Quantitative Liver MRI Combining Phase Contrast Imaging,Elastography, and DWI: Assessment of Reproducibility and Postprandial Effect at 3.0 T

Purpose

To quantify short-term reproducibility (in fasting conditions) and postprandial changes after a meal in portal vein (PV) flow parameters measured with phase contrast (PC) imaging, liver diffusion parameters measured with multiple b value diffusion-weighted imaging (DWI) and liver stiffness (LS) measured with MR elastography (MRE) in healthy volunteers and patients with liver disease at 3.0 T.

Materials and Methods

In this IRB–approved prospective study, 30 subjects (11 healthy volunteers and 19 liver disease patients; 23 males, 7 females; mean age 46.5 y) were enrolled. Imaging included 2D PC imaging, multiple b value DWI and MRE. Subjects were initially scanned twice in fasting state to assess short-term parameter reproducibility, and then scanned 20 min. after a liquid meal. PV flow/velocity, LS, liver true diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (PF) and apparent diffusion coefficient (ADC) were measured in fasting and postprandial conditions. Short-term reproducibility was assessed in fasting conditions by measuring coefficients of variation (CV) and Bland-Altman limits of agreement. Differences in MR metrics before and after caloric intake and between healthy volunteers and liver disease patients were assessed.

Results

PV flow parameters, D, ADC and LS showed good to excellent short-term reproducibility in fasting state (CV <16%), while PF and D* showed acceptable and poor reproducibility (CV = 20.4% and 51.6%, respectively). PV flow parameters and LS were significantly higher (p<0.04) in postprandial state while liver diffusion parameters showed no significant change (p>0.2). LS was significantly higher in liver disease patients compared to healthy volunteers both in fasting and postprandial conditions (p<0.001). Changes in LS were significantly correlated with changes in PV flow (Spearman rho = 0.48, p = 0.013).

Conclusions

Caloric intake had no/minimal/large impact on diffusion/stiffness/portal vein flow, respectively. PC MRI and MRE but not DWI should be performed in controlled fasting state.     

Increased Circulating ANG II and TNF-α Represents Important Risk Factors in Obese Saudi Adults with Hypertension Irrespective of Diabetic Status and BMI

Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m²), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m²), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m²) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m²). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk.     

Disparities in Outcomes following Admission for Cholangitis

Introduction

Few have examined determinants of adverse outcomes in patients presenting with ascending cholangitis. The objective of this study was to examine factors associated with in-hospital mortality, prolonged length of stay (LOS) and increased hospital charges (HC) in patients presenting with acute cholangitis.

Methods

Within the Health Care Utilization Project Nationwide Inpatient Sample (NIS), we focused on patients, 18 years and older, admitted to the emergency department with cholangitis as primary diagnosis (1998–2009). Models were fitted to predict likelihood of in-hospital mortality, prolonged LOS and increased HC. Covariates included race, day of admission, insurance status, socio-economical status and other patient and hospital characteristics.

Results

Overall, weighted estimates of 248,942 patients were admitted with acute cholangitis between 1998 and 2009, of which 13,534 (5.4%) died during the admission. Multivariable analyses revealed that relative to Caucasian patients, African American, Hispanic and Asian and Pacific Islander patients were more likely to die (OR = 1.61, p<0.001, OR = 1.20, p = 0.01 and OR = 1.26, p = 0.008), to experience a prolonged LOS (OR = 1.77, p<0.001, OR = 1.30, p<0.001, 1.34, p<0.001), and to incur high HC (OR = 1.83, p<0.001, OR = 1.51, p<0.001, OR = 1.56, p<0.001). Moreover, Medicaid and Medicare patients were more likely to die (OR = 1.64, p<0.001, OR = 1.24, p<0.001), to experience a prolonged LOS (1.74, p<0.001, OR = 1.25, p<0.001) and to incur high HC (OR = 1.23, p = 0.002, OR = 1.12, p = 0.002) compared to privately insured patients. In subgroup analysis, there were no differences for Medicare patients age 65 years and over. However, those under 65, most of whom have disability or end stage renal disease, were more likely to experience the negative outcomes.

