[Troponins as biomarkers for myocardial injury and myocardial infarction]. / Troponine als Biomarker bei Myokardschaden und Myokardinfarkt.

Elevation of cardiac troponins above the 99th percentile of a healthy reference population is established as a marker for myocardial cell damage and is crucial for the diagnosis of myocardial infarction. In addition, corresponding clinical evidence of acute myocardial ischemia i.e. symptoms, changes in the electrocardiogram (ECG), wall motion abnormalities or suggestive angiographic findings are required for the diagnosis of myocardial infarction. Using modern highly sensitive assays myocardial infarction can be detected more frequently and earlier. On the other hand myocardial infarction can be ruled out with a higher diagnostic accuracy. Cardiac troponins are specific for myocardial cell damage but not for myocardial infarction and can be elevated in numerous other disease states. In these cases myocardial injury can be diagnosed independently of myocardial ischemia. Typical dynamics with rise and fall of troponin levels can distinguish acute myocardial injury (e. g. pericarditis/myocarditis and pulmonary embolism) from chronic myocardial injury (e. g. cardiomyopathy). Clinically, highly sensitive troponin assays are currently recommended in addition to the 0/3 h and 0/1 h algorithms for rapid inclusion or exclusion of myocardial infarction.

[Acute coronary syndrome with ST-elevation]. / Akutes Koronarsyndrom mit ST­Strecken-Hebung.

The current guidelines of the European Society of Cardiology have up-dated and confirmed the role of a primary percutaneous coronary intervention (PCI) as the preferred reperfusion therapy in patients with acute coronary syndrome and ST-elevation. The establishment of regional network structures for implementation of this reperfusion strategy is recommended and described. Primary PCI should preferably be carried out via the transradial route and should include the implantation of modern drug-eluting stents. In most cases of coronary multivessel disease, primary PCI should be limited to the treatment of the infarcted artery. Routine mechanical thrombus aspiration during primary PCI is no longer recommended. Recommendations for a specific anti-thrombotic and secondary prophylactic medication after primary PCI are highlighted.

[Acute coronary syndrome without ST-elevation (NSTE-ACS)]. / Akutes Koronarsyndrom ohne ST-Hebung (NSTE-ACS).

The timing of an invasive diagnosis and treatment strategy in patients with an acute coronary syndrome without ST-elevation (NSTE-ACS) depends on the patient's risk profile. In addition to the clinical symptoms, ST/T alterations in the resting ECG as well as an increase and kinetics of troponin are of crucial importance in this setting. For the majority of patients the highly sensitive troponin enables a rapid rule in or rule out strategy of a non-ST-segment elevation myocardial infarction (NSTEMI) with a 0/3 h algorithm. An even faster 0/1 h algorithm is increasingly being used; however, troponin only helps to identify patients with NSTEMI. Troponin-negative patients can still suffer from unstable angina pectoris. A dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASS) and an ADP receptor antagonist should be initiated in the acute phase and continued for 12 months, irrespective of the initial treatment strategy, e.g. percutaneous coronary intervention (PCI), bypass surgery or conservative treatment. In patients with a high bleeding risk a duration of 6 months only may be considered, whereas in patients with a high risk of ischemia the DAPT might be prolonged for up to 36 months.

The predictive value of different equations for estimation of glomerular filtration rate in patients with coronary artery disease - Results from the AtheroGene study.

BACKGROUND: Impaired renal function leads to dramatically increased risk for the development and progression of coronary artery disease (CAD). Therefore we aimed to assess the predictive value of different equations for estimated glomerular filtration rate (eGFR) in CAD-patients. METHODS: From the AtheroGene study 2135 patients were included. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (4MDRD) equation for serum creatinine (sCr), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for sCr and cystatin C (CysC) each alone, and in combination (CysC/sCr). eGFR was assessed regarding the combined outcome of cardiovascular death and non-fatal myocardial infarction and regarding complex CAD represented by a SYNTAX score ≥23. Median follow-up was 4.3years. RESULTS: Only the CKD-EPI equation using CysC could differentiate between eGFR >90ml/min/1.73m(2) vs. eGFR 60-90ml/min/1.73m(2) according to the occurrence of an endpoint event (log-rank test p=0.009). In the Cox regression analysis only eGFR calculated by CKD-EPI equation for CysC (Hazard ratio per 1 standard deviation (HR) 1.27 (95% CI 1.07-1.50); p=0.007) and for CysC/sCr (HR 1.22 (95% CI 1.02-1.46); p=0.026) were predictive regarding the outcome after adjustment for cardiovascular risk factors and Nt-proBNP. Furthermore, only eGFR calculated by CKD-EPI equation for CysC (odds ratio (OR) 1.57 (95% CI 1.36-1.78); p<0.001) and for CysC/sCr (OR 1.32 (95% CI 1.13-1.53); p<0.001) were significantly associated with a SYNTAX score ≥23. CONCLUSION: In patients with CAD the CKD-EPI equation for CysC and for CysC/sCr provided the best predictive value regarding the prognosis and the severity of CAD.

