Coefficient Of Variation Of R-R Intervals Research Articles

Effects of continuous supplementation of Acanthopanax senticosus Harms on the cardiac autonomic function of community-dwelling elderly individuals during resting and standing tests: a randomized controlled trial.

Cardiac autonomic function (CAF) decreases with aging, and Acanthopanax senticosus Harms (ASH) consumption reportedly induces anti-stress effects. This study aimed to assess the effect of continuous supplementation of ASH on CAF during resting and standing tests in the elderly population. This double-blind, randomized controlled trial was conducted in the morning in a laboratory setting and was carried out between June 2017 and July 2017 at Kambaikan, Doshisha University (Karasuma-higashi-iru, Imadegawa-dori, Kamigyo-ku, Kyoto 602-8580, Japan). In total, 28 community-dwelling elderly individuals (mean ± standard deviation = 72.5 ± 4.5 years) were included. Each subject was instructed to consume ASH or placebo supplements twice daily for 4 weeks. An autonomic reflex orthostatic tolerance recorder was used to measure CAF in pre- and post-intervention phases. Parameters were measured in a seated position and included coefficient of variation of R-R intervals (CVRR), low frequency (LF), high frequency (HF), LF/HF ratio, blood pressure, and heart rate (HR). Changes in each parameter were evaluated before and after standing. All parameters were defined as the difference between the mean value obtained in a standing position for 2 min and that obtained in a 2-min seated position. A two-way analysis of variance revealed a significant group-time interaction effect on CVRR, HF, and ΔLF/HF ratio. Following the intervention, CVRR, HF, LF/HF ratio, systolic blood pressure (SBP), HR, ΔLF/HF ratio, ΔSBP, and ΔHR improved significantly in the ASH group only. Four-week supplementation of ASH improved CAF in community-dwelling elderly individuals during resting and standing tests. https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000031218, UMIN Clinical Trials Registry (UMIN000027251).

Simplified electrophysiological approach combining a point-of-care nerve conduction device and an electrocardiogram produces an accurate diagnosis of diabetic polyneuropathy.

This study aimed to investigate the diagnostic potential of two simplified tests, a point-of-care nerve conduction device (DPNCheck™) and a coefficient of variation of R-R intervals (CVR-R ), as an alternative to traditional nerve conduction studies for the diagnosis of diabetic polyneuropathy (DPN) in patients with diabetes. Inpatients with type 1 or type 2 diabetes (n = 167) were enrolled. The study population consisted of 101 men, with a mean age of 60.8 ± 14.8 years. DPN severity was assessed using traditional nerve conduction studies, and differentiated based on Baba's classification (BC). To examine the explanatory potential of variables in DPNCheck™ and CVR-R regarding the severity of DPN according to BC, a multiple regression analysis was carried out, followed by a receiver operating characteristic analysis. Based on BC, 61 participants (36.5% of the total) were categorized as having DPN severity of stage 2 or more. The multiple regression analysis yielded a predictive formula with high predictive power for DPN diagnosis (estimated severity of DPN in BC = 2.258 - 0.026 × nerve conduction velocity [m/s] - 0.594 × ln[sensory nerve action potential amplitude (μV)] + 0.528In[age(years)] - 0.178 × ln[CVR-R ], r = 0.657). The area under the curve in receiver operating characteristic analysis was 0.880. Using the optimal cutoff value for DPN with severer than stage 2, the predictive formula showed good diagnostic efficacy: sensitivity of 83.6%, specificity of 79.2%, positive predictive value of 51.7% and negative predictive value of 76.1%. These findings suggest that DPN diagnosis using DPNCheck™ and CVR-R could improve diagnostic efficiency and accessibility for DPN assessment in patients with diabetes.

Associations of age-adjusted coefficient of variation of R-R intervals with autonomic and peripheral nerve function in non-elderly persons with diabetes.

Early diagnosis of diabetes-associated cardiac autonomic neuropathy using the coefficient of variation of R-R intervals (CVRR) may improve outcomes for individuals with diabetes. The present study examined the associations of decreased CVRR at rest and during deep breathing (DB) with other autonomic nerve function parameters. The electronic records of 141 inpatients with diabetes (22-65 years) admitted to our hospital between March 2015 and March 2019 were analyzed retrospectively. After assessment by exclusion criteria, 51 inpatients were included. All inpatients were assessed for peripheral and autonomic nerve function, clinical characteristics, and physical abilities. Inpatients with decreased CVRR at rest (n = 9 (17.6%)) and during DB (n = 12 (23.5%)) had a longer duration of known diabetes, a higher prevalence of diabetic retinopathy, lower body mass index (BMI), skeletal mass index (SMI), and knee extension strength, and a higher proportion of impaired standing balance. Decreased CVRR at rest was associated with a greater fall in diastolic BP from supine to standing, higher resting HR, longer QTc, longer time of voiding, and sensory symptoms. Decreased CVRR at rest and during deep breathing was associated with lower BMI, SMI, and knee strength and a higher proportion of impaired standing balance among non-elderly inpatients with diabetes. Decreased CVRR at rest appeared more strongly associated with a greater orthostatic BP decline, higher resting heart rate, longer QTc, lower urinary tract dysfunction, and sensory symptoms than a decreased CVRR during deep breathing.

