Classical Risk Research Articles

Estimation of extreme Component-wise Excess design realization: a hydrological application

The classic univariate risk measure in environmental sciences is the Return Period (RP). The RP is traditionally defined as “the average time elapsing between two successive realizations of a prescribed event”. The notion of design quantile related with RP is also of great importance. The design quantile represents the “value of the variable(s) characterizing the event associated with a given RP”. Since an individual risk may strongly be affected by the degree of dependence amongst all risks, the need for the provision of multivariate design quantiles has gained ground. In contrast to the univariate case, the design quantile definition in the multivariate setting presents certain difficulties. In particular, Salvadori, G., De Michele, C. and Durante F. define in the paper called “On the return period and design in a multivariate framework” (Hydrol Earth Syst Sci 15:3293–3305, 2011) the design realization as the vector that maximizes a weight function given that the risk vector belongs to a given critical layer of its joint multivariate distribution function. In this paper, we provide the explicit expression of the aforementioned multivariate risk measure in the Archimedean copula setting. Furthermore, this measure is estimated by using Extreme Value Theory techniques and the asymptotic normality of the proposed estimator is studied. The performance of our estimator is evaluated on simulated data. We conclude with an application on a real hydrological data-set.

OPTIMALISASI SHARI’A COMPLIANT ASSET PRICING MODEL TERHADAP RATE OF RETURN PADA JAKARTA ISLAMIC INDEX

This study aimed to compare the three models SCAPM, namely SCAPM without risk free, SCAPM inflation and SCAPM zakat to know which model is more optimal use. The method used is the analysis of explanatory power and linear regression. The data used is secondary data, the inflation data, zakat, sharia shares incorporated in Jakarta Islamic Index (JII) from 2011 to 2015.The results are based on the analysis of explanatory power, SCAPM inflation is more optimal than SCAPM zakat and SCAPM without risk free. The results are supported by the results of the analysis graph illustrating SCAPM inflation has a higher volatility than other SCAPM, it indicates that the more profitable inflation SCAPM models are accompanied by greater risks, in accordance with the principles of the classical high risk high return.

Abstract TMP53: Preeclampsia Leads to Long Term Cerebral White Matter Damage and Cortical Atrophy: a Magnetic Resonance Imaging Study

Introduction: Women with a history of preeclampsia have a two-fold higher risk of acute ischemic stroke even after controlling for classic cardiovascular risk factors. We determined whether specific patterns in cerebral damage are present after preeclampsia that may explain this risk. Methods: We performed brain magnetic resonance imaging in women between 5 and 15 years after either a preeclamptic or normotensive pregnancy. Analysis of white matter structure was undertaken using voxel-based segmentation of fluid attenuation inversion recovery sequences to assess white matter lesion volume and diffusion tensor imaging to measure microstructural integrity. Voxel-based analysis of grey matter volumes was performed in T1 weighted sequences with adjustment for skull size. Cardiovascular, obstetric profiles were assessed. Results: Thirty-four previously preeclamptic women (aged 42.8 ± 5.1 years, mean ± SD) and 49 controls were included. Previously preeclamptic women had reduced cortical grey matter volume (523.2 ± 30.1 vs 544.4 ± 44.7 ml, p<0.05) and, although both groups displayed frontal white matter damage, changes were more extensive in previously preeclamptic women. They displayed increased temporal lobe white matter disease (lesion volume: 23.2 ± 24.9 vs 10.9 ± 15.0 ml, p<0.05) and altered microstructural integrity (radial diffusivity 538 ± 19 vs. 526 ± 18*10 -6 mm 2 /sec, p<0.01), which also extended to occipital and parietal lobes. The degree of temporal lobe white matter change in previously preeclamptic women was independent of their current cardiovascular risk profile (p<0.05) and increased with time from index pregnancy (Figure). Conclusions: A history of preeclampsia is associated with temporal lobe white matter damage and cortical atrophy in young women, which is out of proportion to their classic cardiovascular risk profile and increases with time from pregnancy, consistent with ongoing susceptibility and cumulative brain damage.

Impact of postprandial hyperglycemia at clinic visits on the incidence of cardiovascular events and all-cause mortality in patients with type 2 diabetes.

