Periodic Limb Movements During Sleep Linked to Cardiovascular Disease, Death

Andrey Zinchuk, MD

Credit: Yale School of Medicine

Periodic limb movements during sleep are linked to cardiovascular disease (CVD) events or death, a new study found.¹

“Our study revealed that individuals with AHI <30 events/hour have an increased risk of CVD or death by 5% for every 10‐event/hour increase in [periodic limb movements index],” wrote investigators.

Led by Andrey Zinchuk, MD, from the section of pulmonary, critical care, and sleep medicine at Yale University School of Medicine, investigators wanted to see if periodic limb movements during OSA were independent or synergistic factors for CVD events or death.

Studies have found both OSA and periodic limb movements are linked to cardiovascular outcomes. OSA and periodic limb movements may coexist, as about 48% of adults with OSA have periodic limb movements. A study featured at SLEEP 2023 found effective treatment of OSA led to a greater frequency of periodic limb movement of sleep.²

To assess if OSA and periodic limb movements serve as synergistic factors for incident CVD, Zinchuk and colleagues obtained data from the Determining Risk of Vascular Events by Apnea Monitoring (DREAM) study.¹ This was a sleep laboratory-based observational cohort of 2041 veterans from 3 Veterans Affairs Medical Centers, enrolled from 2000 – 2004 and followed up through 2013 for incident CVD or death.

Zinchuk and colleagues’ study included 1049 veterans with an apnea-hypopnea index of < 30 events per hour and assessed the relationships between the apnea-hypopnea index and periodic limb movement index with the primary outcome of incident CVD or death using a Cox proportional hazards time to event model. They also adjusted for age, sex, race and ethnicity, obesity, baseline risk of mortality, and the Charlson Comorbidity Index.

The majority of participants were men (93.4%) and White (80.1%), with a mean age of 57.3 years, a mean BMI of 33.7 kg/m2, and a median AHI of 5.5 (1.6–13.4) events/hour.

After a follow-up of 5.1 years, 13.4% died, 6.3% experienced acute coronary syndrome, 1.5% experienced transient ischemic attack, and 1.4% experienced stroke (total: 237 participants). Unadjusted analyses demonstrated an increased risk of incident CVD or death every 10-event or hour increase in periodic limb movement index (hazard ratio [HR], 1.08; 95% CI, 1.05 – 1.13) and apnea-hypopnea index (HR, 1.17; 95% CI, 1.01 – 1.37).

Assessment associations of the apnea-hypopnea index and periodic limb movement index with the primary outcome demonstrated no significant interactions (P = .80).

“Notably, we did not find an interaction between [apnea‐hypopnea index] and [periodic limb movements index] for risk of the primary outcome, suggesting an absence of synergy between mild-moderate OSA and [periodic limb movements] for risk of CVD or death,” investigators wrote.

Adjusted analyses showed periodic limb movement index—not apnea-hypopnea index—was linked to an increased risk of incident CVD or death (HR, 1.05; 95% CI, 1.00 – 1.09). Moreover, the categorized analyses showed periodic limb movement of ≥ 30/h group was linked to an increased risk of incident CVD and death (HR, 1.87; 95% CI, 1.36 – 2.57).

Limitations the investigators stated included having a cohort of mainly male veterans, not scoring periodic limb movements separately from respiratory events, using continuous positive airway pressure which could have reduced the risk of incident CVD among participants with OSA, most of the events being deaths so the risk of CVD may not have been effectively evaluated, and the study lacked information on restless leg syndrome, a CVD risk factor.

“Our analyses showed that [periodic limb movements] remained a significant independent risk factor for CVD or death, whereas mild/moderate OSA did not, after controlling for important baseline risk factors and sensitivity analyses, including accounting for degree of hypoxia, hypertension and its treatment, and validated baseline cardiovascular risk index, [Framingham risk score],” investigators wrote.

^References

1. ^{Zinchuk A, Srivali N, Qin L, et al. Association of Periodic Limb Movements and Obstructive Sleep Apnea With Risk of Cardiovascular Disease and Mortality. J Am Heart Assoc. Published online January 19, 2024. doi:10.1161/JAHA.123.031630}
2. ^{Grossi, G. Pediatric Obstructive Sleep Apnea Treatment Linked with Periodic Limb Movement of Sleep. HCPLive. June 3, 2023. https://www.hcplive.com/view/pediatric-obstructive-sleep-apnea-treatment-linked-periodic-limb-movement-of-sleep. Accessed January 26, 2024.}