Kristina Shkirkova, BSc

Del Brutto OH, Mera RM, Costa AF, Castillo PR. Effect of Heart Rate Variability on the Association Between the Apnea-Hypopnea Index and Cerebral Small Vessel Disease. Stroke. 2019;50:2486–2491.

Obstructive Sleep Apnea (OSA) is a form of sleep-disordered breathing that has been increasingly implicated in the pathogenesis of cerebral small vessel disease (cSVD). OSA is associated with recurrent episodes of hypoxia, altered cerebral autoregulation, and sympathetic overactivity, which may be contributing triggers for pathophysiology of cSVD. A recent study by Del Brutto et al. used nighttime Heart Rate Variability (HRV) as a measure of sympathetic upregulation to study the association between OSA and cSVD. HRV measures variation in the intervals between heartbeats and is used as a reflection of the balance between sympathetic and parasympathetic tone. Apnea-Hypopnea Index was used to access the degree of OSA and the total cSVD score was chosen to quantify cSVD burden. The study used data from the Atahualpa Project, which included elderly (age above 60) residents of the Atahualpa rural village on the coast of Ecuador. A total of 176 participants who underwent clinical assessment, magnetic resonance imaging (MRI), single-night polysomnography, and 24-hour Holter monitoring were selected for the analysis.

Among study participants, the mean age was 71.8, and 64% were women. The univariate analysis showed that daytime HRV below the 50th percentile was associated with female gender and lower mean percentage of O2 saturation. The nighttime HRV below the 50th percentile was associated with body mass index (BMI) higher than 30 kg/m2. In the generalized linear model analysis, with and without confounding variables, there was a significant association between the cSVD score and AHI (p=0.026). Furthermore, a negative association was observed between sCVD and nighttime HRV, but not daytime HRV (p=0.001). Interaction model analysis showed a significant interaction of nighttime HRV on the relationship between AHI and the cSVD score (P=0.001). The total effect between AHI and the cSVD score mediated by HRV was 30.8%. Additionally, contour plots showed the effect of nighttime HRV on the association between AHI and the cSVD score.

Based on the results of this study, the authors conclude that there is a significant role of nighttime HRV on the association between cSVD burden and OSA. Participants of the study, who had a low nighttime HRV together with a low cSVD burden, also demonstrated a low AHI score. Low HRV during nighttime is associated with reduced parasympathetic activity. However, studies in the past also showed that high nighttime HRV is associated with poor cardiovascular health. Although the literature on OSA and cSVD is inconsistent, their relationship is likely to be bi-directional. The diffuse subcortical vascular damage sustained from cSVD can result in disruption of periventricular fibers, which are part of breathing control pathways mediating apneic episodes.

It is important to note that the study population was homogeneous and consisted primarily of older adults of Amerindian ancestry. Thus, extrapolation of these findings should be done with caution, and future studies in more diverse population samples are needed. The authors speculate that AHI is an important variable, which may serve as a new avenue of research for future studies that aim to assess the complex relationship between nighttime HRV and stroke risks.