Values Of Heart Rate Variability Indices Research Articles

Вариабельность сердечного ритма крыс-самок Вистар в условиях различной физической активности

Objective: to study the characteristics of heart rate variability in female Wistar rats under conditions of normal wakefulness, moderate physical activity and during recovery. Materials and methods. The study was carried out on 48 female Wistar rats aged 5-6 months. Heart rate variability (HRV) was recorded using Physiobelt 2.5.1 (Neurobotics, Russia). HRV analysis was performed using statistical, geometric, and spectral indicators. Physical activity was created using a two-minute treadmill run at a speed of 15 m/min at an angle of 15°. During the experiment we made 3 records of cardiosignal in each anumal: 1 - before the load, 2 - immediately after the load, 3 - after 15-minute rest. Results. Physical activity led to significant changes in a number of statistical and geometric indexes, but no differences in the spectral indexes of all the records were not found. In this regard, we performed cluster analysis on TP, HF, LF indexes of the record 1 that allowed us to form 2 groups: with low and high spectrum values (LSV and HSV). In each group, we observed significant changes in the values of HRV indexes between the records: in the group with LSV, physical activity led to a change in HR, RRNN, Mo, HF (ms2), LF (ms2, %), VLF (ms2, %), LF/HF, IC, in the group with HSV - HR, RRNN, Mo, Amo, IVR, PAPR, VLF (ms2), LF (%), IC. 15-minute recovery contributed to a further change in the value of HRV parameters. Conclusion. The results of the current study demonstrated that physical activity led to activation of the sympathetic nervous system, mobilization of neurohumoral regulation, as well as a change in the level of regulation of the cardiorhythm from peripheral to the central one. The analysis of HRV parameters in females with LSV and HSV allowed us to establish the features of neurohumoral regulation of the functional state of the organism in groups of animals initially different in spectral characteristics.

The effect of visceral reception activation (water load test) on autonomic activity and gastric myoelectric activity in gastrointestinal malignancies.

The aim of this study was to analyze the effect of water load test (WLT) on heart rate variability (HRV), blood pressure variability (BPV), hemodynamic parameters and gastric myoelectric activity in gastrointestinal (GI) cancer patients. WLT activates gastrointestinal mechanoreception and osmoreception, and hence, can indirectly modulate autonomic activity. Eighty patients (mean age 61.2 years) were enrolled, along with the group of healthy controls. HRV, BPV and electrogastrography (EGG) were recorded at rest (in a fasted state) and after water uptake at 100 ml/min. WLT contributed to an increase in the percentages of normogastria time, from 37.3 % to 50.0 % (p=0.02) and from 42.3 % to 47.7 % (p=0.01), respectively in colon and rectal cancer. Cancer patients presented lower values of HRV indices determined on linear analysis at rest and after WLT. A slight predominance of the sympathetic component was observed in response to WLT, which was reflected by changes in hemodynamic parameters. The response to WLT is a consequence of GI mechanoreception and osmoreception activation and resultant pressure reaction. This effect was disrupted by the neoplastic process within the GI tract, especially in gastric and colon malignancies, but not in rectal cancer (Tab. 2, Fig. 12, Ref. 40). Text in PDF www.elis.sk Keywords: autonomic nervous system, gastric myoelectric activity, water uptake, heart rate variability, blood pressure variability, gastrointestinal cancer.

Effects of physical exercise on baroreflex sensitivity and renal sympathetic nerve activity in chronic nicotine-treated rats.

Chronic nicotine exposure may increase cardiovascular risk by impairing the cardiac autonomic function. Besides, physical exercise (PE) has shown to improve cardiovascular health. Thus, we aimed to investigate the effects of PE on baroreflex sensitivity (BRS), heart rate variability (HRV), and sympathetic nerve activity (SNA) in chronically nicotine-exposed rats. Male Wistar rats were assigned to four independent groups: Control (treated with saline solution), Control+Ex (treated with saline and submitted to treadmill training), Nicotine (treated with Nicotine), and Nicotine+Ex (treated with nicotine and submitted to treadmill training). Nicotine (1mg·kg-1) was administered daily for 28 consecutive days. PE consisted of running exercise (60%-70% of maximal aerobic capacity) for 45min, 5 days per week, for 4 weeks. At the end of the protocol, cardiac BRS, HRV, renal SNA (rSNA), and renal BRS were assessed. Nicotine treatment decreased absolute values of HRV indexes, increased low frequency/high frequency ratio of HRV, reduced the bradycardic and sympatho-inhibitory baroreceptor reflex responses, and reduced the rSNA. PE effectively restored time-domain HRV indexes, the bradycardic and sympatho-inhibitory reflex responses, and the rSNA in chronic nicotine-treated rats. PE was effective in preventing the deterioration of time-domain parameters of HRV, arterial baroreceptor dysfunction, and the rSNA after nicotine treatment.

On the Variability of Heart Rate Variability-Evidence from Prospective Study of Healthy Young College Students.

Heart rate variability (HRV) has been widely used as indices for autonomic regulation, including linear analyses, entropy and multi-scale entropy based nonlinear analyses, and however, it is strongly influenced by the conditions under which the signal is being recorded. To investigate the variability of healthy HRV under different settings, we recorded electrocardiograph (ECG) signals from 56 healthy young college students (20 h for each participant) at campus using wearable single-lead ECG device. Accurate R peak to R peak (RR) intervals were extracted by combing the advantages of five commonly used R-peak detection algorithms to eliminate data quality influence. Thorough and detailed linear and nonlinear HRV analyses were performed. Variability of HRV metrics were evaluated from five categories: (1) different states of daily activities; (2) different recording time period in the same day during free-running daily activities; (3) body postures of sitting and lying; (4) lying on the left, right and back; and (5) gender influence. For most of the analyzed HRV metrics, significant differences (p < 0.05) were found among different recording conditions within the five categories except lying on different positions. Results suggested that the standardization of ECG data collection and HRV analysis should be implemented in HRV related studies, especially for entropy and multi-scale entropy based analyses. Furthermore, this preliminary study provides reference values of HRV indices under various recording conditions of healthy young subjects that could be useful information for different applications (e.g., health monitoring and management).

Combination of Composite Autonomic Symptom Score 31 and Heart Rate Variability for Diagnosis of Cardiovascular Autonomic Neuropathy in People with Type 2 Diabetes.

Objective Cardiovascular autonomic neuropathy (CAN) is a common but severe problem of diabetes, which a timely diagnosis may have important clinical implications. This study was carried out to investigate the diagnostic performance of Composite Autonomic Symptom Score 31 (COMPASS 31) combined with heart rate variability (HRV) for cardiovascular autonomic neuropathy in type 2 diabetes. Methods A total of 103 hospitalized subjects with type 2 diabetes were recruited in the study. All cases received clinical data collection, laboratory examination, and related complication examinations. Cardiovascular autonomic function was assessed using CARTs, COMPASS 31, and HRV analyses. A score of at least 2 based on CARTs was defined as CAN. Results Of the 103 subjects with type 2 diabetes, 41.8% were diagnosed with confirmed CAN. Participants with CAN had considerably higher COMPASS 31 scores. The CAN group showed a significant decrease in all HRV indices. COMPASS 31 scores and HRV indices were closely correlated with CARTs (P < 0.05). Receiver operating characteristics (ROC) curve results showed that COMPASS 31 score identified CAN with an AUC value of 0.816, while the AUC values of HRV indices were 0.648 to 0.919, among which SDNN and LF had the best diagnostic value, with the AUC values of 0.919 and 0.865, respectively. When combining COMPASS 31 score with SDNN and LF, the AUC value increased to 0.958, with a sensitivity of 90.7% and a specificity of 86.7%. Conclusions The combination of COMPASS 31 and HRV could improve the diagnostic performance of CAN in type 2 diabetes, which might be conducive to the diagnosis of CAN.

Are signs and symptoms in cardiovascular rehabilitation correlated with heart rate variability? An observational longitudinal study.