Complete AV block in Lyme carditis: an important differential diagnosis.

Lyme disease is a tick-borne spirochetal infection that may affect the heart. Cardiac manifestations include conduction disturbances and other pathologies of the heart. We report on a 37-year old male, who was admitted to the emergency department because of dizziness and generalized tiredness. Physical examination and the initial laboratory values revealed no abnormalities. The patient's electrocardiogram on admission revealed newly diagnosed bradycardia due to atrioventricular heart block. The ventricular heart rate was 35/min. The patient was admitted to the ICU. Lyme serology and Western blot were positive for Borrelia antibodies. After institution of antibiotic therapy with ceftriaxone, atrioventricular heart block resolved rapidly. We therefore have to assume that in this patient Lyme carditis was the cause of third-degree AV block.

Activated thrombin activatable fibrinolysis inhibitor levels are associated with the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study.

BACKGROUND: Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis. Results on the association between TAFI levels and the risk of coronary artery disease (CAD) are inconsistent. OBJECTIVES: We investigated the association between TAFI levels and the risk of cardiovascular events in CAD. PATIENTS/METHODS: 1668 individuals with angiographically proven CAD at baseline were followed for a median of 2.3 years, as part of the prospective AtheroGene cohort. Fifty-six deaths from cardiovascular (CV) causes and 35 non-fatal CV events were observed. RESULTS: At baseline, three TAFI measurements were available: one evaluating the total amount of TAFI (t-TAFI), one measuring the TAFIa/TAFIai amount, and the last the released activated peptide (TAFI-AP). TAFIa/TAFIai levels were associated with increased risk of CV death [hazard ratio (HR) for one tertile increase, 2.38 (1.56-3.63); P < 10(-4)]. This association remained significant after adjustment for conventional risk factors, CRP levels, white blood count and markers of thrombin generation and fibrinolysis [HR = 1.69 (1.07-2.67); P = 0.01]. In addition, CPB2 gene polymorphisms explained 12%, 6%, and 3% of t-TAFI, TAFIa/TAFIai and TAFI-AP levels, respectively, but none was associated with CV events. CONCLUSIONS: The amount of activated TAFI, measured by TAFIa/TAFIai ELISA, but not of the t-TAFI is independently associated with the risk of CV death.

Polymorphisms of the tumor necrosis factor-alpha (TNF) and the TNF-alpha converting enzyme (TACE/ADAM17) genes in relation to cardiovascular mortality: the AtheroGene study.

Tumor necrosis factor (TNF) is a major cytokine involved in inflammatory reaction and a mortality predictor in patients with coronary artery disease (CAD). Plasma levels of soluble TNF (sTNF) depend on the rate of its synthesis but also on its shedding from cell surface, a mechanism mainly regulated by the TNF alpha converting enzyme (TACE or ADAM17). We investigated the relationship between ADAM17 and TNF polymorphisms, circulating levels of shed ADAM17 substrates (sTNF, sTNFR1 and sTNFR2), and cardiovascular risk in a prospective cohort of CAD patients. Five tag single-nucleotide polymorphisms (SNPs) of the ADAM17 gene as well as four previously described TNF SNPs were genotyped in the Atherogene Study composed of 1,400 CAD patients among which 136 died from a cardiovascular (CV) cause. sTNF, sTNFR1, and sTNFR2 concentrations were all significantly elevated in patients with future CV death, independently of other clinical/biological variables. While none of the studied TNF SNPs was associated with sTNF, sTNFR1, nor sTNFR2 levels, the ADAM17 -154A allele was found associated with a 14% increase of sTNF levels as compared to the -154C allele (p = 0.0066). Moreover, individuals carrying the 747Leu allele displayed a borderline increased risk of future cardiovascular death [odds ratio, 2.06 (1.05-4.04), p = 0.03]. These results suggest a role of ADAM17 in the regulation of sTNF plasma levels and identifies ADAM17 gene as a candidate for CAD. Tumor necrosis factor (TNF) is a major cytokine involved in inflammatory reaction and a mortality predictor in patients with coronary artery disease (CAD). We have studied the association of ADAM17 and TNF polymorphisms with circulating levels of shed ADAM17 substrates (sTNF, sTNFR1 and sTNFR2) and with cardiovascular risk in a large population of individuals with CAD (Atherogene Study, n = 1,400). Two newly identified polymorphisms, obtained by a systematic sequencing of the ADAM17 gene, C-154A and Ser747leu, slightly influence respectively sTNF plasma levels and the risk of cardiovascular death.

