Standard Risk Scores Research Articles

Metabolomic Pattern Predicts Incident Coronary Heart Disease.

Objective- Alterations in the serum metabolome may be detectable in at-risk individuals before the onset of coronary heart disease (CHD). Identifying metabolomic signatures associated with CHD may provide insight into disease pathophysiology and prevention. Approach and Results- Metabolomic profiling (chromatography-mass spectrometry) was performed in 2232 African Americans and 1366 European Americans from the ARIC study (Atherosclerosis Risk in Communities). We applied Cox regression with least absolute shrinkage and selection operator to select metabolites associated with incident CHD. A metabolite risk score was constructed to evaluate whether the metabolite risk score predicted CHD risk beyond traditional risk factors. After 30 years of follow-up, we observed 633 incident CHD cases. Thirty-two metabolites were selected by least absolute shrinkage and selection operator to be associated with CHD, and 19 of the 32 showed significant individual associations with CHD, including a sugar substitute, erythritol. Theophylline (hazard ratio [95% CI] =1.16 [1.09-1.25]) and gamma-linolenic acid (hazard ratio [95% CI] =0.89 [0.81-0.97]) showed the greatest positive and negative associations with CHD, respectively. A 1 SD greater standardized metabolite risk score was associated with a 1.37-fold higher risk of CHD (hazard ratio [95% CI] =1.37 [1.27-1.47]). Adding the metabolite risk score to the traditional risk factors significantly improved model predictive performance (30-year risk prediction: Δ C statistics [95% CI] =0.016 [0.008-0.024], continuous net reclassification index [95% CI] =0.522 [0.480-0.556], integrated discrimination index [95% CI] =0.038 [0.019-0.065]). Conclusions- We identified 19 metabolites from known and novel metabolic pathways that collectively improved CHD risk prediction. Visual Overview- An online visual overview is available for this article.

Prediction of Onset of Substance-Induced Psychotic Disorder and Its Progression to Schizophrenia in a Swedish National Sample

The objective of this study was to clarify the etiology of substance-induced psychotic disorder and its progression to schizophrenia in a Swedish national sample. Individuals with a registration of substance-induced psychotic disorder between 1997 and 2015 in national medical registries (N=7,606) were followed up for a mean of 84 months. Data from medical, criminal, and pharmacy registries on first-degree through third-degree relatives were used to calculate familial risk scores for nonaffective psychosis, drug abuse, and alcohol use disorder. Individuals with substance-induced psychotic disorder had large elevations in standardized familial risk scores for drug abuse (+1.09, 95% CI=1.02, 1.15) and alcohol use disorder (+0.98, 95% CI=0.93, 1.03) and modest elevations for nonaffective psychosis (+0.35, 95% CI=0.30, 0.41). The cumulative risk for progression to schizophrenia was 11.3%; it was lowest for alcohol-induced and highest for cannabis-induced psychotic disorder, and it was predicted by early age at diagnosis of substance-induced psychotic disorder, male sex, and further registrations for episodes of drug abuse, alcohol use disorder, and substance-induced psychotic disorder. A risk prediction model found that 47% of individuals who converted to schizophrenia were in the upper 20% of risk. Familial risk scores for drug abuse and alcohol use disorder did not significantly discriminate those who converted to schizophrenia from those who did not, while familial risk score for nonaffective psychosis did (0.67, 95% CI=0.40, 0.95, versus 0.33, 95% CI=0.28, 0.39). Familial risk scores for nonaffective psychosis were indistinguishable between individuals with schizophrenia with and without prior substance-induced psychosis. Assignment of early retirement by the Swedish Social Insurance Agency strongly discriminated between individuals with substance-induced psychotic disorder with and without later schizophrenia. Substance-induced psychotic disorder appears to result from substantial drug exposure in individuals at high familial risk for substance abuse and moderately elevated familial risk for psychosis. Familial risk for psychosis, but not substance abuse, predicts progression from substance-induced psychosis to schizophrenia. Schizophrenia following substance-induced psychosis is likely a drug-precipitated disorder in highly vulnerable individuals, not a syndrome predominantly caused by drug exposure.

DEEP PHENOTYPING AND PREDICTION OF LONG-TERM HEART FAILURE BY MACHINE LEARNING

Machine learning may be useful to characterize cardiovascular risk, predict outcomes, and identify biomarkers in population studies. To test the ability of random survival forests, a machine learning technique, to predict heart failure (HF) in comparison to standard cardiovascular risk scores. We

Practical Risk Stratification Score for Prediction of Contrast-Induced Nephropathy After Primary Percutaneous Coronary Intervention in Patients With Acute ST-Segment Elevation Myocardial Infarction.

