Machine learning applied to ambulatory blood pressure monitoring: a new tool to diagnose autonomic failure?

BACKGROUND: Autonomic failure (AF) complicates Parkinson's disease (PD) in one-third of cases, resulting in complex blood pressure (BP) abnormalities. While autonomic testing represents the diagnostic gold standard for AF, accessibility to this examination remains limited to a few tertiary referral centers. OBJECTIVE: The present study sought to investigate the accuracy of a machine learning algorithm applied to 24-h ambulatory BP monitoring (ABPM) as a tool to facilitate the diagnosis of AF in patients with PD. METHODS: Consecutive PD patients naïve to vasoactive medications underwent 24 h-ABPM and autonomic testing. The diagnostic accuracy of a Linear Discriminant Analysis (LDA) model exploiting ABPM parameters was compared to autonomic testing (as per a modified version of the Composite Autonomic Symptom Score not including the sudomotor score) in the diagnosis of AF. RESULTS: The study population consisted of n = 80 PD patients (33% female) with a mean age of 64 ± 10 years old and disease duration of 6.2 ± 4 years. The prevalence of AF at the autonomic testing was 36%. The LDA model showed 91.3% accuracy (98.0% specificity, 79.3% sensitivity) in predicting AF, significantly higher than any of the ABPM variables considered individually (hypotensive episodes = 82%; reverse dipping = 79%; awakening hypotension = 74%). CONCLUSION: LDA model based on 24-h ABPM parameters can effectively predict AF, allowing greater accessibility to an accurate and easy to administer test for AF. Potential applications range from systematic AF screening to monitoring and treating blood pressure dysregulation caused by PD and other neurodegenerative disorders.

Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy.

Despite its prevalence, clinical and prognostic impact, diabetic autonomic neuropathy, is widely under-diagnosed. The need for training and expertise to perform the cardiovascular tests (usually the task of diabetologists) is one possible reason. The availability of computer-assisted systems has allowed a wider diffusion of testing, but has also highlighted the need for an adequate knowledge of physiopathological backgrounds for their correct application and interpretation. The recommendations presented here were developed by the Neuropathy Study Group of the Italian Society of Diabetology and then endorsed by the Italian Association for the Study of Neurovegetative System, to promote the widespread adoption of good clinical practice in diabetic cardiovascular autonomic testing by outlining main evidence-based aspects, i.e. which tests, how to perform them, adequate interpretation of the results and their diagnostic use, confounding conditions that can impact on tests reliability. Therefore, these recommendations include the essential aspects of the physiopathological substrate of the tests, the controversial points in their analysis, their diagnostic characteristics, as well as safety. Detailed information is given on the physiological (age, weight, body position, resting heart rate and blood pressure, respiratory pattern, exercise, meals, acute blood glucose changes) and pathophysiological confounding factors, with emphasis on the effects of drugs. Instructions on how to perform the tests and interpret their results are also considered together with indications of candidate patients and periodicity of testing. A patient instruction sheet on why and how to perform the tests is included. Finally, the specific requirements for computerized systems to perform and evaluate cardiovascular tests are provided.

Screening indexes for cardiovascular autonomic failure in Parkinson's disease.

Autonomic failure (AF) is a common source of orthostatic hypotension (OH) in Parkinson's disease (PD). The diagnosis of AF is difficult on clinical grounds alone. We used autonomic testing and 24-h BP monitoring (ABPM) in 122 PD patients to evaluate the diagnostic accuracy of AF by (1) the reduced heart rate increase to fall in blood pressure (BP) ratio (ΔHR/ΔSBP), (2) reverse dipping (RD), and (3) increased diurnal systolic BP standard deviation (SD-SBP). Among patients with OH, ΔHR/ΔSBP yielded the best accuracy (85%), with excellent sensitivity (92%) and acceptable specificity (67%). RD and, to a lesser extent, SD-SBP had high specificity (93% and 73%, respectively) but low sensitivity, resulting in overall moderate accuracy (66% and 55%, respectively). In patients with OH, the addition of ABPM indexes to ΔHR/ΔSBP did not result in a significant improvement of accuracy. In patients without OH, RD and SD-SBP may be useful showing an accuracy of 72% and 81%, respectively, with high negative predictive value when both RD and increased SD-SBP are absent. The integration of bedside (∆HR/∆SBP) and ABPM-derived indexes can assist the clinician in screening PD patients for AF and guide referral to autonomic testing.

High prevalence of neuropathies in patients with end-stage liver disease.

