Severity Of Cardiovascular Autonomic Neuropathy Research Articles

Impacts of Chemerin Levels and Antioxidant Capacity on the Severity of Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes and Prediabetes.

Existing evidence supports an association between chemerin levels and cardiovascular risk, while reduced thiol levels are linked to diabetes mellitus. It is hypothesized that chemerin may contribute to autonomic dysfunction and cardiovascular risk in type 2 diabetes mellitus (T2DM), potentially mediated by the antioxidant capacity of patients with well-controlled T2DM and prediabetes. Comprehensive cardiovascular autonomic testing and biomarker assessments were conducted for all participants. The severity of cardiovascular autonomic neuropathy (CAN) was evaluated using the composite autonomic scoring scale (CASS). A mediation model was employed to explore the potential relationships among chemerin levels, antioxidant capacity (indicated by thiol levels), and CAN severity (indicated by CASS values). A total of 184 participants were enrolled in this study, comprising 143 individuals with T2DM and 40 individuals with prediabetes. The findings reveal a significant negative association between thiols levels (r = -0.38, p < 0.0001) and the CASS values, while a positive association is observed between chemerin levels (r = 0.47, p < 0.0001) and the CASS values. Linear regression analysis identified chemerin and thiols as independent variables significantly associated with CASS values. Subsequent mediation analysis elucidated that thiols levels act as mediators in the relationship between elevated chemerin levels and an increased CASS value. This study shows that poor cardiovascular function, higher chemerin levels, and reduced antioxidant capacity coexist in individuals with T2DM and prediabetes. Mediation analysis suggests a pathophysiological link between high chemerin levels and low antioxidant capacity, adversely impacting CAN severity.

Features characterising cardiac autonomic neuropathy in diabetes using ensembled classification

ObjectiveUsing supervised machine learning to classify the severity of cardiovascular autonomic neuropathy (CAN). The aims were 1) to investigate which features contribute to characterising CAN 2) to generate an ensembled set of features that best describes the variation in CAN classification. MethodsEighty-two features from demographic, beat-to-beat, biochemical, and inflammation were obtained from 204 people with diabetes and used in three machine-learning-classifiers, these are: support vector machine, decision tree, and random forest. All data were ensembled using a weighted mean of the features from each classifier. ResultsThe 10 most important features derived from the domains: Beat-to-beat, inflammation markers, disease-duration, and age. ConclusionsBeat-to-beat measures associate with CAN as diagnosis is mainly based on cardiac reflex responses, disease-duration and age are also related to CAN development throughout disease progression. The inflammation markers may reflect the underlying disease process, and therefore, new treatment modalities targeting systemic low-grade inflammation should potentially be tested to prevent the development of CAN. SignificanceCardiac reflex responses should be monitored closely to diagnose and classify severity levels of CAN accurately. Standard clinical biochemical analytes, such as glycaemic level, lipidic level, or kidney function were not included in the ten most important features. Beat-to-beat measures accounted for approximately 60% of the features in the ensembled data.

Sex differences and sex steroids influence on the presentation and severity of cardiovascular autonomic neuropathy of patients with type 1 diabetes

BackgroundSex differences characterize cardiovascular outcomes in patients with type 1 diabetes. Cardioautonomic neuropathy is a common complication of type 1 diabetes that associates increased morbi-mortality. Data regarding the interplay between sex and cardiovascular autonomic neuropathy are scarce and controversial in these patients. We aimed to address sex-related differences in the prevalence of seemingly asymptomatic cardioautonomic neuropathy in type 1 diabetes, and their associations with sex steroids.MethodsWe conducted a cross-sectional study including 322 consecutively recruited patients with type 1 diabetes. Cardioautonomic neuropathy was diagnosed using Ewing's score and power spectral heart rate data. We assessed sex hormones by liquid chromatography/tandem mass spectrometry.ResultsWhen considering all subjects as a whole, asymptomatic cardioautonomic neuropathy prevalence was not significantly different between women and men. When age was taken into account, the prevalence of cardioautonomic neuropathy was similar among young men and those > 50 years. However, in women > 50 years, the prevalence of cardioautonomic neuropathy doubled that of young women [45.8% (32.6; 59.7) vs. 20.4% (13.7; 29.2), respectively]. The OR of having cardioautonomic neuropathy was 3.3 higher in women > 50 years than in their younger counterparts. Furthermore, women presented more severe cardioautonomic neuropathy than men. These differences were even more marked when women were classified according their menopausal status instead of age. Peri- and menopausal women had an OR 3.5 (1.7; 7.2) of having CAN compared with their reproductive-aged counterparts [CAN prevalence: 51% (37; 65) vs. 23% (16; 32), respectively]. A binary logistic regression model (R2: 0.161; P = 0.001) displayed age > 50 years as a significant determinant of cardioautonomic neuropathy only in women. Androgens were positively associated with heart rate variability in men, and negatively in women. Accordingly, cardioautonomic neuropathy was associated with increased testosterone/estradiol ratio in women but to decreased testosterone concentrations in men.ConclusionsMenopause in women with type 1 diabetes is accompanied by an increase in the prevalence of asymptomatic cardioautonomic neuropathy. This age-related excess risk of cardioautonomic neuropathy is not observed in men. Men and women with type 1 diabetes have opposite associations between circulating androgens and indexes of cardioautonomic function.Trial registration ClinicalTrials.gov Identifier: NCT04950634.

