losartan-potassium and Hypotension--Orthostatic

Orthostatic hypotension is a common problem among elderly patients, associated with significant morbidity and mortality. While acute orthostatic hypotension is usually secondary to medication, fluid or blood loss, or adrenal insufficiency, chronic orthostatic hypotension is frequently due to altered blood pressure regulatory mechanisms and autonomic dysfunction. The diagnostic evaluation requires a comprehensive history including symptoms of autonomic nervous system dysfunction, careful blood pressure measurement at various times of the day and after meals or medications, and laboratory studies. Laboratory investigation and imaging studies should be based upon the initial findings with emphasis on excluding diagnoses of neurodegenerative diseases, amyloidosis, diabetes, anemia, and vitamin deficiency as the cause. Whereas asymptomatic patients usually need no treatment, those with symptoms often benefit from a stepped approach with initial nonpharmacological interventions, including avoidance of potentially hypotensive medications and use of physical counter maneuvers. If these measures prove inadequate and the patient remains persistently symptomatic, various pharmacotherapeutic agents can be added, including fludrocortisone, midodrine, and nonsteroidal anti-inflammatory drugs. The goals of treatment are to improve symptoms and to make the patient as ambulatory as possible rather then trying to achieve arbitrary blood pressure goals. With proper evaluation and management, the occurrence of adverse events, including falls, fracture, functional decline, and myocardial ischemia, can be significantly reduced.

Topics: Adrenergic alpha-Agonists; Aged; Aged, 80 and over; Aging; Anti-Inflammatory Agents; Blood Pressure Determination; Caffeine; Central Nervous System Stimulants; Dose-Response Relationship, Drug; Erythropoietin; Fludrocortisone; Geriatrics; Humans; Hypotension, Orthostatic; Midodrine; Posture; Prevalence; Prostaglandin Antagonists; Risk Reduction Behavior; United States

Topics: Anemia; Erythropoietin; Humans; Hypotension, Orthostatic

We experienced a patient on continuous ambulatory peritoneal dialysis (CAPD) who showed hypererythropoietinemia (Epo concentration: 86.7 mU/ml, normal range: 8-36 mU/ml), erythrocytosis, high renin concentration (26.5 pg/ml) and chronic hypotension. In this patient the erythrocytosis progressed along with exacerbation of the chronic severe hypotensive state. This patient had systemic circulatory insufficiency as suggested by the fact that he had a fibrous myocardium and an increased anion gap. We hypothesized that circulatory insufficiency due to chronic severe hypotension may lead to the stimulation of the Epo production, due to a decreased oxygen supply to peripheral tissues and/or to the stimulation of the renin angiotensin system even in patients with end-stage renal failure.

Topics: Aged; Chronic Disease; Erythropoietin; Fatal Outcome; Humans; Hypotension, Orthostatic; Kidney; Kidney Failure, Chronic; Male; Myocardium; Peritoneal Dialysis, Continuous Ambulatory; Renin

Many of the physiologic consequences of weightlessness and the cardiovascular abnormalities on return from space could be due, at least in part, to alterations in the regulation of the autonomic nervous system. In this article, the authors review the rationale and evidence for an autonomic mediation of diverse changes that occur with spaceflight, including the anemia and hypovolemia of weightlessness and the tachycardia and orthostatic intolerance on return from space. This hypothesis is supported by studies of two groups of persons known to have low catecholamine levels: persons subjected to prolonged bedrest and persons with syndromes characterized by low circulating catecholamines (Bradbury-Eggleston syndrome and dopamine beta-hydroxylase deficiency). Both groups exhibit the symptoms mentioned. The increasing evidence that autonomic mechanisms underlie many of the physiologic consequences of weightlessness suggests that new pharmacologic approaches (such as administration of beta-blockers and/or sympathomimetic amines) based on these findings may attenuate these unwanted effects.

Topics: Anemia; Blood Volume; Catecholamines; Erythropoietin; Heart Rate; Humans; Hypotension, Orthostatic; Kidney; Posture; Receptors, Adrenergic; Space Flight; Sympathetic Nervous System; Weightlessness

Topics: Adult; Anemia; Blood Pressure; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Erythropoietin; Female; Follow-Up Studies; Humans; Hypotension, Orthostatic; Middle Aged; Recombinant Proteins; Time Factors