PS-BPC10-4: THE CLINICOPATHOLOGICAL FINDINGS IN NON-DIABETIC CKD PATIENTS WITH CARDIOVASCULAR AUTONOMIC NEUROPATHY

Background: Cardiovascular autonomic neuropathy (CAN) is common as the process of kidney injury. Coefficient of variation of R-R interval (CVR-R) is one of the most convenient, noninvasive tests of heart rate variability, and is widely used to assess cardiac autonomic nerve function. However, the clinical and pathological findings in non-diabetic CKD patients with CAN has not been fully elucidated. This current study investigated the characteristics of non-diabetic CKD patients with CAN diagnosed by CVR-R. Method: Subjects who underwent percutaneous kidney biopsy and performed CVR-R test at the Jikei University School of Medicine Hospital, Tokyo, Japan were retrospectively examined. Patients with arrhythmia, diabetes, and post transplantation were excluded. CAN was defined using the reference values of CVR-R based on age and sex. The proportion of glomerulosclerosis (GS) and interstitial fibrosis/tubular atrophy (IF/TA) were assessed. The severity of arteriosclerosis was determined by the extent of thickening of the intima: grade0 = intimal thickening< thickness of media grade1 = intimal thickening> thickness of media. Results: Ninety subjects were identified (Age 45.7 ± 14.9 (mean ± SD) years old; Male 56%; heart rate 69 ± 11 /min; eGFR 60.0 ± 29.5 mL/min/1.73m2; 24h-urinary protein excretion 0.55 [0.24–1.30] (median [IQR]) g/day; CVR-R rest 3.7 ± 1.7%; GS 11.6 [3.6–24.8] %, IFTA 20 [10–30] %.) Eleven patients were diagnosed as CAN, with nephrosclerosis [n = 4], acute tubulointerstitial nephritis [n = 2], IgA nephropathy [n = 1], IgA vasculitis [n = 1], membranous nephropathy [n = 1], lupus nephritis [n = 1], and focal segmental glomerular sclerosis [n = 1]. Patients with CAN had a higher triglyceride (P = 0.030) and higher IF/TA(P = 0.005) than those without CAN. The severity of arteriosclerosis increased in patients with CAN. (P = 0.017) Conclusion: These results indicated that that arteriosclerosis and IF/TA were associated with CAN in non-diabetic CKD patients.

PS-BPR02-10: SYMPATHETIC NERVE TONE AND THE INDOOR ENVIRONMENT IN A HIGHLY INSULATED AND AIRTIGHT MODEL HOUSE DURING THE COLD WINTER SEASON

While evidence for lifestyle modification such as salt reduction, weight loss, exercise, sobriety, and smoking cessation has accumulated for perfect blood pressure control, there is a lack of evidence on blood pressure fluctuations due to housing environments such as thermal protection and heating. In particular, blood pressure fluctuation due to the difference in room temperature between the living room and the dressing room, toilet, and bedroom is known to be a major risk during the winter season. Therefore, this study focused on the autonomic nervous system as one of the factors causing blood pressure fluctuations, and compared the fluctuations when the same subjects spent two days each at home and in a highly insulated, airtight model house. JOURNAL/jhype/04.03/00004872-202301001-00877/figure1/v/2023-10-24T163949Z/r/image-jpeg Subjects were 6 males and 5 females with 20–70 years old. Autonomic activity was measured and calculated using portable electrocardiography (Heartnote: JSR corporation, Tokyo) for the 8 subjects for whom it was possible to measure heart rate, CVRR (Coefficient of variation of R-R interval) and LF(low frequency)/HF(high frequency) ratio. An sympathetic hyperactivation was defined to show more than +2SD for distribution within an individual in LF/HF calculated every 10 seconds. The salivary amylase was measured at several times per day. The indoor environment temperatures were recorded by installing data loggers equipped with temperature sensors in various rooms and taking continuous measurements at 10-min intervals. In the model house, room temperatures were kept constant at 18°C or more. However, in the home, there were large temperature differences between rooms, and in one case, a room temperature in the bedroom was recorded at 6.3°C. In the overall analysis of heart rate and CVRR, there were large individual differences in both absolute values and diurnal variations, and no obvious differences by housing environment. In a detailed analysis focusing on early morning (2 hours after waking), two subjects showed excessive sympathetic activation in the early morning at home, but not in the model house. There was no correlation between this change and salivary amylase. In terms of sleep quality, there were no differences by housing environment. This case of early morning sympathetic activation in a residential setting suggests the importance of the residential setting in the management of early morning hypertension.