OBJECTIVES: Peripheral neuropathy has been reported in association with end-stage liver disease, but there is only a limited number of reports on the incidence and features of these neuropathies. MATERIALS AND METHODS: In this study, 83 patients awaiting liver transplantation were evaluated for the presence of peripheral and autonomic neuropathy. RESULTS: Sixty-five percent of the patients had evidence of neuropathy, in agreement with peripheral NCS or cardiovascular autonomic function test. The neuropathy was more frequent in patients with advanced hepatic failure, evaluated with the MELD score. The most frequent abnormalities in nerve conduction studies were sensory-motor neuropathies and sensory neuropathies, with a length-dependent pattern. CONCLUSION: Peripheral neuropathy and autonomic neuropathy are common in patients with end-stage liver disease with different etiology and correlate with the severity of the liver disease.

Cognitive decline and low blood pressure: the other side of the coin.

Low blood pressure has been found to be associated with cognitive decline and dementia in cross-sectional studies. Two mechanisms have been proposed to interpret this association: blood pressure levels decrease during the course of the dementia process, and low blood pressure induces or accelerates cognitive decline by lowering cerebral blood flow. Results of the prospective studies are contradictory. Low blood pressure and orthostatic hypotension have been found to predict cognitive impairment in the elderly population in some studies only. While hypotension may play a protective role in healthy elderly people, low blood pressure levels in frail elderly patients with associated diseases may cause cerebral hypoperfusion and accelerate cognitive decline.

Relationship between QT interval and cardiovascular risk factors in healthy young subjects.

A prolongation of QT interval increases the risk for coronary heart disease, ventricular arrhythmias, and sudden death in diabetic patients, after myocardial infarction, and in the elderly. An association between QT prolongation and cardiovascular risk factors has been demonstrated in middle-aged and elderly subjects. Aims of this study were to evaluate the prevalence of a prolonged corrected QT interval (QTc) in a healthy young population (n=170, age 22-25 years, 84 males) and to investigate the association of QTc and QT dispersion (QTd) with cardiovascular risk factors (body mass index, blood pressure, fasting blood glucose and cholesterol, smoking habits, and hypertensive familiarity). A prolonged QTc was observed in 10% of female and 5% of male subjects; in multiple regression analysis, QTc showed a significant positive relationship with blood glucose in females (P=0.04) and systolic blood pressure in male subjects (P=0.03), while QTd was not significantly related with any of the factors. In conclusion, the association between QTc length, glucose levels, and blood pressure is present also in young healthy subjects. QT measurement may represent a useful marker in the screening of young subjects for cardiovascular prevention. Journal of Human Hypertension (2005) 19, 623-627. doi:10.1038/sj.jhh.1001874; published online 19 May 2005.

Orthostatic hypotension in a cohort of hypertensive patients referring to a hypertension clinic.

The prevalence of orthostatic hypotension (OH) in hypertensive patients ranges from 3 to 26%. Drugs are a common cause of non-neurogenic OH. In the present study, we retrospectively evaluated the medical records of 9242 patients with essential hypertension referred to our Hypertension Unit. We analysed data on supine and standing blood pressure values, age, sex, severity of hypertension and therapeutic associations of drugs, commonly used in the treatment of hypertension. OH was present in 957 patients (10.4%). Drug combinations including α-blockers, centrally acting drugs, non-dihydropyridine calcium-channel blockers and diuretics were associated with OH. These pharmacological associations must be administered with caution, especially in hypertensive patients at high risk of OH (elderly or with severe and uncontrolled hypertension). Angiotensin-receptor blocker (ARB) seems to be not related with OH and may have a potential protective effect on the development of OH.

Alcohol ingestion lowers supine blood pressure, causes splanchnic vasodilatation and worsens postural hypotension in primary autonomic failure.

Patients with pure autonomic failure (PAF) and multiple system atrophy (MSA) may complain of feeling light-headed after alcohol ingestion particularly on assumption of the upright posture. The reasons for this have not been investigated. We therefore studied the effects of oral alcohol (40% vodka in sugar-free orange juice) and placebo (juice only) on the systemic and regional (including superior mesenteric artery, SMA) blood flow in nine patients with PAF and six patients with MSA. After alcohol, there was a fall in supine blood pressure (BP) and vasodilatation in the SMA but no change in cardiac output, or forearm muscle and cutaneous blood flow in either PAF or MSA; BP fell further during head-up tilt with no changes in levels of plasma catecholamines. After placebo, there were no changes while supine. We conclude that alcohol lowers supine BP and dilates the SMA with no change in muscle or cutaneous blood flow. Alcohol also enhances the fall in BP during head-up tilt. This may explain the symptoms experienced by PAF and MSA patients after alcohol.