Prognostic value of plasma tissue factor and tissue factor pathway inhibitor for cardiovascular death in patients with coronary artery disease: the AtheroGene study.

BACKGROUND: Tissue factor (TF) and its specific inhibitor, tissue factor pathway inhibitor (TFPI), are important contributors to the initiation of the coagulation process. OBJECTIVES: To compare plasma levels of soluble TF (sTF) and free-TFPI (f-TFPI) between patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) and to assess the impact of the two variables on long-term prognosis. PATIENTS/METHODS: Patients with SAPs (n = 1146) and acute coronary syndrome (n = 523) from the AtheroGene study were included and followed for 2.3 years. Because of the strong impact of unfractionated heparin (UFH) on f-TFPI levels, but not on sTF levels, patients having received UFH before blood drawing were excluded from the analyses on f-TFPI (n = 226). RESULTS: On admission, no significant differences in sTF levels were observed between SAP and ACS patients. By comparison to patients with stable angina, f-TFPI levels significantly increased in patients with acute unstable angina and further increased in patients presenting with non-ST-elevation myocardial infarction and ST-elevation myocardial infarction (P < 10(-4)). Among the 1669 individuals with a coronary artery disease, 56 died from a cardiovascular cause. In prospective analyses, high sTF levels were independently associated with an increased risk of cardiovascular death in individuals with ACS (fully adjusted hazard ratio associated with one quartile increase = 2.06; 95% confidence interval 1.24-3.45; P = 0.006) but not in those with SAP (hazard ratio = 1.07; 95% confidence interval 0.78-1.46; P = 0.67). In SAP and ACS patients, high f-TFPI levels were not independently associated with an increased risk of cardiovascular death. CONCLUSIONS: Plasma sTF levels were predictive of cardiovascular mortality in individuals with ACS, whereas f-TFPI levels were associated with the severity of myocardial damage on admission but were not independently related to outcome.

Long-term cost-effectiveness of clopidogrel in patients with acute coronary syndrome without ST-segment elevation in Germany.

Patients with acute coronary syndrome without ST-segment elevation receiving clopidogrel in addition to acetylsalicylic acid (ASA) showed a 20% risk reduction in comparison to patients receiving ASA monotherapy (CURE trial). Economic models for assessing the impact on costs exist for several countries but not for Germany on a long-term basis. The objective of this model adaptation is to assess the long-term economic impact of clopidogrel taken in addition to ASA in Germany. A Markov model with six states [at risk, first year with stroke, following years with stroke, first year with new myocardial infarction (MI), following years with MI, and death] was adapted for Germany. Model outcome was life-years saved. Effects of 1-year treatment were calculated based on the CURE trial. Resource use for the different health states was based on published data, which included costs for drugs, outpatient care, hospitalization, rehabilitation and nursing. Risk data for MI and stroke were based on Swedish data and validated for the German adaptation. The model calculates lifetime costs and survival length. Costs were estimated from the payers' perspective. A series of one-way sensitivity analyses was conducted (follow-up costs, discount rates). The Markov analysis predicts a survival of 8.89years in the placebo treatment group and 9.02 years in the clopidogrel treatment group. The cumulated costs were euro 8,548 and euro 8,953, respectively. The incremental cost-effectiveness ratio (ICER) was euro 3,113 for each life-year saved. The model was robust regarding variations in key parameters in the sensitivity analysis, resulting in a range of ICER from euro 1,338 to euro 9,322. Our results are in line with the results for other healthcare systems. Adding clopidogrel to ASA for patients with acute coronary syndrome without ST-segment elevation generated an additional life-year saved at a comparably low value of euro 3,113. One-year treatment with clopidogrel is a cost-effective treatment option in patients with acute coronary syndrome from the perspective of a third-party payer in Germany.

