Diabetic neuropathies, a family of nerve disorders caused by diabetes, affect about 60% to 70% of people with the disease. Diabetes is a persistent disease that impacts the way the body procedures blood glucose (glucose). The complex effect of the Valsalva maneuver on cardiovascular function is the basis of its usefulness as a measure of autonomic function. As some researchers have reported, the incidence of reduced HRV (measured using PSA) has been shown to be 15% in children (176). Diabetes and Parkinson's disease are two examples of . Recently, the administration of metoprolol to ramipril-treated type 1 diabetic patients with abnormal albuminuria has been shown to improve autonomic dysfunction (189). Gastroparesis should be suspected in individuals with erratic glucose control. Some investigators, however, have questioned whether the association between CAN and silent myocardial ischemia is a causal one (79), suggesting instead that underlying coronary artery disease might be a cause of both autonomic dysfunction and silent myocardial ischemia (80). Suarez GA, Kottke TE, Callahan MJ, Norell JE, OBrien PC, Dyck PJ: Is autonomic neuropathy an important cause of sudden death in diabetes mellitus? BP, blood pressure; CVD, cardiovascular disease; E:I difference = mean expiration to inspiration difference in R-R intervals over six consecutive breaths; R-R interval, time interval between successive ECG R-waves; sBP, systolic blood pressure. Careful examination of these studies suggests, however, that the relationship between autonomic neuropathy and hypoglycemic unawareness may be more complex than these reports suggest. (75) measured the anginal perceptual threshold (i.e., the time from onset of 0.1 mV ST depression to the onset of angina pectoris during exercise) in individuals with and without diabetes. Hilsted J, Jensen SB: A simple test for autonomic neuropathy in juvenile diabetics. Life-threatening symptoms, such as difficulty breathing or irregular heartbeat. There are several additional published studies that have examined the relationship between autonomic dysfunction and silent myocardial ischemia in diabetic individuals but that are not included in the meta-analysis because the raw numbers of case and control subjects among individuals with and without cardiovascular autonomic dysfunction were not presented (7578). A sudden transient increase in intrathoracic and intra-abdominal pressures, with a consequent hemodynamic response, results. The portion of the ANS concerned with conservation and restoration of energy. Disruption of microvascular skin blood flow and sudomotor function may be among the earliest manifestations of DAN and lead to dry skin, loss of sweating, and the development of fissures and cracks that allow microorganisms to enter. Burgos et al. It should be noted that half of the deaths in individuals with abnormal autonomic function tests were from renal failure, and 29% were from sudden death. The variance among prevalence studies also reflects the type and number of tests performed and the presence or absence of signs and symptoms of autonomic neuropathy. Evaluation of bladder dysfunction should be performed for individuals with diabetes who have recurrent urinary tract infections, pyelonephritis, incontinence, or a palpable bladder. Proactive measures are required, because if those patients at high risk or those shown to be in early stages are not treated until advanced symptomatology is present, little has been achieved. Alternately, excess nitric oxide production may result in formation of peroxynitrite and damage endothelium and neurons, a process referred to as nitrosative stress (14,15). Because of the technical requirements for these tests, they should be performed at the point-of-care office or in a clinical laboratory setting. A descriptive term meaning a demonstrable disorder, either clinically evident or subclinical, that occurs in the setting of diabetes mellitus without other causes for peripheral neuropathy. But people with this condition usually have a life expectancy of only about 5 to 10 . Low P, Lagerlund TD, McManis PG: Nerve blood flow and oxygen delivery in normal, diabetic, and ischemic neuropathy. American Diabetes Association and American Academy of Neurology: Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. In. DAN plausibly could cause or contribute to hypoglycemia unawareness, but this relationship is complex. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology: Heart rate variability: standards of measurement, physiological interpretation and clinical use. Mathias CJ, da Costa DF, Fosbraey P, Christensen NJ, Bannister R: Hypotensive and sedative effects of insulin in autonomic failure. Gerritsen J, Dekker JM, ten Voorde BJ, Kostense PJ, Heine RJ, Bouter LM, Heethaar RM, Stehouwer CD: Impaired autonomic function is associated with increased mortality, especially in subjects with diabetes, hypertension, or a history of cardiovascular disease: the Hoorn Study. This can lead to the death of almost 25 percent to 50 percent of people suffering from diabetic neuropathy, within a period as short as 5 to 10 years. Based on these findings, they suggested that there was no causal relation between DAN and unawareness of hypoglycemia or inadequate hypoglycemic counterregulation (142). Horrobin DF: Essential fatty acids in the management of impaired nerve function in diabetes. The Valsalva maneuver transiently increases intrathoracic, intraocular, and intracranial pressure, creating, for example, a small theoretical risk of intraocular hemorrhage and lens dislocation (163). Bosman DR, Osborne CA, Marsden JT, Macdougall IC, Gardner WN, Watkins PJ: Erythropoietin response to hypoxia in patients with diabetic autonomic neuropathy and non-diabetic chronic renal failure. Autonomic neuropathy affects the autonomic nerves, which control the bladder, intestinal tract, and genitals, among other organs. Orthostatic hypotension is defined as a fall in blood pressure (i.e., >20 mmHg for systolic or >10 mmHg for diastolic blood pressure) in response to postural change, from supine to standing (51). : Changes in autonomic nervous function during the 4-year follow-up in middle-aged diabetic and nondiabetic subjects initially free of coronary heart disease. Double-isotope scintigraphy to measure solid-phase gastric emptying; this requires ingestion of a solid labeled with radionuclides. : Diabetic autonomic neuropathy: the prevalence of impaired heart rate variability in a geographically defined population. Spectral indexes were power and density and were compared with standard Ewing tests of HRV (I:E difference, Valsalva ratio, and 30:15 ratio). GI manifestations of DAN are diverse, and symptoms and pathogenic mechanisms have been categorized according to which section of the GI tract is affected: Esophageal enteropathy (disordered peristalsis, abnormal lower esophageal sphincter function), Gastroparesis diabeticorum (nonobstructive impairment of gastric propulsive activity; brady/tachygastria, pylorospasm), Diarrhea (impaired motility of the small bowel [bacterial overgrowth syndrome], increased motility and secretory activity [pseudocholeretic diarrhea]), Constipation (dysfunction of intrinsic and extrinsic intestinal neurons, decreased or absent gastrocolic reflex), Fecal incontinence (abnormal internal anal sphincter tone, impaired rectal sensation, abnormal external sphincter). In healthy subjects, there is a characteristic and rapid increase in heart rate in response to standing that is maximal at approximately the 15th beat after standing. Upper-GI symptoms should lead to consideration of all possible causes, including autonomic dysfunction. Autonomic Dysfunction - Autonomic dysfunction is a type of diabetic neuropathy that affects the autonomic nerves that regulate blood pressure and heart rate. In a study by Levitt et al. The orthostatic stress of tilting evokes a sequence of compensatory cardiovascular responses to maintain homeostasis. This test can be used to determine sweat gland density, sweat droplet size, and sweat volume per area. Intensive therapy can slow the progression and delay the appearance of abnormal autonomic function tests (37). This can lead to the death of almost 25 percent to 50 percent of people suffering from diabetic neuropathy, within a period as short as 5 to 10 years. Kahn JK, Sisson JC, Vinik AI: Prediction of sudden cardiac death in diabetic autonomic neuropathy. Improved nutrition and reduced alcohol and tobacco consumption are additional options available to patients with diabetes who are identified with autonomic nerve dysfunction. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB: Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. Results of parasympathetic tests (1,2,3) were scored 0 = normal, 1 = borderline, 2 = abnormal. The impact of autonomic dysfunction on the risk of the development of strokes was examined by Toyry et al. Autonomic Neuropathy Life Expectancy (Prognosis) What is end stage neuropathy? A large body of evidence indicates that these factors can, to various degrees, affect the cardiovascular ANS and potentially other autonomic organ systems (157). Independent tests of both parasympathetic and sympathetic function should be performed. There is a predominately peripheral component, but pain generates a centrally mediated response. Learn about complications of diabetes and how they affect your well-being. The most advanced Autonomic test patterns of weak Parasympathetic function are Diabetic Autonomic Neuropathy (DAN), and Cardiac Autonomic Neuropathy (CAN) which has a 50% mortality rate within 5 years. Relative risk = 2.25 (1.134.45); diabetic subjects (, Unique diagnostic criteria defined by scoring 3 or more, Copyright American Diabetes Association. Finally, knowledge of early autonomic dysfunction can encourage patient and physician to improve metabolic control and to use therapies such as ACE inhibitors and -blockers, proven to be effective for patients with CAN. It is important to note that tests that specifically evaluate cardiovascular autonomic function are part of the consensus guidelines. DCCT Research Group: The effect of intensive diabetes therapy on measures of autonomic nervous system function in the Diabetes Control and Complications Trial (DCCT). One of the most overlooked of all serious complications of diabetes is cardiovascular autonomic neuropathy (CAN), 1-3 which encompasses damage to the autonomic nerve fibers that innervate the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics. Clark CM, Vinicor F: Introduction: Risks and benefits of intensive management in non-insulin-dependent diabetes mellitus: the fifth Regenstrief conference. Identifying individuals at risk is only the first step in managing patients and ultimately affecting outcomes. Since the symptoms are so . Retrograde ejaculation into the bladder also occurs in diabetic males. The response to standing is mediated by sympathetic nerve fibers. Case-control study of transplant recipients (pancreas-kidney or kidney alone). These tests include the quantitative sudomotor axon reflex test (QSART), the sweat imprint, the thermoregulatory sweat test (TST), and the sympathetic skin response. Benadryl (diphenhydramine). The response to performance of the Valsalva maneuver has four phases and in healthy individuals can be observed as follows: Phase I: Transient rise in blood pressure and a fall in heart rate due to compression of the aorta and propulsion of blood into the peripheral circulation. (156) suggested that the significant relationship between reduced bone mineral density and severity of diabetic neuropathy in the lower extremities of individuals with Charcot neuroarthropathy may reflect the severity of autonomic neuropathy. OBrien IA, OHare JP, Lewin IG, Corrall RJ: The prevalence of autonomic neuropathy in insulin-dependent diabetes: a controlled study based on heart rate variability. Maser RE, Mitchell BD, Vinik AI, Freeman R: The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes. Once diagnosed, treatment may include withdrawal from offending medications coupled with psychological counseling, medical treatment, or surgery. These changes ultimately contribute to the development of ulcers, gangrene, and limb loss. Patients with DAN are more likely to exhibit only a small diastolic blood pressure rise. There is no response in the presence of either a proximal or distal ANS lesion. A: Association of CAN and mortality in 15 studies. To detect abnormalities, the nurse can assess the patient's sensations, reflexes, and response to stimuli. In addition, trials of gluten-free diet, restriction of lactose, cholestyramine, clonidine, somatostatin analog, pancreatic enzyme supplements, and antibiotics such as metronidazole may be indicated. Reduced heart rate variation is the earliest indicator of CAN (44). Pacher P, Liaudet L, Soriano FG, Mabley JG, Szabo E, Szabo C: The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes. By opposing the sympathetic stimulus, they may restore the parasympathetic-sympathetic balance. A total of 16 individuals did not experience angina, and 10 of these had diabetes. Because late stages of CAN are indicators of poor prognosis in diabetic patients, early prognostic capabilities offer a significant contribution to diagnosis and subsequent therapy. Therefore the amount of time one can live with peripheral neuropathy is much determined by the . There are differences in the glabrous and hairy skin circulations. Blood pressure normally changes only slightly on standing from a sitting or supine position. Worldwide, it affects more than 70 million people. Results of parasympathetic tests (1,2,3) were scored 0 = normal, 1 = borderline, 2 = abnormal. Toyry JP, Niskanen LK, Lansimies EA, Partanen KPL, Uusitupa MIJ: Autonomic neuropathy predicts the development of stroke in patients with non-insulin-dependent diabetes mellitus. In people with diabetes, the body's capability to utilize or produce insulin, a hormone . The heart rate slows at or around the 30th beat. Greene DA, Lattimer SA, Sima AA: Are disturbances of sorbitol, phosphoinositide, and Na+-K+-ATPase regulation involved in pathogenesis of diabetic neuropathy? This measure, called the 30:15 ratio, reflects the overall condition of the parasympathetic