BackgroundContrast-induced nephropathy (CIN) is a common complication of percutaneous coronary intervention (PCI). This study aimed to develop a new risk stratification score that is simpler and more practical than the standard Mehran risk score (MRS) in prediction of CIN after primary PCI in ST-segment elevation myocardial infarction (STEMI) patients.MethodsA prognostic prediction research with clinical risk score development was conducted. All STEMI patients who underwent primary PCI at the Central Chest Institute from June 1, 2017 to June 30, 2018 were included. Multivariable logistic regression analysis was used to identify independent predictors of CIN with a significant P value < 0.05. Logistic coefficients of each predictor were used for score weighting and transformation. Predictive performance was validated and compared between newly-derived risk score and the MRS by non-parametric receiver operating characteristic (ROC) regression.ResultsA total of 217 patients, 43 (19.8%) with CIN and 174 (80.2%) without CIN, were included for score derivation. A total of 13 potential predictors were explored under multivariable logistic regression model and were subsequently eliminated. The new risk score was based on three final predictors which were ejection fraction of less than 40%, triple-vessel disease as findings from angiogram, and the use of intra-aortic balloon pump (IABP). With only three predictor variables, the score predicted the risk of CIN with good discriminative ability (area under the receiver operating characteristic curve (AuROC): 0.83, 95% confidence interval (CI): 0.76 - 0.90) which was higher than that of the MRS (AuROC: 0.78, 95% CI: 0.69 - 0.87). The score was categorized into low-risk (positive predictive value (PPV): 9.9, 95% CI: 5.4 - 14.4) and high-risk (PPV: 56.5, 95% CI: 42.4 - 70.8) groups at the cut-off point of 2.ConclusionsThe newly developed score was proved to have good predictive performance with fewer numbers of predictors and could be practically applied for risk stratification of CIN in STEMI patients who required emergent primary PCI.

SU23 - ASSOCIATIONS OF POLYGENIC RISK OF SCHIZOPHRENIA AND MAJOR DEPRESSION IN STUDIES OF BIPOLAR DISORDER AND MAJOR DEPRESSION

Background Large Genome-Wide Association Studies (GWAS) have identified common genetic variants that underlie Schizophrenia (SCZ) and Major Depressive Disorder (MDD), although Bipolar Disorder (BD) remains elusive. Cross disorder analysis has shown a strong genetic correlation of SCZ with BD, with modest correlations of SCZ with MDD, and MDD with BD. We used polygenic risk scores to examine shared genetic variation among disorders and to dissect the genetic contribution to shared clinical features, such as psychotic symptoms. Methods Participants from the Kaiser Permanente Research Program on Genes, Environment, and Health (9,080 MDD cases; 54,808 controls) and a multi-ethnic GWAS of bipolar 1 disorder (BD1) (5,056 cases; 54,808 controls) were genotyped on the Affymetrix Axiom system, using ancestry-specific arrays, and the data imputed to the 1000 Genome Project (March 2012 release). We calculated standardized polygenic risk scores for SCZ (SCZ-GRS) and MDD (MDD-GRS) as the weighted sum of risk alleles using 128 SNPs and 47 SNPs that were significantly associated with SCZ and MDD, respectively, in independent GWAS. Two SNPs were common to both scores. Logistic regression analyses of the association of SCZ-GRS and MDD-GRS with BD1 and MDD, separately, included gender, age, and principal components for adjustment of ancestry. Analyses were conducted separately in race-ethnicity groups and by gender. Results The SCZ-GRS and MDD-GRS were significantly and independently associated with BD1 in non-Hispanic whites (3,725 cases, 52,430 controls) in an analysis including both (Odds Ratio (OR)-MDD-GRS=1.138; 95% CI=1.099, 1.178; p= 2.646×10–13; OR-SCZ-GRS=1.146 95% CI=1.107, 1.187; p= 1.241×10–14), with similar results in the smaller samples of minorities, and in men and women. There was no interaction between the scores. Among BD1 cases, the SCZ-GRS was significantly associated with psychotic symptoms and hospitalization for BD; the MDD-GRS was also modestly associated with psychotic symptoms and nominally with rapid cycling of moods, a hallmark of BD. In analyses of MDD in non-Hispanic whites (7,833 cases; 43,581 controls), the MDD-GRS was significantly associated with MDD (OR=1.147; 95% CI=1.119,1.176; p=3.13×10–27), but the SCZ-GRS was not (OR=1.017; 95% CI=0.992, 1.042; p=0.189). Similar results were found in race-ethnic minorities, and in men and women. There was no interaction. Neither the MDD-GRS nor the SCZ-GRS was associated with hospitalization or psychotic symptoms in MDD, although the prevalence was much lower in MDD than BD. Discussion BD has both cognitive and affective components, most often including depressive episodes like those in MDD, but also frequently including psychotic symptoms, as does SCZ. The independent association of the MDD-GRS and SCZ-GRS with BD1 suggests that different genetic variants may contribute to the cognitive and affective clinical features of BD. In this study, genetic variation associated with SCZ was not associated with MDD, or with psychotic symptoms in MDD. Identification of genetic variation that influences specific disorders and specific features of disorders increases knowledge about the genetic etiology of disorders and may contribute to understanding the underlying biology of disorders and identification of new targets for treatment.