Retracted: Association of QT interval indices with cardiac autonomic neuropathy in diabetic patients

Background. Cardiovascular autonomic neuropathy (CAN) is a severely debilitating yet underdiagnosed condition in patients with diabetes mellitus. The prevalence can range from 2.5% (based on the primary prevention cohort in the Diabetes Control and Complications Trial) to as high as 90% of diabetic patients. Clinical manifestations range from orthostasis to myocardial infarction. The diagnosis is made using multiple autonomic function tests to assess both sympathetic and parasympathetic function. This study was conducted to assess the relationship between Cardiac autonomic neuropathy and QT interval. Material and methods. This was a cross-sectional study conducted in 100 patients attending a tertiary care hospital in India. Deep breathing test, Valsalva ratio, immediate heart rate response to standing 30 : 15, BP rise with sustained hand grip and postural hypotension were evaluated. Scoring was done for cardiac autonomic neuropathy. QT interval and QTc interval were determined and association with CAN was obtained. Results. Out of 100 type 2 diabetic patients, 60% were males and 40% were females. 25 patients having no cardiac autonomic neuropathy and had no prolonged QTc interval. While, 75 patients had QTc prolonged were associated with early and severe CAN cardiac autonomic neuropathy. The prolonged QTc was significantly associated with CAN in diabetic patients when compared without CAN and controls (P &lt; 0.0001). The grading score for CAD showed that 75% cases were having score &gt; 2 were 25% of cases had score &lt; 2. Out of 75 patients 44 were between score 2–4 and 31 were above score 4. A significant association between QTc and Diabetic CAN patients observed when compared non CAN and controls. Conclusions. Diabetic cardiac autonomic neuropathy is associated with increase in prolongation of QTc intervals. Hence, there is need for regular checkup of autonomic nervous system in diabetic patient to prevent further complications.

Effectiveness of Different Methods for Baroreflex Sensitivity Assessment in Determining the Severity of Cardiovascular Autonomic Neuropathy in Patients With Parkinson's Disease.

BackgroundAutonomic disorders are an important non-motor feature of Parkinson’s disease (PD). Baroreflex sensitivity (BRS) is often used as an indicator of cardiovascular autonomic function, and it is clinically significant. Several different methods of BRS assessment have been described. We evaluated and compared the efficiency of several methods of BRS assessment for additional insight into the underlying physiology and the determination of its severity in patients with PD.Materials and MethodsEighty-five patients with PD underwent cardiovascular autonomic testing. The Composite Autonomic Scoring Scale (CASS) was used to grade the severity of autonomic impairment and to define the presence of cardiovascular autonomic neuropathy (CAN). BRS was assessed using the Valsalva maneuver (BRS_VM). In addition, spontaneous BRS was computed using the sequence method and the spectral method.Results and ConclusionThere was considerable agreement between the different methods of BRS assessment. Nevertheless, BRS_VM exhibited a higher degree of correlation with cardiovascular autonomic function than spontaneous BRS indexes obtained by the sequence or spectral method. BRS_VM, rather than spontaneous BRS, also had a predictive value for the presence of CAN to the diagnostic criteria by CASS in patients with PD.

