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Rose Anne Kenny - One of the best experts on this subject based on the ideXlab platform.
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Orthostatic Blood Pressure variability is associated with lower visual contrast sensitivity function findings from the irish longitudinal study on aging
Experimental Gerontology, 2019Co-Authors: Blaithin Ni Bhuachalla, Neil Oleary, Christine Mcgarrigle, Kwadwo Owusu Akuffo, Tunde Peto, Stephen Beatty, Rose Anne KennyAbstract:Abstract Background Hypertension is established to cause vascular end-organ damage. Other forms of dysregulated Blood Pressure (BP) behaviour, such as Orthostatic hypotension have also been associated with cardiovascular (CV) events. The eye is potentially vulnerable to dysregulated systemic BP if ocular circulation autoregulation is impaired. We investigated whether phenotypes of abnormal BP stabilisation after orthostasis, an autonomic stressor, had a relationship with contrast sensitivity (CS), an outcome measure of subtle psychophysical visual function. Methods This was a cross-sectional study from wave 1 of The Irish Longitudinal Study on Ageing (TILDA). From beat-to-beat Orthostatic BP (BP), measured by digital photoplethysmography during active stand, 4 phenotypes have been defined 1) normal stabilisation 2) Orthostatic hypotension, 3) Orthostatic hypertension 4) BP variability. Contrast sensitivity was measured using a Functional Visual Analyzer. Multivariable linear regression models investigated the relationship between Orthostatic BP phenotypes and contrast sensitivity in 4289 adults aged ≥50 years adjusting for, demographics, cardiovascular risk factors, self-reported eye pathologies, objective hypertension and antihypertensives. A sensitivity analysis adjusted for age-related macular degeneration, glaucoma, diabetic retinopathy and maculopathy identified on retinal photographs. Finally models were compared, adjusting for alternative measures of cataract versus not, to examine the potential effect of cataract on any associations. Results Systolic Orthostatic BP variability was associated with worse contrast sensitivity, in the primary and the sensitivity analysis. Adjusting for alternative measures of clinical cataract attenuated the association by 18%. Conclusions Orthostatic BP variability is associated with worse contrast sensitivity, independent of hypertension and retinal pathology and may be a cardiovascular biomarker of early ocular pathology.
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single agent antihypertensive therapy and Orthostatic Blood Pressure behaviour in older adults using beat to beat measurements the irish longitudinal study on ageing
PLOS ONE, 2016Co-Authors: Mark Canney, Matthew D L Oconnell, Catriona Murphy, Neil Oleary, Mark A Little, Conall M Oseaghdha, Rose Anne KennyAbstract:Background Impaired Blood Pressure (BP) stabilisation after standing, defined using beat-to-beat measurements, has been shown to predict important health outcomes. We aimed to define the relationship between individual classes of antihypertensive agent and BP stabilisation among hypertensive older adults.
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age related normative changes in phasic Orthostatic Blood Pressure in a large population study findings from the irish longitudinal study on ageing tilda
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample.
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age related normative changes in phasic Orthostatic Blood Pressure in a large population study findings from the irish longitudinal study on ageing tilda
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:Background—In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample. Methods and Results—Participants were recruited from a nationally representative cohort study (≥50 years). Beat-to-beat systolic BP, diastolic BP, and heart rate records were analyzed among those who underwent an active stand test (n=4475). Normograms were estimated by use of generalized additive models for location, shape, and scale with Box-Cox power exponential distribution. Prevalence estimates of impaired BP stabilization, initial Orthostatic hypotension, and Orthostatic hypotension are reported. Orthostatic BP responses in adults aged 50 to 59 years stabilized within 30 seconds of standing, with older groups taking 30 seconds or longer. The total prevalence of impaired BP stabilization was 15.6% (95% co...
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age related normative changes in phasic Orthostatic Blood Pressure in a large population studyclinical perspective
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:Background— In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample. Methods and Results— Participants were recruited from a nationally representative cohort study (≥50 years). Beat-to-beat systolic BP, diastolic BP, and heart rate records were analyzed among those who underwent an active stand test (n=4475). Normograms were estimated by use of generalized additive models for location, shape, and scale with Box-Cox power exponential distribution. Prevalence estimates of impaired BP stabilization, initial Orthostatic hypotension, and Orthostatic hypotension are reported. Orthostatic BP responses in adults aged 50 to 59 years stabilized within 30 seconds of standing, with older groups taking 30 seconds or longer. The total prevalence of impaired BP stabilization was 15.6% (95% confidence interval [CI], 14.1%–17.1%), increasing with age to 41.2% (95% CI, 30.0%–52.4%) in people ≥80 years old. Initial Orthostatic hypotension occurred in 32.9% (95% CI, 31.2%–34.6%) of the population aged ≥50 years, with no age gradient evident. The prevalence of Orthostatic hypotension was 6.9% (95% CI, 5.9%–7.8%) in the total population, increasing to 18.5% (95% CI, 9.0%–28.0%) in those aged ≥80 years old. Conclusions— Significant age-related differences exist in the time course of postural BP responses, with abnormal responses taking longer than 30 seconds to stabilize. Impaired BP stabilization is more common as we age, affecting more than two-fifths of the population aged ≥80 years, and may play a future role in the management of falls and syncope. # CLINICAL PERSPECTIVE {#article-title-40}
Paul J Thuluvath - One of the best experts on this subject based on the ideXlab platform.
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a vasopressin receptor antagonist vpa 985 improves serum sodium concentration in patients with hyponatremia a multicenter randomized placebo controlled trial
Hepatology, 2003Co-Authors: M Florence D Wong, Andres T Blei, Laurence M Blendis, Paul J ThuluvathAbstract:Hyponatremia in advanced cirrhosis and ascites or congestive heart failure (CHF) is the result of an inappropriate increase in vasopressin secretion, which acts through activation of specific V2 receptors in the distal renal nephron to increase water reabsorption. This study investigates the efficacy and safety of 3 different doses of the V2 receptor antagonist, VPA-985, in correcting hyponatremia over a 7-day inpatient study period. Forty-four hospitalized patients (33 patients with cirrhosis, 6 with CHF, and 5 with syndrome of inappropriate antidiuretic hormone (SIADH) were studied on a constant sodium intake, with VPA doses of 25, 125, and 250 mg twice daily or placebo. Serum sodium measurements were repeated after every daily dose, and the next dose withheld for excessive serum sodium rises. Fluid intake was adjusted according to previous 24-hour urinary outputs. Adverse events were based on clinical signs of dehydration or encephalopathy. VPA-985 produced a significant overall aquaretic response compared with placebo, with significant dose related increases in free water clearance (P < .05) and serum sodium (P < .05), without significant changes in Orthostatic Blood Pressure or serum creatinine levels. Five patients (50%) on 250 mg twice daily had to have medication withheld on multiple occasions. End-of-study plasma vasopressin levels increased significantly in the 2 larger dose groups. In conclusion, VPA-985 appears effective and safe in appropriate doses in correcting abnormal renal water handling and hyponatremia in conditions associated with water retention. Higher doses of VPA-985 may produce significant dehydration and will require close monitoring with their use. (HEPATOLOGY 2003;37:182-191.)
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a vasopressin receptor antagonist vpa 985 improves serum sodium concentration in patients with hyponatremia a multicenter randomized placebo controlled trial
Hepatology, 2003Co-Authors: M Florence D Wong, Andres T Blei, Laurence M Blendis, Paul J ThuluvathAbstract:Hyponatremia in advanced cirrhosis and ascites or congestive heart failure (CHF) is the result of an inappropriate increase in vasopressin secretion, which acts through activation of specific V2 receptors in the distal renal nephron to increase water reabsorption. This study investigates the efficacy and safety of 3 different doses of the V2 receptor antagonist, VPA-985, in correcting hyponatremia over a 7-day inpatient study period. Forty-four hospitalized patients (33 patients with cirrhosis, 6 with CHF, and 5 with syndrome of inappropriate antidiuretic hormone (SIADH) were studied on a constant sodium intake, with VPA doses of 25, 125, and 250 mg twice daily or placebo. Serum sodium measurements were repeated after every daily dose, and the next dose withheld for excessive serum sodium rises. Fluid intake was adjusted according to previous 24-hour urinary outputs. Adverse events were based on clinical signs of dehydration or encephalopathy. VPA-985 produced a significant overall aquaretic response compared with placebo, with significant dose related increases in free water clearance (P < .05) and serum sodium (P < .05), without significant changes in Orthostatic Blood Pressure or serum creatinine levels. Five patients (50%) on 250 mg twice daily had to have medication withheld on multiple occasions. End-of-study plasma vasopressin levels increased significantly in the 2 larger dose groups. In conclusion, VPA-985 appears effective and safe in appropriate doses in correcting abnormal renal water handling and hyponatremia in conditions associated with water retention. Higher doses of VPA-985 may produce significant dehydration and will require close monitoring with their use.
Chie Wei Fan - One of the best experts on this subject based on the ideXlab platform.