Male-female differences in aortic valve and combined aortic valve/coronary surgery: a national cohort study in the Netherlands

ObjectiveThe outcome of female patients after adult cardiac surgery has been reported to be less favourable compared with the outcome of male patients. This study compares men with women with...

Identifying the best body-weight-status index associated with metabolic risk in youth.

This study investigated the association of six different anthropometric markers with metabolic syndrome to find the most suited to predict children at risk. Sample comprises 1324 Portuguese youth (701 girls, 623 boys), aged 10-17years. Six anthropometric markers were included: body mass index (BMI), BMI z-score, tri-ponderal index (TPI), waist circumference (WC), WC/height ratio (WC/H), and WC/H adjusted ratio (WC/Hadj ). A standardized metabolic risk score (zMR) was computed by summing of standardized values for fasting glucose, triglycerides, high-density lipoprotein cholesterol, and mean arterial blood pressure. The associations between zMR and anthropometric markers were assessed using univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal values that best predict metabolic risk of each anthropometric marker. Among the studied predictors, BMI z-score, followed by BMI and WC, was most highly associated with zMR, while WC/Hadj was the weakest predictor. ROC analyses showed significant AUCs for all markers, yet the discrimination was poor (AUCs from 0.60 to 0.68), with sensitivity ranging from 45.5% to 67.5% and specificity from 72.6% to 81.9%. The optimal cut-off values to predict metabolic risk were 1.62, 23.1kg/m2 , 71.0cm, 18.0kg/m3 , 0.47, and 0.50, for BMI z-score, BMI, WC, TPI, WC/H, and WC/Hadj , respectively. BMI z-score, followed by BMI and WC, were the most relevant anthropometric markers to predict metabolic risk in youth, while WC/Hadj was the worst predictor. Results suggest that anthropometric markers should continue to be used as clinical tools to identify youth at risk.

Physical activity intensity, bout-duration, and cardiometabolic risk markers in children and adolescents

Objectives:To determine the role of physical activity intensity and bout-duration in modulating associations between physical activity and cardiometabolic risk markers.Methods:A cross-sectional study using the International Children’s Accelerometry Database (ICAD) including 38,306 observations (in 29,734 individuals aged 4–18 years). Accelerometry data was summarized as time accumulated in 16 combinations of intensity thresholds (≥500 to ≥3000 counts/min) and bout-durations (≥1 to ≥10 min). Outcomes were body mass index (BMI, kg/m2), waist circumference, biochemical markers, blood pressure, and a composite score of these metabolic markers. A second composite score excluded the adiposity component. Linear mixed models were applied to elucidate the associations and expressed per 10 min difference in daily activity above the intensity/bout-duration combination. Estimates (and variance) from each of the 16 combinations of intensity and bout-duration examined in the linear mixed models were analyzed in meta-regression to investigate trends in the association.Results:Each 10 min positive difference in physical activity was significantly and inversely associated with the risk factors irrespective of the combination of intensity and bout-duration. In meta-regression, each 1000 counts/min increase in intensity threshold was associated with a −0.027 (95% CI: −0.039 to −0.014) standard deviations lower composite risk score, and a −0.064 (95% CI: −0.09 to −0.038) kg/m2 lower BMI. Conversely, meta-regression suggested bout-duration was not significantly associated with effect-sizes (per 1 min increase in bout-duration: −0.002 (95% CI: −0.005 to 0.0005) standard deviations for the composite risk score, and −0.005 (95% CI: −0.012 to 0.002) kg/m2 for BMI).Conclusions:Time spent at higher intensity physical activity was the main determinant of variation in cardiometabolic risk factors, not bout-duration. Greater magnitude of associations was consistently observed with higher intensities. These results suggest that, in children and adolescents, physical activity, preferably at higher intensities, of any bout-duration should be promoted.