Wearable sensor device-based detection of decreased heart rate variability in Parkinson's disease.

The evidence that heart rate variability (HRV) decreases during early Parkinson's disease (PD) largely depends on electrocardiogram data. In this study, we examined HRV in PD using wearable sensors and assessed various evaluation methods for detecting disease-related alterations. We evaluated 27 patients with PD and 23 disease controls. The wearable sensors POLAR V800 HR and POLAR H10 were used for the HRV measurements. The participants wore the two sensors for approximately 24h, and long-term HRV data were acquired. We analyzed the standard deviation of normal R-R intervals (SDNN) and coefficient of variation of R-R intervals (CVRR) for every 100 consecutive beats. Focusing on the fluctuation of SDNN and CVRR, we extracted the minimum, first decile, first quartile, and median values of SDNN and CVRR. The area under the receiver operating characteristic curve (AUC) for each HRV parameter was calculated to differentiate PD from the disease controls. The minimum values of SDNN and CVRR had the highest AUC (SDNN: AUC 0.90, 95% confidence interval [CI] 0.78-0.96; CVRR: AUC 0.90, CI 0.76-0.96) among the evaluation methods tested. The minimum values of SDNN and CVRR were significantly decreased in PD (SDNN: 9.5 ± 4.0ms vs. 4.4 ± 2.0ms, p < 0.0001; CVRR: 1.15 ± 0.33% vs. 0.65 ± 0.24%, p < 0.0001). We detected decreased HRV in PD using wearable sensors. Analyzing the minimum values of the HRV parameter in long-term recordings appears to be appropriate for detecting the decrease in HRV in PD.

Abstract 9185: Diagnostic Utility of R-R Interval Variations Under Deep Breathing Load in Patients With Cardiac Amyloidosis

Introduction: Autonomic disorder is one of important characteristics of cardiac amyloidosis. However, the prevalence of autonomic disorder in wild-type transthyretin amyloidosis (ATTR wt ) remains to be elucidated. Analysis of coefficient of variation of R-R interval (CVR-R) is a non-invasive method to measure the autonomic nervous system. In normal subjects, CVR-R values are higher during deep breathing load than those at rest. Diminished response of CVR-R to deep breathing reflects the parasympathetic nervous system disorder. We aimed to assess autonomic disorder of ATTRwt and investigate the utility of CVR-R for the detection of ATTRwt from other cardiac disease. Methods: Fifty patients with chronic heart failure (HF) patients aged >70 were investigated. The etiology of HF was as follows: ATTR wt , n=10; previous myocardial infarction (MI), n=20; and left ventricular hypertrophy (LVH) due to other disease (e.g. aortic stenosis); n=20. Serum cardiac troponin I and plasma brain natriuretic peptide (BNP) were measured in all patients. Cardiac function was evaluated by echocardiography. We measured CVR-R at rest (CVR-R rest ), CVR-R with deep breaths (CVR-R beath ) and their change rate (CVR-R diff rate ). Relative change formula is CVR-R diff rate = (CVR-R beath - CVR-R rest )/ CVR-R rest . Results: There was no difference in age among the three groups. Plasma BNP levels, troponin I levels and left ventricular mass index were significantly higher in ATTR wt group. There was no difference in CVR-R rest levels among the three groups. CVR-R diff rate levels in ATTR wt group were significantly lower (ATTR wt : -8.77 [-43.8-10.9]; LVH: 67.4 [38.7-89.4]; MI: 83.7 [60.4-142.9], respectively). In the ROC analysis to identify ATTR wt in HF, the best cutoff value for CVR-R diff rate was 1.197 (AUC: 0.848). Conclusions: Autonomic nervous disorder is frequently observed in the patients with ATTR wt . Measurement of CVR-R is convenient support tool for detection of ATTRwt.

The Association Between Heart Rate Variability and Quality of Life in Patients with Functional Somatic Syndrome and Healthy Controls.

