The relationship between cardiovascular disease and hearing loss has already been proven. However literature does not provide information on the prevalence of hearing loss in adults with cardiovascular disease. Previous studies provide contradictory information regarding the audiological characteristics in this population. Data relating to the South African context is minimal. The objectives of this descriptive survey research study were to describe the prevalence of hearing loss in adults with this cardiovascular disease and determine the variables which may influence hearing thresholds in this population. Ninety two individuals diagnosed with coronary artery disease or cardiomyopathy were recruited using a non-probability, purposive sampling strategy. This sample, with an average age of 48 years and five months, consisted of more males than females and more participants with coronary artery disease than cardiomyopathy. Participants underwent a comprehensive audiological evaluation including an otoscopic examination, immittance audiometry, pure-tone audiometry, speech audiometry, as well as distortion product otoacoustic emissions. Content analysis, descriptive statistics, t-tests and an analysis of covariance revealed a hearing loss prevalence of 5%. These participants presented with a low frequency sensorineural hearing loss with the right ear being more affected. It was found that duration of cardiovascular disease influenced hearing thresholds. Implications of this study include the importance of prevention and early identification of hearing loss. This highlights the need to establish the role of audiologists within a multi-disciplinary team and the management of individuals with this disease.

archives@tulane.edu / Background Ankle brachial index (ABI) is a noninvasive measure of subclinical cardiovascular disease (CVD) and atherosclerosis of the lower extremities. Low and high levels of ABI are associated with cardiovascular mortality and vascular calcification in dialysis chronic kidney disease (CKD) patients. However, the association of the spectrum of vascular calcification with low and high ABI is not well studied in pre-dialysis CKD patients. The purpose of this study is to investigate the association of both low and high ABI with the risk of vascular calcification in CKD patients. Methods We recruited 243 patients with pre-dialysis CKD from the great New Orleans area between 2010 and 2012. Our study used a cross-sectional design with ABI and CAC measured at the same visit. Continuous ABI measurements were taken and further classified into four categories : <=0.9 (low ABI) >0.9-<1.0 (borderline), 1.0-<1.4 (normal), >=1.4 (high). Level of vascular calcification were considered as the outcome and calculated by agatston score. Three categories of CAC is defined as: CAC agaston score=0, 0-100, >100. Three cumulative logit models were applied to the data. The first is an unadjusted univariate model, the second adjusts for baseline demographics, and the third adjusts for baseline demographics and covariates that are associated with CAC. Logistic regression methods were used to calculate the odds ratio of having a higher CAC score for CKD patients. Results We found a significant association between ABI and vascular calcification. All three models returned consistently significant result (p=0.0005, 0.0005, 0.0037, respectively) for the association between ABI and CAC. In addition, low ABI (ABI≤0.9) is also associated with an increased risk of CAC and severe CAC (OR=6.183, 95%CI(1.085, 35.228)). High ABI (>1.4) is also associated with an increase in CAC and severe CAC (OR=5.064, 95%CI (1.696, 15.122)). Borderline ABI (0.9<ABI<1.0) is not associated with an increase in CAC or severe CAC (OR=2.704, 95% CI (0.702, 10.418). Conclusion Compared to normal ABI level, low and high ABIs are both significantly associated with an increased risk of coronary artery calcification and severe coronary artery calcification in CKD patients. / 1 / Shuo Bai

<p> </p><p>The aim of the study was auditing medical records examine postoperative blood glucose levels after undergoing CABG surgery. Furthermore the aim was to determine if the ward staff abides the local guidelines frame of reference concerning each ward, regarding blood glucose measurements and blood glucose levels. The study included 70 patients undergoing CABG surgery at the cardiothoracic surgery, Uppsala University Hospital. The study was conducted by retrospective medical record auditing. Studied factors were postoperative blood glucose levels, number of registered blood glucose measurements, a current diagnosis of DM and preoperative HbA_1c. Mean level of blood glucose levels stayed continuously above the local guidelines frame of reference for both