Cardiac Autonomic Neuropathy in Diabetes: A Predictor of Cardiometabolic Events

Autonomic nervous system (ANS) imbalance manifesting as cardiac autonomic neuropathy in the diabetic population is an important predictor of cardiovascular events. Symptoms and signs of ANS dysfunction, such as resting heart rate elevations, diminished blood pressure responses to standing, and altered time and frequency domain measures of heart rate variability in response to deep breathing, standing, and the Valsalva maneuver, should be elicited from all patients with diabetes and prediabetes. With the recognition of the presence of ANS imbalance or for its prevention, a rigorous regime should be implemented with lifestyle modification, physical activity, and cautious use of medications that lower blood glucose. Rather than intensifying diabetes control, a regimen tailored to the individual risk of autonomic imbalance should be implemented. New agents that may improve autonomic function, such as SGLT2 inhibitors, should be considered and the use of incretins monitored. One of the central mechanisms of dysfunction is disturbance of the hypothalamic cardiac clock, a consequence of dopamine deficiency that leads to sympathetic dominance, insulin resistance, and features of the metabolic syndrome. An improvement in ANS balance may be critical to reducing cardiovascular events, cardiac failure, and early mortality in the diabetic population

Addition of 24‐hour heart rate variability parameters to the Cardiovascular Health Study stroke risk score and prediction of incident stroke: The Cardiovascular Health Study

Background Heart rate variability (HRV) characterizes cardiac autonomic functioning. The association of HRV with stroke is uncertain. We examined whether 24‐hour HRV added predictive value to the Cardiovascular Health Study clinical stroke risk score (CHS‐SCORE), previously developed at the baseline examination. Methods and Results N=884 stroke‐free CHS participants (age 75.3±4.6), with 24‐hour Holters adequate for HRV analysis at the 1994–1995 examination, had 68 strokes over ≤8 year follow‐up (median 7.3 [interquartile range 7.1–7.6] years). The value of adding HRV to the CHS‐SCORE was assessed with stepwise Cox regression analysis. The CHS‐SCORE predicted incident stroke (HR=1.06 per unit increment, P=0.005). Two HRV parameters, decreased coefficient of variance of NN intervals (CV%, P=0.031) and decreased power law slope (SLOPE, P=0.033) also entered the model, but these did not significantly improve the c‐statistic (P=0.47). In a secondary analysis, dichotomization of CV% (LOWCV% ≤12.8%) was found to maximally stratify higher‐risk participants after adjustment for CHS‐SCORE. Similarly, dichotomizing SLOPE (LOWSLOPE <−1.4) maximally stratified higher‐risk participants. When these HRV categories were combined (eg, HIGHCV% with HIGHSLOPE), the c‐statistic for the model with the CHS‐SCORE and combined HRV categories was 0.68, significantly higher than 0.61 for the CHS‐SCORE alone (P=0.02). Conclusions In this sample of older adults, 2 HRV parameters, CV% and power law slope, emerged as significantly associated with incident stroke when added to a validated clinical risk score. After each parameter was dichotomized based on its optimal cut point in this sample, their composite significantly improved prediction of incident stroke during ≤8‐year follow‐up. These findings will require validation in separate, larger cohorts. Keywords: autonomic nervous system, clinical stroke risk model, heart rate variability, prediction, predictors, risk prediction, risk stratification, strok

Management strategies for gastrointestinal, erectile, bladder, and sudomotor dysfunction in patients with diabetes

There are substantial advances in understanding disordered gastrointestinal autonomic dysfunction in diabetes. It occurs frequently. The underlying pathogenesis is complex involving defects in multiple interacting cell types of the myenteric plexus as well. These defects may be irreversible or reversible. Gastrointestinal symptoms represent a major and generally underestimated source of morbidity for escalating health care costs in diabetes. Acute changes in glycaemia are both determinants and consequences of altered gastrointestinal motility. 35–90% of diabetic men have moderate‐to‐severe erectile dysfunction (ED). ED shares common risk factors with CVD. Diagnosis is based on medical/sexual history, including validated questionnaires. Physical examination and laboratory testing must be tailored to patient's complaints and risk factors. Treatment is based on PDE5‐inhibitors (PDE5‐I). Other explorations may be useful in patients who do not respond to PDE5‐I. Patients at high cardiovascular risk should be stabilized by their cardiologists before sexual activity is considered or ED treatment is recommended. Estimates on bladder dysfunction prevalence are 43–87% of type 1 and 25% of type 2 diabetic patients, respectively. Common symptoms include dysuria, frequency, urgency, nocturia and incomplete bladder emptying. Diagnosis should use validated questionnaire for lower urinary tract symptoms. The type of bladder dysfunction is readily characterized with complete urodynamic testing. Sudomotor dysfunction is a cause of dry skin and is associated with foot ulcerations. Sudomotor function can be assessed by thermoregulatory sweat testing, quantitative sudomotor axon reflex test, sympathetic skin response, quantitative direct/indirect axon reflex testing and the indicator plaster. Copyright © 2011 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87058/1/1223_ftp.pd

