Coronary Artery Disease: Kristensen SD

Daemen J, Simoons ML, Wijns W, Bagust A, Bos G, Bowen JM, Braunwald E, Camenzind E, Chevaliers B, DiMario C, Fajadeto J, Gitt A, Guagliumi G, Hillege HL, James S, Jüni P, Kastrati A, Kloth S, Kristensen SD, Krucoff M, Legrand V, Pfisterer M, Rothman M, Serruys PW, Silber S, Steg PG, Tariah I, Wallentin L, Windecker SW, Aimonetti A, Allocco D, Berenger M, Boam A, Calle JP, Campo G, Carlier S, de Schepper J, Di Bisceglie G, Dobbels H, Farb A, Ghislain JC, Hellbardt S, ten Hoedt R, Isaia C, de Jong P, Lekehal M, LeNarz L, Mhullain FN, Nagai H, Patteet A, Paunovic D, Potgieter A, Purdy I, Raveau-Landon C, Ternstrom S, Van Wuytswinkel J, Waliszewski M, Anonymous00071. · Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands. · EuroIntervention. · Pubmed #19284063 No free full text.

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Schmidt EB, Arnesen H, Christensen JH, Rasmussen LH, Kristensen SD, De Caterina R. · Department of Preventive Cardiology, Aalborg Sygehus, Arhus University Hospitals, Denmark. · Thromb Res. · Pubmed #15668184 No free full text.

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Ziegler BK, Rasmussen LH, Kristensen SD, Hildebrandt PR, Nielsen HK, Husted SE. · Arhus Universitetshospital, Arhus Amtssygehus, Klinisk Farmakologisk Afdeling, Aalborg Sygehus, Kardiologisk Afdeling. · Ugeskr Laeger. · Pubmed #12772393 No free full text.

Abstract: Acute manifestations of atherosclerosis, e.g. myocardial infarction and ischaemic stroke, are among the most common causes of death in the western part of the world. Rupture of an atherosclerotic plaque results in activation, adhesion and aggregation of platelets. Antithrombotic treatment has shown to reduce mortality and morbidity and is used in both primary and secondary prevention. The thienopyridine Clopidogrel specifically and irreversibly inhibits the binding of ADP to platelet surface ADP-receptors, thereby inhibiting platelet activation and aggregation. In this publication the pharmacological background and clinical documentation for the use of Clopidogrel both as monotherapy and in combination with Acetylicsalisylic acid are reviewed.

Kristensen SD, Lassen JF, Ravn HB. · Department of Cardiology B and Institute of Experimental Clinical Research, Aarhus University Hospital, Skejby Sygehus, Arhus N, Denmark. · Semin Interv Cardiol. · Pubmed #11054908 No free full text.

Abstract: Detailed knowledge of the pathophysiology as well as the dynamic nature of coronary thrombus formation provides a valuable tool for correct management and proper adjunctive therapy in patients with acute coronary syndromes. Coronary thrombosis is in the majority of cases caused by disruption or fissuring of an atherosclerotic plaque. At the lesion thrombogenic material will be exposed to the flowing blood leading to activation of platelets and the formation of a platelet clot. Simultaneously, the coagulation system is activated resulting in increased thrombin formation. Thrombin is a key mediator in arterial thrombosis, due to its effect on both platelets and fibrin generation. Thrombin contributes to the stabilization of an initially loose platelet clot by generating cross-bound fibrin within the thrombus. During the course of an acute coronary syndrome, the patient presents changing chest pain and dynamic ischaemic ECG findings. This is likely to be related to the dynamic nature of the pathophysiology. The presence of a non-occlusive coronary thrombus may deprive the myocardium its normal blood flow and oxygen supply, leading to ischaemic pain. During lysis or embolization, blood supply may be restored, but the presence of thrombus fragments in the microcirculation holds the potential to sustained interference with myocardial metabolism. The emboli contain activated platelets which release vasoconstrictors that may compromise the microcirculation. Recurrent thrombus formation at the lesion site may result in occlusion of the artery adding to the dynamic nature of the clinical presentation. In conclusion, platelets, the coagulation system, and the endothelium cause a dynamic process of intermittent occlusion, vasospasm and embolization of thrombus material.

Kristensen SD, Andersen HR, Falk E. · Department of Cardiology B, Skejby Hospital, Aarhus, Denmark. · Semin Interv Cardiol. · Pubmed #10406063 No free full text.