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.

Tackling the Inflammatory Burden of Psoriasis: A Multidisciplinary Approach

Prof Girolomoni provided an overview of psoriasis, considering how patients are frequently affected by other comorbidities. Cost, he explained, can be a constraint for optimal anti-tumour necrosis factor (TNF) treatment, with biosimilars representing an important opportunity for providing more patients with effective therapy. Data from X-ray crystallography studies, neutralisation studies, and clinical trials were presented, demonstrating that biosimilars have comparable efficacy to reference treatments. Prof Sattar explained how to define the overall cardiovascular disease (CVD) risk score in psoriasis; the standard risk score should be multiplied by 1.5 for patients with young onset or more severe disease. Throughout the presentation he stressed that all CVD risk factors need to be taken into consideration. Just because someone has severe psoriasis does not mean they are necessarily at high risk of CVD, and just because someone has mild psoriasis does not mean they are at low risk. In the second part of his talk, Prof Sattar reviewed evidence suggesting that psoriasis and obesity are interlinked, and discussed benefits of weight loss. Dr Behrens considered the hypotheses for psoriatic arthritis (PsA) genetic predisposition in patients with psoriasis. He reviewed data suggesting that psoriasis and PsA are different diseases, with psoriasis acting as a trigger for PsA. Dr Behrens went on to discuss predictors of PsA in patients with psoriasis and the importance of individualising treatment to phenotype. Dr Gecse reviewed the aetiology, disease course, prognostic factors, and characteristics of inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC). She explained how the prevalence of CD and UC is four-times higher in patients with psoriasis versus the general population, with the highest rates occurring in patients with both psoriasis and PsA. She went on to present studies showing how interleukin (IL)-17 inhibitors, which show promising effects in psoriasis, worsened in IBD.

Association of anthropometric indices with continuous metabolic syndrome in children and adolescents: the CASPIAN-V study.

This study aims to examine the association of anthropometric indices with continuous metabolic syndrome (cMetS) among Iranian children and adolescents. This multicentric study was conducted on 14138 students aged 7-18years, who participated in a national surveillance program. Fasting blood sample was obtained from a subsample of 3843 randomly selected students. Physical examination including the measurement of anthropometric indices and blood pressure was conducted; fasting blood glucose and lipid profile were measured; and cMetS score was computed. Standardized residuals (z-scores) were calculated for MetS components. A higher cMetS score indicates a less favorable metabolic profile. Linear regression models were applied to determine the association between cMetS and anthropometric indices. The study participants consisted of 3843 children and adolescents (52.3% boys) with mean (SD) age of 12.45 ± 3.04years. All anthropometric indices had positive correlation with standardized scores of mean arterial pressure, waist circumference and cMetS (P < 0.05). Standardized scores of triglycerides were positively correlated with weight and body mass index (P < 0.05). In multivariate model, general and abdominal obesity, as well as high circumferences of neck, wrist, and hip circumferences increased the standardized cMetS risk score to 1.8, 1.9, 1.6, 1.5 and 1.5, respectively (P < 0.05 for all variables). The results demonstrated that higher anthropometric indices are associated with higher cMetS risk score in children and adolescents. This information could be valuable for screening and prevention of MetS at population level. V, cross-sectional descriptive study (National surveillance study).

Cardiovascular Event Prediction by Machine Learning: The Multi-Ethnic Study of Atherosclerosis.

