Nighttime Heart Rate Variability Research Articles

Effects of chronotype on sleep, mood and cardiovascular circadian rhythms in rotating night shift medical workers.

Whether chronotype affects the health outcomes of night shift work populations is unknown. This study aimed to assess the influence of different chronotypes in the rotating night shift population on sleep status, mood, blood pressure (BP), and heart rate variability (HRV), as well as the circadian rhythm of BP and HRV. A total of 208 rotating night shift workers were included. All participants completed structured questionnaires to assess chronotype, mood and sleep status. During their daily lives outside of the night shift, they underwent 24-hour Holter electrocardiogram monitoring and 24-hour ambulatory blood pressure monitoring. Day-time and night-time BP and BP dipping were obtained. Day-time and night-time HRV values (SDNN, RMSSD, LF, HF, LF nu, SD1, SD2 and SD2/SD1) were calculated and fitted to the cosine period curve. Three circandian parameters (mesor, amplitude and acrophase) were extracted to quantify the circadian rhythm of the HRV indices. Among all three groups, E-type showed more fatigue and sleepiness. In addition, E-type showed blunted diastolic BP dipping. Notably, E-type showed association with higher RMSSD, LF, HF and SD1 in the night time, and higher mesors of RMSSD and LF and amplitude of SD2/SD1 in circadian analysis. Chronotype is a factor affecting fatigue, sleepiness and cardiovascular circadian rhythms of rotating night shift workers. Chronotype should be taken into consideration for managing night-shift rotation to promote occupational health.

Heart Rate and Heart Rate Variability in Healthy Preterm-Born Young Adults and Association with Vitamin D: A Wearable Device Assessment.

Prematurity has been associated with impaired parasympathetic cardiac regulation later in life. Changes in heart rate (HR) and heart rate variability (HRV) may indicate a risk for future cardiac dysfunction. The putative role of Vitamin D on cardiac autonomic function in individuals born preterm (PT) remains unknown. This study involves monitoring autonomic cardiac regulation and Vitamin D concentrations in 30 PT and 16 full-term (FT) young adults in a free-living context. The PT subjects were born between 1994 and 1997 at Oulu University Hospital. The inclusion criteria were (1) being born ≤ 32 gestation weeks or (2) being born < 34 gestation weeks with a birth weight under 1500 g. Participants wore an Oura ring sleep tracer, a smart ring device, for 2 weeks to monitor cardiac autonomic function. Parameters related to autonomic cardiac regulation, lowest nighttime resting HR, and the root mean square of successive differences (RMSSD) to describe HRV were collected. PT males exhibited a tendency toward lower RMSSD (71.8 ± 22.6) compared to FT males (95.63 ± 29.0; p = 0.10). Female participants had a similar mean RMSSD in the FT and PT groups at 72.04 ± 33.2 and 74.0 ± 35.0, respectively. Serum 25-hydroxyvitamin D concentration did not correlate with cardiac autonomic function parameters. When assessing the lowest resting nighttime HRs and HRVs in a long-term, real-world context, healthy female PT young adults performed similarly to their FT peers. In contrast, the present study's results suggest that male PT young adults exhibit impaired autonomic cardiac function, potentially putting them at risk for cardiovascular disease later in adulthood.

Association of intra-shift nap duration with heart rate variability in medical night shift workers.

Napping during night shifts effectively reduces disease risk and improves work performance, but few studies have investigated the association between napping and physiological changes, particularly in off-duty daily lives. Changes in the autonomic nervous system precede diseases like cardiovascular disease, diabetes, and obesity. Heart rate variability is a good indicator of autonomic nervous system. This study aimed to investigate the link between night shift nap durations and heart rate variability indices in the daily lives of medical workers. As indicators of chronic and long-term alterations, the circadian patterns of heart rate variability indices were evaluated. We recruited 146 medical workers with regular night shifts and divided them into four groups based on their self-reported nap durations. Heart rate variability circadian parameters (midline-estimating statistic of rhythm, amplitude, and acrophase) were obtained by obtaining 24-h electrocardiogram on a day without night shifts, plotting the data of the heart rate variability indices as a function of time, and fitting them into periodic cosine curves. Using clinical scales, depression, anxiety, stress, fatigue, and sleepiness were assessed. Linear regression analysis revealed a positive relationship between 61-120-min naps and 24-h, daytime, and night-time heart rate variability indices, and the parasympathetic activity oscillation amplitude (indexed by high-frequency power, the square root of the mean of the sum of squares of differences between adjacent normal intervals, standard deviation of short-term R-R-interval variability) within one circadian cycle. This study indicated that napping for 61-120 min during night shifts could benefit medical workers' health, providing physiological evidence to promote nap management.

Nocturnal Heart Rate Variability Might Help in Predicting Severe Obstructive Sleep-Disordered Breathing.