Abstract: Basic knowledge of the sequence of cellular events that change the relative benign disease coronary atherosclerosis into a life-threatening acute coronary syndrome is of great importance for the interventional cardiologist in order to understand and choose the correct pharmacological and interventional management in patients with acute myocardial infarction. Plaque disruption, or fissuring, with superimposed thrombosis frequently complicates the course of coronary atherosclerosis. Small ruptures often remain clinically silent, whereas more extensive plaque rupture may lead to the development of unstable angina, acute myocardial infarction, and sudden cardiac death. The risk of plaque disruption depends more on plaque composition than on plaque size and stenosis severity. Major determinants of a plaque's vulnerability to rupture are: the size and consistency of the lipid-rich atheromatous core, the thickness of the fibrous cap covering the core, and inflammation and repair within the cap. The elevation of fibrinogen and C-reactive protein in patients with unstable angina may be markers of ongoing plaque inflammation. Both plaque vulnerability and rupture triggers are important for plaque disruption. The resultant thrombotic response, which is important for the clinical presentation and outcome, is in part determined by the reactivity of the circulating platelets and the balance between the fibrinolytic and coagulation systems. New ways of identification and treatment of the dangerous vulnerable plaques responsible for infarction and death and optimization of anti-thrombotic treatment are highly warranted in order to prevent and treat life-threatening coronary thrombosis.

Mortensen J, Poulsen TS, Grove EL, Refsgaard J, Nielsen HL, Pedersen SB, Thygesen SS, Hvas AM, Kristensen SD. · Department of Cardiology, Aarhus University Hospital Skejby, Aarhus, Denmark. · Scand J Clin Lab Invest. · Pubmed #18651324 No free full text.

Abstract: OBJECTIVE: Low platelet response to aspirin has been reported to be associated with a high incidence of vascular events. The reported prevalence of aspirin low-responsiveness varies, which may be explained by poor reproducibility of the methods used to evaluate aspirin response and low compliance. The Platelet Function Analyzer-100 (PFA-100) is a commonly used platelet function test. We aimed to assess the reproducibility of the PFA-100 and the agreement with optical platelet aggregometry (OPA) in healthy volunteers and in patients with coronary artery disease (CAD) treated with low-dose aspirin. MATERIAL AND METHODS: Twenty-one healthy volunteers and 43 patients with CAD took part in the study. During treatment with aspirin 75 mg daily, all participants had platelet function assessed in duplicate with the PFA-100 and OPA on 4 consecutive days. Additionally, platelet function was assessed before aspirin treatment in healthy subjects. Serum-thromboxane B(2) (S-TxB(2)) was measured to assess compliance. RESULTS: In healthy volunteers not receiving aspirin, duplicate measurements resulted in coefficients of variation (CV) of 7.9 % for the PFA-100 and 5.2 % for OPA. During aspirin treatment, CVs were significantly higher (healthy volunteers: PFA-100: 15.6 %, OPA: 19.2 %; patients: PFA-100: 26.6 %, OPA: 16.8 %). Two of the 64 participants were classified as aspirin low-responders with both methods, indicating poor agreement (Kappa coefficient 0.05). Compliance was excellent, as S-TxB(2) was completely inhibited in all participants. CONCLUSIONS: Aspirin treatment affects the reproducibility of both PFA-100 and OPA. This imprecision should be considered carefully if the methods are used for monitoring aspirin treatment. Additionally, these methods do not identify the same individuals as being aspirin low-responders.

Hedegaard SS, Hvas AM, Grove EL, Refsgaard J, Rocca B, Daví G, Kristensen SD. · Department of Cardiology, Aarhus University Hospital Skejby, Denmark. · Thromb Res. · Pubmed #19215971 No free full text.

