HDL and sleep: beyond cardiovascular diseases and allergy

High-density lipoprotein (HDL) particles are heterogeneous and composed of a vast array of proteins and lipids. They are formed in the liver and intestine via interactions between lipid-poor apolipoprotein A-I (apoA-I) and the cholesterol-phospholipid transporter, followed by the acquisition of additional lipids and apolipoproteins [1]. It is well known that the cholesterol content of HDL (HDL-C) is inversely correlated with a risk of atherosclerotic cardiovascular diseases (CVDs), and that it is a key component for predicting cardiovascular risk [2]. Therefore, compared with low-density lipoprotein (LDL) cholesterol, HDL-C is generally considered to be “good cholesterol” with regard to its role in atherosclerosis and therapeutic potential in CVDs [2, 3].

The role of HDL in humans is not limited to CVDs. HDL was reported to have an important role in allergy including asthma [4]. Epidemiological studies showed that low-serum HDL-C was associated with wheezing [5] and low pulmonary function [6] in adults, although other studies reported conflicting or nonsignificant results [4]. Lower levels of HDL-C in childhood were associated with an increased risk of asthma in adolescence [7], supporting the potential role of HDL-C in the pathogenesis of pediatric asthma. Barochia et al. reported that serum levels of HDL were related to systemic type 2 inflammation [8] and airflow limitation [1] in atopic asthma, but not in nonatopic nonasthma, indicating that HDL might have some protective effects on the pathogenesis of asthma. In addition to asthma, HDL is considered to modulate eosinophil effector responses in other allergic diseases such as allergic rhinitis and atopic dermatitis [4].

However, HDL seems to be involved in human health and diseases beyond CVDs and allergy. According to a study by Shu and Wang [9], it may also have beneficial effects on sleep quality. They evaluated the blood lipid levels and sleep quality of 1013 adult subjects in the Midlife in the United States (MIDUS) study and found that elevated blood HDL-C levels were associated with reduced risk of poor sleep quality in subjects with asthma, but not in those without asthma, even after adjusting for demographic characteristics and lifestyle. Unfortunately, because sleep was only assessed by self-reported questionnaires, without objective measures such as actigraphs or polysomnography, how HDL-C might contribute to reduced risk of poor sleep quality cannot be estimated. Does HDL-C directly or indirectly affect sleep quality? Is sleep apnea involved in it? Considering that this result was observed only in patients with asthma, the above-mentioned significant interrelationship between HDL-C and asthma might have affected the relationship with sleep. Further studies are required to investigate these interrelationships. Therefore, it appears that the effects of HDL start at the arteries, and travel through the airways to the final destination, the brain!

It is really surprising to see the recent advances in knowledge in HDL. In addition to the study by Shu and Wang [9], other recent studies reported that HDL has a role in various areas beyond CVDs and allergy, including infectious diseases, dementia, diabetes, and mortality [3]. Additionally, high HDL levels are sometimes associated with negative outcomes. HDL-C raising drugs did not improve CVA outcomes [4, 10], suggesting HDL-C is no longer simple “good cholesterol” as we previously thought [3, 4, 10]. It is important to remember the real shape of HDL, which is enclosed by various proteins and lipids! Thus, “good cholesterol” may only be one superficial layer that covers HDL. By striping HDL off the complex in observational studies and basic experiments, we will be able to reveal the real shape of mysterious HDL in the future. We are looking forward to this by continuing our research.

Declarations

Conflict of interest

There is no conflict of interest with regard to this article.