PLMS Are Another Risk Factor for Cardiovascular Disease in OSA, Study Suggests

Periodic limb movements during sleep (PLMS) are an additional risk factor for cardiovascular disease in obstructive sleep apnea (OSA), according to a study published in Journal of Sleep Research.

PLMS and OSA are both linked with increased sympathetic tone and have been proposed as risk factors for heart diseases, including cardiovascular disease in particular, the authors wrote. Because sympathetic system activation may lead to dyslipidemia, PLMS could be an extra risk factor for cardiovascular disease in patients with OSA.

The study aim was to determine if the presence of PLMS affects serum lipid levels in patients with OSA. PLMS are linked with a significant but small increase in daytime blood pressure values in patients with OSA, suggesting that additional mechanisms, like dyslipidemia, could be plausible for PLMS-associated cardiovascular risk in OSA.

First, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, and triglyceride (TG) levels were examined in 4138 patients with OSA in the European Sleep Apnea Database cohort, separated into those with a PLMS index of at least 15 per hour (n = 628) and controls (n = 3510). Analysis of covariance adjusted for age, sex, body mass index (BMI), apnea-hypopnea index (AHI), alcohol intake, smoking status, diabetes, insomnia, and study site was used to evaluate differences in lipid levels between PLMS and controls.

Of the patients with PLMS, 24% were female, the mean (SD) age was 54.4 (12.1) years, the mean BMI was 31.9 (5.8) kg/m², and the mean (SD) AHI was 36.7 (25.4) per hour. This group had higher mean (SD) TG (1.81 [1.04] vs 1.69 [0.90] mmol/L^–1; P = .002) and lower high-density lipoprotein cholesterol (1.19 [0.34] vs 1.24 [0.37] mmol/L^–1; P = .002) levels compared with control patients. There was no difference in total cholesterol (4.98 [1.10] vs 4.94 [1.07] mmol/L^–1), LDL cholesterol (3.04 [0.96] vs 2.98 [0.98] mmol L^–1) or non-HDL cholesterol (3.78 [1.10] vs 3.70 [1.05] mmol/L^–1) concentrations (all P > .05).

Of interest, in patients without obesity (having a BMI <30 kg/m­²), no significant difference in lipid levels was found. This may indicate that a certain amount of adipose tissue is required for the sympathetic surges to liberate free fatty acids, which ultimately form TGs.

Muscle sympathetic nerve activity surges, possibly due to PLMS according to previous studies, were associated with increased blood pressure and heart rate in this study, confirming the current literature.

In the present analysis, researchers did not identify significantly higher blood pressure values or higher prevalence of hypertension in patients with PLMS. This finding may be hidden by the ongoing treatment with antihypertensive drugs or the higher OSA severity in the non-PLMS group. Additional data suggest that the relationship between PLMS and long-term cardiovascular risk depends on the disease severity of PLM.

Also, researchers found significantly higher TG and lower HDL cholesterol evels in patients with PLMS after adjustment for the most pertinent factors. These observations were confirmed when patients without fasting lipid values and those taking lipid-lowering, anti-Parkinson, and anti-epileptic medications weren’t included. Of the most importance, they confirmed these differences with inverse probability treatment weighting.

One limitation of this analysis was its cross-sectional nature, and therefore a causal relationship between PLMS and dyslipidemia only can be hypothesized. Prospective, interventional studies are needed to analyze this further.

Overall, PLMS was found to be linked with high TG and low HDL-C levels in patients with OSA, which emphasizes the significance of PLMS as a possible cardiovascular trait.

“However, this hypothesis needs to be tested by interventional studies. We believe that our findings could serve as a potential basis to design these trials,” concluded the researchers.

Reference

Bikov A, Bailly S, Testelmans D, et al. The relationship between periodic limb movement during sleep and dyslipidaemia in patients with obstructive sleep apnea. J Sleep Res. Published online August 19, 2023. doi.org:10.1111/jsr.14012