Andrew D. Calvin

Effects of Experimental Sleep Restriction on Caloric Intake and Activity Energy Expenditure

BACKGROUND Epidemiologic studies link short sleep duration to obesity and weight gain. Insufficient sleep appears to alter circulating levels of the hormones leptin and ghrelin, which may promote appetite, although the effects of sleep restriction on caloric intake and energy expenditure are unclear. We sought to determine the effect of 8 days/8 nights of sleep restriction on caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. METHODS We conducted a randomized study of usual sleep vs a sleep restriction of two-thirds of normal sleep time for 8 days/8 nights in a hospital-based clinical research unit. The main outcomes were caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. RESULTS Caloric intake in the sleep-restricted group increased by +559 kcal/d (SD, 706 kcal/d, P=.006) and decreased in the control group by -118 kcal/d (SD, 386 kcal/d, P=.51) for a net change of +677 kcal/d (95% CI, 148-1,206 kcal/d; P=.014). Sleep restriction was not associated with changes in activity energy expenditure (P=.62). No change was seen in levels of leptin (P=.27) or ghrelin (P=.21). CONCLUSIONS Sleep restriction was associated with an increase in caloric consumption with no change in activity energy expenditure or leptin and ghrelin concentrations. Increased caloric intake without any accompanying increase in energy expenditure may contribute to obesity in people who are exposed to long-term sleep restriction. TRIAL REGISTRATION ClinicalTrials.gov; No.: NCT01334788; URL: www.clinicaltrials.gov.

Aspirin for the Primary Prevention of Cardiovascular Events: A systematic review and meta-analysis comparing patients with and without diabetes

OBJECTIVE The negative results of two randomized controlled trials (RCTs) have challenged current guideline recommendations for using aspirin for primary prevention of cardiovascular events among patients with diabetes. We therefore sought to determine if the effect of aspirin for primary prevention of cardiovascular events and mortality differs between patients with and without diabetes. RESEARCH DESIGN AND METHODS We conducted a systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus since their inceptions until November 2008 for RCTs of aspirin for primary prevention of cardiovascular events. Blinded pairs of reviewers evaluated studies and extracted data. Random-effects meta-analysis and Bayesian logistic regression were used to estimate the ratios of relative risks (RRs) of outcomes of interest among patients with and without diabetes. A 95% CI that crosses 1.00 indicates that the effect of aspirin does not differ between patients with and without diabetes. RESULTS Nine RCTs with moderate to high methodological quality contributed data to the analyses. The ratios of RRs comparing the benefit of aspirin among patients with diabetes compared with patients without diabetes for mortality, myocardial infarction, and ischemic stroke were 1.12 (95% CI 0.92–1.35), 1.19 (0.82–1.17), and 0.70 (0.25–1.97), respectively. CONCLUSIONS Whereas estimates of benefit among patients with diabetes remain imprecise, our analysis suggests that the relative benefit of aspirin is similar in patients with and without diabetes.

Contrast-induced acute kidney injury and diabetic nephropathy.

Contrast-induced acute kidney injury (CIAKI) is a leading cause of iatrogenic renal failure. Multiple studies have shown that patients with diabetic nephropathy are at high risk of CIAKI. This Review presents an overview of the pathogenesis of CIAKI in patients with diabetic nephropathy and discusses the currently available and potential future strategies for CIAKI prevention.

Out of context: clinical practice guidelines and patients with multiple chronic conditions: a systematic review.

Background:Poor fidelity to practice guidelines in the care of people with multiple chronic conditions (MCC) may result from patients and clinicians struggling to apply recommendations that do not consider the interplay of MCC, socio-personal context, and patient preferences. Objective:The objective of the study was to assess the quality of guideline development and the extent to which guidelines take into account 3 important factors: the impact of MCC, patients’ socio-personal contexts, and patients’ personal values and preferences. Research Design:We conducted a systematic search of clinical practice guidelines for patients with type 2 diabetes mellitus published between 2006 and 2012. Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Scopus, EBSCO CINAHL, and the National Guideline Clearinghouse were searched. Two reviewers working independently selected studies, extracted data, and evaluated the quality of the guidelines. Results:We found 28 eligible guidelines, which, on average, had major methodological limitations (AGREE II mean score 3.8 of 7, SD=1.6). Patients or methodologists were not included in the guideline development process in 20 (71%) and 24 (86%) guidelines, respectively. There was a complete absence of incorporating the impact of MCC, socio-personal context, and patient preferences in 8 (29%), 11 (39%), and 16 (57%) of the 28 guidelines, respectively. When mentioned, MCC were considered biologically, but not as contributors of complexity or patient work or as motivation to focus on patient-centered outcomes. Conclusions:Extant clinical practice guidelines for one chronic disease sometimes consider the context of the patient with that disease, but only do so narrowly. Guideline panels must remove their contextual blinders if they want to practically guide the care of patients with MCC.

