Identifying an acceptable number of ambulatory blood pressure measurements for accuracy of average blood pressure and nocturnal dipping status.

We aimed to identify the minimum number of ambulatory blood pressure (ABP) measures to accurately determine daytime and nighttime systolic blood pressure (BP) averages and nocturnal dipping status (i.e., relative daytime:nighttime change). A total of 43 midlife participants wore an ABP monitor for 24 h with measurements every 20/30 min during the daytime/nighttime, as identified by a sleep diary. We calculated daytime/nighttime systolic BP average and dipping status from all available measurements per participant (i.e., normative data). We then calculated daytime and nighttime BP per participant based on a random selection of 8-20 and 4-10 measurements and replicated random selections 1,000 times. We calculated accuracy by checking the proportion from 1,000 different randomly selected samples for a particular number of measurements that systolic BP was ±5 mmHg of normative data, and dipping status remained unchanged for each participant compared with the normative value. The best fit for the regression model estimated the minimal number of measurements for an accuracy of 95% in BP averages. For a 95% accuracy in estimating daytime and nighttime systolic BP, 11 daytime and 8 nighttime measurements were required. The highest accuracy for dipping status was 91.6 ± 13.4% using 20 daytime and 10 nighttime measures, while the lowest was (83.4 ± 15.1%) using 8 daytime and 4 nighttime measures. In midlife adults, 11 daytime and 8 nighttime measurements are likely enough to calculate average systolic BPs accurately. However, no minimum number is suggested to accurately calculate dipping status.NEW & NOTEWORTHY We found that a minimum of 11 blood pressure (BP) measures are necessary to calculate an accurate average daytime BP, and 8 nighttime measures are necessary to calculate an accurate nighttime average if 95% accuracy is acceptable. Regarding BP dipping status, the current recommendations (20 daytime/7 nighttime) inaccurately classified the dipping status 10.5% of the time, suggesting that guidelines may need to be updated to classify patients as nocturnal dippers or nondippers correctly.

Chronological distribution of readings in ambulatory blood pressure monitoring exams affects the nighttime average and the magnitude of blood pressure dipping.

STUDY OBJECTIVES: Averaged nighttime blood pressure (BP) is superior to daytime BP for cardiovascular risk stratification, and the relative change between daytime/nighttime BP (dipping%) significantly predicts cardiovascular risk. Newer reports suggest that 4 measurements at night may be enough for cardiovascular risk stratification. Since BP oscillates across the night, the temporal distribution of measurements across the night may impact nighttime BP and dipping%. Therefore, we compared average nighttime BP and dipping% when using measurements in the first half (1st-half), second (2nd-half), and a combination of both (combined). METHODS: Forty-three (17 females and twenty-six males) midlife adults aged 50±10 years old wore an ambulatory BP monitor for 24 hours at home, programmed to measure BP every 20 minutes when scheduled for daytime and every 30 minutes during a self-selected 8-hour nighttime for time-in-bed. We compared the nighttime BP averages and dipping% when using either the first four measurements from the 1st-half or 2nd-half of the nighttime and combined. RESULTS: Nighttime Systolic BP was significantly different across 1st-half, 2nd-half, and combined (111±9 vs.107±11 vs. 109±9 mmHg, p<0.01), respectively, with significant pairwise differences across all categories (p<0.01 for each). Systolic BP dipping% was significantly different across 1st-half, 2nd-half, and combined (9.9±5.5 vs.13.5±6.4 vs. 11.7±5.0 %, p<0.01), respectively, with significant pairwise differences across all categories (p<0.01 for each. Diastolic BP and diastolic dipping% were similar across the three different bins. CONCLUSION: In midlife adults, systolic nighttime BP and dipping% may depend upon when BP measurements are taken during the night.

Inverse correlation between plasma 2-arachidonoylglycerol levels and subjective severity of depression.