Aims/IntroductionWe evaluated the impact of postprandial hyperglycemia at clinic visits on the incidence of cardiovascular diseases (CVD) and all‐cause mortality independently of mean glycosylated hemoglobin in type 2 diabetes patients in a real‐world setting.Materials and MethodsThe present retrospective observational cohort study included 646 type 2 diabetes patients. All of the participants had their initial consultations at the Institute for Diabetes Care and Research, Asahi Life Foundation affiliated Marunouchi Hospital, Tokyo, Japan, during the period from 1995 to 1996, visited the clinic ≥4 times, had their 2‐h post‐breakfast blood glucose (2h‐PBBG) levels measured and were followed up for ≥1 year. The 646 patients were followed up for survival. Of the 646 patients, 618 had no history of CVD at the first visit and had measured 2h‐PBBG until the first CVD onset or censorings. These two cohorts were followed up through June 2012, and subsequently questionnaires were mailed. Multivariate Cox proportional hazard models were used to evaluate the risk of CVD incidence and death.Results CVD occurred in 78 patients, and 56 patients died. The median follow‐up periods of the CVD cohort and the mortality cohort were 15.6 and 15.9 years, respectively. The mean 2h‐PBBG is a significant predictor of the CVD incidence and all‐cause mortality after adjusting for the mean glycosylated hemoglobin, the number of 2h‐PBBG measurements, age, sex and classical risk factors.ConclusionsPostprandial hyperglycemia represented by the mean level of 2h‐PBBG at clinic visits is associated with CVD incidence and all‐cause mortality independently of the mean glycosylated hemoglobin level in type 2 diabetes patients. Prospective interventional trials are warranted to confirm the present findings.

Control beliefs and risk for 4-year mortality in older adults: a prospective cohort study

BackgroundControl beliefs are important psychological factors that likely contribute to heterogeneity in health outcomes for older adults. We evaluated whether control beliefs are associated with risk for 4-year mortality, after accounting for established “classic” biomedical risk factors. We also determined if an enhanced risk model with control beliefs improved identification of individuals with low vs. high mortality risk.MethodsWe used nationally representative data from the Health and Retirement Study (2006–2012) for adults 50 years or older in 2006 (n = 7313) or 2008 (n = 6301). We assessed baseline perceived global control (measured as 2 dimensions—“constraints” and “mastery”), and health-specific control. We also obtained baseline data for 12 established biomedical risk factors of 4-year mortality: age, sex, 4 medical conditions (diabetes mellitus, cancer, lung disease and heart failure), body mass index less than 25 kg/m2, smoking, and 4 functional difficulties (with bathing, managing finances, walking several blocks and pushing or pulling heavy objects). Deaths within 4 years of follow-up were determined through interviews with respondents’ family and the National Death Index.ResultsAfter accounting for classic biomedical risk factors, perceived constraints were significantly associated with higher mortality risk (third quartile scores odds ratio [OR] 1.37, 95% CI 1.03–1.81; fourth quartile scores OR 1.45, 95% CI, 1.09–1.92), while health-specific control was significantly associated with lower risk (OR 0.69–0.78 for scores above first quartile). Higher perceived mastery scores were not consistently associated with decreased risk. The enhanced model with control beliefs found an additional 3.5% of participants (n = 222) with low predicted risk of 4-year mortality (i.e., 4% or less); observed mortality for these individuals was 1.8% during follow-up. Compared with participants predicted to have low mortality risk only by the classic biomedical model, individuals identified by only the enhanced model were older, had higher educational status, higher income, and higher prevalence of diabetes mellitus and cancer.ConclusionControl beliefs were significantly associated with risk for 4-year mortality; accounting for these factors improved identification of low-risk individuals. More work is needed to determine how assessment of control beliefs could enable targeting of clinical interventions to support at-risk older adults.

Effects of High-Intensity Training of Professional Runners on Myocardial Hypertrophy and Subclinical Atherosclerosis.