TIVA/TIMA and the care ward throughout the continuity of patient care. The number of registered blood glucose measurements per postoperative day at TIVA/TIMA where within the local guidelines. The result showed that the local guidelines frame of reference concerning the ward were not reached. A difference could be seen between patients with DM and patients without DM regarding the previously mentioned factors. Preoperative elevated levels of HbA_1c could have influenced the number of postoperative blood glucose measurements. Recommendations will therefore be too audit the current local guideline that concerns the treatment, therapy goals and the number of blood glucose measurements. Establishing criterions regarding termination of blood glucose measurements and the transfer day between TIVA/TIMA and the care ward are recommended.</p><p> </p>

Introduction : Linflammation intervient à tous les stades dans la pathogénie de l'athérosclérose. Initialement, la maladie est caractérisée par une dysfonction endothéliale favorisée par les facteurs de risque cardiovasculaires classiques, des forces hémodynamiques anormales, et des substances vasoactives. A la faveur de cette dysfonction, des processus inflammatoires participent à la formation de la plaque dathérosclérose (1).Les lipoprotéines de basse densité pénètrent dans l'intima artérielle et subissent des modifications chimiques oxydatives responsables de réactions inflammatoires secondaires via la transcription nucléaire du facteur B. Des monocytes circulants activés adhèrent ensuite à la surface endothéliale, la traversent et se différencient en macrophages (activation via l'expression de molécules d'adhésion à la surface endothéliale : VCAM-1 et ICAM-1, qui lient des ligands de la famille des intégrines présents sur la membrane des leucocytes ; sélectines E et P). Cette migration subendothéliale est favorisée par la présence de chémoattractants. Les macrophages se transforment en cellules spumeuses en phagocytant les LDL oxydées via des récepteurs "scavengers". Les lipides d'abord intracellulaires vont devenir extracellulaires et se regrouper pour former un amas appelé le cur lipidique. Des lymphocytes T activés sont aussi présents et interagissent avec les macrophages, entretenant une réaction inflammatoire chronique qui favorise la croissance de la plaque. La plaque adulte est composée d'une chape fibro-musculaire (cellules musculaires lisses, protéines de matrice extracellulaire) séparant le coeur lipidique de la lumière artérielle. Au début, la croissance de la plaque nimplique pas obligatoirement une réduction de la lumière, laugmentation du volume de la plaque dans la paroi étant compensée par une majoration de la taille du vaisseau (remodelage positif). Des cytokines pro-inflammatoires (TNF-, interleukines 1, ...) induisent l'expression de métalloprotéinases par les cellules de la plaque ce qui conduit à sa fragilisation. Dautres cytokines ont des propriétés anti-inflammatoires et l'activité des métalloprotéinases peut être neutralisée par des inhibiteurs spécifiques naturels (TIMP-1, TIMP-2). La stabilité de la plaque résulte donc déquilibres complexes encore imparfaitement compris. La rupture de la plaque est le point de départ de l'évolution thrombotique dont l'importance est variable mais il est vraisemblable que certaines érosions ou ruptures n'entraînent pas de thrombose, favorisant par contre la croissance de la plaque. Activation inflammatoire induite par l'angioplastie dans les syndromes coronariens stables et instables, influence des dommages myocardiques : La CRP ultrasensible (CRPus) possède un pouvoir prédictif de complications chez les patients atteints d'infarctus aigu du myocarde, d'angor stable ou instable. L'origine de cette inflammation est incertaine : réaction inflammatoire au sein même de la plaque ? embolisation a partir d'une plaque friable avec nécrose infra-clinique ? Nous avons donc étudié l'influence pronostique des marqueurs inflammatoires mesurés avant et après l'angioplastie (ACP) et leur relation avec les marqueurs spécifiques de dommage myocardique (troponines). 200 patients (39 à 85 ans) traités par ACP avec ou sans stent entre 01/97 et 05/99 furent étudiés et suivis afin de dépister la survenue de complications. 