Established Risk Markers Research Articles

Early-Life and Adult Anthropometrics in Relation to Mammographic Image Intensity Variation in the Nurses' Health Studies.

The V measure captures grayscale intensity variation on a mammogram and is positively associated with breast cancer risk, independent of percent mammographic density (PMD), an established marker of breast cancer risk. We examined whether anthropometrics are associated with V, independent of PMD. The analysis included 1,700 premenopausal and 1,947 postmenopausal women without breast cancer within the Nurses' Health Study (NHS) and NHSII. Participants recalled their body fatness at ages 5, 10, and 20 years using a 9-level pictogram (level 1: most lean) and reported weight at age 18 years, current adult weight, and adult height. V was estimated by calculating standard deviation of pixels on screening mammograms. Linear mixed models were used to estimate beta coefficients (ß) and 95% confidence intervals (CI) for the relationships between anthropometric measures and V, adjusting for confounders and PMD. V and PMD were positively correlated (Spearman r = 0.60). Higher average body fatness at ages 5 to 10 years (level ≥ 4.5 vs. 1) was significantly associated with lower V in premenopausal (ß = -0.32; 95% CI, -0.48 to -0.16) and postmenopausal (ß = -0.24; 95% CI, -0.37 to -0.10) women, independent of current body mass index (BMI) and PMD. Similar inverse associations were observed with average body fatness at ages 10 to 20 years and BMI at age 18 years. Current BMI was inversely associated with V, but the associations were largely attenuated after adjustment for PMD. Height was not associated with V. Our data suggest that early-life body fatness may reflect lifelong impact on breast tissue architecture beyond breast density. However, further studies are needed to confirm the results. This study highlights strong inverse associations of early-life adiposity with mammographic image intensity variation.

Plasma N-Glycans as Emerging Biomarkers of Cardiometabolic Risk: A Prospective Investigation in the EPIC-Potsdam Cohort Study.

Plasma protein N-glycan profiling integrates information on enzymatic protein glycosylation, which is a highly controlled ubiquitous posttranslational modification. Here we investigate the ability of the plasma N-glycome to predict incidence of type 2 diabetes and cardiovascular diseases (CVDs; i.e., myocardial infarction and stroke). Based on the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort (n = 27,548), we constructed case-cohorts including a random subsample of 2,500 participants and all physician-verified incident cases of type 2 diabetes (n = 820; median follow-up time 6.5 years) and CVD (n = 508; median follow-up time 8.2 years). Information on the relative abundance of 39 N-glycan groups in baseline plasma samples was generated by chromatographic profiling. We selected predictive N-glycans for type 2 diabetes and CVD separately, based on cross-validated machine learning, nonlinear model building, and construction of weighted prediction scores. This workflow for CVD was applied separately in men and women. The N-glycan-based type 2 diabetes score was strongly predictive for diabetes risk in an internal validation cohort (weighted C-index 0.83, 95% CI 0.78-0.88), and this finding was externally validated in the Finland Cardiovascular Risk Study (FINRISK) cohort. N-glycans were moderately predictive for CVD incidence (weighted C-indices 0.66, 95% CI 0.60-0.72, for men; 0.64, 95% CI 0.55-0.73, for women). Information on the selected N-glycans improved the accuracy of established and clinically applied risk prediction scores for type 2 diabetes and CVD. Selected N-glycans improve type 2 diabetes and CVD prediction beyond established risk markers. Plasma protein N-glycan profiling may thus be useful for risk stratification in the context of precisely targeted primary prevention of cardiometabolic diseases.