To evaluate the effects of long-term exposure to high-intensity training among professional runners on cardiac hypertrophy and subclinical atherosclerosis.Prospective study included runners of both sexes (n = 52) and age and gender matched controls (n = 57), without classical cardiovascular risk factors. Ventricular hypertrophy was quantified by echocardiography by linear method and carotid intima-media thickness (cIMT) by 2-D images obtained by ultrasonography. Endothelial function was evaluated by flow-mediated dilation (FMD). Steroid hormones were quantified by HPLC followed by LC-MS/MS. Higher left ventricular (LV) mass index was found in male athletes (p<0.0001 vs. other groups). When adjusted for gender, the degree of left ventricular mass index classified as mildly, moderately or severely abnormal was obtained in 26%, 35%, and 30%, respectively, of female athletes, and in 39%, 14%, and 21%, respectively, of male athletes. Higher ratio of the early (E) to late (A) ventricular filling velocities was found in athletes of both genders. Male athletes presented lower cIMT in the right (p = 0.012 vs. male controls) and left (p<0.0001 vs. male controls) common carotid arteries, without differences in cIMT between female athletes and controls. FMD results were similar among groups. Higher serum testosterone levels were found in male athletes (p<0.0001 vs. other groups) and they were correlated with LV mass (r = 0.50, p<0.0001). The chronic exposure of high-intensity training among professional runners of both genders was associated with increased ventricular mass and adaptive remodeling. Less subclinical atherosclerosis was found in male athletes. Differences in steroid hormones may account in part for these findings.

Abstract 108: Relative Contributions of Arterial Stiffness and Hypertension to CVD Risk: The Framingham Heart Study

Introduction: The presence and implications of abnormal arterial stiffness, a potential independent predictor of outcomes, in community-dwelling treated hypertensives is unknown. Furthermore, limited data exist regarding the risk of cardiovascular disease (CVD) associated with arterial stiffness across the entire range of blood pressure. Methods: We measured carotid-femoral pulse wave velocity (PWV) and classical CVD risk factors in participants of The Framingham Offspring Cohort. The participants were divided into 4 groups according to hypertension (yes/no), and PWV status (high/low based on age- and sex-specific median values) and followed up for CVD events (CVD death, myocardial infarction, unstable angina, heart failure, and stroke). Results: We studied 2127 community-dwelling individuals (60 years, 57% women). 60% (233 of 390) of controlled and 90% (232 of 258) of uncontrolled treated hypertensives had high PWV. The multivariable-adjusted risk for CVD events ( n =248, median follow-up 12.6 years; Figure) rose from normotension with low PWV (reference) to normotension with high PWV (hazard ratio [HR] 1.33, 95% confidence interval [95% CI] 0.86-2.05) and from hypertension with low PWV (HR 1.53, 95% CI 1.00-2.34) to hypertension with high PWV (HR 2.31, 95% CI 1.58-3.36). Conclusions: A substantial proportion of treated hypertensives have high arterial stiffness, a finding that may explain some of the notable residual CVD risk associated in this group. High PWV is associated with a trend towards increasing CVD risk in both non-hypertensives and hypertensives supporting the use of arterial stiffness measurements in both populations.

Optimal sharing with an infinite number of commodities in the presence of optimistic and pessimistic agents

We prove that under mild conditions individually rational Pareto optima will exist even in the presence of non-convex preferences. We consider decision-makers (DMs) dealing with a countable flow of pay-offs or choosing among financial assets whose outcomes depend on the realization of a countable set of states of the world. Our conditions for the existence of Pareto optima can be interpreted as a requirement of impatience in the first context and of some pessimism or not unrealistic optimism in the second context. A non-existence example is provided when, in the second context, some DM is too optimistic. We furthermore show that at an individually rational Pareto optimum at most one strictly optimistic DM will avoid ruin at each state or date. Considering a risky context, this entails that even if risk averters will share risk in a comonotonic way as usual, at most one classical strong risk lover will avoid ruin at each state or date. Finally, some examples illustrate circumstances when a risk averter could take advantage of sharing risk with a risk lover rather than with a risk averter.