OBJECTIVE: Endocannabinoids have been implicated in the pathophysiology of Major Depressive Disorder (MDD) and might represent potential targets for therapeutic intervention. Objectives of the study were: (1) to measure plasma levels of endocannabinoids in a group of antidepressant-free depressed outpatients; (2) to explore their relationship with the severity of depressive symptoms as subjectively perceived by the patients; and (3) to investigate the effect of the selective serotonin reuptake inhibitor escitalopram on endocannabinoid levels. METHODS: We measured plasma levels of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anadamide), in 12 drug-free outpatients diagnosed with MDD and in 12 matched healthy controls. In the patient group, endocannabinoids plasma levels were assessed at baseline and after 2 months of treatment with escitalopram. RESULTS: Baseline plasma levels of the two endocannabinoids did not differ between depressed patients and healthy controls. However, there was a significant inverse correlation between 2-arachidonoylglycerol levels and the severity of subjectively perceived depressive symptoms. Treatment with escitalopram did not change endocannabinoid levels in depressed patients, although it caused the expected improvement of depressive symptoms. CONCLUSIONS: Our results suggest that 2-arachidonylglycerol, the most abundant endocannabinoid in the central nervous system, might act to mitigate depressive symptoms, and raise the interesting possibility that 2-arachidonylglycerol and anandamide are differentially regulated in patients affected by MDD. Also, our data suggest but do not prove that the endocannabinoid system is not regulated by serotonergic transmission, at least in depressed patients.

Interactions between home, work, and sleep among firefighters.

BACKGROUND: Firefighters endure large occupational burdens and generally operate under conditions of chronic sleep deficiency and circadian disruption due to long shifts, plus interrupted sleep due to emergency calls during the night. A typical shift for firefighters is 24-h on/48-h off, and firefighters are expected to use time-off to recover from any sleep debt, while balancing social, family, and home responsibilities. This qualitative study sets out to assess family dynamics and how firefighters prioritize sleep and recovery at home based on relationship or family status, as well as a fire department's current shift schedule. METHODS: Focus groups were conducted via convenience sampling in Portland, OR, with full-time firefighters, battalion chiefs, and their spouses. Grounded theory, using NVivo 12 Plus, was used to code transcripts to reveal reoccurring concepts and themes. RESULTS: Major themes centered around the increase of nonemergent calls contributing to compassion fatigue. Spouses can help improve the sleep of firefighters by creating opportunities for recuperative sleep at home. However, spouses also conveyed underlying tones of "resentment" relating to their firefighter being unavailable for emotional and instrumental support. While married firefighters discussed choosing family and home obligations over reducing sleep debt to maintain relationships, single and divorced firefighters spoke of fewer conflicts impeding their ability to prioritize sleep at home. CONCLUSIONS: These results improve our understanding of how firefighters prioritize sleep at home based on family dynamics and can inform future decision-making for fire departments in addressing concerns related to work-family conflict, sleep loss, and compassion fatigue among their members.

Role for fatty acid amide hydrolase (FAAH) in the leptin-mediated effects on feeding and energy balance.

Endocannabinoid signaling regulates feeding and metabolic processes and has been linked to obesity development. Several hormonal signals, such as glucocorticoids and ghrelin, regulate feeding and metabolism by engaging the endocannabinoid system. Similarly, studies have suggested that leptin interacts with the endocannabinoid system, yet the mechanism and functional relevance of this interaction remain elusive. Therefore, we explored the interaction between leptin and endocannabinoid signaling with a focus on fatty acid amide hydrolase (FAAH), the primary degradative enzyme for the endocannabinoid N-arachidonoylethanolamine (anandamide; AEA). Mice deficient in leptin exhibited elevated hypothalamic AEA levels and reductions in FAAH activity while leptin administration to WT mice reduced AEA content and increased FAAH activity. Following high fat diet exposure, mice developed resistance to the effects of leptin administration on hypothalamic AEA content and FAAH activity. At a functional level, pharmacological inhibition of FAAH was sufficient to prevent leptin-mediated effects on body weight and food intake. Using a novel knock-in mouse model recapitulating a common human polymorphism (FAAH C385A; rs324420), which reduces FAAH activity, we investigated whether human genetic variance in FAAH affects leptin sensitivity. While WT (CC) mice were sensitive to leptin-induced reductions in food intake and body weight gain, low-expressing FAAH (AA) mice were unresponsive. These data demonstrate that FAAH activity is required for leptin's hypophagic effects and, at a translational level, suggest that a genetic variant in the FAAH gene contributes to differences in leptin sensitivity in human populations.

Optimization of Primary Care Among Black Americans Using Patient Portals: Qualitative Study.

