Ane S. Teisner

Pre-existing IgG antibodies cross-reacting with the Fab region of infliximab predict efficacy and safety of infliximab therapy in inflammatory bowel disease.

Infliximab (IFX) is a chimeric murine/human anti‐TNF antibody (Ab) used for the treatment of Crohns disease (CD) and ulcerative colitis (UC). Loss of response is common and associated with development of anti‐IFX Abs during ongoing therapy. However, human anti‐murine immunoglobulin Abs are common and may cross‐react with the murine part of IFX.

Pregnancy Associated Plasma Protein A, a Novel, Quick, and Sensitive Marker in ST-Elevation Myocardial Infarction

Traditional biomarkers in acute coronary syndromes reflect myocardial necrosis but not the underlying arteriosclerotic disease. Pregnancy-associated plasma protein A (PAPP-A) is a new biomarker in acute coronary syndromes that detects vulnerable plaques in arteriosclerotic disease and identifies acute coronary syndromes earlier than traditionally used biomarkers. Information regarding circulating PAPP-A levels in patients with ST elevation myocardial infarctions (STEMIs) is limited and contradictory. The aim of the present study was to describe the presence and time-related pattern of circulating PAPP-A levels in patients with STEMIs. Consecutive patients (n = 354) referred for primary percutaneous intervention because of STEMI were included in the study. Blood samples for the analysis of PAPP-A, creatine kinase-MB (CKMB), and troponin T were drawn at admission and every 6 to 8 hours until biomarkers of myocardial necrosis were consistently decreasing. PAPP-A was measured using a newly developed sandwich enzyme-linked immunosorbent assay technique based on 2 monoclonal antibodies. In total, 1,091 PAPP-A, 1,049 troponin T, and 1,016 CKMB samples were analyzed. Mean PAPP-A values at admission were significantly higher in patients with STEMIs than in those with non-ST elevation myocardial infarctions or unstable angina pectoris (27.6 vs 12.2 mIU/L, p <0.01). In samples drawn <2 hours after admission, the sensitivity of PAPP-A was superior (93%) to that of CKMB (60%) and troponin T (61%). In conclusion, PAPP-A levels are elevated in >90% of patients presenting with STEMIs if measured <6 hours after the onset of symptoms or <2 hours of primary percutaneous coronary intervention. In the early stages of STEMI, PAPP-A seems to be a more sensitive marker of myocardial infarction than CKMB and troponin T.

Effects of a 14-month low-cost maintenance training program in patients with chronic systolic heart failure: a randomized study.

Background Exercise training is known to be beneficial in chronic heart failure (CH F) patients but there is a lack of studies following patient groups for longer duration with maintenance training programs to defer deconditioning. Methods Study base consisted of all patients diagnosed with CHF in a 3-year period. Sixty-six patients with systolic CHF (ejection fraction < 45, New York Heart Association II-III) were randomized to 12 months of either usual care or home-based maintenance exercise with group training sessions every 2 weeks after an initial 8-week training program. The primary endpoint was maximum workload; secondary endpoints were 6-min walk test, incremental shuttle walk test, sit-to-stand test, quality of life, and serological markers. Results Six patients died and 43 completed the study. The initial 8-week training was associated with small but significant improvement in all of the functional tests. In both groups there was a significant decline in the maximum workload the next 12 months (P = 0.03 and P < 0.001, respectively) but after an adjustment for difference between groups in baseline characteristics, maintenance intervention reduced the decline in the maximum workload by 8.0W (95% CI: 3.0–13.0, P = 0.002). No effect of maintenance intervention was observed for 6-min walk test, incremental shuttle walk test, sit-to-stand test, or quality of life. After 14 months changes in most markers of inflammation, endothelial damage, and glycemic control were more beneficial in the intervention group. Conclusion A low-cost maintenance intervention in CHF patients reduced the decline in the maximum workload compared with usual care but not in other measures of physical function. Results suggest beneficial effects of long-term maintenance training on glycemic control, inflammation, and endothelial function.