Soluble CD40L is associated with insulin resistance, but not with glucose tolerance in obese nondiabetic patients

Objective: The soluble platelet secreted ligand CD40 (sCD40L) has a role in atherosclerosis progression. The aim of the present study was to investigate the link between the levels of sCD40L and some classical cardiovascular risk factors in obese nondiabetic patients. Methods: In the present cross-sectional study, we included76 patients with mean age of 50.7 ± 10.7 years. Oral glucose tolerance test (OGTT) was performed in all participants and levels of sCD40L were measured using enzyme-linked immunosorbent assay (ELISA) method. Results: We found significantly higher levels in patients with insulin resistance compared to those without (6.4 ± 3.7 vs. 4.1 ± 2.4 ng/ml, р = 0.025) and only a tendency toward higher levels in prediabetes compared to normoglycemic patients (5.9 ± 3.6 vs. 5.3 ± 3.4 ng/ml). There was no correlation between sCD40L and platelet count, systolic and diastolic blood pressure and lipid profile. Conclusions: The main factor for increased sCD40L plasma levels was the presence of insulin resistance and not the state of glucose tolerance.

Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk.

Nonalcoholic fatty liver disease (NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use. The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes. A more advanced form of NAFLD, non-alcoholic steatohepatitis, includes inflammation and liver cell injury, progressive to cryptogenic cirrhosis. NAFLD has become the most common cause of chronic liver disease in children and adolescents. The recent rise in the prevalence rates of overweight and obesity likely explains the NAFLD epidemic worldwide. NAFLD is strongly associated with abdominal obesity, type 2 diabetes, and dyslipidemia, and most patients have evidence of insulin resistance. Thus, NAFLD shares many features of the metabolic syndrome (MetS), a highly atherogenic condition, and this has stimulated interest in the possible role of NAFLD in the development of atherosclerosis. Accumulating evidence suggests that NAFLD is associated with a significantly greater overall mortality than in the general population, as well as with increased prevalence of cardiovascular disease (CVD), independently of classical atherosclerotic risk factors. Yet, several studies including the pediatric population have reported independent associations between NAFLD and impaired flow-mediated vasodilatation and increased carotid artery intimal medial thickness-two reliable markers of subclinical atherosclerosis-after adjusting for cardiovascular risk factors and MetS. Therefore, the rising prevalence of obesity-related MetS and NAFLD in childhood may lead to a parallel increase in adverse cardiovascular outcomes. In children, the cardiovascular system remains plastic and damage-reversible if early and appropriate interventions are established effectively. Therapeutic goals for NAFLD should address nutrition, physical activity, and avoidance of smoking to prevent not only end-stage liver disease but also CVD.

Effects of Economic Recession on Road Safety Indexes

During the last years, the investment in both construction and conservation of transport infrastructures has been considerably reduced in several countries, as Spain. After a number of years in which economic circumstances have forced Governments to reduce budgets earmarked for the maintenance and creation of new ways, it is interesting to analyze whether this has taken a toll on accident rates.The paper evaluates if there are significant changes in the road safety through these years in Spain, comparing the annual statistics concerning investment in infrastructure and accidents. Thus, the classical risk, mortality and severity indexes have been analyzed to understand their real trends. Finally, through linear regression techniques, it is shown how these trends are related to the budgets invested each year, in order to draw interesting conclusions about the effect of their reduction.

P-115: Case report of severe heart disease in a hypertensive and diabetic woman 17 years after chest radiation exposure for breast cancer

