Gudrun Lamm

Genetic Polymorphisms in Cytokine and Adhesion Molecule Genes in Coronary Artery Disease

Both inflammation and genetics play an important role in the pathogenesis of atherosclerosis and coronary artery disease. Epidemiological studies have investigated the association between coronary artery disease (CAD) and gene polymorphisms of the inflammatory molecules tumor necrosis factors (TNF) α and β, transforming growth factors (TGF) β-1 and β-2, interleukin (IL)-1 and its receptor antagonist (IL-1ra), CD 14 (the receptor for lipopolysaccharide), P- and E-selectins, and platelet endothelial cell adhesion molecule (PECAM)-1.Current evidence suggests that the TNF polymorphisms explored so far are not linked to CAD. The majority of studies conducted showed no significant association between TGFβ-1 and coronary atherosclerosis, but the data currently available are somewhat controversial. Some polymorphisms may increase the risk of myocardial infarction (MI) within specific ethnic groups or in certain populations. The association between the IL-1 system and atherosclerosis is complex and may vary as a result of a number of factors, such as stage of disease, clinical phenotype, and possibly population characteristics.The E-selectin gene (SELE) Arg128, 98T, and Phe554 alleles may increase the risk of atherosclerosis, but not necessarily the risk of MI. This association seems to be more pronounced in younger patients. The PECAM1 Leu125Val and Ser563Asn polymorphisms may increase the risk of atherosclerosis but not necessarily of MI. This association may be especially important in patients with a low risk for developing atherosclerosis.Current data indicate that screening for CD14-260C/T genotypes is unlikely to be a useful tool for risk assessment and it remains unclear whether CD14 polymorphisms significantly increase the risk of MI.The associations between candidate gene polymorphisms and CAD are complex as a consequence of pleiotropy, variations with age, selection due to the high lethality of the disease, and interactions with other genes and environmental factors. Nonetheless, although the current data is preliminary and partly conflicting, it does provide some evidence that alterations in the genetics of the inflammatory system may modify the risk of CAD.

Ability of neuron-specific enolase to predict survival to hospital discharge after successful cardiopulmonary resuscitation.

BACKGROUND Accurate prediction of survival to hospital discharge in patients who achieve return of spontaneous circulation after cardiopulmonary resuscitation (CPR) has significant ethical and socioeconomic implications. We investigated the prognostic performance of serum neuron-specific enolase (NSE), a biochemical marker of ischemic brain injury, after successful CPR. METHODS In-hospital or out-of-hospital patients with nontraumatic normothermic cardiac arrest who achieved return of spontaneous circulation (ROSC) following at least 5 minutes of CPR were eligible. Neuron-specific enolase levels were assessed immediately, 6 hours, 12 hours and 2 days after ROSC. Subjects were followed to death or hospital discharge. RESULTS Seventeen patients (7 men, 10 women) were enrolled during a 1-year period. Median (range) NSE levels in survivors and non-survivors respectively were as follows: immediately after ROSC: 14.0 microg/L (9.1-51.4 microg/L) versus 25.9 microg/L (10.2-57.5 microg/L); 6 hours after ROSC: 15.2 microg/L (9.7-30.8 microg/L) versus 25.6 microg/L (12.7-38.2 microg/L); 12 hours after ROSC: 14.0 microg/L (8.6-32.4 microg/L) versus 28.5 microg/L (11.0-50.7 microg/L); and 48 hours after ROSC: 13.1 microg/L (7.8-29.5 microg/L) versus 52.0 microg/L (29.1-254.0 microg/L). Non-survivors had significantly higher NSE levels 48 hours after ROSC than surivors (p = 0.04) and showed a trend toward higher values during the entire time course following ROSC. An NSE concentration of >30 microg/L 48 hours after ROSC predicted death with a high specificity (100%: 95% confidence interval [CI] 85%-100%), and a level of 29 microg/L or less at 48 hours predicted survival with a high specificity (100%: 95% CI 83%-100%). CONCLUSIONS Serum NSE levels may have clinical utility for the prediction of survival to hospital discharge in patients after ROSC following CPR over 5 minutes in duration. This study is small, and our results are limited by wide confidence intervals. Further research on ability of NSE to facilitate prediction and clinical decision-making after cardiac arrest is warranted.