Functional somatic syndrome (FSS) includes a spectrum of somatic symptoms with insufficient medical explanation. Its underlying pathophysiology is considered to include dysfunctional stress-responsive systems or autonomic dysfunction. Among the autonomic dysfunction readouts, decreased heart rate variability (HRV) has been shown to be characteristic in patients with FSSs. However, its association with quality of life (QOL) has not been clearly examined. We examined the association between short-term resting HRV and QOL in patients with FSS (n = 47) and healthy controls (n = 28). The time domain parameters of HRV were mean heart rate per minute (HR), coefficient of variation of R-R intervals (CvRR) and root mean square of successive differences (RMSSD). The frequency domain parameters of HRV were low-frequency (LF) power and high-frequency (HF) power by power spectrum analysis. The Japanese version of the WHO's QOL scale (WHOQOL-BREF) (WHO/QOL26) was used for the QOL assessment. There was a significant positive association between the RMSSD and HF power of HRV and all the QOL domains in patients with FSSs who had lower QOL scores on average than controls, while there was no association between HRV and any of the QOL domains in the control group. HF power was more dominantly associated with QOL than the other variables in patients with FSS based on the analysis with a multiple linear regression model. The present study elucidated that the HF power of HRV was dominantly associated with QOL in patients with FSSs who had lower QOL than controls. Vagal index of HRV could be a valuable indicator of the pathological condition and a significant predictor of health-related QOL in patients with FSSs.

Comparison of spinal column alignment and autonomic nervous activity using the intersegmental tenderness test in the segment above.

[Purpose] The thoracolumbar supraspinous intersegmental tenderness test (ITT) in the segment above was performed to compare spinal alignment and autonomic activity in the presence or absence of pain. [Participants and Methods] Thirty young males were grouped into Th1–4 (Cardiopulmonary visceral nerves), Th5–9 (Large visceral nerve), and Th10–12 (Small visceral nerve) by ITT for the presence of pain. Measurements of the spinal alignment and autonomic function were performed. [Results] Those with ITT pain had a significantly lower range of motion in the sagittal plane at Th12, Th12–L1, and L2–3 and in the frontal plane at Th1–2, Th4–5, Th6–7, and L3–4 than those in the no pain group. On autonomic function tests, the pain group had significantly lower Total Power, LF (Low Frequency), and CVRR (Coefficient of variation of R-R interval). [Conclusion] In ITT, patients with pain at Th5–9 have a mixture of reduced sagittal tilt angle and autonomic hypofunction of the adjacent upper and lower thoracic to lumbar vertebrae.

P179 Alterations of resting heart rate and heart rate viability after cryoballon ablation in the patients with paroxysmal atrial fibrillation

Abstract Background While it is generally accepted that cardiac autonomic nervous system (CANS) plays an important role in atrial fibrillation (AF) and pulmonary vein isolation (PVI) by radiofrequency catheter ablation modifies the ganglionated plexi (GP), the alterations of CANS after PVI are not clarified. Purpose The objective of this study was to investigate the alteration of CANS after conventional cryoballoon ablation (CBA) by using a non-invasive examination method of measuring resting heart rate (R-HR) and coefficient of variation of R-R interval (CVR-R) which is a representative parameter of heart rate viability. CVR-R reflects R-R interval variation affected by respiration. It is calculated from the R-R interval of consecutive 100 heart beats of sinus rhythm recorded at rest. Declines of CVR-R indicate the parasympathetic dysfunction and the normal range of it varies depend on the age. As age increases from 30s to 70s, the average value of CVR-R decreases from 4.0% to 2.4%. Methods Consecutive patients of paroxysmal AF treated with initial CBA in our institute participated. Subjects were limited to the patients who maintained sinus rhythm through the study and whose prescription had not been changed after procedure. All patients recorded 12-lead electrocardiogram to measure R-HR and CVR-R before and the day after the procedure. We compared R-HR and CVR-R of all patients before and after CBA. And in addition, we compared them in each of two groups whose pre-procedural H-RH were under 50 bpm (Group-U50) and over 70 bpm (Group-O70). All procedures were performed with second generation 28mm cryoballoon (CB)s under the conscious sedation with Dexmedetomidine. CB temperature was down to a minimum of -60°C and target application time was 180 seconds. Results In the procedure of all 105 patients (male gender, 54%; age, 66.9 ± 10.4years; CHADS2score, 1.15 ± 1.04; diabetes mellitus,14%; beta-blocker therapy, 16%), 1 of touch-up for PVI, 6 of supra vena cava isolation and 21 of cavotricuspid isthmus linear ablations with radiofrequency catheter were added. In all patients, R-HR increased from 58.9 ± 9.2bpm to 72.4 ± 9.5bpm (P < 0.01) and CVR-R decreased from 2.36 ± 1.08% to 1.24 ± 0.68% (P < 0.01), respectively. In Group-U50 (n = 14; male gender 64%; age 67.6 ± 12.4 years), R-HR increased from 47.1 ± 2.1bpm to 64.4 ± 7.9bpm (P < 0.01) and CVR-R decreased from 2.58 ± 1.59% to 1.34 ± 0.82% (P < 0.01), respectively. In Group-O70 (n = 17; male gender 43%; age 67.4 ± 12.6 years), R-HR increased from 73.7 ± 2.8bpm to 81.8 ± 7.4bpm (P < 0.01) and CVR-R decreased from 2.33 ± 0.94% to 1.14 ± 0.52% (P < 0.01), respectively. Values of CVR-R before and after CBA showed no significant difference between the two groups. Conclusions After CBA, R-HR increment and CVR-R decrement were significantly observed. CVR-R was halved regardless of pre–procedural R-HR. Damages to GP by CBA would be reflected as denervation of vagus nerves in CANS. R-HR increase might be associated with parasympathetic suppression of CANS.

