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Item Assessment and Management of Hypertension among Patients on Peritoneal Dialysis(American Society of Nephrology., 2019-02-07) Vaios, Vasilios; Georgianos, Panagiotis I.; Liakopoulos, Vassilios; Agarwal, Rajiv; Medicine, School of MedicineApproximately 7%-10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population.Item Chlorthalidone for Resistant Hypertension in Advanced Chronic Kidney Disease(American Heart Association, 2022) Agarwal, Rajiv; Sinha, Arjun D.; Tu, Wanzhu; Medicine, School of MedicineItem The Effects of Amlodipine Compared to Losartan in Patients With Mild to Moderately Severe Hypertension(Wiley, 2003) Phillips, Robert A.; Kloner, Robert A.; Grimm, Richard H., Jr.; Weinberger, Myron; Medicine, School of MedicineThe calcium channel blocker amlodipine and angiotensin II receptor blocker losartan, with or without hydrochlorothiazide (HCTZ), were compared for the treatment of mild to moderate hypertension in a multicenter, double-blind, parallel-group clinical trial. Following a 2-week placebo run-in, 440 adults (45-80 years old) were randomized to receive either amlodipine 5 mg once daily or losartan 50 mg once daily. Patients who failed to meet the sitting diastolic blood pressure (BP) reduction goal ofItem A Method to Quantify Mean Hypertension Treatment Daily Dose Intensity Using Health Care System Data(American Medical Association, 2021-01-04) Min, Lillian; Ha, Jin-Kyung; Aubert, Carole E.; Hofer, Timothy P.; Sussman, Jeremy B.; Langa, Kenneth M.; Tinetti, Mary; Hyungjin Myra, Kim; Maciejewski, Matthew L.; Gillon, Leah; Larkin, Angela; Chan, Chiao-Li; Kerr, Eve A.; Bravata, Dawn; Cushman, William C.; Medicine, School of MedicineImportance: Simple measures of hypertension treatment, such as achievement of blood pressure (BP) targets, ignore the intensity of treatment once the BP target is met. High-intensity treatment involves increased treatment burden and can be associated with potential adverse effects in older adults. A method was previously developed to identify older patients receiving intense hypertension treatment by low BP and number of BP medications using national Veterans Health Administration and Medicare Part D administrative pharmacy data to evaluate which BP medications a patient is likely taking on any given day. Objective: To further develop and validate a method to more precisely quantify dose intensity of hypertension treatment using only health system administrative pharmacy fill data. Design, setting, and participants: Observational, cross-sectional study of 319 randomly selected older veterans in the national Veterans Health Administration health care system who were taking multiple BP-lowering medications and had a total of 3625 ambulatory care visits from July 1, 2011, to June 30, 2013. Measure development and medical record review occurred January 1, 2017, through November 30, 2018, and data analysis was conducted from December 1, 2019, to August 31, 2020. Main outcomes and measures: For each BP-lowering medication, a moderate hypertension daily dose (HDD) was defined as half the maximum dose above which no further clinical benefit has been demonstrated by that medication in hypertension trials. Patients' total HDD was calculated using pharmacy data (pharmacy HDDs), accounting for substantial delays in refills (>30 days) when a patient's pill supply was stretched (eg, cutting existing pills in half). As an external comparison, the pharmacy HDDs were correlated with doses manually extracted from clinicians' visit notes (clinically noted HDDs). How well the pharmacy HDDs correlated with clinically noted HDDs was calculated (using C statistics). To facilitate interpretation, HDDs were described in association with the number of medications. Results: A total of 316 patients (99.1%) were male; the mean (SD) age was 75.6 (7.2) years. Pharmacy HDDs were highly correlated (r = 0.92) with clinically noted HDDs, with