Conclusion

Race and insurance status represent independent predictors of in-hospital mortality and adverse outcomes in patients presenting with cholangitis. Whether these disparities are due to biological predisposition or unequal quality of care requires further investigation. Regardless, efforts should be made to reduce these outcome disparities.     

Gender Differences in In-Hospital Clinical Outcomes after Percutaneous Coronary Interventions: An Insight from a Japanese Multicenter Registry

Background

Gender differences in clinical outcomes after percutaneous coronary intervention (PCI) among different age groups are controversial in the era of drug-eluting stents, especially among the Asian population who are at higher risk for bleeding complications.

Methods and Results

We analyzed data from 10,220 patients who underwent PCI procedures performed at 14 Japanese hospitals from September 2008 to April 2013. A total of 2,106 (20.6%) patients were women. Women were older (72.7±9.7 vs 66.6±10.8 years, p<0.001), and had a lower body mass index (23.4±4.0 vs 24.3±3.5, p<0.001), with a higher prevalence of hypertension (p<0.001), hyperlipidemia (p<0.001), insulin-dependent diabetes (p<0.001), renal failure (p<0.001), and heart failure (p<0.001) compared with men. Men tended to have more bifurcation lesions (p = 0.003) and chronic totally occluded lesions (p<0.001) than women. Crude overall complications (14.8% vs 9.5%, p<0.001) and the rate of bleeding complications (5.3% vs 2.8%, p<0.001) were significantly higher in women than in men. On multivariate analysis in the total cohort, female sex was an independent predictor of overall complications (OR, 1.47; 95% CI, 1.26–1.71; p<0.001) and bleeding complications (OR, 1.74; 95% CI, 1.36–2.24; p<0.001) after adjustment for confounding variables. A similar trend was observed across the middle-aged group (≥55 and <75 years) and old age group (≥75 years).

Conclusions

Women are at higher risk than men for post-procedural complications after PCI, regardless of age.     

Male Gender,Increased Blood Viscosity,Body Mass Index and Triglyceride Levels Are Independently Associated with Systemic Relative Hypertension in Sickle Cell Anemia

Patients with sickle cell anemia (SCA) have usually lower diastolic, systolic and mean blood pressure (BP) than the general population. However, BP values ≥120/70 mmHg considerably increase the risk for acute and chronic complications in SCA. The aim of this study was to identify biological factors associated with relative hypertension in adults with SCA. We compared the hematological, lipid and hemolytic profiles, as well as blood viscosity, between SCA patients with normal BP (<120/70 mmHg, n = 54) and those with relative hypertension (BP≥120/70 mmHg, n = 43). Our results demonstrated that male gender (OR: 3.49; 95%CI 1.20 to 10.16, p<0.05), triglycerides (OR: 9.19; 95% CI 2.29 to 36.95, p<0.01), blood viscosity (OR: 1.35; 95% CI 1.01 to 1.81, p<0.05) and body mass index (OR: 1.37; 95% CI 1.14 to 1.64, p<0.01) were independent risks factors for relative hypertension in SCA. No association was found between the BP status and the positive history of painful vaso-occlusive crisis or acute chest syndrome. An association between triglycerides level and the occurrence of these two major acute complications was detected. Our study suggests that male gender, increased triglycerides level, BMI and blood viscosity could increase the risk for developing relative hypertension in SCA. In addition, our results support a role of moderately elevated triglycerides in the pathophysiology of vaso-occlusive events.     

Unique Antibody Responses to Malondialdehyde-Acetaldehyde (MAA)-Protein Adducts Predict Coronary Artery Disease

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease.     

Explicit and Implicit Emotional Expression in Bulimia Nervosa in the Acute State and after Recovery