2237-PUB: Validation of the Simple Diagnostic Criteria in Japan

Introduction: The simple diagnostic criteria (SDC) proposed by Diabetic Neuropathy Study Group in Japan has been widely accepted in our country. However, the diagnostic ability has not yet been fully validated. In the present study, we examined the usefulness of SDC in diagnosis of diabetic polyneuropathy (DPN). Methods: We evaluated admitted 114 diabetic subjects who were diagnosed as DPN employing three independent decision rules consisting SDC: physical signs and symptoms (PHY), nerve conduction study (NCS), or coefficient of variation of RR interval (CVR-R) on electrocardiogram (CVRR). #1. PHY rule: satisfied any two or more of following three items: the presence of symptoms considered to be due to DPN, the decrease or disappearance of bilateral Achilles tendon reflexes, and decreased vibration in the bilateral medial malleoli. #2. NCS rule: one or more nerve conduction abnormalities in two or more nerves out of 12 peripheral nerves. #3. CVRR rule: less than 2% of CVR-R. The diagnostic accuracy was evaluated using the NCS rule as the reference standard. Result: 1. Ninety-six subjects (84.2%) diagnosed as DPN. The proportions of DPN were 37.7% for PHY, 74.6% for NCS, and 43.9% for CVRR. 2. The diagnostic accuracy of PHY and/or CVRR. Discussion: Diagnosis by NCS showed the highest prevalence. The sensitivity of PHY was improved by a combination with CVRR. DPN can be identified effectively utilizing SDC. Disclosure T. Himeno: None. Y. Shibata: None. H. Shimoda: None. M. Kondo: None. S. Tsunekawa: None. Y. Kato: Speaker's Bureau; Self; Merck & Co., Inc. J. Nakamura: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Japan Tobacco Inc., Kissei Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceu. Co. Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. H. Kamiya: Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K.K., MSD K.K., Novartis Pharma K.K., Novo Nordisk Oharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K.

Changes in Heart Rate Variability During Heartfulness Meditation: A Power Spectral Analysis Including the Residual Spectrum.

Background: Meditation refers to a group of practices commonly proposed to treat stress-related conditions and improve overall wellness. In particular, meditation might exert beneficial actions on heart rate variability (HRV) by acting on autonomic tone with an increase in the vagal activity. The effects of heartfulness meditation (HM) on HRV remain poorly defined.Methods: We investigated the effects of HM on HRV in a group of 26 healthy subjects. Subjects were regularly practicing this form of meditation on a daily basis. We assessed the HRV and residual HRV (rHRV) at rest and during meditation. We also used as control a period of respiratory rhythm imposed by an auditory signal, with the imposed breathing rhythm being identical to the spontaneous rhythm recorded during meditation.Results: During deep meditation period, the standard deviation of RR intervals (SDRR), coefficient of variation of RR intervals (CVRR), and total power (TP) were decreased while the low-frequency power (LFP), normalized LFP (nLFP), and normalized residual LFP (nrLFP) were increased as compared with those at rest, suggesting that the global vagal modulation was suppressed while the baroreflex was increased during deep medication. At the end of meditation, the LFP, residual LFP (rLFP), nLFP, nrLFP, low-/high-frequency power ratio (LHR), and residual LHR (rLHR) were increased while the residual very low-frequency power (rVLFP), normalized high-frequency power (nHFP), and normalized residual HFP (nrHFP) were decreased, as compared with those during paced breathing, suggesting that the vagal modulation was decreased while the sympathetic modulation was increased by deep meditation. During paced breathing period, the SDRR, CVRR, TP, LFP, rLFP, nLFP, nrLFP, LHR, and rLHR were decreased while nHFP and nrHFP were increased as compared with at rest, suggesting that paced breathing could suppress the sympathetic modulation and enhance the vagal modulation.Conclusion: HM can induce a suppression of global vagal modulation and increased the sympathetic modulation and baroreflex. In addition, paced breathing can suppress the sympathetic modulation and enhance the vagal modulation. Unlike studies using other types of meditation, we did not identify evidence of increased vagal tone during HM.