365 Left Atrial Functional Index is a Predictor of Persistent/permanent Non-Valvular Atrial Fibrillation

Chronicity of atrial fibrillation (AF) has been associated with poor cardiovascular outcomes. Left atrial function index (LAFI) is a rhythm-independent measure of LA reservoir function adjusted for LA size and stroke volume and is an established marker of risk for cardiac disease states. We sought to evaluate the role of LA function by LAFI in predicting persistent/permanent AF. Patients attending our institution between Jan 2013 and Dec 2017 were assessed. Patients with history of non-valvular AF who received transthoracic echocardiogram (TTE) evaluation were included. In these patients, we evaluated demographic profiles, AF history, clinical comorbidities and echocardiographic data. We excluded patients with valvular AF, poor quality TTE images and incomplete clinical data. Of the 665 patients (67.78±13.62years, 52% male) included, 27.8% had persistent/permanent AF. Persistent/permanent AF was associated with older age (p<0.01), heart failure (p<0.01), diabetes mellitus (p=0.02), ischaemic heart disease (p=0.02), obstructive sleep apnoea (p=0.04), renal impairment (p<0.01), lower left ventricular ejection fraction (p<0.01), higher E/e’ (p<0.01), larger LA volume index (p<0.01) and lower LAFI (p<0.01). Multi-variable analysis revealed both heart failure (OR 3.024, 95% CI 1.737 to 5.265, p<0.01) and LAFI (OR 4.881, 95% CI 2.503 to 9.519, p<0.01) as independent predictors of persistent/permanent AF. Receiver operating characteristic curve showed LAFI (Figure1; AUC 0.75, 95% CI 0.703 to 0.793, p<0.01) of less than 16.5 to have a 70% sensitivity and 70% specificity in detecting persistent/permanent AF LAFI, an echocardiographic measure of atrial mechanical function, may be a useful tool in risk stratification for patients with non-valvular AF.

Non-invasive estimation of relative pressure in turbulent flow using virtual work-energy.

Vascular pressure differences are established risk markers for a number of cardiovascular diseases. Relative pressures are, however, often driven by turbulence-induced flow fluctuations, where conventional non-invasive methods may yield inaccurate results. Recently, we proposed a novel method for non-turbulent flows, νWERP, utilizing the concept of virtual work-energy to accurately probe relative pressure through complex branching vasculature. Here, we present an extension of this approach for turbulent flows: νWERP-t. We present a theoretical method derivation based on flow covariance, quantifying the impact of flow fluctuations on relative pressure. νWERP-t is tested on a set of in-vitro stenotic flow phantoms with data acquired by 4D flow MRI with six-directional flow encoding, as well as on a patient-specific in-silico model of an acute aortic dissection. Over all tests νWERP-t shows improved accuracy over alternative energy-based approaches, with excellent recovery of estimated relative pressures. In particular, the use of a guaranteed divergence-free virtual field improves accuracy in cases where turbulent flows skew the apparent divergence of the acquired field. With the original νWERP allowing for assessment of relative pressure into previously inaccessible vasculatures, the extended νWERP-t further enlarges the method's clinical scope, underlining its potential as a novel tool for assessing relative pressure in-vivo.

Is proteomics of value in cardiovascular risk assessment?

To briefly summarize recently published evidence in the field of cardiovascular proteomics, focusing on its ability to improve cardiovascular risk stratification and critically discussing still open and burning issues and future perspectives of proteomics research. Several epidemiological studies have demonstrated an improvement in cardiovascular risk prediction beyond traditional risk factors by adding novel biomarkers, identified by both discovery and targeted proteomics. However, only a moderate improvement in risk discrimination over clinical variables was observed. Moreover, despite different outcomes there was also a strong overlap of identified candidates, with several of them being already well established cardiovascular risk markers such as growth differentiation factor 15, natriuretic peptides, C-reactive protein, interleukins, and metalloproteases. Although proteomics plays a crucial role in biomarker discovery, the modest discriminative ability of this technique raises the possibility that there are still hidden mechanisms in protein regulatory networks, which urgently need to be evaluated to improve a cardiovascular risk assessment to a clinically significant extent.

3056Orthogonal P wave morphology, traditional P wave indices, and the risk of atrial fibrillation in the general population