Expression of emotional state is considered to be a core facet of an individual''s emotional competence. Emotional processing in BN has not been often studied and has not been considered from a broad perspective. This study aimed at examining the implicit and explicit emotional expression in BN patients, in the acute state and after recovery. Sixty-three female participants were included: 22 BN, 22 recovered BN (R-BN), and 19 healthy controls (HC). The clinical cases were drawn from consecutive admissions and diagnosed according to DSM-IV-TR diagnostic criteria. Self reported (explicit) emotional expression was measured with State-Trait Anger Expression Inventory-2, State-Trait Anxiety Inventory, and Symptom Check List-90 items-Revised. Emotional facial expression (implicit) was recorded by means of an integrated camera (by detecting Facial Feature Tracking), during a 20 minutes therapeutic video game. In the acute illness explicit emotional expression [anxiety (p<0.001) and anger (p<0.05)] was increased. In the recovered group this was decreased to an intermediate level between the acute illness and healthy controls [anxiety (p<0.001) and anger (p<0.05)]. In the implicit measurement of emotional expression patients with acute BN expressed more joy (p<0.001) and less anger (p<0.001) than both healthy controls and those in the recovered group. These findings suggest that there are differences in the implicit and explicit emotional processing in BN, which is significantly reduced after recovery, suggesting an improvement in emotional regulation.     

Drug-Related Problems in Patients with Benign Prostatic Hyperplasia: A Cross Sectional Retrospective Study

Benign Prostatic Hyperplasia (BPH) patients are at risk of acquiring drug-related problems (DRPs), as it is present in the majority of aging men. To date, DRPs among BPH patients have not been well studied. We conducted this retrospective study in a tertiary hospital in Malaysia from January 2009 to June 2012 with the aim of identifying the factors associated with DRPs among BPH patients. The Pharmaceutical Care Network Europe Classification Version (PCNE) 5.01 was used as a tool to classify DRPs. We enrolled 203 patients from 259 hospital admissions. A total of 390 DRPs were found and there was an average of 1.5±1.3 problems per hospitalization. 76.1% of hospital admissions included at least one DRP. The most common DRP categories encountered were drug choice problems (45.9%), drug interactions (24.9%), and dosing problems (13.3%). Factors such as advanced age (p = 0.005), a hospital stay of more than 6 days (p = 0.001), polydrug treatments (p<0.001), multiple comorbidities (p<0.001), and comorbid cardiovascular disease (p = 0.011), diabetes mellitus(p = 0.001), hypertension (p<0.001) and renal impairment (p = 0.011) were significantly associated with the occurrence of DRPs. These data indicated that the prevalence of DRPs is high among BPH patients. The identification of different subtypes of DRPs and the factors associated with DRPs may facilitate risk reduction for BPH patients.     

High Levels of Asymmetric Dimethylarginine Are Strongly Associated with Low HDL in Patients with Acute Myocardial Infarction

Objectives

Low levels of high-density lipoprotein (HDL) cholesterol are associated with an increased risk of acute myocardial infarction possibly through impaired endothelial atheroprotection and decreased nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA) mediates endothelial function by inhibiting nitric oxide synthase activity. In patients with acute myocardial infarction, we investigated the relationship between serum levels of HDL and ADMA.

Approach and Results

Blood samples from 612 consecutive patients hospitalized for acute MI <24 hours after symptom onset were taken on admission. Serum levels of ADMA, its stereoisomer, symmetric dimethylarginine (SDMA) and L-arginine were determined using high-performance liquid chromatography. Patients with low HDL (<40 mg/dL for men and <50 mg/dL for women) were compared with patients with higher HDL. Most patients (59%) had low HDL levels. Median ADMA levels were markedly higher in the low HDL group (0.69 vs. 0.50 µmole/L, p<0.001). In contrast, SDMA and L-arginine levels were similar for the two groups (p = 0.120 and p = 0.064). Notably, ADMA, but not SDMA or L-arginine, was inversely correlated with HDL (r = −0.311, p<0.001). In stratified analysis, this relationship was only found for low HDL levels (r = −0.265, p<0.001), but not when HDL levels were higher (r = −0.077, p = 0.225). By multivariate logistic regression analysis, ADMA level was strongly associated with low HDL levels (OR(95%CI):6.06(3.48–10.53), p<0.001), beyond traditional confounding factors.

Conclusions

Our large population-based study showed for the first time a strong inverse relationship between HDL and ADMA in myocardial infarction patients, suggesting a functional interaction between HDL and endothelium, beyond metabolic conditions associated with low HDL levels.     