20% des patients présentaient avant lACP une CRP us > à 6 mg/l. Après ACP, les taux de CRP us > à 6 mg/l et à 12 mg/l étaient respectivement de 40,8 % et 26,4%. Avant lACP, tous les patients présentaient une valeur de troponine I normale alors qu'après lACP, 10,6 % avaient une troponine I > à 5µg/l. Durant le suivi moyen de 38 mois, nous avons recensé 52 événements cardiovasculaires majeurs : 9 décès, 12 infarctus, 5 pontages aorto-coronaire, 26 resténoses, 13 ACP sur une autre lésion que celle traitée initialement. En analyse multivariée, étaient prédictifs de complication : la troponine I après ACP, la CRP us après ACP, les antécédents d'hypertension artérielle et dACP préalable (p<0.05). Nous avons évalué une association entre entre la CRP us après ACP et l'élévation de troponine. Le test t de Student montrait une différence moyenne entre les taux de CRP us pré- et post-ACP de 3,75 mg/l chez les patients avec troponine < à 5µg/l après ACP et de 6,85 mg/l chez ceux avec troponine >5µg/l (p < 0,02). Dans cette étude, l'inflammation et lembolisation après ACP sont prédictives d'événements cardiovasculaires à moyen terme le. L'association entre la CRP us et la troponine après ACP suggère un lien entre ces 2 marqueurs, les patients présentant une inflammation accrue courant un risque supérieur dembolisations péri-procédurales, ce qui pourrait expliquer leur pronostic moins favorable (2). Impact pronostique à long terme de l'activation inflammatoire dans les syndromes coronariens stables Limportance pronostique de la CRP us dans l'angor stable n'est pas établie; la plupart des études préalables évaluaient le court terme or les événements plus tardifs reflètent plus la progression de l'athérosclérose qu'une complication de l'angioplastie à proprement parler. Nous avons donc analysé l'impact pronostique à long terme de la CRP us avant et après ACP et l'influence de l'amplitude de lélévation de ce marqueur sur le devenir à long terme des patients dilatés pour un angor stable. Entre 08/98 et 05/99, 89 patients traités pour un angor stable furent inclus prospectivement et suivis pendant 6 ans. La CRP us moyenne était de 3,35 mg/l avant ACP et de 8,69 mg/l après. La plupart des patients présentait une élévation de ce paramètre ( CRP moyen = 5,34 mg/l ; ≥ à 3 mg/l chez 43 patients). Nous n'avons pas retrouvé de corrélation entre une élévation de CRP > à 3 mg/l et une élévation de troponine T >0,01µg/l. Durant le suivi, 38 patients ont présenté une complication cardiovasculaire (3 décès, 6 infarctus, 6 pontages, 12 ACP sur une autre lésion que celle traitée initialement, 11 resténoses). On notait un taux supérieur d'événements chez les patients présentant une  CRP > à 3 mg/l à la fois à un an de suivi (18 vs 2,2 %; p < 0,001) et à 6,6 ans (39,3 vs 3,4 %; p < 0,001).En analyse multivariée, les paramètres prédictifs indépendants étaient un antécédent d'infarctus du myocarde préalable, une  troponine T > à 0,01µg/l et une  CRP > à 3 mg/l (p = 0, 004, p = 0,013 et p = 0,004 respectivement).L'élévation de CRP us > 3 mg/l après ACP présentait une valeur prédictive d'événements cardiovasculaires supérieure à celle de la CRP us, considérée isolément avant ou après ACP. Donc, bien que le niveau inflammatoire basal soit important, lindice prédictif de complication le plus puissant est l'augmentation de ce marqueur induit par langioplastie. Une élévation importante de CRP ultrasensible après ACP chez certains patients pourrait refléter l'hyperréactivité de leur système inflammatoire aux agressions vasculaires. Une telle hyperréactivité pourrait être un marqueur de progression de l'athérosclérose et/ou d'instabilité clinique future (3). Activation neutrophilique dans les syndromes coronariens instables Nous avons évalué l'existence dune activation des polynucléaires secondaires à une angioplastie avec pose simultanée dune endoprothèse (stenting direct) au niveau d'une lésion responsable d'un syndrome coronarien instable. Nous avons aussi mesuré, la libération de cytokines associée. L'activation des polynucléaires a été évaluée par la mesure des taux de myéloperoxydase (MPO), de lactoferrine (LCF) et d'élastase.Vingt patients en angor instable furent étudiés (19 hommes; âge moyen : 53,9 ± 12,1 ans). Ils furent séparés en 2 groupes : groupe A : 15 patients traités par stenting direct de la lésion responsable ; groupe B : 5 patients n'ayant pas subi de revascularisation. Des prélèvements biologiques étaient réalisés chez les patients après l'insertion de l'introducteur fémoral (T0), 30après lACP ou après la procédure diagnostique (T1), puis 30 minutes, 3, 6, 12 et 24 heures après (T2 à T6). Les deux groupes étaient comparables du point de vue clinique et angiographique. Dans le groupe contrôle, aucune variation ne fut observée pour les dosages de MPO et de LCF. Dans le groupe A, une augmentation plasmatique du niveau de MPO fut observée immédiatement après l'angioplastie (p = 0,0009 à T1 vs T0; p < 0,0001 à T2 vs T0; p = 0,008 pour T3 vs T0). Pour la LCF, l'élévation était similaire (p = 0,004 pour T1 vs T0 et pour T2 vs T0). Des différences significatives furent observées à T1, T2 et T3 entre les groupes A et B pour la MPO (p = 0,015; p = 0,005; p = 0,042 respectivement) et pour la LCF (p = 0,0001; p = 0,0005; p = 0,003 