[Diabetes, obesity, hypertension and the autonomic nervous system]. / Diabete, obesità, ipertensione e sistema nervoso vegetativo.

Functional changes of the autonomic nervous system may represent a common pathophysiologic factor in the association between non insulin-dependent diabetes, obesity, and essential hypertension. In all these conditions a number of sympathetic and/or parasympathetic dysfunctions consistent with autonomic neuropathy or simply with functional adaptations to haemodynamic changes have been reported. Autonomic neuropathy is a well known diabetic complication which is responsible for some clinical aspects of different severity. Subtle sympathetic and parasympathetic abnormalities possibly affecting thermogenesis have been shown in obese people. An increased sympathetic activity has been proposed as one of the pathogenetic mechanisms of essential hypertension. Finally, the association between diabetes, obesity, hypertension and sympathetic overactivity could be explained by a common trans-membrane ionic disturbance with an increase of intracellular calcium and a decrease of both intracellular magnesium and pH.

Autonomic nervous activity in obese subjects before and after caloric restriction.

The heart rate response to deep breathing (DB test) and standing (30:15 r test) and the blood pressure response to standing (LS test) and sustained handgrip (HG test) were assessed in 19 obese subjects and 15 age matched lean controls. The results of DB, 30:15 r and LS tests were not significantly different in both groups. The diastolic blood pressure increase during handgrip was significantly higher in obese than in control subjects. After a period of caloric restriction the tests were repeated in 9 patients who had obtained a weight loss of at least 5 kg: a significant decrease in heart rate, diastolic blood pressure and 30:15 r results was observed, whereas the caloric restriction did not cause significant variations in the results of DB, LS and HG tests. Our results suggest that in obese patients some autonomic nervous changes can occur before and after weight loss.

[ACE inhibitors and vagal activity: the effect of captopril and lisinopril on cardiovascular reflexes]. / ACE-inibitori e attività vagale: effetto di captopril e lisinopril su alcuni riflessi cardiovascolari.

The influence of the ACE-inhibitors captopril and lisinopril on parasympathetic activity in normotensive subjects was evaluated. Three cardiovascular tests which explored chiefly parasympathetic function (deep breathing, lying to standing and Valsalva test) were performed in 10 normotensive volunteers (mean age 26.1 years) in both basal conditions and after four days of treatment with either captopril (25 mg twice a day) or lisinopril (20 mg once a day). Mean blood pressure was not influenced by captopril, whereas it was significantly lowered with lisinopril (from 94.4 +/- 6.8 to 88.7 +/- 5.7 mmHg; p < 0.05). Neither drug interfered with heart rate or with the results of the deep breathing and Valsalva tests. The 30/15 ratio, an index of heart rate variability during the lying to standing test, significantly worsened after assumption of both captopril (from 1.37 +/- 0.18 to 1.21 +/- 0.14; p < 0.05) and lisinopril (from 1.31 +/- 0.17 to 1.20 +/- 0.11; p < 0.05). Although our subjects had a lisinopril-induced drop in blood pressure, their heart rate remained steady. This finding confirms previous studies reporting the lack of reflex tachycardia during ACE-inhibition. The slight effect of ACE-inhibitors on the results of deep breathing and Valsalva tests suggests that such drugs do not directly stimulate vagal activity; the significant decrease of the 30/15 ratio may be due to a functional impairment of the baroreflex mechanism.

Sympathetic nervous system, diabetes, and hypertension.

Hypertension is twice as frequent in diabetic patients than in the general population. Its prevalence is higher in Type 2 than in Type 1 diabetes: in the former, the onset of hypertension often precedes the diagnosis of diabetes, whereas, in the latter it is strictly related to the presence of nephropathy. Sympathetic nerve overactivity is crucial in the pathogenesis of hypertension in diabetes. It can be related to the activation of the renin-angiotensin-aldosterone (RAA) system in Type 1 diabetic patients with chronic renal failure, or to a condition of insulin resistance/hyperinsulinemia in Type 2 patients with the metabolic syndrome. In patients with early autonomic neuropathy, vagal impairment can lead to a relative predominance of sympathetic activity in the sympatho-vagal balance. In these patients, the onset of hypertension is frequently preceded by reduced nocturnal dipping. Sympathetic overactivity stimulates RAA activity, promotes sodium reabsorption, and increases heart rate, stroke volume and peripheral vascular resistance, thus inducing hypertension and increasing cardiovascular risk. A number of drugs acting either directly or indirectly on sympathetic activity are available for the treatment of hypertension in diabetic subjects. Opinions on the potential advantages of the metabolic profile of some of these drugs are as yet conflicting.