Usefulness of Pregnancy-Associated Plasma Protein A in Patients With Acute Coronary Syndrome

To investigate whether pregnancy-associated plasma protein-A (PAPP-A) is a prognostic marker in patients admitted with high-risk acute coronary syndrome. In patients admitted with high-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and ST-segment elevation myocardial infarction (STEMI), risk stratification is primarily determined by the markers of myocardial necrosis and known demographic risk profiles. However, it has recently been proposed that the presence and extent of vulnerable plaques might influence the prognosis significantly. A marker for the vulnerable plaque could identify patients at high risk who would potentially benefit from intensive treatment and surveillance. Two populations of consecutive patients admitted with high-risk NSTE-ACS (n = 123) and STEMI (n = 314) were evaluated with serial measurements of PAPP-A. The incidence of mortality and nonfatal myocardial infarction was prospectively registered for 2.66 to 3.47 years. In the patients with high-risk NSTE-ACS, PAPP-A was related to the risk of nonfatal myocardial infarction (p = 0.02) and death (p = 0.03). This result was consistent on multivariate analysis of the combination of mortality or nonfatal myocardial infarction (odds ratio 2.65, 95% confidence interval 1.40 to 5.03) but not for mortality alone (p = NS). In patients with STEMI, PAPP-A was related to the risk of death (p = 0.01) but not the composite outcome of myocardial infarction and death. This was also true after adjustment for other univariate predictors of death (odds ratio 2.19, 95% confidence interval 1.16 to 4.16). In conclusion, PAPP-A seems to be valuable in predicting the outcomes of patients admitted with high-risk NSTE-ACS or STEMI.

Pregnancy associated plasma protein-A (PAPP-A) is not a marker of the vulnerable atherosclerotic plaque

OBJECTIVE To investigate if pregnancy associated plasma protein-A (PAPP-A) was present in the vulnerable plaque, and if not, to find alternative hypothesis for the release of PAPP-A. DESIGN AND METHODS Vulnerable plaques and control tissues were examined by immunohistochemistry. Volunteers and patients with non-atherosclerotic disease were examined for release of PAPP-A during ischemia and medical treatment. Non-atherosclerotic tissue samples were examined after incubation with heparins. RESULTS We were not able to detect PAPP-A in vulnerable plaques. Patients and volunteers experiencing ischemic events without atherosclerotic lesions only had elevated PAPP-A when treated with heparin. When tissue from normal artery wall was incubated with heparin, PAPP-A was eluted. This was not the case for non-arterial tissue samples. CONCLUSION Elevation of PAPP-A in patients with acute coronary syndromes seems to be caused by heparin induced release of PAPP-A from the arterial wall and not due to excretion from vulnerable plaques.

Pregnancy-associated plasma protein-A, a marker for outcome in patients suspected for acute coronary syndrome.

OBJECTIVES To examine if pregnancy-associated plasma protein-A (PAPP-A) in patients with chest pain, could identify patients at risk for death or myocardial infarction. DESIGN AND METHODS Patients admitted with chest pain and both normal ECG and normal biomarkers were evaluated by serial measurement of PAPP-A. Main outcome measures were mortality and non-fatal myocardial infarction. RESULTS Median age of patients included (415) was 67years and 43% were women. The risk of death or non-fatal myocardial infarction after 3 months was 15% in the highest quartile of circulating PAPP-A compared with 3% in the lowest quartile (relative risk 3.7, p<0.01). Corresponding numbers after 1 year were 24% and 10% (relative risk 2.4, p=0.01). CONCLUSION In patients admitted with chest pain and both normal ECG and normal biomarkers PAPP-A seems to be valuable for predicting patients at high risk of death or non-fatal myocardial infarction.

Pregnancy associated plasma protein A, a potential marker for vulnerable plaque in patients with non-ST-segment elevation acute coronary syndrome

OBJECTIVES To describe the presence and time-related pattern of circulating pregnancy associated plasma protein A (PAPP-A) levels in patients with non ST-segment elevation acute coronary syndrome (NSTE-ACS). DESIGN AND METHODS Consecutively admitted patients (N=573) with clinical signs of NSTE-ACS were included. Blood samples for analysis of PAPP-A were drawn at admission and every 6-8 h until levels of biomarkers of myocardial necrosis showed a consistent decrease. RESULTS High-risk NSTE-ACS was diagnosed in 123 patients (23%). Significantly more patients with high-risk NSTE-ACS (63%) had detectable PAPP-A than did those with low-risk NSTE-ACS (49%) (P<0.001). PAPP-A concentrations were significantly associated with typical angina at admission, significant ST-depressions on the ECG, multivessel disease and presence of high-risk NSTE-ACS. CONCLUSION PAPP-A seems to be a marker ischaemia both in patients with low- and high-risk NSTE-ACS, possibly due to the release of PAPP-A from the vulnerable plaque.