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age related normative changes in phasic Orthostatic Blood Pressure in a large population study findings from the irish longitudinal study on ageing tilda
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample.
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age related normative changes in phasic Orthostatic Blood Pressure in a large population study findings from the irish longitudinal study on ageing tilda
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:Background—In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample. Methods and Results—Participants were recruited from a nationally representative cohort study (≥50 years). Beat-to-beat systolic BP, diastolic BP, and heart rate records were analyzed among those who underwent an active stand test (n=4475). Normograms were estimated by use of generalized additive models for location, shape, and scale with Box-Cox power exponential distribution. Prevalence estimates of impaired BP stabilization, initial Orthostatic hypotension, and Orthostatic hypotension are reported. Orthostatic BP responses in adults aged 50 to 59 years stabilized within 30 seconds of standing, with older groups taking 30 seconds or longer. The total prevalence of impaired BP stabilization was 15.6% (95% co...
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age related normative changes in phasic Orthostatic Blood Pressure in a large population studyclinical perspective
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:Background— In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample. Methods and Results— Participants were recruited from a nationally representative cohort study (≥50 years). Beat-to-beat systolic BP, diastolic BP, and heart rate records were analyzed among those who underwent an active stand test (n=4475). Normograms were estimated by use of generalized additive models for location, shape, and scale with Box-Cox power exponential distribution. Prevalence estimates of impaired BP stabilization, initial Orthostatic hypotension, and Orthostatic hypotension are reported. Orthostatic BP responses in adults aged 50 to 59 years stabilized within 30 seconds of standing, with older groups taking 30 seconds or longer. The total prevalence of impaired BP stabilization was 15.6% (95% confidence interval [CI], 14.1%–17.1%), increasing with age to 41.2% (95% CI, 30.0%–52.4%) in people ≥80 years old. Initial Orthostatic hypotension occurred in 32.9% (95% CI, 31.2%–34.6%) of the population aged ≥50 years, with no age gradient evident. The prevalence of Orthostatic hypotension was 6.9% (95% CI, 5.9%–7.8%) in the total population, increasing to 18.5% (95% CI, 9.0%–28.0%) in those aged ≥80 years old. Conclusions— Significant age-related differences exist in the time course of postural BP responses, with abnormal responses taking longer than 30 seconds to stabilize. Impaired BP stabilization is more common as we age, affecting more than two-fifths of the population aged ≥80 years, and may play a future role in the management of falls and syncope. # CLINICAL PERSPECTIVE {#article-title-40}
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age related normative changes in phasic Orthostatic Blood Pressure in a large population studyclinical perspective findings from the irish longitudinal study on ageing tilda
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:Background— In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample. Methods and Results— Participants were recruited from a nationally representative cohort study (≥50 years). Beat-to-beat systolic BP, diastolic BP, and heart rate records were analyzed among those who underwent an active stand test (n=4475). Normograms were estimated by use of generalized additive models for location, shape, and scale with Box-Cox power exponential distribution. Prevalence estimates of impaired BP stabilization, initial Orthostatic hypotension, and Orthostatic hypotension are reported. Orthostatic BP responses in adults aged 50 to 59 years stabilized within 30 seconds of standing, with older groups taking 30 seconds or longer. The total prevalence of impaired BP stabilization was 15.6% (95% confidence interval [CI], 14.1%–17.1%), increasing with age to 41.2% (95% CI, 30.0%–52.4%) in people ≥80 years old. Initial Orthostatic hypotension occurred in 32.9% (95% CI, 31.2%–34.6%) of the population aged ≥50 years, with no age gradient evident. The prevalence of Orthostatic hypotension was 6.9% (95% CI, 5.9%–7.8%) in the total population, increasing to 18.5% (95% CI, 9.0%–28.0%) in those aged ≥80 years old. Conclusions— Significant age-related differences exist in the time course of postural BP responses, with abnormal responses taking longer than 30 seconds to stabilize. Impaired BP stabilization is more common as we age, affecting more than two-fifths of the population aged ≥80 years, and may play a future role in the management of falls and syncope.
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age related normative changes in phasic Orthostatic Blood Pressure in a large population study
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:Background—In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample. Methods and Results—Participants were recruited from a nationally representative cohort study (≥50 years). Beat-to-beat systolic BP, diastolic BP, and heart rate records were analyzed among those who underwent an active stand test (n=4475). Normograms were estimated by use of generalized additive models for location, shape, and scale with Box-Cox power exponential distribution. Prevalence estimates of impaired BP stabilization, initial Orthostatic hypotension, and Orthostatic hypotension are reported. Orthostatic BP responses in adults aged 50 to 59 years stabilized within 30 seconds of standing, with older groups taking 30 seconds or longer. The total prevalence of impaired BP stabilization was 15.6% (95% co...