Heart Rate Variability and Non-Linear Dynamics in Risk Stratification

The time-domain measures and power–spectral analysis of heart rate variability (HRV) are classic conventional methods to assess the complex regulatory system between autonomic nervous system and heart rate and are most widely used. There are abundant scientific data about the prognostic significance of the conventional measurements of HRV in patients with various conditions, particularly with myocardial infarction. Some studies have suggested that some newer measures describing non-linear dynamics of heart rate, such as fractal measures, may reveal prognostic information beyond that obtained by the conventional measures of HRV. An ideal risk indicator could specifically predict sudden arrhythmic death as the implantable cardioverter-defibrillator (ICD) therapy can prevent such events. There are numerically more sudden deaths among post-infarction patients with better preserved left ventricular function than in those with severe left ventricular dysfunction. Recent data support the concept that HRV measurements, when analyzed several weeks after acute myocardial infarction, predict life-threatening ventricular tachyarrhythmias in patients with moderately depressed left ventricular function. However, well-designed prospective randomized studies are needed to evaluate whether the ICD therapy based on the assessment of HRV alone or with other risk indicators improves the patients’ prognosis. Several issues, such as the optimal target population, optimal timing of HRV measurements, optimal methods of HRV analysis, and optimal cutpoints for different HRV parameters, need clarification before the HRV analysis can be a widespread clinical tool in risk stratification

Associations Between Heart Rate Variability and Metabolic Syndrome Risk Factors

Metabolic syndrome (MetS) is a clustering of risk factors for cardiovascular disease (CVD) and type 2 diabetes (T2D) – two major causes of morbidity and mortality worldwide. Heart rate variability (HRV) is a non-invasive measure of cardiac autonomic regulation that predicts mortality and morbidity. Additionally, HRV is reduced in CVD, T2D and MetS. As such, HRV has potential to be a novel cardiometabolic risk factor to be included in clinical risk assessment. Therefore, the purpose of this thesis was to examine the relationships between MetS and HRV. A systematic review of cross-sectional studies examining relationships between HRV and MetS was completed to consolidate existing evidence and to guide future studies. This was followed by a cross-sectional investigation of time and frequency domain and nonlinear HRV in a population with MetS risk factors to determine which MetS risk factors were associated with HRV parameters. A pilot study was then conducted to study the feasibility of conducting a mobile health (mHealth) and exercise intervention in a rural population, which was followed by a 24-week randomized clinical trial to examine the effects of the interactive mHealth exercise intervention compared to standard of care exercise in participants with MetS risk factors. Overall, HRV was reduced in women with MetS compared to those without, though there were no differences in men. Waist circumference and lipid profiles were most commonly related to HRV parameters when studied cross-sectionally. The changes in waist circumference and fasting plasma glucose were associated with the change in HRV parameters when studied longitudinally. Following the intervention period, waist circumference and blood pressure were improved with no other changes in MetS risk factors. HRV parameters indicative of vagal activity were reduced over the intervention period, but there were no changes in other HRV parameters. There were no differences in changes between the intervention and control groups. In conclusion, MetS and HRV are associated in women but not men. However, there were no clear associations between MetS and HRV to suggest that HRV would be a valuable clinical risk factor

Cardiac Autonomic Dysfunction In Chronic Stroke Women Is Attenuated After Submaximal Exercise Test, As Evaluated By Linear And Nonlinear Analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Background: We evaluated cardiac autonomic modulation in women with chronic ischemic stroke (at least 4 years post-stroke) at rest and in response to submaximal exercise test. Methods: Fourteen post-stroke women (S group) and 10 healthy women (C group) participated in this study. Autonomic modulation (using linear and nonlinear analysis), blood pressure and metabolic variables at rest were evaluated immediately after the exercise test and during the recovery period (20 min). All participants underwent submaximal exercise test on cycle ergometer with gas analysis. Results: At rest, the S group displayed higher lactate concentration, systolic (SBP) and diastolic blood pressure (DBP) values when compared to C group. Furthermore, the S group had lower heart rate variability (HRV) in time domain (SDNN: S = 30 +/- 5 vs. 40 +/- 8 ms; rMSSD: S = 14 +/- 2 vs. C = 34 +/- 3 ms), decreased high frequency band of pulse interval (S = 8.4 +/- 2 vs. 33.1 +/- 9 %) and 2V pattern of symbolic analysis (S = 17.3 +/- 1 vs. 30 +/- 3 %) (both indicators of cardiac vagal modulation) when compared to C group. Immediately after exercise, S group presented higher values of lactate, SBP, DBP and double product when compared to C group, as well as decreased heart rate recovery (HRR) measured at the first, second and third minutes. At recovery time, all HRV parameters in time and frequency domains improved in the S group; however, HF band remained lower when compared to C group. Conclusions: After the exercise test, women with chronic stroke presented reduced heart rate variability, reduced cardiac vagal modulation, as well as reduced HRR, while displayed an improvement of heart rate variability and cardiac vagal modulation when compared to their baseline. These results reinforce the importance of a physically active lifestyle for cardiovascular autonomic disorders observed in chronic stroke women.15Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP