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Xiping Xu - One of the best experts on this subject based on the ideXlab platform.
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a gender specific association of the polymorphism ile197met in the kininogen 1 gene with plasma Irbesartan concentrations in chinese patients with essential hypertension
Journal of Human Hypertension, 2018Co-Authors: Shengnan Hu, Shanqun Jiang, Scott A Venners, Xiping Xu, Justin Weinstock, Jun Cheng, Suwen WuAbstract:This study was conducted to explore interactions in the association of the kininogen (KNG1) Ile197Met polymorphism and gender with plasma concentrations of Irbesartan in Chinese patients with essential hypertension. A total of 1100 subjects with essential hypertension received a daily oral dose of 150 mg Irbesartan for twenty-eight consecutive days. High-performance liquid chromatography-fluorescence (HPLC) was used to detect plasma Irbesartan concentrations on day 28. The KNG1 Ile197Met gene polymorphism was determined using high-throughput TaqMan technology. The frequency distribution of KNG1 Ile197Met genotype conformed to the Hardy-Weinberg equilibrium. After 28 days of treatment, patients with the GG genotype had significantly lower Irbesartan concentrations (P = 0.033) compared to homozygous TT genotype carriers. After stratifying by gender, male G allele carriers had significantly lower Irbesartan concentrations (GG, P = 0.015; TG, P = 0.015, respectively) relative to TT genotype after adjusting for age, region, body mass index (BMI), smoking, and alcohol consumption. However, there was no significant difference in female subjects. A further test for a multiplicative interaction between the KNG1 Ile197Met polymorphism and gender in association with ln-plasma Irbesartan concentrations in a multiple linear regression model was also significant (P for interaction = 0.033). This is the first study to suggest that gender may influence the association of the Ile197Met variant of KNG1 with ln-plasma Irbesartan concentration. This finding may indicate that the interaction of gender and the KNG1 Ile197Met gene polymorphism can influence plasma trough Irbesartan concentrations, which may contribute to a better development of personalized hypertensive treatment in Chinese patients.
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interactive effect of the kcnj11 ile337val polymorphism and cigarette smoking on the antihypertensive response to Irbesartan in chinese hypertensive patients
American Journal of Hypertension, 2016Co-Authors: Shanqun Jiang, Scott A Venners, Houxun Xing, Xiaobin Wang, Xiping Xu, Justin Weinstock, Binyan WangAbstract:This study was designed to detect the association of the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene polymorphism with antihypertensive therapeutic response to Irbesartan in a large-scale Chinese hypertensive population.A total of 1,099 patients with essential hypertension were enrolled to receive a daily dose of 150mg Irbesartan for 27 days. Pretreatment baseline blood pressure (BP) and posttreatment BP on the 28th day were measured. Plasma Irbesartan concentrations were measured by high-performance liquid chromatography-fluorescence. The KCNJ11 I337V gene polymorphism was determined using high-throughput TaqMan technology.The HapMap data in the Han Chinese population showed that the I337V was used as a representative for 4 common functional polymorphisms. Our results showed that the association of antihypertensive response to Irbesartan and the KCNJ11 genetic variant in the total sample was not significant. However, in nonsmokers, relative to the GG genotype, subjects with the homozygous AA genotype had a significantly higher therapeutic response to Irbesartan (adjusted beta ± SE: 4.7±1.9mm Hg, P = 0.015). In smokers, the subjects with the homozygous AA genotype had a significantly lower therapeutic response to Irbesartan (adjusted beta ± SE: -5.6±2.5mm Hg, P = 0.026). A multivariate linear regression model confirmed that there was a significant interactive effect between the KCNJ11 gene and smoking on Irbesartan treatment (interaction P = 0.001).The interactive effect of smoking status and the KCNJ11 genotype may influence the antihypertensive effects of Irbesartan, which indicates a consideration for future individualized antihypertensive drug treatment.
