Association of Incident Cardiovascular Disease With Periodic Limb Movements During Sleep in Older Men

Abstract

Background Periodic limb movements during sleep (PLMS) cause repetitive sympathetic activation and may be associated with increased cardiovascular risk. We hypothesized that PLMS frequency (PLMI) and PLMS arousal frequency (PLMAI) are predictive of incident cardiovascular disease, including coronary heart disease (CHD), peripheral arterial disease (PAD) and cerebrovascular disease (CBD) in an elderly male cohort. Methods and Results 2,911 men in the observational MrOS sleep study cohort underwent in-home polysomnography with PLMS measurement and were followed four years for the outcomes CHD, CBD, PAD and all-cause cardiovascular disease (cCVD): CHD, CBD or PAD. Cox proportional hazards regression assessed association between PLMI, PLMAI and these outcomes. Models were minimally adjusted for age, clinic and body mass index, then fully adjusted for conventional cardiovascular risk factors. During follow-up, 500 men experienced cCVD: 345 CHD, 117 CBD and 98 PAD events. In fully adjusted models, men with PLMAI≥5 compared to the referent PLMA<1 group had 1.26-fold increased relative hazard (RH) for cCVD. Similar findings were observed for PLMI and cCVD. For PAD, men with PLMI≥30 compared to the referent PLMI<5 group had a 2-fold increased RH (1.14–3.49, p=0.025). Compared to the referent group, men with PLMI ≥30 had an increased risk of CHD (RH=1.31, 1.01–1.70; p=0.045) after minimal adjustment, but this association attenuated after further adjustments. After stratification, risk of incident cCVD among high PLMI and PLMAI groups was significantly elevated only for men without prevalent hypertension (p interactions <0.10). Conclusions These findings provide evidence that PLMS frequency is associated with incident cardiovascular disease in community dwelling elderly men.

Periodic Limb Movements in Sleep are Associated with Greater Cognitive Decline in Older Men without Dementia

“…Detailed descriptive statistics are not presented in this short note, but characteristics of similar study samples can be found in previous publications. 2,3,11 After multivariable adjustment, the rate of increase in Trails B test time (decline in function) was significantly greater for those with a PLMI ≥ 30, whereas the rate of decrease in 3MS scores was smaller, but not significant, for those with a PLMI ≥ 30. The adjusted increase in Trails B test completion time over 3.4 y were 3.5, 6.3, and 8.1 sec for PLMI category of < 5, 5 to 30, and ≥ 30, respectively (P for trend = 0.02); adjusted decline in 3MS score for PLMI categories were 1.3, 0.9, and 1.0 points over 3 y, respectively (P for trend = 0.23).…”

“…There are a few potential mechanisms. PLMS has been associated with increased sympathetic activity, elevated blood pressure and incident cardiovascular diseases, 3,20 which all contribute to vascular-related cognitive impairment, as featured by impairment in executive function. [21][22][23] Moreover, dopamine deficit, as a frequently suggested cause of PLMS, 4 also plays a key role in neurodegeneration and affects particularly the prefrontal cortex area, which regulates executive function.…”

“…It has a reported prevalence of 45% among elderly adults, 1 and has been associated with sleep fragmentation and risk of cardiovascular diseases in older men. 2,3 The exact mechanism of PLMS is unclear, but impaired dopaminergic transmission is frequently suggested. [4][5][6] Notably, a high prevalence of PLMS has been reported among patients with Parkinson disease (PD) and Lewy body dementia, 5,6 further supporting a potentially close link between PLMS and dopaminergic hypoactivity.…”

The Determining Risk of Vascular Events by Apnea Monitoring (DREAM) study: design, rationale, and methods

“…Measurements of physiologic components other than breathingincluding sleep disruption, heart rate variability, or periodically occurring limb movements-have been shown to track with hypertension and cardiovascular disease [15][16][17]. Previous research, however, has not adequately integrated these diverse physiologic measures to evaluate potential cardiovascular associations in a combined approach; instead, most studies have focused on singular measures, usually AHI.…”

Periodic Limb Movements and Heart Rate Changes

“…This chain of events is most probably under the general control of a common mechanism, i.e., "the cyclic alternating pattern," which has been shown to have a gating control function on the generation of PLM. 9,10 The recently reported association of incident cardiovascular disease with PLM during sleep in a large cohort of community dwelling elderly men living in the US, 11 and the increased mortality risk in patients with systolic heart failure and PLMI ≥ 5, 12 emphasize the need for further studies addressing the possible mechanisms by which PLM could be involved in the pathogenesis of cardiovascular disorders. …”