Renal function is associated with risk of atrial fibrillation after cardiac surgery

BACKGROUND Atrial fibrillation (AF) frequently occurs after cardiac surgery and is responsible for increased morbidity and resource use. The aim of the present study was to evaluate the association of impaired renal function and the development of postoperative AF. METHODS AND RESULTS Patients undergoing elective cardiac surgery in the absence of significant left ventricular dysfunction (n=253; average age 65+/-11 years) were recruited to the present prospective study. Ninety-nine patients (39.1%) developed AF during the postoperative period. Creatinine clearance, estimated by the calculated glomerular filtration rate (GFR), was prospectively assessed to determine the association of baseline renal function and the development of postoperative AF. Baseline calculated GFR was assessed as a continuous and a categorical variable (normal: greater than 90 mL/min/1.73 m(2); mildly decreased: 60 mL/min/1.73 m(2) to 89 mL/min/1.73 m(2); and moderately to severely decreased: less than 60 mL/min/1.73 m(2)). Baseline creatinine clearance was 72+/-22.2 mL/min/1.73 m(2) and 78.8+/-23.5 mL/min/1.73 m(2) in patients with and without postoperative AF, respectively (P=0.02). There was an independent association between decreasing calculated GFR and the development of postoperative AF (OR for 10 mL decrease in calculated GFR: 1.21, 95% CI 1.02 to 1.39). In addition to calculated GFR, surgery for valvular heart disease (versus coronary artery bypass grafting [OR 2.23, 95% CI 1.09 to 3.14; P<0.01]), age (OR per 10-year increase in age 1.92, 1.18 to 2.59) and perioperative nonuse of beta-adrenergic blockers (OR 1.62, 95% CI 1.12 to 3.55; P<0.01) were identified as independent predictors of postoperative AF. CONCLUSIONS In the setting of cardiac surgery, impaired calculated GFR is associated with an increased risk for the development of postoperative AF. These data provide additional evidence supporting the association between renal dysfunction and adverse cardiovascular outcomes.

Bilateral intermittent claudication and the aorta.

With the increasing utilization of imaging strategies such as transesophageal echocardiography and magnetic resonance imaging, thrombi of the aorta are becoming increasingly recognized as sources of peripheral emboli. This report describes a 70-year-old man with bilateral intermittent claudication. Arteriography revealed occlusion of the distal part of the right tibialis posterior artery and the left tibialis anterior artery, but no occlusive atherosclerotic disease of the iliac, femoral, or popliteal artery. Additionally, no calcification of the vessels could be demonstrated. In contrast, a giant thrombus of the descending aorta was identified as the source of systemic thromboembolism. The patient was treated successfully with long-term anticoagulation.

What do small serum creatinine changes tell us about outcomes after acute myocardial infarction

Acute kidney injury (AKI), mostly defined as a rise in serum creatinine concentration of more than 0.5 mg/dl, is a common, serious, and potentially preventable complication of percutaneous coronary intervention and is associated with adverse outcomes including an increased risk of inhospital mortality. Recent data from the National Cardiovascular Data Registry/Cath-PCI registry including 985,737 consecutive patients undergoing percutaneous coronary intervention suggest that approximately 7% experienced AKI with a reported incidence of 3–19%. In patients undergoing primary percutaneous coronary intervention for acute myocardial infarction (AMI), AKI occurs more frequently with rates up to 20% depending on patient and procedural characteristics. However, varying definitions of AKI limit comparisons of AKI rates across different studies. Recently, most studies have adopted the Acute Kidney Injury Network (AKIN) criteria for definition and classification of AKI. Beyond the AKIN criteria for AKI, other classifications such as the risk, injury, failure, loss and end-stage kidney disease (RIFLE) and kidney disease: improving global outcomes (KDIGO) criteria are used to define AKI. Notably, even small increases in serum creatinine beyond AKI may be associated with adverse outcomes including increased hospital length of stay and excess. Acute kidney injury (AKI) is a serious and potentially preventable complication of percutaneous coronary intervention (PCI). Worsening renal function is associated with adverse outcomes including a higher rate of in-hospital mortality. In patients undergoing primary PCI for acute myocardial infarction (AMI), AKI occurs up to 20% of such individuals. Varying definitions of AKI limit comparisons of AKI rates across different studies. Additionally, even small increases in serum creatinine beyond lavels meeting AKI definitions may be associated with adverse outcomes including increased hospital length of stay.

Letter Regarding Article by Mandal et al, “Association of Anti–Heat Shock Protein 65 Antibodies With Development of Postoperative Atrial Fibrillation”

To the Editor: Mandal and colleagues1 report a novel association between anti–heat shock protein (HSP) 65 antibodies and the occurrence of postoperative atrial fibrillation (AF), indicating a possible role for antibody-mediated immune response in its pathogenesis. The authors report significant associations between postoperative AF and anti-HSP65 antibodies, a history of previous myocardial infarction, duration of cardiopulmonary bypass, number of distal anastomoses, and duration of ventilation by univariate analysis. In addition, lower levels of anti-HSP65 antibodies and grafting the left anterior descending artery seemed to be independently associated with a decreased occurrence of postoperative AF by multivariate analysis. The present study did …