Nocturnal heart rate variability in 1-year-old infants analyzed by using the Least Square Cosine Spectrum Method.

BACKGROUND: To evaluate the dynamic nature of nocturnal heart rate variability, RR intervals recorded with a wearable heart rate sensor were analyzed using the Least Square Cosine Spectrum Method. METHODS: Six 1-year-old infants participated in the study. A wearable heart rate sensor was placed on their chest to measure RR intervals and 3-axis acceleration. Heartbeat time series were analyzed for every 30 s using the Least Square Cosine Spectrum Method, and an original parameter to quantify the regularity of respiratory-related heart rate rhythm was extracted and referred to as "RA (RA-COSPEC: Respiratory Area obtained by COSPEC)." The RA value is higher when a cosine curve is fitted to the original data series. RESULTS: The time sequential changes of RA showed cyclic changes with significant rhythm during the night. The mean cycle length of RA was 70 ± 15 min, which is shorter than young adult's cycle in our previous study. At the threshold level of RA greater than 3, the HR was significantly decreased compared with the RA value less than 3. CONCLUSIONS: The regularity of heart rate rhythm showed dynamic changes during the night in 1-year-old infants. Significant decrease of HR at the time of higher RA suggests the increase of parasympathetic activity. We suspect that the higher RA reflects the regular respiratory pattern during the night. This analysis system may be useful for quantitative assessment of regularity and dynamic changes of nocturnal heart rate variability in infants.

Non-dipping blood pressure variations in adult Kazakhs are derived from decreased daytime physical activity and increased nighttime sympathetic activity.

Many of the elderly Kazakhs have been found to exhibit non-dipping blood pressure variations (BPV). Such variations are seen in both normotensive and hypertensive Kazakhs. The purpose of this study was (1) to determine whether middle-aged Kazakhs also include large numbers of non-dippers, (2) to compare the characteristics of non-dipping and dipping, and (3) to clarify the mechanisms responsible for non-dipping type BPV by examining the autonomic nervous activity and physical activity. We performed ambulatory blood pressure (BP) monitoring. The subjects were divided into two groups (dipping and non-dipping type). We monitored the subjects' physical activity with accelerometry and assessed their autonomic nerve activity by performing a frequency domain analysis of their heart rate variability (HRV). The power spectral density (PSD) of the HRV was calculated using fast Fourier transformation. We analyzed the systolic blood pressure (SBP) variations with the maximum entropy method (MEM). The dippers and non-dippers accounted for 48% and 52% of the subjects, respectively. MEM analysis revealed that the SBP variations of the non-dippers exhibited a 24 hour periodicity with a very weak PSD as well as an ultradian periodicity. The non-dippers exhibited higher low-frequency/high-frequency (LF/HF) ratio and lower HF/(LF + HF) ratios than the dippers, particularly during the nighttime. In addition, the non-dippers performed less physical activity than the dippers. These differences in cardiac autonomic function and physical activity might contribute to the generation of a weak circadian rhythm in SBP, and thus, ultimately lead to the non-dipping SBP variations observed in non-dipper Kazakhs.

Association of the c.385C>A (p.Pro129Thr) polymorphism of the fatty acid amide hydrolase gene with anorexia nervosa in the Japanese population.

The functional c.385C>A single-nucleotide polymorphism (SNP) in the fatty acid amide hydrolase (FAAH) gene, one of the major degrading enzymes of endocannabinoids, is reportedly associated with anorexia nervosa (AN). We genotyped the c.385C>A SNP (rs324420) in 762 lifetime AN and 605 control participants in Japan. There were significant differences in the genotype and allele frequencies of c.385C>A between the AN and control groups. The minor 385A allele was less frequent in the AN participants than in the controls (allele-wise, odds ratio = 0.799, 95% confidence interval [CI] 0.653-0.976, P = 0.028). When the cases were subdivided into lifetime restricting subtype AN and AN with a history of binge eating or purging, only the restricting AN group exhibited a significant association (allele-wise, odds ratio = 0.717, 95% CI 0.557-0.922, P = 0.0094). Our results suggest that having the minor 385A allele of the FAAH gene may be protective against AN, especially restricting AN. This finding supports the possible role of the endocannabinoid system in susceptibility to AN.

No association of brain-derived neurotrophic factor Val66Met polymorphism with anorexia nervosa in Japanese.

The Met66 allele of the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been reported to be associated with anorexia nervosa (AN), and also lower minimum body mass index (BMI) and higher harm avoidance in AN. We genotyped the Val66Met polymorphism (rs6265) in 689 AN cases and 573 control subjects. There were no significant differences in the genotype or allele frequencies of the Val66Met between AN and control subjects (allele wise, odds ratio = 0.920, 95% CI 0.785-1.079, P = 0.305). No difference was found in minimum BMIs related to Val66Met in AN (one-way ANOVA, P > 0.05). Harm avoidance scores on the Temperament and Character Inventory were lower in the Met66 allele carriers (P = 0.0074) contrary to the previous report. Thus we were unable to replicate the previous findings that the Met66 allele of the BDNF is associated with AN and that the minimum BMI is lower or the harm avoidance score is higher in AN patients with the Met66 allele.