a mean (SD) of 2.7 (1.8) for pharmacy HDDs and 2.8 (1.8) for clinically noted HDDs. Pharmacy HDDs correlated with high-intensity, clinically noted HDDs ranging from a C statistic of 92.8% (95% CI, 92.0%-93.7%) for 2 or more clinically noted HDDs to 88.1% (95% CI, 85.5%-90.6%) for 6 or more clinically noted HDDs. Conclusions and relevance: This study suggests that health system pharmacy data may be used to accurately quantify hypertension regimen dose intensity. Together with clinic-measured BP, this tool can be used in future health system-based research or quality improvement efforts to fine-tune, manage, and optimize hypertension treatment in older adults.Item Remote Monitoring Compared With In-Office Surveillance of Blood Pressure in Patients With Pregnancy-Related Hypertension: A Randomized Controlled Trial(Wolters Kluwer, 2023) Arkerson, Brittany J.; Finneran, Matthew M.; Harris, Solita R.; Schnorr, Jessica; McElwee, Eliza R.; Demosthenes, Lauren; Sawyer, Renata; Obstetrics and Gynecology, School of MedicineObjective: To compare the rate of blood pressure ascertainment within 10 days of postpartum discharge among individuals with hypertensive disorders of pregnancy randomized either to in-office blood pressure assessment or at-home monitoring. Methods: This was a multisite randomized controlled trial of postpartum patients diagnosed with a hypertensive disorder of pregnancy before discharge between April 2021 and September 2021 and was performed at two academic training institutions. Patients were randomized to either an in-office blood pressure check or remote monitoring through a web-enabled smartphone platform. The primary outcome was the rate of any blood pressure ascertainment within 10 days of discharge. Secondary outcomes include rates of initiation of antihypertensive medication, readmission, and additional office or triage visits for hypertension. Assuming a 10-day postdischarge blood pressure ascertainment rate of 50% in the in-office arm, we estimated that 186 participants would provide 80% power to detect a 20% difference in the primary outcome between groups. Results: One hundred ninety-seven patients were randomized (96 remote, 101 in-office). Patients with remote monitoring had higher rates of postpartum blood pressure ascertainment compared with in-office surveillance (91.7% [n=88] vs 58.4% [n=59]; P<.001). There were 11 (11.5%) patients in the intervention arm whose only qualifying blood pressure was a postdischarge in-person ascertainment, yielding a true remote monitoring uptake rate of 80.2%. In those with remote blood pressure uptake (n=77), the median number of blood pressure checks was 15 (interquartile range 6-26) and the median duration of remote monitoring use was 14 days (interquartile range 9-16). There were no differences in rates of readmission for hypertension (5.0% [n=5] vs 4.2% [n=4], P=.792) or initiation of antihypertensive medications after discharge (9.4% [n=9] vs 6.9% [n=7], P=.530). Rates of unscheduled visits were increased in the remote monitoring arm, but this did not reach statistical significance (5.0% [n=5] vs 12.5% [n=12], P=.059). When stratifying the primary outcome by race and randomization group, Black patients had lower rates of blood pressure ascertainment than White patients when assigned to in-office surveillance (41.2% [n=14] vs 69.5% [n=41], P=.007), but there was no difference in the remote management group (92.9% [n=26] vs 92.9% [n=52], P>.99). Conclusion: Remote monitoring can increase postpartum blood pressure ascertainment within 10 days of discharge for women with hypertensive disorders of pregnancy and has the potential to promote health equity.Item Specific Lowering of Asymmetric Dimethylarginine by Pharmacological Dimethylarginine Dimethylaminohydrolase Improves Endothelial Function, Reduces Blood Pressure and Ischemia-Reperfusion Injury(American Society for Pharmacology and Experimental Therapeutics, 