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interactive effect of angiotensin ii type 1 receptor agt1r polymorphisms and plasma Irbesartan concentration on antihypertensive therapeutic responses to Irbesartan
Journal of Hypertension, 2011Co-Authors: Shanqun Jiang, Scott A Venners, Yan Zhang, Houxun Xing, Xiaobin Wang, Xiping XuAbstract:Background To investigate the interactive effect of plasma Irbesartan concentration and angiotensin II type 1 receptor (AGT1R) gene polymorphisms on blood pressure (BP) response to Irbesartan treatment. Methods This study included 1049 Chinese hypertensive patients who were treated with daily oral 150 mg Irbesartan for 4 weeks. BP at predose and 28th day of treatment and trough plasma Irbesartan concentration (on 28th day of treatment) were measured. Four AGT1R gene polymorphisms (rs2640539, rs1492097, rs388915, rs5186) were genotyped. Multiple linear regression models were used to assess interactive effect of plasma Irbesartan concentration and gene polymorphisms on BP response, with adjustment for covariates. Results When stratified by genotypes, patients carrying allele C of single-neucleotide polymorphism (SNP) rs5186 showed positive association between Irbesartan concentration and BP response [SBP: β ± SE = 6.1 ± 2.3 with false discovery rate (FDR) P= 0.029; DBP: β ± SE = 2.7 ± 1.0 with FDR P = 0.029], but this was not seen in patients with AA genotype. There was a significant interaction between plasma Irbesartan concentration and SNP rs5186 on SBP response (interaction P=0.0335) and DBP response (interaction P = 0.0190). There also were significant interactions between plasma Irbesartan concentration and hap3, hap5 and hap6 (constructed by four genotyped SNPs) on SBP response (FDR P< 0.001), but not on DBP response. Conclusion Our data suggest that AGT1R gene polymorphisms and plasma concentration of Irbesartan can act interactively to modulate individual response to antihypertensive therapy using Irbesartan.
Shanqun Jiang - One of the best experts on this subject based on the ideXlab platform.
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CYP2C9 Ile359Leu polymorphism, plasma Irbesartan concentration and acute blood pressure reductions in response to Irbesartan treatment in Chinese hypertensive patients
Methods and Findings in Experimental and Clinical Pharmacology, 2020Co-Authors: Guangliang Chen, Shanqun Jiang, Yan Zhang, Shanchun Zhang, Xiumei Hong, Gengfu Tang, Zhiping Li, Houxun XingAbstract:Abstract Our previous study demonstrated that the CYP2C9*3 gene variant was significantly associated with elevated plasma Irbesartan concentration and blood pressure decline, assessed by a 4-week follow-up and revisit following daily administration of Irbesartan. We conducted a further analysis to examine the acute effects of the CYP2C9 polymorphism on plasma concentration and blood pressure through remeasurement 6 h after administration of Irbesartan. We used an extreme-sampling approach by selecting individuals from the top and bottom deciles of blood pressure response residuals to Irbesartan from the previous study population in Anhui, Taihu, and Dongzhi Counties, in China. A total of 196 subjects were available for the analysis. Pre- and posttreatment systolic and diastolic blood pressures (SBP and DBP), and venous blood samples (0.5, 2, and 6 h following the first treatment) were collected from each individual. Plasma Irbesartan concentrations were determined by a standard HPLC/fluorescence method. The observed frequencies were 97.7% for CYP2C9*1 (Ile359) and 2.3% for CYP2C9*3 (Leu359). Subjects with the CYP2C9*1/CYP2C9*3 genotype had significantly higher plasma Irbesartan concentrations when compared with those with the CYP2C9*1/CYP2C9*1 genotype (beta +/- SE = 81 +/- 36) and greater DBP response (beta +/- SE = 5.6 +/- 2.5 mmHg) at the 6-h time point after adjusting for important confounders. Our finding suggests that the CYP2C9*3 gene variant significantly alters the plasma concentration and acute DBP response at the 6-h point following Irbesartan treatment in Chinese hypertensive patients.
