Association of a glucagon-like peptide-1 receptor gene variant with glucose response to a mixed meal.

Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous glucagon-like peptide-1 (GLP-1). We hypothesized that genetic variation in the gene encoding the GLP-1 receptor (GLP1R) could affect the metabolic response to DPP-4 inhibition. To evaluate the relationship between the GLP1R rs6923761 variant (G-to-A nucleic acid substitution) and metabolic responses, we performed mixed meal studies in individuals with type 2 diabetes mellitus and hypertension after 7-day treatment with placebo and the DPP-4 inhibitor sitagliptin. This analysis is a substudy of NCT02130687. The genotype frequency was 13:12:7 GG:GA:AA among individuals of European ancestry. Postprandial glucose excursion was significantly decreased in individuals carrying the rs6923761 variant (GA or AA) as compared with GG individuals during both placebo (P = 0.001) and sitagliptin treatment (P = 0.045), while intact GLP-1 levels were similar among the genotype groups. In contrast, sitagliptin lowered postprandial glucose to a greater degree in GG as compared with GA/AA individuals (P = 0.035). The relationship between GLP1R rs6923761 genotype and therapies that modulate GLP-1 signalling merits study in large populations.

Highly Reactive Isolevuglandins Promote Atrial Fibrillation Caused by Hypertension.

Oxidative damage is implicated in atrial fibrillation (AF), but antioxidants are ineffective therapeutically. The authors tested the hypothesis that highly reactive lipid dicarbonyl metabolites, or isolevuglandins (IsoLGs), are principal drivers of AF during hypertension. In a hypertensive murine model and stretched atriomyocytes, the dicarbonyl scavenger 2-hydroxybenzylamine (2-HOBA) prevented IsoLG adducts and preamyloid oligomers (PAOs), and AF susceptibility, whereas the ineffective analog 4-hydroxybenzylamine (4-HOBA) had minimal effect. Natriuretic peptides generated cytotoxic oligomers, a process accelerated by IsoLGs, contributing to atrial PAO formation. These findings support the concept of pre-emptively scavenging reactive downstream oxidative stress mediators as a potential therapeutic approach to prevent AF.

DPP (Dipeptidyl Peptidase)-4 Inhibition Potentiates the Vasoconstrictor Response to NPY (Neuropeptide Y) in Humans During Renin-Angiotensin-Aldosterone System Inhibition.

DPP (dipeptidyl peptidase)-4 inhibitors are antidiabetic drugs that may increase heart failure in high-risk patients. NPY (neuropeptide Y) is coreleased with norepinephrine, causes vasoconstriction via the Y1 receptor, and is degraded by DPP4 to NPY (3-36) in vitro. NPY (3-36) decreases release of norepinephrine via the Y2 receptor. We tested the hypothesis that DPP4 inhibition would potentiate the vasoconstrictor effect of NPY. Eighteen nonsmokers (12 healthy controls and 6 with type 2 diabetes mellitus) participated in 1 of 2 randomized, double-blind, placebo-controlled crossover studies. First, subjects were randomized to order of treatment with sitagliptin 100 mg/d versus placebo for 7 days separated by 4-week washout. On the last day of treatment, NPY was infused by brachial artery and forearm blood flow was measured using plethysmography. Blood samples were collected after each dose. NPY infusions were repeated after 90-minute washout and intra-arterial enalaprilat. Second, 5 healthy subjects were randomized to crossover treatment with sitagliptin 100 mg/d plus valsartan 160 mg/d versus placebo plus valsartan. NPY infusions were performed on the seventh day of treatment. NPY caused dose-dependent vasoconstriction. During enalaprilat, sitagliptin significantly potentiated NPY-induced vasoconstriction in controls and diabetics ( P≤0.02 for forearm blood flow in either group). Baseline norepinephrine release was increased during sitagliptin and enalaprilat, but not further by NPY. Sitagliptin increased the ratio of NPY to NPY (3-36). During valsartan, sitagliptin also significantly potentiated NPY-induced vasoconstriction ( P=0.009 for forearm blood flow). Potentiation of endogenous NPY could contribute to cardiovascular effects of DPP4 inhibitors in patients taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.

B-type natriuretic peptides help in cardioembolic stroke diagnosis: pooled data meta-analysis.

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.

Correlation Between Hypertension, C-Reactive Protein and Serum Uric Acid With Psychological Well-being.