Abstract Background A substantial portion of the risk of atrial fibrillation (AF) remains unexplained by the established risk markers. However, accurate assessment of AF risk would be beneficial, especially among stroke patients and subjects with symptoms attributable to arrhythmia. Purpose To study the associations of P-wave indices with AF risk in the general population. Methods Electrocardiograms, including orthogonal leads, of 7217 Finnish subjects aged over 30 years who took part in the baseline examinations of the Mini-Finland Health Survey in 1978–80, were digitized. P-wave duration, third-degree interatrial block (IAB), and P terminal force (PTF) were assessed manually. PTF was considered abnormal when the amplitude of the negative terminal part of the P wave in lead V1 was ≥0.1mV and duration ≥40ms. Third-degree IAB was defined as P-wave duration ≥120ms and the presence of ≥2 +/− biphasic P-waves in the inferior leads. Orthogonal P-wave morphology, which is related to left atrial breakthrough site and affected by atrial fibrosis (1 being considered benign, 2 borderline, and 3 shown to be associated with adverse events), was assessed with an automated algorithm, and ascertained manually. Subjects were followed 10 years for AF hospitalization and mortality. The risk of AF associated with P wave parameters was assessed using Cox proportional hazards models. Model discrimination improvement was quantified by the change in C index, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). Results There were 5489 subjects (47.8% male, mean age 50.5 years) with a readable ECG, sinus rhythm, no missing data, and a predefined orthogonal P-wave morphology. Type 3 orthogonal P morphology (n=216, multivariate adjusted HR [maHR] 3.01, 95% confidence interval [CI] 1.66–5.45, p&lt;0.001), P-wave duration ≥120ms (n=752, maHR 1.67, 95% CI 1.06–2.64, p=0.027), and third-degree IAB (n=103, maHR 3.18, 95% CI 1.66–6.13, p=0.001) were independently associated with the risk of AF in separate models. PTF did not independently predict AF. Subjects presenting with both Type 1 orthogonal P-wave morphology and P-wave duration &lt;110ms (n=2074) were at low risk of AF (maHR 0.46, 95% CI 0.26–0.83, p=0.006) when compared to the rest of the subjects. The inclusion of variables combining orthogonal P-wave morphology and P-wave duration to a multivariate model including conventional AF risk factors improved C index from 0.815 to 0.832 (change 0.017, 95% CI 0.001–0.033), IDI was 0.012 (95% CI 0.006–0.051), and cNRI was 0.220 (95% CI 0.048–0.357). Conclusions P-wave indices and orthogonal P-wave morphology can be used to identify subjects at high and low risk for AF and possibly direct extensive AF screening protocols towards high-risk subjects in the general population in order to decrease the risk of cardioembolic stroke. However, more research is needed in this topic. Acknowledgement/Funding Finnish Medical Foundation, Onni and Hilja Tuovinen's Foundation, Orion Research Foundation, Paavo Nurmi's Foundation, Veritas Foundation

P4449Incident cardiovascular disease in patients with type 2 diabetes: Established cardiovascular disease versus traditional risk markers

Abstract Background/Introduction It is well established that patients with both T2D and established cardiovascular disease (CVD) are at high-risk of a re-event and should be treated with either a glucagon-like peptide-1 (GLP-1) analogue or a sodium-glucose transporter-2 (SGLT-2) inhibitor. Other high-risk patients with T2D may also benefit from these treatments. Whether traditional risk markers can identify patients with T2D without CVD with a similar incidence of CVD events as patients with T2D with established CVD is unknown. Purpose To compare the CVD incidence in patients with T2D with and without established CVD, stratified according to mid-regional pro-atrial natriuretic peptide (MR-proANP), albuminuria, electrogardiogram (ECG), echocardiography and age, to identify patients without established CVD who are at high risk of a CVD event. Methods In this prospective cohort study, patients with T2D (n=921) from a specialized diabetes clinic were examined at baseline regarding the different risk markers. Increasing cut-offs for MR-proANP were analysed to identify high-risk patients. Albuminuria included both micro- and macroalbuminuria. An abnormal ECG was defined as the presence of ST-/T-changes, bundle branch block or atrial fibrillation, and an abnormal echocardiography was defined as either heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction. Established CVD was reported at baseline as prior myocardial infarction, coronary revascularization, cerebrovascular disease or peripheral artery disease. Information regarding CVD events was retrieved through national registers and a CVD event was similarly defined as established CVD, but in addition also included hospitalisation for heart failure and CVD death. Results In total, 224 (24%) patients had established CVD at baseline. Median [interquartile range] of follow-up was 4.7 [4.0–5.3] years. The incidence of CVD events among patients with established CVD was 95.7 per 1000-person years. Using a cut-off for MR-proANP of 190 pmol/l revealed that patients with a value above had similar incidence (93.9 per 1000-person years) and was found in 47 of 697 (6.7%) patients without CVD. In contrast, patients without CVD and with albuminuria (146 of 685 (21.3%) patients) or abnormal ECG (147 of 679 (21.6%)) or abnormal echocardiography (221 of 618 (35.7%)) or an age&gt;65 years (335 of 697 (35.7%)) had substantial lower incidence (47.1, 35.1, 32.7 and 33.7 per 1000-person years, respectively). Kaplan-Meier curves Conclusion(s) In patients with T2D without established CVD, using a range of traditional risk markers, we were only able to identify a subgroup of patients with MR-proANP values above 190 pmol/l who had a similar high incidence of CVD as T2D patients with established CVD. This subgroup may benefit from treatment with a GLP-1 analog or a SGLT-2 inhibitor. In contrast, the presence of other traditional risk markers in T2D was not associated with risk of incident CVD similar to patients with established CVD. Acknowledgement/Funding Thermo Fisher Scientific (Germany) funded the MR-proANP kits