Ciaran Finucane - One of the best experts on this subject based on the ideXlab platform.
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age related normative changes in phasic Orthostatic Blood Pressure in a large population study findings from the irish longitudinal study on ageing tilda
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample.
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age related normative changes in phasic Orthostatic Blood Pressure in a large population study findings from the irish longitudinal study on ageing tilda
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:Background—In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample. Methods and Results—Participants were recruited from a nationally representative cohort study (≥50 years). Beat-to-beat systolic BP, diastolic BP, and heart rate records were analyzed among those who underwent an active stand test (n=4475). Normograms were estimated by use of generalized additive models for location, shape, and scale with Box-Cox power exponential distribution. Prevalence estimates of impaired BP stabilization, initial Orthostatic hypotension, and Orthostatic hypotension are reported. Orthostatic BP responses in adults aged 50 to 59 years stabilized within 30 seconds of standing, with older groups taking 30 seconds or longer. The total prevalence of impaired BP stabilization was 15.6% (95% co...
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age related normative changes in phasic Orthostatic Blood Pressure in a large population studyclinical perspective
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:Background— In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample. Methods and Results— Participants were recruited from a nationally representative cohort study (≥50 years). Beat-to-beat systolic BP, diastolic BP, and heart rate records were analyzed among those who underwent an active stand test (n=4475). Normograms were estimated by use of generalized additive models for location, shape, and scale with Box-Cox power exponential distribution. Prevalence estimates of impaired BP stabilization, initial Orthostatic hypotension, and Orthostatic hypotension are reported. Orthostatic BP responses in adults aged 50 to 59 years stabilized within 30 seconds of standing, with older groups taking 30 seconds or longer. The total prevalence of impaired BP stabilization was 15.6% (95% confidence interval [CI], 14.1%–17.1%), increasing with age to 41.2% (95% CI, 30.0%–52.4%) in people ≥80 years old. Initial Orthostatic hypotension occurred in 32.9% (95% CI, 31.2%–34.6%) of the population aged ≥50 years, with no age gradient evident. The prevalence of Orthostatic hypotension was 6.9% (95% CI, 5.9%–7.8%) in the total population, increasing to 18.5% (95% CI, 9.0%–28.0%) in those aged ≥80 years old. Conclusions— Significant age-related differences exist in the time course of postural BP responses, with abnormal responses taking longer than 30 seconds to stabilize. Impaired BP stabilization is more common as we age, affecting more than two-fifths of the population aged ≥80 years, and may play a future role in the management of falls and syncope. # CLINICAL PERSPECTIVE {#article-title-40}
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age related normative changes in phasic Orthostatic Blood Pressure in a large population studyclinical perspective findings from the irish longitudinal study on ageing tilda
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:Background— In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample. Methods and Results— Participants were recruited from a nationally representative cohort study (≥50 years). Beat-to-beat systolic BP, diastolic BP, and heart rate records were analyzed among those who underwent an active stand test (n=4475). Normograms were estimated by use of generalized additive models for location, shape, and scale with Box-Cox power exponential distribution. Prevalence estimates of impaired BP stabilization, initial Orthostatic hypotension, and Orthostatic hypotension are reported. Orthostatic BP responses in adults aged 50 to 59 years stabilized within 30 seconds of standing, with older groups taking 30 seconds or longer. The total prevalence of impaired BP stabilization was 15.6% (95% confidence interval [CI], 14.1%–17.1%), increasing with age to 41.2% (95% CI, 30.0%–52.4%) in people ≥80 years old. Initial Orthostatic hypotension occurred in 32.9% (95% CI, 31.2%–34.6%) of the population aged ≥50 years, with no age gradient evident. The prevalence of Orthostatic hypotension was 6.9% (95% CI, 5.9%–7.8%) in the total population, increasing to 18.5% (95% CI, 9.0%–28.0%) in those aged ≥80 years old. Conclusions— Significant age-related differences exist in the time course of postural BP responses, with abnormal responses taking longer than 30 seconds to stabilize. Impaired BP stabilization is more common as we age, affecting more than two-fifths of the population aged ≥80 years, and may play a future role in the management of falls and syncope.