Sleep-Disordered Breathing and Excessive Daytime Sleepiness in Patients With Atrial Fibrillation

BACKGROUND An important consequence of sleep-disordered breathing (SDB) is excessive daytime sleepiness (EDS). EDS often predicts a favorable response to treatment of SDB, although in the setting of cardiovascular disease, particularly heart failure, SDB and EDS do not reliably correlate. Atrial fibrillation (AF) is another highly prevalent condition strongly associated with SDB. We sought to assess the relationship between EDS and SDB in patients with AF. METHODS We conducted a prospective study of 151 patients referred for direct current cardioversion for AF who also underwent sleep evaluation and nocturnal polysomnography. The Epworth Sleepiness Scale (ESS) was administered prior to polysomnography and considered positive if the score was ≥ 11. The apnea-hypopnea index (AHI) was tested for correlation with the ESS, with a cutoff of ≥ 5 events/h for the diagnosis of SDB. RESULTS Among the study participants, mean age was 69.1 ± 11.7 years, mean BMI was 34.1 ± 8.4 kg/m(2), and 76% were men. The prevalence of SDB in this population was 81.4%, and 35% had EDS. The association between ESS score and AHI was low (R(2) = 0.014, P = .64). The sensitivity and specificity of the ESS for the detection of SDB in patients with AF were 32.2% and 54.5%, respectively. CONCLUSIONS Despite a high prevalence of SDB in this population with AF, most patients do not report EDS. Furthermore, EDS does not appear to correlate with severity of SDB or to accurately predict the presence of SDB. Further research is needed to determine whether EDS affects the natural history of AF or modifies the response to SDB treatment.

Experimental Sleep Restriction Causes Endothelial Dysfunction in Healthy Humans

Background Epidemiologic evidence suggests a link between short sleep duration and cardiovascular risk, although the nature of any relationship and mechanisms remain unclear. Short sleep duration has also been linked to an increase in cardiovascular events. Endothelial dysfunction has itself been implicated as a mediator of heightened cardiovascular risk. We sought to determine the effect of 8 days/8 nights of partial sleep restriction on endothelial function in healthy humans. Methods and Results Sixteen healthy volunteers underwent a randomized study of usual sleep versus sleep restriction of two‐thirds normal sleep time for 8 days/8 nights in a hospital‐based clinical research unit. The main outcome was endothelial function measured by flow‐mediated brachial artery vasodilatation (FMD). Those randomized to sleep restriction slept 5.1 hours/night during the experimental period compared with 6.9 hours/night in the control group. Sleep restriction was associated with significant impairment in FMD (8.6±4.6% during the initial pre‐randomization acclimation phase versus 5.2±3.4% during the randomized experimental phase, P=0.01) whereas no change was seen in the control group (5.0±3.0 during the acclimation phase versus 6.73±2.9% during the experimental phase, P=0.10) for a between‐groups difference of −4.40% (95% CI −7.00 to −1.81%, P=0.003). No change was seen in non‐flow mediated vasodilatation (NFMD) in either group. Conclusion In healthy individuals, moderate sleep restriction causes endothelial dysfunction. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT01334788.

The association between atrial fibrillation and stroke in patients with obstructive sleep apnea: a population-based case-control study.

