Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 54

Publication Record

Connections

Prospective Study of Cardiac Events During Proteasome Inhibitor Therapy for Relapsed Multiple Myeloma.
Cornell RF, Ky B, Weiss BM, Dahm CN, Gupta DK, Du L, Carver JR, Cohen AD, Engelhardt BG, Garfall AL, Goodman SA, Harrell SL, Kassim AA, Jadhav T, Jagasia M, Moslehi J, O'Quinn R, Savona MR, Slosky D, Smith A, Stadtmauer EA, Vogl DT, Waxman A, Lenihan D
(2019) J Clin Oncol 37: 1946-1955
MeSH Terms: Adult, Aged, Aged, 80 and over, Bortezomib, Cardiovascular Diseases, Disease-Free Survival, Electrocardiography, Female, Heart Diseases, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Molecular Targeted Therapy, Multiple Myeloma, Natriuretic Peptide, Brain, Neoplasm Recurrence, Local, Oligopeptides, Prospective Studies, Proteasome Inhibitors, Risk Factors, Time-to-Treatment, Treatment Outcome, Troponin I, Troponin T
Show Abstract · Added November 12, 2019
PURPOSE - Cardiovascular adverse events (CVAEs) can occur during proteasome inhibitor (PI) therapy. We conducted a prospective, observational, multi-institutional study to define risk factors and outcomes in patients with multiple myeloma (MM) receiving PIs.
PATIENTS AND METHODS - Patients with relapsed MM initiating carfilzomib- or bortezomib-based therapy underwent baseline assessments and repeated assessments at regular intervals over 6 months, including cardiac biomarkers (troponin I or T, brain natriuretic peptide [BNP], and N-terminal proBNP), ECG, and echocardiography. Monitoring occurred over 18 months for development of CVAEs.
RESULTS - Of 95 patients enrolled, 65 received carfilzomib and 30 received bortezomib, with median 25 months of follow-up. Sixty-four CVAEs occurred, with 55% grade 3 or greater in severity. CVAEs occurred in 51% of patients treated with carfilzomib and 17% of those treated with bortezomib ( = .002). Median time to first CVAE from treatment start was 31 days, and 86% occurred within the first 3 months. Patients receiving carfilzomib-based therapy with a baseline elevated BNP level higher than 100 pg/mL or N-terminal proBNP level higher than 125 pg/mL had increased risk for CVAE (odds ratio, 10.8; < .001). Elevated natriuretic peptides occurring mid-first cycle of treatment with carfilzomib were associated with a substantially higher risk of CVAEs (odds ratio, 36.0; < .001). Patients who experienced a CVAE had inferior progression-free survival (log-rank = .01) and overall survival (log-rank < .001). PI therapy was safely resumed in 89% of patients, although 41% required chemotherapy modifications.
CONCLUSION - CVAEs are common during PI therapy for relapsed MM, especially with carfilzomib, particularly within the first 3 months of therapy. CVAEs were associated with worse overall outcomes, but usually, discontinuation of therapy was not required. Natriuretic peptides were highly predictive of CVAEs; however, validation of this finding is necessary before uniform incorporation into the routine management of patients receiving carfilzomib.
0 Communities
1 Members
0 Resources
25 MeSH Terms
NT-proBNP, race and endothelial function in the Multi-Ethnic Study of Atherosclerosis.
Yang S, Huang S, Daniels LB, Yeboah J, Lima JAC, Cannone V, Burnett JC, Beckman JA, Carr JJ, Wang TJ, Gupta DK
(2019) Heart 105: 1590-1596
MeSH Terms: African Americans, Asian Americans, Atherosclerosis, Cross-Sectional Studies, Endothelium, Vascular, Female, Humans, Male, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Risk Factors, United States, Vasodilation
Show Abstract · Added January 10, 2020
OBJECTIVE - Natriuretic peptides (NPs) are hormones with cardioprotective effects. NP levels vary by race; however, the pathophysiological consequences of lower NP levels are not well understood. We aimed to quantify the association between NPs and endothelial function as measured by flow-mediated dilation (FMD) and the contribution of NP levels to racial differences in endothelial function.