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a gender specific association of the polymorphism ile197met in the kininogen 1 gene with plasma Irbesartan concentrations in chinese patients with essential hypertension
Journal of Human Hypertension, 2018Co-Authors: Shengnan Hu, Shanqun Jiang, Scott A Venners, Xiping Xu, Justin Weinstock, Jun Cheng, Suwen WuAbstract:This study was conducted to explore interactions in the association of the kininogen (KNG1) Ile197Met polymorphism and gender with plasma concentrations of Irbesartan in Chinese patients with essential hypertension. A total of 1100 subjects with essential hypertension received a daily oral dose of 150 mg Irbesartan for twenty-eight consecutive days. High-performance liquid chromatography-fluorescence (HPLC) was used to detect plasma Irbesartan concentrations on day 28. The KNG1 Ile197Met gene polymorphism was determined using high-throughput TaqMan technology. The frequency distribution of KNG1 Ile197Met genotype conformed to the Hardy-Weinberg equilibrium. After 28 days of treatment, patients with the GG genotype had significantly lower Irbesartan concentrations (P = 0.033) compared to homozygous TT genotype carriers. After stratifying by gender, male G allele carriers had significantly lower Irbesartan concentrations (GG, P = 0.015; TG, P = 0.015, respectively) relative to TT genotype after adjusting for age, region, body mass index (BMI), smoking, and alcohol consumption. However, there was no significant difference in female subjects. A further test for a multiplicative interaction between the KNG1 Ile197Met polymorphism and gender in association with ln-plasma Irbesartan concentrations in a multiple linear regression model was also significant (P for interaction = 0.033). This is the first study to suggest that gender may influence the association of the Ile197Met variant of KNG1 with ln-plasma Irbesartan concentration. This finding may indicate that the interaction of gender and the KNG1 Ile197Met gene polymorphism can influence plasma trough Irbesartan concentrations, which may contribute to a better development of personalized hypertensive treatment in Chinese patients.
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interactive effect of the kcnj11 ile337val polymorphism and cigarette smoking on the antihypertensive response to Irbesartan in chinese hypertensive patients
American Journal of Hypertension, 2016Co-Authors: Shanqun Jiang, Scott A Venners, Houxun Xing, Xiaobin Wang, Xiping Xu, Justin Weinstock, Binyan WangAbstract:This study was designed to detect the association of the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene polymorphism with antihypertensive therapeutic response to Irbesartan in a large-scale Chinese hypertensive population.A total of 1,099 patients with essential hypertension were enrolled to receive a daily dose of 150mg Irbesartan for 27 days. Pretreatment baseline blood pressure (BP) and posttreatment BP on the 28th day were measured. Plasma Irbesartan concentrations were measured by high-performance liquid chromatography-fluorescence. The KCNJ11 I337V gene polymorphism was determined using high-throughput TaqMan technology.The HapMap data in the Han Chinese population showed that the I337V was used as a representative for 4 common functional polymorphisms. Our results showed that the association of antihypertensive response to Irbesartan and the KCNJ11 genetic variant in the total sample was not significant. However, in nonsmokers, relative to the GG genotype, subjects with the homozygous AA genotype had a significantly higher therapeutic response to Irbesartan (adjusted beta ± SE: 4.7±1.9mm Hg, P = 0.015). In smokers, the subjects with the homozygous AA genotype had a significantly lower therapeutic response to Irbesartan (adjusted beta ± SE: -5.6±2.5mm Hg, P = 0.026). A multivariate linear regression model confirmed that there was a significant interactive effect between the KCNJ11 gene and smoking on Irbesartan treatment (interaction P = 0.001).The interactive effect of smoking status and the KCNJ11 genotype may influence the antihypertensive effects of Irbesartan, which indicates a consideration for future individualized antihypertensive drug treatment.