Anemia is a common complication of autonomic failure and reduced red blood cell mass may contribute to the orthostatic hypotension of these patients. We investigated whether treatment with recombinant erythropoietin improves anemia and increases blood pressure in patients with primary autonomic failure. Three patients with multiple system atrophy and autonomic failure and one with pure autonomic failure were studied. All patients had normocytic normochromic anemia and low (n = 2) or normal (n = 2) serum levels of erythropoietin. Treatment with erythropoietin, 4000 U subcutaneously biweekly for 6 weeks, increased hematocrit and blood pressure in all patients. Hematocrit increased from 33.9 +/- 0.7 to 44.3 +/- 1.4%, blood pressure in supine position increased from 150 +/- 8/87 +/- 8 (systolic/diastolic; mean +/- SD) to 166 +/- 25/92 +/- 12 mmHg, and after 3 min in the head-up tilt position from 86 +/- 21/47 +/- 15 to 102 +/- 23/63 +/- 12 mmHg, (p < 0.05). All patients reported improvement in orthostatic symptoms and increased tolerance to standing. The study shows that treatment with erythropoietin improves anemia, increases blood pressure and ameliorates orthostatic hypotension in patients with primary autonomic failure.

Topics: Aged; Anemia; Autonomic Nervous System Diseases; Blood Pressure; Erythropoietin; Female; Heart Rate; Hematocrit; Hemoglobins; Humans; Hypotension, Orthostatic; Male; Middle Aged; Recombinant Proteins

Impaired orthostatic blood pressure (BP) stabilization is prevalent in patients with chronic kidney disease (CKD) and is associated with adverse outcomes. We aimed to test the hypothesis that reduced hemoglobin is an important contributor to orthostatic intolerance in CKD in the present study. This study included 262 patients with non-dialysis-dependent CKD. Seated and standing BP was measured, and orthostatic BP reduction was calculated for both systolic BP (∆ SBP) and diastolic BP (∆ DBP). The association between orthostatic BP reduction and hemoglobin was determined by multiple linear regression models. We also performed mediation analysis to test to what extent the effect of renal dysfunction on impaired orthostatic BP stabilization can be explained by reduced hemoglobin. The mean age of the patients was 57.7 (±14.5) years, and 61.5% were male. Both ∆ SBP and ∆ DBP correlated negatively with estimated glomerular filtration rate (eGFR). With adjustment for age and sex, hemoglobin level was negatively associated with ∆ SBP (β = -1.4, SE = 0.4, P < .001) and ∆ DBP (β = -0.6, SE = 0.2, P = .009). The associations remained significant with further adjustment for additional covariates. When eGFR was introduced as a covariate, it did not eliminate the significance (both P < .05). The associations remained essentially unchanged in a sensitivity analysis excluding those with concurrent erythropoietin use. Mediation analysis demonstrated that reduced hemoglobin accounted for 35.4% (P = .004) of the effect of eGFR on ∆ SBP and 47.7% (P = .032) on ∆ DBP. Our study suggests that reduced hemoglobin is a potentially important contributor to the development of orthostatic hypotension in CKD.

Topics: Adult; Aged; Blood Pressure; Blood Pressure Determination; Case-Control Studies; China; Cross-Sectional Studies; Erythropoietin; Female; Glomerular Filtration Rate; Hemoglobins; Humans; Hypotension, Orthostatic; Male; Middle Aged; Posture; Prevalence; Pulse Wave Analysis; Renal Insufficiency, Chronic

Erythropoietin (EPO)-deficient anaemia has been described in Type 1 diabetic patients with both severe autonomic neuropathy (AN) and proteinuria. This study was aimed at distinguishing between the effects of AN and nephropathy on haemoglobin and EPO levels in Type 2 diabetic patients at an early stage of diabetic nephropathy.. In 64 Type 2 diabetic patients (age 52 +/- 10 years, duration 10 +/- 9 years) without overt nephropathy and other causes of anaemia or EPO deficit, we assessed cardiovascular tests of AN, 24-h blood pressure (BP) monitoring, urinary albumin excretion rate (UAE), a full blood count, and serum EPO.. Although the Type 2 diabetic patients with AN did not show differences in haemoglobin and EPO when compared with patients without AN, the presence of haemoglobin < 13 g/dl was associated with the presence of AN (chi(2)= 3.9, P < 0.05) and of postural hypotension (chi(2)= 7.8, P < 0.05). In a multiple regression analysis including as independent variables gender, body mass index, duration of diabetes, smoking, creatinine, 24-h UAE, 24-h diastolic BP, ferritin, erythrocyte sedimentation rate, and autonomic score, we found that the only variables independently related to haematocrit were autonomic score, ferritin and erythrocyte sedimentation rate. Finally, the physiological inverse relationship between EPO and haemoglobin present in a control group of 42 non-diabetic non-anaemic subjects was completely lost in Type 2 diabetic patients. The slopes of the regression lines between EPO and haemoglobin of the control subjects and the Type 2 diabetic patients were significantly different (t = 14.4, P < 0.0001).. This study documents an early abnormality of EPO regulation in Type 2 diabetes before clinical nephropathy and points to a contributory role of AN in EPO dysregulation.

