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Jean-louis Montastruc - One of the best experts on this subject based on the ideXlab platform.
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Adrenergic supersensitivity in parkinsonians with Orthostatic Hypotension.
European Journal of Clinical Investigation, 2008Co-Authors: Jean-michel Senard, Jean-louis Montastruc, Philippe Valet, Geneviève Durrieu, Michel Berlan, Marie-antoinette Tran, André Rascol, Paul MontastrucAbstract:. The adrenergic status was studied through evaluation of platelet α2-adrenoceptor number ([3H]-yohimbine binding sites), plasma catecholamine levels and blood pressure response to noradrenaline infusion in three groups of subjects (1) Parkinsonians with Orthostatic Hypotension; (2) Parkinsonians without Orthostatic Hypotension; and (3) control subjects. In Parkinsonians with Orthostatic Hypotension, systolic and diastolic blood pressures significantly (P < 0.05) decreased from 144 pM 9 and 76 pM 6 mmHg in the lying position to 95 pM 12 and 60 pM 7 mmHg after 5 min standing. In these patients, noradrenaline plasma levels were significantly low (62 pM 11 pg ml-1, (P < 0.05) when compared with controls (219 pM 13 pg ml-1) whereas no difference was noticed in Parkinsonians without Orthostatic Hypotension (195 pM 14 pg ml-1). The noradrenaline dose required for a 25 mmHg increase in systolic blood pressure was significantly (P < 0.01) lower in Parkinsonians with Orthostatic Hypotension (019 pM 0.03 μg kg-1) when compared with Parkinsonians without Orthostatic Hypotension (0.86 pM 0.11 μg kg-1) or with controls (0.68 pM 0.l μg kg-1). Platelet x2-adrenoceptor number was higher in Parkinsonians with Orthostatic Hypotension (313 pM 52 fmol mg-1 protein) than in Parkinsonians without Orthostatic Hypotension (168 pM 9 fmol mg-1 protein) or in controls (175 pM 4 fmol mg-1 protein) with no change in Kd. This study demonstrates that in patients with Parkinson's disease, Orthostatic Hypotension is associated with an increase in both vascular sensitivity to noradrenaline and platelet α2-adrenoceptor number. These observations suggest the existence of an α-adrenergic supersensitivity in response to the low levels of plasma noradrenaline.
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Orthostatic Hypotension in Patients with Parkinson’s Disease
Drugs & Aging, 2001Co-Authors: Jean-michel Senard, O. Rascol, Christine Brefel-courbon, Jean-louis MontastrucAbstract:Orthostatic Hypotension is common in elderly patients, and is now considered to be an important prognostic factor for cognitive decline and mortality. In patients with Parkinson’s disease, the prevalence of symptomatic Orthostatic Hypotension may be as high as 20%. Two factors could explain this high prevalence. First, dopaminergic drugs may induce or worsen Orthostatic Hypotension. Secondly, Parkinson’s disease is a cause of primary autonomic failure with an involvement of the peripheral autonomic system as shown by the ubiquitous distribution of Lewy bodies and reduced iobenguane [metaiodobenzylguanidine (MIBG)] cardiac uptake. These pathological and pharmacological characteristics clearly differentiate autonomic failure of Parkinson’s disease from multiple system atrophy. If autonomic abnormalities appear to be present from the first stage of the disease, early onset (within the first year) of symptomatic Orthostatic Hypotension in the course of parkinsonism can be considered as an exclusion criteria for idiopathic Parkinson’s disease. No specific clinical trials have evaluated the effects of antihypotensive drugs in patients with Parkinson’s disease and thus no specific therapeutic strategy can be recommended. The management of Orthostatic Hypotension in patients with Parkinson’s disease should always start with patient education and nonpharmacological treatment. Drug therapy should be reserved for symptomatic patients who do not get benefit from nonpharmacological management. Among the available drugs, α_1-adrenergic agonists (mainly midodrine) or plasma volume expanders (mainly fludrocortisone) are the most frequently used. There are also some drugs that are currently investigational such as yohimbine and droxidopa. Other drugs such as desmopressin or octreotide may be of interest in some situations. Domperidone is widely used in patients with parkinsonism with no proven effect on Orthostatic Hypotension.