Obstructive sleep apnea (OSA) can have long-term cardiovascular and metabolic effects. The identification of OSA-related impairments would provide diagnostic and prognostic value. Heart rate variability (HRV) as a measure of cardiac autonomic regulation is a promising candidate marker of OSA and OSA-related conditions. We took advantage of the Physionet Apnea-ECG database for two purposes. First, we performed time- and frequency-domain analysis of nocturnal HRV on each recording of this database to evaluate the cardiac autonomic regulation in patients with nighttime sleep breathing disorders. Second, we conducted a logistic regression analysis (backward stepwise) to identify the HRV indices able to predict the apnea-hypopnea index (AHI) categories (i.e., "Severe OSA", AHI ≥ 30; "Moderate-Mild OSA", 5 ≥ AHI < 30; and "Normal", AHI < 5). Compared to the "Normal", the "Severe OSA" group showed lower high-frequency power in normalized units (HFnu) and higher low-frequency power in normalized units (LFnu). The standard deviation of normal R-R intervals (SDNN) and the root mean square of successive R-R interval differences (RMSSD) were independently associated with sleep-disordered breathing. Our findings suggest altered cardiac autonomic regulation with a reduced parasympathetic component in OSA patients and suggest a role of nighttime HRV in the characterization and identification of sleep breathing disorders.

Abstract 13: Circadian Misalignment is Associated With Impaired Heart Rate Variability in Adolescents

Introduction: Adequate sleep has been recognized by AHA as part of Life’s Essential 8 in the prevention of cardiovascular disease (CVD). The circadian system, which governs the sleep-cycle, is also involved in cardiac, metabolic and autonomic regulation. Heart rate variability (HRV), a marker of cardiac autonomic modulation (CAM), is known to predict CVD. As a result, circadian misalignment of the sleep-wake cycle, which is highly prevalent in adolescents, may impact CAM and be a potential risk factor for adverse CVD outcomes in early life. Hypothesis: We hypothesize that deviations in the circadian timing of sleep are associated with blunted HRV in adolescents. Methods: We analyzed data from 337 population-based randomly-selected adolescents from the Penn State Child Cohort (median 16 years; 47% female; 21% racial/ethnic minority) who had at least 3-night at-home actigraphy (ACT), in-lab 9-h polysomnography (PSG) and 24-h Holter-monitoring heart rate variability (HRV) data. ACT-sleep duration and sleep midpoint (SM) were calculated as the intra-individual mean total sleep time and midpoint of the sleep period, respectively. ACT-sleep variability and sleep regularity (SR) were calculated as the intra-individual standard deviation of sleep duration and sleep midpoint across nights, respectively. Frequency and time-domain HRV indices, including HR oscillations at high frequencies (HF), standard deviation between normal heart beats or R-R intervals (SDNN), and root mean square of successive differences between normal heartbeats (RMSSD), were primary outcomes. Linear regression models tested SM and SR as predictors of HRV indices, while accounting for sex, race/ethnicity, age, body mass index, ACT-sleep duration, ACT-sleep variability, and PSG-apnea/hypopnea index. Results: While there were no meaningful associations between SM or SR with daytime HRV, there were significant associations between SM with nighttime HRV. A later SM was associated with lower nighttime Log-HF, SDNN and RMSSD, yet higher nighttime LF/HF (all p&lt;0.03). For each standard deviation increase in SM (i.e., 1.5 hours later), there was a decrease of -5.50ms (1.92) in nighttime RMSSD (p=0.004). More specifically, the nighttime RMSSD of adolescents with a SM at 5:30 (i.e., sleep onset at 2:00, sleep offset at 9:00), was 18.2ms (6.7) lower (p=0.007) than that of adolescents with a SM at 2:30 (i.e., sleep onset at 23:00, sleep offset at 6:00). Conclusions: A delayed sleep phase is associated with impaired CAM in adolescents. These data support that circadian misalignment of the sleep-wake cycle may independently contribute to CVD risk.

Abstract MP47: Sleep Disordered Breathing is Adversely Associated With Cardiac Autonomic Modulation in Adolescents