Topics: Adult; Aged; Albuminuria; Autonomic Nervous System Diseases; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Erythropoietin; Female; Hemoglobins; Humans; Hypotension, Orthostatic; Male; Middle Aged

A 71-year-old man, who was diagnosed with familial amyloidosis type I, was admitted for treatment of severe orthostatic hypotension associated with recurrent syncopal attacks. Head-up tilt testing demonstrated severe orthostatic hypotension (114/72 mmHg in the supine position and 62/34 mmHg in the upright position) with syncope or presyncope. Oral midodorine and fludrocortisone therapies failed to prevent his symptoms. After administration of subcutaneous erythropoietin, his blood pressure drop in the upright position was decreased and symptoms disappeared unassociated with improvement of anemia. Although previous reports have shown that the mechanism by which erythropoietin improves orthostatic hypotension is related to improvement in anemia, other mechanisms may also play a role.

Topics: Aged; Amyloid Neuropathies, Familial; Blood Pressure; Erythropoietin; Humans; Hypotension, Orthostatic; Male; Recombinant Proteins; Syncope; Tilt-Table Test

A 47-year-old man with a known and substituted vitamin B12 deficiency presented with increasing symptoms associated with orthostatic hypotension, neck pain and micturitional and visual disturbances.. Catecholamines were strongly reduced in plasma and urine.. A pure autonomic failure was diagnosed and therapy with fludrocortisone, yohimbine and erythropoetine was started. Symptoms with the exception of micturitional disturbances improved strongly.. Multiple-drug treatment of pure autonomic failure is successful. The prognosis is good.

Topics: Adrenergic alpha-Antagonists; Anemia, Pernicious; Autonomic Nervous System Diseases; Blood Pressure; Catecholamines; Diagnosis, Differential; Drug Therapy, Combination; Erythropoietin; Fludrocortisone; Humans; Hypotension, Orthostatic; Male; Middle Aged; Mineralocorticoids; Neck Pain; Prognosis; Pulse; Urination Disorders; Vision Disorders; Vitamin B 12; Yohimbine

Serum erythropoietin (EPO) levels are partially controlled by the sympathetic outflow to the kidney. We have studied whether patients with multiple system atrophy (MSA), known to be associated with dysautonomia, are EPO-deficient. Eighteen MSA patients were studied along with 32 idiopathic Parkinson's disease (PD) patients, 23 controls with iron-deficiency anaemia, and 18 healthy individuals. Serum creatinine was normal in all groups. Mean haemoglobin (Hb) concentration in MSA patients was 13.7 +/- 1.7 g/dL. Four MSA patients had unexplained anaemia (minimum Hb: 10.5 g/dL) and abnormal autonomic function tests including significant postural hypotension, whereas none of the PD patients was anaemic. Serum EPO levels were suppressed in relation to anaemia in MSA patients compared to elevated EPO levels in iron-deficiency anaemia patients (difference of regression lines P < 0.001), indicating EPO deficiency in the anaemic MSA patients. Serum EPO levels in PD patients were within normal range. A subset of MSA patients has anaemia and postural hypotension, which may be associated with EPO deficiency. This may have therapeutic implications.

Topics: Anemia; Autonomic Nervous System Diseases; Cardiovascular System; Creatinine; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Heart Rate; Hemoglobins; Humans; Hypotension, Orthostatic; Male; Middle Aged; Multiple System Atrophy; Severity of Illness Index

We report the case of a 52-year-old woman with long-term type 1 diabetes mellitus, complicated with proliferative retinopathy, autonomic neuropathy and microalbuminuria and moderate renal failure. A normochromic, normocytic are generative anaemia had been diagnosed for three years. Clinical and biological investigations for the aetiology of anaemia remained normal or negative. Anaemia was associated with a concentration of erythropoietin (EPO) in the normal range, but inappropriately low regarding anaemia. Treatment with recombinant EPO induced a rapid increase in haemoglobin level and improved the patient's quality of life. The role of diabetic neuropathy in the genesis of anaemia, in conjunction with a modest renal impairment is discussed.