Machine learning may be useful to characterize cardiovascular risk, predict outcomes, and identify biomarkers in population studies. To test the ability of random survival forests, a machine learning technique, to predict 6 cardiovascular outcomes in comparison to standard cardiovascular risk scores. We included participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Baseline measurements were used to predict cardiovascular outcomes over 12 years of follow-up. MESA was designed to study progression of subclinical disease to cardiovascular events where participants were initially free of cardiovascular disease. All 6814 participants from MESA, aged 45 to 84 years, from 4 ethnicities, and 6 centers across the United States were included. Seven-hundred thirty-five variables from imaging and noninvasive tests, questionnaires, and biomarker panels were obtained. We used the random survival forests technique to identify the top-20 predictors of each outcome. Imaging, electrocardiography, and serum biomarkers featured heavily on the top-20 lists as opposed to traditional cardiovascular risk factors. Age was the most important predictor for all-cause mortality. Fasting glucose levels and carotid ultrasonography measures were important predictors of stroke. Coronary Artery Calcium score was the most important predictor of coronary heart disease and all atherosclerotic cardiovascular disease combined outcomes. Left ventricular structure and function and cardiac troponin-T were among the top predictors for incident heart failure. Creatinine, age, and ankle-brachial index were among the top predictors of atrial fibrillation. TNF-α (tissue necrosis factor-α) and IL (interleukin)-2 soluble receptors and NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) levels were important across all outcomes. The random survival forests technique performed better than established risk scores with increased prediction accuracy (decreased Brier score by 10%-25%). Machine learning in conjunction with deep phenotyping improves prediction accuracy in cardiovascular event prediction in an initially asymptomatic population. These methods may lead to greater insights on subclinical disease markers without apriori assumptions of causality. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Does adiposity mediate the relationship between physical activity and biological risk factors in youth?: a cross-sectional study from the International Children's Accelerometry Database (ICAD).

To model the association between accumulating 60 daily minutes of moderate-to-vigorous physical activity and a composite score of biological risk factors into a direct and an indirect effect, using abdominal obesity as the mediator. Cross-sectional data from the International Children's Accelerometry Database (ICAD) including 6-18-year-old children and adolescents (N=3412) from 4 countries providing at least 3 days of accelerometry-assessed physical activity. A standardized composite risk score was calculated from systolic blood pressure and fasting blood samples of insulin, glucose, triacylglycerol and inverse HDL-cholesterol. Abdominal obesity was assessed by the waist-circumference:height ratio. Two-stage regression analysis, allowing for exposure-mediator interaction, was used for the effect decomposition. Participants achieving 60 daily minutes of moderate-to-vigorous physical activity had a 0.31 (95% CI: -0.39, -0.23) standard deviations lower composite risk score than those achieving less than 60 min. Modelling the associations suggested that 0.24 standard deviations (95% CI: -0.32, -0.16) was attributed to the direct effect and -0.07 (95% CI: -0.11, -0.02) to the indirect effect indicating that 22% of the total effect was mediated by central adiposity. Modelling 30 and 90 min of moderate-to-vigorous physical activity per day resulted in changes in the direct but not the indirect effect. One hour of daily moderate-to-vigorous physical activity was associated with clinically relevant differences in metabolic control compared to engagement in less than this minimally recommended amount. The majority of the difference was explained by the direct effect of physical activity.International Journal of Obesity advance online publication, 31 October 2017; doi:10.1038/ijo.2017.241.

The Prognostic Value of Heart Type Fatty Acid Binding Protein in Patients with Suspected Acute Coronary Syndrome: A Systematic Review.

Background:Heart type fatty acid protein (HFABP) is a cytosolic protein released early after acute coronary syndrome (ACS) even in the absence of myocardial necrosis.Objectives:The purpose of this systematic review was to determine whether HFABP levels in patients with suspected, or confirmed ACS, improve risk stratification when added to established means of risk assessment.Methods:We searched Medline, Pubmed and Embase databases from inception to July 2015 to identify prospective studies with suspected or confirmed ACS, who had HFABP measured during the index admission with at least 1 month follow up data. A prognostic event was defined as all-cause mortality or acute myocardial infarction (AMI).Results:7 trials providing data on 6935 patients fulfilled inclusion criteria. There were considerable differences between studies and this was manifest in variation in prognostic impact of elevated HFABP(Odds ratio range 1.2-15.2 for death). All studies demonstrated that HFABP provide unadjusted prognostic information and in only one study this was negated after adjusting for covariates. A combination of both negative troponin and normal HFABP conferred a very low event rate. No study evaluated the incremental value of HFABP beyond that of standard risk scores. Only one study used a high sensitive troponin assay.Conclusion:There was marked heterogeneity in prognostic impact of HFABP in ACS between studies reflecting differences in sampling times and population risk. Prospective studies of suspected ACS with early sampling of HFABP in the era of high sensitivity troponin are necessary to determine the clinical value of HFABP. HFABP should not currently be used clinically as a prognostic marker in patients with suspected ACS.

