The role of various risk factors in the prevalence of cardiac autonomic neuropathy and associated diseases

The objectives of this thesis were three-fold: The first aim was to investigate the roles of various markers in the prevalence and complications of CAN and associated diseases with emphasis on diabetes mellitus. Specifically, this study investigated the role of heart rate variability (HRV) markers as well as the roles of genetic and family history risk factors. The second aim of this study was to develop mechanisms to predict CAN disease occurrence. The third aim of this current study was to develop a model for predicting diabetes mellitus (DM) and cardiovascular disease (CVD) simultaneously using common risk factors

Measurement of Autonomic Function in Renal Disease and Diabetes

Renal disease and diabetes lead to dysautonomia resulting in consequences ranging from gastroparesis to sudden death. New technologies to detect dysautonomia, such as 24-hr heart rate variability, are being evaluated and compared to traditional evoked tests. These advances have, however, lead to a lack of standardization in testing batteries, procedures, and reporting formats. This series of 3 studies psychometrically assessed measures of autonomic function (AF) and explored relationships among objective and subjective measures in healthy adults and uremic patients. Participants underwent evoked tests that included change in heart rate with deep breathing and Valsalva. In addition, measures of 24-hr HRV (time-domain: SDNN, SDANN, RMSSD; frequency-domain: total power, low and high frequency) and symptomatology were obtained. Study 1 examined the development and psychometric testing of the Autonomic Symptom Checklist (ASC), an instrument designed to assess autonomic symptomatology, with uremic patients (n=244) and healthy adults (n=34). Findings showed the ASC was able to differentiate among healthy and uremic patients with and without diabetes. Test-retest reliability was moderate to high for most categories. Study 2 established normal, borderline, and abnormal AF values and determined if these values could distinguish healthy (n=158) from uremic adults (n=363). Abnormal values were established at the 2.3 quantile of healthy adults. Uremic patients, especially those with diabetes, had much poorer values than healthy adults. The influence of age and gender on AF measures was attenuated in uremic as compared to healthy adults. Study 3 examined relationships among and the clinical utility of evoked tests, 24- hr HRV, and the ASC. Data were obtained from pre (n=130) and post (n=55) kidney and kidney-pancreas transplant recipients (n=130), and healthy adults (n=22). The frequency of abnormal values was used to identify the most sensitive measure. Measures of 24-hr HRV were more sensitive than evoked measures, with frequency measures being most sensitive. In conclusion, this series of studies established reliability and validity for the ASC, referent values for AF tests, devised a scoring system for AF tests, and found 24-hr HRV measures more sensitive than evoked measures

Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management

The Cardiovascular Autonomic Neuropathy (CAN) Subcommittee of the Toronto Consensus Panel on Diabetic Neuropathy worked to update CAN guidelines, with regard to epidemiology, clinical impact, diagnosis, usefulness of CAN testing, and management. CAN is the impairment of cardiovascular autonomic control in the setting of diabetes after exclusion of other causes. The prevalence of confirmed CAN is around 20%, and increases up to 65% with age and diabetes duration. Established risk factors for CAN are glycaemic control in type 1 and a combination of hypertension, dyslipidaemia, obesity, and glycaemic control in type 2 diabetes. CAN is a risk marker of mortality and cardiovascular morbidity, and possibly a progression promoter of diabetic nephropathy. Criteria for CAN diagnosis and staging are: (1) one abnormal cardiovagal test result identifies possible or early CAN; (2) at least two abnormal cardiovagal test results are required for definite or confirmed CAN; and (3) the presence of orthostatic hypotension in addition to abnormal heart rate test results identifies severe or advanced CAN. Progressive stages of CAN are associated with increasingly worse prognosis. CAN assessment is relevant in clinical practice for (1) diagnosis of CAN clinical forms, (2) detection and tailored treatment of CAN clinical correlates (e.g. tachycardia, orthostatic hypotension, non‐dipping, QT interval prolongation), (3) risk stratification for diabetic complications and cardiovascular morbidity and mortality, and (4) modulation of targets of diabetes therapy. Evidence on the cost‐effectiveness of CAN testing is lacking. Apart from the preventive role of intensive glycaemic control in type 1 diabetes, recommendations cannot be made for most therapeutic approaches to CAN. Copyright © 2011 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86954/1/1239_ftp.pd