To analyze the correlation between the appearance of signs/symptoms during a cardiovascular rehabilitation program and linear indexes of the heart rate variability (HRV) at rest. To carry out the present observational longitudinal study, 48 patients were analyzed. The protocol was divided into two stages. First, the patients had their personal details collected, and the autonomic modulation at rest was evaluated by HRV. Second, they underwent 36 sessions of the cardiovascular rehabilitation program to evaluate signs/symptoms. Then, just for analysis of the data, they were divided into two groups: the group without signs/symptoms (n = 26; 65.15 ± 9.7 years); and the group with signs/symptoms (n = 22; 66.77 ± 14.4 years). The HRV indexes were compared by ancova. The effect size was measured through the partial eta-squared. Pearson's and Spearman's correlations (P < 0.05) were used to analyze the data, and linear regression was applied. A total of 103 signs/symptoms occurred. The group with signs/symptoms presented lower values of HRV indexes when compared with the group without signs/symptoms, especially for the parasympathetic indexes with a large effect size. The root mean square of successive differences (rMSSD), percentage of adjacent RR intervals with a difference of duration >50 ms (pNN50), high-frequency spectral component (HF) varying from 0.15 to 0.4 Hz (expressed as ms2 ), dispersion of the points perpendicular to the line of identity and represents the instantaneous record of the beat-to-beat variability (SD1) and SD1/scatter of points along the identity line and represents the HRV in long-term records (SD2) index presented a negative correlation with the appearance of signs/symptoms. When the linear regression was applied, the rMSSD, SD1 and SD1/SD2 showed negative values of β (P < 0.05). Patients with lower HRV are more likely to have signs/symptoms. The rMSSD, pNN50, HF (expressed as ms2 ), SD1 and SD1/SD2 index presented a negative correlation with the appearance of signs/symptoms. For rMSSD, SD1 and SD1/SD2, the lower the values of these HRV indexes, the greater the risk of appearance of signs/symptoms. Geriatr Gerontol Int 2020; 20: 853-859.

Risk Factors for the Presence and Progression of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes: ADDITION-Denmark.

To examine the course of cardiovascular autonomic neuropathy (CAN) and related cardiometabolic risk factors in patients with type 2 diabetes. CAN and cardiometabolic risk factors were assessed in the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care (ADDITION-Denmark) at 6-year (n = 777) and 13-year (n = 443) follow-up examinations. Cardiovascular autonomic reflex tests (CARTs)-that is, lying to standing, deep breathing, and the Valsalva maneuver-and 2-min resting heart rate variability (HRV) indices were obtained as the main measures of CAN. Risk factors related to CAN status, as determined by CARTs, were studied by using multivariate logistic regressions. The effects of risk factors on continuous CARTs and HRV indices, and their changes over time, were estimated in linear mixed models. A progressive yet heterogeneous course of CAN occurred between the 6- and 13-year follow-ups. Higher HbA1c, weight, BMI, and triglycerides were associated with prevalent CAN. No significant effect of risk factors on CARTs was found when they were analyzed as continuous variables. CART indices decreased over time, and a trend of decreasing HRV indices was seen. Higher HbA1c and BMI were associated with lower HRV index values, but these differences diminished over time. These data confirm that hyperglycemia, obesity, and hypertriglyceridemia are negatively related to indices of CAN, although these effects diminish over time. The observed heterogeneous course of CAN may challenge the present clinical approach of categorically classifying CARTs to diagnose CAN and the notion of CAN being irreversible.

Baroreflex sensitivity and heart rate variability are predictors of mortality in patients with aneurysmal subarachnoid haemorrhage

ObjectWe aimed to investigate the link between the autonomic nervous system (ANS) impairment, assessed using baroreflex sensitivity (BRS) and heart rate variability (HRV) indices, and mortality after aneurysmal subarachnoid haemorrhage (aSAH). MethodsA total of 57 patients (56 ± 18 years) diagnosed with aSAH were retrospectively enrolled in the study, where 25% of patients died in the hospital. BRS was calculated using a modified cross–correlation method. Time– and frequency–domain HRV indices were calculated from a time–series of systolic peak intervals of arterial blood pressure signals. Additionally, cerebral autoregulation (CA) was assessed using the mean velocity index (Mxa), where Mxa > 0 indicates impaired CA. ResultsBoth BRS and HRV indices were lower in non–survivors than in survivors. The patients with disturbed BRS and HRV had more extensive haemorrhage in the H-H scale (p = .040) and were more likely to die (p = .013) when compared to patients with the intact ANS. The logistic regression model for mortality included: the APACHE II score (p = .002; OR 0.794) and the normalised high frequency power of the HRV (p < <.001; OR 0.636). A positive relationship was found between the Mxa and BRS (R = 0.48, p = .003), which suggests that increasing BRS is moderately strongly associated with worsening CA. ConclusionOur results indicated that lower values of HRV indices and BRS correlate with mortality and that there is a link between cerebral dysautoregulation and the analysed estimates of the ANS in aSAH patients.

Coffee Consumption and Heart Rate Variability: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Cohort Study.

