Screening of biomarkers for prediction of multisite artery disease in patients with recent myocardial infarction.

A few studies have examined biomarkers in patients with myocardial infarction (MI) and peripheral artery disease (PAD), i.e. multisite artery disease (MSAD). The aim of the study was firstly, to associate biomarkers with the occurrence of PAD/MSAD and secondly, if those can, in addition to clinical characteristics, identify MI patients with MSAD.In two prospectively observational studies including unselected patients with recent MI, PAD was defined as an abnormal ankle-brachial index (ABI) score (<0.9 or >1.4). The proximity extension assay (PEA) technique was used, simultaneously analyzing 92 biomarkers with association to cardiovascular disease. Biomarkers were tested for univariate associations with PAD. Random forest was used to identify biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics was analyzed by the c-statistics. Nine biomarkers were identified as significantly associated with MSAD/PAD in the primary patient cohort, analyzed early after the MI. In the prediction analysis, six biomarkers were identified associated with PAD. Three of these; Tumor necrosis factor receptor (TNFR-1), Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) improved c-statistics when added to clinical characteristics from 0.683 (95% CI 0.610-0.756) to 0.715 (95% CI 0.645-0.784) in the primary patient cohort with a similar result, 0.729 (95% CI 0.687-0.770) to 0.752 (95% CI 0.771-0.792) in the secondary patient cohort. Biomarkers associated with inflammatory pathways are associated with MSAD in MI patients. Three biomarkers of 92; TNFR-1, TNFR-2 and GDF-15, in this exploratory added information in the prediction of MSAD and emphasis the importance of further studies.

New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting. METHODS AND RESULTS: All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7-14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80-0.95), but more than doubled the bleeding (HR: 2.34; 2.06-2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies. CONCLUSION: In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.

Low Walking Impairment Questionnaire score after a recent myocardial infarction identifies patients with polyvascular disease.

OBJECTIVES: To evaluate whether the Walking Impairment Questionnaire score could identify patients with polyvascular disease in a population with recent myocardial infarction and their association with cardiovascular events during two-year follow-up. DESIGN: A prospective observational study. SETTING: Patients admitted to the acute coronary care unit, the Department of Cardiology, Uppsala University Hospital. PARTICIPANTS: Patients admitted with acute Non-STEMI- or STEMI-elevation myocardial infarction. MAIN OUTCOME MEASURES: The Walking Impairment Questionnaire, developed as a self-administered instrument to assess walking distance, speed, and stair climbing in patients with peripheral artery disease, predicts future cardiovascular events and mortality. Two hundred and sixty-three patients with recent myocardial infarction answered Walking Impairment Questionnaire. Polyvascular disease was defined as abnormal findings in the coronary- and carotid arteries and an abnormal ankle-brachial index. The calculated score for each of all three categories were divided into quartiles with the lowest score in first quartile. RESULTS: The lowest (worst) quartile in all three Walking Impairment Questionnaire categories was associated with polyvascular disease, fully adjusted; distance, odds ratio (OR) 5.4 (95% confidence interval (CI) 1.8-16.1); speed, OR 7.4 (95% CI 1.5-36.5); stair climbing, OR 8.4 (95% CI 1.0-73.6). In stair climbing score, patients with the lowest (worst) score had a higher risk for the composite cardiovascular endpoint compared to the highest (best) score; hazard ratio 5.3 (95% CI 1.5-19.0). The adherence to medical treatment was high (between 81.7% and 99.2%). CONCLUSIONS: The Walking Impairment Questionnaire is a simple tool to identify myocardial infarction patients with more widespread atherosclerotic disease and although well treated medically, stair climbing predicts cardiovascular events.

Ankle brachial index most important to identify polyvascular disease in patients with non-ST elevation or ST-elevation myocardial infarction.