Investigation of cardiovascular autonomic function - Ewing`s battery

Използването на различни автономни тестове допълва клиничната оценка при нарушение на автономните функции. Автономното тестуване има ясен фокус върху сърдечно-съдовата система (ССС) и взаимодействието й с дихателната система. Ewing и Clarke предлагат изпълнението на пет автономни теста (три предимно парасимпатикови и два предимно симпатикови), включени в т.нар. „стандартна батерия` (Ewing`s battery). Нито един тест самостоятелно не може да даде обща оценка на автономната функция. Нормативните стойности на тестовете зависят от много фактори. Ewing и Clarke въвеждат променливите - абнормни, гранични и нормални за всеки един от тестовете.The use of different autonomous tests complement clinical assessment in violation of autonomous functions. Autonomous testing has a clear focus on the cardiovascular system and its interaction with the respiratory system. Ewing and Clarke propose the implementation of the five autonomous tests (three primarily parasympathetic and sympathetic mostly two) included in the so called „Standard battery` („Ewing‘s battery). Not one test alone can not provide an overall assessment of autonomic function. Normative values of tests depend on many factors. Ewing and Clarke introduced variable - abnormal, border and normal limit for each of the tests

Heart rate and blood pressure variability : association with white matter lesions and cognitive function following stroke

Dementia presents a significant health care burden. Older post-stroke patients suffer high rates of dementia. Subcortical ischaemia may be an important mechanism of cognitive decline, particularly in older patients with cerebrovascular disease. It is hypothesised that abnormal heart rate and blood pressure variability will increase white matter lesion volume through hypoperfusion. This may lead to a subcortical pattern of cognitive decline characterised for example by deficits in attention and concentration. Stroke patients aged > 75 years and free of dementia had a series of cardiovascular autonomic, brain imaging and neuropsychometric investigations performed more than three months following incident stroke. Annual neuropsychometric assessment included CAMCOG score and measures of reaction time and concentration using a series of visual and numerical tasks presented on computer (Cognitive Drug Research Assessment System). Autonomic function is impaired in older stroke patients in the long term after stroke. These deficits are weakly associated with cross-sectional measures of sub-cortical performance but do not predict subsequent decline in cognitive function. Twenty-four hour blood pressure variability is associated with white matter disease and excessive nocturnal dipping is associated with impaired cognitive function. Again blood pressure variability does not help predict subsequent change in white matter lesion burden or cognitive function. This study provides limited support for the hypoperfusion theory of post-stroke cognitive impairment. However it does not indicate a role for heart rate and blood pressure variability in the mechanism of increasing white matter disease or decline in cognition in the two years following stroke.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

HIV-associated Neuropathy and Autonomic Dysfunction in South Africans on established ART impacts daily living

Introduction A common complication of Human Immunodeficiency Virus (HIV) and anti-retroviral therapy (ART) is distal sensory polyneuropathy (DSP). Older age and previous TB are risk factors for DSP among HIVinfected Africans before and shortly after ART initiation. Little is known about autonomic dysfunction in Africans on long-term ART and the impact of DSP and autonomic impairment on their quality of life. Our aim was to describe the frequency, characteristics and functional consequences of DSP and autonomic dysfunction in a healthy HIV-infected community-based cohort after at least 5 years of ART. Methods HIV-infected South Africans on the government-sponsored ART program for at least 5 years were included in this cross-sectional analysis. Each consenting participant underwent a focussed neurological assessment using the Brief Peripheral Neuropathy Screen (BPNS) and a reduced version of the Total Neuropathy Score (rTNS). DSP was defined as the presence of at least 2 neuropathic signs in a distal and symmetrical distribution, and symptomatic DSP (SDSP) when accompanied by neuropathic symptoms. Heart rate variability and orthostatic hypotension were measured as described by the Ewing classic battery, and the Survey of Autonomic Symptoms (SAS) questionnaire assessed the presence and severity of autonomic symptoms. We used a modified version of the Lower Extremity Functional Scale (LEFS) to assess lower limb physical ability. Results The 67 participants had a median age of 41 years (interquartile range (IQR) 36-46) and 61 (91 %) were women. The median duration of ART was 7 years (IQR 6-10). DSP criteria were met in 54 (80.6%) and 24 (44.4%) had symptomatic DSP. Comparing participants with DSP to those without DSP, there was no difference in sex (P=0.39), age (P=0.79), current CD4 (P=0.69), viral suppression (P=0.34), ART duration (P=0.22) or previous tuberculosis (TB) (P=0.72) in those with DSP. Similar outcomes were obtained for SDSP. Abnormal autonomic tests were present in 60%. Those with SDSP had more severe autonomic symptoms than those with asymptomatic DSP (P=0.0008). We found that those with DSP and SDSP had significantly lower LEFS percentage scores than those without (P=0.039 and P=0.013 respectively). 5 Conclusion DSP remains a common complication of HIV in the modern era of ART and can lead to significant functional impairment. Autonomic dysfunction is prevalent in SDSP