METHODS - In this cross-sectional study of 2938 Multi-Ethnic Study of Atherosclerosis participants (34% Caucasian, 20% African-American, 20% Asian-American and 26% Hispanic) without cardiovascular disease at baseline, multivariable linear regression models were used to examine the association between serum N-terminal pro-B-type NP (NT-proBNP) and natural log-transformed FMD. We also tested whether NT-proBNP mediated the relationship between race and FMD using the product of coefficients method.
RESULTS - Among African-American and Chinese-American individuals, lower NT-proBNP levels were associated with lower FMD, β=0.06 (95% CI: 0.03 to 0.09; p<0.001) and β=0.06 (95% CI: 0.02 to 0.09; p=0.002), respectively. Non-significant associations between NT-proBNP and FMD were found in Hispanic and Caucasian individuals. In multivariable models, endothelial function differed by race, with African-American individuals having the lowest FMD compared with Caucasians, p<0.001. Racial differences in FMD among African-Americans and Chinese-Americans were mediated in part by NT-proBNP levels (African-Americans, mediation effect: -0.03(95% CI: -0.05 to -0.01); Chinese-Americans, mediation effect: -0.03(95% CI: -0.05 to -0.01)).
CONCLUSIONS - Lower NP levels are associated with worse endothelial function among African-Americans and Chinese-Americans. A relative NP deficiency in some racial/ethnic groups may contribute to differences in vascular function.
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Acute effects of insulin on circulating natriuretic peptide levels in humans.
Bachmann KN, Deger SM, Alsouqi A, Huang S, Xu M, Ferguson JF, Su YR, Niswender KD, Ikizler TA, Wang TJ
(2018) PLoS One 13: e0196869
MeSH Terms: Adult, Aged, Atrial Natriuretic Factor, Female, Glucose Clamp Technique, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Natriuretic Peptide, Brain, Obesity, Peptide Fragments
Show Abstract · Added April 2, 2019
BACKGROUND - The natriuretic peptide hormones play an important role in salt and blood pressure regulation. In observational studies, obesity and insulin resistance have been consistently associated with lower concentrations of natriuretic peptides. It has been proposed that insulin influences natriuretic peptide production.
OBJECTIVE - We sought to determine the acute effects of insulin administration on natriuretic peptide concentrations.
METHODS - 31 men and women (11 lean, 10 overweight, and 10 obese), ages 30-70 years, without cardiovascular disease or overt diabetes underwent a hyperinsulinemic-euglycemic insulin clamp. Plasma concentrations of N-terminal pro atrial natriuretic peptide (NT-proANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured at baseline and steady-state (the final 30 minutes of the clamp protocol).
RESULTS - From baseline to steady-state, insulin levels increased from a mean level of 9.5 to 176.7 μU/ml (p<0.001). Over this period, circulating NT-proANP concentrations decreased by 9% (-1933 ng/L, p = 0.01). The changes in NT-proANP did not differ between lean, overweight, and obese individuals. Steady-state NT-proANP levels, adjusted for baseline, were lower in individuals with greater insulin resistance, independent of BMI. In contrast to NT-proANP, NT-proBNP levels did not change significantly during the clamp (p = 0.41).
CONCLUSION - Insulin administration was associated with a moderate decrease in circulating NT-proANP, but not NT-proBNP. The lowest NT-proANP concentrations were found in insulin-resistant individuals. Further investigations are warranted to elucidate potential mechanisms underlying the effects of insulin on the cardiac hormonal axis.
0 Communities
1 Members
0 Resources
MeSH Terms
Differences in Natriuretic Peptide Levels by Race/Ethnicity (From the Multi-Ethnic Study of Atherosclerosis).