ASSOCIATION of QT INTERVAL INDICES WITH CARDIAC AUTONOMIC NEUROPATHY IN DIABETIC PATIENTS

Relevance. Cardiovascular autonomic neuropathy (CAN) is a severely debilitating yet underdiagnosed condition in patients with diabetes. The prevalence can range from 2.5% (based on the primary prevention cohort in the Diabetes Control and Complications Trial) to as high as 90% of diabetic patients. Clinical manifestations range from orthostasis to myocardial infarction. The diagnosis is made using multiple autonomic function tests to assess both sympathetic and parasympathetic function. &#x0D; Objective: this study was conducted to assess the relationship between Cardiac autonomic neuropathy and QT interval.&#x0D; Methods. Cross sectional study was conducted in 100 patients attending tertiary care hospital. Deep breathing test, Valsalva ratio, immediate heart rate response to standing 30:15, B.P rise with sustained hand grip and postural hypotension. Scoring was done for cardiac autonomic neuropathy. QT interval and QTc interval were determined and association with CAN was obtained.&#x0D; Results. Out of 100 type-2 diabetic patients, 60% were males and 40% females. 25 patients having no cardiac autonomic neuropathy and had no prolonged QTc interval. While, 75 patients had QTc prolonged were associated with early and severe CAN cardiac autonomic neuropathy. The prolonged QTc was significantly associated with CAN in diabetic patients when compared without-CAN and controls (P&lt;0001).&#x0D; Conclusion. Diabetic cardiac autonomic neuropathy is associated with increase in prolongation of QTc intervals. Hence there is need for regular checkup of autonomic nervous system in diabetic patient to prevent further complications.

Diagnosis, staging, and associated conditions of cardiovascular autonomic neuropathy in Libyan patients with diabetes

Background: Cardiovascular autonomic neuropathy (CAN) can affect daily activities and patients' quality of life and evoke potentially life-threatening outcomes in diabetes mellitus (DM). Objectives: We aimed to identify and characterize CAN and associated disorders in Libyan patients with DM at National Diabetes Hospital. Patients and Methods: Ninety-nine patients with DM seen in the outpatient clinics from October 2017 to April 2018 at National Diabetes Hospital were prospectively evaluated. Assessments for CAN were made by clinical symptoms and signs, cardiovascular autonomic reflex tests, and echocardiogram. Patients with potentially confounding concomitant medical conditions were excluded. CAN is defined as possible (one abnormal cardiovagal test), confirmed (two abnormal such tests), and severe (with concomitant orthostatic hypotension and heart rate abnormality). Results: Sixty-two percent of the studied patients (mean age: 52 ± 1.5 years, 53% – female) with DM had CAN. CAN diagnosis was possible in 18% of these patients, confirmed in 6%, and severe in 38%. The presence of severe CAN was associated with hypoglycemic unawareness (P = 0.01), dyslipidemia (P = 0.012), and microvascular diabetic complications (P = 0.04). Conclusions: In this cohort of relatively old and high-risk cardiovascular disease, patients with diabetes, uncontrolled blood pressure, associated dyslipidemia, presence of microvascular complication of diabetes, and history of hypoglycemic unawareness were strongly associated with a severe form of cardiac autonomic neuropathy with potentially serious clinical consequences. Larger and more detailed studies are needed to elucidate further the complex association between hypoglycemia and cardiac autonomic dysfunction.

Early detection of cardiovascular autonomic neuropathy: A multi-class classification model based on feature selection and deep learning feature fusion

The conventional diagnostic process and tools of cardiovascular autonomic neuropathy (CAN) can easily identify the two main categories of the condition: severe/definite CAN and normal/healthy without CAN. Conventional techniques encounter significant challenges when identifying CAN in its early or atypical stages due to the inherent imbalanced and incompleteness condition in the collected clinical multimodal data, including electrocardiogram (ECG) data from ECG sensors, blood chemistry, podiatry, and endocrinology features. Therefore, most detection tools and techniques are limited to binary CAN classification. However, early diagnosis of CAN or diagnosis of the atypical stages of CAN is more important than the diagnosis of severe CAN, which, in fact, is easily identifiable with a few diagnostic reports. In this paper, we propose a novel multi-class classification approach for timely CAN detection. The proposed classification algorithm develops a multistage fusion model by combining feature selection and multimodal feature fusion techniques. The proposed method develops a performance criterion-based feature selection technique to guarantee highly significant features. A multimodal feature fusion technique was developed using deep learning feature fusion and selected original features. The experimental results obtained from testing with a large CAN dataset indicate that the proposed algorithm significantly improved the diagnostic accuracy of CAN compared to conventional Ewing battery features. The algorithm also identified the early or atypical stages of CAN with an AUC score of 0.931 using leave-one-out cross-validation.

Feasibility of combining heart rate variability and electrochemical skin conductance as screening and severity evaluation of cardiovascular autonomic neuropathy in type 2 diabetes.