Introduction: Sleep disordered breathing (SDB), as measured by the apnea/hypopnea index (AHI), is a known risk factor for cardiovascular disease (CVD) in adults. Although SDB is prevalent in pediatric populations, there has been less focus on SDB as a primary risk factor for CVD in youth. The recent AHA scientific statement on SDB and CVD in children and adolescents suggests that, in order to better understand the long-term CVD-related risk associated with SDB in youth, additional longitudinal studies incorporating noninvasive markers of CVD are needed. The current study aimed to fill this important gap. Hypothesis: We hypothesized that SDB is associated with decreased HRV in adolescents. Methods: We studied 421 subjects from the Penn State Child Cohort who were 8.7 (1.7) years old at baseline and were followed-up as adolescents 16.5 (2.3) years old. We estimated the AHI from 9-hour, in-lab polysomnography (PSG), and frequency and time-domain heart rate variability (HRV) indices from 24-h Holter EKG monitoring immediately following PSG. We stratified 24-h HRV data into daytime and nighttime periods. Linear regression analyses examined the association between AHI with 24-h HRV indices, while adjusting for age, sex, race/ethnicity, BMI percentile, and metabolic syndrome (MetS) score in adolescence as well as AHI and nighttime HRV indices in childhood. Results: While there were no significant associations between AHI and daytime (p=0.233) or nighttime (p=0.147) HR, there were significant associations with frequency and time-domain HRV indices. A higher AHI was associated with lower Log-HF, Log-LF, SDNN and RMSSD, yet higher LF/HF, for both daytime and nighttime periods (all p&lt;0.05). For example, for each additional apnea or hypopnea per hour of sleep there was a decrease of -1.74ms (0.73) and -1.65ms (0.77) in SDNN during the daytime (p=0.018) and nighttime (p=0.033), respectively, even after adjusting for all covariates including MetS, childhood AHI and SDNN. More specifically, the 24-h SDNN of adolescents with an AHI≥5, indicative of moderate-to-severe SDB, was 10.9ms (4.4) lower than that of adolescents with an AHI=0 (p=0.014). Conclusions: SDB is associated with impaired cardiac autonomic balance in adolescence independently of MetS, prior SDB and prior HRV status. These data further support the role of SDB as an independent risk factor for CVD early in life.

Night-Time Heart Rate Variability during an Expedition to Mt Everest: A Case Report

Mt Everest has been gaining popularity from casual hiking athletes, climbers, and ultra-endurance marathon runners. However, living and sleeping at altitude increases the risk of injury and illness. This is because travel to high altitudes adversely affects human physiology and performance, with unfavourable changes in body composition, exercise capacity, and mental function. This is a case report of a climber who reached the summit of Mt Everest from the north side. During his 40-day expedition, we collected sleep quality data and night-time heart rate variability. During the night inside the tent, the air temperature ranged from -12.9 to 1.8 °C (-5.8 ± 4.9 °C) and the relative humidity ranged from 26.1 to 78.9% (50.7 ± 16.9%). Awake time was 17.1 ± 6.0% of every sleep-time hour and increased with altitude (r = 0.42). Sleep time (r = -0.51) and subjective quality (r = 0.89) deteriorated with altitude. Resting heart rate increased (r = 0.70) and oxygen saturation decreased (r = -0.94) with altitude. The mean NN, RMSSD, total power, LF/HF, and SD1 and SD2 were computed using the NN time series. Altitude reduced the mean ΝΝ (r = -0.73), RMSSD (r = -0.31), total power (r = -0.60), LF/HF ratio (r = -0.40), SD1 (r = -0.31), and SD2 (r = -0.70). In conclusion, this case report shows that sleeping at high altitudes above 5500 m results in progressively reduced HRV, increased awakenings, as well as deteriorated sleep duration and subjective sleep quality. These findings provide further insight into the effects of high altitude on cardiac autonomic function and sleep quality and may have implications for individuals who frequently spend time at high altitudes, such as climbers.

A post-exercise infrared sauna session improves recovery of neuromuscular performance and muscle soreness after resistance exercise training.

The aim of this study was to investigate effects of a single infrared sauna (IRS) session on post-exercise recovery of neuromuscular performance, autonomic nervous system function, subjective sleep quality, and muscle soreness. Male basketball players (n = 16) performed two trials consisting of a complex resistance exercise protocol (maximal strength with plyometrics), followed by either 20 min passive recovery (PAS) or IRS (temperature 43 ± 5°C), in a randomized crossover design, with trials separated by one week. Recovery of neuromuscular performance was assessed using 20 m maximal sprint, maximal countermovement-jump (CMJ), and isometric leg press tests, performed 14 hours after exercise. Heart rate (HR), heart rate variability (HRV), sleep diary, muscle soreness, and indirect muscle damage markers were measured pre and post exercise. The decrease in CMJ performance from pre- to post-exercise was attenuated after IRS compared to PAS (p < 0.01). The IRS session resulted in higher HR and lower root mean square of successive differences between normal heartbeats (RMSSD), and high and low frequency power, compared to PAS (p < 0.002). Post-exercise night-time HR and HRV did not differ following IRS vs. PAS. Muscle soreness was less severe, and perceived recovery was higher after IRS compared to PAS (p < 0.01). Post-exercise IRS attenuated the drop in explosive performance and decreased subjective muscle soreness after resistance training, which may enhance mood, readiness, and physical performance of an athlete. A single IRS session had no detrimental effects on recovery of the autonomic nervous system.