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interactive effect of angiotensin ii type 1 receptor agt1r polymorphisms and plasma Irbesartan concentration on antihypertensive therapeutic responses to Irbesartan
Journal of Hypertension, 2011Co-Authors: Shanqun Jiang, Scott A Venners, Yan Zhang, Houxun Xing, Xiaobin Wang, Xiping XuAbstract:Background To investigate the interactive effect of plasma Irbesartan concentration and angiotensin II type 1 receptor (AGT1R) gene polymorphisms on blood pressure (BP) response to Irbesartan treatment. Methods This study included 1049 Chinese hypertensive patients who were treated with daily oral 150 mg Irbesartan for 4 weeks. BP at predose and 28th day of treatment and trough plasma Irbesartan concentration (on 28th day of treatment) were measured. Four AGT1R gene polymorphisms (rs2640539, rs1492097, rs388915, rs5186) were genotyped. Multiple linear regression models were used to assess interactive effect of plasma Irbesartan concentration and gene polymorphisms on BP response, with adjustment for covariates. Results When stratified by genotypes, patients carrying allele C of single-neucleotide polymorphism (SNP) rs5186 showed positive association between Irbesartan concentration and BP response [SBP: β ± SE = 6.1 ± 2.3 with false discovery rate (FDR) P= 0.029; DBP: β ± SE = 2.7 ± 1.0 with FDR P = 0.029], but this was not seen in patients with AA genotype. There was a significant interaction between plasma Irbesartan concentration and SNP rs5186 on SBP response (interaction P=0.0335) and DBP response (interaction P = 0.0190). There also were significant interactions between plasma Irbesartan concentration and hap3, hap5 and hap6 (constructed by four genotyped SNPs) on SBP response (FDR P< 0.001), but not on DBP response. Conclusion Our data suggest that AGT1R gene polymorphisms and plasma concentration of Irbesartan can act interactively to modulate individual response to antihypertensive therapy using Irbesartan.
Pablo Lapuerta - One of the best experts on this subject based on the ideXlab platform.
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A comparison of the efficacy and safety of Irbesartan/HCTZ combination therapy with Irbesartan and HCTZ monotherapy in the treatment of moderate hypertension
Journal of Human Hypertension, 2007Co-Authors: Joel M. Neutel, Pablo Lapuerta, Stanley S. Franklin, Amitabha Bhaumik, Agata PtaszynskaAbstract:A comparison of the efficacy and safety of Irbesartan/HCTZ combination therapy with Irbesartan and HCTZ monotherapy in the treatment of moderate hypertension
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efficacy and safety of Irbesartan hctz combination therapy as initial treatment for rapid control of severe hypertension
Journal of Clinical Hypertension, 2006Co-Authors: Joel M. Neutel, Stanley S. Franklin, Amitabha Bhaumik, Agata Ptaszynska, Suzanne Oparil, Pablo LapuertaAbstract:Severe hypertension is difficult to control. This prospective, randomized, double-blind, active-controlled, multicenter trial compared efficacy and safety of once-daily Irbesartan/hydrochlorothiazide (HCTZ) combination therapy with Irbesartan monotherapy in severe hypertension. Patients who were untreated or uncontrolled on monotherapy (seated diastolic blood pressure [BP] ≥110 mm Hg) received fixed-dose Irbesartan 150 mg/HCTZ 12.5 mg combination therapy for 7 weeks, force-titrated to Irbesartan 300 mg/HCTZ 25 mg at week 1 (n=468); or Irbesartan 150 mg monotherapy, force-titrated to 300 mg at week 1 (n=269). Significantly more patients on combination therapy achieved seated diastolic BP <90 mm Hg at week 5 (primary end point) compared with monotherapy recipients (47.2% vs 33.2%; P=.0005). Likewise, significantly more patients attained goals per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) (<140/90 mm Hg) at week 5 (34.6% vs 19.2%, respectively; P<.0001), while the mean difference between combination and monotherapy in seated diastolic BP and seated systolic BP was 4.7 mm Hg and 9.7 mm Hg (P<.0001). Greater and more rapid BP reduction with Irbesartan/HCTZ was achieved without additional side effects.