Association Between Vascular Cell Adhesion Molecule 1 and Atrial Fibrillation

Accumulating evidence links inflammation and atrial fibrillation (AF). To assess whether markers of systemic and atrial inflammation are associated with incident AF in the general population. The Bruneck Study is a prospective, population-based cohort study with a 20-year follow-up (n = 909). The population included a random sample of the general community aged 40 to 79 years. Levels of 13 inflammation markers were measured at baseline in 1990. Findings were replicated in a case-control sample nested within the prospective Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study (n = 1770). Data analysis was performed from February to May 2016. Levels of 13 inflammation markers. Incident AF over a 20-year follow-up period in the Bruneck Study. Of the 909 participants included in the Bruneck Study, mean [SD] age was 58.8 (11.4) years and 448 (49.3%) were women. Among the 880 participants free of prevalent AF (n = 29) at baseline, 117 developed AF during the 20-year follow-up period (incidence rate, 8.2; 95% CI, 6.8-9.6 per 1000 person-years). The levels of soluble vascular cell adhesion molecule 1 (VCAM-1) and osteoprotegerin were significantly associated with incident AF (hazard ratio [HR], 1.49; 95% CI, 1.26-1.78; and 1.46; 95% CI, 1.25-1.69, respectively; P < .001 with Bonferroni correction for both), but osteoprotegerin lost significance after age and sex adjustment (HR, 1.05; 95% CI, 0.87-1.27; P > .99 with Bonferroni correction). Matrix metalloproteinase 9, metalloproteinase inhibitor 1, monocyte chemoattractant protein-1, P-selectin, fibrinogen, receptor activator of nuclear factor-κB ligand, high-sensitivity C-reactive protein, adiponectin, leptin, soluble intercellular adhesion molecule 1, and E-selectin all fell short of significance (after Bonferroni correction in unadjusted and age- and sex-adjusted analyses). The HR for a 1-SD higher soluble VCAM-1 level was 1.34 (95% CI, 1.11-1.62; Bonferroni-corrected P = .03) in a multivariable model. The association was of a dose-response type, at least as strong as that obtained for N-terminal pro-B-type natriuretic peptide (multivariable HR for a 1-SD higher N-terminal pro-B-type natriuretic peptide level, 1.15; 95% CI, 1.04-1.26), internally consistent in various subgroups, and successfully replicated in the SAPHIR Study (age- and sex-adjusted, and multivariable odds ratios for a 1-SD higher soluble VCAM-1 level, 1.91; 95% CI, 1.24-2.96, P = .003; and 2.59; 95% CI, 1.45-4.60; P = .001). Levels of soluble VCAM-1, but not other inflammation markers, are significantly associated with new-onset AF in the general community. Future studies should address whether soluble VCAM-1 is capable of improving AF risk classification beyond the information provided by standard risk scores.

The Role of Marrow Fibrosis in the Prognosis and Treatment of Myelodysplastic Syndromes: a Single Center Retrospective Study

▪Background:The presence of significant marrow fibrosis has previously been shown to be a poor prognostic factor in patients with myelodysplastic syndrome (MDS). Associations between fibrosis and higher transfusion requirements, multilineage dysplasia, and an increased rate of leukaemic transformation have been demonstrated. Currently, the presence of fibrosis is not included in standard risk scores for MDS such as the Revised International Prognostic Scoring System (IPSS-R) nor is fibrosis included in the current WHO classification for MDS. It is also not certain whether the presence of fibrosis should alter current treatment algorithms for patients. More information is needed to further assess both the prognostic and therapeutic implications of the presence of significant fibrosis in this patient population.Methods:We conducted a retrospective study utilizing a database of 247 patients with diagnosed MDS in a single center from 2000-2014. Bone marrow trephine samples for 200 of these patients were assessed using the European consensus on grading bone marrow fibrosis. Data was collected on: age, gender, WHO classification, marrow blast percentage, cytogenetics, progression to AML, treatment with azacitadine, and overall survival. These characteristics were compared between patients without significant fibrosis (grade 0/1) and those with significant fibrosis (grade 2/3). Our aim was to identify potential significant associations with MDS fibrosis and to assess whether treatment with azacitadine influenced these parameters or overall survival between the two groups.Results:Of 200 patients, 38 were found to have significant fibrosis (19%) versus 162 without significant fibrosis (81%).There was no significant difference in age or gender between the two groups.The commonest WHO category in both groups was RCMD (31.58% v 48.77%) in the fibrosis and non-fibrosis groups respectively. IPSS-R score was determined for 152 patients where data was available. There was no significant difference observed in IPSS-R Score between the two groups.Cytogenetic data was available on 175 patients. The commonest cytogenetic result in both groups was normal karyotype (55.3% v 52.5%). In the fibrosis group this was followed by complex cytogenetics (> 2 abnormalities) (23.68%) and trisomy 8 (7.89%). The presence of a cytogenetic abnormality was not significantly different in those with or without fibrosis (p=0.69).A significant difference was found between patients' marrow blast percentage at diagnosis (average 5.4% blasts in fibrotic patients versus 3.6% in non-fibrotic patients (p=0.04)). There were no differences in diagnostic haemoglobin level, neutrophil count, and platelet count.Acute Myeloid Leukaemia (AML) developed in 31 patients. The presence of fibrosis was associated with an increased rate of AML transformation with 27% compared with 13.5% in patients without fibrosis (p=0.05).Median overall survival was decreased in the fibrosis group compared to the non-fibrosis group (29 months versus 42 months, p=0.02).A total of 36 patients (25 of whom progressed to AML) received azacitadine treatment (9 (24%) patients with fibrosis and 27 (17%) patients without fibrosis). Patients with fibrosis had a longer median survival than those without (29 months and 19 months respectively) but this difference was not statistically significant (p=0.48).Conclusion:Marrow fibrosis adversely affects overall survival in patients with MDS. Patients with fibrosis are more likely to present with higher marrow blast counts and to progress to AML. Patients with fibrosis who received azacitadine appeared to have an overall higher survival than those without fibrosis. However, the numbers of patients who received azacitadine were small.This study confirms the adverse prognostic influence of marrow fibrosis in patients with MDS, but the presence of fibrosis may not adversely affect the responsiveness to azacitadine therapy. [Display omitted] [Display omitted] DisclosuresDesmond:Novartis: Honoraria.

