Abstract:
BACKGROUND:Diminished growth hormone (GH) is associated with impaired endothelial function and fibrinolysis. GH-releasing hormone is the primary stimulus for GH secretion and a substrate of dipeptidyl peptidase-4. We tested the hypothesis that dipeptidyl peptidase-4 inhibition with sitagliptin increases stimulated GH secretion, vasodilation, and tissue plasminogen activator (tPA) activity. METHODS AND RESULTS:Healthy adults participated in a 2-part double-blind, randomized, placebo-controlled, crossover study. First, 39 patients (29 women) received sitagliptin or placebo on each of 2 days separated by a washout. One hour after study drug, blood was sampled and then arginine (30 g IV) was given to stimulate GH. Vasodilation was assessed by plethysmography and blood sampled for 150 minutes. Following a washout, 19 of the original 29 women received sitagliptin alone versus sitagliptin plus antagonist to delineate GH receptor (GHR)- (n=5), nitric oxide- (n=7), or glucagon-like peptide-1 receptor- (n=7) dependent effects. Sitagliptin enhanced stimulated GH secretion (P<0.01 versus placebo, for 30 minutes) and free insulin-like growth factor-1 (P<0.001 versus placebo, after adjustment for baseline) in women. Vasodilation and tPA increased in all patients, but sitagliptin enhanced vasodilation (P=0.01 versus placebo) and increased tPA (P<0.001) in women only. GHR blockade decreased free insulin-like growth factor-1 (P=0.04 versus sitagliptin alone) and increased stimulated GH (P<0.01), but decreased vascular resistance (P=0.01) such that nadir vascular resistance correlated inversely with GH (rs=-0.90, P<0.001). GHR blockade suppressed tPA. Neither nitric oxide nor glucagon-like peptide-1 receptor blockade affected vasodilation or tPA. CONCLUSIONS:Sitagliptin enhances stimulated GH, vasodilation, and fibrinolysis in women. During sitagliptin, increases in free insulin-like growth factor-1 and tPA occur via the GHR, whereas vasodilation correlates with GH but occurs through a GHR-independent mechanism. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01701973.
journal_name
J Am Heart Assocjournal_title
Journal of the American Heart Associationauthors
Wilson JR,Brown NJ,Nian H,Yu C,Bidlingmaier M,Devin JKdoi
10.1161/JAHA.117.008000subject
Has Abstractpub_date
2018-02-25 00:00:00issue
5issn
2047-9980pii
JAHA.117.008000journal_volume
7pub_type
杂志文章,随机对照试验abstract:BACKGROUND:Perioperative antiplatelet agents potentially increase bleeding after non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). The protease-activated receptor 1 antagonist vorapaxar reduced cardiovascular events and was associated with increased bleeding versus placebo in NSTE ACS, but its efficacy an...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1161/JAHA.115.002546
更新日期:2015-12-15 00:00:00
abstract::Background Atrial fibrillation (AF) has been shown to be associated with an increased risk of dementia as well as Alzheimer disease in observational studies. Whether this association reflects causal association is still unclear. The purpose of this study was to examine the causal association of AF with Alzheimer disea...
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pub_type: 杂志文章
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doi:10.1161/JAHA.115.002012
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abstract::See Article Shah et al. ...
journal_title:Journal of the American Heart Association
pub_type: 评论,社论
doi:10.1161/JAHA.119.012833
更新日期:2019-06-04 00:00:00
abstract::Background Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage renal disease. Heart rhythm complexity analysis has been shown to be useful in predicting outcomes in various diseases; however, data on patients with end-stage renal disease are limited. In this study, we anal...
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pub_type: 杂志文章
doi:10.1161/JAHA.119.013036
更新日期:2020-01-21 00:00:00
abstract::Background Platelets play a role in promoting inflammatory responses under several disease conditions. Platelets are activated in hypertensive patients. However, the mechanisms responsible for platelet-mediating vascular inflammation are unknown. The present study investigated the role of platelets in promoting vascul...