HEART RATE VARIABILITY IS AFFECTED IN YOUNG ADULT CELIAC PATIENTS, INDICATING AUTONOMIC DYSFUNCTION AND INCREASED CARDIOVASCULAR RISK

Aim: Celiac Disease (CD) is a common autoimmune disease that can present at any age with varied symptoms. Cardiac involvement including vascular and arrhythmic disturbances has an important prognostic value in patients with autoimmune disorders. The aim of this study was to evaluate the effects of CD on cardiovascular autonomic functions by measuring the indices of heart rate variability (HRV).&#x0D; Materials and Methods: Ninety-one CD patients and the ninety-three healthy volunteers were included in the study. We examined both time domain and frequency domain indices of HRV measured by 24-hour ambulatory electrocardiography.&#x0D; Results: All of the time domain and frequency domain HRV parameters, with the exceptions of low frequency power and low frequency to high frequency ratio, were significantly lower in patients with CD compared to the control (p &lt; 0.01). This difference retained for most of the HRV parameters when daytime and nighttime HRV parameters were compared separately. Correlation analysis revealed significant associations of HRV parameters with hemoglobin and ferritin levels and with duration of CD (p &lt; 0.01). No correlation was found between HRV parameters and anti-tissue transglutaminase IgA and IgG levels which indicate the activity of the disease.&#x0D; Conclusion: The study confirmed that patients with CD have reduced HRV, indicating the presence of objective autonomic dysfunction and increased cardiovascular risk.

The cumulative effect of chronic stress and depressive symptoms affects heart rate in a working population.

BackgroundChronic stress and depressive symptoms have both been linked to increased heart rate (HR) and reduced HR variability. However, up to date, it is not clear whether chronic stress, the mechanisms intrinsic to depression or a combination of both cause these alterations. Subclinical cases may help to answer these questions. In a healthy working population, we aimed to investigate whether the effect of chronic stress on HR circadian rhythm depends on the presence of depressive symptoms and whether chronic stress and depressive symptoms have differential effects on HR reactivity to an acute stressor.Methods1,002 individuals of the SWEET study completed baseline questionnaires, including psychological information, and 5 days of electrocardiogram (ECG) measurements. Complete datasets were available for 516 individuals. In addition, a subset (n = 194) of these participants completed a stress task on a mobile device. Participants were grouped according to their scores for the Depression Anxiety Stress Scale (DASS) and Perceived Stress Scale (PSS). We explored the resulting groups for differences in HR circadian rhythm and stress reactivity using linear mixed effect models. Additionally, we explored the effect of stress and depressive symptoms on night-time HR variability [root mean square of successive differences (RMSSD)].ResultsHigh and extreme stress alone did not alter HR circadian rhythm, apart from a limited increase in basal HR. Yet, if depressive symptoms were present, extreme chronic stress levels did lead to a blunted circadian rhythm and a lower basal HR. Furthermore, blunted stress reactivity was associated with depressive symptoms, but not chronic stress. Night-time RMSSD data was not influenced by chronic stress, depressive symptoms or their interaction.ConclusionThe combination of stress and depressive symptoms, but not chronic stress by itself leads to a blunted HR circadian rhythm. Furthermore, blunted HR reactivity is associated with depressive symptoms and not chronic stress.

The temporal relationships between sleep disturbance and autonomic dysregulation: A co-twin control study

IntroductionSleep disturbance is associated with autonomic dysregulation, but the temporal directionality of this relationship remains uncertain. The objective of this study was to evaluate the temporal relationships between objectively measured sleep disturbance and daytime or nighttime autonomic dysregulation in a co-twin control study. MethodsA total of 68 members (34 pairs) of the Vietnam Era Twin Registry were studied. Twins underwent 7-day in-home actigraphy to derive objective measures of sleep disturbance. Autonomic function indexed by heart rate variability (HRV) was obtained using 7-day ECG monitoring with a wearable patch. Multivariable vector autoregressive models with Granger causality tests were used to examine the temporal directionality of the association between daytime and nighttime HRV and sleep metrics, within twin pairs, using 7-day collected ECG data. ResultsTwins were all male, mostly white (96%), with mean (SD) age of 69 (2) years. Higher daytime HRV across multiple domains was bidirectionally associated with longer total sleep time and lower wake after sleep onset; these temporal dynamics were extended to a window of 48 h. In contrast, there was no association between nighttime HRV and sleep measures in subsequent nights, or between sleep measures from previous nights and subsequent nighttime HRV. ConclusionsDaytime, but not nighttime, autonomic function indexed by HRV has bidirectional associations with several sleep dimensions. Dysfunctions in autonomic regulation during wakefulness can lead to subsequent shorter sleep duration and worse sleep continuity, and vice versa, and their influence on each other may extend beyond 24 h.

