Nonalcoholic fatty liver disease and non-liver comorbidities.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excess fat accumulation in the liver. It is closely associated with metabolic syndrome, and patients with NAFLD often have comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia. In addition to liver-related complications, NAFLD has been associated with a range of non-liver comorbidities, including cardiovascular disease, chronic kidney disease, and sleep apnea. Cardiovascular disease is the most common cause of mortality in patients with NAFLD, and patients with NAFLD have a higher risk of developing cardiovascular disease than the general population. Chronic kidney disease is also more common in patients with NAFLD, and the severity of NAFLD is associated with a higher risk of developing chronic kidney disease. Sleep apnea, a disorder characterized by breathing interruptions during sleep, is also more common in patients with NAFLD and is associated with the severity of NAFLD. The presence of non-liver comorbidities in patients with NAFLD has important implications for the management of this disease. Treatment of comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia may improve liver-related outcomes in patients with NAFLD. Moreover, treatment of non-liver comorbidities may also improve overall health outcomes in patients with NAFLD. Therefore, clinicians should be aware of the potential for non-liver comorbidities in patients with NAFLD and should consider the management of these comorbidities as part of the overall management of this disease.

The Utility of Home Sleep Apnea Testing in the Advanced Heart Failure Populations.

Untreated sleep disorders form a risk of coronary artery disease, hypertension, obesity, and diabetes mellitus. Access to polysomnography is limited, especially during the COVID-19 pandemic, with home sleep apnea testing (HSAT) being a potentially viable alternative. We describe an HSAT protocol in patients with advanced heart failure (HF). In a single-center, observational analysis between 2019 and 2021 in patients with advanced HF and heart transplant (HT), 135 screened positive on the STOP-Bang sleep survey and underwent a validated HSAT (WatchPAT, ZOLL-Itamar). HSAT was successful in 123 patients (97.6%), of whom 112 (91.1%; 84 HF and 28 HT) tested positive for sleep apnea. A total of 91% of sleep apnea cases were obstructive, and 63% were moderate to severe. Multivariable linear regression showed that the apnea hypopnea index was 34% lower in the HT group than in the HF group (p = 0.046) after adjusting for gender, and that this effect persisted in White patients but not among African-Americans. Patient characteristics were similar between groups, with coronary artery disease, diabetes mellitus, and hypertension as the most prevalent co-morbidities. In conclusion, sleep apnea remains prevalent in patients with HF with a high co-morbidity burden. HSAT is a feasible and effective tool for screening and diagnosis in this population.

Nasal and Parotid Blood Pool Activity Is Significantly Correlated with Metabolic Syndrome Components and Sleep Apnea.

Background: Patients with metabolic syndrome components were frequently noted to have increased nasal and parotid activity on clinically referred scintigraphic whole-body blood pool scans. This increase in activity was not observed in patients without metabolic syndrome. Increased nasal blood pool activity in patients with elevated body mass indices (BMIs) has implications for (1) sleep apnea, (2) risk of nasal infection, and (3) possible impaired nasal lymphatic drainage of brain waste proteins. Methods: To follow-up this clinical observation, a retrospective study was performed on 200 patients having whole-body blood pool scans referred over a 3-year period. The whole-body blood pool scans were evaluated for an association between nose and parotid region of interest (ROI) to heart ROI maximum (max) pixel ratios as correlated with clinical conditions, including obesity, diabetes, hypertension, and sleep apnea. Continuous variables of BMI, hemoglobin A1c (HbA1c), blood glucose, and blood lipids were also correlated with these ratios. Results: A direct association of nose to heart max ratio (NHMR) with diabetes, sleep apnea, and hypertension was found with an increase in the ratio of +0.10 (P = 0.002), +0.13 (P = 0.0002), +0.08 (P = 0.0123), respectively. Correlation of NHMR with continuous variables had moderate correlation with BMI (r = 0.36, P < 0.0001), glucose (r = 0.27, P = 0.0001), HbA1c (r = 0.25, P = 0.0008) and less association with the number of diabetes medications (r = 0.22, P = 0.0021). Similar associations were found for parotid to heart max ratios but were weaker than the NHMR. Conclusions: Patients with metabolic syndrome components have significantly increased nasal and parotid activity on blood pool scans. These associations have implications for the treatment of sleep apnea, for nasal infections involving such agents as Covid-19, and for the risk of dementias related to decreased clearance of brain waste proteins through nasal turbinate lymphatics in patients with metabolic syndrome. If further studies support these findings, the nasal turbinates and the increased parasympathetic activity controlling their dilation could become a new therapeutic target.