GDF-15 in solid vs non-solid treatment-naïve malignancies.

AimGDF‐15 is an established cardiovascular risk marker but is equally implicated in tumour biology. Elevated levels of GDF‐15 have indeed been observed in distinct tumour entities. This study aimed to explore the relation of GDF‐15 to other cardiac biomarkers and the general association of GDF‐15 on prognosis in an unselected cohort of treatment‐naïve cancer patients.MethodsWe prospectively enrolled 555 consecutive patients at time of diagnosis of malignant disease prior receiving anticancer therapy. Plasma GDF‐15 concentrations were determined alongside other cardiac and routine laboratory markers. All‐cause mortality was defined as primary endpoint.ResultsGDF‐15 levels were 338 ng/L (IQR:205‐534) for the total cohort, and values were comparable for different tumour entities except breast cancer. Metastatic disease was characterized by higher plasma GDF‐15 [435 ng/L (IQR:279‐614) vs 266 ng/L (IQR:175‐427), P < .001]. GDF‐15 correlated positively with inflammatory status reflected by CRP, SAA and IL‐6 [r = .31, P < .001, r = .23, P < .001 and r = .14, P = .002] and cardiac biomarkers as NT‐proBNP, hsTnT, MR‐proADM and CT‐proET‐1 [r = .46; r = .46; r = .59 and r = .50; P < .001 for all]. GDF‐15 was significantly associated with all‐cause mortality after multivariate adjustment [adj.HR for ln(GDF‐15) 1.78, 95%CI:1.47‐2.16, P < .001]. There was a significant interaction between solid and haematological malignancies with loss of association of GDF‐15 with outcome in myelodysplastic and myeloproliferative disease.ConclusionsElevated plasma GDF‐15 is associated with progressing disease severity and poor prognosis in solid tumours of treatment‐naïve cancer patients. GDF‐15 increase is accompanied by worsening systemic inflammation and a subclinical functional impairment of different organs including the heart. GDF‐15 represents a promising target for our pathophysiologic understanding in cardio‐oncology linking conditions of both cardiac and neoplastic disease.

Skin autofluorescence as a measure of advanced glycation end product levels is associated with carotid atherosclerotic plaque burden in an elderly population.

Advanced glycation end product is an established risk marker in diabetic vascular disease, but its possible associations with atherosclerosis in a general population are yet to be investigated. We studied the degree of carotid atherosclerosis and its association with skin autofluorescence in an elderly population. Carotid ultrasound and skin autofluorescence measurements were performed in a subpopulation within the 'Malmö Diet and Cancer Cardiovascular Cohort' re-examination study (n = 523). Total plaque area including all prevalent plaques in the right carotid artery was calculated. Complete data on all variables were available for 496 subjects (mean age 72 years). Each 1 standard deviation increment of skin autofluorescence was associated with increased risk of prevalent large plaques (odds ratio, 1.32; 95% confidence interval, 1.05-1.66; p = 0.018) independently of diabetes and cardiovascular risk factors. The top versus bottom tertile of the skin autofluorescence was associated with an approximately twofold risk of being in the population with the highest plaque burden [top quartile with total plaque area ⩾ 35 mm2 (odds ratio, 1.88; 95% confidence interval, 1.05-3.39; p for trend = 0.027)] in fully adjusted analysis. In an elderly population, skin autofluorescence was associated with increasing degree of carotid atherosclerosis measured as total plaque area, independently of diabetes and cardiovascular risk factors.

