Johann Auer

Arterial stiffness, wave reflections, and the risk of coronary artery disease.

Background—Increased arterial stiffness, determined invasively, has been shown to predict a higher risk of coronary atherosclerosis. However, invasive techniques are of limited value for screening and risk stratification in larger patient groups. Methods and Results—We prospectively enrolled 465 consecutive, symptomatic men undergoing coronary angiography for the assessment of suspected coronary artery disease. Arterial stiffness and wave reflections were quantified noninvasively using applanation tonometry of the radial artery with a validated transfer function to generate the corresponding ascending aortic pressure waveform. Augmented pressure (AP) was defined as the difference between the second and the first systolic peak, and augmentation index (AIx) was AP expressed as a percentage of the pulse pressure. In univariate analysis, a higher AIx was associated with an increased risk for coronary artery disease (OR, 4.06 for the difference between the first and the fourth quartile [1.72 to 9.57; P <0.01]). In multivariate analysis, after controlling for age, height, presence of hypertension, HDL cholesterol, and medications, the association with coronary artery disease risk remained significant (OR, 6.91; P <0.05). The results were exclusively driven by an increase in risk with premature vessel stiffening in the younger patient group (up to 60 years of age), with an unadjusted OR between AIx quartiles I and IV of 8.25 (P <0.01) and a multiple-adjusted OR between these quartiles of 16.81 (P <0.05). Conclusions—AIx and AP, noninvasively determined manifestations of arterial stiffening and increased wave reflections, are strong, independent risk markers for premature coronary artery disease.

Prolonged mechanical systole and increased arterial wave reflections in diastolic dysfunction

Objective: To evaluate whether left ventricular ejection time indexed for heart rate (left ventricular ejection time index (LVETI)) and arterial wave reflections (augmented pressure (AP)) are increased in patients with diastolic dysfunction (DD). Design: Prospective observational study. Setting: University teaching hospital providing primary and tertiary care. Subjects: 235 consecutive patients undergoing left heart catheterisation were categorised as having definite DD, possible DD or no DD (controls) on the basis of their left ventricular end diastolic pressures and N-terminal brain natriuretic peptide concentrations. Main outcome measures: LVETI and AP were prospectively assessed non-invasively by radial applanation tonometry. In addition, all patients underwent comprehensive echocardiography, including tissue Doppler imaging of mitral annulus velocity in early diastole (E′). Results: LVETI was longer in patients with definite DD than in patients with possible DD and in controls (433.6 (SD 17.2), 425.9 (17.9) and 414.3 (13.6) ms, respectively, p < 0.000001). Arterial wave reflections were higher in definite DD than in possible DD and control groups (AP was 19.4 (SD 8.9), 15.2 (8.0) and 10.7 (6.8) mm Hg, respectively, p < 0.000001). In receiver operating characteristic curve analysis, LVETI detected DD as well as echocardiography (E:E′). Area under the curve for LVETI to differentiate patients with definite DD from normal controls was 0.81 (95% CI 0.72 to 0.89, p < 0.0001). In multivariable logistic regression analysis, LVETI added significant independent power to clinical and echocardiographic variables for prediction of DD. Conclusions: Mechanical systole is prolonged and arterial wave reflections are increased in most patients with DD. Rapid non-invasive assessment of these parameters may aid in confirming or excluding DD.

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.

Pheochromocytoma crisis presenting with shock and tako-tsubo-like cardiomyopathy

Pheochromocytoma usually presents with hypertension but it may also be an unusual aetiology of cardiogenic shock in order to catecholamine induced myocardial dysfunction. We report the devastating course of a patient with tako-tsubo like apical cardiomyopathy during pheocytoma crisis who presented with classical transient left ventricular apical ballooning 6 months before.

Serum neopterin and activity of coronary artery disease.