Attaining role confirmation in nurse practitioner practice.

Although nurse practitioners (NPs) as a collective group have reached the stage of role confirmation, in new settings they must transition through several phases of role development. The role confirmation issues for a team of NPs who were hired to work in a large academic teaching hospital in the Southeastern part of the United States are explored over a 3-year period. Characteristics of the organization and strategies that the NPs implemented over time impacted favorably on the evolution of the NP role in that setting. The NPs gained prescriptive privileges, independent practice, and market-place salaries. Effective negotiation and marketing strategies enhanced both personal and professional development.

The effect of captopril on the superior mesenteric artery and portal venous blood flow in normal man.

1. Measurements of superior mesenteric artery and portal venous blood flow were made non-invasively along with systemic and other regional (cardiac index, forearm and cutaneous blood flow) vascular responses to acute ingestion of the ACE inhibitor captopril (50 mg) or placebo (50 mg vitamin C), in 12 healthy subjects while supine and during head-up tilt. 2. After captopril, superior mesenteric artery and portal blood flow rose markedly with a reduction in superior mesenteric artery vascular resistance. Supine blood pressure was unchanged but cardiac index and forearm blood flow rose; during head-up tilt, blood pressure fell in some subjects. 3. There was a rise in levels of plasma renin activity and a fall in levels of plasma angiotensin II after captopril. After placebo, there were no significant changes in splanchnic blood flow, systemic or other regional responses and in biochemical measurements, while supine. 4. Our studies indicate that captopril is a potent dilator of the splanchnic vascular bed and suggest that this action may contribute to its therapeutic effects. The studies indicate a role for angiotensin II in the control of this large vascular bed although other agents (bradykinin, prostacyclin) may contribute.

Differential responses in superior mesenteric artery blood flow may explain the variant pressor responses to clonidine in two groups with sympathetic denervation.

1. Measurement of superior mesenteric artery blood flow along with systemic and regional haemodynamic changes in blood pressure, heart rate, cardiac index, forearm blood flow, digital skin blood flow and index finger temperature were made before and after administration of clonidine (2 micrograms/kg body weight intravenously) in 10 patients with multiple-system atrophy, 10 patients with pure autonomic failure and 15 age-matched healthy control subjects. 2. After clonidine, blood pressure fell in patients with multiple-system atrophy and control subjects but not in patients with pure autonomic failure. 3. Resting superior mesenteric artery blood flow was similar in patients with multiple-system atrophy and control subjects, but was higher in patients with pure autonomic failure. The fall in blood pressure after clonidine was accompanied by active dilatation of the superior mesenteric artery in patients with multiple-system atrophy and control subjects. This did not occur in patients with pure autonomic failure. 4. After clonidine, there was a fall in cardiac index in patients with multiple-system atrophy. 5. After clonidine, changes in other haemodynamic parameters were not significant in any group, except for a fall in forearm blood flow and a rise in index finger temperature in control subjects. 6. We conclude that after clonidine there are differential superior mesenteric artery blood flow responses in the two groups with autonomic failure (multiple-system atrophy and pure autonomic failure). These may relate to differences in the site of the sympathetic lesion, which is considered to be mainly central in multiple-system atrophy but peripheral in pure autonomic failure.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of autonomic neuropathy on hypotension during hemodialysis.

UNLABELLED: Many patients with chronic renal failure experience profound hypotension during hemodialysis. This phenomenon may be caused by hypovolemia, autonomic or cardiac dysfunction, vascular resistance defects or vasoactive substances such as nitric oxide or adrenomedullin. The aim of the study was to evaluate the influence of autonomic neuropathy on the occurrence of hypotension during hemodialysis. Fifty-three patients with chronic renal failure on maintenance hemodialysis underwent a standard battery of cardiovascular tests for the diagnosis of autonomic neuropathy. The study population was then divided into two groups, with (AN+) and without (AN-) autonomic neuropathy. Blood pressure (BP) was recorded before, during and after hemodialysis for 10 consecutive dialysis sessions and the mean value was calculated. RESULTS: Of the patients, 38% were AN+. During hemodialysis, systolic BP was lower in AN+ than in AN- patients at the third hour (110.0 +/- 17.5 vs 128.0 +/- 26.2; p = 0.049). Systolic BP reduction during hemodialysis was greater in AN+ than AN-patients (-21.2 +/- 10.9 vs -13.5 +/- 10.6% change, p = 0.013). CONCLUSION: The presence of autonomic neuropathy is associated with a more severe BP fall during hemodialysis. Routine evaluation of autonomic function may be helpful in defining patients at risk for dialysis-induced hypotension.