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doi:10.1161/JAHA.118.009600
更新日期:2018-11-06 00:00:00
abstract:BACKGROUND:The p.Gln554X mutation in desmocollin-2 (DSC2) is prevalent in ≈10% of the Hutterite population. While the homozygous mutation causes severe biventricular arrhythmogenic right ventricular cardiomyopathy, the phenotypic features and prognosis of heterozygotes remain incompletely understood. METHODS AND RESUL...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.114.001407
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.003414
更新日期:2016-07-05 00:00:00
abstract::Background Limited data are available on the prospective relationship between beverage consumption and plasma lipid and lipoprotein concentrations. Two major sources of sugar in the US diet are sugar-sweetened beverages (SSBs) and 100% fruit juices. Low-calorie sweetened beverages are common replacements. Methods and ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.014083
更新日期:2020-03-03 00:00:00
abstract:BACKGROUND:Obesity is closely associated with various cardiovascular diseases (CVDs). Adipose tissue inflammation and perturbation of adipokine secretion may contribute to the pathogenesis of CVD. This study aimed to evaluate whether the 2 most abundant adipokines, adipocyte-fatty acid binding protein (A-FABP) and adip...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.112.004176
更新日期:2013-01-15 00:00:00
abstract:BACKGROUND:Transcription of the myristoylated alanine-rich C kinase substrate (MARCKS) is upregulated in animal models of intimal hyperplasia. MARCKS knockdown inhibits vascular smooth muscle cell (VSMC) migration in vitro; however, the mechanism is as yet unknown. We sought to elucidate the mechanism of MARCKS-mediate...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.115.002255
更新日期:2015-10-08 00:00:00
abstract:BACKGROUND:Oxidative stress is implicated in the etiology of coronary heart disease (CHD). New measures to capture oxidative stress are warranted. Fluorescent oxidation products (FlOPs) can be measured in plasma and have been shown to reflect levels of oxidative stress and to predict risk of CHD in men over 6 years of ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.113.000195
更新日期:2013-10-08 00:00:00
abstract:BACKGROUND:Coronary heart disease and peripheral arterial disease (PAD) affect different vascular territories. Supplementing baseline findings with assays from stored serum, we compared their 20-year predictors. METHODS AND RESULTS:We randomly recruited 15 737 disease-free men and women aged 30 to 75 years across Scot...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.117.005967
更新日期:2017-09-18 00:00:00
abstract:BACKGROUND:Diagnosis of atrial fibrillation (AF) can be difficult, requiring cumbersome investigations. We aimed to determine the association of established whole-blood gene expression scores with prevalent AF and to evaluate their performance for the identification of AF in a SIRS (Steroids in Cardiac Surgery) trial c...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1161/JAHA.117.006057
更新日期:2017-06-30 00:00:00
abstract::Background Ischemic heart disease continues to be a leading cause of mortality in patients. Extracellular vesicles (EVs) provide a potential for treatment that may induce collateral vessel growth to increase myocardial perfusion. Methods and Results Nineteen male Yorkshire pigs were given a high-fat diet for 4 weeks, ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.012617
更新日期:2019-08-06 00:00:00
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journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.014742
更新日期:2020-06-02 00:00:00
abstract::Background Sex differences in outcome have been reported in patients with congenital long QT syndrome. We aimed to report on the incidence of time-dependent life-threatening events in male and female patients with long QT syndrome with an implantable cardioverter defibrillator (ICD). Methods and Results A total of 60 ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.016398
更新日期:2020-10-20 00:00:00
abstract:BACKGROUND:Transseptal puncture is a critical step in achieving left atrial (LA) access for a variety of cardiac procedures. Although the mechanical Brockenbrough needle has historically been used for this procedure, a needle employing radiofrequency (RF) energy has more recently been approved for clinical use. We soug...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,随机对照试验
doi:10.1161/JAHA.113.000428
更新日期:2013-09-17 00:00:00