Gupta DK, Daniels LB, Cheng S, deFilippi CR, Criqui MH, Maisel AS, Lima JA, Bahrami H, Greenland P, Cushman M, Tracy R, Siscovick D, Bertoni AG, Cannone V, Burnett JC, Carr JJ, Wang TJ
(2017) Am J Cardiol 120: 1008-1015
MeSH Terms: Aged, Aged, 80 and over, Atherosclerosis, Biomarkers, Continental Population Groups, Ethnic Groups, Female, Follow-Up Studies, Humans, Male, Middle Aged, Morbidity, Natriuretic Peptide, Brain, Peptide Fragments, Prevalence, Prognosis, Prospective Studies, Risk Factors, United States
Show Abstract · Added September 11, 2017
Natriuretic peptides (NP) are cardiac-derived hormones with favorable cardiometabolic actions. Low NP levels are associated with increased risks of hypertension and diabetes mellitus, conditions with variable prevalence by race and ethnicity. Heritable factors underlie a significant proportion of the interindividual variation in NP concentrations, but the specific influences of race and ancestry are unknown. In 5597 individuals (40% white, 24% black, 23% Hispanic, and 13% Chinese) without prevalent cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis, multivariable linear regression and restricted cubic splines were used to estimate differences in serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels according to, ethnicity, and ancestry. Ancestry was determined using genetic ancestry informative markers. NT-proBNP concentrations differed significantly by race and ethnicity (black, median 43 pg/ml [interquartile range 17 to 94], Chinese 43 [17 to 90], Hispanic 53 [23 to 107], white 68 [34 to 136]; p = 0.0001). In multivariable models, NT-proBNP was 44% lower (95% confidence interval -48 to -40) in black and 46% lower (-50 to -41) in Chinese, compared with white individuals. Hispanic individuals had intermediate concentrations. Self-identified blacks and Hispanics were the most genetically admixed. Among self-identified black individuals, a 20% increase in genetic European ancestry was associated with 12% higher (1% to 23%) NT-proBNP. Among Hispanic individuals, genetic European and African ancestry were positively and negatively associated with NT-proBNP levels, respectively. In conclusion, NT-proBNP levels differ according to race and ethnicity, with the lowest concentrations in black and Chinese individuals. Racial and ethnic differences in NT-proBNP may have a genetic basis, with European and African ancestry associated with higher and lower NT-proBNP concentrations, respectively.
Copyright © 2017 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
19 MeSH Terms
B-Type Natriuretic Peptide, Aldosterone, and Fluid Management in ARDS.
Semler MW, Marney AM, Rice TW, Nian H, Yu C, Wheeler AP, Brown NJ, NIH NHLBI ARDS Network
(2016) Chest 150: 102-11
MeSH Terms: Adult, Aged, Aldosterone, Biomarkers, Female, Fluid Therapy, Hospital Mortality, Humans, Male, Middle Aged, Natriuretic Peptide, Brain, Outcome Assessment, Health Care, Respiratory Distress Syndrome, Adult, Statistics as Topic, Water-Electrolyte Balance
Show Abstract · Added April 6, 2017
BACKGROUND - Conservative fluid management increases ventilator-free days without influencing overall mortality in acute respiratory distress syndrome. Plasma concentrations of B-type natriuretic peptide (a marker of ventricular filling) or aldosterone (a marker of effective circulating volume) may identify patients for whom fluid management impacts survival.
METHODS - This was a retrospective analysis of the Fluid and Catheter Treatment Trial (FACTT), a randomized trial comparing conservative with liberal fluid management in acute respiratory distress syndrome. Using plasma collected at study enrollment, we measured B-type natriuretic peptide and aldosterone by immunoassay. Multivariable analyses examined the interaction between B-type natriuretic peptide or aldosterone concentration and fluid strategy with regard to 60-day in-hospital mortality.
RESULTS - Among 625 patients with adequate plasma, median B-type natriuretic peptide concentration was 825 pg/mL (interquartile range, 144-1,574 pg/mL), and median aldosterone was 2.49 ng/dL (interquartile range, 1.1-4.3 ng/dL). B-type natriuretic peptide did not predict overall mortality, correlate with fluid balance, or modify the effect of conservative vs liberal fluid management on outcomes. In contrast, among patients with lower aldosterone concentrations, conservative fluid management increased ventilator-free days (17.1 ± 9.8 vs 12.5 ± 10.3, P < .001) and decreased mortality (19% vs 30%, P = .03) (P value for interaction = .01).
