Poor sleep quality, impaired cardiac autonomic control, and metabolic syndrome: a tricky relationship?

The occurrence of metabolic syndrome (MetS) is highly favored by a lack of physical activity, a sedentary lifestyle, and an unbalanced diet. The number of cases has been constantly increasing in the last 40 years, affecting up to more than 40% of people over 50 years old in the United States [1]. Although it remains asymptomatic for several years, MetS evolves silently and should be taken very seriously. Indeed, over time, MetS considerably increase the risk of developing serious diseases such as type 2 diabetes, liver, chronic kidney, or cardiovascular diseases [2, 3]. To improve the prevention of MetS and reduce its complications, many research teams are working to better understand its pathophysiological mechanisms. Although these mechanisms are intricate and complex, excess abdominal (or central) fat deposition appears to play an important role [4–6]. Indeed, adipose tissue is far from being an inert fat mass. They participate in the regulation of metabolism and impacts health by secreting several mediators that allow it to communicate with other organs such as the liver, muscles, heart, or blood vessels. In MetS, this metabolic regulation is chronically altered, leading to abnormalities in the use, and storage of lipids, as well as low-grade inflammatory phenomena that are harmful to the body [6]. Progress in the understanding of these dysfunctions will give hope to reestablishing a normal dialogue between the adipose tissue and the rest of the body and, thereby, limit the systemic consequences of MetS. Sleep, which represents approximately 30% of our life, could represent a cornerstone in MetS development [7]. Several epidemiological studies have demonstrated that short sleep duration, i.e. less than 6 hr is frequently associated with the onset of MetS and its subcomponents while long sleep duration (>9hr) does not impact MetS prevalence or incidence [8–10]. Of interest, the metabolic impact of short sleep duration has been demonstrated in adults as well as in children and persisted after adjustment for all the usual confounding factors related to obesity [8]. Pathophysiological mechanisms explaining this association include the suggestion that short sleep duration may decrease leptin levels and increase ghrelin levels. Thus, the regulation of the sensation of hunger and satiety could be altered, resulting in a craving for high-calorie and/or high-carbohydrate foods [11, 12]. Autonomic nervous system (ANS) dysfunction is a recognized major risk predictor of metabolic risks, diabetes, and all-cause mortality in the general adult population [13]. Changes in ANS equilibrium, manifested by altered heart rate variability (HRV) analysis may be an intermediate pathophysiological mechanism involved in the relationship between decreased sleep duration and MetS [14]. Noninvasive analysis of ANS using HRV showed a shift in the sympatho-vagal balance toward a predominance of the sympathetic nervous system and a withdrawal of the parasympathetic nervous system in the context of chronic sleep restriction [15, 16]. Our research team found in the PROOF (Prognostic indicator of cardiovascular and cerebrovascular events: role of autonomic nervous system activity and decline) cohort study, an elderly population-based cohort of 65 years old participants, that MetS was associated with a decrease in global indices of HRV in both short (5 min) and long-term (nighttime and 24 hr) measurements [17]. This ANS alteration was further confirmed by several cross-sectional studies and meta-analysis showing reduced global HRV [18], increased muscle sympathetic nerve activity [19], and altered baroreflex sensitivity [20]. However, to the best of our knowledge, only two longitudinal studies reported that basal enhanced sympathetic activity might influence the metabolic status increasing the incidence of MetS over time [21, 22]. ANS dysregulation could be one of the triggers for the development of metabolic abnormalities and some years later for the occurrence of cardiovascular diseases. In such a context, the study published in this issue of SLEEP examined the effects of poor sleep quality, reduced HRV, or both on MetS in the midlife of participants in The United States II study [23]. The authors found an independent deleterious effect of self-reported poor sleep quality, defined by Pittsburgh Sleep Quality Index abnormal score, on the odds of MetS after adjustment for confounding. Furthermore, higher time-domain and/or frequency-domain HRV parameters (SDNN, rMSSD, LF, and HF), reflecting higher ANS equilibrium, were associated with significantly decreased odds of MetS. Interestingly enough, the authors showed that the combined effect of poor sleep and low HRV strengthen the association with MetS compared to normal sleep quality and HRV. If these results are interesting and confirm previous observations made on population cohorts, the methodological limitations underlined by the authors of this work are important to note. In particular, the short-term HRV analysis used, i.e. 11 min of recording, must be read as an uncommon and parceled modality of analysis of the ANS functioning [23]. The impact of the environment and of the recording conditions, although standardized, can have an important influence on the ANS parameters. In a previous publication, we demonstrated a closer association between both nighttime and 24-hr HRV parameters with MetS than short-term HRV (5 min) did [17]. The analysis over 24 hr, as recommended by the HRV Task Force [24], or at least over the night [25], increases the predictive power of HRV parameters compared to short-term analysis [26] and avoids a potential “white-coat” effect, which is similar to the one observed when measuring blood pressure in the office. Similarly, the self-reported evaluation of sleep quality has important limits even if the Pittsburgh Sleep Quality Index is well validated. The overestimation or on the contrary the underestimation of sleep time (depending on the population interviewed) is often reported [27]. Moreover, Nevels et al. did not adjust for OSA status in their analysis whereas it is generally accepted that OSA and MetS share common risk factors [7]. Still, some sleep disorders such as obstructive sleep apnea/hypopnea or chronic insomnia could worsen the clinical consequences of altered sleep quality through sympathetic overdrive and consequently increase the risk of MetS [7, 28]. Despite these limits, this cross-sectional study confirms the dysmetabolic effects of a dangerous combination of poor sleep quality and impaired short-term cardiac autonomic control [23]. However, one should keep in mind that “association” does not mean “causation” and it is now important to better understand the direct links of these two abnormalities with the subsequent occurrence of the factors that make up MetS. The associations found in cross-sectional studies between sleep quality, MetS, and altered HRV appear to be robust. However, few studies have examined the longitudinal relationship between all these variables. Is it the poor sleep that determines MetS development or the opposite? Similarly, does low HRV favor MetS occurrence or does MetS increase the risk of low HRV? These associations are likely bi- or tri-directional, and future longitudinal studies are required to determine the causal relationship of these associations between low HRV, poor sleep quality, and MetS. Anyway, the study by Nevels et al. reminds us that sleep is an important modifiable lifestyle risk factor that must be considered along with diet and physical activity in the prevention of MetS and its secondary cardiovascular complications. Interestingly, recent intervention studies have shown that improving one behavior, whether it be sleep habits, diet, or physical activity, can have positive effects on other behaviors. Thus, intervention studies focusing on the resumption of regular physical activity and changes in sleep habits (in particular fighting against sleep restriction) should be promptly considered from the early phase of MetS and probably before the appearance of the criteria that assert this diagnosis. This is in line with the American guidelines on MetS [29] which recommends lifestyle changes in the first-line management of these patients who are more and more numerous in our consultations. Financial disclosure: none to declare. Nonfinancial disclosure: none to declare.