BACKGROUND: Multiple population-based human studies have established a strong association between increasing levels of serum C-reactive protein, uric acid and subsequent development of hypertension. OBJECTIVES: We aimed to investigate the association between mental well-being with presence of hypertension, hyperuricemia and hs-CRP levels. ‬‬ PATIENTS AND METHODS: This was a cross sectional study of 801 individuals aged 35-85 years old in Broujerd, Iran, included by randomized cluster sampling. General Health Questionnaire (GHQ-12) for assessing mental health/distress level, MONICA standard questions for evaluating hypertension history, serum hs-CRP and Serum Uric Acid (SUA) were evaluated Data were analyzed by appropriate statistical test such as chi-square, T-test and correlation. RESULTS: One hundred eighty five patients (23.1%) had high distress/minor psychiatric disorders. SUA had significant association with hypertension (r = 0.64, P = 0.034). No significant relation was observed between hs-CRP and hypertension. The correlation between GHQ and hs-CRP was not significant but a weak and negative correlation was found between GHQ and SUA SUA (P = 0.012, r = -0.089). CONCLUSIONS: The weak and strong correlation among these parameters indicate that mental wellbeing relays on physical wellness and interact with each other; therefore, controlling hypertension along with uric acid control may effect mental health of any kind of patients.

Atrial dissociation in a middle aged patient: a case report.

Atrial dissociation is characterized by different types of P waves captured in an electrocardiogram, usually seen in critically ill or post-cardiac transplantation patients. Our case demonstrates a 55-year-old man, presenting with chest pain (unstable angina) in the emergency department with transient double-P waves; representing the phenomenon. Our case did not have any of the suggested causes or any known cardiac problems; therefore, with ruling out other differential diagnosis, researches must be done to find another explanation, if repeated.

The diagnostic value of N-terminal pro-brain natriuretic peptide in differentiating cardioembolic ischemic stroke.

BACKGROUND: There has been debate regarding whether natriuretic peptides can be used as a marker to distinguish cardioembolic (CE) origin of ischemic stroke from other subtypes. Therefore, the aim of this study was to study the value of N-terminal pro B-type natriuretic peptide (NT-proBNP) in differentiating CE from other subtypes of stroke in patients with acute ischemic stroke. METHODS: All 125 consecutive patients with acute ischemic stroke in a 1-year period were included. Admission blood samples of all patients were analyzed for the serum level of NT-proBNP. Patients were evaluated for etiology of stroke by imaging modalities and classified based on Trial of Org 10172 in Acute Stroke Treatment criteria. Medical history and risk factors for vascular diseases were also obtained. Receiver operating characteristic (ROC) analysis was used for estimating the diagnostic performance of NT-proBNP levels. RESULTS: Patients were a mean of 67.5 ± 12.6 years of age, and 60 (48%) were men. The most frequent subtype of stroke (57 patients) was CE (45.6%). Levels of NT-proBNP at admission were significantly higher in the CE group (P = .001). After omitting confounding variables, NT-proBNP levels and age were independent predictors of CE stroke subtype. ROC analysis revealed that the diagnostic performance of NT-proBNP levels (area under the curve), optimum cutoff point and its sensitivity and specificity were 0.882 ± 0.031pg/mL, 342 pg/mL, 93%, and 75%, respectively. CONCLUSIONS: NT-proBNP has an acceptable diagnostic value in distinguishing CE ischemic stroke from other subtypes. It can be used to differentiate the stroke subtype and facilitate the treatment process in these patients.

Electrocardiographic findings and serum troponin I in carbon monoxide poisoned patients.

Carbon monoxide (CO) poisoning, though with different sources, is one of the most deadly emergencies in all countries. CO can threaten men's life by several paths especially cardiac complications, which can mimic other cardiac problems such as myocardial infarction. The objective of this study was to determine ECG findings and serum troponin I levels in CO poisoned patients. In this analytical cross-sectional study, 63 CO poisoning patients were consecutively included from hospital's emergency departments. CO content was measured by a CO-oximeter and an electrocardiography was taken first thing on admission. Arterial blood gas (ABG), troponin I and other data was collected afterwards. Data were divided by age groups (adults and children) and gender. CO content was significantly higher only in subjects with normal T wave compared to patients with inverted T wave in their initial ECG (P=0.016). No other significant difference was noticed. None of the ABG findings correlated significantly with CO content. Also no significant correlation was found with CO content after stratification by gender and age groups, but pH in children (r=-0.484, P=0.026). CO content was significantly higher in adults (P=0.023), but other ABG data were not significantly different. Only 3 patients had elevated troponin I. Receiver operating characteristic (ROC) analysis showed no significant cutoff points in CO content for ECG changes. No significant specific change in electrocardiograms (ECG) could contribute carboxyhemoglobin content in carbon monoxide poisoned patients. In addition, no specific difference was found between adults and pediatric subjects' ECGs. All other findings seemed to be accidental.

A huge coronary artery aneurysm in osteogenesis imperfecta: a case report.

Osteogenesis imperfecta (OI) as an inherited connective tissue disorder can affect all tissues that contains type I collagen. Well-known cardiac complications of this disease such as aortic root dilatation, aortic regurgitation and mitral valve prolapse have been rarely reported in the literature. Coronary artery aneurysm is a rare cardiac complication in OI, as reported in a 19 year old female presenting with myocardial infarction and hypotension.