CONCLUSIONS - In acute respiratory distress syndrome, B-type natriuretic peptide does not modify the effect of fluid management on outcomes. Lower initial aldosterone appears to identify patients for whom conservative fluid management may improve mortality.
Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.
Kato N, Loh M, Takeuchi F, Verweij N, Wang X, Zhang W, Kelly TN, Saleheen D, Lehne B, Leach IM, Drong AW, Abbott J, Wahl S, Tan ST, Scott WR, Campanella G, Chadeau-Hyam M, Afzal U, Ahluwalia TS, Bonder MJ, Chen P, Dehghan A, Edwards TL, Esko T, Go MJ, Harris SE, Hartiala J, Kasela S, Kasturiratne A, Khor CC, Kleber ME, Li H, Yu Mok Z, Nakatochi M, Sapari NS, Saxena R, Stewart AFR, Stolk L, Tabara Y, Teh AL, Wu Y, Wu JY, Zhang Y, Aits I, Da Silva Couto Alves A, Das S, Dorajoo R, Hopewell JC, Kim YK, Koivula RW, Luan J, Lyytikäinen LP, Nguyen QN, Pereira MA, Postmus I, Raitakari OT, Scannell Bryan M, Scott RA, Sorice R, Tragante V, Traglia M, White J, Yamamoto K, Zhang Y, Adair LS, Ahmed A, Akiyama K, Asif R, Aung T, Barroso I, Bjonnes A, Braun TR, Cai H, Chang LC, Chen CH, Cheng CY, Chong YS, Collins R, Courtney R, Davies G, Delgado G, Do LD, Doevendans PA, Gansevoort RT, Gao YT, Grammer TB, Grarup N, Grewal J, Gu D, Wander GS, Hartikainen AL, Hazen SL, He J, Heng CK, Hixson JE, Hofman A, Hsu C, Huang W, Husemoen LLN, Hwang JY, Ichihara S, Igase M, Isono M, Justesen JM, Katsuya T, Kibriya MG, Kim YJ, Kishimoto M, Koh WP, Kohara K, Kumari M, Kwek K, Lee NR, Lee J, Liao J, Lieb W, Liewald DCM, Matsubara T, Matsushita Y, Meitinger T, Mihailov E, Milani L, Mills R, Mononen N, Müller-Nurasyid M, Nabika T, Nakashima E, Ng HK, Nikus K, Nutile T, Ohkubo T, Ohnaka K, Parish S, Paternoster L, Peng H, Peters A, Pham ST, Pinidiyapathirage MJ, Rahman M, Rakugi H, Rolandsson O, Ann Rozario M, Ruggiero D, Sala CF, Sarju R, Shimokawa K, Snieder H, Sparsø T, Spiering W, Starr JM, Stott DJ, Stram DO, Sugiyama T, Szymczak S, Tang WHW, Tong L, Trompet S, Turjanmaa V, Ueshima H, Uitterlinden AG, Umemura S, Vaarasmaki M, van Dam RM, van Gilst WH, van Veldhuisen DJ, Viikari JS, Waldenberger M, Wang Y, Wang A, Wilson R, Wong TY, Xiang YB, Yamaguchi S, Ye X, Young RD, Young TL, Yuan JM, Zhou X, Asselbergs FW, Ciullo M, Clarke R, Deloukas P, Franke A, Franks PW, Franks S, Friedlander Y, Gross MD, Guo Z, Hansen T, Jarvelin MR, Jørgensen T, Jukema JW, Kähönen M, Kajio H, Kivimaki M, Lee JY, Lehtimäki T, Linneberg A, Miki T, Pedersen O, Samani NJ, Sørensen TIA, Takayanagi R, Toniolo D, BIOS-consortium, CARDIo GRAMplusCD, LifeLines Cohort Study, InterAct Consortium, Ahsan H, Allayee H, Chen YT, Danesh J, Deary IJ, Franco OH, Franke L, Heijman BT, Holbrook JD, Isaacs A, Kim BJ, Lin X, Liu J, März W, Metspalu A, Mohlke KL, Sanghera DK, Shu XO, van Meurs JBJ, Vithana E, Wickremasinghe AR, Wijmenga C, Wolffenbuttel BHW, Yokota M, Zheng W, Zhu D, Vineis P, Kyrtopoulos SA, Kleinjans JCS, McCarthy MI, Soong R, Gieger C, Scott J, Teo YY, He J, Elliott P, Tai ES, van der Harst P, Kooner JS, Chambers JC
(2015) Nat Genet 47: 1282-1293
MeSH Terms: Adult, Aged, Aged, 80 and over, Asian Continental Ancestry Group, Blood Pressure, Cardiovascular Diseases, DNA Methylation, European Continental Ancestry Group, Female, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Polymorphism, Single Nucleotide, Regression Analysis, Risk Factors
Show Abstract · Added February 22, 2016
We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