Studies have shown that acute coffee ingestion can affect cardiovascular autonomic activity, although the chronic effects on heart rate variability (HRV) remain controversial. Method: A cross-sectional study with baseline data (2008–2010) from ELSA-Brasil cohort of 15,105 (aged 35–74), based in six Brazilian states. Coffee consumption in the previous 12 months was measured using the semi-quantitative food frequency questionnaire, and HRV was obtained through electrocardiographic tracings during 10 min at rest. Independent association between the frequency of coffee consumption “never or almost never”, “≤1 cup/day”, “2–3 cups/day”, “≥3 cups/day”, and HRV was estimated using generalized linear regression, adjusting for socio-demographic characteristics, health-related behavior, markers of abnormal metabolism, and the presence of coronary artery disease. Further, we applied Bonferroni correction in the full models. Results: The mean age was 52 years (standard deviation (SD) = 9.1), and 52% was female; 9.5% never/almost never consumed coffee. In univariate analysis, coffee consumers had reduced values of HRV indexes, but after full adjustments and correction for multiple comparisons, these associations disappeared. A trend of reduction in HRV vagal indexes was observed in those that consumed ≥3 cups of coffee/day. Conclusion: Most of the effects attributed to the chronic use of coffee on the HRV indexes is related to the higher prevalence of unhealthy habits in coffee users, such as smoking and alcohol use. Adjustment for confounding factors weaken this association, making it non-significant. The effect of higher daily doses of coffee on the autonomic system should be evaluated in further studies.

Cardiac autonomic responses after resistance exercise in treated hypertensive subjects.

The aim of this study was to assess and to compare heart rate variability (HRV) after resistance exercise (RE) in treated hypertensive and normotensive subjects. Nine hypertensive men [HT: 58.0 ± 7.7 years, systolic blood pressure (SBP) = 133.6 ± 6.5 mmHg, diastolic blood pressure (DBP) = 87.3 ± 8.1 mmHg; under antihypertensive treatment] and 11 normotensive men (NT: 57.1 ± 6.0 years, SBP = 127 ± 8.5 mmHg, DBP = 82.7 ± 5.5 mmHg) performed a single session of RE (2 sets of 15–20 repetitions, 50% of 1 RM, 120 s interval between sets/exercise) for the following exercises: leg extension, leg press, leg curl, bench press, seated row, triceps push-down, seated calf flexion, seated arm curl. HRV was assessed at resting and during 10 min of recovery period by calculating time (SDNN, RMSSD, pNN50) and frequency domain (LF, HF, LF/HF) indices. Mean values of HRV indices were reduced in the post-exercise period compared to the resting period (HT: lnHF: 4.7 ± 1.4 vs. 2.4 ± 1.2 ms2; NT: lnHF: 4.8 ± 1.5 vs. 2.2 ± 1.1 ms2, p < 0.01). However, there was no group vs. time interaction in this response (p = 0.8). The results indicate that HRV is equally suppressed after RE in normotensive and hypertensive individuals. These findings suggest that a single session of RE does not bring additional cardiac autonomic stress to treated hypertensive subjects.

Handheld ECG in analysis of arrhythmia and heart rate variability in children with Fontan circulation

BackgroundOur aim was to evaluate the intermittent use of a handheld ECG system for detecting silent arrhythmias and cardiac autonomic dysfunction in children with univentricular hearts. MethodsTwenty-seven patients performed intermittent ECG recordings with handheld devices during a 14-day period. A manual arrhythmia analysis was performed. We analyzed heart rate variability (HRV) using scatter plots of all interbeat intervals (Poincaré plots) from the total observation period. Reference values of HRV indices were determined from Holter-ECGs in 41 healthy children. ResultsOne asymptomatic patient had frequent ventricular extra systoles. Another patient had episodes with supraventricular tachycardia (with concomitant palpitations). Seven patients showed reduced HRV. ConclusionsAsymptomatic arrhythmia was detected in one patient. The proposed method for pooling of intermittent recordings from handheld or similar devices may be used for detection of arrhythmias as well as for cardiac autonomic dysfunction.

Is applying the same exercise-based inpatient program to normal and reduced left ventricular function patients the best strategy after coronary surgery? A focus on autonomic cardiac response

