[Liver disorders in adults: ALT and AST]. / Leveraandoeningen bij volwassenen: ALAT en ASAT.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are commonly used biomarkers for liver damage. As well as in liver tissue, AST is also present in cardiac and skeletal muscle and in erythrocytes, making ALT the most specific marker for liver damage. Here, we describe two patients with sustained increases in ALT and AST levels. The first patient is a 79-year-old woman who developed elevated serum transaminases shortly after having a myocardial infarction. The second patient, an obese 40-year-old woman presented with increased ALT and AST levels in the absence of physical symptoms. Notably, her father died of liver cirrhosis without a history of alcohol abuse. Based upon these case reports we discuss the differential diagnostic work-up of elevated serum transaminase levels. Furthermore, we explain monitoring, test performance, reference values and analytical pitfalls of these biomarkers.

Lamin A/C mutation is independently associated with an increased risk of arterial and venous thromboembolic complications.

BACKGROUND: Lamin A/C (LMNA) mutation carriers suffer from a variety of clinical phenotypes, including dilated cardiomyopathy (DCM). Although it has been suggested that carriers are at risk for thromboembolic complications, it is unknown whether this risk is higher than can be expected from the underlying cardiac abnormalities. The purpose of this study was to determine whether a LMNA mutation is associated with an increased risk of thromboembolic complications. METHODS: We compared a cohort of 76 LMNA mutation carriers with a cohort of 224 idiopathic DCM patients without a LMNA mutation, with respect to the prevalence of arterial and venous thromboembolic complications. Furthermore, we carried out a case-control study to explore whether a prothrombotic phenotype was present in LMNA mutation carriers without DCM or atrial tachyarrhythmias (n=14) and compared this with mutation negative relatives (n=13). RESULTS: The prevalence of thromboembolic complications was higher in the cohort of LMNA mutation carriers than in DCM patients (22 vs 11%; p<0.05), after respectively mean follow-up of 42 ± 12 and 49 ± 12 years. After adjustment for possible confounders, including atrial tachyarrhythmias and left ventricular ejection fraction, LMNA mutation carriership was independently associated with an increased risk of thromboembolic complications (HR 4.8, 95% CI: 2.2-10.6). The results of the case-control study suggested a prothrombotic phenotype in LMNA mutation carriers, as reflected by an altered platelet function and increased thrombin generation. CONCLUSIONS: LMNA mutation is independently associated with an increased risk of arterial and venous thromboembolic complications. Laboratory research in LMNA mutation carriers without severe cardiac abnormalities suggests a prothrombotic phenotype.

Arterial stiffness is increased in families with premature coronary artery disease.

OBJECTIVE: A positive family history of premature coronary artery disease (CAD) is a risk factor for cardiovascular disease (CVD), independent of traditional risk factors. Therefore, currently used risk algorithms poorly predict risk in these individuals. Novel methods are thus needed to assess cardiovascular risk. Pulse-wave velocity (PWV) might be such a method, but it is unknown whether PWV is increased in first-degree relatives of patients with premature CAD. DESIGN: Observational case-control study. SETTING: Academic hospital. PATIENTS: Patients with premature CAD and a positive family history of premature CVD (n=50), their first-degree relatives without CVD (n=50) and unrelated controls (n=50). INTERVENTIONS: None. MAIN OUTCOME MEASURES: PWV was measured with using an Arteriograph system. Differences in PWV were assessed by a generalised linear model and multinomial logistic regression. RESULTS: Patients with premature CAD had a higher PWV compared with first-degree relatives and controls (9.69±2.90 m/s vs 8.15±1.96 m/s and 7.38±1.08 m/s; p<0.05 patients vs all groups). Linear regression showed all groups related to PWV, with patients having the highest PWV and controls the lowest (p<0.0001). Furthermore, PWV was associated with first-degree relatives (OR 1.32, 95% CI 1.02 to 1.72; p<0.05) and premature CAD (OR 1.72, 95% CI 1.32 to 2.24; p<0.05) compared with controls. These findings were independent of blood pressure and other traditional risk factors. CONCLUSIONS: Patients with premature CAD and their first-degree relatives had higher PWV compared with controls, independent of other risk factors. This holds promise for the future, in which arterial stiffness might play a role in risk prediction within families with premature CAD.

Platelets in patients with premature coronary artery disease exhibit upregulation of miRNA340* and miRNA624*.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts. CONCLUSION/SIGNIFICANCE: Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective study.

