Plasma brain-derived neurotrophic factor and reverse dipping pattern of nocturnal blood pressure in patients with cardiovascular risk factors.

Basic studies have shown that brain-derived neurotrophic factor (BDNF) has critical roles in the survival, growth, maintenance, and death of central and peripheral neurons, while it is also involved in regulation of the autonomic nervous system. Furthermore, recent clinical studies have suggested potential role of plasma BDNF in the circulatory system.We investigated the mutual relationships among plasma BDNF, patterns of nocturnal blood pressure changes (dippers, non-dippers, extra-dippers, and reverse-dippers), and cardiac autonomic function as determined by heart rate variability (HRV).This was a cross-sectional study of patients registered in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA) Study from October 2010 to November 2012.Two-hundred fifty patients with 1 or more cardiovascular risk factor(s) (obesity, smoking, presence of cardiovascular event history, hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease) were enrolled.Plasma BDNF levels (natural logarithm transformed) were significantly (p = 0.001) lower in reverse-dipper patients (7.18±0.69 pg/ml, mean ± SD, n = 36) as compared to dippers (7.86±0.86 pg/ml, n = 100). Multiple logistic regression analysis showed that BDNF (odds ratios: 0.417, 95% confidence interval: 0.228-0.762, P = 0.004) was the sole factor significantly and independently associated with the reverse-dippers as compared with dippers. Furthermore, plasma BDNF level was significantly and positively correlated with the time-domain (SDNN, SDANN5, CVRR) and frequency-domain (LF) of HRV parameters. Finally, multiple logistic regression analyses showed that the relationship between plasma BDNF and the reverse-dippers was weakened, yet remained significant or borderline significant even after adjusting for HRV parameters.Low plasma BDNF was independently associated with patients showing a reverse-dipper pattern of nocturnal blood pressure, in which an imbalance of cardiac autonomic function may be partly involved

Associations of Sleep Quality and Awake Physical Activity with Fluctuations in Nocturnal Blood Pressure in Patients with Cardiovascular Risk Factors.

BACKGROUND:Sleep quality and awake physical activity are important behavioral factors involved in the occurrence of cardiovascular diseases, potentially through nocturnal blood pressure (BP) changes. However, the impacts of quantitatively measured sleep quality and awake physical activity on BP fluctuation, and their relationships with several candidate causal factors for nocturnal hypertension are not well elucidated. METHODS:This cross-sectional study included 303 patients registered in the HSCAA study. Measurements included quantitatively determined sleep quality parameters and awake physical activity obtained by actigraph, nocturnal systolic BP (SBP) fall [100 × (1- sleep SBP/awake SBP ratio)], apnea hypopnea index, urinary sodium and cortisol secretion, plasma aldosterone concentration and renin activity, insulin resistance index, parameters of heart rate variability (HRV), and plasma brain-derived neurotrophic factor (BDNF). RESULTS:Simple regression analysis showed that time awake after sleep onset (r = -0.150), a parameter of sleep quality, and awake physical activity (r = 0.164) were significantly correlated with nocturnal SBP fall. Among those, time awake after sleep onset (β = -0.179) and awake physical activity (β = 0.190) were significantly and independently associated with nocturnal SBP fall in multiple regression analysis. In a subgroup of patients without taking anti-hypertensive medications, both time awake after sleep onset (β = -0.336) and awake physical activity (β = 0.489) were more strongly and independently associated with nocturnal SBP falls. CONCLUSION:Sleep quality and awake physical activity were found to be significantly associated with nocturnal SBP fall, and that relationship was not necessarily confounded by candidate causal factors for nocturnal hypertension

Sleep Apnea and Physical Movement During Sleep, But Not Sleep Duration, Are Independently Associated With Progression of Left Ventricular Diastolic Dysfunction: Prospective Hyogo Sleep Cardio‐Autonomic Atherosclerosis Cohort Study

Background Although co‐occurrence of sleep disorder with heart failure is known, it is not clear whether that condition is a cause or consequence of heart failure. The present study was conducted as a longitudinal examination of the predictive value of sleep parameters on progression of left ventricular diastolic dysfunction. Methods and Results Four‐hundred fifty‐two subjects were followed for a mean of 34.7 months. An outcome of diastolic dysfunction was defined as increase in early inflow velocity/early diastolic tissue velocity >14. Sleep apnea‐hypopnea index, minimal oxygen saturation, sleep duration, and activity index (physical movement during sleep time, a potential parameter of poor sleep quality) were determined using apnomonitor and actigraphy findings, while heart rate variability was measured with a 24‐hour active tracer device. Sixty‐six of the patients developed diastolic dysfunction during the follow‐up period, with a median time of 25 months. Kaplan–Meier analysis results revealed that those with sleep apnea classified as moderate (apnea‐hypopnea index 15 to <30, P<0.01 versus none) or severe (apnea‐hypopnea index ≥30, P<0.01 versus none), and with a high activity index (Q3 or Q4, P<0.01 versus Q1), but not short sleep duration (P=0.27) had a significantly greater risk for a diastolic dysfunction event. Results of multivariable Cox proportional hazards regression analysis indicated that moderate to severe sleep apnea after a follow‐up period of 3 years (hazard ratio [HR], 9.26 [95% CI, 1.89–45.26], P<0.01) and high activity index (HR, 1.85 [95% CI, 1.01–3.39], P=0.04) were significantly and independently associated with future diastolic dysfunction. Moreover, significant association of high activity index with the outcome was not confounded by either minimal oxygen saturation or heart rate variability. Conclusions Sleep apnea and physical movement during sleep, but not sleep duration and autonomic nervous dysfunction, are independent important predictors for progression of left ventricular diastolic dysfunction

Pearson's correlation coefficients among objective parameters for sleep disturbances, ambulatory physical activity, and nocturnal SBP fall in all subjects and subgroup patients without anti-hypertensive medications.

<p>The parameters of objective sleep disturbances and ambulatory physical activity were natural logarithm-transformed (ln) to achieve a normal distribution. In all subjects, time awake after sleep onset (r = -0.150, P = 0.009) and awake physical activity (r = 0.164, P = 0.004) were significantly associated with nocturnal SBP fall (Fig 1A). In subgroup patients without anti-hypertensive medications, only awake physical activity (r = 0.344, P < 0.001) were significantly associated with nocturnal SBP fall (Fig 1B). SBP denotes systolic blood pressure. r: Pearson's correlation coefficient.</p

Plasma BDNF independently associated with reverse-dipper pattern of nocturnal blood pressure change.

<p>Multiple logistic regression analyses were performed. The covariates included age, male sex, classical cardiovascular risk factors (body mass index, current smoking, cardiovascular disease history, dyslipidemia, diabetes mellitus, eGFR), medical hypertension treatment (calcium-channel blocker, α or β blocker, ACE inhibitor or ARB, diuretic agent), AHI and BDNF. BDNF was natural logarithm-transformed (ln) to achieve a normal distribution. OR; odds ratio, CI; confidence interval, eGFR; estimated glomerular filtration rate, ACE: angiotensin converting enzyme, ARB; angiotensin receptor blocker, AHI; apnea hypopnea index, BDNF; brain-derived neurotrophic factor.</p

Correlation coefficients between time awake after sleep onset, awake physical activity and clinical factors.

<p>Correlation coefficients between time awake after sleep onset, awake physical activity and clinical factors.</p

Multiple linear regression analyses among sleep quality, awake physical activity and nocturnal SBP fall.

<p>Multiple linear regression analyses among sleep quality, awake physical activity and nocturnal SBP fall.</p