BACKGROUND: Atherosclerosis is a systemic disease. In patients with acute myocardial infarction (MI) the extent of polyvascular disease (PvD) is largely unknown. In this study we investigate the prevalence and clinical characteristics predictive of PvD in patients with non-ST-elevation (NSTEMI) and ST-elevation (STEMI) MI. METHOD: 375 patients with acute MI included in the REBUS (Relevance of Biomarkers for Future Risk of Thromboembolic Events in Unselected Post-myocardial Infarction Patients) study were examined. Atherosclerotic changes were assessed in three arterial beds by coronary angiography, carotid ultrasound and ankle brachial index (ABI). Results compared findings of atherosclerosis in three arterial beds to fewer than 3 beds. PvD was defined as atherosclerosis in all three arterial beds. RESULTS: A medical history of MI, peripheral artery disease (PAD) or stroke was reported at admission in 17.9%, 2.1% and 3.7% of the patients, respectively. After evaluation, abnormal ABI was found in 20.3% and carotid artery atherosclerosis in 54.9% of the patients. In the total population, PvD was found in 13.8% of patients with no significant differences observed between NSTEMI and STEMI patients. Age (p<0.001), diabetes (p=0.039), previous PAD (p=0.009) and female gender (p=0.016) were associated with PvD. ABI was the most important predictor of PvD with a positive predictive value of 68.4% (95% CI 57.7-79.2%) and specificity of 92.4% (95% CI 89.5-95.4%). CONCLUSIONS: PvD is underdiagnosed in patients suffering from MI, both NSTEMI and STEMI. ABI is a useful and simple measurement that appears predictive of widespread atherosclerosis in these patients.

Effect of Gender on Patients With ST-Elevation and Non-ST-Elevation Myocardial Infarction Without Obstructive Coronary Artery Disease.

The aim of this study was to compare the prognoses of patients with ST-segment elevation myocardial infarction (STEMI) and those with non-ST-segment elevation myocardial infarction (NSTEMI) without obstructive coronary artery disease (CAD) and the risk associated with gender for future cardiovascular events. The study population was selected from 95,849 patients who underwent coronary angiography for myocardial infarction from 2005 to 2010 and registered in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Outcome analyses, including all-cause death, myocardial infarction, congestive heart failure, stroke, and revascularization, were performed in 2,268 patients with STEMI and 10,904 with NSTEMI without obstructive CAD (<50% stenosis). Hazard ratios and 95% confidence intervals comparing women with men were calculated for events, adjusting for cardiovascular risk factors and age. Nonobstructive CAD was found in 7% of patients with STEMI (6% men, 10% women) and in 17% of those with NSTEMI (11% men, 28% women). During a median follow-up of 2.6 years, 8% of patients with STEMI and 5% of those with NSTEMI died. Gender-associated differences in risk were observed in patients with NSTEMI, with adjusted hazard ratios lower in women than men for mortality (hazard ratio 0.90, 95% confidence interval 0.50 to 0.73) and congestive heart failure (hazard ratio 0.61, 95% confidence interval 0.52 to 0.72). In the 2 groups, women underwent less revascularization. In conclusion, nonobstructive CAD was more common in patients with NSTEMI than those with STEMI, as well as in women compared with men. Long-term mortality in patients with nonobstructive CAD was higher after STEMI than NSTEMI. The gender differences in outcomes suggest gender differences in the underlying pathogenesis of myocardial infarction without obstructive CAD.

[Children and adolescents with Down syndrome. Continuous ophthalmological monitoring crucial!]. / Barn och ungdomar med Downs syndrom. Ogonuppföljning måste ske kontinuerligt!

Children with Down's syndrome are at increased risk of ocular manifestations, which is confirmed by a study in Uppsala, Sweden. Sixty percent of the children were wearing glasses and/or had other ocular problems. However, lapses were found in follow-up and referral to the eye clinic. Good visual function is an important prerequisite for optimal quality of life of children and adults with Down's syndrome. Since this group does not always spontaneously get in touch with the health care system including ophthalmologists, the infant must be referred by the pediatrician immediately after birth. The number of individuals with Down's syndrome in Sweden is large (3,500-5,000), and an ophthalmological follow-up program, as presented in this paper, is of key importance.