BACKGROUND: Reduced patient portal use has previously been reported among Black Americans when compared with that of the general population. This statistic is concerning because portals have been shown to improve the control of chronic conditions that are more prevalent and severe in Black Americans. At their very simplest, portals allow patients to access their electronic health records and often provide tools for patients to interact with their own health information, treatment team members, and insurance companies. However, research suggests that Black American patients have greater concerns over a lack of support, loss of privacy, and reduced personalization of care compared with other Americans, which results in a disparity of portal use. OBJECTIVE: This qualitative investigation of primary care experiences of Black Americans from across the United States who participated in remote focus groups in April and May 2020 aims to explore the use and perceived value of patient portals to better understand any barriers to optimized treatment in the primary care setting. METHODS: We performed an inductive thematic analysis of 8 remote focus group interviews with 29 Black American patients aged 30-60 years to qualitatively assess the experiences of Black American patients with regular access to portals. RESULTS: Thematic analysis uncovered the following interrelated themes regarding patient portals in primary care: the optimization of care, patient empowerment, patient-provider communication, and patient burden. CONCLUSIONS: In contrast to what has been described regarding the reluctance of Black Americans to engage with patient portals, our focus groups revealed the general acceptance of patient portals, which were described overwhelmingly as tools with the potential for providing exceptional, personalized care that may even work to mitigate the unfair burden of disease for Black Americans in primary care settings. Thus, opportunities for better health care will clearly arise with increased communication, experience, and adoption of remote health care practices among Black Americans.

Circadian Rhythm of Vascular Function in Midlife Adults.

Objective- Adverse cardiovascular events occur more frequently in the morning than at other times of the day. Vascular endothelial function (VEF)-a robust cardiovascular risk marker-is impaired during this morning period. We recently discovered that this morning impairment in VEF is not caused by either overnight sleep or the inactivity that accompanies sleep. We determined whether the endogenous circadian system is responsible for this morning impairment in VEF. We also assessed whether the circadian system affects mechanistic biomarkers, that is, oxidative stress (malondialdehyde adducts), endothelin-1, blood pressure, and heart rate. Approach and Results- Twenty-one (11 women) middle-aged healthy participants completed a 5-day laboratory protocol in dim light where all behaviors, including sleep and activity, and all physiological measurements were evenly distributed across the 24-hour period. After baseline testing, participants underwent 10 recurring 5-hour 20-minute behavioral cycles of 2-hour 40-minute sleep opportunities and 2 hours and 40 minutes of standardized waking episodes. VEF, blood pressure, and heart rate were measured, and venous blood was sampled immediately after awakening during each wake episode. Independent of behaviors, VEF was significantly attenuated during the subjective night and across the morning ( P=0.04). Malondialdehyde adducts and endothelin-1 exhibited circadian rhythms with increases across the morning vulnerable period and peaks around noon ( P≤0.01). Both systolic ( P=0.005) and diastolic blood pressure ( P=0.04) were rhythmic with peaks in the late afternoon. Conclusions- The endogenous circadian system impairs VEF and increases malondialdehyde adducts and endothelin-1 in the morning vulnerable hours and may increase the risk of morning adverse cardiovascular events in susceptible individuals. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02202811.

Separate and interacting effects of the endogenous circadian system and behaviors on plasma aldosterone in humans.

Measurements of aldosterone for diagnosis of primary aldosteronism are usually made from blood sampled in the morning when aldosterone typically peaks. We tested the relative contributions and interacting influences of the circadian system, ongoing behaviors, and prior sleep to this morning peak in aldosterone. To determine circadian rhythmicity and separate effects of behaviors on aldosterone, 16 healthy participants completed a 5-day protocol in dim light while all behaviors ranging from sleep to exercise were standardized and scheduled evenly across the 24-h circadian period. In another experiment, to test the separate effects of prior nocturnal sleep or the inactivity that accompanies sleep on aldosterone, 10 healthy participants were studied across 2 nights: 1 with sleep and 1 with maintained wakefulness (randomized order). Plasma aldosterone was measured repeatedly in each experiment. Aldosterone had a significant endogenous rhythm ( P < 0.001), rising across the circadian night and peaking in the morning (~8 AM). Activity, including exercise, increased aldosterone, and different behaviors modulated aldosterone differently across the circadian cycle (circadian phase × behavior interaction; P < 0.001). In the second experiment, prior nocturnal sleep and prior rested wakefulness both increased plasma aldosterone ( P < 0.001) in the morning, to the same extent as the change in circadian phases between evening and morning. The morning increase in aldosterone is due to effects of the circadian system plus increased morning activities and not prior sleep or the inactivity accompanying sleep. These findings have implications for the time of and behaviors preceding measurement of aldosterone, especially under conditions of shift work and jet lag.

A peripheral endocannabinoid mechanism contributes to glucocorticoid-mediated metabolic syndrome.