Value of history-taking in syncope patients: in whom to suspect long QT syndrome?

AIMS: Long QT syndrome (LQTS), a potentially fatal disorder, has to be distinguished from non-fatal conditions. Our aim was to investigate whether history-taking can be used in identifying patients likely to have LQTS. METHODS AND RESULTS: We compared the characteristics of a group of LQTS patients with syncope patients presenting at the emergency department (ED) and vasovagal patients younger than 40 years of age. Thirty-two LQTS patients were included. We included 113 patients at the ED and 69 vasovagal patients. Family history of syncope, sudden cardiac death, or cardiovascular disease was found more often in LQTS patients. Palpitations were the only symptom reported more often in this group. Syncope while supine, during emotional stress and associated with exercise was also more common among LQTS. Standing as a trigger was found more often in ED and vasovagal patients. CONCLUSION: We conclude that a family history for syncope and sudden cardiac death, palpitations as a symptom, supine syncope, syncope associated with exercise, and emotional stress place patients at higher risk for LQTS. These findings should alert physicians to the potentially life-threatening illness of LQTS, and act accordingly by obtaining an electrocardiogram and paying specific attention to the QT interval.

High diagnostic yield and accuracy of history, physical examination, and ECG in patients with transient loss of consciousness in FAST: the Fainting Assessment study.

BACKGROUND: Transient loss of consciousness (TLOC) is a common clinical problem. OBJECTIVE: The aim of this study was to assess the yield and accuracy of the initial evaluation, consisting of standardized history, physical examination, and ECG performed by attending physicians in patients with TLOC. METHODS AND RESULTS: Five hundred and three adult patients (mean age 53 +/- 19; 56% male) presenting with TLOC to the Academic Medical Center Amsterdam between February 2000 and May 2002 were included in this study. After initial evaluation, the physician made a certain, a highly likely (>80% certain), or no initial diagnosis. Initially undiagnosed patients received additional cardiological testing, additional history taking, and autonomic function tests. After 2 years of follow-up, an expert committee determined the final diagnoses. Two-year follow-up was obtained in 99% of the patients. The yield of certain diagnoses after the initial evaluation was 24%, increasing to 63% after including the highly likely diagnoses. The diagnostic accuracy of the initial certain diagnoses was 93% (95% CI 87-97%), decreasing to 88% (95% CI 84-91%) after inclusion of the initial highly likely diagnoses. CONCLUSION: Attending physicians can make a diagnosis based on initial evaluation in 63% of patients with TLOC, with an overall diagnostic accuracy of 88%. The use of additional testing, beyond history, physical examination, and ECG can be avoided in many patients with TLOC.

Multi-center study on the characteristics and treatment strategies of patients with Graves' orbitopathy: the first European Group on Graves' Orbitopathy experience.

UNLABELLED: To improve management of patients with Graves' orbitopathy, a multi-center collaborative approach is necessary in order to have large enough sample sizes for meaningful randomized clinical trials. This is hampered by a lack of consensus on how to investigate the eye condition. The European Group on Graves' Orbitopathy aims to overcome this and has designed a preliminary case record form (CRF) to assess Graves' orbitopathy patients. This form was used in this first multi-center study. AIM: To investigate patient characteristics and treatment strategies in 152 new consecutively referred patients with thyroid eye disease seen in nine large European referral centers. METHODS: Newly referred patients with Graves' orbitopathy were included who were seen between September and December 2000. Demographic data and a complete ophthalmological assessment were recorded. RESULTS: One-hundred and fifty-two patients (77% females) were included. Diabetes was present in 9%, and glaucoma or cataract in 14% of patients. Forty percent were current smokers, 9% also had dermopathy, and only 33% reported a positive family history of thyroid disease. Mild eye disease was seen in 40%, moderately severe eye disease was seen in 33% and severe eye disease was seen in 28% of patients. Soft tissue involvement was the most frequent abnormality (seen in 75%), proptosis > or =21 mm was found in 63%, eye motility dysfunction in 49%, keratopathy in 16% and optic nerve involvement was found in 21% of patients. According to the clinical impression, 60% had active eye disease. Immunosuppressive treatment was planned more frequently in active patients (57/86; 66%) than in inactive patients (5/57, 9%; Chi-square 46.16; P<0.02). There were no important differences among the eight centers regarding the severity and the activity of their patients. CONCLUSIONS: In view of the large number of patients recruited in only 4 months, multi-center studies in the eight EUGOGO centers appear to be feasible.