respectivement). Le test ANOVA démontrait une valeur de p < à 0,0001 pour la MPO et la LCF dans le groupe A. Pour l'élastase et le TNF-, nous n'avons pas observé de différence significative au sein des groupes et entre les groupes. Nous avons observé une élévation plasmatique de l'IL-6 dans les 2 groupes (test ANOVA : p= 0,0065 pour le groupe B et p< 0,0001 pour le groupe A). Pour la première fois, nous rapportons une élévation rapide et intense d'enzymes neutrophiliques spécifiques (MPO et LCF) après pose dun stent coronarien (4). Cette libération pourrait en partie être responsable de la libération secondaire de cytokines (IL-6, IL-12, IL-8, CRP us). Il reste à déterminer si ces phénomènes peuvent influencer le pronostic clinique ou représenter une cible thérapeutique. Activation neutrophilique dans les syndromes coronariens stables; comparaison avec les tableaux cliniques instables L'activation des polynucléaires neutrophiles est donc impliquée dans la physiopathologie des syndromes coronariens instables et est aussi observée après ACP. Les leucocytes activés relâchent de la MPO, un agent oxydant puissant dont l'activité entraîne la production de dérivés d'oxygène réactif. Cette enzyme est augmentée chez les patients présentant un syndrome coronarien aigu, plus particulièrement chez ceux qui vont présenter une évolution clinique défavorable. Actuellement, on ignore si la MPO intervient dans la rupture de plaque ou contribue directement aux lésions tissulaires. Elle favorise l'athérogenèse via la production de molécules pro-athérogènes (dérivés oxydés de l'oxyde nitrique par exemple) et en utilisant comme substrat l'oxyde nitrique qui lui est athéroprotecteur. Nous avons comparé l'expression des cytokines inflammatoires et l'activation leucocytaire induites par un direct stenting chez des patients en angor stable par rapport aux instables. Quinze patients (groupe A) en angor instable furent comparés à 11 patients (groupe B) en angor stable. Tous présentaient une seule lésion sévère cible, traitable par langioplastie et pose simultanée dun stent. Les échantillons sanguins furent prélevés comme décrit dans létude précédente. A l'exception d'un âge moyen supérieur dans le groupe B, tous les paramètres cliniques et biologiques étaient similaires dans les deux groupes. Dans le groupe A, une augmentation du niveau plasmatique de MPO fut observée immédiatement après la pose du stent avec une élévation parallèle de la LCF. Dans le groupe B, nous avons également observé une élévation de MPO et de LCF après l'intervention qui était néanmoins inférieure que dans le groupe A (ANOVA test : p < 0,001 à la fois pour la MPO et la LCF dans les deux groupes). Pour l'élastase, aucune différence significative ne fut observée entre les groupes. Les niveaux plasmatiques d'IL-8 et dIL-12 ne furent pas significativement affectés dans chacun des groupes mais leurs valeurs moyennes étaient supérieures chez les patients stables, bien que restant dans les limites de la normale (< 30pg/ml chez les patients normaux; n = 34). Nous avons également observé une élévation significative de lIL-6, 12 heures après l'intervention dans les 2 groupes. Le pic sérique de ces cytokines survenait néanmoins plus tard par rapport à la libération aiguë de MPO et de LCF. Cette observation souligne l'importante activation des neutrophiles après pose de stent, démontrant que la rupture mécanique d'une plaque d'athérosclérose par un stent, est rapidement suivie d'une libération denzymes spécifiques. Lactivation des polynucléaires neutrophiles est plus intense dans les syndromes coronariens aigus que dans les situations cliniques stables. Donc, parallèlement aux modifications des taux de MPO trans-cardiaque observées dans l'angor instable (reflétant l'inflammation généralisée de l'arbre coronaire), nous rapportons pour la première fois que le stenting coronarien a un effet direct sur lélévation de la MPO.(5) Conclusions : Nos travaux montre que : 1) Langioplastie coronaire est associée à une élévation des paramètres inflammatoires systémiques, limportance de ces manifestations inflammatoires possédant une signification pronostique. 2) Le niveau basal et lincrément secondaire des paramètres inflammatoires sont hautement prédictifs des évènements cardio-vasculaires futurs suggérant que la réactivité individuelle est déterminante. 3) Les neutrophiles par leurs enzymes spécifiques interviennent précocement dans la cascade inflammatoire induite. 4) Lintensité de la réponse est différente en fonction de la présentation clinique (Hyper-réactivité diffuse? Composition de la plaque?). Une meilleure compréhension de la pathogénie de linsuffisance coronarienne devrait permettre une meilleure stratification du risque impliquant une prise en charge thérapeutique maximalisée et le développement de stratégies thérapeutiques alternatives plus efficaces tant en prévention primaire que secondaire. Références : 1. Gach O, Piérard L, Legrand V. Inflammation and atherosclerosis. State of the Art in 2004-2005. Rev Med Liège 2005; 60: 235-241. 