Restless legs syndrome is associated with long-COVID in women.

STUDY OBJECTIVES: Sleep disturbance is common in long-COVID (LC). Restless legs syndrome (RLS) is characterized by sleep disturbance and has been reported after viral infections. Therefore, we evaluated RLS symptoms cross-sectionally in individuals with LC at both current and pre-coronavirus disease 2019 (pre-COVID-19) time points. METHODS: Adults on LC-focused Facebook pages were recruited for an online assessment of symptoms before COVID-19 infection and during their present LC state in a cross-sectional manner. The LC group documented baseline symptoms retrospectively. Questions were included about the presence/severity of RLS symptoms and assessments of fatigue, quality of life, and sleep apnea. A control group was recruited and included individuals ≥ 18 years of age who never had overt symptoms of COVID-19. Pregnancy was an exclusion criterion for both groups. RESULTS: There were 136 participants with LC (89.7% females, age 46.9 ± 12.9 years) and 136 controls (65.4% females, age 49.2 ± 15.5). RLS prevalence in females with LC was 5.7% pre-COVID-19 and 14.8% post-COVID-19 (P < .01) vs 6.7% in control females. Severity of RLS was moderate in both groups. Logistic regression predicting post-COVID-19 RLS among females with LC failed to find significant effects of hospitalization, sleep apnea, neuropathic pain severity, or use of antihistamines and antidepressants. CONCLUSIONS: The baseline prevalence of RLS in females with LC was similar to the general population group as well as to patients in epidemiological studies. The prevalence significantly increased in the LC state. Postinfectious immunological mechanisms may be at play in the production for RLS symptoms. CITATION: Weinstock LB, Brook JB, Walters AS, Goris A, Afrin LB, Molderings GJ. Restless legs syndrome is associated with long-COVID in women. J Clin Sleep Med. 2022;18(5):1413-1418.

Association of Sleep-Related Hypoxia With Risk of COVID-19 Hospitalizations and Mortality in a Large Integrated Health System.

Importance: The influence of sleep-disordered breathing (SDB) and sleep-related hypoxemia in SARS-CoV-2 viral infection and COVID-19 outcomes remains unknown. Controversy exists regarding whether to continue treatment for SDB with positive airway pressure given concern for aerosolization with limited data to inform professional society recommendations. Objective: To investigate the association of SDB (identified via polysomnogram) and sleep-related hypoxia with (1) SARS-CoV-2 positivity and (2) World Health Organization (WHO)-designated COVID-19 clinical outcomes while accounting for confounding including obesity, underlying cardiopulmonary disease, cancer, and smoking history. Design, Setting, and Participants: This case-control study was conducted within the Cleveland Clinic Health System (Ohio and Florida) and included all patients who were tested for COVID-19 between March 8 and November 30, 2020, and who had an available sleep study record. Sleep indices and SARS-CoV-2 positivity were assessed with overlap propensity score weighting, and COVID-19 clinical outcomes were assessed using the institutional registry. Exposures: Sleep study-identified SDB (defined by frequency of apneas and hypopneas using the Apnea-Hypopnea Index [AHI]) and sleep-related hypoxemia (percentage of total sleep time at <90% oxygen saturation [TST <90]). Main Outcomes and Measures: Outcomes were SARS-CoV-2 infection and WHO-designated COVID-19 clinical outcomes (hospitalization, use of supplemental oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation, and death). Results: Of 350 710 individuals tested for SARS-CoV-2, 5402 (mean [SD] age, 56.4 [14.5] years; 3005 women [55.6%]) had a prior sleep study, of whom 1935 (35.8%) tested positive for SARS-CoV-2. Of the 5402 participants, 1696 were Black (31.4%), 3259 were White (60.3%), and 822 were of other race or ethnicity (15.2%). Patients who were positive vs negative for SARS-CoV-2 had a higher AHI score (median, 16.2 events/h [IQR, 6.1-39.5 events/h] vs 13.6 events/h [IQR, 5.5-33.6 events/h]; P < .001) and increased TST <90 (median, 1.8% sleep time [IQR, 0.10%-12.8% sleep time] vs 1.4% sleep time [IQR, 0.10%-10.8% sleep time]; P = .02). After overlap propensity score-weighted logistic regression, no SDB measures were associated with SARS-CoV-2 positivity. Median TST <90 was associated with the WHO-designated COVID-19 ordinal clinical outcome scale (adjusted odds ratio, 1.39; 95% CI, 1.10-1.74; P = .005). Time-to-event analyses showed sleep-related hypoxia associated with a 31% higher rate of hospitalization and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.57; P = .005). Conclusions and Relevance: In this case-control study, SDB and sleep-related hypoxia were not associated with increased SARS-CoV-2 positivity; however, once patients were infected with SARS-CoV-2, sleep-related hypoxia was an associated risk factor for detrimental COVID-19 outcomes.