Purpose: To assess whether the same exercise-based inpatient program applied to patients with normal and reduced left ventricular function (LVF) evokes a similar cardiac autonomic response after coronary artery bypass graft (CABG). Method: Forty-four patients post-CABG, subgrouped according to normal LVF [LVFN: n = 23; left ventricular ejection fraction (LVEF) ≥ 55%] and reduced LVF (LVFR: n = 21; LVEF 35–54%), were included. All initiated the exercise protocol on post-operative day 1 (PO1), following a whole progressive program until discharge. Cardiac autonomic response was assessed by the indices of heart rate variability (HRV) at rest and during exercise (extremity range of motion and ambulation). Results: During ambulation, lower values of HRV indices were found in the LVFR group compared with the LVFN group [standard deviation of all RR (STDRR; 6.1 ± 2.7 versus 8.9 ± 4.7 ms), baseline width of the RR histogram (TINN; 30.6 ± 14.8 versus 45.8 ± 24.9 ms), SD2 (14.8 ± 8.0 versus 21.3 ± 9.0 ms), Shannon entropy (3.6 ± 0.5 versus 3.9 ± 0.4) and correlation dimension (0.08 ± 0.2 versus 0.2 ± 0.2)]. Also, when comparing the ambulation to rest change, lower values were observed in the LVFR group for linear (STDRR, TINN, RR TRI, rMSSD) and non-linear (SD2 and correlation dimension) HRV indices (p < 0.05). On PO1, we observed only intra-group differences between rest and exercise (extremity range of motion), for mean intervals between heart beats and heart rate. Conclusion: For patients with LVFN, the same inpatient exercise protocol triggered a more attenuated autonomic response compared with patients with LVFR. These findings have implications as to how exercise should be prescribed according to LVF in the early stages following recovery from CABG.Implications for RehabilitationExercise-based inpatient program, performed by post-CABG patients who have normal left ventricular function, triggered a more attenuated cardiac autonomic response compared with patients with reduced left ventricular function.Volume of the inpatient exercises should be prescribed according to the left ventricular function in the early stages following recovery from CABG.

Personal Adaptive Method to Assess Mental Tension during Daily Life Using Heart Rate Variability

The aim of this study is to present a method of assessing psychological tension that is optimized to every individual on the basis of the heart rate variability (HRV) data which, to eliminate the influence of the inter-individual variability, are measured in a long time period during daily life. HRV and body accelerations were recorded from nine normal subjects for two months of normal daily life. Fourteen HRV indices were calculated with the HRV data at 512 seconds prior to the time of every mental tension level report. Data to be analyzed were limited to those with body accelerations of 30 mG (0.294 m/s²) and lower. Further, the differences from the reference values in the same time zone were calculated with both the mental tension score (Δtension) and HRV index values (ΔHRVI). The multiple linear regression model that estimates Δtension from the scores for principal components of ΔHRVI were then constructed for each individual. The data were divided into training data set and test data set in accordance with the twofold cross validation method. Multiple linear regression coefficients were determined using the training data set, and with the optimized model its generalization capability was checked using the test data set. The subjects' mean Pearson correlation coefficient was 0.52 with the training data set and 0.40 with the test data set. The subjects' mean coefficient of determination was 0.28 with the training data set and 0.11 with the test data set. We proposed a method of assessing psychological tension that is optimized to every individual based on HRV data measured over a long period of daily life.

Power-law behavior of heart rate variability in Chagas’ disease

Beta slope is a nonlinear index derived from the power-law analysis of 24-hour heart rate variability (HRV); in healthy subjects, the β index is typically near −1, suggesting a fractal behavior of HRV. There is scarce data on HRV in Chagas’ disease. This transversal study intends to describe power-law and linear HRV patterns in different forms of Chagas’ disease. Patients and healthy controls (n = 26) without other diseases were submitted to a standardized protocol, including electrocardiography, echocardiography, and 24-hour Holter monitoring. Patients with Chagas’ disease were divided into groups according to their left ventricular (LV) systolic function: normal (group 1, n = 85), segmental abnormalities (group 2, n = 49), and reduced ejection fraction (group 3, n = 26). The temporal series were carefully processed to obtain the HRV indexes and β slope. Despite the differences in the LV systolic function, the 3 groups were comparable in terms of long-term HRV index values. After adjustment for covariates, short-term HRV index values were consistently reduced in the Chagas’ disease groups. The β-index values were also diminished in Chagas’ disease groups (group 1: −1.09 ± 0.03, group 2: −1.11 ± 0.06; group 3: −1.14 ± 0.03; and controls: 0.95 ± 0.03, p <0.001). This breakdown of fractal long-range correlation of RR interval dynamics, a strong predictor of mortality in other cardiomyopathies, may reflect cardiac dysautonomia that may have gone undetected in long-term time-domain analysis. This abnormality may explain the increased risk for arrhythmic sudden death found in Chagas’ disease even in the absence of signs of LV dysfunction.

