Sanjay R. Patel

Short Sleep Duration and Weight Gain: A Systematic Review

Objective: The recent obesity epidemic has been accompanied by a parallel growth in chronic sleep deprivation. Physiologic studies suggest sleep deprivation may influence weight through effects on appetite, physical activity, and/or thermoregulation. This work reviews the literature regarding short sleep duration as an independent risk factor for obesity and weight gain.

Age-Related Changes in Sleep/Wake Patterns Among Korean Teenagers

Introduction. As children go through the transition from childhood to adolescence, many shifts occur in sleep/wake patterns related to intrinsic and extrinsic developmental changes. These shifts have been shown to result in corresponding shifts in sleep phase (later sleep onset) and sleep deprivation among teenagers in Western societies. However, the effect of these developmental changes on the sleep habits of Korean teenagers has not been analyzed. This study aims to quantify age-related changes in sleep/wake patterns among Korean teenagers and elucidate cultural and other factors causing these changes. Methods. The School Sleep Habits Survey was administered in homeroom classes to students in grades 5 to 12 (mean age: 13.7 ± 2.4 years) selected via a 2-way stratification sampling method. The survey included items regarding usual sleep/wake patterns over the previous 2 weeks as well as measures of daytime sleepiness, sleep/wake-problem behavior, depressed mood, and morningness/eveningness. Results. A total of 1457 students (52.9% male) completed the survey. The higher the grade, the later bedtime was found to be on both school days and weekends. There was a similar relationship between increasing grade and earlier wake time on school days, but higher grades were associated with later wake time on weekends. Total sleep time decreased by ∼3 hours on school nights and 1 hour on weekend nights from grades 5 to 12. Adolescents were severely sleep deprived, with mean school-night total sleep times of 6.02, 5.62, and 4.86 hours for 10th-, 11th-, and 12th-graders, respectively. In the higher grades, there was a greater discrepancy between school nights and weekends in terms of bedtime and wake time, and the magnitude of weekend oversleep increased. Older students also reported more daytime sleepiness, more sleep/wake-problem behavior, more depressed mood, and more eveningness preference. The chief reasons students cited for their sleep deprivation differed across grades: Academic demands and entertainment (such as Internet and television) were reported by 5th- and 6th-graders, entertainment and then academic demands by 7th-, 8th-, and 9th-graders, and early school start time and academic demands by 10th-, 11th- and 12th-graders. Conclusions. This study clearly demonstrates that Korean adolescents do not get adequate sleep and that they have profound discrepancies in their sleep/wake patterns between school and weekend nights. Compared with previous studies from other countries, Korean students display even greater sleep deprivation and also more irregular sleep/wake patterns. This study also demonstrates that academic demands/stress and early school start time are the most important contributing factors for sleep deprivation among Korean adolescents. These findings stress the need to promote awareness of the magnitude of adolescent sleep deprivation and its detrimental effects in Korean society.

Mendelian randomization of blood lipids for coronary heart disease.

Aims To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. Methods and results We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a prior meta-analysis (threshold P < 2 × 10−6); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P ≤ 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestricted allele score (48 SNPs) was associated with CHD (OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). Conclusion The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.

Epidemiology, Risk Factors, and Consequences of Obstructive Sleep Apnea and Short Sleep Duration

We will review the epidemiology, risk factors, and consequences of obstructive sleep apnea (OSA) and short/long sleep duration. Obstructive sleep apnea is a disease characterized by recurrent upper airway obstruction during sleep. Obstructive sleep apnea is common, with moderate to severe disease present in approximately 9% of middle aged men and 4% of women. The prevalence of OSA in certain patient populations (such as elderly patients, hypertensive patients, patients with coronary disease, and prebariatric surgery patients) is even greater. There are a number or risk factors for disease including obesity, male sex, and family history. Obstructive sleep apnea negatively impacts quality of life and is also associated with a number of adverse safety and health consequences including cardiovascular disease and motor vehicle crashes. Short habitual sleep duration can result in excessive daytime sleepiness and reduced neurocognitive function. Sleep loss may have long-term health consequences and may lead to premature death, cardiovascular disease, and the development of diabetes.