Aims/IntroductionClinical studies show that either heart rate variability (HRV) or electrochemical skin conductance (ESC) alone can serve as a simple and objective method for screening cardiovascular autonomic neuropathy (CAN). We tested the hypothesis that combining these two quantitative approaches can not only reinforce accuracy in CAN screening but also provide a better estimate of CAN severity in patients with type 2 diabetes (T2DM) who had already had CAN in outpatient clinics.Materials and MethodsEach patient received a complete battery of cardiovascular autonomic reflex tests (CARTs), with ESC measured by SUDOSCAN, time domain of HRV measured by standard deviation of all normal RR intervals (SDNN) and frequency domain of HRV (low frequency [LF], high frequency [HF], and LF/HF ratio), and peripheral blood studies for vascular risk factors. Severity of CAN was measured by CAN score.ResultsThe 90 T2DM patients included 50 males and 40 females. Those with more severe CAN had lower values in feet ESC (P = 0.023) and SDNN (P < 0.0001). Multiple linear regression analysis also showed that feet ESC and SDNN value (P = 0.003 and P < 0.0001) were significantly associated with CAN score. Combining SDNN and feet ESC also can increase the diagnostic accuracy of CAN with respective to sensitivity and specificity by using receiver operating characteristic analysis.ConclusionsCombining the results of SDNN and feet ESC can not only assess, but also quantitatively reflect the progress or improvement of autonomic nerve function (including sympathetic and parasympathetic activity) in patients with T2DM.

Impairment of microvascular blood flow in patients with type 2 diabetes and cardiovascular autonomic neuropathy

BACKGROUND: Diabetic autonomic neuropathy is the reason for early morbidity and mortality on diabetic patients. The pathology not only cardiac innervation but microvascular is presented.AIMS: We estimated the parameters of skin microvascular blood flow in accordance with cardiovascular autonomic neuropathy (CAN) staging in diabetic patients. We also assessed other risk factors of CAN in patients with diabetes.MATERIALS AND METHODS: We included 76 patients with type 2 diabetes in the study (24 patients with resent-onset diabetes and/or diabetes without microvascular complications, 26 with diabetic sensorimotor neuropathy (SMN) and 26 with SMN and previous history of diabetic foot amputation). The SMN was diagnosed on the basis of patients complaints, anamnesis and data of clinical neurological examinations. CAN was detected using several cardiovascular autonomic reflex tests (CART) as a gold standard of diagnosis: the tilt-table test, a deepbreathing and Valsalva Maneuver, handgrip test, cold-stress vasoconstriction. According to the Toronto Diabetic Neuropathy Expert Group Recommendation all patients was separated on the groups: CAN 0 (all CARTs were normal), CAN 1 (possible/early CAN — one abnormal CART was presented), CAN 2 (definite/confirmed CAN –at least two abnormal CARTs were found), CAN 3 (severe/advanced CAN — in the cases of orthostatic hypotension in addition to CARTs abnormalities). Microvascular blood flow of skin at the nail roller of fingers skin was valuated at rest as well as in functional cold test by the method of High-frequency Ultrasonic Dopplerography using the “Minimax Doppler K” device (LLC JV “Minimax”, St. Petersburg, Russia).RESULTS: CAN 1 was found in 8% diabetic patients without microvascular complications, 42 and 21% patients with SMN and diabetic foot amputations respectively. CAN 2 was diagnosed in 27% patients with SMN and 58% patients history of diabetic foot amputations. CAN 3 in 8% and 19% cases in patients with SMN and history of diabetic foot amputations respectively. The parameters of microvascular blood flow at rest were significantly decreased in patients with confirmed/severe CAN in comparison with early staging of CAN and patients without CAN (Vm=2.5±0.66 sm/sec vs. 4.4±0.54 sm/sec and 5.1±1.01 sm/sec respectively; p=0.0033). The abnormal result of cold test was detected in 94% patients with confirmed/ severe CAN and 26% patients with CAN 1.CONCLUSIONS: This investigation has demonstrated in a cohort with type 2 diabetes patients with/without SMN and with/ without history of previously foot amputations that decrease the Vm (the variable of microvascular blood flow assessed by High-frequency Ultrasonic Dopplerography) lower than 2.4 sm/sec is associated with 6.4 times increased likelihood of confirmed/severe CAN as well as positive cold test result. That the patients with positive cold test results were 28.6 times more likely have confirmed/severe CAN.