Abstract: INTRODUCTION: Aspirin reduces cardiovascular events in patients with coronary artery disease (CAD), but studies report a highly variable response to aspirin, often referred to as 'aspirin low-responsiveness'. We investigated whether 75 mg of daily non-enteric coated aspirin would completely inhibit the platelet cyclooxygenase-1 activity to a comparable extent in healthy individuals and stable CAD patients. METHODS: We assessed serum thromboxane B2 (S-TxB2), urinary 11-dehydro-TxB2 (U-TxM) and arachidonic acid-induced optical platelet aggregometry (OPA) in 44 CAD patients on aspirin and in 22 healthy individuals before and after aspirin. OPA was performed in duplicate for four consecutive days during aspirin treatment after one week of treatment. Compliance was optimized by face-to-face interviews and pill counting and confirmed by S-TxB(2) measurements. RESULTS: Aspirin inhibited S-TxB2 >99% in healthy individuals (median 1.1 ng/mL, interquartile range (IQR) = 0.8;1.9 after aspirin) and in patients, S-TxB2 was reduced to a similar level (0.9 ng/mL (0.7;1.5)). Healthy individuals had a median U-TxM of 278.5 pg/mg creatinine (229.5;380.0) before aspirin and 68.5 pg/mg creatinine (59.0;99.7) on aspirin corresponding to an average 74% inhibition of the endogenous TxA2 biosynthesis. In patients median U-TxM was 67.5 pg/mg creatinine (54.0;85.5). Seven study participants (11%) were aspirin low-responders according to OPA, but none had S-TxB2 in the highest quartile. CONCLUSIONS: Low-dose aspirin suppressed S-TxB(2) to comparable levels in CAD patients and healthy individuals. Despite an almost complete inhibition of S-TxB2, some participants were low-responders according to OPA. Thorough compliance control and use of thromboxane-specific assays are important when measuring platelet response to aspirin.

Grove EL, Hvas AM, Kristensen SD. · Department of Cardiology, Aarhus University Hospital Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark. · Thromb Haemost. · Pubmed #19132202 No free full text.

Abstract: Platelets newly released from the bone marrow are RNA-containing and more haemostatically active than mature platelets. Immature platelets are reliably quantified by flow cytometry, and the immature platelet fraction (IPF) reflects platelet production and the rate of platelet turnover. It was the objective of this study to evaluate the presence of immature platelets in healthy subjects, patients with stable coronary artery disease (CAD) and patients with acute coronary syndromes. Flow cytometric determination of immature platelets was performed with an automated analyzer (Sysmex XE-2100) using RNA fluorescent dyes. IPF was determined in 420 individuals: 22 healthy subjects, 39 patients with stable CAD, 182 patients with unstable angina/non-ST-segment elevation myocardial infarction (non-STEMI) and 177 patients with acute STEMI. The geometric mean [95% confidence interval] of IPF was 2.51 [2.04-3.10] in healthy subjects, 2.87 [2.45-3.36] in CAD patients, 2.93 [2.72-3.15] in the non-STEMI/unstable angina group and 3.71 [3.45-3.99] in patients with STEMI (ANOVA: p < 0.0001). This difference remained significant after adjusting for baseline characteristics (p = 0.0003). In active smokers, IPF was 18% higher than in non-smoking individuals (p = 0.007), and IPF was 16% higher in diabetics compared with non-diabetics (p = 0.060). In conclusion, the fraction of immature platelets is increased in acute coronary syndromes, especially in the acute phase of STEMI. Immature platelets with an increased haemostatic potential may contribute to coronary thrombus formation.

Nielsen HL, Kristensen SD, Thygesen SS, Mortensen J, Pedersen SB, Grove EL, Hvas AM. · Department of Cardiology, Aarhus University Hospital Skejby, Denmark. · Thromb Res. · Pubmed #18499236 No free full text.

Abstract: INTRODUCTION: Patients with inadequate platelet inhibition by aspirin, referred to as aspirin resistance, might have an increased risk of suffering cardiovascular events. Therefore, identification of these patients by measuring platelet function is of great interest. Our objectives were to evaluate performance parameters of VerifyNow and to determine the agreement between VerifyNow and light transmission aggregometry (LTA) ad modum Born. MATERIALS AND METHODS: We included 21 healthy volunteers and 40 patients with stable coronary artery disease. Duplicate measurements of platelet aggregation were performed using VerifyNow and LTA (arachidonic acid 1.0 mM) in healthy volunteers before aspirin and in all participants on four consecutive days during treatment with non-enteric-coated aspirin 75 mg daily. VerifyNow test results were expressed in Aspirin Reaction Units (ARU) and LTA test results in percent of maximal aggregation. The cut-off for determination of aspirin resistance was > or =550 ARU and > or =20%, respectively. RESULTS: All participants were compliant, confirmed by complete suppression of serum-thromboxane B(2). VerifyNow was highly repeatable with a coefficient of variance of 0.5% at baseline and 3.0% during aspirin treatment. No individuals were identified as aspirin resistant with VerifyNow, whereas seven (12%) individuals were identified with LTA. ROC analysis using LTA as the gold standard showed poor sensitivity and good specificity with a cut-off at 550 ARU. CONCLUSION: VerifyNow was highly repeatable, but further studies are needed to investigate the relevance of the cut-off level at 550 ARU for detecting aspirin resistance.