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cost effectiveness of early Irbesartan treatment versus control standard antihypertensive medications excluding ace inhibitors other angiotensin 2 receptor antagonists and dihydropyridine calcium channel blockers or late Irbesartan treatment in patie
Diabetes Care, 2004Co-Authors: Andrew J Palmer, Lieven Annemans, S Roze, Mark Lamotte, Pablo Lapuerta, Roland Chen, S Gabriel, P Carita, Roger A Rodby, Dick De ZeeuwAbstract:OBJECTIVE —The aim of this study was to determine the most cost-effective time point for initiation of Irbesartan treatment in hypertensive patients with type 2 diabetes and renal disease. RESEARCH DESIGN AND METHODS —This study was a Markov model–simulated progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, end-stage renal disease, and death in hypertensive patients with type 2 diabetes. Two Irbesartan strategies were created: early Irbesartan 300 mg daily (initiated with microalbuminuria) and late Irbesartan (initiated with overt nephropathy). These strategies were compared with control, which consisted of antihypertensive therapy with standard medications (excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) with comparable blood pressure control, initiated at microalbuminuria. Transition probabilities were taken from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial, and other published sources. Costs and life expectancy, discounted at 3% yearly, were projected over 25 years for 1,000 simulated patients using a third-party payer perspective in a U.S. setting. RESULTS —Compared with control, early and late Irbesartan treatment in 1,000 patients were projected to save (mean ± SD) $11.9 ± 3.3 million and $3.3 ± 2.7 million, respectively. Early use of Irbesartan added 1,550 ± 270 undiscounted life-years (discounted 960 ± 180), whereas late Irbesartan added 71 ± 40 life-years (discounted 48 ± 27) in 1,000 patients. Early Irbesartan treatment was superior under a wide-range of plausible assumptions. CONCLUSIONS —Early Irbesartan treatment was projected to improve life expectancy and reduce costs in hypertensive patients with type 2 diabetes and microalbuminuria. Later use of Irbesartan in overt nephropathy is also superior to standard care, but Irbesartan should be started earlier and continued long term.
Bobby V Khan - One of the best experts on this subject based on the ideXlab platform.
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Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome results of the Irbesartan and lipoic acid in endothelial dysfunction island study
Circulation, 2005Co-Authors: Srikanth Sola, Faiz A Cheema, Nadya Khanmerchant, Rekha G Menon, Sampath Parthasarathy, Bobby V KhanAbstract:Background— The metabolic syndrome is associated with increased angiotensin II activity, induction of a proinflammatory and oxidative state, and endothelial dysfunction. We evaluated the ability of Irbesartan, an angiotensin receptor blocker, and lipoic acid, an antioxidant, to affect endothelial function and inflammation in patients with the metabolic syndrome. Methods and Results— We randomized 58 subjects with the metabolic syndrome in a double-blinded manner to Irbesartan 150 mg/d (n=14), lipoic acid 300 mg/d (n=15), both Irbesartan and lipoic acid (n=15), or matching placebo (n=14) for 4 weeks. Endothelium-dependent and -independent flow-mediated vasodilation was determined under standard conditions. Plasma levels of interleukin-6, plasminogen activator-1, and 8-isoprostane were measured. After 4 weeks of therapy, endothelium-dependent flow-mediated vasodilation of the brachial artery was increased by 67%, 44%, and 75% in the Irbesartan, lipoic acid, and Irbesartan plus lipoic acid groups, respective...
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Irbesartan an angiotensin type 1 receptor inhibitor regulates markers of inflammation in patients with premature atherosclerosis
Journal of the American College of Cardiology, 2001Co-Authors: Sushant Navalkar, Sampath Parthasarathy, Nalini Santanam, Bobby V KhanAbstract:OBJECTIVES This study assessed the role of angiotensin II type 1 (AT1) receptor antagonists on inflammatory mechanisms involved in atherogenesis. Specific inflammatory markers included solubilized tumor necrosis factor-alpha receptor II (sTNF-αRII), vascular cell adhesion molecule-1 (VCAM-1) and superoxide. In addition, the AT1receptor blocker Irbesartan was evaluated for its ability to suppress these markers in individuals with atherosclerosis. BACKGROUND Mechanisms involved in the complex process of atherogenesis include alterations in the inflammatory responses. The use of compounds that suppress these responses may reduce the degree of damage seen in atherosclerosis. METHODS With a cross-sectional study design, 33 normotensive patients with stable coronary artery disease (CAD) were treated with Irbesartan for a 24-week period. These patients were compared against a control population with no known coronary atherosclerosis. Marker levels were measured by enzyme-linked immunosorbent assay technique and lucigenin chemiluminescence assay and statistically evaluated by two-way repeated measures analysis of variance. RESULTS All patients with coronary artery disease had increased levels of inflammatory molecules over those of control patients. Treatment with Irbesartan in these patients significantly reduced levels of inflammatory molecules measured. Soluble VCAM-1 levels were reduced by 36%; soluble TNF-alpha levels were reduced by 54% and superoxide level decreased by 52%. Maximal suppression of inflammatory markers by Irbesartan therapy in patients with CAD was seen at 12 weeks. CONCLUSIONS The effect of Irbesartan on each inflammatory marker is significant. Our results show that use of Irbesartan may retard the inflammatory process seen in premature forms of atherosclerosis.