abstract::Background We aimed to determine the change in treatment strategies and times to treatment over the first 5 years of the Mission: Lifeline program. Methods and Results We assessed pre- and in-hospital care and outcomes from 2008 to 2012 for patients with ST -segment-elevation myocardial infarction at US hospitals, usi...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.118.008096
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abstract:BACKGROUND:The 4-variable risk score from University of California, Los Angeles (UCLA) demonstrated superior discrimination in advanced heart failure, compared to established risk scores. However, the model has not been externally validated, and its suitability as a selection tool for heart transplantation (HT) and lef...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.114.000998
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abstract::Background Crossover dilutes treatment effect and reduces statistical power of intention-to-treat analysis. We examined incidence and impact on cardiac surgery randomized controlled trial (RCT) outcomes of crossover from experimental to control interventions, or vice versa. Methods and Results MEDLINE, EMBASE, and Coc...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,meta分析
doi:10.1161/JAHA.119.013711
更新日期:2019-11-05 00:00:00
abstract:BACKGROUND:The scientific evidence base in support of population-wide salt reduction is strong, but current high-quality data about salt intake levels in India are mostly absent. This project sought to estimate daily salt consumption levels in selected communities of Delhi and Haryana in north India and Andhra Pradesh ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.004547
更新日期:2017-01-06 00:00:00
abstract:BACKGROUND:In atrial fibrillation (AF), a more extensively fibrotic left atrium (LA) provides a substrate for arrhythmias and increases risk of relapse following ablation. Fibrocytes are bone marrow-derived circulating mesenchymal progenitors that have been identified in the atrium of patients with AF who have valvular...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.008083
更新日期:2018-03-13 00:00:00
abstract:BACKGROUND:Previous studies indicated that patients undergoing coronary artery bypass graft (CABG) surgery are less likely to receive guideline-based secondary prevention therapy than are those undergoing percutaneous coronary intervention (PCI) after an acute myocardial infarction. We aimed to evaluate whether these d...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.112.002733
更新日期:2012-08-29 00:00:00
abstract:BACKGROUND:Fatty acids constitute the critical components of cell structure and function, and dysregulation of fatty acid composition may exert diverging vascular effects including proliferation, migration, and differentiation of vascular smooth muscle cells (VSMCs). However, direct evidence for this hypothesis has bee...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.004014
更新日期:2016-11-23 00:00:00
abstract::Background We aim to generate a line of "universal donor" human induced pluripotent stem cells (hi PSC s) that are nonimmunogenic and, therefore, can be used to derive cell products suitable for allogeneic transplantation. Methods and Results hi PSC s carrying knockout mutations for 2 key components (β2 microglobulin ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.010239
更新日期:2018-12-04 00:00:00
abstract:BACKGROUND:Although guidelines for antiarrhythmic drug therapy in atrial fibrillation (AF) were published in 2006, it remains uncertain whether adherence to these guidelines affects patient outcomes. METHODS AND RESULTS:We retrospectively evaluated the records of 5976 consecutive AF patients who were prescribed at lea...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.115.001793
更新日期:2015-04-06 00:00:00
abstract:BACKGROUND:Cardiac sodium channel (NaV1.5) dysfunction contributes to arrhythmogenesis during pathophysiological conditions. Nav1.5 localizes to distinct subcellular microdomains within the cardiomyocyte, where it associates with region-specific proteins, yielding complexes whose function is location specific. We herei...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007622
更新日期:2017-12-08 00:00:00
abstract::Background The management of the cardiorenal syndrome in advanced heart failure is challenging, and the role of inotropic drugs has not been fully defined. Our aim was to compare the renal effects of levosimendan versus dobutamine in patients with heart failure and renal impairment. Methods and Results In a randomized...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,随机对照试验
doi:10.1161/JAHA.117.008455
更新日期:2018-08-21 00:00:00