多数研究的横断面性质无法评估它们与关注变量（即RLS和/或CVD）之间的因果关系。最后，只有极少的研究调整了对其他心血管危险因素的分析，这些因素包括糖尿病，心肌梗塞病史，BMI，血脂异常和吸烟状况，这些因素可能是混杂因素或调解人。总之，基于纵向的人群研究和荟萃分析将是必要的，以便为该主题建立足够有力的证据。大多数研究的横断面性质无法评估它们与目标变量（即RLS和/或CVD）之间的因果关系。最后，只有极少的研究调整了对其他心血管危险因素的分析，这些因素包括糖尿病，心肌梗塞病史，BMI，血脂异常和吸烟状况，这些因素可能是混杂因素或调解人。总之，基于纵向的人群研究和荟萃分析将是必要的，以便为该主题建立足够有力的证据。大多数研究的横断面性质无法评估它们与目标变量（即RLS和/或CVD）之间的因果关系。最后，只有极少的研究调整了对其他心血管危险因素的分析，这些因素包括糖尿病，心肌梗塞病史，BMI，血脂异常和吸烟状况，这些因素可能是混杂因素或调解人。总之，基于纵向的人群研究和荟萃分析将是必要的，以便为该主题建立足够有力的证据。和吸烟状况，可能会成为混杂因素或调解人。总之，基于纵向的人群研究和荟萃分析将是必要的，以便为该主题建立足够有力的证据。和吸烟状况，可能会成为混杂因素或调解人。总之，基于纵向的人群研究和荟萃分析将是必要的，以便为该主题建立足够有力的证据。