Decreased Nighttime Heart Rate Variability and Progression of White Matter Hyperintensities of Presumed Vascular Origin. A Prospective Study in Community-Dwelling Older Adults

ObjectivesEvidence on the role of autonomic dysfunction on white matter hyperintensities (WMH) progression is limited. This study aims to assess the impact of a low nighttime heart rate variability (HRV) on WMH progression in community-dwelling older adults. Materials and methodsFollowing a prospective longitudinal study design, all individuals aged ≥60 years enrolled in the Atahualpa Project Cohort from 2012 to 2019 were invited to receive baseline HRV determinations through 24-h Holter monitoring, together with clinical interviews and brain MRIs. These individuals were periodically followed by means of annual door-to-door surveys, and those who also received brain MRIs at the end of the study (May 2021) were included in the analysis. Poisson regression models, adjusted for relevant confounders, were fitted to assess the incidence rate ratio (IRR) of WMH progression according to nighttime standard deviation of normal-to-normal R-R intervals (SDNN). ResultsThis study included 254 individuals aged ≥60 years (mean age: 65.4 ± 5.9 years; 55% women). The mean nighttime SDNN was 116.8 ± 36.3 ms. Follow-up MRIs showed WMH progression in 103 (41%) individuals after a median follow-up of 6.5 years. In unadjusted analyses, nighttime SDNN was lower among participants who developed WMH progression than in those who did not (p < 0.001). A Poisson regression model, adjusted for relevant covariates, disclosed a significantly inverse association between nighttime SDNN and WMH progression (IRR: 0.99; 95% C.I.: 0.98–0.99; p = 0.014). ConclusionsStudy results show an inverse association between nighttime SDNN and WMH progression, and provide support for the role of sympathetic overactivity in this relationship.

The differences between daytime and nighttime heart rate variability may usefully predict the apnea-hypopnea index in patients with obstructive sleep apnea.

The association between daytime/nighttime heart rate variability (HRV) and the apnea-hypopnea index (AHI) remains unclear. We sought a relationship between AHI and the daytime-to-nighttime HRV ratio as measured by 24-hour Holter monitoring in patients with obstructive sleep apnea. We prospectively enrolled 66 patients who visited our sleep clinic complaining of habitual snoring or sleep apnea. All underwent 24-hour Holter monitoring (to measure HRV) combined with full-night polysomnography. Sixty-two met our enrollment criteria. We evaluated the associations between HRV frequency domains and the polysomnography indices. We also considered medical histories and anthropometric data. The nighttime very-low-frequency (VLF), low-frequency (LF), and high-frequency HRVs were significantly higher than the daytime values. On correlation analysis, the day/night VLF (r = .550, P < .001), LF (r = .556, P < .001), and high-frequency (r = .303, P = .017) HRVs were significantly related to the AHI. Of the day/night HRV ratios, the VLF (P for trend = .003) and LF (P for trend = .013) ratios decreased significantly by obstructive sleep apnea severity. Multivariable analysis showed that the day/night VLF (β = 16.387, P < .001) and day/night LF (β = 25.248, P < .001) were independently (and significantly) associated with the AHI. Twenty-four-hour Holter monitoring may usefully predict AHI. The day/night VLF and day/night LF ratios tended to decrease by obstructive sleep apnea severity and were independently associated with the AHI. Nam E-C, Chun KJ, Won JY, Kim J-W, Lee WH. The differences between daytime and nighttime heart rate variability may usefully predict the apnea-hypopnea index in patients with obstructive sleep apnea. J Clin Sleep Med. 2022;18(6):1557-1563.

Relationship between heart rate variability, low grade inflammation and glycated hemoglobin. A sugary sweet story

Abstract Background Low grade inflammation (LGI) is significantly associated with microvascular complications in diabetes mellitus (DM). Reduced and impaired Heart rate variability (HRV) is a strong marker of autonomic dysfunction and neuropathy and strongly associated with microvascular disease in DM. New studies and observations indicate that the diabetic neuropathic process starts early during pre-diabetes. On the other hand, HRV and LGI are closely interrelated. Our aim was to evaluate whether LGI or hyperglycemia (i.e. high HbA1c) is associated with the autonomic dysfunction or reduced HRV among people with diabetes and pre-diabetes. Methods and materials This study is based on The Copenhagen Holter Study, in which 678 community dwelling subjects aged 55 – 75 years who were free of previous cardiovascular disease, except from well controlled hypertension, and who underwent a 48-hours Holter recording. Analysis of HRV including night-time HRV were available for 653 participants and this population included 133 people with well-controlled and newly recognized T2DM (mean HbA1c 55 mmol/mol (7.2%)) and 386 people with pre-diabetes defined as HbA1c between 39 mmol/mol (5.7%) and 47 mmol/mol (6.4%). We selected high-sensitive CRP, as markers of LGI. As measures of HRV we used the standard deviation of normal-to-normal (N-N) beats (SDNN), the root mean square of N-N beats (RMSSD) which has been acknowledged to be best linked to vagal parasympathetic tone, and the mean time between N-N complexes (meanNN) which represents the average 24-hour heart rate (60.000/meanNN = average 24-hour HR in beats/min) Results Measures of HRV were associated with HgbA1c among both people with T2DM and pre-diabetes. Among people with pre-diabetes HbA1c was inversely associated with 24-hour RMSSD (r=−0.11, p=0.03) and night-time SDNN (r=−0,13, p&amp;gt;0.01), while among T2DM HgbA1c was only associated with 24-hour RMSSD (r=−0.21, p=0.02). These association stayed significant when adjusted for sex, age, BMI, smoking, HOMA-ir, hs-CRP and systolic blood pressure in multiple linear regression (Table 1). LGI was only associated with HRV in diabetes. HbA1c was not associated with any measures of HRV or LGI among people with normal glucose metabolism. Conclusion HRV is closely and inversely associated with HbA1c in both diabetes and prediabetes, but only in diabetes LGI is associated with HRV. This indicates that the process of autonomic dysfunction/neuropathy starts at an early phase during pre-diabetes and probably provoked by postprandial hyperglycemia, while in diabetes both HbA1c and LGI are associated with HRV showing that LGI is activated later in the disease process probably provoked by long-term postprandial hyperglycemia, indicating treatment of hyperglycemia and postprandial hyperglycemia in the prediabetes state may be helpful. Funding Acknowledgement Type of funding sources: None.