Pregnancy-associated plasma protein A in non-cardiac conditions

OBJECTIVE PAPP-A is a promising new marker in coronary heart disease. It is important to investigate its specificity in order to establish its clinical utility as a marker of coronary heart disease. DESIGN AND METHODS PAPP-A was measured within 24 h following hospital admission in 1448 consecutive patients admitted with diagnoses other than acute coronary syndromes. RESULTS PAPP-A was detectable (> or = 4.0 mIU/L) in 278 (19.2%) patients, among whom the mean level was 6.3 mIU/L (95% C.I., 6.1-6.5 mIU/L). The 95 and 99 percentiles for PAPP-A were 7.3 and 9.4 mIU/L, respectively. There was no difference in the mean PAPP-A of different diagnoses (p=0.33). None of the specific diagnoses known to influence established coronary markers appeared to influence the level of circulating PAPP-A. CONCLUSION PAPP-A is low in patients without known coronary heart disease. PAPP-A levels seem to be a potentially highly specific marker for heart disease.

Release patterns of pregnancy-associated plasma protein A in patients with acute coronary syndromes assessed by an optimized monoclonal antibody assay.

Objective. Pregnancy‐associated plasma protein A (PAPP‐A) is expressed in eroded and ruptured atheromatous plaques, and circulating levels are elevated in acute coronary syndromes (ACS). Our objective was to investigate release patterns of PAPP‐A in ACS and whether they differ among different types of ACS. Methods. In 40 patients, PAPP‐A concentrations were measured in serially collected samples assessed by a novel ELISA technique. The patients were grouped according to type of ACS. Results. Release patterns for ST elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (pPCI) showed a single substantial PAPP‐A increase shortly after pPCI, followed by an abrupt return to normal levels without secondary peaks. STEMI, high‐risk and low‐risk non‐ST elevation myocardial infarction/unstable angina pectoris (NSTEMI/UAP) patients without pPCI showed highly variable patterns with primary peaks followed by secondary PAPP‐A increases. All patients with elevated PAPP‐A levels reached the upper reference level within 24 h. There was a significant difference in median peak levels between STEMI (23.2 mIU/L) and low‐risk ACS patients (6.35 mIU/L) (p = 0.004) and between high‐risk (median = 15.3 mIU/L) and low‐risk ACS patients (p = 0.01). Among high‐risk ACS patients, NSTEMI patients had significantly higher peak levels than UAP patients (p = 0.003). Conclusion. PAPP‐A serum levels increase above normal values within 24 h after onset of symptoms in ACS. There are significant differences in PAPP‐A peak levels and release patterns across the spectrum of ACS patients.

Exercise training in older patients with systolic heart failure: Adherence, exercise capacity, inflammation and glycemic control

Objectives. Training improves exercise capacity in patients with heart failure (CHF) but most evidence is on selected younger patients with systolic CHF. Design. All patients diagnosed with CHF over 3 years were screened for inclusion and exclusion criteria. Fifty two patients with systolic CHF (LVEF<45, NYHA II-III) received supervised exercise training twice weekly for 8 weeks. Results. Mean age was 68.2 (+/−SD 11.3) years. Despite marked improvements in physical fitness (workload, 6 minute walk test, incremental shuttle walk test and sit to stand test), there were no changes in serological markers of glycemic control (glucose, insulin, glycerol, free fatty acids, HbA1c), inflammation and endothelial function (hsCRP, orosomucoid, interleukin 6, TNF-alpha, urine-orosomucoid and -albumin/creatinin), lipid metabolism, NT-proBNP or other regulatory hormones (cortisol, epinephrine and IGF-1). There were no changes in quality of life. Conclusions. The effect of exercise training in these older CHF-patients was not as impressive as reported in younger and more selected patients. More studies on the efficiency of exercise training that reflect the age- and co-morbidity of the majority of CHF-patients are needed.