2. Gach O, Louis O, Martinez C, Legrand V. Impact of markers of myocardial damage and inflammation after PCI on late outcome. Heart 2002; 87. 3. Gach O, Legrand V, Biessaux Y, Chapelle JP, Vanbelle S, Pierard L. Long term prognostic significance of High-Sensitivity C-Reactive Protein before and after coronary angioplasty in patients with stable angina pectoris. Am J Cardiol, 2007, 99:31-35. 4. Gach O, Biemar C, Nys M , Deby-Dupont G, Chapelle JP, Deby C, Lamy M, Pierard LA, Legrand V. Early release of neutrophil markers of activation after direct stenting in patients with unstable angina. Coron Artery Dis 2005; 16: 59-65. 5. Gach O, Nys M, Deby-Dupont G, Chapelle JP, Lamy M, Piérard LA, Legrand V. Acute neutrophil activation in direct stenting: comparison of stable and unstable angina patients. Int J Cardiol. 2006; 112(1): 59-65.

Atherosclerosis is characterized by a chronic inflammation, involving autoimmune components, in the arterial wall. An increase in proinflammatory activity relative to anti-inflammatory activity is considered to cause a progression of the disease towards plaque instability and risk of atherothrombotic events, such as acute coronary syndrome (ACS). Cortisol, the end product of the hypothalamus-pituitary-adrenal (HPA) axis, is a powerful endogenous anti-inflammatory mediator. Disturbances in the HPA axis have been reported in chronic inflammatory/autoimmune diseases, like rheumatoid arthritis. The aim of this thesis was to study various markers of systemic inflammation in patients with acute and stable conditions of coronary artery disease (CAD) and relate these findings to the cortisol response. Both patients with ACS and patients with stable CAD had high levels of C-reactive protein (CRP), interleukin (IL)-6 and IL-1 receptor antagonist, compared with healthy controls. In addition, patients with stable CAD had significantly more neutrophil-platelet aggregates than controls, as a possible indicator of neutrophil activation. The cortisol response was determined in two different cohorts of CAD patients; one consisting of patients with a first-time myocardial infarction and one consisting of patients with long-term stable CAD. From the acute phase to 3 months, the patients with a myocardial infarction showed a higher 24-h cortisol secretion and a flattened diurnal slope caused by higher cortisol levels in the evening, as compared with healthy controls. The patients with long-term stable CAD showed similarly high levels of cortisol in the evening. The levels of evening cortisol were strongly correlated with CRP and IL-6. When exposed to acute physical or acute psychological stress at 3 months, the ACS patients showed a markedly blunted cortisol response compared with healthy controls. Following the stress tests, a significant increase in CRP was observed in the patients but not in the controls, indicating a failure of the HPA axis to compensate for stress-induced inflammation in CAD. In the ACS patients, the time course of matrix metalloproteinases (MMPs) and their tissue inhibitor TIMP-1 was determined during the 3 months follow-up. A major finding was that the MMP-9 and TIMP-1 levels remained significantly higher in the patients at all time points compared to the controls. MMP-9 and TIMP-1, but not MMP-2, MMP-3 or MMP-7, were related to inflammatory activity, as assessed by CRP and IL-6. MMP-9 and TIMP-1 showed significant correlation with evening cortisol, even after adjustment for CRP and IL-6, lending further support for a link between ´high´ flat cortisol rhythm and systemic inflammatory activity. The activation status of neutrophils in stable CAD was further examined by measuring the expression, affinity state and signalling capacity of b2-integrins and the innate production of reactive oxygen species (ROS). However, the neutrophils in patients were not more activated in vivo than were cells in healthy controls, neither were they more prone to activation ex vivo. The data rather indicated an impaired function of neutrophils in stable CAD. The neutrophils in CAD patients showed a significantly lower number of total glucocorticoid receptors (GRs) and a lower GRa:GRb ratio compared to healthy controls, indicating a chronic over activation of the HPA axis and, possibly, a state of glucocorticoid resistance. Moreover, the evening cortisol levels in patients were associated with an overexpression of annexin-1, the ´second messenger´ of glucocorticoid action. In contrast to neutrophils in controls, the neutrophils in