Resistant Hypertension,Patient Characteristics,and Risk of Stroke

Background

Little is known about the prognosis of resistant hypertension (RH) in Asian population. This study aimed to evaluate the impacts of RH in Taiwanese patients with hypertension, and to ascertain whether patient characteristics influence the association of RH with adverse outcomes.

Methods and Results

Patients aged ≥45 years with hypertension were identified from the National Health Insurance Research Database. Medical records of 111,986 patients were reviewed in this study, and 16,402 (14.6%) patients were recognized as having RH (continuously concomitant use of ≥3 anti-hypertensive medications, including a diuretic, for ≥2 years). Risk of major adverse cardiovascular events (MACE, a composite of all-cause mortality, acute coronary syndrome, and stroke [included both fatal and nonfatal events]) in patients with RH and non-RH was analyzed. A total of 11,856 patients experienced MACE in the follow-up period (average 7.1±3.0 years). There was a higher proportion of females in the RH group, they were older than the non-RH (63.1 vs. 60.5 years) patients, and had a higher prevalence of cardiovascular co-morbidities. Overall, patients with RH had higher risks of MACE (adjusted HR 1.17; 95%CI 1.09–1.26; p<0.001). Significantly elevated risks of stroke (10,211 events; adjusted HR 1.17; 95%CI 1.08–1.27; p<0.001), especially ischemic stroke (6,235 events; adjusted HR 1.34; 95%CI 1.20–1.48; p<0.001), but not all-cause mortality (4,594 events; adjusted HR 1.06; 95%CI 0.95–1.19; p = 0.312) or acute coronary syndrome (2,145 events; adjusted HR 1.17; 95%CI 0.99–1.39; p = 0.070) were noted in patients with RH compared to those with non-RH. Subgroup analysis showed that RH increased the risks of stroke in female and elderly patients. However, no significant influence was noted in young or male patients.

Conclusions

Patients with RH were associated with higher risks of MACE and stroke, especially ischemic stroke. The risks were greater in female and elderly patients than in male or young patients.     

Impact of Renal Sympathetic Denervation on Left Ventricular Structure and Function at 1-Year Follow-Up

Background

Catheter-based sympathetic renal denervation (RDN) is a recent therapeutic option for patients with resistant hypertension. However, the impact of RDN in left ventricular (LV) mass and function is not completely established. Our aim was to evaluate the effects of RDN on LV structure and function (systolic and diastolic) in patients with resistant hypertension (HTN).

Methods and Results

From a single centre prospective registry including 65 consecutive patients with resistant HTN submitted to RDN between July-2011 and April-2015, 31 patients with baseline and 1-year follow-up echocardiogram were included in this analysis. Mean age was 65±7 years, 48% were males, 71% had type 2 diabetes. Most had hypertension lasting for more than 10 years (90%), and were being treated with a median number of 6 anti-hypertensive drugs, including 74% on spironolactone. At 1-year, there was a significant decrease both on office SBP (176±24 to 149±13mmHg, p<0.001) and DBP (90±14 to 79±11mmHg, p<0.001), and also in 24h ABPM SBP (150±20 to 132±14mmhg, p<0.001) and DBP (83±10 to 74±9mmHg, p<0.001). There was also a significant decrease in LV mass from 152±32 to 136±34g/m² (p<0.001), an increase in LV end diastolic volume (93±18 to 111±27 mL, p = 0.004), an increase in LV ejection fraction (65±9 to 68±9%, p = 0.001) and mitral valve E deceleration time (225±49 to 247±51ms, p = 0.015) at 1-year follow up. There were no significant changes in left atrium volume index or in the distribution of patients among the different left ventricle geometric patterns and diastolic function subgroups.

Conclusions

In this single centre registry of patients with resistant hypertension, renal denervation was associated with significant reduction in both office and ABPM blood pressure and a significant decrease in left ventricle mass evaluated by transthoracic echocardiogram at 1 year follow-up.     

Chronic Medical Conditions and Risk of Sepsis

Background

We sought to determine the associations between baseline chronic medical conditions and future risk of sepsis.

Methods

Longitudinal cohort study using the 30,239 community-dwelling participants of the REGARDS cohort. We determined associations between baseline chronic medical conditions and incident sepsis episodes, defined as hospitalization for an infection with the presence of infection plus two or more systemic inflammatory response syndrome criteria.