Haemostatic factors and the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study.

OBJECTIVE: To get a better insight into the role of hemostasis in coronary artery disease (CAD), we assessed the impact of von Willebrand factor (vWF), fibrinogen, thrombin-antithrombin (TAT) complexes, D-dimers, and plasmin-antiplasmin (PAP) complexes on the risk of cardiovascular event in a prospective cohort of CAD patients. METHODS AND RESULTS: The prospective Atherogene cohort includes 1057 individuals with an angiographically proven coronary artery disease at baseline. After a median follow-up of 6.6 years, 135 individuals died from a cardiovascular cause and 97 had a nonfatal cardiovascular event. Higher levels of all 5 hemostatic markers at baseline were associated with an increased risk of cardiovascular death, but not of nonfatal event. Except for vWF, these associations remained significant after adjustment for conventional cardiovascular risk factors and C-reactive protein (CRP) levels (P for trend according to increasing tertiles=0.20, 0.011, 0.026, 0.019, and 0.01 for vWF, fibrinogen, TAT, D-Dimer, and PAP, respectively). When including the 5 hemostatic markers in a stepwise Cox regression analysis where conventional risk factors and CRP were forced into the model, fibrinogen and D-dimers remained independently associated with the risk of cardiovascular death. Adjusted hazard ratios (95% CI) associated with one SD increase of fibrinogen and D-dimers were 1.27 (1.04 to 1.55) and 1.29 (1.09 to 1.53), respectively. CONCLUSIONS: In patients with coronary artery disease, fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death. Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease.

[Cardiovascular secondary prevention]. / Kardiovaskuläre Sekundärprävention.

Cardiovascular secondary prevention plays a fundamental role due to the rising average age of the population. The reorganization of the health care system is also becoming more important. Especially the needs of high-risk patients have to be prioritized. A change of habits (e. g. abnegation of nicotine, change in eating habits, obtaining a BMI<25) is the basis of preventive measures in order to maximize the effectivity of drug therapy. Here the application of statins takes center stage (if there are no contraindications) which minimizes the risk of coronary incidences by 30%. In case of high lipid blood level, fibrates have to be applied at a low level of HDL-cholesterol and omega-3 fatty acids at high values of triglycerides. Omega-3 fatty acids must be given in the form of 1 g ethyl esters of EPA and DHA, otherwise a significant reduction of fatal cardiovascular incidences cannot be proven. Recently ACE inhibitors have gained in importance because of their ability to reduce the formation of plaques. Furthermore beta-blockers and aspirin can be applied for therapeutic measures, whereas different periods of treatment are recommended by the guidelines. With the aid of algorithms it is possible to specify the risk of experiencing a second myocardial infarction.

Revascularisation of a giant coronary artery aneurysm in suspected incomplete Kawasaki-disease.

Kawasaki disease leads to typical vascular complications in up to 20 % of untreated cases. We describe a 47-year-old patient with coronary vessel disease, involving the right coronary artery with a huge aneurysmatic dilatation, suspicious for an incomplete form of Kawasaki disease. We found little information about the surgical treatment and postoperative course of this disease in adults. Typically, these infrequent patients present with acute myocardial infarction and require interdisciplinary decision-making.

[Carotid stenosis concomitant to coronary artery disease]. / Karotisstenose als Zusatzbefund bei koronarer Herzkrankheit.

Carotid stenosis is frequent in patients with coronary artery disease (CAD). In the literature, 9-28% of patients with CAD have additional carotid artery stenosis, predictors of which are advanced age, smoking, diabetes mellitus, arterial hypertension, coronary multivessel disease, and peripheral arterial disease. Moreover, patients with unstable coronary syndromes and those with elevated inflammatory markers such as C-reactive protein or fibrinogen more often have concomitant CAD and carotid artery stenosis. The long-term prognosis of these patients is worse than with CAD only. Therefore, patients with CAD should be screened for additional carotid artery stenosis, especially if coronary artery bypass grafting is planned. Continuous wave Doppler sonography and color-coded duplex sonography are suitable methods to screen for carotid artery stenosis.