BACKGROUND Obstructive sleep apnea (OSA) has been shown to be an independent risk factor for ischemic stroke and may increase the risk of atrial fibrillation (AF) by up to fourfold. Given these relationships, it is possible that OSA may provide a link between stroke and AF. A case-control study was conducted to examine the association between AF and stroke in patients with OSA. METHODS Olmsted County, MN, USA, residents with a new diagnosis of OSA based on polysomnography (PSG) between 2005 and 2010 (N = 2980) who suffered a first-time ischemic stroke during the same period were identified as cases. Controls with no history of stroke were randomly chosen from the same database. Univariate and multiple logistic regression analyses were performed with age, gender, body mass index (BMI), smoking, hypertension, hyperlipidemia, diabetes mellitus, apnea-hypopnea index (AHI) and coronary artery disease (CAD) as co-variates, with the diagnosis of AF as the variable of interest. RESULTS A total of 108 subjects were studied. Mean age of cases (n = 34) was 73 ± 12 years and 53% were men. Among controls (n = 74), mean age was 61 ± 16 years and 55% were male. On univariate analyses, AF was significantly more common in the cases than among controls (50.0% vs 10.8%, p < 0.01). On multivariate regression analyses, the association between AF and stroke was significant after controlling for age, BMI, coronary artery disease, hypertension, diabetes mellitus, hyperlipidemia and smoking status (corrected odds ratio (OR): 5.34; 95% confidence interval (CI): 1.79-17.29). CONCLUSIONS Patients with OSA who had a stroke had higher rates of AF even after accounting for potential confounders.

Obstructive sleep apnea is a risk factor for Barrett's esophagus.

BACKGROUND & AIMS Common risk factors for obstructive sleep apnea (OSA) and Barretts esophagus (BE) include obesity and gastroesophageal reflux disease (GERD). The aims of this study were to assess the association between OSA and BE and to determine whether the association is independent of GERD and body mass index (BMI). METHODS Patients who had undergone a diagnostic polysomnogram and esophagogastroduodenoscopy were identified by using Mayo Clinic (Rochester, Minnesota) databases from January 2000-November 2011. They were randomly matched for age, sex, and BMI at time of polysomnogram into the following groups: BE but no OSA (n = 36), OSA but no BE (n = 78), both (n = 74), or neither (n = 74). Clinical and demographic variables were abstracted from medical records. The association between OSA and BE was assessed by using a multiple variable logistic model that incorporated age, sex, BMI, clinical diagnosis of GERD, and smoking history. RESULTS Subjects with OSA had an 80% increased risk for BE compared with subjects without OSA (odds ratio, 1.8; 95% confidence interval, 1.1-3.2; P = .03). These findings were independent of age, sex, BMI, GERD, and smoking history. Increasing severity of OSA, measured by using the apnea-hypopnea index, was associated with an increased risk of BE (odds ratio, 1.2 per 10-unit increase in apnea-hypopnea index; 95% confidence interval, 1.0-1.3; P = .03). CONCLUSIONS In this case-control study, OSA was associated with an increased risk of BE, potentially through BMI and GERD independent mechanisms. Patients with OSA may benefit from evaluation for BE.

Severity of obstructive sleep apnea is associated with elevated plasma fibrinogen in otherwise healthy patients

PurposeObstructive sleep apnea (OSA) has been implicated in both cardiovascular and cerebrovascular diseases. Systemic inflammation and coagulation may be related to cardiovascular pathophysiology in patients with OSA. Fibrinogen is a major coagulation protein associated with inflammation, and long-term elevated plasma fibrinogen is associated with an increased risk of major cardiovascular diseases. We assessed whether severity of OSA is associated with levels of fibrinogen in newly diagnosed, untreated, and otherwise healthy OSA patients.MethodsWe studied 36 men with OSA and 18 male control subjects (apnea–hypopnea index [AHI] <5 events/h). OSA patients were divided into mild (AHI ≥5 < 15 events/h) and severe (AHI ≥15 events/h) OSA groups. Morning fibrinogen levels in OSA patients were compared to those in control subjects of similar age, body mass index, blood pressure, smoking habits, and alcohol consumption.ResultsFibrinogen levels were significantly elevated in patients with severe OSA compared to both control (P = 0.003) and mild OSA (P = 0.02) subjects after adjustment for covariates. However, there were no significant differences in fibrinogen levels between mild OSA and control subjects. Fibrinogen levels were directly related to AHI and arousal index and inversely related to mean and lowest oxygen saturation during sleep.ConclusionsSeverity of OSA was associated with increased fibrinogen level independent of other factors, suggesting that apneic events and oxygen desaturation during sleep are mechanisms for increased fibrinogen levels in patients with OSA.

Sleep-disordered breathing, hypertension, and obesity in retired National Football League players.

To the Editor: In 1994, the Centers for Disease Control and Prevention conducted a study evaluating retired National Football League (NFL) players. Linemen were 3 times more likely than other position players to die of heart disease and had a 52% higher risk of cardiovascular death than the