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Prevalence of Orthostatic Hypotension in Parkinson’s disease
Journal of Neurology Neurosurgery and Psychiatry, 1997Co-Authors: Jean-michel Senard, André Rascol, Maryse Lapeyre-mestre, C Brefel, O. Rascol, Jean-louis MontastrucAbstract:OBJECTIVES To investigate the prevalence of Orthostatic Hypotension and the nature of the postural events related to a fall in blood pressure in patients with Parkinson’s disease. METHODS Blood pressure was measured first in a supine position after a rest of at least 15 minutes and every minute during 10 minutes of an active standing up procedure. Orthostatic Hypotension was considered as present when a fall of at least 20 mm Hg of systolic blood pressure was recorded. Postural events which occurred during the standing test were identified from a questionnaire and self reporting. Statistical analysis was performed to determine the relation between Orthostatic Hypotension and disease characteristics (duration, severity) and the use of antiparkinsonian drugs. Ninety one consecutive patients with Parkinson’s disease (48 women, 43 men, mean age 66 (SD 9) years) participated to the study. RESULTS A fall of at least 20 mm Hg of systolic blood pressure was found in 58.2% of the patients. Orthostatic Hypotension was asymptomatic in 38.5% and associated with postural events in 19.8% of the patients. Symptomatic (but not asymptomatic) Orthostatic Hypotension was related to duration and severity of the disease and with the use of higher daily levodopa and bromocriptine doses. The analysis of the relation between the postural symptoms (and the need for standing test abortion) with the fall in systolic blood pressure allowed the identification of six clinical criteria specific of Orthostatic Hypotension. A direct relation between the postural changes in systolic blood pressure and the number of clinical events in this clinical scale was found. CONCLUSION The frequency of Orthostatic Hypotension in Parkinson’s disease is high and it is possible to establish a clinical rating scale which could be used to assess the effects of drugs employed in the management of Orthostatic Hypotension.
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prevalence of Orthostatic Hypotension in parkinson s disease
Journal of Neurology Neurosurgery and Psychiatry, 1997Co-Authors: Jean-michel Senard, C Brefel, O. Rascol, Maryse Lapeyremestre, A Rascol, Jean-louis MontastrucAbstract:OBJECTIVES To investigate the prevalence of Orthostatic Hypotension and the nature of the postural events related to a fall in blood pressure in patients with Parkinson’s disease. METHODS Blood pressure was measured first in a supine position after a rest of at least 15 minutes and every minute during 10 minutes of an active standing up procedure. Orthostatic Hypotension was considered as present when a fall of at least 20 mm Hg of systolic blood pressure was recorded. Postural events which occurred during the standing test were identified from a questionnaire and self reporting. Statistical analysis was performed to determine the relation between Orthostatic Hypotension and disease characteristics (duration, severity) and the use of antiparkinsonian drugs. Ninety one consecutive patients with Parkinson’s disease (48 women, 43 men, mean age 66 (SD 9) years) participated to the study. RESULTS A fall of at least 20 mm Hg of systolic blood pressure was found in 58.2% of the patients. Orthostatic Hypotension was asymptomatic in 38.5% and associated with postural events in 19.8% of the patients. Symptomatic (but not asymptomatic) Orthostatic Hypotension was related to duration and severity of the disease and with the use of higher daily levodopa and bromocriptine doses. The analysis of the relation between the postural symptoms (and the need for standing test abortion) with the fall in systolic blood pressure allowed the identification of six clinical criteria specific of Orthostatic Hypotension. A direct relation between the postural changes in systolic blood pressure and the number of clinical events in this clinical scale was found. CONCLUSION The frequency of Orthostatic Hypotension in Parkinson’s disease is high and it is possible to establish a clinical rating scale which could be used to assess the effects of drugs employed in the management of Orthostatic Hypotension.