Objectifs Irradiation of the heart in patients with breast cancer increases the risk of the so-called “radiation-induced heart disease” (RIHD). Among risk factors of RIHD, overweight, hypertension and diabetes mellitus take a major place. To describe a clinical case of an obese hypertensive diabetes mellitus woman with breast cancer since the begining of her radiotherapy until heart failure on the basis of the report from the European Association of Cardiovascular Imaging consensus for evaluation of cardiovascular complications of radiotherapy in adults. Download : Download high-res image (75KB) Download : Download full-size image Abstract P-115 – Figure: Evaluation of Cardiovascular complications of Radiotherapy in a 67 yeats old woman. Methodes A 67 years old woman came to the emergency room with recent worsening of breathlessness. She has had uncontrolled hypertension since 27 years, diabetes mellitus since 17 years and obesity (31kg/m2). She had a complex past medical history. In 1997th she has had breast cancer followed by surgery and radiotherapy with a high cumulative dose of 50 Gy. At this time she was in complete remission. Ten years after, she developed coronary artery disease with subsequent coronary artery bypass surgery. Then she underwent mechanical aortic valve replacement related to mixed aortic valve disease followed by monochamber device for syncopal complete heart block. Few months later she developed heart failure despite upgrading her device to two chambers device. Physical examination: BP/HR: 120/70mmHg/70bpm under medical therapy. Shortness of breath (NYHA class III). Heart: Systolic murmur was audible over the mitral area and substitute sounds of her prosthetic aortic valve. The patient was taking ramipril 5mg daily, furosemide 80 mg daily, spironolactone 25mg daily, warfarin with an international normalized ratio (INR) between 3 and 4; rosuvastatin 20mg daily and beta blockers that was given previously had to be stopped for occurrence of heart failure. Echocardiography: leaflet calcifications on the mitral valve with a mixed lesion; good function of her bileaflet mechanical aortic valve. Depressed left systolic function and markedly elevated pulmonary artery pressure. Resultats After control of her risks factors and optimizing her medical therapy, patient felt much better after two weeks with decreasing of her pulmonary artery pressure. We follow her data closely. Conclusion This case suggests that patients with classical cardiovascular risk factors must be treated in a meticulous way in collaboration with oncologist and radiotherapist. Modifying risk factors as well as early detection and treatment of RIHD may improve the long-term cardiovascular outcome.

Diabetes mellitus and symptoms of sleep apnea are associated with adverse delivery outcomes

Materials and methods In a prospective cohort design, 158 women answered a version of the STOP-Bang questionnaire adapted for pregnant women using age cutoff at 35 yrs. and excluding male gender (STOP-Ban); risk for sleep apnea was considered present when score>2. Obstetric history and physical examination were obtained. Both gestational and pre-gestational diabetes were considered for the analyses. The hospital records were reviewed for delivery outcomes. Preterm birth, premature rupture of membranes, non-elective cesarean section, low birth weight, and non-reassuring fetal condition were considered adverse delivery outcomes. Seven classical gestational risk factors were used to adjust the multivariate models.

Abstract 15578: Adiposity, Systolic Blood Pressure, Smoking and Atrial Fibrillation: Analyses of 2.3 Million US Adults Attending Cardiovascular Screening

Aims: Unlike other vascular conditions, and for reasons that are incompletely understood, the prevalence of atrial fibrillation (AF) is rising sharply. Analysis of a large healthy cohort which was screened for AF allows reliable assessment of its association with several classical vascular risk factors. Methods: Between 2009 and 2013, around 3 million US adults attended cardiovascular screening clinics and had an ECG to identify AF. Personal and family medical history, medication use, smoking and alcohol consumption were recorded via questionnaires, and height, weight and blood pressure were measured. Age and gender-specific incidence of AF and associations between body mass index (BMI), systolic blood pressure (SBP) and smoking were measured in 2,320,190 participants with no reported prior history of AF, stroke or CHD. Results: The median age was 65, and two-thirds were female. The overall incidence of AF was 0.36%, but it was over twice as common in males (0.59%) than in females (0.23%) and rose sharply with age, doubling in each decade in both men and women. A positive association was seen between adiposity and AF in men and women across all ages studied: approximately 50% increase per 5 unit rise in BMI. By contrast, AF was only weakly associated with SBP - 10% increase per 10mmHg rise in SBP among participants aged under 70 years, and flat or even inversely associated among those over 70 years. Smoking was not associated with AF in men or women at any age (Odds Ratio for current vs never smokers = 0.97 [95% CI 0.79-1.19]). Conclusion: A 10 unit increase in BMI (ie, going from an “ideal” weight to “obese”) doubled the risk of AF. However, blood pressure was less strongly associated with AF, and only in those under 70 years, suggesting some other mechanism behind the BMI - AF association. Current smoking was not associated with AF. Rising rates of obesity may be driving the observed increase in AF in the developed world.