Widespread Cardiac and Vasomotor Autonomic Dysfunction in Non-Val30Met Hereditary Transthyretin Amyloidosis.

Objective The autonomic functions of hereditary transthyretin (ATTRm) amyloidosis, traditionally referred to as familial amyloid polyneuropathy, have primarily been investigated in patients with Val30Met mutations, and information regarding non-Val30Met patients is scarce. The aim of this study was to systematically investigate the cardiac and peripheral vasomotor autonomic functions in non-Val30Met patients. Methods The coefficient of variation of R-R intervals (CVR-R), responses to the Valsalva manoeuvre, head-up tilt test results, noradrenaline infusion test results, and the (123)I-metaiodobenzylguanidine (MIBG) uptake on myocardial scintigraphy were assessed in five patients. The predominant manifestations were neuropathy in three patients (Val94Gly, Val71Ala, and Pro24Ser), cardiomyopathy in one (Thr60Ala), and oculoleptomeningeal involvement in one (Tyr114Cys). Results Although one patient with predominant cardiomyopathy did not manifest orthostatic hypotension during the head-up tilt test, the CVR-R, responses to the Valsalva manoeuvre, and myocardial MIBG uptake indicated the presence of cardiac sympathetic and parasympathetic dysfunction in all patients. The total peripheral resistance at 60° tilt did not increase from the baseline values in any of the examined patients. An infusion of low-dose noradrenaline induced an increase in the systolic blood pressure, except in one patient with mild neuropathy. Conclusion Cardiac and peripheral vasomotor autonomic dysfunctions were prevalent in non-Val30Met patients, irrespective of their phenotype, suggesting a common pathology of autonomic involvement. However, the vasoconstrictor function was preserved, even in a patient with advanced neuropathy.

Change in Autonomic Nervous Activity during Ingestion of Soft Food in Older Nursing Home Residents.

The deterioration in masticatory function often seen in older adults rules out the consumption of hard foods, while a common decline in autonomic nervous response often observed in older adults may result in maladjustment to environmental stresses. The purpose of this study was to investigate whether autonomic nervous activity in older adults increased during the mastication of soft foods compared to at rest. The participants comprised 9 volunteer nursing home residents aged 78 to 100 years. All consumed soft rice as a grain dish and coarsely chopped food as side dishes. The coefficient of variation of R-R intervals (CVRR) and high-frequency (HF) power on electrocardiograph (ECG) served as indices of parasympathetic nervous activity, while the low-frequency (LF)/HF ratio served as an index of sympathetic nervous activity. Total power, reflecting the level of autonomic nervous activity, was also measured. We measured autonomic nervous activity while nursing home residents were eating lunch. HF was 3,457.4±3,037.5 ms2 at rest and 4,085.1±3,697.7 ms2 during mastication. The CVRR was 26.8±16.9% at rest and 26.1±16.1% during mastication. No significant difference was observed in HF or CVRR. On the other hand, the LF/HF ratio was 0.77±0.24 ms2 at rest and 31.0±3.77 ms2 during mastication (p=0.011). A significant difference was observed in the LF/HF ratio between the resting and masticating conditions. Total power was 6,244.1±5,752.5 ms2 at rest and 8,417.7±7,266.4 ms2 during mastication (p=0.038). A significant difference was also observed in total power between resting and masticating conditions. These results suggest that mastication of soft foods stimulates autonomic nervous activity in older adults. In conclusion, autonomic nervous activity increased during chewing soft foods compared to that during the resting level in older adults.

Cardiac and peripheral vasomotor autonomic functions in late-onset transthyretin Val30Met familial amyloid polyneuropathy.