Prevalence of abdominal aortic aneurysms and its relation with cardiovascular risk stratification: protocol of the Risk of Cardiovascular diseases and abdominal aortic Aneurysm in Varese (RoCAV) population based study.

BackgroundRecent meta-analyses suggested that screening program for abdominal aortic aneurysms (AAA) in 65-year old males is cost-effective at prevalence of about 1%. Since some events occur also in females and among the youngers, screening could be feasible among those at higher risk, such as smokers or individuals with a family history of AAA. The RoCAV (Risk of Cardiovascular diseases and abdominal aortic Aneurysms in Varese) Project is a population-based study aimed to evaluate AAA prevalence in Northern Italy in males over-65 years as well as among females and younger males, and to identify new markers for risk stratification by collecting a large set of CVD risk factors. The aims of the project are: (i) cross-sectional evaluation of AAA prevalence (ii); evaluation of standard CVD risk score as criteria for selecting subgroup at higher risk to be included in a screening program; (iii) identification of new risk markers and risk score algorithm for AAA and CVD risk stratification; (iv) cost-effective evaluation during the follow-up.MethodsMales aged 50–75 years and females aged 60–75 years, resident in the city of Varese (Lombardy Region), were randomly selected from the civil registry. Among 5198 successfully invited, 3777 subjects accepted to participate and were finally recruited (participation rate 63.8%) from June 2013 to May 2016. Trained operators administered a computerized anamnestic questionnaire, measured anthropometric parameters (BMI, body circumferences, skinfolds), blood pressure, ankle-brachial index, pulse wave velocity and performed abdominal aortic ultrasound scan, ECG and spirometry. All methods were internationally validated. A blood sample was collected and stored in biobank. A follow-up will be carried out through linkage with electronic records.DiscussionParticipation rate and data quality assessment were as expected and will reasonably allow to reach the project aims. The expected impact in public health of the RoCAV project will be the potential implementation of a AAA screening program to the whole region as well as the formulation of new criteria for risk assessment of AAA and CVD.

The National Early Warning Score (NEWS) for outcome prediction in emergency department patients with community-acquired pneumonia: results from a 6-year prospective cohort study.