Multiple, objectively measured sleep dimensions including hypoxic burden and chronic kidney disease: findings from the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Poor sleep may contribute to chronic kidney disease (CKD) through several pathways, including hypoxia-induced systemic and intraglomerular pressure, inflammation, oxidative stress and endothelial dysfunction. However, few studies have investigated the association between multiple objectively measured sleep dimensions and CKD. METHODS: We investigated the cross-sectional association between sleep dimensions and CKD among 1895 Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study participants who completed in-home polysomnography, wrist actigraphy and a sleep questionnaire. Using Poisson regression models with robust variance, we estimated separate prevalence ratios (PR) and 95% CIs for moderate-to-severe CKD (glomerular filtration rate <60 mL/min/1.73 m2 or albuminuria >30 mg/g) among participants according to multiple sleep dimensions, including very short (≤5 hours) sleep, Apnoea-Hypopnoea Index and sleep apnoea-specific hypoxic burden (SASHB) (total area under the respiratory event-related desaturation curve divided by total sleep duration, %min/hour)). Regression models were adjusted for sociodemographic characteristics, health behaviours and clinical characteristics. RESULTS: Of the 1895 participants, mean age was 68.2±9.1 years, 54% were women, 37% were white, 28% black, 24% Hispanic/Latino and 11% Asian. Several sleep metrics were associated with higher adjusted PR of moderate-to-severe CKD: very short versus recommended sleep duration (PR=1.40, 95% CI 1.06 to 1.83); SASHB (Box-Cox transformed SASHB: PR=1.06, 95% CI 1.02 to 1.12); and for participants in the highest quintile of SASHB plus sleep apnoea: PR=1.28, 95% CI 1.01 to 1.63. CONCLUSIONS: Sleep apnoea associated hypoxia and very short sleep, likely representing independent biological mechanisms, were associated with a higher moderate-to-severe CKD prevalence, which highlights the potential role for novel interventions.

Contribution of pulmonary diseases to COVID-19 mortality in a diverse urban community of New York.

We examined the relative contribution of pulmonary diseases (chronic obstructive pulmonary disease, asthma and sleep apnea) to mortality risks associated with Coronavirus Disease (COVID-19) independent of other medical conditions, health risks, and sociodemographic factors. Data were derived from a large US-based case series of patients with COVID-19, captured from a quaternary academic health network covering New York City and Long Island. From March 2 to May 24, 2020, 11,512 patients who were hospitalized were tested for COVID-19, with 4,446 (38.62%) receiving a positive diagnosis for COVID-19. Among those who tested positive, 959 (21.57%) died of COVID-19-related complications at the hospital. Multivariate-adjusted Cox proportional hazards modeling showed mortality risks were strongly associated with greater age (HR = 1.05; 95% CI: 1.04-1.05), ethnic minority (Asians, Non-Hispanic blacks, and Hispanics) (HR = 1.26; 95% CI, 1.10-1.44), low household income (HR = 1.29; 95% CI: 1.11, 1.49), and male sex (HR = 0.85; 95% CI: 0.74, 0.97). Higher mortality risks were also associated with a history of COPD (HR = 1.27; 95% CI: 1.02-1.58), obesity (HR = 1.19; 95% CI: 1.04-1.37), and peripheral artery disease (HR = 1.33; 95% CI: 1.05-1.69). Findings indicate patients with COPD had the highest odds of COVID-19 mortality compared with patients with pre-existing metabolic conditions, such as obesity, diabetes and hypertension. Sociodemographic factors including increased age, male sex, low household income, ethnic minority status were also independently associated with greater mortality risks.