Mean age of subjects was 42.3 (21.2) years. Mean PLMI was 19.3 (22.0). Iron deficiency was the most common form of secondary RLS observed, with 59 patients having a serum ferritin < 50 ng/mL (54% of subjects for whom ferritin measurements were available). Two women were pregnant at the time of enrollment and none of the patients had end-stage renal disease. Thirty-nine percent of subjects were men and 15% were African-American. Medical comorbidities were common, with hypertension being the most common (). However, diagnosed cardiovascular disease (coronary artery disease, cardiomyopathy, or congestive heart failure) and cerebrovascular disease (stroke or transient ischemic attack) were uncommon, each occurring in only four percent of subjects.
Demographic and clinical features
Periodic leg movements were significantly associated with many covariates (). PLMI was significantly higher in subjects with co-morbid hypertension, diabetes, hyperlipidemia, and cerebrovascular disease. Men and patients on medications with CRP-lowering effects also had higher mean PLMIs. Higher levels of PLMs were also significantly correlated with age, BMI, and RDI.
Relationships between PLMs and covariates (univariate analyses)
PLMs were unrelated to TNF-alpha levels (Spearman correlation r(135) = −0.05, p = 0.54). Those with the highest quartile of TNF-alpha values had similar mean PLMs to those with the lowest quartile (20.9 vs 16.7, t(53) = −0.91, p = 0.36). PLMs were unrelated to IL-6 (Spearman correlation r(135) = 0.04, p = 0.63). Those patients with the highest quartile IL-6 values did not have higher mean PLMs than those with the lowest quartile (20.6 vs 18.8, t(67) = −0.31, p = 0.76).
In contrast, PLMs were modestly but significantly correlated with log-CRP values (r(129)) = 0.19, p = 0.03, ). In the unadjusted logistic model, the odds of elevated CRP were significantly higher for those with PLMs ≥ 45/hour (OR 3.56, 95% CI 1.26 to 10.03, p = 0.02, df = 1, n = 131 for model). Relative to the low-intermediate CRP patients, those with high CRP were more likely to be female, had higher mean BMI, were more likely to have clinically-suspected OSA, and tended toward having higher measured RDIs (). Adjusting the regression model for age, gender, race, diabetes, hypertension, hyperlipidemia, CRP-lowering medication, inflammatory conditions, and body mass index, PLMs >45/hour remained a significant predictor of CRP (OR 8.60, 95% CI 1.23 to 60.17, p = 0.03, df = 10, n = 101). Female gender (OR 32.6, p = 0.0007) and body mass index (OR = 3.7, p = 0.0006) were the only other significant predictors of high CRP in the multivariate model. Including serum ferritin level as a dichotomous variable (less than or greater than 50 ng/mL) resulted in a model that ran on fewer subjects, but PLMS, female gender, and body mass index remained the only significant predictors of elevated CRP (data not shown). Similarly, when including clinically-suspected OSA in the multivariate model, the same three variables (PLMs, gender, BMI) remained significant predictors of elevated CRP.
Patients with restless legs syndrome who have frequent periodic leg movements of sleep are more likely to have elevated levels of C-reactive protein, but not IL-6 or TNF-alpha.