Abstract 18834: IF1 And ApoA-I Serum Concentrations, but Not HDL-cholesterol, Predict Mortality in Coronary Artery Disease Patients: The Genes Study

Introduction: High-density lipoprotein cholesterol (HDL-C) may not be the best clinical measure of HDL for assessing cardiovascular risk. Serum inhibitor factor 1 (IF1), an endogenous inhibitor of the ecto-F1-ATPase apoA-I receptor, has been identified as an independent determinant of HDL-C associated with low risk of coronary artery disease (CAD). Objective: To determine the relationship between serum IF1 concentration and mortality in stable CAD patients in comparison with HDL-C and apoA-I Methods: Serum IF1 was measured in 577 coronary male patients (enrollment age 45-74 years; enrollment period, 2001-2004) from the GENES (Genetique et ENvironement en Europe du Sud) study. Vital status was assessed yearly through December 31, 2013. Results: During a median follow up of 11 years, mortality rate was 29.5%. Cardiovascular mortality accounted for the majority (62.5%) of deaths. Serum IF1 (median value: 0.42 mg/mL) was positively correlated with HDL-C and apoA-I, and negatively with triglycerides and the severity of CAD (Gensini, Duke-Jeopardy scores). Mortality was lower the higher the quartile score for IF1 and apoA-I, but not for HDL-C. Inverse associations of IF1 and apoA-I with mortality remained significant, even after multivariate adjustments for classical cardiovascular risk factors - age, smoking, diabetes, dyslipidemia, waist circumference, physical activity and CRP. Furthermore, associations of the highest IF1 quartile with mortality reduction remained significant after further adjustment for clinical parameters proven to be predictive of complications in CAD patients, such as ankle-brachial index, heart rate and CAD duration. Interestingly, when levels of both IF1 and apoA-I were high, mortality was much lower than when only one of these was high. Conclusions: IF1 is a new biological marker strongly predictive of mortality in CAD patients. Among patients with normal or elevated apoA-I levels, IF1 measurement may help to identify those who are at low risk of complications and those who are not. IF1 measurement could be use in a panel of other emerging biomarkers that have been proven to be better than HDL-C level, for the better assessment of cardiovascular risk or in the setting of pharmacotherapy.

Abstract P181: Circulating Second-messenger Glycerophosphocholines and Cardiovascular Risk Factors in a Population-based Sample of Adolescents

Circulating second-messenger glycerophosphocholines (smGPCs), including lysophosphatidylcholines and platelet-activating factors, are low-abundance plasma phospholipids that modulate atherosclerosis and inflammation and, in turn, the risk for cardiovascular disease (CVD). Although CVD is a slow-progressing disease culminating in middle-to-late adulthood, its initial stages may be seen already in adolescence. Here, we investigated whether circulating smGPCs are associated with classical CVD risk factors - excess body fat, elevated BP, insulin resistance and low-grade inflammation - during adolescence. We studied a population-based sample of 1029 adolescents (52% females, 12-18 years), as part of the Saguenay Youth Study. We used targeted serum lipidomics (LC-ESI-MS) to identify and quantify circulating smGPCs within the 440-640 Da range. In all participants, we also measured: (i) visceral fat with MRI and total body fat with bioimpedance; (ii) blood pressure (BP) beat-by-beat for five minutes under standard clinical conditions; and (iii and iv) fasting serum insulin (as an index of insulin resistance) and CRP (as an index of low-grade inflammation). We identified a total of 81 smGPCs that varied by the length and saturation of their fatty acyl residues and the type of linkage these residues are attached to the glycerol backbone. Over 30 of them were associated with multiple CVD risk factors (p&lt;6x10 -4 ). Most of these associations were inverse and involved ‘medium’ mass smGPCs. Positive associations were also seen and these involved ‘low’ or ‘high’ mass smGPCs. Most strongly inversely associated smGPCs were: (i) PC(20:6/0:0) and PC(O-18:6/2:0), which were associated with total body fat (p&lt;3x10 -14 ) and CRP (p&lt;8x10 -36 ); and (ii) PC(16:0/2:0), which was associated with visceral fat (p=2x10 -18 ) and BP (p&lt;1x10 -5 ). The most strongly positively associated smGPC was PC(14:1/0:0), which was associated with visceral fat (p=8x10 -8 ) and fasting insulin (p=2x10 -24 ). Thus, specific circulating smGPCs are strongly associated with multiple CVD risk factors in adolescence; some of these associations may be ‘protective’ whereas others ‘adverse’. Circulating smGPCs may serve as novel biomarkers of early risk for CVD.