Night-time heart rate variability identifies high-risk people among people with uncomplicated type 2 diabetes mellitus.

Low heart rate variability (HRV) reflects cardiac autonomic neuropathy, which is associated with increased cardiovascular mortality in people with type 2 diabetes mellitus (T2DM). Measuring HRV is challenged by environmental noise, mental stress and physical activity during daytime. Night-time HRV during sleep may be a more valid tool to measure cardiac autonomic neuropathy and therefore may improve prediction of cardiovascular (CV) events in low-risk people with T2DM. Copenhagen Holter Study included 678 community-dwelling participants aged 55-75years who were free of previous CV disease. Day and night-time HRV were available for 653 participants. The population included 133 people with well-controlled T2DM and newly recognized T2DM (mean HbA1c 55mmol/mol [7.2%]). HRV is defined as standard deviation for the mean value of normal-to-normal complexes (SDNN). Night-time HRV measurements were pre-defined from 2:00 to 2:15 AM. Cardiovascular events were defined as CV death, myocardial infarction, stroke or coronary revascularization. Median follow-up time was 14.4years. During this period, 245 death and 149 CV events (CV death 36, myocardial infarction 42, revascularisation procedures 46, stroke 70) occurred in total. Among people with T2DM, 41 CV events were observed (CV death 13, myocardial infarction 13, revascularisation procedures 17, stroke 18). Night-time SDNN was inversely associated with CV events in people with T2DM, (hazard ratio [HR]: 0.74 95% confidence interval [CI]:0.61-0.89) for each 10-millisecond increment in SDNN after adjustment for the conventional risk factors sex, age, LDL cholesterol, smoking, systolic blood pressure and by also including glucose CRP and NT-proBNP in adjustment. Twenty-four-hour HRV was not associated with CV events, but associated with all-cause mortality in people with T2DM. Conventional risk factors had a receiver operating characteristic (ROC) value of 0.704 (95% CI 0.602-0.806) to predict CV events in people with T2DM. The prediction of CV events by conventional risk factors was improved in people with T2DM by the addition of night-time SDNN; ROC 0.765 (95% CI 0.669-0.862), p=0.037, but ROC was not improved by addition of CRP and NT-proBNP in the model. In people with T2DM and night-time SDNN ≤30ms, the 10-year risk of CV death and CV event rate was 12% and 45%, respectively, which re-allocated them to a 'very high-risk' group according to current guidelines. Reduced night-time HRV predicts increased risk of CV events in people with well-controlled T2DM, thus night-time HRV may add to traditional risk factors in predicting CV events in people with T2DM.

Night heart rate variability identifies cardiovascular risk in community dwelling people with uncomplicated type 2 diabetes mellitus