The objective of this study was to systematically investigate cardiac and peripheral vasomotor autonomic functions in late-onset transthyretin Val30Met familial amyloid polyneuropathy (FAP ATTR Val30Met) patients from non-endemic areas. The coefficient of variation of R-R intervals (CVR-R), responses to the Valsalva manoeuvre, head-up tilt test with impedance cardiography, noradrenaline infusion test, and (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy were assessed in eight patients. Although only four patients manifested orthostatic hypotension during the head-up tilt test, CVR-R, responses to the Valsalva manoeuvre, and myocardial MIBG uptake indicated a higher prevalence of cardiac sympathetic and parasympathetic dysfunction. Total peripheral resistance at 60° tilt did not increase from baseline values in five of six examined patients. An infusion of low-dose noradrenaline induced an increase in systolic blood pressure in all patients. The extent of the change in systolic blood pressure negatively correlated to that in total peripheral resistance (p<0.05). Patients with poor vasoconstrictor responses to orthostatic stress tended to exhibit severe reduction of unmyelinated fibres in sural nerve biopsy specimens. In conclusion, both cardiac and peripheral vasomotor autonomic dysfunctions were prevalent in late-onset FAP ATTR Val30Met patients from non-endemic areas, even in those without orthostatic intolerance. However, vasoconstriction by alpha-adrenoceptor agonists was preserved even after denervation, carrying important implications for the management of orthostatic hypotension in FAP.

Effect of chewing or compressing food on autonomic nervous activity in older adults

To determine if autonomic nervous activity increases in older people during mastication and how this activity is related to the softness of food. We hypothesised that the coefficient of variation of R-R intervals (CVRR), high-frequency (HF) power, low-frequency (LF) power, LF/HF ratio and total power increase during chewing foods within the range of softness from moderate food to extremely soft food in older adults. Participants were 20 older volunteers (71-90year old). CVRR and HF on the electrocardiogram (ECG) were used as indices of parasympathetic nervous activity. LF and the LF/HF ratio on the ECG were used as indices of sympathetic nervous activity. Total power, reflecting the level of autonomic nervous activity, was also measured. Participants were asked to chew gum with three different degrees of softness, or to compress extremely soft gum between their palate and tongue. There were significant differences in HF between at resting and all chewing/compressing conditions, but no significant differences relating to food softness. There were significant differences in total power between at resting and all chewing/compressing conditions, but no significant differences relating to food softness. There were no significant differences in LF, LF/HF and CVRR among all conditions. Autonomic nervous activity, especially parasympathetic activity in older adults, increased during chewing and compressing food when compared to activity while at rest. Within the range of food's softness from moderate to extreme soft, food's softness had no measurable effect on autonomic nervous activity.

Skin Autofluorescence is Associated with Early-stage Atherosclerosis in Patients with Type 1 Diabetes

Aim: Accumulation level of fluorescent advanced glycation end products (AGEs) in the skin can be measured non-invasively as skin autofluorescence (skin AF) by autofluorescence reader. The aim of this study was to assess possible associations between skin AF and diabetic complications, especially early-stage atherosclerosis, in Japanese type 1 diabetic patients.Methods: Skin AF was measured by AGE reader® in 105 Japanese type 1 diabetic patients (34 men and 71 women, aged 37.4 ± 12.4 years (± SD)) and 23 age-matched healthy non-diabetic subjects. Ultrasonic carotid intima-media thickness (IMT), ankle-brachial index (ABI), and brachial ankle pulse wave velocity (baPWV) were evaluated as indices of early-stage diabetic macroangiopathy. Urinary albumin-to-creatinine ratio (UACR), the coefficient of variation of R-R intervals (CVR-R), and presence of retinopathy were also evaluated.Results: Skin AF values were significantly higher in type 1 diabetic patients than in healthy controls (2.07 ± 0.50 (mean ± SD) and 1.90 ± 0.26, respectively, p = 0.024). Skin AF was associated with carotid IMT (r = 0.446, p <0.001) and baPWV (r = 0.450, p <0.001), but not with ABI (r = −0.019, p = 0.8488). Notably, skin AF was an independent risk factor for IMT thickening. Similarly, skin AF was associated with log (UACR) (r = 0.194, p = 0.049) and was an independent risk factor for UACR. Furthermore, skin AF values were significantly higher in patients with diabetic retinopathy than in those without (2.21 ± 0.08 and 1.97 ± 0.06, respectively, p = 0.020).Conclusions: Skin AF was significantly associated with the presence and/or severity of diabetic complications and was an independent risk factor for carotid atherosclerosis.