A Whole-Genome Scan for Obstructive Sleep Apnea and Obesity

Obstructive sleep apnea (OSA) is a common, chronic, complex disease associated with serious cardiovascular and neuropsychological sequelae and with substantial social and economic costs. Along with male gender, obesity is the most characteristic feature of OSA in adults. To identify susceptibility loci for OSA, we undertook a 9-cM genome scan in 66 white pedigrees (n=349 subjects) ascertained on the basis of either an affected individual with laboratory-confirmed OSA or a proband who was a neighborhood control individual. Multipoint variance-component linkage analysis was performed for the OSA-associated quantitative phenotypes apnea-hypopnea index (AHI) and body mass index (BMI). Candidate regions on chromosomes 1p (LOD score 1.39), 2p (LOD score 1.64), 12p (LOD score 1.43), and 19p (LOD score 1.40) gave the most evidence for linkage to AHI. BMI was also linked to multiple regions, most significantly to markers on chromosomes 2p (LOD score 3.08), 7p (LOD score 2.53), and 12p (LOD score 3.41). Extended modeling indicated that the evidence for linkage to AHI was effectively removed after adjustment for BMI, with the exception of the candidate regions on chromosomes 2p (adjusted LOD score 1.33) and 19p (adjusted LOD score 1.45). After adjustment for AHI, the primary linkages to BMI remained suggestive but were roughly halved. Our results suggest that there are both shared and unshared genetic factors underlying susceptibility to OSA and obesity and that the interrelationship of OSA and obesity in white individuals may be partially explained by a common causal pathway involving one or more genes regulating both AHI and BMI levels.

The Association between Sleep Duration and Obesity in Older Adults

Background:Reduced sleep has been reported to predict obesity in children and young adults. However, studies based on self-report have been unable to identify an association in older populations. In this study, the cross-sectional associations between sleep duration measured objectively and measures of weight and body composition were assessed in two cohorts of older adults.Methods:Wrist actigraphy was performed for a mean (s.d.) of 5.2 (0.9) nights in 3055 men (age: 67–96 years) participating in the Osteoporotic Fractures in Men Study (MrOS) and 4.1 (0.8) nights in 3052 women (age: 70–99 years) participating in the Study of Osteoporotic Fractures (SOF). A subgroup of 2862 men and 455 women also underwent polysomnography to measure sleep apnea severity.Results:Compared to those sleeping an average of 7–8 h per night, and after adjusting for multiple risk factors and medical conditions, a sleep duration of less than 5 h was associated with a body mass index (BMI) that was on average 2.5 kg/m2 (95% confidence interval (CI): 2.0–2.9) greater in men and 1.8 kg/m2 (95% CI: 1.1–2.4) greater in women. The odds of obesity (BMI ⩾30 kg/m2) was 3.7-fold greater (95% CI: 2.7–5.0) in men and 2.3-fold greater in women (95% CI: 1.6–3.1) who slept less than 5 h. Short sleep was also associated with central body fat distribution and increased percent body fat. These associations persisted after adjusting for sleep apnea, insomnia and daytime sleepiness.Conclusions:In older men and women, actigraphy-ascertained reduced sleep durations are strongly associated with greater adiposity.

Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society.

ABSTRACT Sleep is essential for optimal health. The American Academy of Sleep Medicine (AASM) and Sleep Research Society (SRS) developed a consensus recommendation for the amount of sleep needed to promote optimal health in adults, using a modified RAND Appropriateness Method process. The recommendation is summarized here. A manuscript detailing the conference proceedings and evidence supporting the final recommendation statement will be published in SLEEP and the Journal of Clinical Sleep Medicine.