Abstract Introduction Low Heart rate variability (HRV) reflects cardiac autonomic neuropathy, associated with increased cardiovascular mortality in type 2 diabetes (T2DM) patients. Measuring HRV is challenged by environmental noise, mental stress and physical activity during the day-time. Thus, measuring night-time HRV during sleep may be a better tool to predict cardiovascular (CV) events in low risk T2DM patients without previous cardiovascular disease. Methods Copenhagen Holter Study included 678 community dwelling subjects aged 55–75 years free of previous cardiovascular disease. Day- and night-time HRV were available for 653. The population included 133 well-controlled T2DM patients (mean HbA1c 7.2%). Median follow- up was 14.4 years. HRV is defined as standard deviation for the mean value of normal-to-normal complexes (SDNN). Night-time HRV measurements were pre-defined from 2:00 to 2:15 AM. CV events were defined as CV death, myocardial infarction, stroke, or coronary revascularization. Results The rate of CV events was 17 and 31 per 1000 patient-year in patients without and with T2DM, respectively (p=0.015). Night-time SDNN was inversely associated with CV events in T2DM patients with a HR of 0.74 (0.61–0.89), P=0.001, for each 10 ms increment in SDNN, after adjustment for sex, age, LDL, smoking, systolic BP, glucose, CRP and NT pro-BNP (table 1). Twenty-four-hours HRV was not associated with cardiovascular events (table 1). Conventional risk factors had an AUC of 0.704 (95% CI 0.602–0.806) to predict CV events in T2DM. Prediction was improved by the addition of night-time SDNN; AUC 0.765 (95% CI 0.669–0.862), P=0.037, but not by CRP or NT-proBNP (Figure 1). In subjects with well-controlled T2DM and night-time SDNN ≤30 ms, the 10-year risk of CV death and CV even-rate were 12% and 45%, respectively. This allocates these T2DM patients in a “very high-risk” group, and more aggressive targets for blood-pressure and lipids according to the current guidelines. Conclusion Reduced night-time HRV associates with increased risk of CV events in persons with well-controlled T2DM. We observed improved risk prediction of cardiovascular events in T2DM by night-time HRV, which may have therapeutic consequences. Figure 1. ROC Curve Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Danish Heart Foundation

In Amateur Athletes With Type 1 Diabetes, a 9-Day Period of Cycling at Moderate-to-Vigorous Intensity Unexpectedly Increased the Time Spent in Hyperglycemia, Which Was Associated With Impairment in Heart Rate Variability.

In type 1 diabetes, autonomic dysfunction may occur early as a decrease in heart rate variability (HRV). In populations without diabetes, the positive effects of exercise training on HRV are well-documented. However, exercise in individuals with type 1 diabetes, particularly if strenuous and prolonged, can lead to sharp glycemic variations, which can negatively impact HRV. This study explores the impact of a 9-day cycling tour on HRV in this population, with a focus on exercise-induced glycemic excursions. Twenty amateur athletes with uncomplicated type 1 diabetes cycled 1,500 km. HRV and glycemic variability were measured by heart rate and continuous glucose monitoring. Linear mixed models were used to test the effects of exercise on HRV, with concomitant glycemic excursions and subject characteristics considered as covariates. Nighttime HRV tended to decrease with the daily distance traveled. The more time the subjects spent in hyperglycemia, the lower the parasympathetic tone was. This result is striking given that hyperglycemic excursions progressively increased throughout the 9 days of the tour, and to a greater degree on the days a longer distance was traveled, while time spent in hypoglycemia surprisingly decreased. This phenomenon occurred despite no changes in insulin administration and a decrease in carbohydrate intake from snacks. In sports enthusiasts with type 1 diabetes, multiday prolonged exercise at moderate-to-vigorous intensity worsened hyperglycemia, with hyperglycemia negatively associated with parasympathetic cardiac tone. Considering the putative deleterious consequences on cardiac risks, future work should focus on understanding and managing exercise-induced hyperglycemia.

Sleep Quality Is Associated With Nighttime Heart Rate Variability In Young Adults

Heart rate variability (HRV) reflects autonomic nervous system function, and low nighttime HRV is linked to reduced parasympathetic control. Optimal parasympathetic function is important for the induction and maintenance of sleep, overall wellbeing, and is inversely associated with chronic disease. In young adults, 60% of whom report poor sleep quality, disrupted parasympathetic function may reflect suboptimal health and lifestyle behaviors. While there is an established relationship between physical activity (PA), stress, and nighttime HRV, the associations between HRV and other lifestyle-related factors such as sleep quality and social jet lag (SJL) in young adult populations are yet to be determined. PURPOSE: The purpose of this study was to determine the relationship between nighttime HRV and sleep characteristics in young adults. METHODS: Healthy young adults (n=33, 18.6 ± 0.7 years, 69.6% female) wore a chest-strap heart rate monitor for 24 hours and a triaxial accelerometer on the non-dominant wrist for 7 days during free-living PA and sleep. Average sleep duration and SJL were determined from objective sleep data, with SJL calculated as the difference in hours between the midpoint of sleep on weeknights (school) and weekend (free) nights. The Pittsburgh Sleep Quality Index (PSQI) and Perceived Stress Scale were used as subjective measures of sleep quality and stress. Nighttime HRV outcomes were calculated using R-R intervals between the hours of 1:00 AM - 5:00 AM. Linear regression assessed multivariate relationships among sleep duration, quality, SJL, and HRV while controlling for moderate-to-vigorous PA and perceived stress. RESULTS: Independent of average sleep duration and SJL, perceived sleep quality was associated with the HRV outcomes low frequency (LF; B= -10.62 ± 4.85, 95% CI: -20.56, -.67) and high frequency power (HF; B= 10.55 ± 4.84, 95% CI: .61, 20.49). Following control for PA and stress, these relationships remained significant and the association between SJL and LF/HF ratio approached significance (B= -.33 ± .18, 95% CI: -.69, .04). CONCLUSIONS: Our findings suggest that both LF and HF HRV components are related to sleep quality in young adults, highlighting a potential relationship between sleep quality and nighttime autonomic nervous system function.

Almonds Improve Endothelial Function and Lower LDL Cholesterol, But Do Not Affect Liver Fat in Adults at Moderate Risk of Cardiovascular Disease: A Randomized Controlled Trial

Abstract Objectives The ATTIS study aimed to investigate whether substituting almonds for typical snacks (high in refined starch, free sugars and saturated fats, and low in fibre) influenced cardiometabolic risk factors. Primary outcomes, endothelial function and liver fat, were measured in healthy adults aged 30–70 y who were habitual snackers and at moderate risk of developing cardiovascular disease (CVD). It was hypothesized that snacking on almonds would improve endothelial function and decrease liver fat. Methods Following a 2-week run-in period consuming control snacks, a 6-week parallel arm trial was conducted where participants were randomized to isoenergetic treatments: 1) control snacks (mini-muffins) replicating an average snack nutrient profile, calculated from snack foods identified in 4-d food diaries from a national dietary intake database, or 2) dry-roasted whole almonds, providing 20% estimated energy requirement. Endothelial function (via flow-mediated dilation (FMD)); abdominal subcutaneous and visceral fat, and liver, muscle and pancreatic fat (via MRI/MRS); day- and night-time heart rate variability (HRV) and 24 h ambulatory blood pressure (ABP); blood biomarkers of insulin sensitivity and lipid profile; and fecal short chain fatty acids (SCFA) were assessed at baseline and endpoint. A total of 107 participants (75 F, 32 M; mean age 56.2 y, SD 10.4) were randomized and 105 subjects completed the trial. Results Almonds significantly increased FMD (mean difference 4.1%, 95% CI 2.2, 5.9), the long-phase HRV index, night-time very-low frequency power (mean difference 337 ms2, 95% CI 12, 661) and plasma oleic acid levels (mean difference 228 μmol, 95% CI 7, 449) relative to control adjusted for baseline BMI and baseline dependent outcome values, but there were no treatment differences in ABP and subcutaneous, visceral, liver, muscle and pancreatic fat. Plasma LDL cholesterol levels were significantly decreased by almonds (mean difference −0.25 mmol/L, 95% CI −0.45, −0.04), but no differences were found in other blood lipids, insulin sensitivity, nor fecal SCFA levels. Conclusions These novel findings suggest almonds may be cardioprotective by increasing availability of nitric oxide and improving cardiac autonomic function, in addition to their well-established LDL cholesterol-lowering properties. Funding Sources Almond Board of California.

Effect of Heart Rate Variability on the Association Between the Apnea-Hypopnea Index and Cerebral Small Vessel Disease.

Background and Purpose- The apnea-hypopnea index (AHI) is associated with cerebral small vessel disease (cSVD), but pathogenesis of this association is elusive. We aimed to assess the effect of nighttime heart rate variability (HRV)-as a proxy of sympathetic upregulation-on the aforementioned association. Methods- Atahualpa residents aged ≥60 years undergoing brain magnetic resonance imaging, polysomnography, and 24-hour Holter monitoring (N=176) were included. The presence of moderate-to-severe white matter hyperintensities, deep cerebral microbleeds, lacunar infarcts, and >10 enlarged basal ganglia perivascular spaces were added for estimating the cSVD score. Interaction models were fitted to assess the effect modification of nighttime HRV in the association between the AHI and the cSVD score, and mediation analysis was utilized to assess the proportion of total effect by nighttime HRV on this association. Results- Generalized linear models showed a significant association between the AHI and the cSVD score (P=0.025), as well as a significant inverse association between nighttime HRV and the cSVD score (P=0.002), but no association between daytime HRV and the cSVD score (P=0.097). Interaction models showed a significant interaction of nighttime HRV on the association between AHI and the cSVD score (P=0.001), and mediation analysis found that the percent of total effect between AHI and cSVD score mediated by HRV was 30.8%. Predictive marginal means of the cSVD score were highly significant when the 10th percentile of nighttime HRV was compared across categories of 10th and 90th percentiles of the AHI (cSVD score margins, 0.61 [95% CI, 0.37-0.86] versus 1.67 [95% CI, 1.26-2.09]). Contour plots showed the effect of nighttime (but not daytime) HRV on the association between AHI and the cSVD score. Conclusions- This study shows an important effect of nighttime HRV on the association between the AHI and the cSVD score and provides further support for the role of sympathetic overactivity on this association.