fibers. : Heart rate variability and cardiovascular tests in young patients with diabetes mellitus type 1. Heating and gravity. (85) reported the results of a study designed to assess the risk of mortality due to CAN among patients with CAN but without a clinical manifestation of severe complications (proteinuria, proliferative retinopathy, coronary artery disease, or stroke) 8 years after their first clinical examination. Position paper: Orthostatic hypotension, multiple system atrophy (the Shy Drager syndrome) and pure autonomic failure. Xueli Z, Baidi Z, Guoxian H, Xixing Z, et al. Howorka K, Pumprla J, Schabmann A: Optimal parameters for short-term heart rate spectrogram for routine evaluation of diabetic cardiovascular autonomic neuropathy. The defect is associated with a reduction in the amplitude of vasomotion and resembles premature aging (153). Battle WM, Snape WJ Jr, Alavi A, Cohen S, Braunstein S: Colonic dysfunction in diabetes mellitus. I have breathing issues and arithmia's. My doctor refuses to discuss life expectancy. The blood glucose should be normal at the time of testing because hyperglycemia decreases gastric motility. The tests are valid as specific markers of autonomic neuropathy if end-organ failure has been carefully ruled out and other potential factors such as concomitant illness, drug use (including antidepressants, over-the-counter antihistamines and cough/cold preparations, diuretics, and aspirin), lifestyle issues (such as exercise, smoking, and caffeine intake), and age are taken into account. Sundkvist G: Autonomic nervous function in asymptomatic diabetic patients with signs of peripheral neuropathy. These data form the strongest body of evidence for the importance of detecting and monitoring impaired autonomic function in patients with diabetes (6,7). (108) showed that the presence of autonomic neuropathy contributed to a poor outcome in a study of 196 post-MI diabetic patients. Additionally, risk factors for type 2 . Even with mild symptoms, gastroparesis interferes with nutrient delivery to the small bowel and therefore disrupts the relationship between glucose absorption and exogenous insulin administration. Occasionally, anorectal manometry and other specialized tests typically performed by the gastroenterologist may be helpful. It is again emphasized that lifestyle interventions (e.g., adherence to diet and exercise) can reduce the incidence of type 2 diabetes (174). Hormonal evaluation (luteinizing hormone, testosterone, free testosterone, prolactin), Psychological evaluation (Minnesota Multiphasic Personality Inventory [MMPI]). Specialized tests for the assessment of diabetic diarrhea will typically be performed by a gastroenterologist. Clinical manifestations of autonomic dysfunction and other microvascular complications frequently occur concurrently but in inconsistent patterns (41). . In some cases, no cause can be identified and this is termed idiopathic neuropathy. Ewing DJ, Campbell IW, Clark BF: Assessment of cardiovascular effects in diabetic autonomic neuropathy and prognostic implications. Those with CAN had greater prevalence of other complications, but in multivariate analysis, CAN was the most important predictor of mortality. Pharmacological blockade studies using atropine, phentolamine (an -adrenergic antagonist), and propranolol (a nonspecific -adrenergic blocker) confirm dual involvement of autonomic nerve branches for the response to this maneuver by demonstrating the drugs varied effects of attenuation or augmentation of the hemodynamic response to the maneuver at specific times during the response (162). Long-term follow-up studies are needed to distinguish the exact roles of cardiovascular risk factors, nephropathy, and CAN in the etiology of cardiovascular disease. Major clinical manifestations of DAN include resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastroparesis, erectile dysfunction, sudomotor dysfunction, impaired neurovascular function, brittle diabetes, and hypoglycemic autonomic failure. The main advantage of power spectral analysis (PSA) is that HRV can be measured across a range of frequencies and that less patient participation is necessary (165). (177) demonstrated that early puberty is a critical period for the development of CAN and suggested that all type 1 diabetic patients should be screened for CAN beginning at the first stage of puberty. (50) showed that some diabetic patients with autonomic neuropathy have a reduced hypoxic-induced ventilatory drive. A study by OBrien (36) reported 5-year mortality rates of 27% in patients having asymptomatic autonomic neuropathy compared with an 8% mortality rate in diabetic subjects with normal autonomic function tests. The hemodynamic response to standing is a commonly performed