patients also showed a hyper responsiveness to exogenous annexin-1 resulting in impaired neutrophil function. To conclude, clinically stable CAD was associated with a systemic inflammatory activity, involving a high MMP-9:TIMP-1 ratio and an increased inflammatory response to acute stress but not any activation of neutrophils. This inflammatory activity was associated with a dysregulated cortisol secretion, defined by a flat diurnal rhythm and a blunted cortisol response to stress. Although the clinical relevance remains to be verified, an intriguing hypothesis is that a hyporesponsive HPA axis favours the development towards plaque instability. / On the day of the defence date the title of article III was: "A sustained elevation of serum matrix metalloproteinase-9 is associated with diurnal salivary cortisol in patients with acute myocardial infarction-a 3-month follow-up".

The aim of the study was auditing medical records examine postoperative blood glucose levels after undergoing CABG surgery. Furthermore the aim was to determine if the ward staff abides the local guidelines frame of reference concerning each ward, regarding blood glucose measurements and blood glucose levels. The study included 70 patients undergoing CABG surgery at the cardiothoracic surgery, Uppsala University Hospital. The study was conducted by retrospective medical record auditing. Studied factors were postoperative blood glucose levels, number of registered blood glucose measurements, a current diagnosis of DM and preoperative HbA1c. Mean level of blood glucose levels stayed continuously above the local guidelines frame of reference for both TIVA/TIMA and the care ward throughout the continuity of patient care. The number of registered blood glucose measurements per postoperative day at TIVA/TIMA where within the local guidelines. The result showed that the local guidelines frame of reference concerning the ward were not reached. A difference could be seen between patients with DM and patients without DM regarding the previously mentioned factors. Preoperative elevated levels of HbA1c could have influenced the number of postoperative blood glucose measurements. Recommendations will therefore be too audit the current local guideline that concerns the treatment, therapy goals and the number of blood glucose measurements. Establishing criterions regarding termination of blood glucose measurements and the transfer day between TIVA/TIMA and the care ward are recommended.

Each year in the United States over a million people experience a myocardial infarction. The majority of these attacks are caused by coronary artery plaque cap rupture with subsequent thrombus formation. Because rupture is a mechanical event and the tendency of a plaque to rupture is due in part to increases in the mechanical stresses in the fibrous cap, mechanical analyses are important to understanding plaque stability. Histology is the only method capable of identifying plaque features that are associated with vulnerability. Therefore, minimally distorted histologic sections should serve as a basis for constructing the models used in mechanical analyses. Further, because substantial longitudinal variations in geometry and mechanical properties often exist, models should be three-dimensional (3-D). Finally, given the complex geometries of atherosclerotic plaques and the fact that they are composed of different materials, the finite element (FE) method should be used to determine the distribution of stress under physiological loading. Until now, a critical need has existed to determine the distribution of stress in 3-D FE models of human coronary atherosclerotic plaques based on minimally distorted histologic sections. In this research study, a method to measure and correct for distortions caused by acrylic histologic processing was first created. The devised strain-based method yields a limited set of parameters needed for a first order correction. Thus, corrections can be easily implemented using FE methods. Next, a methodology to create 3-D finite FE models of human coronary atherosclerotic plaques based on stable acrylic histologic sections was developed. Models of plaques, ranging in disease severity, were generated using the developed methodology. Lastly, the distributions of stress in these models were obtained and the effects of some plaque features on stresses were determined. Results from this study confirm that morphological description of a plaque is not sufficient to predict plaque rupture. The findings suggest that in many cases the 3-D stress field within a plaque must be known in order to assess plaque stability. Finally, the results show that patient specific models must be developed if the 3-D stress field within a plaque is to be determined.

