Osteoprotegerin concentrations in patients with suspected reversible myocardial ischemia: observations from the Akershus Cardiac Examination (ACE) 1 Study.

Increased circulating osteoprotegerin (OPG) levels have been associated with the prevalence and severity of coronary artery disease and the risk of cardiovascular death. OPG is a cytokine of the tumor necrosis factor receptor superfamily and is expressed in various cell types in the body, including osteoblasts, inflammatory cells, vascular smooth muscle cells/endothelial cells and cardiomyocytes. The main sources determining OPG levels in the circulation however, are not well understood, and whether reversible myocardial ischemia influences OPG levels are not known. Accordingly, OPG levels were measured in 198 patients referred for exercise stress testing and myocardial perfusion imaging (MPI). In addition OPG levels were measured in 8 healthy control subjects performing a maximal bicycle stress test. Plasma samples were collected before, immediately after, 1.5h and 4.5h after exercise stress testing with MPI. OPG levels at baseline were not different in patient with reversible myocardial ischemia (n=19) and patients without reversible ischemia (n=179) (4.7 [3.6-5.5]pmol/L vs. 4.3 [3.4-5.2]pmol/L, p=0.21), and there was an increase in OPG levels immediately after exercise regardless of whether or not the patient had reversible ischemia on MPI (absolute increase: 0.2 [0-0.55]pmol/L vs. 0.3 [0-0.5]pmol/L, p=0.72). OPG levels also increased immediately after stress in the 8 control subjects (3.5 (3.2-3.8)pmol/L at baseline to 3.8 (3.5-4.7), p=0.008). In conclusion, OPG levels increase acutely during exercise stress testing, but this increase is likely caused by mechanisms other than myocardial ischemia.

Troponin I measured by a high-sensitivity assay in patients with suspected reversible myocardial ischemia: data from the Akershus Cardiac Examination (ACE) 1 study.

BACKGROUND: Whether cardiac troponin concentrations are increased by reversible myocardial ischemia is controversial. Differences in the structure of cardiac troponin I (cTnI) and cTnT may have implications for diagnostic utility. METHODS: cTnI was measured with a prototype high-sensitivity (hs) assay in 198 patients referred for myocardial perfusion imaging (MPI) before exercise stress testing, immediately after, and 1.5 and 4.5 h later. We categorized patients according to MPI results and compared hs-cTnI concentrations with hs-cTnT concentrations. RESULTS: Baseline hs-cTnI was higher in patients with reversible myocardial ischemia (n = 19) vs the other patients (n = 179): median 4.4 (quartiles 1-3: 2.3-7.1) vs 2.5 (1.4-4.3) ng/L, P = 0.003. Baseline hs-cTnI and hs-cTnT concentrations were correlated (r = 0.46, P < 0.001) and the areas under the ROC curve for hs-cTnI and hs-cTnT in diagnosing reversible ischemia were similar: 0.71 vs 0.69, P = 0.77. Whereas hs-cTnI increased immediately after exercise (P < 0.001 vs baseline measurements) in patients without ischemia, it increased after 4.5 h in patients with reversible ischemia (P = 0.01). The increment in hs-cTnI concentrations was comparable between groups; thus, measuring hs-cTnI after exercise stress testing did not improve diagnostic accuracy over baseline measurements, and hs-cTnI concentrations were not found to be associated with reversible myocardial ischemia in multivariate analysis. By linear regression analysis, age, male sex, history of hypertension, angiotensin-converting enzyme inhibitor use, and lower left ventricular ejection fraction were associated with higher baseline hs-cTnI concentrations. CONCLUSIONS: In patients referred to MPI, hs-cTnI concentrations were not closely associated with reversible myocardial ischemia, but rather were influenced by variables associated with structural alterations of the myocardium.

Diagnostic utility of a single-epitope sandwich B-type natriuretic peptide assay in stable coronary artery disease: data from the Akershus Cardiac Examination (ACE) 1 Study.