Нарушение микроциркуляторного кровотока у больных сахарным диабетом 2 типа и кардиоваскулярной автономной нейропатией

BACKGROUND : Diabetic autonomic neuropathy is the reason for early morbidity and mortality on diabetic patients. The pathology not only cardiac innervation but microvascular is presented. AIMS : We estimated the parameters of skin microvascular blood flow in accordance with cardiovascular autonomic neuropathy (CAN) staging in diabetic patients. We also assessed other risk factors of CAN in patients with diabetes. MATERIALS AND METHODS : We included 76 patients with type 2 diabetes in the study (24 patients with resent-onset diabetes and/or diabetes without microvascular complications, 26 with diabetic sensorimotor neuropathy (SMN) and 26 with SMN and previous history of diabetic foot amputation). The SMN was diagnosed on the basis of patients complaints, anamnesis and data of clinical neurological examinations. CAN was detected using several cardiovascular autonomic reflex tests (CART) as a gold standard of diagnosis: the tilt-table test, a deepbreathing and Valsalva Maneuver, handgrip test, cold-stress vasoconstriction. According to the Toronto Diabetic Neuropathy Expert Group Recommendation all patients was separated on the groups: CAN 0 (all CARTs were normal), CAN 1 (possible/early CAN — one abnormal CART was presented), CAN 2 (definite/confirmed CAN –at least two abnormal CARTs were found), CAN 3 (severe/advanced CAN — in the cases of orthostatic hypotension in addition to CARTs abnormalities). Microvascular blood flow of skin at the nail roller of fingers skin was valuated at rest as well as in functional cold test by the method of High-frequency Ultrasonic Dopplerography using the “Minimax Doppler K” device (LLC JV “Minimax”, St. Petersburg, Russia). RESULTS : CAN 1 was found in 8% diabetic patients without microvascular complications, 42 and 21% patients with SMN and diabetic foot amputations respectively. CAN 2 was diagnosed in 27% patients with SMN and 58% patients history of diabetic foot amputations. CAN 3 in 8% and 19% cases in patients with SMN and history of diabetic foot amputations respectively. The parameters of microvascular blood flow at rest were significantly decreased in patients with confirmed/severe CAN in comparison with early staging of CAN and patients without CAN (Vm=2.5±0.66 sm/sec vs. 4.4±0.54 sm/sec and 5.1±1.01 sm/sec respectively; p=0.0033). The abnormal result of cold test was detected in 94% patients with confirmed/ severe CAN and 26% patients with CAN 1. CONCLUSIONS : This investigation has demonstrated in a cohort with type 2 diabetes patients with/without SMN and with/ without history of previously foot amputations that decrease the Vm (the variable of microvascular blood flow assessed by High-frequency Ultrasonic Dopplerography) lower than 2.4 sm/sec is associated with 6.4 times increased likelihood of confirmed/severe CAN as well as positive cold test result. That the patients with positive cold test results were 28.6 times more likely have confirmed/severe CAN.

The Role of Electrochemical Skin Conductance as a Screening Test of Cardiovascular Autonomic Neuropathy in Patients with Parkinson's Disease.

Autonomic disorders have been recognized as an important non-motor feature in Parkinson’s disease (PD). However, there is a paucity of information on the presence and severity of cardiovascular autonomic neuropathy (CAN) among different motor phenotypes. The aims of this study were to examine the feasibility of electrochemical skin conductance (ESC) measured by Sudoscan as a screening service for CAN in patients with PD and investigate the severity of CAN among different motor phenotypes. Design: This was a cross-sectional observational study that enrolled 63 patients with PD. Patients were divided into three phenotypes, postural instability/gait difficulty (PIGD), tremor-dominant (TD), and akinetic-rigid (AR), according to their motor symptoms. Cardiovascular autonomic function was measured, and the presence and severity of CAN was determined according to the composite autonomic scoring scale (CASS). Functional scores were measured by the Hoehn and Yahr (HY) stage and the Unified Parkinson’s Disease Rating Scale (UPDRS). The median HY stage was 2.0 [1.5, 3.0]. Median UPDRS total score was 23.0 (17.5, 30.5), 10.0 (6.0, 11.0) and 14.0 (6.3, 23.8) in groups of PIGD, TD and AR, respectively (p = 0.001). Mean CASS was 1.7 ± 1.3, 0.6 ± 0.4, and 1.8 ± 1.5 in groups of PIGD, TD and AR, respectively (p = 0.204). Although the ESC was not strongly associated with the cardiovascular autonomic parameters, the CAN risk score provided by Sudoscan significantly correlated with parameters of cardiovascular autonomic function, including heart rate response to deep breathing (HR_DB), Valsalva ratio (VR), and baroreflex sensitivity (BRS). By receiver-operating characteristic (ROC) analysis, if a patient’s CAN risk score is higher than 33.5 (%), it is recommended to be aware of the presence of CAN even in PD patients who are asymptomatic. The area under ROC curve was 0.704. Based on our results, CAN risk score may be used for screening of CAN in patients with PD before resorting to the more sophisticated and specific, but ultimately more time-consuming, complete autonomic function testing.