Results

Over the mean observation time of 4.6 years (February 5, 2003 through October 14, 2011), there were 975 incident cases of sepsis. Incident sepsis episodes were associated with older age (p<0.001), white race (HR 1.39; 95% CI: 1.22–1.59), lower education (p<0.001) and income (p<0.001), tobacco use (p<0.001), and alcohol use (p = 0.02). Incident sepsis episodes were associated with baseline chronic lung disease (adjusted HR 2.43; 95% CI: 2.05–2.86), peripheral artery disease (2.16; 1.58–2.95), chronic kidney disease (1.99; 1.73–2.29), myocardial infarction 1.79 (1.49–2.15), diabetes 1.78 (1.53–2.07), stroke 1.67 (1.34–2.07), deep vein thrombosis 1.63 (1.29–2.06), coronary artery disease 1.61 (1.38–1.87), hypertension 1.49 (1.29–1.74), atrial fibrillation 1.48 (1.21–1.81) and dyslipidemia 1.16 (1.01–1.34). Sepsis risk increased with the number of chronic medical conditions (p<0.001).

Conclusions

Individuals with chronic medical conditions are at increased risk of future sepsis events.     

Effects of Radiofrequency Catheter Ablation of Atrial Fibrillation on Soluble P-Selectin,Von Willebrand Factor and IL-6 in the Peripheral and Cardiac Circulation

Background

Catheter ablation (CA) of atrial fibrillation (AF) is associated with inflammatory response, endothelial damage and with increased risk of thrombosis. However, whether these processes differ in peripheral and cardiac circulation is unknown.

Methods

Plasma markers (von Willebrand factor (vWf), soluble P-selectin (sPsel) and interleukin-6 (IL-6)) were measured by ELISA at three time points in 80 patients (62±10 years, 63% males, 41% paroxysmal AF) undergoing CA. These were at baseline – from femoral vein (FV) and left atrium (LA) before ablation; directly after ablation – from the pulmonary vein (PV), LA and FV; and 24 hours after procedure – from a cubital vein (CV).

Results

The levels of vWF and IL6 – but not sP-sel – increased significantly 24h after procedure (p<0.001). Baseline vWF was significantly associated with persistent AF (Beta = .303, p = 0.006 and Beta = .300, p = 0.006 for peripheral and cardiac levels, respectively), while persistent AF (Beta = .250, p = 0.031) and LAA flow pattern (Beta = .386, p<0.001) remained associated with vWF in cardiac blood after ablation. Advanced age was significantly associated with IL6 levels at baseline and after ablation in peripheral and cardiac blood. There were no clinical, procedural or anti-coagulation characteristics associated with sP-sel levels in cardiac blood, while peripheral sP-sel levels were associated with hypertension before (Beta = −.307, p = 0.007) and with persistent AF after ablation (Beta = −.262, p = 0.020).

Conclusions

vWF levels are higher in persistent AF and are associated with LAA rheological pattern after AF ablation. Increase of peripheral vWF and IL6 levels after procedure supports current AF ablation management with careful control of post-procedural anticoagulation to avoid ablation-related thromboembolism.     

Traumatic Intracranial Hemorrhage Correlates with Preinjury Brain Atrophy,but Not with Antithrombotic Agent Use: A Retrospective Study

Background

The impact of antithrombotic agents (warfarin, clopidogrel, ASA) on traumatic brain injury outcomes is highly controversial. Although cerebral atrophy is speculated as a risk for acute intracranial hemorrhage, there is no objective literature evidence.

Materials and Methods

This is a retrospective, consecutive investigation of patients with signs of external head trauma and age ≥60 years. Outcomes were correlated with antithrombotic-agent status, coagulation test results, admission neurologic function, and CT-based cerebral atrophy dimensions.