PP.13.24

Objective: Jupiter Study supports the clinical use of the inflammatory status to limit cardiovascular events.Inflammation is now a theoretic concept which will start to be applied in practice to evaluate CV risk and the therapeutic target. The aim of this study is to investigate the relation between the classical cardiovascular risk factors and inflammation markers (hsCRP, TNF-alpha, MPO-mieloperoxidase, AOPP-advance oxidation protein products) in an adult patients group with metabolic syndrome (MetS). Design and method: MPO and AOPP were assessed spectrophotommetrically, hs-CRP and TNF-alpha by sandwich ELISA, and all the other risk factors (BMI, fasting glucose, lipid profile) by validated standard procedures, respectively, in a group of 108 patients diagnosed with the metabolic syndrome, free of coronary desease or cardiac insufficiency and without having any treatment vs. 33 age-, and sex-matched control group patients (C). Results: The CV SCORE risk for MetS group was moderate. The MPO level was not statistical significantly different between the two groups.The AOPP level and the other inflammatory markers consideredwas were higher in MetS group. TNF-alpha was strongly correlated with the number of inclusion criteria in MetS, was average correlated with weight, waist, BMI, FPG, serum TG, HDL-c and is not correlated with the values of blood pressure, uric acid, LDL-c, TC. HsCRP are significantly higher than the control group and are strongly correlated with the number of criteria for MetS, waist, FPG, HbA1c, LDL-C and has an average correlation with SBP, BMI. Conclusions: The MPO level was not statistical significantly different between the two groups, probably because of one of the inclusion criteria, the absence of the coronary disease, which translate into the absence of an important atherosclerotic plaque, which can potentially break down. Moreover for the MetS group we found higher values not only for the AOPP level, but also for all the other inflammatory markers considered, probably due to the inclusion of patients with DM type II or with modified glucose tolerance who already have an endothelial dysfunction, even though most of the patients were non-smokers and were not diagnosed with end organ damage.

Dispute and morality in the perception of societal risks: extending the psychometric model

The psychometric paradigm has identified two classic dimensions, dread and unknown risk, structuring the perception of risks. We propose that disputed risk and morality are two additional dimensions that are relevant to describe the cognitive representation of societal risks. Disputed risk captures two aspects of a societal risk: first, that consensus about scientific evidence is low, and second, that the public debate about the risk issue is highly controversial. Morality refers to judgments of reprehensibility, capturing the fact that societal risks frequently involve violations of moral principles. In a survey study employing two samples, a household sample (N = 418) and a student sample (N = 88), participants evaluated 24 societal risks on 23 psychometric scales intended to assess the four constructs dread, unknown risk, disputed risk, and morality. Principal component analyses yielded three dimensions: a common dimension of dread and morality, a disputed risk dimension, and unknown risk. We also assessed judgments of overall riskiness for all risks. Morality and dread both proved to be strong and distinctive predictors of perceived overall riskiness in regression analyses; disputed risk and unknown risk, in contrast, do not play a substantial role as predictors. These findings were replicated across both samples. We conclude that disputed risk constitutes a novel and unique psychometric dimension; morality, on the other hand, coincides with dread in the cognitive representation of societal risks, while still showing a distinct and strong effect in the prediction of risk judgments.