Glucocorticoids are known to promote the development of metabolic syndrome through the modulation of both feeding pathways and metabolic processes; however, the precise mechanisms of these effects are not well-understood. Recent evidence shows that glucocorticoids possess the ability to increase endocannabinoid signaling, which is known to regulate appetite, energy balance, and metabolic processes through both central and peripheral pathways. The aim of this study was to determine the role of endocannabinoid signaling in glucocorticoid-mediated obesity and metabolic syndrome. Using a mouse model of excess corticosterone exposure, we found that the ability of glucocorticoids to increase adiposity, weight gain, hormonal dysregulation, hepatic steatosis, and dyslipidemia was reduced or reversed in mice lacking the cannabinoid CB1 receptor as well as mice treated with the global CB1 receptor antagonist AM251. Similarly, a neutral, peripherally restricted CB1 receptor antagonist (AM6545) was able to attenuate the metabolic phenotype caused by chronic corticosterone, suggesting a peripheral mechanism for these effects. Biochemical analyses showed that chronic excess glucocorticoid exposure produced a significant increase in hepatic and circulating levels of the endocannabinoid anandamide, whereas no effect was observed in the hypothalamus. To test the role of the liver, specific and exclusive deletion of hepatic CB1 receptor resulted in a rescue of the dyslipidemic effects of glucocorticoid exposure, while not affecting the obesity phenotype or the elevations in insulin and leptin. Together, these data indicate that glucocorticoids recruit peripheral endocannabinoid signaling to promote metabolic dysregulation, with hepatic endocannabinoid signaling being especially important for changes in lipid metabolism.

Trouble in transit: Organizational barriers to workers' health.

BACKGROUND: Valuable insights on the health and behavior of transit workers can be obtained from qualitative research that considers the social environment, which affects job performance and determines levels of perceived stress. METHODS: Using a grounded theory approach, semi-structured interviews were conducted with American transit workers (n = 32). Recorded interviews were transcribed and analyzed using a constant comparative method. RESULTS: Participants described categories related to entrenched organizational practices, particularly managements' leadership style, which created an atmosphere of distrust. High demanding work schedules, as a result of technological advances, were discussed in relation to diminished breaks, fatigue, and unhealthy diets. Transit workers also attributed increased work demands and irregular working hours to compromised time with family and friends. CONCLUSIONS: The described barriers to positive health behaviors and social support underscore the need for interventions that ensure adequate breaks and recovery between shifts and increase safety for transit passengers. Am. J. Ind. Med. 60:350-367, 2017. © 2017 Wiley Periodicals, Inc.

Cardiovascular disease risk: it is complicated, but race and ethnicity are key, a Bayesian network analysis.

Background: Cardiovascular diseases are the leading cause of morbidity and mortality in the United States. Despite the complexity of cardiovascular disease etiology, we do not fully comprehend the interactions between non-modifiable factors (e.g., age, sex, and race) and modifiable risk factors (e.g., health behaviors and occupational exposures). Objective: We examined proximal and distal drivers of cardiovascular disease and elucidated the interactions between modifiable and non-modifiable risk factors. Methods: We used a machine learning approach on four cohorts (2005-2012) of the National Health and Nutrition Examination Survey data to examine the effects of risk factors on cardiovascular risk quantified by the Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE). We estimated a network of risk factors, computed their strength centrality, closeness, and betweenness centrality, and computed a Bayesian network embodied in a directed acyclic graph. Results: In addition to traditional factors such as body mass index and physical activity, race and ethnicity and exposure to heavy metals are the most adjacent drivers of PCE. In addition to the factors directly affecting PCE, sleep complaints had an immediate adverse effect on FRS. Exposure to heavy metals is the link between race and ethnicity and FRS. Conclusion: Heavy metal exposures and race/ethnicity have similar proximal effects on cardiovascular disease risk as traditional clinical and lifestyle risk factors, such as physical activity and body mass. Our findings support the inclusion of diverse racial and ethnic groups in all cardiovascular research and the consideration of the social environment in clinical decision-making.

Belonging, endurance, and resistance: Black placemaking theory in primary care.

Black-Americans continue to experience pervasive health disparities. Factors contributing to increased disease risk include a general mistrust of biomedical institutions among Black Americans. The purpose of this focus group study was to identify, among Black patients who regularly seek care from a primary provider, salient themes regarding barriers to 1) receiving quality primary care; and 2) adhering to medical recommendations. We examined transcripts of eight focus groups held remotely with 29 Black patients (aged 30-60 years) who had established primary care providers. Using grounded theory and an inductive thematic analysis of the transcripts, we identified three themes (belonging, endurance, and resistance) consistent with Black placemaking theory. Our findings suggest that reducing health disparities for Black Americans will require clinical initiatives that emphasize: 1) attention to social influences on health behavior and to features of medical institutions that mark them as White spaces (belonging); 2) recognition of, as well as sensitivity to, community awareness of the systemic and interpersonal barriers to health and safety that many Black adults endure; and 3) reframing avoidant (resistant) behaviors as protective strategies among Black patients. Examining primary care in this way-through the lens of Black placemaking theory-reveals how culturally meaningful approaches to harnessing the specialized knowledge and resilience that clearly exists among many Black communities can improve health care delivery.