Kawasaki disease (KD) is the most common cause of paediatric acquired heart disease, which may be attributed to the combined effects of infection, immunological response, and genetic susceptibility. The most severe complication in KD is acute coronary artery lesions (CALs), including myocardial infarction and coronary artery aneurysms. Mounting evidence indicates that adhesion molecules and chemokines play an important role in inflammation and cardiovascular disease on basis of pathogenesis. Thus, this study aimed to investigate the association of seven single nucleotide polymorphisms (SNPs) of adhesion molecules and chemokines (P-selectin 290G>A, PSGL-1 62G>A, MCP-1 -2518A>G, SDF-1 -801G>A, PECAM-1 L125V, PECAM-1 S563N and PECAM-1 R670G) with the risk of KD, sequelae of CALs and initial intravenous immunoglobulin (IVIG) treatment failure. A total of 301 KD children (185 without acute and chronic CALs, 81 with acute but without chronic CALs, and 33 with acute and chronic CALs) and 246 sex-matched healthy controls were recruited in the case-control study. In addition, 166 cases from the above KD children and 332 parents were recruited to carry out case-parent trio study. We found that PECAM-1 3 SNPs polymorphisms were not associated with above several risks, except for CALs in chronic stage. As compared with non-Leu-Ser-Arg haplotype, Leu-Ser-Arg haplotype was associated with a significant increased risk for CALs in the chronic stage (AOR 2.50, 95% CI 1.05-6.00, P=0.039). Analyses based on the diplotypes of PECAM-1 also showed that Leu-Ser-Arg allele had a significant increased risk of CALs in chronic stage in dominant manner (AOR 2.98, 95% CI 1.15-7.72, P=0.024). In addition, carriers of Leu-Ser-Arg allele had significant increased counts of platelet (¡Ñ1000/Cumm) (672.6¡Ó207.6 versus 563.1¡Ó196.8; P=0.027) within 10 days of diagnosis of KD. Moreover, we also found a significant correlation between each SNP and polymorphonuclear neutrophil counts by genotype analysis. As for other genes, there were no markedly different outcomes regardless of the risk of KD, sequelae of CALs or initial IVIG treatment failure. In conclusion, the haplotype Leu-Ser-Arg of PECAM-1 is a genetic marker of susceptibility to sequelae of chronic CALs for KD patients. However, the role of PECAM-1 SNPs in CALs formation in the chronic stage in KD patients still needs further evaluation.

Background: The presence of calcified deposits in the coronary arteries has become established as a marker of coronary atherosclerosis. Design and Setting: Single medical center observational study. Study objective: 1) To determine the sensitivity and specificity of coronary calcium by cinefluoroscopy (CF) and to validate the reliability of CF in the angiographic detection of > 50% coronary artery stenosis. 2) To assess the financial benefit of adding CF-determined coronary calcium into the self-paid executive physical examination items. 3) To evaluate whether an algorithm using CF to assess coronary calcium has potential as an initial cost-effective testing pathway for diagnosis of > 50% coronary artery stenosis. Methods: Between November 1, 2004 and April 25, 2005, 333 patients who underwent angiography for diagnosis of and determine the extent of coronary artery disease were enrolled in the study. All patients received CF to determine presence or absence of calcium in the coronary artery system prior to selective angiography. Sensitivity and specificity were then obtained to confirm CF as a reliable non-invasive test for diagnosing > 50% coronary artery stenosis. Direct cost, total cost and estimated profit were calculated with and without the cost of cardiac catheterization laboratory at Chang Gung Memorial Hospital, which has an average of 475 patients/month who undergo self-paid executive physical examinations. Direct cost, total cost and estimated loss of coronary calcium by electron beam computed tomography (EBCT) were calculated for the acquisition of an EBCT machine by Chang Gung Memorial Hospital. A test model was applied to examine the costs and cost-effectiveness of the following diagnostic modalities: the traditional treadmill exercise (TMET); stress thallium and positron emission tomography (THALLIUM); coronary calcium by EBCT calcium score > 0 and > 168; and, coronary calcium by CF for diagnosis of obstructive coronary artery disease (CAD) as a function of pretest likelihood (i.e., prevalence) of disease. Results: Two hundred fifty three men and 80 women were enrolled in this study (mean age, 