Leptin mediate central obesity on the severity of cardiovascular autonomic neuropathy in well-controlled type 2 diabetes and prediabetes

BackgroundEvidences support the view that central obesity is an independently cardiovascular risk. It is thought that leptin contributes to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM). This raises the possibility that leptin might mediate the relationship between central obesity and the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes.MethodsThe complete cardiovascular reflex tests and biomarkers were assessed for each patient. The severity of CAN was assessed using composite autonomic scoring scale (CASS). A single-level three-variable mediation model was used to investigate the possible relationships among central obesity [as indicated by waist circumference (WC)], leptin level, and severity of CAN (as indicated by CASS value).ResultsA total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. The results demonstrate that increased WC is associated with increased severity of CAN (r = 0.242, P = 0.017). We further discovered that leptin level is positively correlated with WC (r = 0.504, P < 0.0001) and the CASS value (r = 0.36, P < 0.0001). Further mediation analysis shows that leptin level serves as mediators between higher WC and higher CASS.ConclusionsOur results highlighted the relationship among leptin, central obesity, and severity of CAN. As the leptin level serves as mediator between central obesity and severity of CAN, a longitudinal study is needed to confirm that control of WC can decrease leptin levels and can be effective in reducing CAN progression.

Severity of Cardiovascular Autonomic Neuropathy Is a Predictor Associated With Major Adverse Cardiovascular Events in Adults With Type 2 Diabetes Mellitus: A 6-Year Follow-up Study

ObjectivesCardiovascular autonomic function impairment has been reported in patients with type 2 diabetes mellitus and is associated with cardiovascular events. In this study, we test the hypothesis that the severity of cardiovascular autonomic neuropathy is a predictor associated with subsequent 3-point major adverse cardiovascular events (3-P MACE; combined endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke). MethodsIn this prospective study, we enrolled 168 patients with type 2 diabetes mellitus over a 6-year follow-up period. We constructed the Composite Autonomic Scoring Scale as a measure of the severity of cardiovascular autonomic neuropathy and examined baseline clinical and laboratory data of 168 patients with diabetes. Cardiovascular autonomic testing included heart rate response to deep breathing, Valsalva ratio and baroreflex sensitivity. Therapeutic outcome was defined as 3-P MACE. ResultsThe overall incidence of new 3-P MACE was 23.2% and overall fatality rate was 9.5% during the 6-year follow-up period. Only underlying coronary heart disease and Composite Autonomic Scoring Scale were independently associated with subsequent 3-P MACE in the Cox proportional hazards model. Any increase of 1 point in Composite Autonomic Scoring Scale would increase the risk of new 3-P MACE by 9.7%. Area under the curve on receiver-operating characteristic curve analysis was 0.72 in predicting subsequent 3-point MACE in combined heart rate response to deep breathing and Valsalva ratio. ConclusionsBesides underlying coronary heart disease, the severity of cardiovascular autonomic neuropathy is strongly associated with subsequent 3-P MACE. Combined heart rate response to deep breathing and Valsalva ratio testing can increase sensitivity and specificity in predicting subsequent 3-point MACE, and it can serve as a time-effective cardiovascular autonomic screening service in the outpatient clinic sitting.

Prevalence and Correlates of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes in Uganda: A Hospital-Based Cross-sectional Study

Background:Cardiovascular autonomic neuropathy (CAN) is a common complication in individuals with diabetes mellitus (DM) but often overlooked in clinical practice. The burden and correlates of CAN have not been extensively studied in low-income countries, particularly in sub-Saharan Africa.Objectives:To determine the prevalence and correlates of CAN among adults in ambulatory diabetes care in southwestern Uganda.Method:We conducted a cross-sectional study among adults with diabetes from November 2018 to April 2019. CAN was assessed using the five autonomic function tests: deep breathing, Valsalva maneuver, postural index on standing, change in blood pressure during standing and diastolic blood pressure response to isometric exercise. We estimated the prevalence of CAN and fit regression models to identify its demographic and clinical correlates.Results:We enrolled 299 individuals. The mean age was 50.1 years (SD ± 9.8), mean HbA1c was 9.7 (SD ± 2.6) and 69.6% were female. CAN was detected in 156/299 (52.2%) of the participants on the basis of one or more abnormal cardiovascular autonomic reflex tests. Out of 299 participants, 88 (29.4%) were classified as early CAN while 61/299 (20.4%) and 7/299 (2.3%) were classified as definite and severe (advanced) CAN respectively. In multivariable regression models, age over 50 years (aOR 3.48, 95%CI 1.35 –8.99, p = 0.010), duration of diabetes over 10 years (aOR 4.09, 95%CI 1.78 –9.38, p = 0.001), and presence of diabetic retinopathy (aOR 2.25, 95%CI 1.16 –4.34, p = 0.016) were correlated with CAN.Conclusions:Our findings reveal a high prevalence of CAN among individuals in routine outpatient care for diabetes mellitus in Uganda. Older age, longer duration of diabetes and coexistence of retinopathy are associated with CAN. Future work should explore the clinical significance and long term outcomes associated with CAN in this region.