Roland Chen - One of the best experts on this subject based on the ideXlab platform.
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cost effectiveness of early Irbesartan treatment versus control standard antihypertensive medications excluding ace inhibitors other angiotensin 2 receptor antagonists and dihydropyridine calcium channel blockers or late Irbesartan treatment in patie
Diabetes Care, 2004Co-Authors: Andrew J Palmer, Lieven Annemans, S Roze, Mark Lamotte, Pablo Lapuerta, Roland Chen, S Gabriel, P Carita, Roger A Rodby, Dick De ZeeuwAbstract:OBJECTIVE —The aim of this study was to determine the most cost-effective time point for initiation of Irbesartan treatment in hypertensive patients with type 2 diabetes and renal disease. RESEARCH DESIGN AND METHODS —This study was a Markov model–simulated progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, end-stage renal disease, and death in hypertensive patients with type 2 diabetes. Two Irbesartan strategies were created: early Irbesartan 300 mg daily (initiated with microalbuminuria) and late Irbesartan (initiated with overt nephropathy). These strategies were compared with control, which consisted of antihypertensive therapy with standard medications (excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) with comparable blood pressure control, initiated at microalbuminuria. Transition probabilities were taken from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial, and other published sources. Costs and life expectancy, discounted at 3% yearly, were projected over 25 years for 1,000 simulated patients using a third-party payer perspective in a U.S. setting. RESULTS —Compared with control, early and late Irbesartan treatment in 1,000 patients were projected to save (mean ± SD) $11.9 ± 3.3 million and $3.3 ± 2.7 million, respectively. Early use of Irbesartan added 1,550 ± 270 undiscounted life-years (discounted 960 ± 180), whereas late Irbesartan added 71 ± 40 life-years (discounted 48 ± 27) in 1,000 patients. Early Irbesartan treatment was superior under a wide-range of plausible assumptions. CONCLUSIONS —Early Irbesartan treatment was projected to improve life expectancy and reduce costs in hypertensive patients with type 2 diabetes and microalbuminuria. Later use of Irbesartan in overt nephropathy is also superior to standard care, but Irbesartan should be started earlier and continued long term.
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the cost effectiveness of Irbesartan in the treatment of hypertensive patients with type 2 diabetic nephropathy
Clinical Therapeutics, 2003Co-Authors: Roger A Rodby, Andrew J Palmer, Lieven Annemans, S Roze, Teresa A. Simon, Chionfang Chiou, Jeffrey T Borenstein, Allison Smitten, Nishan Sengupta, Roland ChenAbstract:Abstract Background: End-stage renal disease (ESRD)-related health care costs are substantial. Improving clinical outcomes in patients at risk of progression to ESRD could lead to considerable health care savings. Objective: We estimated the cost-effectiveness of Irbesartan compared with placebo or amlodipine in the treatment of patients with type 2 diabetes mellitus, hypertension, and overt nephropathy. Methods : Three treatments for hypertensioe patients with type 2 diabetes mellitus and nephropathy were assessed: (1) Irbesartan, (2) amlodipine, and (3) placebo. A Markov model was developed based on primary data from the Irbesartan in Diabetic Nephropathy Trial and the United States Renal Data System. Projected survival and costs were compared for each treatment at 3-, 10-, and 25-year time horizons. Different assumptions of treatment benefits and costs were tested with use of sensitivity analyses. Results: At 10 and 25 years, the model projected Irbesartan to be both the least costly and most effective (ie, demonstrating a survival advantage) strategy. At 25