Cardiovascular magnetic resonance imaging feature tracking: Impact of training on observer performance and reproducibility

BackgroundCardiovascular magnetic resonance feature tracking (CMR-FT) is increasingly used for myocardial deformation assessment including ventricular strain, showing prognostic value beyond established risk markers if used in experienced centres. Little is known about the impact of appropriate training on CMR-FT performance. Consequently, this study aimed to evaluate the impact of training on observer variance using different commercially available CMR-FT software.MethodsIntra- and inter-observer reproducibility was assessed prior to and after dedicated one-hour observer training. Employed FT software included 3 different commercially available platforms (TomTec, Medis, Circle). Left (LV) and right (RV) ventricular global longitudinal as well as LV circumferential and radial strains (GLS, GCS and GRS) were studied in 12 heart failure patients and 12 healthy volunteers.ResultsTraining improved intra- and inter-observer reproducibility. GCS and LV GLS showed the highest reproducibility before (ICC >0.86 and >0.81) and after training (ICC >0.91 and >0.92). RV GLS and GRS were more susceptible to tracking inaccuracies and reproducibility was lower. Inter-observer reproducibility was lower than intra-observer reproducibility prior to training with more pronounced improvements after training. Before training, LV strain reproducibility was lower in healthy volunteers as compared to patients with no differences after training. Whilst LV strain reproducibility was sufficient within individual software solutions inter-software comparisons revealed considerable software related variance.ConclusionObserver experience is an important source of variance in CMR-FT derived strain assessment. Dedicated observer training significantly improves reproducibility with most profound benefits in states of high myocardial contractility and potential to facilitate widespread clinical implementation due to optimized robustness and diagnostic performance.

Association between emergency department utilization and the risk of child maltreatment in young children

BackgroundThis study aims to assess the association between emergency department (ED) utilization and the risk of child maltreatment.MethodsUsing ED discharge data from the California’s Office of Statewide Health Planning (OSHPD) and Development for 2008–2013, we performed a nested case-control study to examine the relationship between the frequency of ED visits and child maltreatment diagnosis under 4 years of age among children born in California between 2008 and 2009 who visited the ED.ResultsThe study sample consisted of 3772 children diagnosed with child maltreatment (cases) and 7544 children selected by incidence density sampling (controls). After adjustment for demographic characteristics, the estimated odds ratios of child maltreatment were 1.72 (95% CI:1.55–1.90) for those with two to three ED visits and 3.03 (95% CI: 2.69–3.41) for those with four or more ED visits, compared to children with one visit. Race/ethnicity, insurance status, and location of residence were also significantly associated with the risk of child maltreatment.ConclusionsYoung children with higher frequency of ED visits are at significantly increased risk of being victims of child maltreatment. ED utilization patterns and other established risk markers may assist healthcare professionals in identifying and treating victims of child maltreatment.

Association of High Sensitive C - Reactive Protein with Severity of the Left Ventricular Systolic Dysfunction in Acute Anterior ST Elevation Myocardial Infarction

High Sensitive C-reactive protein (hs- CRP) is an established risk marker in coronary artery disease. It is a marker of inflammation activated early after Acute Myocardial Infarction (AMI) and its quantity depends upon extent of myocardial damage. Release of inflammatory marker occur after acute myocardial infarction leading to cardiac remodeling which clinically manifests as Heart failure (HF). Heart failure is a common complication after acute anterior myocardial infarction (AMI). The prevalence of post-infarct Left Ventricular Systolic Dysfunction (LVSD) ranges from 27 to 60 % and half of patients having early post-infarct LVSD subsequently develop chronic heart failure. The purpose of this study is to show association between hs-CRP with LVSD in AMI and early detection of HF. This was a cross-sectional analytical study in which hs-CRP was done among all the study subjects between 24-48 hours after onset of AMI. The study population was categorized into groups I, II, II according to the lowest to highest hs-CRP level. Transthoracic echocardiography was done between 24-48 hours of anterior ST Elevation Myocardial Infarction (STEMI). Then LVSD was assessed between those three groups and searched for association. Severely reduced ejection fraction (EF) was found in patients of group III (highest hs-CRP tertile) only. Severe and moderately reduced EF and FS was found significantly more in group III and II than group I (mid and lowest hs-CRP tertile) (p&lt;0.001). High level of hs-CRP in patient of acute anterior STEMI patients was associated with moderate to severe reduction in EF and Fractional Shortening (FS). So hs- CRP may be a prognostic marker in acute anterior STEMI complicating LVSD and early management would improved the short and long term prognosis.