Inflammation plays a key role in the pathogenesis of atherosclerosis. In coronary artery disease (CAD), the release of different cytokines activates cellular defense. Infiltration of neutrophils and monocytes/macrophages is detected in the vessel wall in patients with CAD. Macrophages activated by interferon gamma synthesize metalloproteinases and neopterin, a pteridin derivative that has been used as an immune marker. To determine neopterin levels in patients with chronic CAD and acute coronary syndromes, the authors studied 116 subjects: 1) 25 consecutive patients (18 men, 7 women; mean age 68.5 +/- 14.3, range 40 to 86 years) with unstable angina or acute myocardial infarction (AMI); 2) 31 consecutive patients (25 men, 6 women; mean age 64 +/- 12.7, range 47 to 83 years) with signs and symptoms of clinically stable CAD; and 3) 60 consecutive healthy blood donors (38 men, 22 women; mean age 54.4 +/- 6.23, range 44 to 66 years). Neopterin levels were determined with a commercially available enzyme-linked immunosorbent assay method. In patients with unstable angina and AMI before thrombolytic therapy, neopterin levels were not significantly different from levels in patients with stable CAD (5.97 +/- 1.4 versus 7.84 +/- 3.56 nmol/L; P = 0.15). Neopterin levels in both patient groups did not significantly differ from levels in control subjects (P > 0.1). Neopterin levels in patients with unstable angina and AMI were measured four times during a 72-hour period. The lowest value was observed at baseline and differed significantly from values after 72 hours (P < 0.001; 5.97 +/- 1.4 versus 9.25 +/- 2.36). Neopterin levels after 72 hours were also significantly different from initial values in patients with stable CAD (P < 0.001). There was no correlation between neopterin and creatine kinase (CK) levels, CK-MB isoenzyme, or troponin I as markers for the extent of the myocardial injury during the observation period. These data do not support previous reports of higher baseline levels of serum neopterin in patients with unstable angina or AMI compared with patients with chronic, stable CAD and healthy controls. Neopterin as a marker of macrophage activation is significantly increased in patients with AMI and unstable angina shortly after the onset of symptoms (after a period of 72 hours), supporting the hypothesis of monocyte and macrophage activation in patients with an acute coronary syndrome or AMI.

Spontaneous coronary artery dissection involving the left main stem: assessment by intravascular ultrasound

This case report describes the devastating consequences of spontaneous coronary dissection in a 36 year old female patient who otherwise had a normal coronary arteriogram. Intravascular ultrasound showed coronary artery dissection and intramural haematoma at the left main stem coronary artery. Acute coronary syndrome developed and subsequently surgical revascularisation was performed successfully.

Plasma concentrations of D-dimer predict mortality in acute type A aortic dissection

Acute type A aortic dissection is a relatively uncommon, although potentially life threatening, disease. Given the high mortality, predictive tools to identify patients at increased risk of death are needed to assist clinicians in optimal treatment. Known prognostic parameters are: age > 70 years; abrupt onset of chest pain; hypotension, shock, or tamponade; renal failure at presentation; pulse deficit; and abnormal ECG, particularly ST segment elevation.1 Recently we found that concentrations of D-dimer, a degradation product of cross linked fibrin, were raised in all cases of acute aortic dissection and, therefore, normal D-dimer concentrations can be used to rule out the disease.2 Our results were subsequently confirmed by others.3 However, owing to small patient numbers in both studies, no firm conclusions about the prognostic significance of absolute D-dimer concentrations can be drawn. We measured plasma concentrations of D-dimer in 27 patients with acute type A dissection of the …

Muscle- and skeletal-related side-effects of statins: tip of the iceberg?

The clinical spectrum of muscle- and skeletal-related side-effects of statins includes varied myalgias and weakness, an asymptomatic increase in the concentration of creatine kinase and other biochemical parameters, myositis and rhabdomyolysis. Currently, there is no consensus on the definition of ‘statin myopathy’. Evidence suggests that deleterious effects may also be associated with the volume or dosage of structured exercise and/or the intensity of physical activity. Moreover, non-muscle adverse effects on the joints and tendons are often overlooked and underemphasized. The incidence of myopathy associated with statin treatment typically ranges between 1.5% and 10%. Few data are available regarding the prevalence of muscle- related symptoms associated with different statins and the distribution of affected muscles. Furthermore, discrepancies between clinical trials and daily practice may emanate, in part, because of inconsistent definitions or exclusion criteria. The pathophysiology of statin-related myopathy is incompletely understood. A dose-dependent and proapoptotic effect, direct effects on mitochondria, drug interactions and genetic factors, or combinations thereof, may be involved. Recently, a rare immune-mediated myopathy triggered by statin use has been described. With the increasing number of patients treated with statins and with more patients being prescribed high doses of potent statins to achieve low-density lipoprotein targets, muscle-related side-effects will become more prevalent. Currently, the only effective treatment is the discontinuation of statin use. Further research is needed to develop alternative LDL-lowering drugs when statins are not well tolerated and to establish additional effective strategies to manage lipids and lipoproteins.

C-Reactive Protein in Patients With Acute Myocardial Infarction

To the Editor: Sano et al1 investigated the relation between lesion morphology as seen under preintervention intravascular ultrasound and C-reactive protein (CRP) in the acute phase of acute myocardial infarction (AMI). They found that elevated CRP concentrations may be related to the presence of ruptured plaque and concluded that in the setting of AMI, elevated CRP levels may reflect the inflammatory activity of a ruptured plaque. The presence of inflammatory infiltrates in unstable coronary plaques suggests that inflammatory processes may contribute to the pathogenesis of acute coronary syndromes.2 In patients with acute coronary syndromes, coronary atherosclerotic plaques are characterized by the presence of macrophages and, to a …

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.