Time in Range, as a Novel Metric of Glycemic Control, Is Reversely Associated with Presence of Diabetic Cardiovascular Autonomic Neuropathy Independent of HbA1c in Chinese Type 2 Diabetes.

Objective The objective of this study is to investigate the relationship between time in range (TIR), a new metric of continuous glucose monitoring (CGM) and cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes mellitus (T2DM). Methods A total of 349 individuals with T2DM were enrolled in this study. Evaluating by the standard cardiac autonomic reflex tests (CARTs), there were 228 diabetic individuals without cardiovascular autonomic neuropathy (without confirmed CAN) including absent CAN (n = 83 cases) and early CAN (n = 83 cases) and early CAN (n = 83 cases) and early CAN (n = 83 cases) and early CAN (Results The total presence of CAN was 34.67% (definite CAN 31.23% and severe CAN 3.44%). Patients with more severe CAN had lower TIR (P < 0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (P < 0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (P < 0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (P < 0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (Conclusion TIR is associated with the presence of CAN independent of HbA1c and GV metrics in Chinese type 2 diabetes.

The evaluation of QTc prolongation and QT dispersion in type 2 diabetes mellitus as an indicator of cardiac autonomic neuropathy

Background: Diabetes mellitus refers to group of metabolic disorders characterized by hyperglycemia due to an absolute or relative deficit in insulin production or action. Diabetes mellitus produces pathological changes in most organs of the body including heart, blood vessels, kidneys, nerves and eyes. Cardiovascular autonomic neuropathy (CAN) is a severely debilitating yet underdiagnosed complication of diabetes. Diabetes-associated cardiovascular autonomic neuropathy damages autonomic nerve fibers that innervate the heart and blood vessels causing abnormalities in heart rate and vascular dynamics.Methods: Total 80 cases of diabetes mellitus were selected. Cardiac autonomic neuropathy in them was diagnosed by a series of tests recommended by Ewing et al, which include - Valsalva ratio, Deep Breath Test, Heart rate response to standing, Postural Hypotension, SHGT Increase in diastolic BP on sustained hand grip. They were divided into 2 groups A and B depending on presence or absence of cardiac autonomic neuropathy. ECG was done to calculate QTc and QTd.Results: In group A mean QTc was 0.344 sec and in group B in patients with mild CAN mean QTc was 0.432, moderate CAN mean QTc was 0.444, and in patients of severe CAN mean QTc was 0.481. p value was 0.001 that it is highly significant. Means more was degree of CAN more was prolongation of QT and similarly more the degree of CAN more was QTd.Conclusions: Diagnosis of cardiac autonomic neuropathy by battery of cardiac autonomic function tests is a comlex procedure. The prolongation of QTc interval and more specifically QTd interval on ECG is a marker in diagnosis of cardiac autonomic neuropathy which can be easily evaluated.

Severity of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Mellitus Patients : Correlation with Duration of Diabetes

&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Introduction&#x0D; Cardiovascular Autonomic Neuropathy (CAN) is one of the most overlooked complications of DM and is clinically important because of its life threatening consequences. CAN results from damage to the autonomic nerve fibers that innervate the heart and blood vessels.&#x0D; Aims and Objectives&#x0D; The aim of the present study is to assess the correlation between severity of cardiovascular autonomic functions in type 2 DM and duration of diabetes.&#x0D; Method&#x0D; The study included 30 cases of type 2 diabetes mellitus without diabetic retinopathy and 30 cases of type 2 diabetes mellitus with non proliferative diabetic retinopathy (NPDR). 60 non diabetic healthy volunteers matched for age and gender were included in the study to serve as control. The study group was classified into 3 groups according to duration of diabetes. All the subjects performed five different autonomic function tests as given by Ewing's and Clarke. The score value was obtained from various tests and a scoring system was applied as recommended by Bellavere F et al (1983).4 The results obtained were analysed statistically by one-way ANOVA and intergroup comparisons were made using post hoc Tukey multiple comparison test.&#x0D; Results&#x0D; The observations suggest that cardiac autonomic function declines in type 2 diabetics and CAN is more in diabetic patients with associated retinopathy The observations revealed that number of patients with autonomic dysfunction was more when duration of DM was long (&gt;7 years) (83.3% in group 1 and 81.2% in group 2). The number of patients with CAN increased with duration of DM. Correlation between disease duration and cardiovascular autonomic score indicates significant positive correlation (r=0.5920).&#x0D; Conclusion&#x0D; The cardiac autonomic functions were found to be altered significantly in diabetics. Diabetic patients with longer duration of diabetes showed more severe dysfunction of cardiovascular functions. Hence, Evaluation of cardiovascular reflexes should be included as a routine in the work-up of patients of Type 2 diabetes mellitus.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