CPAP versus Oxygen in Obstructive Sleep Apnea

BACKGROUND Obstructive sleep apnea is associated with hypertension, inflammation, and increased cardiovascular risk. Continuous positive airway pressure (CPAP) reduces blood pressure, but adherence is often suboptimal, and the benefit beyond management of conventional risk factors is uncertain. Since intermittent hypoxemia may underlie cardiovascular sequelae of sleep apnea, we evaluated the effects of nocturnal supplemental oxygen and CPAP on markers of cardiovascular risk. METHODS We conducted a randomized, controlled trial in which patients with cardiovascular disease or multiple cardiovascular risk factors were recruited from cardiology practices. Patients were screened for obstructive sleep apnea with the use of the Berlin questionnaire, and home sleep testing was used to establish the diagnosis. Participants with an apnea-hypopnea index of 15 to 50 events per hour were randomly assigned to receive education on sleep hygiene and healthy lifestyle alone (the control group) or, in addition to education, either CPAP or nocturnal supplemental oxygen. Cardiovascular risk was assessed at baseline and after 12 weeks of the study treatment. The primary outcome was 24-hour mean arterial pressure. RESULTS Of 318 patients who underwent randomization, 281 (88%) could be evaluated for ambulatory blood pressure at both baseline and follow-up. On average, the 24-hour mean arterial pressure at 12 weeks was lower in the group receiving CPAP than in the control group (-2.4 mm Hg; 95% confidence interval [CI], -4.7 to -0.1; P=0.04) or the group receiving supplemental oxygen (-2.8 mm Hg; 95% CI, -5.1 to -0.5; P=0.02). There was no significant difference in the 24-hour mean arterial pressure between the control group and the group receiving oxygen. A sensitivity analysis performed with the use of multiple imputation approaches to assess the effect of missing data did not change the results of the primary analysis. CONCLUSIONS In patients with cardiovascular disease or multiple cardiovascular risk factors, the treatment of obstructive sleep apnea with CPAP, but not nocturnal supplemental oxygen, resulted in a significant reduction in blood pressure. (Funded by the National Heart, Lung, and Blood Institute and others; HeartBEAT ClinicalTrials.gov number, NCT01086800 .).

Plasma PCSK9 Concentrations Correlate with LDL and Total Cholesterol in Diabetic Patients and Are Decreased by Fenofibrate Treatment

BACKGROUND Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment. METHODS We developed a sandwich ELISA using recombinant human PCSK9 protein and 2 affinity-purified polyclonal antibodies directed against human PCSK9. We measured circulating PCSK9 concentrations in 115 diabetic patients from the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study before and after fenofibrate treatment. RESULTS We found that plasma PCSK9 concentrations correlate with total (r = 0.45, P = 0.006) and LDL (r = 0.54, P = 0.001) cholesterol but not with triglycerides or HDL cholesterol concentrations in that cohort. After 6 weeks of treatment with comicronized fenofibrate (200 mg/day), plasma PCSK9 concentrations decreased by 8.5% (P = 0.041 vs pretreatment). This decrease correlated with the efficacy of fenofibrate, as judged by a parallel reduction in plasma triglycerides (r = 0.31, P = 0.015) and LDL cholesterol concentrations (r = 0.27, P = 0.048). CONCLUSIONS We conclude that this decrease in PCSK9 explains at least in part the LDL cholesterol-lowering effects of fenofibrate. Fenofibrate might be of interest to further reduce cardiovascular risk in patients already treated with a statin.

Effect of increased lung volume on sleep disordered breathing in patients with sleep apnoea

Background: Previous studies have shown that changes in lung volume influence upper airway size and resistance, particularly in patients with obstructive sleep apnoea (OSA), and that continuous positive airway pressure (CPAP) requirements decrease when the lung volume is increased. We sought to determine the effect of a constant lung volume increase on sleep disordered breathing during non-REM sleep. Methods: Twelve subjects with OSA were studied during non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. The increase in lung volume due to CPAP (at a therapeutic level) was determined with four magnetometer coils placed on the chest wall and abdomen. CPAP was then stopped and the subjects were studied for 1 hour in three conditions (in random order): (1) no treatment (baseline); (2) at “CPAP lung volume”, with the increased lung volume being reproduced by negative extrathoracic pressure alone (lung volume 1, LV1); and (3) 500 ml above the CPAP lung volume(lung volume 2, LV2). Results: The mean (SE) apnoea/hypopnoea index (AHI) for baseline, LV1, and LV2, respectively, was 62.3 (10.2), 37.2 (5.0), and 31.2 (6.7) events per hour (p = 0.009); the 3% oxygen desaturation index was 43.0 (10.1), 16.1 (5.4), and 12.3 (5.3) events per hour (p = 0.002); and the mean oxygen saturation was 95.4 (0.3)%, 96.0 (0.2)%, 96.3 (0.3)%, respectively (p = 0.001). Conclusion: An increase in lung volume causes a substantial decrease in sleep disordered breathing in patients with OSA during non-REM sleep.