Results

Of 198 consecutive patients, 36% were antithrombotic-negative and 64% antithrombotic-positive. ASA patients had higher arachidonic acid inhibition (p = 0.04) and warfarin patients had higher INR (p<0.001), compared to antithrombotic-negative patients. Antithrombotic-positive intracranial hemorrhage rate (38.9%) was similar to the antithrombotic-negative rate (31.9%; p = 0.3285). Coagulopathy was not present on the ten standard coagulation, thromboelastography, and platelet mapping tests with intracranial hemorrhage and results were similar to those without hemorrhage (p≥0.1354). Hemorrhagic-neurologic complication (intracranial hemorrhage progression, need for craniotomy, neurologic deterioration, or death) rates were similar for antithrombotic-negative (6.9%) and antithrombotic-positive (8.7%; p = 0.6574) patients. The hemorrhagic-neurologic complication rate was increased when admission major neurologic dysfunction was present (63.2% versus 2.2%; RR = 28.3; p<0.001). Age correlated inversely with brain parenchymal width (p<0.001) and positively with lateral ventricular width (p = 0.047) and cortical atrophy (p<0.001). Intracranial hemorrhage correlated with cortical atrophy (p<0.001) and ventricular width (p<0.001).

Conclusions

Intracranial hemorrhage is not associated with antithrombotic agent use. Intracranial hemorrhage patients have no demonstrable coagulopathy. The association of preinjury brain atrophy with acute intracranial hemorrhage is a novel finding. Contrary to antithrombotic agent status, admission neurologic abnormality is a predictor of adverse post-admission outcomes. Study findings indicate that effective hemostasis is maintained with antithrombotic therapy.     

Clinical Outcomes and Cost Effectiveness of Accelerated Diagnostic Protocol in a Chest Pain Center Compared with Routine Care of Patients with Chest Pain

Aims

The aim of this study was to compare in patients presenting with acute chest pain the clinical outcomes and cost-effectiveness of an accelerated diagnostic protocol utilizing contemporary technology in a chest pain unit versus routine care in an internal medicine department.

Methods and Results

Hospital and 90-day course were prospectively studied in 585 consecutive low-moderate risk acute chest pain patients, of whom 304 were investigated in a designated chest pain center using a pre-specified accelerated diagnostic protocol, while 281 underwent routine care in an internal medicine ward. Hospitalization was longer in the routine care compared with the accelerated diagnostic protocol group (p<0.001). During hospitalization, 298 accelerated diagnostic protocol patients (98%) vs. 57 (20%) routine care patients underwent non-invasive testing, (p<0.001). Throughout the 90-day follow-up, diagnostic imaging testing was performed in 125 (44%) and 26 (9%) patients in the routine care and accelerated diagnostic protocol patients, respectively (p<0.001). Ultimately, most patients in both groups had non-invasive imaging testing. Accelerated diagnostic protocol patients compared with those receiving routine care was associated with a lower incidence of readmissions for chest pain [8 (3%) vs. 24 (9%), p<0.01], and acute coronary syndromes [1 (0.3%) vs. 9 (3.2%), p<0.01], during the follow-up period. The accelerated diagnostic protocol remained a predictor of lower acute coronary syndromes and readmissions after propensity score analysis [OR = 0.28 (CI 95% 0.14–0.59)]. Cost per patient was similar in both groups [($2510 vs. $2703 for the accelerated diagnostic protocol and routine care group, respectively, (p = 0.9)].

Conclusion

An accelerated diagnostic protocol is clinically superior and as cost effective as routine in acute chest pain patients, and may save time and resources.     

Basal and Ischemia-Induced Transcardiac Troponin Release into the Coronary Circulation in Patients with Suspected Coronary Artery Disease

Background

Cardiac troponin is a specific biomarker for cardiomyocyte necrosis in acute coronary syndromes. Troponin release from the coronary circulation remains to be determined because of the lower sensitivity of the conventional assay. We sought to determine basal and angina-induced troponin release using a highly sensitive troponin assay.