0 Communities
2 Members
0 Resources
22 MeSH Terms
Racial differences in circulating natriuretic peptide levels: the atherosclerosis risk in communities study.
Gupta DK, Claggett B, Wells Q, Cheng S, Li M, Maruthur N, Selvin E, Coresh J, Konety S, Butler KR, Mosley T, Boerwinkle E, Hoogeveen R, Ballantyne CM, Solomon SD
(2015) J Am Heart Assoc 4:
MeSH Terms: African Americans, Atherosclerosis, European Continental Ancestry Group, Female, Humans, Hypertension, Male, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Residence Characteristics, Risk Factors
Show Abstract · Added April 6, 2017
BACKGROUND - Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking.
METHODS AND RESULTS - We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996-1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], -43, -36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP.
CONCLUSIONS - African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in this population.
© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
0 Communities
1 Members
0 Resources
12 MeSH Terms
B-type natriuretic peptides help in cardioembolic stroke diagnosis: pooled data meta-analysis.
Llombart V, Antolin-Fontes A, Bustamante A, Giralt D, Rost NS, Furie K, Shibazaki K, Biteker M, Castillo J, Rodríguez-Yáñez M, Fonseca AC, Watanabe T, Purroy F, Zhixin W, Etgen T, Hosomi N, Jafarian Kerman SR, Sharma JC, Knauer C, Santamarina E, Giannakoulas G, García-Berrocoso T, Montaner J
(2015) Stroke 46: 1187-95
MeSH Terms: Aged, Aged, 80 and over, Electrocardiography, Embolism, Female, Humans, Male, Middle Aged, Natriuretic Peptide, Brain, Predictive Value of Tests, Stroke
Show Abstract · Added April 25, 2016
BACKGROUND AND PURPOSE - Determining the underlying cause of stroke is important to optimize secondary prevention treatment. Increased blood levels of natriuretic peptides (B-type natriuretic peptide/N-terminal pro-BNP [BNP/NT-proBNP]) have been repeatedly associated with cardioembolic stroke. Here, we evaluate their clinical value as pathogenic biomarkers for stroke through a literature systematic review and individual participants' data meta-analysis.
METHODS - We searched publications in PubMed database until November 2013 that compared BNP and NT-proBNP circulating levels among stroke causes. Standardized individual participants' data were collected to estimate predictive values of BNP/NT-proBNP for cardioembolic stroke. Dichotomized BNP/NT-proBNP levels were included in logistic regression models together with clinical variables to assess the sensitivity and specificity to identify cardioembolic strokes and the additional value of biomarkers using area under the curve and integrated discrimination improvement index.
RESULTS - From 23 selected articles, we collected information of 2834 patients with a defined cause. BNP/NT-proBNP levels were significantly elevated in cardioembolic stroke until 72 hours from symptoms onset. Predictive models showed a sensitivity >90% and specificity >80% when BNP/NT-proBNP were added considering the lowest and the highest quartile, respectively. Both peptides also increased significantly the area under the curve and integrated discrimination improvement index compared with clinical models. Sensitivity, specificity, and precision of the models were validated in 197 patients with initially undetermined stroke with final pathogenic diagnosis after ancillary follow-up.