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Which drug for which Orthostatic Hypotension
Fundamental & Clinical Pharmacology, 1996Co-Authors: Jean-michel Senard, Jean-louis MontastrucAbstract:Summary— This review focuses on the actual limits of the clinical pharmacology of drugs used for the treatment of Orthostatic Hypotension. The evidences for heterogeneity of the pathophysiological mechanisms of primary Orthostatic Hypotension and autonomic failure are discussed. The available data on the efficacy of some drugs used in Orthostatic Hypotension are also discussed.
Ruth Peters - One of the best experts on this subject based on the ideXlab platform.
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Orthostatic Hypotension and symptomatic subclinical Orthostatic Hypotension increase risk of cognitive impairment an integrated evidence review and analysis of a large older adult hypertensive cohort
European Heart Journal, 2018Co-Authors: Ruth Peters, Kaarin J Anstey, Andrew Booth, Nigel Beckett, Jane Warwick, Riitta AntikainenAbstract:Aims: Systematically reviewing the literature found Orthostatic Hypotension (OH) to be associated with an increased risk of incident dementia but limited data were available in those at highest risk, the hypertensive oldest-old. Our aim was to analyse the relationship between OH and incident cognitive decline or dementia in this group and to synthesize the evidence base overall. Method and results: Participants aged ≥80 years, with hypertension, were from the Hypertension in the Very Elderly Trial (HYVET) cohort. Orthostatic Hypotension was defined as a fall of ≥15 mmHg in systolic and or ≥7 mmHg in diastolic pressure after 2 min standing from a sitting position. Subclinical Orthostatic Hypotension with symptoms (SOH) was defined as a fall
unsteadiness, light-headedness, or faintness in the week before blood pressure measurement. Proportional hazard regression was used to examine the relationship between baseline OH, SOH, and cognitive outcomes. There were 3121 in the analytical sample, 538 with OH. Orthostatic Hypotension was associated with increased risk of cognitive decline (906 events), hazard ratio (HR) 1.36 (95% confidence interval 1.14-1.59). For incident dementia (241 events), HR 1.34 (0.98-1.84). When competing risk of cardiovascular events were taken into account results were HR 1.39 (1.19-1.62) and HR 1.34 (1.05-1.73), respectively. Subclinical Orthostatic Hypotension was associated with an increased risk of cognitive decline HR 1.56 (1.12-2.17) and dementia HR 1.79 (1.00-3.20). Combining the results from the HYVET cohort in a meta-analysis with the existing published literature in this area found a 21% (9-35%) increased risk of dementia with OH. Conclusion: Orthostatic Hypotension indicates an increased risk of dementia and cognitive decline. SOH may also be considered a risk factor, at least in older hypertensive adults. Questions remain regarding the mechanisms and whether interventions to reduce impact of OH could protect cognition.
Riitta Antikainen - One of the best experts on this subject based on the ideXlab platform.