HbA1C Variability Is Strongly Associated With the Severity of Cardiovascular Autonomic Neuropathy in Patients With Type 2 Diabetes After Longer Diabetes Duration.

BackgroundVariability in the glycated hemoglobin (HbA1c) level is associated with a higher risk of microvascular complications in patients with type 2 diabetes. We tested the hypothesis that HbA1c variability is not only strongly associated with the presence but also the degree of severity of cardiovascular autonomic neuropathy (CAN) in patients with long diabetes durations (more than 10 years).MethodsFor each patient, the intrapersonal mean, standard deviation (SD), and coefficient of variation (CV) for HbA1c were calculated using all measurements obtained 3 years before the study. We constructed the composite autonomic scoring scale (CASS) as a measure of the severity of cardiovascular autonomic functions. Stepwise logistic regression and linear regression analyses were performed to evaluate the presence of CAN and the influence of independent variables on the mean CASS, respectively.ResultsThose with CAN had a higher mean age, a higher low-density lipoprotein cholesterol (LDL-C), HbA1c-SD, HbA1c-CV, mean HbA1c, and index HbA1c, higher prevalence of retinopathy as the underlying disease, and lower high-density lipoprotein (HDL) levels. Stepwise logistic regression showed that HbA1c-SD and retinopathy were risk factors that were independently associated with the presence of CAN. Mean HbA1c, HbA1c-CV, HbA1c-SD, and index HbA1c were positively correlated with mean CASS, and a multiple linear regression analysis revealed that HbA1c-SD was independently associated with the mean CASS.ConclusionHbA1c variability is strongly associated with not only the presence but also the degree of severity of CAN. A longitudinal study is required to confirm whether controlling blood glucose level is effective in reducing CAN progression.

Nocturnal ventricular arrhythmias are associated with the severity of cardiovascular autonomic neuropathy in type 2 diabetes

Cardiovascular autonomic neuropathy (CAN) is a risk factor for arrhythmias and adverse cardiovascular events, but the relationship between CAN severity and nocturnal arrhythmias needs to be clarified. This study evaluated the association between nocturnal arrhythmias and CAN severity in patients with type 2 diabetes (T2D). In all, 219 T2D patients were recruited from January 2017 to May 2018. Subjects were classified into no CAN (NCAN), early CAN (ECAN), definite CAN (DCAN), or advanced CAN (ACAN) based on cardiovascular autonomic reflex tests (CARTs). A 24-hour electrocardiogram was recorded and daytime (0700-2300 hours) and night-time (2300-0700 hours) heartbeats were analyzed separately. After adjusting for age, the incidence of ventricular arrhythmias increased with CAN severity at night-time (18.6%, 29.9%, 36.2%, and 60.0% in the NCAN, ECAN, DCAN, and ACAN groups, respectively; Ptrend = 0.034). Patients with nocturnal ventricular arrhythmias (NVAs) had higher CART scores (2.0 ± 1.0 vs 1.5 ± 0.9; P < 0.001) and lower heart rate variability (HRV) during deep breathing (9.5 ± 5.7 vs 11.6 ± 6.6 b. p. m; P = 0.021), HRV during the Valsalva maneuver (1.2 ± 0.1 vs 1.2 ± 0.2; P = 0.006), and postural blood pressure change (-8.8 ± 15.5 vs -4.1 ± 11.2 mmHg; P = 0.023). Multivariate regression analysis revealed that CAN stage (odds ratio 1.765; 95% confidence interval 1.184-2.632; P = 0.005) was independently associated with NVAs. In T2D, CAN stage was independently associated with the presence of NVAs. Early detection, diagnosis, and treatment of CAN may help predict and prevent adverse cardiovascular events and cardiovascular mortality in diabetes.