Implications of High-Sensitivity Cardiac Troponin I in Cardiology Clinical Practice

Background: High sensitivity troponin (hsTn) has better sensitivity for myocardial tissue injury detection compared to standard troponin assays, despite lower diagnostic specificity and lack of hsTn assay standardization. Objectives: To examine implications of introducing hsTnI in clinical practice. Methods: We retrospectively collected information of patients presented to a single tertiary cardiac referral centre with suspected acute coronary syndrome (ACS), who had ≥1 hsTnI sample (Abbott ARCHITECT STAT), from 1st June 2016-17th August 2016. Upper range limit (URL), i.e. 99th percentile, was defined as 34.2 ng/L, 15.6 ng/L and 26.2 ng/L for male, female and both gender (“overall”) respectively. Patients were divided into 4 groups - Group 1: hsTnURL but b3 times URL, Group 3: hsTn between 3-5 times URL and Group 4: hsTnN5 times URL. Results: Data from 366 patients was analysed: 227(62.0%), 34(9.3%), 13(3.6%), 92(25.1%) in Group 1, 2, 3 and 4 respectively. In Group 1 to 4, the proportion of ACS was 8.8%, 38.0%, 53.8%, 82.6% and proportion of MI were 0.8%, 29.4%, 53.8%. 82.6%. By using N5 times URL as cut-off, hsTnI has higher specificity and PPV, but lower sensitivity and NPV in diagnosis of ACS {(sensitivity:0.66, specificity:0.0.94, PPV0.83, NPV0.85), with ROC curve AUC:0.896, pb0.001, 95% CI:0.861-0.931}. Our analysis showed serial paired hsTn samples increase the PPV of hsTn to detect ACS. There was no significant difference between using hsTn URL “overall” or “gender-specific” for ACS diagnosis. Kaplan-Meier analysis showed 30-day all-cause mortality in the group with maximal hsTn value NURL is significant higher (pb0.001). Multiple-logistic regression showed that URL of hsTn was an independent variable for 30-day all-cause mortality (p<0.001). Conclusions: Introducing hsTnI has led to the recognition of a large proportion of patients with minor cardiac troponin increases (above URL of 99th percentile but b5 times URL), the majority of whom do not have ACS or MI. There is no significant difference in using “overall” and “gender-specific” URL in diagnosing ACS. Using 5 times above URL and serial hsTn will increase PPV to detect ACS. Maximal HsTn value N99th percentile is independently associated with 30-day all-cause mortality

Comparison of Resting PD/PA with Fractional Flow Reserve Using a Monorail Pressure Catheter

Background: The RXi™ system (ACIST Medical Systems, MN, USA) is a new Fractional Flow Reserve (FFR) technology utilising an ultrathinmonorail microcatheter (Navvus®; ACIST Medical Systems) with an optical pressure sensor located close to the distal catheter tip. FFR measurement using monorail microcatheter is comparable to the conventional pressure wires. However, the predictive value of resting distal coronary artery pressure/aortic pressure (Pd/Pa) on hyperemic FFR value in the real world practice is unknown. Objective: To explore the diagnostic accuracy of resting Pd/Pa in relation to hyperemic FFR using the monorail pressure catheter. Methods: Resting Pd/Pa and FFR were measured using monorail pressure catheter in 67 consecutive patients with intermediate coronary artery lesions (30% to 80% diameter stenoses) between 01-03-2016 to 17-01-2017. Of 121 studied lesions, 29 (23.97%) were excluded because of no hyperemic FFR due to postive resting Pd/Pa (n=17), severe or non-critical stenosis (n=11) and suboptimal acquisition (n=1), leaving 92 lesions for final analysis. Hyperemic FFR was induced with intracoronary adenosine. The selection of coronary wire and the dose of intracoronary nitroglycerine were at the operators’ discretions. Results: Bland-Altman plots showed a moderate degree of scatter between Pd/Pa and FFR value. On average, Pd/Pa exceeded FFR by 0.066 (-0.09 to +0.22). Receiver-operating characteristic curves of the resting Pd/Pa with FFR≤0.80 as the reference variable showed an area under the curve of 0.78 (95% confidence intervals 0.680 to 0.881, pb0.001), with a diagnostic accuracy of 79.3% when the resting Pd/Pa was ≤0.86. Certain cutoff values of Pd/Pa can reliably predict whether hyperemic FFR was positive or negative (FFR cutoff≤0.80). Resting Pd/Pa value of N0.96 had a negative predictive value (NPV) of 100% and sensitivity of 100%; the resting Pd/Pa value of ≤0.82 had a positive predictive value (PPV) of 100% and specificity of 98.3%. These were consistent regardless of coronary vessel, location of lesion or degree of diameter stenosis. Conclusions: Certain range of resting Pd/Pa measured by monorail pressure catheter had excellent NPV and sensitivity or excellent PPV and specificity to predict hyperemic FFR. Clinical outcome studies are required to determine whether the results might obviate the need for hyperemia in selected patients

Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: multicentre, prospective cohort study

Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HR) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% (HR: 0.28; 95% confidence intervals (CI): 0.16 to 0.50, P-trend <0.001). The corresponding association of tea with HCC risk was 0.41 (95% CI: 0.22 to 0.78, P-trend=0.003). There was no compelling evidence of heterogeneity of these associations across strata of important HCC risk factors, including hepatitis B or hepatitis C status (available in a nested case-control study). The inverse, monotonic associations of coffee intake with HCC were apparent for caffeinated (P-trend=0.009), but not decaffeinated (P-trend=0.45) coffee for which, however, data were available for a fraction of subjects. Results from this multi-centre, European cohort study strengthen the existing evidence regarding the inverse association between coffee/tea and HCC risk. Given the apparent lack of heterogeneity of these associations by HCC risk factors and that coffee/tea are universal exposures, our results could have important implications for high HCC risk subjects

Prognostic Value of N-terminal B-type Natriuretic Peptide in Patients with Acute Myocardial Infarction: A Multicenter Study

Background: Several models have been developed to help the clinician in risk stratification for Acute Coronary Syndrome (ACS),such as the TIMI and GRACE risk scores. However, there is conflicting evidence for the prognostic value of NT-ProBNP in acute myocardial infarction (AMI). Objective: (1) To explore the association of NT-proBNP with 30-day clinical outcome in AMI patients. (2) To compare the prognostic value of NT-proBNP with TIMI and GRACE risk scores in AMI patients. Methods: We conducted a multicenter, prospective observational study recruiting patients presented with AMI between 29-October-2015 and 14-January-2017, involving 1 cardiology referral centre and 4 non-cardiology hospitals. NT-proBNP level (Alere Triage®, US)was measured within 24 hours fromthe diagnosis of AMI. Patientswere followed-up for 1 month. Results: A total of 186 patients were recruited, 143 from tertiary cardiology centre and 43 from non-cardiology hospitals. Mean age was 54.7±10.0 years, 87.6% male and 64% were STEMI. The NT-proBNP level ranged from 60 to 16700pg/ml, with a median of 714pg/ml. Using the 75th centile as the cutoff, Kaplan-Meier survival analysis for the 30-day cardiac related mortality was significantly higher for patient with NT-proBNP level of ≥1600pg/ml (6.4% vs. 0.7%, p=0.02). Cox-regression analysis showed that NT-proBNP level of ≥1600pg/ml was an independent predictor of 30-day cardiac related mortality, regardless of TIMI risk score, GRACE score, LV ejection fraction and study hospitals (HR 9.274, p=0.054, 95%CI 0.965, 89.161). Readmission for heart failure at 30-day was also higher for patient with NT-proBNP level of ≥1600pg/ml (HR 9.308, p=0.053, 95%CI 0.969, 89.492). NT-proBNP level was not associated with all-cause mortality, risk of readmission for ACS, arrhythmia and stroke (pN0.05). By adding 50 score to GRACE risk score for NT-proBNP level of ≥1600pg/ml, combination of GraceNT-proBNP scores of more than 200 appeared to be a better independent predictor for 30-day cardiac related mortality (HR:28.28, p=0.004, 95%CI 2.94, 272.1). ROC analysis showed that this new score had 75% sensitivity and 91.2% specificity in predicting 30-day cardiac related mortality (AUC 0.791, p=0.046). Conclusions: NT-proBNP is a useful point-of-care risk stratification biomarker in AMI. It can be combined to the current risk score model for better risk stratification in AMI patients