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Orthostatic Hypotension and symptomatic subclinical Orthostatic Hypotension increase risk of cognitive impairment an integrated evidence review and analysis of a large older adult hypertensive cohort
European Heart Journal, 2018Co-Authors: Ruth Peters, Kaarin J Anstey, Andrew Booth, Nigel Beckett, Jane Warwick, Riitta AntikainenAbstract:Aims: Systematically reviewing the literature found Orthostatic Hypotension (OH) to be associated with an increased risk of incident dementia but limited data were available in those at highest risk, the hypertensive oldest-old. Our aim was to analyse the relationship between OH and incident cognitive decline or dementia in this group and to synthesize the evidence base overall. Method and results: Participants aged ≥80 years, with hypertension, were from the Hypertension in the Very Elderly Trial (HYVET) cohort. Orthostatic Hypotension was defined as a fall of ≥15 mmHg in systolic and or ≥7 mmHg in diastolic pressure after 2 min standing from a sitting position. Subclinical Orthostatic Hypotension with symptoms (SOH) was defined as a fall
unsteadiness, light-headedness, or faintness in the week before blood pressure measurement. Proportional hazard regression was used to examine the relationship between baseline OH, SOH, and cognitive outcomes. There were 3121 in the analytical sample, 538 with OH. Orthostatic Hypotension was associated with increased risk of cognitive decline (906 events), hazard ratio (HR) 1.36 (95% confidence interval 1.14-1.59). For incident dementia (241 events), HR 1.34 (0.98-1.84). When competing risk of cardiovascular events were taken into account results were HR 1.39 (1.19-1.62) and HR 1.34 (1.05-1.73), respectively. Subclinical Orthostatic Hypotension was associated with an increased risk of cognitive decline HR 1.56 (1.12-2.17) and dementia HR 1.79 (1.00-3.20). Combining the results from the HYVET cohort in a meta-analysis with the existing published literature in this area found a 21% (9-35%) increased risk of dementia with OH. Conclusion: Orthostatic Hypotension indicates an increased risk of dementia and cognitive decline. SOH may also be considered a risk factor, at least in older hypertensive adults. Questions remain regarding the mechanisms and whether interventions to reduce impact of OH could protect cognition.
Wilbert S Aronow - One of the best experts on this subject based on the ideXlab platform.
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Orthostatic Hypotension and incident heart failure in community dwelling older adults
Journals of Gerontology Series A-biological Sciences and Medical Sciences, 2014Co-Authors: Kannayiram Alagiakrishnan, Kanan Patel, Ravi V Desai, Momanna B Ahmed, Gregg C Fonarow, Daniel E Forman, Michel White, Inmaculada Aban, Thomas E Love, Wilbert S AronowAbstract:Orthostatic Hypotension, a blood pressure dysregu- lation, has been shown to be a risk factor for incident heart failure (HF) in middle-aged adults (1,2). Although Orthostatic Hypotension is common in older adults (3–5) and other blood pressure disorders such as isolated systolic hypertension (6) and isolated diastolic Hypotension (7) are common risk factors for incident HF, little is known about the association of Orthostatic Hypotension with incident HF in older adults. In the Rotterdam Study, among an all-white cohort of adults, aged 55 years or older, Orthostatic Hypotension was associated with higher risk of coronary heart disease and all-cause mortality but had no significant association with incident HF (8). Because Orthostatic Hypotension is often associated with other HF risk factors such as prior acute myocardial infarction and isolated systolic hypertension and diabetes (2,9), to what extent its association with outcomes are intrinsic in nature remains unclear. Regression-based risk adjustments may not ensure that baseline confounders are properly balanced between the two study groups, in which case, the adjusted association may not be reflective of the true association (10). Therefore, in the current study, we examined the independence of association of Orthostatic Hypotension with incident HF in a propensity-matched cohort of older adults in the Cardiovascular Health Study.
Jean-michel Senard - One of the best experts on this subject based on the ideXlab platform.
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Adrenergic supersensitivity in parkinsonians with Orthostatic Hypotension.