Depression, Anxiety, and Cognitive Impairment : Comorbid Mental Health Disorders in Heart Failure.

Depression, anxiety, and cognitive impairment constitute established risk markers for incident cardiovascular disease (CVD) and are associated with impaired life expectancy and quality of life and high hospitalization rates and healthcare expenditure. This review summarizes current knowledge about mental health disorders in patients with CVD and heart failure (HF). Emerging evidence suggests various shared pathophysiological mechanisms between psychological comorbidities and CVD (e.g., systemic inflammation and autonomic dysfunction). Bi-directional interactions involving the central nervous and cardiovascular systems may help explain the rising prevalence of comorbid mood disorders with increasing CVD severity and support the concept of alternative pathophysiological mechanisms in the presence of severe somatic illness, making symptoms less responsive or unresponsive to psychotropic pharmacotherapy. Considering high prevalence and negative impact of psychological comorbidities in CVD and HF, routine care should integrate screening for these conditions. Multidisciplinary treatment approaches with active patient participation in disease management were shown to improve outcomes. However, better understanding of factors mediating the adverse prognostic effects of mood disorders is needed. This might enable more targeted treatment and possibly also facilitate better understanding of the pathophysiological mechanisms driving CVD.

Changes in NT-proCNP levels in patients with end stage renal failure before and after kidney allotrasplantation

Aim: N-terminal fragment of C-type natriuretic peptide (NT-proCNP) is a paracrine growth factor expressed in the vascular endothelium and shown to be associated with arterial stiffness, endothelial dysfunction, and early atherosclerosis. It also contributes to prediction of estimated glomerular filtration rate (eGFR) decline on top of established risk markers in type 2 diabetes. However, the change in plasma NT-proCNP level after kidney transplantation has not been studied previously.

Application of competing risks analysis improved prognostic assessment of patients with decompensated chronic heart failure and reduced left ventricular ejection fraction

ObjectiveThe Kaplan–Meier method may overestimate absolute mortality risk (AMR) in the presence of competing risks. Urgent heart transplantation (UHT) and ventricular assist device implantation (VADi) are important competing events in heart failure. We sought to quantify the extent of bias of the Kaplan–Meier method in estimating AMR in the presence of competing events and to analyze the effect of covariates on the hazard for death and competing events in the clinical model of decompensated chronic heart failure with reduced ejection fraction (DCHFrEF). Study Design and SettingWe studied 683 patients. We used the cumulative incidence function (CIF) to estimate the AMR at 1 year. CIF estimate was compared with the Kaplan–Meier estimate. The Fine–Gray subdistribution hazard analysis was used to assess the effect of covariates on the hazard for death and UHT/VADi. ResultsThe Kaplan–Meier estimate of the AMR was 0.272, whereas the CIF estimate was 0.246. The difference was more pronounced in the patient subgroup with advanced DCHF (0.424 vs. 0.338). The Fine–Gray subdistribution hazard analysis revealed that established risk markers have qualitatively different effects on the incidence of death or UHT/VADi. ConclusionCompeting risks analysis allows more accurately estimating AMR and better understanding the association between covariates and major outcomes in DCHFrEF.

Abstract 692: Systemic inflammation and survival in colon and rectal cancer patients: Results from the ColoCare Study