2021) Lee, Young; Mehrotra, Purvi; Basile, David; Ullah, Mahbub; Singh, Arshnoor; Skill, Nicholas; Younes, Subhi Talal; Sasser, Jennifer; Shekhar, Anantha; Singh, Jaipal; Cellular and Integrative Physiology, School of MedicineMultiple clinical and preclinical studies have demonstrated that plasma levels of asymmetric dimethylarginine (ADMA) are strongly associated with hypertension, diabetes, and cardiovascular and renal disease. Genetic studies in rodents have provided evidence that ADMA metabolizing dimethylarginine dimethylaminohydrolase (DDAH)-1 plays a role in hypertension and cardiovascular disease. However, it remains to be established whether ADMA is a bystander, biomarker, or sufficient contributor to the pathogenesis of hypertension and cardiovascular and renal disease. The goal of the present investigation was to develop a pharmacological molecule to specifically lower ADMA and determine the physiologic consequences of ADMA lowering in animal models. Further, we sought to determine whether ADMA lowering will produce therapeutic benefits in vascular disease in which high ADMA levels are produced. A novel long-acting recombinant DDAH (M-DDAH) was produced by post-translational modification, which effectively lowered ADMA in vitro and in vivo. Treatment with M-DDAH improved endothelial function as measured by increase in cGMP and in vitro angiogenesis. In a rat model of hypertension, M-DDAH significantly reduced blood pressure (vehicle: 187 ± 19 mm Hg vs. M-DDAH: 157 ± 23 mm Hg; P < 0.05). Similarly, in a rat model of ischemia-reperfusion injury, M-DDAH significantly improved renal function as measured by reduction in serum creatinine (vehicle: 3.14 ± 0.74 mg/dl vs. M-DDAH: 1.1 ± 0.75 mg/dl; P < 0.01), inflammation, and injured tubules (vehicle: 73.1 ± 11.1% vs. M-DDAH: 22.1 ± 18.4%; P < 0.001). These pharmacological studies have provided direct evidence for a pathologic role of ADMA and the therapeutic benefits of ADMA lowering in preclinical models of endothelial dysfunction, hypertension, and ischemia-reperfusion injury. SIGNIFICANCE STATEMENT: High levels of ADMA occur in patients with cardiovascular and renal disease. A novel modified dimethylarginine dimethylaminohydrolase by PEGylation effectively lowers ADMA, improves endothelial function, reduces blood pressure and protects from ischemia-reperfusion renal injury.Item Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life: An Individual Participant Data Meta-Analysis(American Medical Association, 2023-09-05) Lennon, Matthew J.; Lam, Ben Chun Pan; Lipnicki, Darren M.; Crawford, John D.; Peters, Ruth; Schutte, Aletta E.; Brodaty, Henry; Thalamuthu, Anbupalam; Rydberg-Sterner, Therese; Najar, Jenna; Skoog, Ingmar; Riedel-Heller, Steffi G.; Röhr, Susanne; Pabst, Alexander; Lobo, Antonio; De-la-Cámara, Concepción; Lobo, Elena; Bello, Toyin; Gureje, Oye; Ojagbemi, Akin; Lipton, Richard B.; Katz, Mindy J.; Derby, Carol A.; Kim, Ki Woong; Han, Ji Won; Oh, Dae Jong; Rolandi, Elena; Davin, Annalisa; Rossi, Michele; Scarmeas, Nikolaos; Yannakoulia, Mary; Dardiotis, Themis; Hendrie, Hugh C.; Gao, Sujuan; Carrière, Isabelle; Ritchie, Karen; Anstey, Kaarin J.; Cherbuin, Nicolas; Xiao, Shifu; Yue, Ling; Li, Wei; Guerchet, Maëlenn M.; Preux, Pierre-Marie; Aboyans, Victor; Haan, Mary N.; Aiello, Allison E.; Ng, Tze Pin; Nyunt, Ma Shwe Zin; Gao, Qi; Scazufca, Marcia; Sachdev, Perminder S. S.; Psychiatry, School of MedicineImportance: The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. Objectives: To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group. Data source and study selection: Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece). Data extraction and synthesis: Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines. Main outcomes and measures: The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group. Results: The analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses. Conclusions and relevance: This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.