Grove EL, Ørntoft TF, Lassen JF, Jensen HK, Kristensen SD. · Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Denmark. · J Intern Med. · Pubmed #15147527 No free full text.

Abstract: OBJECTIVES: Platelet glycoprotein (GP) receptor IIb/IIIa plays a key role in the development of myocardial infarction (MI), and Pl(A2) is a polymorphism in the gene encoding this receptor. The prevalence of Pl(A2) shows pronounced geographical variation and has to our knowledge not been presented for a Scandinavian population before. Platelets from Pl(A2)-positive individuals show increased aggregability compared with platelets from Pl(A2)-negative individuals, and Pl(A2) genotypes might be associated with MI. The purpose of this study was to investigate the relation between the Pl(A2) polymorphism and MI in a large Scandinavian population. DESIGN: Case-control study. We included patients with angiographically verified CAD with and without previous MI and a group of healthy individuals matched for age, race, and sex. RESULTS: We studied the frequency of Pl(A2) in 1191 healthy individuals and 1019 patients with coronary artery disease (CAD). Amongst these patients, 529 subjects had suffered an MI previously. Pl(A2) was present in 28% of healthy individuals, 28% of patients with CAD but no MI, and in 35% of patients with CAD and MI. The difference between healthy individuals and MI patients was significant (P = 0.002). Furthermore, a graded relationship between the number of Pl(A2) alleles and the risk of MI was seen (P = 0.011). Associations between Pl(A2) and traditional cardiovascular risk factors as well as mean platelet volume were investigated. We found a significant interaction between Pl(A2) and serum cholesterol. CONCLUSION: In our Scandinavian study population the common platelet polymorphism Pl(A2) is significantly associated with an increased risk of MI, but not of CAD. Clinically, typing for Pl(A2) might have implications for antiplatelet therapy of patients with MI.

Thuesen L, Andersen HR, Krusell LR, Kristensen SD. · Department of Cardiology, Skejby Sygehus, Aarhus University Hospital, Denmark. · Scand Cardiovasc J. · Pubmed #10872707 No free full text.

Abstract: This study was conducted to evaluate the short- and long-term clinical and angiographic results of implantation of a flexible, coiled stainless steel stent, the Freedom Coronary Stent. During the study period this stent was used as an alternative to the Palmaz-Schatz PS153 coronary stent in long or tortuous lesions. The study was designed as a prospectively planned outcome analysis. Implantation of Freedom stents was attempted in 62 consecutive patients (56% males, mean age 63+/-10 years) with a total of 65 coronary lesions. Indications for stent implantation were: restenosis, 8%; recoil, 26%; visible dissection, 32%; threatening occlusion, 15%; chronic total occlusion, 18%. The average stent length was 30+/-16 mm and 67% of the lesions were type C. Rate of successful stent implantation, acute complications, angiographic restenosis after 6 months and major cardiac events (death, myocardial infarction, target vessel revascularization) during follow-up were assessed. The success rate of stent implantation was 94%. One patient died after an emergency bypass operation and one patient suffered a subacute stent thrombosis, which was successfully treated with re-percutaneous transluminal coronary angioplasty (PTCA). There were no Q- or non-Q myocardial infarctions. Clinical follow-up was carried out in 56 patients (97%) and 57 vessels were assessed by angiography (93%). Mean length of the follow-up period was 6.8+/-2.3 months. During the 6 months' follow-up period, one patient died, two patients suffered an acute non-Q myocardial infarction and eight patients had revascularization of the target vessel. Major cardiac event rate for all patients where stent implantation was intended was 23%. Angina CCS class declined from 3.0+/-0.9 to 1.1+/-0.8 (p < 0.01) before PTCA to follow-up. Overall restenosis rate was 28%. In 14 lesions with a stented segment length of <20 mm, the restenosis rate was 21%; in 31 lesions with a stented segment length > or =20 and <30 mm, the restenosis rate was 26%; and in 13 lesions with a stented segment length of > or =30 mm, the restenosis rate was 42%. Although there was a high procedural success rate after implantation of the Freedom stent in long or tortuous lesions, problems with high restenosis rates in long lesions remain unresolved.

Kristensen SD, Baumgartner H, Casadei B, Drexler H, Eeckhout E, Filippatos G, Fox KA, Perk J, Pierard LA, Poldermans D, Schunkert H, Vardas PE, van der Wall EE, Fox K, Bax JJ. · Aarhus University Hospital, Skejby, Aarhus, Denmark. · J Am Coll Cardiol. · Pubmed #19055996 No free full text.

This publication has no abstract.