CONCLUSIONS - Natriuretic peptides are strongly increased in cardioembolic strokes. Future multicentre prospective studies comparing BNP and NT-proBNP might aid in finding the optimal biomarker, the best time point, and the optimal cutoff points for cardioembolic stroke identification.
© 2015 American Heart Association, Inc.
0 Communities
1 Members
0 Resources
11 MeSH Terms
Dipeptidyl-peptidase 4 inhibition and the vascular effects of glucagon-like peptide-1 and brain natriuretic peptide in the human forearm.
Devin JK, Pretorius M, Nian H, Yu C, Billings FT, Brown NJ
(2014) J Am Heart Assoc 3:
MeSH Terms: Adult, Cross-Over Studies, Dipeptidyl-Peptidase IV Inhibitors, Double-Blind Method, Female, Forearm, Glucagon-Like Peptide 1, Healthy Volunteers, Humans, Male, Middle Aged, Natriuretic Peptide, Brain, Pyrazines, Regional Blood Flow, Sitagliptin Phosphate, Triazoles, Vasodilation
Show Abstract · Added January 20, 2015
BACKGROUND - Dipeptidyl-peptidase 4 (DPP4) inhibitors improve glycemic control in patients with diabetes mellitus by preventing the degradation of glucagon-like peptide-1 (GLP-1). GLP-1 causes vasodilation in animal models but also increases sympathetic activity; the effect of GLP-1 in the human vasculature and how it is altered by DPP4 inhibition is not known. DPP4 also degrades the vasodilator brain natriuretic peptide (BNP) to a less potent metabolite. This study tested the hypothesis that DPP4 inhibition potentiates the vasodilator responses to GLP-1 and BNP in the human forearm.
METHOD AND RESULTS - Seventeen healthy subjects participated in this randomized, double-blinded, placebo-controlled crossover study. On each study day, subjects received DPP4 inhibitor (sitagliptin 200 mg by mouth) or placebo. Sitagliptin increased forearm blood flow and decreased forearm vascular resistance without affecting mean arterial pressure and pulse. GLP-1 and BNP were infused in incremental doses via brachial artery. Venous GLP-1 concentrations were significantly higher during sitagliptin use, yet there was no effect of GLP-1 on forearm blood flow in the presence or absence of sitagliptin. BNP caused dose-dependent vasodilation; however, sitagliptin did not affect this response. GLP-1 and BNP had no effect on net norepinephrine release.
CONCLUSIONS - These data suggest that GLP-1 does not act as a direct vasodilator in humans and does not contribute to sympathetic activation. Sitagliptin does not regulate vascular function in healthy humans by affecting the degradation of GLP-1 and BNP.
CLINICAL TRIAL REGISTRATION URL - www.clinicaltrials.gov/ Unique identifier: NCT01413542.
© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
0 Communities
2 Members
0 Resources
17 MeSH Terms
2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW, American College of Cardiology/American Heart Association Task Force on Practice Guidelines
(2014) J Am Coll Cardiol 64: e1-76
MeSH Terms: Anti-Arrhythmia Agents, Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Autonomic Nervous System, C-Reactive Protein, Cardiac Output, Low, Catheter Ablation, Comorbidity, Defibrillators, Implantable, Echocardiography, Transesophageal, Electric Countershock, Electrocardiography, Fibrinolytic Agents, Heart Atria, Heart Conduction System, Humans, Inflammation, Natriuretic Peptide, Brain, Oxidative Stress, Pacemaker, Artificial, Platelet Aggregation Inhibitors, Renin-Angiotensin System, Risk Assessment, Risk Factors, Septal Occluder Device, Stroke, Thromboembolism, Ventricular Remodeling
Added May 27, 2014
0 Communities
1 Members
0 Resources
29 MeSH Terms