HW 01-4 CARDIOANKLE VASCULAR INDEX (CAVI) IN HYPERTENSION

Background: The cardio-ankle vascular index (CAVI) is a new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle, and was essentially derived from the stiffness parameterβtheory proposed by Hayashi. The conspicuous feature of CAVI is independency from blood pressure at the time of measurement. Aim: The purpose is to clarify the meaning of CAVI as a surrogate marker of arteriosclerosis, and also the role of CAVI in the blood pressure control system. Results: We reported that during a prospective study on 1000 patients for 7 years, a high CAVI was shown to be a predictive factor for cardiovascular events. Among antihypertensive drugs, we observed that Olmesartan (ARB) and Efonidipine (CCB) decreased CAVI, as well as decreasing blood pressure, indicating that those depressants would improve arterial stiffness. As for a regulatory factor of blood pressure, we observed that the CAVI value increased when blood pressure decreased during blood removal in the rabbits. And, CAVI value decreased, when blood pressure recovered by blood transfusion. Heart to ankle pulse wave velocity (hsPWV) was changed associating with blood pressure. During hypotensive attacks in patients taking hemodialysis therapy, some cases increased CAVI whereas other cases decreased CAVI. The former 's hypotension is associated with a reduction in cardiac output. The latter's hypotension was not associated with a reduction in cardiac output, but was associated with an increase in the high frequency of the coefficient of variation of R-R intervals (CVRR), indicating that parasympathetic nerve stimulation might decrease blood pressure by decreasing stiffness of the muscular arteries. In patients suffering from hypotension shock by sepsis, CAVI decreased, indicating that endotoxins might dilate the muscular arteries. Conclusion: CAVI was reflecting arterial stiffness, independently from blood pressure at mearing time, and might also reflect a part of vascular resistance. By measuring CAVI, the blood pressure control mechanism could be evaluated in several situations, as well as using it as a surrogate marker for arteriosclerosis.

Myocardial dysfunction identified by three-dimensional speckle tracking echocardiography in type 2 diabetes patients relates to complications of microangiopathy

BackgroundThe clinical effect of diabetic microangiopathy on left ventricular (LV) function is still uncertain. The purpose of this study was to assess the relation between diabetic microvascular complications and comprehensive myocardial deformation measurements using three-dimensional (3D) speckle tracking echocardiography. MethodsSeventy-seven asymptomatic patients with type 2 diabetes mellitus (DM) and 35 age-matched healthy control subjects underwent 3D echocardiography. Patients with coronary artery disease or LV ejection fraction <50% were excluded. Presence of proliferative retinopathy, microalbuminuria as nephropathy, and decreased coefficient of variation of R-R intervals (CVRR) <3% as cardiac autonomic neuropathy were defined as diabetic microvascular complications. ResultsLV ejection fraction, LV mass index, and global radial strain did not differ between control and DM patients. However, global longitudinal and circumferential strain and endocardial area change ratio were lower in patients with DM than in the controls (−12.0±3.0% vs. −16.2±1.9%, −27.7±7.1% vs. 32.2±5.7%, −37.6±7.6% vs. 44.0±6.2%, respectively, p<0.001). In DM patients, longitudinal strain is related to CVRR (R=0.58, p<0.001), retinopathy stage, and nephropathy stage. ConclusionsDiabetic microangiopathy and its accumulated effects significantly related to subclinical LV dysfunction are characterized by impaired longitudinal shortening.

Significant elevation of serum dipeptidyl peptidase-4 activity in young-adult type 1 diabetes

AimsCurrently, inhibition of dipeptidyl peptidase-4 (DPP-4) is widely used in the treatment of type 2 diabetes. Application of this strategy is awaited as a new therapeutic approach for type 1 diabetes, but the scientific basis is still lacking. This report describes the evaluation of serum DPP-4 activity in type 1 diabetes compared with control subjects, and assessment of relationships between DPP-4 activity and diabetic complication markers and metabolic variables in type 1 diabetes. MethodsWe examined serum DPP-4 activity in Japanese young-adult type 1 diabetes (n=76, females 69.7%, age 30.9±6.2 years, duration of diabetes 16.5±11.1 years; mean±SD) and healthy controls (n=22). Association of the enzymatic activity with diabetic micro- and macro- vascular complication markers and clinical parameters was also assessed. ResultsSubjects with type 1 diabetes displayed significantly higher serum DPP-4 activity than healthy controls (relative value, control: 1.00±0.28, T1D, 1.29±0.38; p=0.0011) independent of other clinical parameters. In type 1 diabetes, DPP-4 activity was positively correlated with duration of diabetes (r=0.248, p=0.031), while not correlated with HbA1c level. In univariate correlation analysis of diabetic complication markers and other metabolic parameters, coefficient of variation of R-R intervals (CVR-R) and gamma (γ)-glutamyltransferase (GGT) levels were correlated with DPP-4 activity. GGT was extracted as an independent variable of DPP-4 activity in multivariate analysis (β=0.213, p=0.035). ConclusionsSerum DPP-4 activity is significantly elevated in Japanese type 1 diabetes, suggesting pathophysiological significance of the enzyme in type 1 diabetes.