measure of autonomic function. The reported prevalence of DAN varies widely depending on the cohort studied and the methods of assessment. Massin et al. Life Expectancy Of Someone With Autonomic Neuropathy. The prevalence of autonomic neuropathy in this study is very similar to the reported prevalence of diabetic peripheral neuropathy (66% in type 1; 59% in type 2) . Ziegler D, Laux G, Dannehl K, Spuler M, et al. Diabetic cystopathy manifests as an increase in threshold of occurrence of a detrusor reflex contraction. Massin MM, Derkenne B, Tallsund M, Rocour-Brumioul D, Ernould C, Lebrethon MC, Bourguignon JP: Cardiac autonomic dysfunction in diabetic children. Additional complicating factors include the wide variety of clinical syndromes and confounding variables such as age, sex, duration of diabetes, glycemic control, diabetes type, height, and other factors. It is known to cause inflammation throughout the body, affecting several body systems. Defective blood flow in the small capillary circulation is found with decreased responsiveness to mental arithmetic, cold pressor, handgrip, and heating. Neither age nor type of diabetes are limiting factors in its emergence, being found in young individuals with newly diagnosed type 1 diabetes and older individuals newly diagnosed with type 2 diabetes (5,24,40,44,113,114). Among individuals who died, there was no difference in duration of diabetes between those with and without autonomic neuropathy. Blaivas JG: The neurophysiology of micturition: a clinical study of 550 patients. . The neurogenic bladder, also called cystopathy, may be due to DAN (62). It causes a reduction in heart rate and blood pressure, facilitates the digestion and absorption of nutrients, and facilitates the excretion of waste products from the body. An expert panel from the AAN reviewed a number of standardized measures and found that noninvasive autonomic tests were found to have a high value-to-risk ratio (163). In the standard Valsalva maneuver, the supine patient, connected to an ECG monitor, forcibly exhales for 15 s against a fixed resistance with an open glottis. This can be performed on short R-R sequences (e.g., 7 min) or on 24-h ECG recordings. The evaluation might include the following: Postvoid ultrasound to assess residual volume and upper-urinary tract dilation, Cystometry and voiding cystometrogram to measure bladder sensation and volume pressure changes associated with bladder filling with known volumes of water and voiding. Karavanaki K, Baum JD: Prevalence of microvascular and neurologic abnormalities in a population of diabetic children. Such symptoms can result in injuries from falling. Less frequently, there is a rise in norepinephrine that may be due to low blood volume or reduced red cell mass (55,56). Pfeifer MA, Cook D, Brodsky J, Tice D, Reenan A, Swedine S, Halter JB, Porte D Jr: Quantitative evaluation of cardiac parasympathetic activity in normal and diabetic man. Hilsted J, Parving HH, Christensen NJ, Benn J, Galbo H: Hemodynamics in diabetic orthostatic hypotension. I have all of the above the autonomic affects my digestion making it impossible to control blood sugars. Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes. Patients with orthostatic hypotension typically present with lightheadedness and presyncopal symptoms. Females with diabetes may have decreased sexual desire and increased pain during intercourse and are at risk of decreased sexual arousal and inadequate lubrication (139). Young MJ, Marshall A, Adams JE, Selby PL, Boulton AJM: Osteopenia, neurological dysfunction, and the development of charcot neuroarthropathy. In this study, conventional methods to calculate max-min, standard deviation, E:I ratio, Valsalva ratio, and 30:15 ratio were used, as were those for the low-frequency (0.020.15 Hz) and high-frequency (0.151.0 Hz) power for the heart rate power spectra of 15 type 1 diabetic patients. Examination features include mild sensory deficits to pain and temperature. Cardiovascular autonomic neuropathy (CAN) is the most studied and clinically important form of DAN. There is a fall in cardiac output due to impaired venous return causing compensatory cardiac acceleration, increased muscle sympathetic activity, and peripheral resistance. Diabetic autonomic neuropathy is dysfunction of the autonomic nervous system (parasympathetic, sympathetic, or both) . Zarich S, Waxman S, Freeman RT, Mittleman M, Hegarty P, Nesto RW: Effect of autonomic nervous system dysfunction on the circadian pattern of myocardial ischemia in diabetes mellitus. Hypotheses concerning the multiple etiologies of diabetic neuropathy include a metabolic insult to nerve fibers, neurovascular insufficiency, autoimmune damage, and neurohormonal growth factor deficiency (8). Results