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age related normative changes in phasic Orthostatic Blood Pressure in a large population study
Circulation, 2014Co-Authors: Ciaran Finucane, Matthew D L Oconnell, Chie Wei Fan, George M Savva, Christopher Soraghan, Hugh Nolan, Hilary Cronin, Rose Anne KennyAbstract:Background—In this report, we provide the first normative reference data and prevalence estimates of impaired Orthostatic Blood Pressure (BP) stabilization, initial Orthostatic hypotension, and Orthostatic hypotension based on beat-to-beat Blood Pressure methods in a population-representative sample. Methods and Results—Participants were recruited from a nationally representative cohort study (≥50 years). Beat-to-beat systolic BP, diastolic BP, and heart rate records were analyzed among those who underwent an active stand test (n=4475). Normograms were estimated by use of generalized additive models for location, shape, and scale with Box-Cox power exponential distribution. Prevalence estimates of impaired BP stabilization, initial Orthostatic hypotension, and Orthostatic hypotension are reported. Orthostatic BP responses in adults aged 50 to 59 years stabilized within 30 seconds of standing, with older groups taking 30 seconds or longer. The total prevalence of impaired BP stabilization was 15.6% (95% co...
M Florence D Wong - One of the best experts on this subject based on the ideXlab platform.
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a vasopressin receptor antagonist vpa 985 improves serum sodium concentration in patients with hyponatremia a multicenter randomized placebo controlled trial
Hepatology, 2003Co-Authors: M Florence D Wong, Andres T Blei, Laurence M Blendis, Paul J ThuluvathAbstract:Hyponatremia in advanced cirrhosis and ascites or congestive heart failure (CHF) is the result of an inappropriate increase in vasopressin secretion, which acts through activation of specific V2 receptors in the distal renal nephron to increase water reabsorption. This study investigates the efficacy and safety of 3 different doses of the V2 receptor antagonist, VPA-985, in correcting hyponatremia over a 7-day inpatient study period. Forty-four hospitalized patients (33 patients with cirrhosis, 6 with CHF, and 5 with syndrome of inappropriate antidiuretic hormone (SIADH) were studied on a constant sodium intake, with VPA doses of 25, 125, and 250 mg twice daily or placebo. Serum sodium measurements were repeated after every daily dose, and the next dose withheld for excessive serum sodium rises. Fluid intake was adjusted according to previous 24-hour urinary outputs. Adverse events were based on clinical signs of dehydration or encephalopathy. VPA-985 produced a significant overall aquaretic response compared with placebo, with significant dose related increases in free water clearance (P < .05) and serum sodium (P < .05), without significant changes in Orthostatic Blood Pressure or serum creatinine levels. Five patients (50%) on 250 mg twice daily had to have medication withheld on multiple occasions. End-of-study plasma vasopressin levels increased significantly in the 2 larger dose groups. In conclusion, VPA-985 appears effective and safe in appropriate doses in correcting abnormal renal water handling and hyponatremia in conditions associated with water retention. Higher doses of VPA-985 may produce significant dehydration and will require close monitoring with their use. (HEPATOLOGY 2003;37:182-191.)
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a vasopressin receptor antagonist vpa 985 improves serum sodium concentration in patients with hyponatremia a multicenter randomized placebo controlled trial
Hepatology, 2003Co-Authors: M Florence D Wong, Andres T Blei, Laurence M Blendis, Paul J ThuluvathAbstract:Hyponatremia in advanced cirrhosis and ascites or congestive heart failure (CHF) is the result of an inappropriate increase in vasopressin secretion, which acts through activation of specific V2 receptors in the distal renal nephron to increase water reabsorption. This study investigates the efficacy and safety of 3 different doses of the V2 receptor antagonist, VPA-985, in correcting hyponatremia over a 7-day inpatient study period. Forty-four hospitalized patients (33 patients with cirrhosis, 6 with CHF, and 5 with syndrome of inappropriate antidiuretic hormone (SIADH) were studied on a constant sodium intake, with VPA doses of 25, 125, and 250 mg twice daily or placebo. Serum sodium measurements were repeated after every daily dose, and the next dose withheld for excessive serum sodium rises. Fluid intake was adjusted according to previous 24-hour urinary outputs. Adverse events were based on clinical signs of dehydration or encephalopathy. VPA-985 produced a significant overall aquaretic response compared with placebo, with significant dose related increases in free water clearance (P < .05) and serum sodium (P < .05), without significant changes in Orthostatic Blood Pressure or serum creatinine levels. Five patients (50%) on 250 mg twice daily had to have medication withheld on multiple occasions. End-of-study plasma vasopressin levels increased significantly in the 2 larger dose groups. In conclusion, VPA-985 appears effective and safe in appropriate doses in correcting abnormal renal water handling and hyponatremia in conditions associated with water retention. Higher doses of VPA-985 may produce significant dehydration and will require close monitoring with their use.