63.9+11.4 years; age range, 35-90 years). Sensitivity and specificity of CF in the detection of patients with angiographically coronary artery stenosis >50% were 96% and 86%, respectively. The profit accrued from implementing the CF test at Chang Gung Memorial Hospital, including the cost of the cardiac catheterization laboratory, was NT$329/patient. At 475 patients per month, this test will produce revenue of NT$156,275/month or NT$1,875,300/year. The profit achieved by implementing the CF test at Chang Gung Memorial Hospital, excluding the cost of the cardiac catheterization laboratory was NT$838.7/patient, or NT$398,382.5/month and NT$4,780,590/year. Conversely, implementing the EBCT test will cost Chang Gung Memorial Hospital NT$ 1,124,990/month or NT$ 13,499,880/year. With disease prevalence at < 0.7, CF examination was the most cost-efficient initial diagnostic testing pathway. However, for the group with prevalence at 1.0, the highest group, initial angiography with no prior non-invasive testing was the most cost-effective strategy for diagnosis of obstructive coronary artery disease. Conclusion: 1) Calcium detection with CF is a highly sensitive and moderately specific test, and a simple, inexpensive, and safe technique for identifying CAD. 2) Instituting CF as a screening test for self-paid executive physical examinations would result in considerable profit for the hospital. Conversely, establishing an EBCT program will produce a substantial financial loss. 3) For patients evaluated for obstructive CAD, a test pathway utilizing CF to detect coronary artery calcium as an initial non-invasive test minimized direct costs and maximized cost-effectiveness. Cinefluoroscopy has been neglected as a noninvasive technique for diagnosis of coronary stenosis and is sufficiently promising to warrant increased clinical use.

Previous studies show that coronary artery disease (CAD) is a multi-factors and chronic inflammatory disease, and is associated with lipid metabolism. IL-1ra is a naturally occurring anti-inflammatory molecules that block the action of IL-1. However, little is known about the imbalance between IL-1ra and inflammatory mediators in CAD. We attempted to investigate the relationships between inflammatory mediators and serum IL-1ra levels in patients with CAD. In 95 patients with angiographically defined CAD, and 70 healthy controls were studied in a case-control manner. Serum levels of cytokines and the risk factor of CAD were examined. Polymorphisms for IL-1ra gene were detected by PCR, and genotypes and allelic frequencies in both groups were compared. Our major finding include: (1) The risk factors such as elevated BMI, systolic BP, smoking, hypertension, blood glucose, and TG was more frequently found in the CAD group than the control group ( p < 0.001). However, the HDL-C and bilirubin were significantly higher in control group than the CAD group. (2) The relative risk of those in the highest quartile of ratio of LDL-C to HDL-C, TC to HDL-C, and TG to HDL-C were significantly elevated. ( OR = 2.98, p < 0.01; OR = 5.31, p <0.001; OR = 8.43, p < 0.001 respectively) (3) Five different inflammatory markers were significantly elevated including IL-1ra, hs-CRP, IL-6, leukocyte count, and neutrophil percentage between healthy controls and CAD patients. ( p < 0.01) (4) Levels of IL-1ra and other variables such as blood glucose, BMI, TG, IL-6, hs-CRP, and leukocyte count has significantly correlated, and were inversed correlation in bilirubin, and HDL-C in all study subjects. ( p < 0.01) (5) In the multiple logistic regression analysis, adjustment was made for variables. The relative risk of CAD for the highest quartile of IL-1ra, as compared with the lowest quartile, had an Odds ratio 2.57 ( 95% confidence intervals, 1.12 - 5.91, p = 0.026 ) increase in risk for CAD. (6) Similar results were obtained hs-CRP, IL-6 in the highest quartile were increase risk for future CAD. ( OR = 5.86 and 5.79 respectively; p < 0.001) (7) The join effect cytokines of hs-CRP, IL-6, IL-1ra concentrations may play important role in CAD risk. ( OR = 10.19, p < 0.001 ) (8) In addition, IL-1ra allele 2 genotype and allelic frequencies were no significant association with increase in IL-1ra with CAD. In conclusion, we find a significant association of elevated IL-1ra levels in the patients with CAD. Thus, these results support the hypothesis that inflammation, anti-inflammation cytokines and lipoprotein metabolism provide a useful marker for predicting the development of CAD events.