ObjectiveTo investigate the accuracy of the National Early Warning Score (NEWS) to predict mortality and adverse clinical outcomes for patients with community-acquired pneumonia (CAP) compared to standard risk scores such as the pneumonia severity index (PSI) and CURB-65.DesignSecondary analysis of patients included in a previous randomised-controlled trial with a median follow-up of 6.1 years.SettingsPatients with CAP included on admission to the emergency departments (ED) of 6 tertiary care hospitals in Switzerland.ParticipantsA total of 925 patients with confirmed CAP were included. NEWS, PSI and CURB-65 scores were calculated on admission to the ED based on admission data.Main outcome measureOur primary outcome was all-cause mortality within 6 years of follow-up. Secondary outcomes were adverse clinical outcome defined as intensive care unit (ICU) admission, empyema and unplanned hospital readmission all occurring within 30 days after admission. We used regression models to study associations of baseline risk scores and outcomes with the area under the receiver operating curve (AUC) as a measure of discrimination.Results6-year overall mortality was 45.1% (n=417) with a stepwise increase with higher NEWS categories. For 30 day and 6-year mortality prediction, NEWS showed only low discrimination (AUC 0.65 and 0.60) inferior compared to PSI and CURB-65. For prediction of ICU admission, NEWS showed moderate discrimination (AUC 0.73) and improved the prognostic accuracy of a regression model, including PSI (AUC from 0.66 to 0.74, p=0.001) and CURB-65 (AUC from 0.64 to 0.73, p=0.015). NEWS was also superior to PSI and CURB-65 for prediction of empyema, but did not well predict rehospitalisation.ConclusionsNEWS provides additional prognostic information with regard to risk of ICU admission and complications and thereby improves traditional clinical-risk scores in the management of patients with CAP in the ED setting.Trial registration numberISRCTN95122877; Post-results.

Aortic valve replacement in the elderly

The treatment of severe symptomatic aortic valve stenosis by conventional aortic valve replacement (AVR) or by transcatheter aortic valve implantation (TAVI) has a good perinterventional prognosis even for patients of advanced age. Having a heart team select the best management strategies based on current guidelines for each individual patient is essential for success. Especially in elderly and increasingly multimorbid patients with sometimes severe preconditions, the detection of functional deficits is relevant not only for the mortality but also for perioperative and postoperative complications as well as the functional outcome. Various methods of geriatric assessment are important supplements to standard risk scores. The aim is to implement targeted interventions to minimize the risk factors and to improve the prognosis for elderly patients. The aim of this article is to provide an overview of the current therapy options for aortic valve replacement and to summarize current aspects of treatment options for elderly patients.

Predicting Device Success and Early Clinical Outcome after Transapical Aortic Valve Implantation

Objective: Pre-procedural evaluation of aortic valve patients is based on the prediction of perioperative risk for a conventional aortic valve replacement (AVR) utilizing standardized risk scores. However, in in the era of transcatheter aortic valve implantation (TAVI) the specific prediction of procedural outcome of an interventional approach seems of growing importance. We aimed to isolate patient- and approach-related factors, predicting procedural outcome of transapical aortic valve implantation (TA-TAVI), especially focusing on parameters not included in standard risk scores (e.g. BMI, intracardiac anatomy, preoperative NT-proBNP). Methods: A cohort of 60 patients suffering from severe aortic stenosis and receiving TA-TAVI at our institution was analyzed (mean age was 77.7 ± 6.3 years, 50% male). All patients exhibited a high risk for conventional AVR (EuroScorelog ≥ 20 or porcelain aorta) and were scheduled for a TA approach using an Edwards Sapien valve following heart-team discussion. Prior the procedure, all patients underwent multi-slice computed tomography examination. In order to evaluate the procedural and clinical outcome after TA-TAVI, three endpoints were defined: More than mild postoperative paravalvular leak (PVL), postoperative mean transvalvular gradient > 14 mmHg and a composite endpoint of 30-day mortality, stroke and myocardial infarction. For isolation of outcome predictors, fourteen different potential predictors were included into primary univariate regression analyses, seven of which entered subsequent multivariate analyses. Results: A BMI ≥ 30 was found in multivariate logistic regression to double the risk for both more than mild PVL and higher postoperative transvalvular gradients, however without reaching statistical significance (OR 2.57 95% CI 0.69-9.52; p=0.157 and OR 2.32 95% CI 0.57-9.45; p=0.242, respectively). Male gender and COPD were both associated with a decreased risk for elevated postoperative gradients. Of the analyzed approach-related parameters, especially a LVOT-aorta angle <120° was associated with an increased risk of the composite end-point (OR 6.65 95% CI 0.93-47.4; p=0.059). Furthermore preoperative NT-proBNP levels <400 ng/ml were found to predict a trend towards higher postoperative transvalvular gradients (OR 5.15 95% CI 0.32-81.9; p=0.246). Conclusion: Standardized risk scores for conventional AVR are limited in terms of predicting the early outcome of TAVI procedures. The current study provides evidence that specific parameters such as the LVOT-aorta angle are likely to improve outcome prediction of patients undergoing TAVI procedures.