Obesity alters the circadian profiles of energy metabolism and glucose regulation in humans.

OBJECTIVE: Given the complex interaction among the circadian system, energy metabolism, and obesity, the authors tested whether having obesity impacts the circadian variation in energy and glucose metabolism in humans. METHODS: Participants with BMI either in the healthy weight or obesity ranges were studied in a 5-day, in-laboratory protocol that equally distributed behaviors (i.e., sleep, eating, exercise) across 24 h. Energy metabolism was measured at rest and during a standardized exercise bout and blood was sampled before and after each identical study meal to assess glucose and insulin levels. RESULTS: In those with a healthy weight, the circadian nadir of energy expenditure, during both rest and exercise, occurred when participants would normally be asleep. However, in those with obesity, this nadir appears to occur during the habitual wake period. Differences in glucose regulation also depended on the circadian phase, such that individuals with obesity appeared to have relatively greater glucose intolerance during the circadian day and produced less insulin during the circadian night. CONCLUSIONS: Obesity is associated with altered circadian energy and glucose metabolism. Understanding and addressing these associations could lead to strategies that improve body weight and metabolic health in people with obesity.

Daily cannabis use is associated with sleep duration differentially across ages.

OBJECTIVE: To assess the relationship between frequency of cannabis use and sleep duration across age in a large US population (235,667 people). METHODS: Multinomial logistic regression was used to evaluate the association between the frequency of cannabis use and sleep duration using cross sectional data from the 2016-2018 Behavioral Risk Factor Surveillance System. RESULTS: When adjusted for sociodemographic factors, health related variables, and stratified by age we found that young adults (18-44 years) who reported daily-use (≥16 uses a month) had an increased risk ratio (RR [95% CI]) for either short or long sleep (1.22 [1.06-1.40] and 1.52 [1.07-2.16]); midlife adults (45-64 years) who reported daily-use had an increased prevalence of long sleep (1.71 [1.03-2.82]); and older adults (≥65 years) who reported daily-use had an increased prevalence of short sleep (1.61 [1.05-2.49]). CONCLUSIONS: Compared to those who reported no cannabis use, individuals who reported daily cannabis use demonstrated a greater prevalence for either short or long sleep duration.

The circadian system modulates the cortisol awakening response in humans.

Background: In humans, circulating cortisol usually peaks 30-60 min after awakening from nocturnal sleep, this is commonly referred to as the cortisol awakening response (CAR). We examined the extent to which the CAR is influenced by the circadian system, independent of behaviors including sleep. Materials and methods: We examined the CAR in 34 adults (20 female) using two complementary multiday in-laboratory circadian protocols performed in dim light, throughout which behavioral factors were uniformly distributed across the 24-hour circadian cycle. Protocol 1 consisted of 10 identical consecutive 5-hour 20-minute sleep/wake cycles, and protocol 2 consisted of 5 identical consecutive 18-hour sleep/wake cycles. Salivary melatonin was used as the circadian phase marker (0° = dim light melatonin onset). During each sleep/wake cycle, salivary cortisol was measured upon scheduled awakening and 50-minutes later, with the change in cortisol defined as the CAR. Cosinor analyses were used to detect any significant circadian rhythmicity in the CAR. In secondary analyses, we adjusted the models for time awake before lights on, total sleep time, percent of rapid eye movement (REM) sleep, and percent of non-rapid eye movement (NREM) sleep. Results: Both protocols revealed a similar circadian rhythm in the CAR, with peaks occurring at a circadian phase corresponding to 3:40-3:45 a.m., with no detectable CAR during the circadian phases corresponding to the afternoon. In addition to the sinusoidal component of the circadian rhythm, total sleep time was also associated with the CAR for protocol 1. The percent of sleep spent in REM or NREM sleep were not associated with the CAR in either protocol. Conclusion: Our results show that the CAR exhibits a robust circadian rhythm that persists even after adjusting for prior sleep. Presuming that the CAR optimizes physiological responses to the anticipated stressors related to awakening, these findings may have implications for shift workers who wake up at unusual circadian phases. A blunted CAR in shift workers upon awakening in the evening may result in diminished responses to stressors.