Abstract 713: Effects of Demographics and Clinical Risk Factors on Human Femoropopliteal Artery Histopathology

Introduction: Disease of the femoropopliteal artery (FPA) is associated with significant morbidity and quality of life impairment. End-stage lesions may be too advanced to determine how demographics and clinical risk factors impact arterial wall damage and lesion development; therefore we investigated the influence of these patient characteristics on various stages of human FPA histopathology. Methods: FPAs were obtained from 14-80 year-old human tissue donors ( n =120). Proximal segments of the arteries were mechanically tested and labeled with Verhoeff-Van Gieson stains. FPA intimal-medial damage severity was assessed and correlated with histology, mechanical properties, subject demographics, risk factors, and physiological stresses and stretches using Pearson correlation r with two-tailed significance levels. Results: Age correlated strongest ( r =0.664, p&lt;0.01) with the degree of FPA intimal-medial damage, explaining 50% of the variation alone. Primarily due to medial calcification, more damaged FPAs were stiffer and demonstrated lower physiological circumferential stretch ( r =-0.510, p&lt;0.01), circumferential stress and longitudinal stress ( r =-0.355, r =-0.379, p&lt;0.01). More damage was associated with larger arterial radii ( r =0.470, p&lt;0.01), thickened arterial walls ( r =0.238, p&lt;0.01), decreased in situ longitudinal pre-stretch ( r =-0.537, p&lt;0.01), less elastin in the arterial wall ( r =-0.432, p&lt;0.01), thinner individual elastin fibers ( r =-0.571, p&lt;0.01), and thinner, less dense, and more discontinuous external elastic laminae ( r =-0.252, r =-0.456, r =0.588, p&lt;0.01). Damage was positively associated with male gender ( r =0.265, p&lt;0.01), higher BMI ( r =0.224, p=0.01), hypertension ( r =0.266, p&lt;0.01), diabetes ( r =0.265, p&lt;0.01) and coronary artery disease ( r =0.375, p&lt;0.01), but not with dyslipidemia ( r =0.117, p=0.161) or smoking history ( r =0.041, p=0.626). Conclusions: More severely damaged FPAs demonstrate elastin loss, medial calcification and increased stiffness compared to less damaged arteries. FPA damage correlates with most classical cardiovascular risk factors, but not with dyslipidemia or tobacco history, suggesting possible unique pathophysiological mechanisms that require further investigation.

Abstract 22: Monocyte Chemotactic Protein-1 and Macrophage Colony-Stimulating Factor Are Strong Predictors of First-Time Myocardial Infarction in the General Population

Objective: Monocytes/macrophages and neutrophils play important roles in the pathogenesis of cardiovascular disease. We hypothesized that mediators governing myeloid cell homeostasis might help predict the incidence of first-time acute myocardial infarction (AMI). Methods: We included 385 individuals who suffered an AMI during a median follow-up of 15.2 years, and 401 age and sex-matched controls that remained event free, recruited from the Malmö Diet and Cancer Study cohort. The participants had no documented coronary artery disease previous to inclusion. We performed parallel measurements of monocyte chemotactic protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), CCL3, CCL4, CCL20, CXCL1, CXCL16, and CX3CL1 in plasma samples collected at baseline, by using a Proximity Ligation Assay. Results: MCP-1 presented a strong positive correlation (HR (95% CI): 2.07 (1.77-2.43), p&lt;0.001), whereas M-CSF had a strong negative correlation with incident AMI (HR (95% CI): 0.49 (0.41-0.58), p&lt;0.001). These relationships were independent of the classic Framingham risk factors (age, ex, smoking, total cholesterol, HDL, systolic blood pressure), diabetes, CRP, and of the other considered myeloid biomarkers. Addition of MCP-1 and M-CSF significantly improved the predictive ability of a model including the Framingham risk factors alone (c-statistic 0.82 [95% CI 0.78-0.85] with MCP-1 and M-CSF vs. 0.66 [95% CI 0.62-0.70], P&lt;0.05). Addition of MCP-1 and M-CSF to the risk model led to a net reclassification improvement (NRI) of 0.51 (95% CI 0.42-0.60), and an integrated discrimination improvement (IDI) of 0.19 (95% CI 0.16-0.21). The model including MCP-1 and M-CSF was particularly effective in controls, leading to a 65% net re-classification into lower risk categories, and in subjects within the intermediate risk group (10-20%), where 70% of individuals were correctly up or down re-classified. Conclusion: MCP-1 and M-CSF have opposite relationships with the risk for AMI in the general population. Addition of MCP-1 and M-CSF significantly improves the predictive power of the Framingham risk model, leading to correct re-classification of a high percentage of individuals, particularly in the intermediate risk group.