European Journal of Clinical Investigation, 2008Co-Authors: Jean-michel Senard, Jean-louis Montastruc, Philippe Valet, Geneviève Durrieu, Michel Berlan, Marie-antoinette Tran, André Rascol, Paul MontastrucAbstract:. The adrenergic status was studied through evaluation of platelet α2-adrenoceptor number ([3H]-yohimbine binding sites), plasma catecholamine levels and blood pressure response to noradrenaline infusion in three groups of subjects (1) Parkinsonians with Orthostatic Hypotension; (2) Parkinsonians without Orthostatic Hypotension; and (3) control subjects. In Parkinsonians with Orthostatic Hypotension, systolic and diastolic blood pressures significantly (P < 0.05) decreased from 144 pM 9 and 76 pM 6 mmHg in the lying position to 95 pM 12 and 60 pM 7 mmHg after 5 min standing. In these patients, noradrenaline plasma levels were significantly low (62 pM 11 pg ml-1, (P < 0.05) when compared with controls (219 pM 13 pg ml-1) whereas no difference was noticed in Parkinsonians without Orthostatic Hypotension (195 pM 14 pg ml-1). The noradrenaline dose required for a 25 mmHg increase in systolic blood pressure was significantly (P < 0.01) lower in Parkinsonians with Orthostatic Hypotension (019 pM 0.03 μg kg-1) when compared with Parkinsonians without Orthostatic Hypotension (0.86 pM 0.11 μg kg-1) or with controls (0.68 pM 0.l μg kg-1). Platelet x2-adrenoceptor number was higher in Parkinsonians with Orthostatic Hypotension (313 pM 52 fmol mg-1 protein) than in Parkinsonians without Orthostatic Hypotension (168 pM 9 fmol mg-1 protein) or in controls (175 pM 4 fmol mg-1 protein) with no change in Kd. This study demonstrates that in patients with Parkinson's disease, Orthostatic Hypotension is associated with an increase in both vascular sensitivity to noradrenaline and platelet α2-adrenoceptor number. These observations suggest the existence of an α-adrenergic supersensitivity in response to the low levels of plasma noradrenaline.
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Orthostatic Hypotension in Patients with Parkinson’s Disease
Drugs & Aging, 2001Co-Authors: Jean-michel Senard, O. Rascol, Christine Brefel-courbon, Jean-louis MontastrucAbstract:Orthostatic Hypotension is common in elderly patients, and is now considered to be an important prognostic factor for cognitive decline and mortality. In patients with Parkinson’s disease, the prevalence of symptomatic Orthostatic Hypotension may be as high as 20%. Two factors could explain this high prevalence. First, dopaminergic drugs may induce or worsen Orthostatic Hypotension. Secondly, Parkinson’s disease is a cause of primary autonomic failure with an involvement of the peripheral autonomic system as shown by the ubiquitous distribution of Lewy bodies and reduced iobenguane [metaiodobenzylguanidine (MIBG)] cardiac uptake. These pathological and pharmacological characteristics clearly differentiate autonomic failure of Parkinson’s disease from multiple system atrophy. If autonomic abnormalities appear to be present from the first stage of the disease, early onset (within the first year) of symptomatic Orthostatic Hypotension in the course of parkinsonism can be considered as an exclusion criteria for idiopathic Parkinson’s disease. No specific clinical trials have evaluated the effects of antihypotensive drugs in patients with Parkinson’s disease and thus no specific therapeutic strategy can be recommended. The management of Orthostatic Hypotension in patients with Parkinson’s disease should always start with patient education and nonpharmacological treatment. Drug therapy should be reserved for symptomatic patients who do not get benefit from nonpharmacological management. Among the available drugs, α_1-adrenergic agonists (mainly midodrine) or plasma volume expanders (mainly fludrocortisone) are the most frequently used. There are also some drugs that are currently investigational such as yohimbine and droxidopa. Other drugs such as desmopressin or octreotide may be of interest in some situations. Domperidone is widely used in patients with parkinsonism with no proven effect on Orthostatic Hypotension.