from earlier research suggested that using a battery of cardiovascular tests (some indicating parasympathetic involvement and others indicating possible sympathetic involvement) would make it possible to follow the progression of autonomic function over time (30). The ANS is also responsible for conveying visceral sensation. Basic diagnostic tests include upper-GI endoscopy or barium series to rule out structural or mucosal abnormalities of the GI tract. All subjects were candidates for pancreas transplantation. This is due, in part, to the long-term commitment that must be made to the practice of preventive measures. Rathmann W, Ziegler D, Jahnke M, et al. In healthy subjects, there is an immediate pooling of blood in the dependent circulation resulting in a fall in blood pressure that is rapidly corrected by baroreflex-mediated peripheral vasoconstriction and tachycardia. This disorder results from damage to the fibers of the ANS with associated abnormalities of heart rate control and vascular dynamics. QTc prolongation was associated with increased mortality risk. Pfeifer MA, Weinberg CR, Cook DL, Reenan A, Halter JB, Ensinck JW, Porte D Jr: Autonomic neural dysfunction in recently diagnosed diabetic subjects. Damage to peripheral nerves may impair sensation, movement, gland, or organ function depending on which nerves are affected; in other words, neuropathy affecting motor, sensory, or autonomic nerves result in different symptoms. Based on these data, they suggested that loss of hypoglycemia awareness is not invariably associated with abnormal cardiovascular autonomic function tests. The specificity is low, however, because it is not able to differentiate between pre- and postganglionic causes of anhidrosis. Overt signs and symptoms of autonomic disease fall into one or more of the following categories. This may be accomplished by means of segmental transit of radiopaque markers that are ingested orally. In, Clinical Management of Diabetic Neuropathy. B: Log relative risks from the 15 studies. It comprises sympathetic, parasympathetic, and enteric nervous systems, which are three anatomically distinct divisions. Mortality in asymptomatic individuals with an isolated abnormality in autonomic function tests was not increased. (Abstract). Prevalence and mortality rates may be higher among individuals with type 2 diabetes, potentially due in part to longer duration of glycemic abnormalities before diagnosis. Treating or managing any underlying cause is key for treatment. Pelvic examination, with careful bimanual examination for women, Three stools tested for occult blood (which, if present, requires that a complete blood count, iron count, TIBG, proctosigmoidoscopy and barium enema, or full colonoscopy be performed). Some tests do, however, carry a small risk for an adverse event. Primary neurogenic causes refers to individuals with an underlying primary disorder that is involved with malfunction of the autonomic nervous system such as multiple system atrophy, Parkinson's disease, pure autonomic failure, dopamine beta-hydroxylase deficiency, Lewy body disease, familial dysautonomia, and non-diabetic autonomic neuropathy. Hemodynamic changes are mostly secondary to mechanical factors. Diabetic autonomic neuropathy is a serious complication of diabetes. The earliest bladder autonomic dysfunctions are sensory abnormalities that result in impaired bladder sensation, an elevated threshold for initiating the micturition reflex and an asymptomatic increase in bladder capacity and retention. But people with this condition usually have a life expectancy of only about 5 to 10 years from their diagnosis. These symptoms often vary depending on how long the nerves have been compressed and the level of damage they have sustained. Evidence from clinical literature can be found that support recommendations for various subpopulations. At least two of these three tests should be performed to provide adequate diagnostic information and to support reimbursement claims. R-R variation between supine and standing position, All subjects with overt diabetic nephropathy. The ability to determine early stages of autonomic dysfunction could intensify the salience of measures such as diet and exercise that directly affect efforts to establish tight glycemic control and delay the development of autonomic dysfunction. While recognizing the importance of clinical measures such as medical and neurological history and physical examination, conference participants also recognized the subjective nature of such measures and emphasized the importance of objective measures, including autonomic function tests in the case of autonomic neuropathy. What is the prognosis for autonomic neuropathy? BP, blood pressure; MCR, mean circular resultant.