Abstract BACKGROUND Systemic inflammation is an established risk marker for colorectal cancer that may also predict survival. We investigated associations between systemic inflammation and overall survival in a prospectively followed cohort of colorectal cancer patients. METHODS Pre-operatively collected serum samples from n=228 newly diagnosed colorectal cancer patients (stage I-IV) from the ColoCare Study were utilized to measure CRP, SAA, IL-6, IL-8, sICAM-1 and sVCAM-1 (Meso Scale Discovery platform). We used Cox proportional hazard models to investigate associations of biomarkers with overall survival after 24 months follow-up overall, and in analyses stratified by colon (n=92) and rectal tumors (n=136). Analyses were adjusted for age, sex, tumor stage and neo-adjuvant therapy (y/n). RESULTS After 24 months follow-up n=45 patients (20%) were deceased. CRP was significantly associated with increased risk of death in colon (HR:1.27; 95% CI: 1.03-1.57; pValue=0.02) but not rectal cancer (HR:1.06; 95% CI: 0.87-1.29; pValue=0.55). A doubling of circulating sICAM and sVCAM concentrations was significantly associated with increased risk of death in colorectal cancer (sICAM: HR:2.82; 95% CI: 1.57-5.05; pValue=0.0005; sVCAM: HR:3.70; 95% CI: 1.93-7.10; pValue&amp;lt;0.0001). For both biomarkers we observed stronger associations in rectal compared to colon cancer (e.g., sVCAM: rectal cancer (HR:8.13; 95% CI: 3.13-21.11; pValue&amp;lt;0.0001); colon cancer (HR:1.42; 95% CI: 0.68-2.98; pValue=0.35). Circulating IL-6 and IL-8 were not associated with increased risk of death in colon and/or rectal cancer. CONCLUSIONS Inflammatory biomarkers are significantly associated with increased risk of death in colorectal cancer patients. Our data suggest that the role of inflammation in disease progression may be particularly strong relevant in rectal cancer. Keywords: colorectal cancer; inflammation, biomarkers, overall survival, Citation Format: Jennifer Ose. Systemic inflammation and survival in colon and rectal cancer patients: Results from the ColoCare Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 692.

Long-term follow-up on biological risk factors, adiposity, and cardiorespiratory fitness development in a physical education intervention: a natural experiment (CHAMPS-study DK)

BackgroundSchools are a key setting for large-scale primordial non-communicable disease prevention in young people, but little data on sustainability of impacts on cardiometabolic risk markers is available.MethodsSix and a half year follow-up of a natural experiment. In 2008, six public schools in the municipality of Svendborg (Denmark) augmented their curricular physical education (intervention) and four matched schools served as controls. At long term follow up in 2015 n = 312 participants aged 5–11 years had complete data (33% of children providing necessary baseline data). The intervention, that consisted of a trebling of weekly physical education lessons and courses provided to physical education teachers, was provided at intervention schools up until 6th grade. Participants attended 6th to 10th grade at follow-up. Differences in the homeostasis model assessment of insulin resistance, blood pressure, triglycerides, cholesterol ratios, cardiorespiratory fitness, waist-circumference, and a composite score of these, between participants attending intervention and control schools were analysed by mixed linear regression models. Differences in physical activity at follow-up was analysed cross-sectionally (no baseline available) in n = 495.ResultsCompared to controls, children at intervention schools had a non-significant − 0.07 (− 0.32 to 0.18) standard deviations lower composite risk score 6.5 years after project initiation. Likewise, no statistically significant differences between intervention and control schools were found for any of the other outcomes (p-values ≥ 0.41). However, six of seven outcomes were in a direction favouring intervention schools. No statistically significant differences between intervention and control schools were observed for physical activity outcomes (p-values ≥ 0.13).ConclusionsAn augmented physical activity program including 270 min of weekly physical education provided for three to seven years did not materialize in statistically significant differences in established risk markers in children from intervention compared to control schools. As the intervention was discontinued after 6th grade, the post-intervention effect of augmented physical education throughout adolescence is unknown. School-based physical activity programs may benefit from incorporating instruments for behaviour translation to leisure time in their intervention models to increase the probability of achieving public health relevance.Trial registrationClinicalTrials.gov Identifier: NCT03510494.

Impact of meal fatty acid composition on postprandial lipaemia, vascular function and blood pressure in postmenopausal women.