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Prevalence of Orthostatic Hypotension in Parkinson’s disease
Journal of Neurology Neurosurgery and Psychiatry, 1997Co-Authors: Jean-michel Senard, André Rascol, Maryse Lapeyre-mestre, C Brefel, O. Rascol, Jean-louis MontastrucAbstract:OBJECTIVES To investigate the prevalence of Orthostatic Hypotension and the nature of the postural events related to a fall in blood pressure in patients with Parkinson’s disease. METHODS Blood pressure was measured first in a supine position after a rest of at least 15 minutes and every minute during 10 minutes of an active standing up procedure. Orthostatic Hypotension was considered as present when a fall of at least 20 mm Hg of systolic blood pressure was recorded. Postural events which occurred during the standing test were identified from a questionnaire and self reporting. Statistical analysis was performed to determine the relation between Orthostatic Hypotension and disease characteristics (duration, severity) and the use of antiparkinsonian drugs. Ninety one consecutive patients with Parkinson’s disease (48 women, 43 men, mean age 66 (SD 9) years) participated to the study. RESULTS A fall of at least 20 mm Hg of systolic blood pressure was found in 58.2% of the patients. Orthostatic Hypotension was asymptomatic in 38.5% and associated with postural events in 19.8% of the patients. Symptomatic (but not asymptomatic) Orthostatic Hypotension was related to duration and severity of the disease and with the use of higher daily levodopa and bromocriptine doses. The analysis of the relation between the postural symptoms (and the need for standing test abortion) with the fall in systolic blood pressure allowed the identification of six clinical criteria specific of Orthostatic Hypotension. A direct relation between the postural changes in systolic blood pressure and the number of clinical events in this clinical scale was found. CONCLUSION The frequency of Orthostatic Hypotension in Parkinson’s disease is high and it is possible to establish a clinical rating scale which could be used to assess the effects of drugs employed in the management of Orthostatic Hypotension.
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prevalence of Orthostatic Hypotension in parkinson s disease
Journal of Neurology Neurosurgery and Psychiatry, 1997Co-Authors: Jean-michel Senard, C Brefel, O. Rascol, Maryse Lapeyremestre, A Rascol, Jean-louis MontastrucAbstract:OBJECTIVES To investigate the prevalence of Orthostatic Hypotension and the nature of the postural events related to a fall in blood pressure in patients with Parkinson’s disease. METHODS Blood pressure was measured first in a supine position after a rest of at least 15 minutes and every minute during 10 minutes of an active standing up procedure. Orthostatic Hypotension was considered as present when a fall of at least 20 mm Hg of systolic blood pressure was recorded. Postural events which occurred during the standing test were identified from a questionnaire and self reporting. Statistical analysis was performed to determine the relation between Orthostatic Hypotension and disease characteristics (duration, severity) and the use of antiparkinsonian drugs. Ninety one consecutive patients with Parkinson’s disease (48 women, 43 men, mean age 66 (SD 9) years) participated to the study. RESULTS A fall of at least 20 mm Hg of systolic blood pressure was found in 58.2% of the patients. Orthostatic Hypotension was asymptomatic in 38.5% and associated with postural events in 19.8% of the patients. Symptomatic (but not asymptomatic) Orthostatic Hypotension was related to duration and severity of the disease and with the use of higher daily levodopa and bromocriptine doses. The analysis of the relation between the postural symptoms (and the need for standing test abortion) with the fall in systolic blood pressure allowed the identification of six clinical criteria specific of Orthostatic Hypotension. A direct relation between the postural changes in systolic blood pressure and the number of clinical events in this clinical scale was found. CONCLUSION The frequency of Orthostatic Hypotension in Parkinson’s disease is high and it is possible to establish a clinical rating scale which could be used to assess the effects of drugs employed in the management of Orthostatic Hypotension.
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Which drug for which Orthostatic Hypotension
Fundamental & Clinical Pharmacology, 1996Co-Authors: Jean-michel Senard, Jean-louis MontastrucAbstract:Summary— This review focuses on the actual limits of the clinical pharmacology of drugs used for the treatment of Orthostatic Hypotension. The evidences for heterogeneity of the pathophysiological mechanisms of primary Orthostatic Hypotension and autonomic failure are discussed. The available data on the efficacy of some drugs used in Orthostatic Hypotension are also discussed.