Possible participation of extracellular calcium-sensing receptor in blood pressure regulation in rats.

The concentration of calcium in the cerebrospinal fluid (CSF) affects systemic blood pressure; an increase in calcium concentration lowers blood pressure, whereas a decrease raises it. Although this phenomenon has been known for more than 50 years, the precise mechanism is not completely understood. We examined whether the extracellular calcium-sensing receptor (CaSR), which was originally cloned from the parathyroid cells and later found in the brain, contributes to blood pressure regulation by calcium in the CSF. In urethane-anesthetized and artificially ventilated Wistar-Kyoto rats, an intracisternal injection of NPS R-467, an allosteric CaSR activator, decreased blood pressure associated with sympatho-inhibition in a dose-dependent manner. Treatment with an inactivator of the CaSR elicited an increase in blood pressure. Similar results were observed in awake and freely moving animals. In contrast, when the CaSR activator/inactivator was administered into the lateral ventricle, the cardiovascular changes were minimal. These results indicate that the CaSR in the brain contributes, at least in part, to the hypotensive effect of centrally administered calcium and suggests that the CaSR in the lower brainstem participates in tonic regulation of blood pressure by sensing a change in the CSF Ca²+ concentration.

Variations in the preproghrelin gene correlate with higher body mass index, fat mass, and body dissatisfaction in young Japanese women.

BACKGROUND: Ghrelin is an endogenous peptide that stimulates growth hormone secretion, enhances appetite, and increases body weight and may play a role in eating disorders. OBJECTIVE: The purpose was to determine whether any preproghrelin gene variants are associated with anthropometric measures, circulating ghrelin, lipid concentrations, insulin resistance, or psychological measures relevant to eating disorders in young women. DESIGN: This cross-sectional study compared outcome measures between preproghrelin genotypes. The participants in the study included 264 Japanese women [university students with a mean (+/-SD) age of 20.4 +/- 0.7] with no history of eating disorders. The main outcomes were responses to the Eating Disorder Inventory-2 (EDI-2), anthropometric measures, measures of depression and anxiety, and fasting blood concentrations of acylated or desacyl ghrelin, lipids, glucose, and insulin. RESULTS: Two single nucleotide polymorphisms (SNPs) whose minor allele frequencies were >0.05--the Leu72Met (408 C-->A) SNP in exon 2 and the 3056 T-->C SNP in intron 2--were used for association analysis. The 3056C allele was significantly associated with a higher acylated ghrelin concentration (P=0.0021), body weight (P=0.011), body mass index (P=0.007), fat mass (P=0.012), waist circumference (P=0.008), and skinfold thickness (P=0.011) and a lower HDL-cholesterol concentration (P=0.02). Interestingly, the 3056C allele was related to elevated scores in the Drive for Thinness-Body Dissatisfaction (DT-BD) subscale of the EDI-2 (P=0.003). CONCLUSION: Our findings suggest that the preproghrelin gene 3056T-->C SNP is associated with changes in basal ghrelin concentrations and physical and psychological variables related to eating disorders and obesity.

Possible role of preproghrelin gene polymorphisms in susceptibility to bulimia nervosa.

Previous investigations have suggested that ghrelin, an endogenous orexigenic peptide, is involved in the pathology of eating disorders. We conducted a study to determine whether any preproghrelin gene polymorphisms are associated with eating disorders. Three hundred thirty-six eating disorder patients, including 131 anorexia nervosa (AN)-restricting types (AN-R), 97 AN-binge eating/purging types (AN-BP) and 108 bulimia nervosa (BN)-purging types (BN-P), and 300 healthy control subjects participated in the study. Genotyping was performed to determine the polymorphisms present, and with this information, linkage disequilibrium (LD) between the markers was analyzed and the distributions of the genotypes, the allele frequencies, and the haplotype frequencies were compared between the groups. The Leu72Met (408 C > A) (rs696217) polymorphism in exon 2 and the 3056 T > C (rs2075356) polymorphism in intron 2 were in LD (D' = 0.902, r2 = 0.454). Both polymorphisms were significantly associated with BN-P (allele-wise: P = 0.0410, odds ratio (OR) = 1.48; P = 0.0035, OR = 1.63, for Leu72Met and 3056 T > C, respectively). In addition, we observed a significant increase in the frequency of the haplotype Met72-3056C in BN-P patients (P = 0.0059, OR = 1.71). Our findings suggest that the Leu72Met (408 C > A) and the 3056 T > C polymorphisms of the preproghrelin gene are associated with susceptibility to BN-P.

Physiological and pathological age-associated changes in diurnal rhythm of energy expenditure in rats.