CVD are the leading cause of death in women globally, with ageing associated with progressive endothelial dysfunction and increased CVD risk. Natural menopause is characterised by raised non-fasting TAG concentrations and impairment of vascular function compared with premenopausal women. However, the mechanisms underlying the increased CVD risk after women have transitioned through the menopause are unclear. Dietary fat is an important modifiable risk factor relating to both postprandial lipaemia and vascular reactivity. Meals rich in SFA and MUFA are often associated with greater postprandial TAG responses compared with those containing n-6 PUFA, but studies comparing their effects on vascular function during the postprandial phase are limited, particularly in postmenopausal women. The present review aimed to evaluate the acute effects of test meals rich in SFA, MUFA and n-6 PUFA on postprandial lipaemia, vascular reactivity and other CVD risk factors in postmenopausal women. The systematic search of the literature identified 778 publications. The impact of fat-rich meals on postprandial lipaemia was reported in seven relevant studies, of which meal fat composition was compared in one study described in three papers. An additional study determined the impact of a high-fat meal on vascular reactivity. Although moderately consistent evidence suggests detrimental effects of high-fat meals on postprandial lipaemia in postmenopausal (than premenopausal) women, there is insufficient evidence to establish the impact of meals of differing fat composition. Furthermore, there is no robust evidence to conclude the effect of meal fatty acids on vascular function or blood pressure. In conclusion, there is an urgent requirement for suitably powered robust randomised controlled trials to investigate the impact of meal fat composition on postprandial novel and established CVD risk markers in postmenopausal women, an understudied population at increased cardiometabolic risk.

A rapid, maskless 3D prototyping for fabrication of capillary circuits: Toward urinary protein detection.

Proteinuria is an established risk marker for progressive renal function loss and patients would significantly benefit from a point-of-care testing. Although extensive work has been done to develop the microfluidic devices for the detection of urinary protein, they need the complicated operation and bulky peripherals. Here, we present a rapid, maskless 3D prototyping for fabrication of capillary fluidic circuits using laser engraving. The capillary circuits can be fabricated in a short amount of time (<10 min) without the requirements of clean-room facilities and photomasks. The advanced capillary components (e.g., trigger valves, retention valves and retention bursting valves) were fabricated, enabling the sequential liquid delivery and sample-reagent mixing. With the integration of smartphone-based detection platform, the microfluidic device can quantify the urinary protein via a colorimetric analysis. By eliminating the bulky and expensive equipment, this smartphone-based detection platform is portable for on-site quantitative detection.

Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure: An Individual Patient Data Meta-Analysis.

Most patients with chronic heart failure have detectable troponin concentrations when evaluated by high-sensitivity assays. The prognostic relevance of this finding has not been clearly established so far. We aimed to assess high-sensitivity troponin assay for risk stratification in chronic heart failure through a meta-analysis approach. Medline, EMBASE, Cochrane Library, and Scopus were searched in April 2017 by 2 independent authors. The terms were "troponin" AND "heart failure" OR "cardiac failure" OR "cardiac dysfunction" OR "cardiac insufficiency" OR "left ventricular dysfunction." Inclusion criteria were English language, clinical stability, use of a high-sensitivity troponin assay, follow-up studies, and availability of individual patient data after request to authors. Data retrieved from articles and provided by authors were used in agreement with the PRISMA statement. The end points were all-cause death, cardiovascular death, and hospitalization for cardiovascular cause. Ten studies were included, reporting data on 11 cohorts and 9289 patients (age 66±12 years, 77% men, 60% ischemic heart failure, 85% with left ventricular ejection fraction <40%). High-sensitivity troponin T data were available for all patients, whereas only 209 patients also had high-sensitivity troponin I assayed. When added to a prognostic model including established risk markers (sex, age, ischemic versus nonischemic etiology, left ventricular ejection fraction, estimated glomerular filtration rate, and N-terminal fraction of pro-B-type natriuretic peptide), high-sensitivity troponin T remained independently associated with all-cause mortality (hazard ratio, 1.48; 95% confidence interval, 1.41-1.55), cardiovascular mortality (hazard ratio, 1.40; 95% confidence interval, 1.33-1.48), and cardiovascular hospitalization (hazard ratio, 1.42; 95% confidence interval, 1.36-1.49), over a median 2.4-year follow-up (all P<0.001). High-sensitivity troponin T significantly improved risk prediction when added to a prognostic model including the variables above. It also displayed an independent prognostic value for all outcomes in almost all population subgroups. The area under the curve-derived 18 ng/L cutoff yielded independent prognostic value for the 3 end points in both men and women, patients with either ischemic or nonischemic etiology, and across categories of renal dysfunction. In chronic heart failure, high-sensitivity troponin T is a strong and independent predictor of all-cause and cardiovascular mortality, and of hospitalization for cardiovascular causes, as well. This biomarker then represents an additional tool for prognostic stratification.