Depressed heart rate variability identifies postinfarction patients who might benefit from prophylactic treatment with amiodarone: A substudy of EMIAT (the European Myocardial Infarct Amiodarone Trial)

OBJECTIVESThis substudy tested a prospective hypothesis that European Myocardial Infarct Amiodarone Trial (EMIAT) patients with depressed heart rate variability (HRV) benefit from amiodarone treatment.BACKGROUNDThe EMIAT randomized 1,486 survivors of acute myocardial infarction (MI) aged ≤75 years with left ventricular ejection fraction (LVEF) ≤40% to amiodarone or placebo. Despite a reduction of arrhythmic mortality on amiodarone, all-cause mortality was not changed.METHODSHeart rate variability was assessed from prerandomization 24-h Holter tapes in 1,216 patients (606 on amiodarone). Two definitions of depressed HRV were used: standard deviation of normal to normal intervals (SDNN) ≤50 ms and HRV index ≤20 units. The survival of patients with depressed HRV was compared in the placebo and amiodarone arms. A retrospective analysis investigated the prospective dichotomy limits. All tests were repeated in five subpopulations: patients with first MI, patients on beta-adrenergic blocking agents, patients with LVEF ≤30%, patients with Holter arrhythmia and patients with baseline heart rate ≥75 beats/min.RESULTSCentralized Holter processing produced artificially high SDNN but accurate HRV index values. Heart rate variability index was ≤20 U in 363 (29.9%) patients (183 on amiodarone) with all-cause mortality 22.8% on placebo and 17.5% on amiodarone (23.2% reduction, p = 0.24) and cardiac arrhythmic mortality 12.8% on placebo and 4.4% on amiodarone (66% reduction, p = 0.0054). Among patients with prospectively defined depressed HRV, the largest reduction of all-cause mortality was in patients with first MI (placebo 17.9%, amiodarone 10.3%, 42.5% reduction, p = 0.079) and in patients with heart rate ≥75 beats/min (placebo 29.0%, amiodarone 19.3%, 33.7% reduction, p = 0.075). Among patients with first MI and depressed HRV, amiodarone treatment was an independent predictor of survival in a multivariate Cox analysis. The retrospective analysis found a larger reduction of mortality on amiodarone in 313 (25.7%) patients with HRV index ≤19 U: 23.9% on placebo and 17.1% on amiodarone (28.4% reduction, p = 0.15). This was more expressed in patients with first MI: 49.4% mortality reduction on amiodarone (p = 0.046), on beta-blockers: 69.0% reduction (p = 0.047) and with heart rate ≥75 beats/min: 37.9% reduction (p = 0.054).CONCLUSIONMeasurement of HRV in a large set of centrally processed Holter recordings is feasible with robust methods of assessment. Patients with LVEF ≤40% and depressed HRV benefit from prophylactic antiarrhythmic treatment with amiodarone. However, this finding needs confirmation in an independent data set before clinical practice is changed.

The natural history of recently diagnosed autonomic neuropathy over a period of 2 years

Background: Patients with diabetic autonomic neuropathy (DAN) have an increased cardiovascular mortality rate compared with normals or diabetic patients without DAN. Indices of standard cardiovascular autonomic function tests and heart rate variability (HRV) are reliable markers of the presence and severity of DAN. Objective: The present prospective study investigated the natural history of values of HRV indices and cardiovascular reflex tests in patients with recently diagnosed asymptomatic DAN, over a period of 2 years, at 3 month intervals. Patients and methods: A total of 30 consecutive patients (nine men and 21 women), of median age 51 (range 25–65) years, eight with type 1 and 22 with Type 2 diabetes mellitus, were included in the study, at the time that the presence of DAN was confirmed, as this was established if at least two of cardiovascular autonomic function tests became abnormal. The expiration/inspiration ( E/I) ratio, S.D. and mean circular resultant of R-R intervals, the Valsalva index, the 30:15 ratio, and the blood pressure response to standing as well as normalised spectral power indices of HRV were used. Results: All measured indices, except the Valsalva index, deteriorated in all 30 patients during the 2 year follow-up. Most of HRV indices values deteriorated significantly in comparison to baseline at month 12, while the values of cardiovascular reflex tests displayed significant deterioration, in comparison to baseline, between months 15 and 21. Fourteen patients developed symptoms of DAN during the 2 year period. Patients with better glycemic control exhibited deterioration of DAN markers at the same time period with those with poor glycemic control. Conclusions: Our data suggest that the progression of DAN is significant during the 2 years subsequent to its discovery. This was defined by the deterioration of the mean values of HRV indices and standard cardiovascular autonomic function tests, and by the development of autonomic symptoms in some patients. HRV indices are the earlier markers of DAN deterioration.