Although the idea that energy metabolism of rats decreases with age has been widely accepted, few studies with regard to the diurnal rhythm of energy expenditure have been reported. Whether age alone altered the diurnal rhythm of energy expenditure was examined in Sprague-Dawley (SD) rats. The same determination was conducted in Otsuka Long Evans Tokushima Fatty (OLETF) rats to examine the effect of insulin resistance and diabetes. OLETF rats were developed as a model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity. The characteristic features of OLETF rats are late onset of hyperglycemia at about 18 weeks of age, followed by insulin deficiency at about 65 weeks. Age-associated changes in diurnal rhythm of energy expenditure were not observed in SD rats. In OLETF rats, the diurnal rhythm of energy expenditure with two peaks was observed at 8 weeks of age, while these two peaks disappeared at 24 weeks of age (with NIDDM). Then, the pattern of diurnal rhythm at 44 weeks of age (with advanced NIDDM) was resembled to that of 62 weeks of age (with insulin deficiency). In conclusion, we clarified the changes in diurnal rhythm of energy expenditure associated with the progress of diabetes, while age alone did not alter the diurnal rhythm.

Circadian heart rate and blood pressure variability considered for research and patient care.

OBJECTIVES: To review mechanisms of circadian variations in heart rate variability (HRV) and blood pressure variability (BPV) and mortality and morbidity due to cardiovascular diseases (CVD). METHODS: Results from 7-day/24-h HRV and BPV are interpreted by gender and age-specified reference values in the context of a Medline search. RESULTS: Abnormal HRV and BPV measured around the clock for 7 days provides information on the risk of subsequent morbid events in subjects without obvious heart disease and without abnormality outside the conventional (in the sense of chronobiologically unquantified) physiological range. Meditation, beta-blockers, ACE inhibitors, n-3 fatty acids and estrogens may have a beneficial influence on HRV, but there is no definitive outcome-validated therapy. Low HRV has been associated with a risk of arrhythmias and arrhythmic death, unstable angina, myocardial infarction, progression of heart failure and atherosclerosis. BPV may be characterized by treatable circadian-hyper-amplitude-tension (CHAT), which can be transient '24-h CHAT' or '7-day-CHAT', MESOR-hypertension and/or an unusually-timed (odd) circadian acrophase (ecphasia), all associated with an increased risk of stroke, stroke death, myocardial infarction, and kidney disease. CONCLUSIONS: Precise insight into the patho-physiology in time of HRV and BPV is needed with development of a consensus on best measures of HRV for clinical purposes and to determine when a 7-day record interpreted chronobiologically suffices and when it does not, for detection within as well as outside the conventional normal range, for diagnostic clinical practice and to direct therapy of risk greater than that associated with hypertension, smoking or any other risk factor.

A peroxisome proliferator-activated receptor gamma agonist influenced daily profile of energy expenditure in genetically obese diabetic rats.

Otsuka Long Evans Tokushima Fatty (OLETF) rats were developed as a model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity. We reported that the daily profiles of energy expenditure associated with two peaks (one between 05:00 and 08:00 and the other between 20:00 and 22:00) were observed at 8 weeks of age (without NIDDM), while these two peaks disappeared at 24 weeks of age with NIDDM. As a new anti-diabetic drug, a peroxisome proliferator-activated receptor y agonist pioglitazone hydrochloride has been developed, we examined whether pioglitazone normalized daily profiles of energy expenditure at 24 weeks of age. A control diet and pioglitazone (0.1%)-containing diet were fed from 6 weeks of age. The two peaks of daily profiles of energy expenditure, which disappeared in OLETF rats with the control diet at 24 weeks of age, were reproduced by administration of pioglitazone. The respiratory quotient was lower and fat derived energy used for combustion was increased by pioglitazone at both ages. The body weight, daily food intake, plasma levels of fat, insulin, leptin and the wet weight of visceral fat were not influenced, but the levels of blood hemoglobin Alc and plasma tumor necrosis factor a were decreased by pioglitazone. Administration of pioglitazone improved daily profiles of energy expenditure via affecting glucose and fat metabolisms.

The effects of postural changes of baroreflex gain in normal and hypertensive pregnancies.

In order to understand the changes of baroreflex gain due to postural changes in normal pregnancies, we measured percentage changes (% changes) in blood pressure (SBP, DBP), heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) as well as cardiac autonomic nervous function (HF as an index of parasympathetic and LF/HF as an index of sympathetic function) and compared these parameters in normal pregnancies with those found in hypertensive pregnancies, such as chronic hypertensive (CHP) and severe preeclamptic pregnancies (PE), in late pregnancy (after 32 wks). When the position was changed from supine to standing in normal and non-pregnant women, the % changes of HR, DBP, TPR and LF/HF were increased and SBP, SV, CO and HF were decreased. The % changes of these parameters, however, were gradually decreased as pregnancy progressed, especially after 20-24 wks of gestation. In hypertensive pregnancies, however, even in late pregnancy, the decreased SBP and increased TPR was still observed and the profound decrease of CO and SV and increase of TPR were characteristic in PE when compared to CHP.