Methods and Results

The cardiac troponin T levels in serum sampled from the peripheral vein (PV), the aortic root (AO), and the coronary sinus (CS) were measured in 105 consecutive stable patients with coronary risk factor(s) and suspected coronary artery disease (CAD) and in 33 patients without CAD who underwent an acetylcholine provocation test. At baseline, there was a significant increase in the troponin levels from AO [9.0 (6.4, 13.1) pg/mL for median (25^th, 75^th percentiles)] to CS [10.3 (7.3, 15.5) pg/mL, p<0.001] in 96 (91.4%) patients and the difference was 1.1 (0.4, 2.1) pg/mL, which reflected basal transcardiac troponin release (TTR). TTR was positively correlated with PV levels (r = 0.22, p = 0.03). Male sex, left ventricular hypertrophy determined by echocardiography, T-wave inversion, and CAD correlated with elevated TTR defined as above: median, 1.1 pg/mL. A significant increase in TTR was noted in 17 patients with coronary spasms [0.6 (0.2, 1.2) pg/mL, p<0.01] but not in 16 patients without spasms [0.0 (−0.5, 0.9) pg/mL, p = 0.73] after the acetylcholine provocation.

Conclusion

Basal TTR in the coronary circulation was observed in most of the patients with suspected CAD and risk factor(s). This sensitive assay detected myocardial ischemia-induced increases in TTR caused by coronary spasms.     

Effects of Moderate Aerobic Exercise Training on Hemorheological and Laboratory Parameters in Ischemic Heart Disease Patients

Background and Design

In this study we set out to determine the effects of long-term physical training on hemorheological, laboratory parameters, exercise tolerability, psychological factors in cardiac patients participating in an ambulatory rehabilitation program.

Methods

Before physical training, patients were examined by echocardiography, tested on treadmill by the Bruce protocol, and blood was drawn for laboratory tests. The enrolled 79 ischemic heart disease patients joined a 24-week cardiac rehabilitation training program. Blood was drawn to measure hematocrit (Hct), plasma and whole blood viscosity (PV, WBV), red blood cell (RBC) aggregation and deformability. Hemorheological, clinical chemistry and psychological measurements were repeated 12 and 24 weeks later, and a treadmill test was performed at the end of the program.

Results

After 12 weeks Hct, PV, WBV and RBC aggregation were significantly decreased, RBC deformability exhibited a significant increase (p<0.05). Laboratory parameters (triglyceride, uric acid, hsCRP and fibrinogen) were significantly decreased (p<0.05). After 24 weeks the significant results were still observed. By the end of the study, IL-6 and TNF-α levels displayed decreasing trends (p<0.06). There was a significant improvement in MET (p<0.001), and the BMI decrease was also significant (p<0.05). The vital exhaustion parameters measured on the fatigue impact scale indicated a significant improvement in two areas of the daily activities (p<0.05).

Conclusions

Regular physical training improved the exercise tolerability of patients with ischemic heart disease. Previous publications have demonstrated that decreases in Hct and PV may reduce cardiovascular risk, while a decrease in RBC aggregation and an increase in deformability improve the capillary flow. Positive changes in laboratory parameters and body weight may indicate better oxidative and inflammatory circumstances and an improved metabolic state. The psychological findings point to an improvement in the quality of life.     

Early Vascular Aging in Young and Middle-Aged Ischemic Stroke Patients: The Norwegian Stroke in the Young Study

Background

Ischemic stroke survivors have high risk of cardiovascular morbidity and mortality even at young age, suggesting that early arterial aging is common among such patients.

Methods

We measured aortic stiffness by carotid-femoral pulse wave velocity (PWV) in 205 patients (69% men) aged 15–60 years with acute ischemic stroke in the prospective Norwegian Stroke in the Young Study. High for age carotid-femoral PWV was identified in the reference normogram.

Results

Patients were on average 49±10 years old, 34% had a history of hypertension and 37% had metabolic syndrome (MetS). In the total study population, higher PWV was associated with history of hypertension (β = 0.18), higher age (β = 0.34), systolic blood pressure (BP) (β = 0.28) and serum creatinine (β = 0.18) and lower high-density lipoprotein (HDL) cholesterol (β = –0.10, all p<0.01) in multivariate linear regression analysis (multiple R² = 0.42, p<0.001). High for age PWV was found in 18% of patients. In univariate analyses, known hypertension was associated with a 6-fold, MetS with a 4-fold and presence of carotid plaque with a 3.7-fold higher risk for high for age PWV (all p<0.01). In multiple logistic regression analysis higher systolic BP (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.02–1.06; p<0.01), history of hypertension (OR 3.59; 95% CI 1.52–8.51; p<0.01), low HDL cholesterol (OR 3.03; 95% CI 1.00–9.09; p = 0.05) and higher serum creatinine (OR 1.04; 95% CI 1.01–1.06; p<0.01) were associated with high for age PWV.

