Association of incident cardiovascular disease with periodic limb movements during sleep in older men: outcomes of sleep disorders in older men (MrOS) study

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 (periodic limb movement index [PLMI]) and PLMS arousal frequency (periodic limb movement arousal index [PLMAI]) are predictive of incident cardiovascular disease, including coronary heart disease, peripheral arterial disease, and cerebrovascular disease, in an elderly male cohort.

Methods and results: A total of 2911 men in the observational Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study cohort underwent in-home polysomnography with PLMS measurement and were followed up for 4 years for the outcomes coronary heart disease, cerebrovascular disease, peripheral arterial disease, and all-cause cardiovascular disease, which included coronary heart disease, cerebrovascular disease, and peripheral arterial disease. Cox proportional hazards regression assessed the association between PLMI, PLMAI, and these outcomes. Models were minimally adjusted for age, clinic, and body mass index and then fully adjusted for conventional cardiovascular risk factors. During follow-up, 500 men experienced all-cause cardiovascular disease: 345 coronary heart disease, 117 cerebrovascular disease, and 98 peripheral arterial disease events. In fully adjusted models, men with PLMAI ≥5 compared with the referent PLMA <1 group had a 1.26-fold increased relative hazard for all-cause cardiovascular disease. Similar findings were observed for PLMI and all-cause cardiovascular disease. For peripheral arterial disease, men with PLMI ≥30 compared with the referent PLMI <5 group had a 2-fold increased relative hazard (95% confidence interval, 1.14 to 3.49; P=0.025). Compared with the referent group, men with PLMI ≥30 had an increased risk of coronary heart disease (relative hazard, 1.31; 95% confidence interval, 1.01 to 1.70; P=0.045) after minimal adjustment, but this association was attenuated after further adjustments. After stratification, risk of incident all-cause cardiovascular disease among high-PLMI and high-PLMAI groups was significantly elevated only for men without prevalent hypertension (P for interactions <0.10).

Conclusion: These findings provide evidence that PLMS frequency is associated with incident cardiovascular disease in community-dwelling elderly men.

Figure 1

Kaplan-Meier curve for incident cCVD by PLMAI category showing an increased event rate for the high PLMAI groups, PLMAI≥5 and 1≤PLMAI<5, compared to the PLMAI<1 group. PLMAI<1 ——— 1≤PLMAI<5 ------- PLMAI≥5 ——— *Figure adjusted for clinic site, age, BMI, race, depression, prevalent diabetes, prevalent hypertension, smoking, alcohol use, physical activity, use of antidepressants, use of benzodiazepines, and AHI.

Figure 2

Kaplan-Meier curve for incident PAD by PLMI category showing an increased event rate for the high PLMI groups, PLMI≥30 and 5≤PLMAI<30, compared to the PLMI<5 group. PLMI<5 ——— 5≤PLMI<30 ------- PLMI≥30 ——— *Figure adjusted for clinic site, age, BMI, race, depression, prevalent diabetes, prevalent hypertension, smoking, alcohol use, physical activity, use of antidepressants, use of benzodiazepines, and AHI.