[Is it possible to prevent andrological complications in the diabetic patient?]. / Si possono prevenire le complicanze andrologiche nel paziente diabetico?

Sexual impotence is the main andrological complication of diabetes mellitus and is the consequence of nervous, vascular and psychological factors which act either separately or in association. An attempt to prevent this complication will be successful if performed early before impotence has became irreversible. Neuropathy-induced impotence can be prevented by obtaining a good metabolic control of diabetes and/or by using some specific drugs such as gangliosides and aldose reductase inhibitors. The vascular causes of erectile failure can be prevented by reducing or removing associated risk factors such as smoking, hypertension, obesity, hypercholesterolemia, sedentariness and insulin-resistance. Finally, correct information and reassurance of the patient and his partner can prevent the negative role played by psychological factors on the sexual dysfunctions complained by the diabetic subject.

The effects of exposure to moderate altitude on cardiovascular autonomic function in normal subjects.

Cardiovascular responses to altitude have been studied on well-trained young subjects, generally at high altitudes (>4000 m). Less known are the effects of exposure to lower altitudes, easily reached by the general population. The aim of the study was to evaluate the effects of exposure to a moderate altitude (2950 m) on heart rate (HR), blood pressure (BP) profile, and cardiovascular autonomic function, and their correlation with hemoglobin oxygen saturation (HbO2S), in untrained subjects of a wide age range. Twenty-seven healthy normotensive subjects (age range 6-83; 8 children, 9 adults, and 10 elderly subjects) underwent a battery of noninvasive cardiovascular reflex tests and 24-h ambulatory BP monitoring. Corrected QT interval was also calculated. HbO2S was measured with a transcutaneous oxymeter. All measurements were performed at about 200 m (s.l.) and repeated at 2950 m. 24-h HR and systolic/diastolic BP mean values increased at 2950 m in children (% change respectively: 6.4 +/- 6.4, p<0.05; 6.5 +/- 4.0/13.5 +/- 6.9, p < 0.05), adults (4.9 +/- 8.1, NS; 6.0 +/- 5.1/8.1 +/- 5.8, p < 0.05), and elderly subjects (7.2 +/- 4.8, p < 0.05; 5.1 +/- 2.3/2.8 +/- 4.1, p < 0.05 for systolic BP only). Standard deviation of BP mean values increased during night-time in the adult group (p < 0.05). All subjects scored normal cardiovascular test results and no differences were observed after exposure to 2950m, at both 1 hour and 24 hours from arrival. After exposure to altitude, HbO2S decreased significantly in the three groups, both on arrival and after 24 hours. No correlation was found between changes in HbO2S and BP/HR responses, and cardiovascular test results. In conclusion, exposure to moderate altitudes, easily and often reached by the general population, causes a small but significant increase in BP and HR in healthy untrained subjects of a wide age range (6-83 years). Some physiological factors (eg, lower environmental temperature and lifestyle modification) together with hypoxia, possibly more than altered cardiovascular reactivity, seem responsible for this cardiovascular change. In terms of end-organ damage, the clinical relevance of this increase in BP and BP variability for repeated exposure is not known.

Effects of oral alcohol on superior mesenteric artery blood flow in normal man, horizontal and tilted.

1. The cardiovascular effects of oral alcohol (0.5 g/kg body weight diluted to 300 ml in sugar-free orange juice) were compared with those of placebo in 10 normal subjects. Measurements were made while the subjects were supine and horizontal for 45 min and after 10 min of 45 degrees head-up tilt. 2. After alcohol, plasma alcohol levels rose from 1.9 +/- 1.3 to 61.6 +/- 6.5 mg/100 ml. After placebo, plasma alcohol levels did not increase. After alcohol and placebo, supine blood pressure was unchanged; heart rate, both supine and during tilt, rose after alcohol only. 3. After alcohol, superior mesenteric artery and digital skin blood flow increased and calculated vascular resistances fell. There was no change after placebo. 4. Forearm blood flow, forearm vascular resistance and cardiac index did not change in either phase, except for a fall in cardiac index during tilt but only after alcohol. 5. In conclusion, the acute ingestion of 0.5 g of alcohol/kg body weight in normal subjects raised heart rate and actively dilated the superior mesenteric artery and digital skin vessels. There was no effect on blood pressure, cardiac output and skeletal muscle vascular tone. During head-up tilt after alcohol, there was a tendency for blood pressure to fall with a compensatory rise in heart rate.