Diatreta Cups, Light in Roman Dining Spaces

Cage cups or Diatreta are ancient Roman glass vessels produced by creating a thick blown blank of glass that, once cooled down, is taken to a glass cutter or diatretarii. The latter would cut and carve away most of the glass leaving a transparent vessel inside and an open-work decoration separated through thin posts of glass. The work is very delicate and exclusive, produced within limited space in time with no record of similar vessels until the late 1800 (Donald B. Harden & Toynbee 1959, p.181). Many of these glass objects have good-will inscriptions or decorations that express the importance of drinking. As for their provenance, most –when found in context- have been found in pagan burials. Nevertheless some fragments have been found in Christian environments or with Christian motifs like the Szekszárd cup. The location of these finds is mostly in the Rhine area –northern Empire, when Milan was one of its capitals (Aquaro 2004)- but the actual extent of finds expand throughout the 4th century extent of the Roman Empire. Considering their typological analysis there are basically two types, beaker and bowl. Beakers are considered drinking vessels as they either display a legend or a mythological reference to drink or wine. Whereas a general consensus agrees that open bowl-form cups were hanging lamps (Whitehouse 1988, p.28) since the 1986 find of a diatreta bowl with copper alloy hanging attachments. It is clear these were luxury objects to be used in special occasions and spaces. The aim of this paper is to understand the space were socialisation and drinking took place and the importance of luxurious objects to adorn, display and use. The paper will also put forward the idea that the beaker shaped diatreta vessels, usually considered for drinking, could have been lamps that encouraged drinking and good will to the guests. This paper is structured to first consider an introduction to late luxury Roman glass and then analysing the typological shape of all, or most of the diatreta currently known; secondly, through assessment by the means of comparison, analyse the writings or decorations the vessels were endowed with. Thirdly, by describing and understanding the people and the space were these vessels would have been used, emphasise the beauty of illuminating such spaces with these vessels. According to Herodotus in his historical investigation –5th century-, dress habits and food regime are elements of extreme importance to understand a people (Caporusso et al. 2011, p.12). This idea is not only valid for Herodotus’ time but it is something anthropology uses time and again to explain different aspects in people’s way of life. Through food and its environment, the dining space, this paper will aim to put the cage cups into a social context in order to give emphasis to the hypothesis of light versus wine

Physical activity attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children

Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (pinteraction= 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Concl

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Association between peri-operative angiotensin-converting enzyme inhibitors and angiotensin-2 receptor blockers and acute kidney injury in major elective non-cardiac surgery: a multicentre, prospective cohort study

The peri-operative use of angiotensin-converting enzyme inhibitors or angiotensin-2 receptor blockers is thought to be associated with an increased risk of postoperative acute kidney injury. To reduce this risk, these agents are commonly withheld during the peri-operative period. This study aimed to investigate if withholding angiotensin-converting enzyme inhibitors or angiotensin-2 receptor blockers peri-operatively reduces the risk of acute kidney injury following major non-cardiac surgery. Patients undergoing elective major surgery on the gastrointestinal tract and/or the liver were eligible for inclusion in this prospective study. The primary outcome was the development of acute kidney injury within seven days of operation. Adjusted multi-level models were used to account for centre-level effects and propensity score matching was used to reduce the effects of selection bias between treatment groups. A total of 949 patients were included from 160 centres across the UK and Republic of Ireland. From this population, 573 (60.4%) patients had their angiotensin-converting enzyme inhibitors or angiotensin-2 receptor blockers withheld during the peri-operative period. One hundred and seventy-five (18.4%) patients developed acute kidney injury; there was no difference in the incidence of acute kidney injury between patients who had their angiotensin-converting enzyme inhibitors or angiotensin-2 receptor blockers continued or withheld (107 (18.7%) vs. 68 (18.1%), respectively; p = 0.914). Following propensity matching, withholding angiotensin-converting enzyme inhibitors or angiotensin-2 receptor blockers did not demonstrate a protective effect against the development of postoperative acute kidney injury (OR (95%CI) 0.89 (0.58–1.34); p = 0.567)

A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Background High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ −6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. Methods The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. Findings In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17–21%), 2% (1–3%), 8% (7–10%) and 6% (3–9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75–0.81), 0.58 (0.53–0.64), 0.71 (0.69–0.74) and 0.67 (0.62–0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92–1.24). Interpretation Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted fo