OBJECTIVES: To assess the merit of a novel single-epitope sandwich (SES) assay specific to the stable part of BNP in patients with reversible myocardial ischemia as post-translational modifications of BNP may influence assay performance. DESIGN AND METHODS: We measured BNP concentration by a conventional assay and the SES-BNP assay in 198 patients referred for myocardial perfusion imaging (MPI). BNP concentration was determined before and immediately after exercise stress testing, and 1.5 and 4.5h later. Patients were categorized according to MPI results. RESULTS: BNP concentration was higher with both assays at all time points in patients with reversible myocardial ischemia (n=19) compared to the other patients (n=179). Measuring BNP after stress testing or calculating the changes in BNP concentration did not improve diagnostic accuracy compared to baseline measurements: SES-BNP: AUC 0.71 (95% CI 0.58-0.84) vs. conventional BNP: 0.71 (0.59-0.83), p=0.96. By linear regression analysis, reversible myocardial ischemia was significantly associated with baseline SES-BNP concentration (p=0.043), but not with measurements by the conventional assay (p=0.089). In multivariate logistic regression models, only baseline measurement with the SES-BNP assay was significantly associated with reversible myocardial ischemia: odds ratio [logarithmical transformed BNP] 2.00 (95% CI 1.16-3.47), p=0.013. The SES-BNP assay, but not the conventional BNP assay, reclassified a significant proportion of the patients towards their correct category on top of the best clinical model of our data set: NRI=0.47, p=0.04. CONCLUSIONS: The SES-BNP assay was significantly associated with reversible myocardial ischemia as assessed by several statistical indices, while a conventional BNP assay was not.

Cardiac troponin T levels and exercise stress testing in patients with suspected coronary artery disease: the Akershus Cardiac Examination (ACE) 1 study.

Whether reversible ischaemia in patients referred for exercise stress testing and MPI (myocardial perfusion imaging) is associated with changes in circulating cTn (cardiac troponin) levels is controversial. We measured cTnT with a sensitive assay before, immediately after peak exercise and 1.5 and 4.5 h after exercise stress testing in 198 patients referred for MPI. In total, 19 patients were classified as having reversible myocardial ischaemia. cTnT levels were significantly higher in patients with reversible myocardial ischaemia on MPI at baseline, at peak exercise and after 1.5 h, but not at 4.5 h post-exercise. In patients with reversible ischaemia on MPI, cTnT levels did not change significantly after exercise stress testing [11.1 (5.2-14.9) ng/l at baseline compared with 10.5 (7.2-16.3) ng/l at 4.5 h post-exercise, P=0.27; values are medians (interquartile range)]. Conversely, cTnT levels increased significantly during testing in patients without reversible myocardial ischaemia [5.4 (3.0-9.0) ng/l at baseline compared with 7.5 (4.6-12.4) ng/l, P<0.001]. In conclusion, baseline cTnT levels are higher in patients with MPI evidence of reversible myocardial ischaemia than those without reversible ischaemia. However, although cTnT levels increase during exercise stress testing in patients without evidence of reversible ischaemia, this response appears to be blunted in patients with evidence of reversible ischaemia. Mechanisms other than reversible myocardial ischaemia may play a role for acute exercise-induced increases in circulating cTnT levels.

[A 60-year-old woman with asthenia and dyspnoea]. / En 60 år gammel kvinne med asteni og dyspné.

Coronary artery aneurysms are uncommon and the prevalence in patients undergoing coronary artery angiography is 1.5-4.9%. The most common cause of coronary artery aneurysm is arteriosclerosis, followed by Kawasaki disease, periarteritis nodosa, systemic lupus erythematosus, syphilis, rheumatic fever, congenital heart disease and trauma. Most coronary aneurysms remain asymptomatic. Patients may present symptoms of angina or myocardial infarction due to thrombosis within the aneurysm. This would lead to occlusion of the coronary artery or to distal thromboembolisms. There is no consensus on how to manage coronary artery aneurysms. Medical therapies include aspirin as well as warfarin. Surgery may be performed in patients with a large aneurysm, i.e. when the risk of rupture or thrombosis is high. We present a 60-year-old female patient with symptoms of a transient ischaemic attack followed by a period of fever, nausea, vomiting and ecchymoses on the lower extremity. Transthoracic and transoesophageal echocardiography was suggestive of a tumour located at the basis of the lateral wall of the right atrium. Heart surgery revealed, however, a large right coronary aneurysm and an atrial septum defect of the secundum type.