Topics: Albuminuria; Anemia; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Electrocardiography; Erythropoietin; Female; Hemoglobins; Humans; Hypotension, Orthostatic; Kidney Failure, Chronic; Middle Aged; Quality of Life; Recombinant Proteins

Previous studies have reported that anemia is a frequent occurrence in patients with severe autonomic failure, that it can be corrected by exogenous erythropoietin and that upright blood pressure improves while on erythropoietin. The objective of this study was to determine the alteration of autonomic control during erythropoietin therapy in a patient with severe autonomic failure and severe symptomatic orthostatic hypotension, evaluated by spectral analysis of heart rate variability. The autonomic response to standing was evaluated before, after 1 month and after 6 months of erythropoietin therapy. The results were compared to an age- and sex-matched control adult. There was no improvement in the orthostatic hypotension during and at the end of the erythropoietin treatment despite an increase in hemoglobin from 9.6 g/dl before treatment to 12.5 g/dl during treatment. The spectral estimates of heart rate variability displayed a low variability at baseline, a paradoxical vagal enhancement and a lack of sympathetic increase on standing (before, during and at the end of the treatment). There was no improvement of baseline activity, nor of the response to standing during and at the end of the treatment with erythropoietin. We conclude that erythropoietin did not improve the autonomic response to standing, although it corrected anemia. Erythropoietin did not alter sympathetic activity, as reflected in the low frequency content of the power spectrum of heart rate fluctuations during and at the end of treatment.

Topics: Autonomic Nervous System Diseases; Erythropoietin; Female; Humans; Hypotension, Orthostatic; Middle Aged; Treatment Failure

Topics: Aged; Autonomic Nervous System Diseases; Erythrocyte Volume; Erythropoietin; Female; Humans; Hypotension, Orthostatic

We hypothesize that reduced sympathetic stimulation of erythropoietin production may maintain the anemia which develops in virtually all space travellers. We tested this hypothesis in a human model of reduced sympathetic activity. Thirty-three patients with the Bradbury-Eggleston syndrome were divided into three groups according to their hemoglobin (Hgb) level. Patients with low Hgb had lower upright norepinephrine and lower upright renin. Patients with anemia also had inappropriately low plasma erythropoietin levels. We administered recombinant erythropoietin (Epogen) 25-50 units/kg s.c. 3 times per week and found that the anemia seen in autonomic failure could be reversed by this treatment. These results support the hypothesis that erythropoiesis is modulated by the sympathetic nervous system and that at such mechanisms may also operate in the microgravity environment where sympathetic activity is reduced.

Topics: Anemia; Catecholamines; Epoetin Alfa; Erythrocyte Volume; Erythropoiesis; Erythropoietin; Humans; Hypotension, Orthostatic; Posture; Recombinant Proteins; Renin; Space Flight; Sympathetic Nervous System; Weightlessness

Patients with orthostatic hypotension caused by autonomic neuropathy frequently have a decreased red-cell mass. This would be expected to compromise their effective circulating blood volume and aggravate the orthostatic hypotension. We studied the effect of increasing the red-cell mass with erythropoietin, given subcutaneously in a dose of 50 U per kilogram of body weight three times a week for 6 to 10 weeks to eight patients with orthostatic hypotension--four men, one teenage boy, and three women (age range, 17 to 68 years). Four patients had type I diabetes mellitus and autonomic neuropathy, three patients had pure autonomic failure, and one patient had sympathotonic orthostatic hypotension. Seven patients received fludrocortisone (0.1 or 0.2 mg per day) before, during, and after the trial of erythropoietin. The red-cell volume, plasma volume, and hemodynamic response to orthostatic stress were measured before and after therapy.. Erythropoietin increased the mean (+/- SD) hematocrit from 0.34 +/- 0.04 to 0.45 +/- 0.04 (P < 0.005) and increased the red-cell volume from 16.8 +/- 3.9 to 25.3 +/- 3.1 ml per kilogram (P < 0.005), but had no effect on plasma volume. The systolic blood pressure increased from 81 +/- 11 to 100 +/- 24 mm Hg (P < 0.01) and the diastolic blood pressure increased from 46 +/- 10 to 63 +/- 18 mm Hg (P < 0.01) while the patients were standing. The average systolic and diastolic blood pressure while the patients were supine did not increase significantly, although hypertension in the supine position developed in three patients. Orthostatic dizziness improved during treatment in six of the eight patients.. In patients with orthostatic hypotension, increasing the red-cell volume with erythropoietin elevates blood pressure while standing. Possible long-term adverse effects are not known.

Topics: Adolescent; Adult; Aged; Autonomic Nervous System Diseases; Blood Pressure; Diabetic Neuropathies; Erythrocyte Volume; Erythropoietin; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Plasma Volume