Conclusions

Higher PWV is common in younger and middle-aged ischemic stroke patients and associated with a clustering of classical cardiovascular risk factors.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01597453","term_id":"NCT01597453"}}NCT01597453     

Alterations of Glucose-Dependent Insulinotropic Polypeptide and Expression of Genes Involved in Mammary Gland and Adipose Tissue Lipid Metabolism during Pregnancy and Lactation

Gastric inhibitory polypeptide (GIP) is a gut derived peptide with multiple emerging physiological actions. Effects of pregnancy and lactation on GIP secretion and related gene expression were studied in Wistar rats. Pregnancy moderately increased feeding (p<0.05), whilst lactation substantially increased food intake (p<0.01 to p<0.001). Circulating GIP was unchanged during pregnancy, but non-fasting plasma glucose was significantly (p<0.01) decreased and insulin increased (p<0.05). Lactation was associated with elevated circulating GIP concentrations (p<0.001) without change of glucose or insulin. Oral glucose resulted in a significantly (p<0.001) decreased glycaemic excursion despite similar glucose-induced GIP and insulin concentrations in lactating rats. Pregnant rats had a similar glycaemic excursion but exhibited significantly lowered (p<0.05) GIP accompanied by elevated (p<0.001) insulin levels. Pregnant rats exhibited increased (p<0.001) islet numbers and individual islet areas were enlarged (p<0.05). There were no significant differences in islet alpha-cell areas, but all groups of rats displayed co-expression of glucagon and GIP in alpha-cells. Lactating rats exhibited significantly (p<0.01) increased intestinal weight, whereas intestinal GIP stores were significantly (p<0.01) elevated only in pregnant rats. Gene expression studies in lactating rats revealed prominent (p<0.01 to p<0.001) increases in mammary gland expression of genes involved in energy turnover, including GIP-R. GIP was present in intestines and plasma of 17 day old foetal rats, with substantially raised circulating concentrations in neonates throughout the period of lactation/suckling. These data indicate that changes in the secretion and action of GIP play an important role in metabolic adaptations during pregnancy and especially lactation.     

Cardiac Repolarization and Autonomic Regulation during Short-Term Cold Exposure in Hypertensive Men: An Experimental Study

Objectives

The aim of our study was to assess the effect of short-term cold exposure, typical in subarctic climate, on cardiac electrical function among untreated middle-aged hypertensive men.

Methods

We conducted a population-based recruitment of 51 hypertensive men and a control group of 32 men without hypertension (age 55–65 years) who underwent whole-body cold exposure (15 min exposure to temperature −10°C, wind 3 m/s, winter clothes). Conduction times and amplitudes, vectorcardiography, arrhythmias, and heart rate variability (autonomic nervous function) were assessed.

Results

Short-term cold exposure increased T-peak to T-end interval from 67 to 72 ms (p<0.001) and 71 to 75 ms (p<0.001) and T-wave amplitude from 0.12 to 0.14 mV (p<0.001) and from 0.17 to 0.21 mV (p<0.001), while QTc interval was shortened from 408 to 398 ms (p<0.001) and from 410 to 401 ms (p<0.001) among hypertensive men and controls, respectively. Cold exposure increased both low (from 390 to 630 ms² (p<0.001) and 380 to 700 ms² (p<0.001), respectively) and high frequency heart rate variability (from 90 to 190 ms² (p<0.001) and 150 to 300 ms² (p<0.001), respectively), while low-to-high frequency-ratio was reduced. In addition, the frequency of ventricular ectopic beats increased slightly during cold exposure. The cold induced changes were similar between untreated hypertensive men and controls.

Conclusions

Short-term cold exposure with moderate facial and mild whole body cooling resulted in prolongation of T-peak to T-end interval and higher T-wave amplitude while QTc interval was shortened. These changes of ventricular repolarization may have resulted from altered cardiac autonomic regulation and were unaffected by untreated hypertension.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02007031","term_id":"NCT02007031"}}NCT02007031