Disseminated intravascular clotting associated with Fc-receptor IIa-mediated platelet activation in a patient with endocarditis after aortic valve replacement.

This report describes fatal disseminated cardiovascular thrombosis associated with Fc-receptor IIa-mediated platelet activation during surgery for aortic valve replacement in a patient with endocarditis. The patient's serum contained antibodies which strongly activated platelets via the Fc-receptor IIa. Antibodies did not bind to platelet factor 4 or aprotinin and binding was independent of heparin. The mechanisms and differential diagnosis for such a complication are discussed. Our data show for the first time in a patient with endocarditis that, beside HIT, other immune complexes can induce massive intravascular coagulation via platelet Fc-receptor IIa activation.

Serum cystatin C--a superior marker of rapidly reduced glomerular filtration after uninephrectomy in kidney donors compared to creatinine.

AIMS: Acute renal failure (ARF), defined by a rapid decrease of glomerular filtration rate (GFR), is associated with high mortality. Early and accurate detection of decreasing GFR is critical to prevent the progression of ARF and to potentially improve its outcome. Serum creatinine, the conventional GFR marker, has major limitations. We prospectively evaluated whether serum cystatin C detected a rapid GFR decrease earlier and more accurately than serum creatinine. METHODS: In ten patients undergoing nephrectomy for living related kidney transplantation, serum creatinine and cystatin C were determined daily. The decrease of GFR was quantitated preoperatively by creatinine clearance and MAG3 scintigraphy. The GFR decrease was defined by a 50-100% increase of cystatin C or creatinine from preoperative values. Ten patients without renal impairment served as controls. RESULTS: Initially, patients had a creatinine clearance of 105 +/- 14 ml/min/1.73 m2. Due to nephrectomy, patients lost 45 +/- 3% of their renal function. Serum cystatin C significantly increased already one, serum creatinine two days after nephrectomy. Cystatin C demonstrated an increase by 50-100% 1.4 +/- 0.9 days earlier than creatinine (p = 0.009). Serum cystatin C performed well detecting the GFR decrease with higher diagnostic values compared to creatinine. This was indicated by a sensitivity of 50, 70 and 80% of cystatin C to detect the GFR decrease on the three days following nephrectomy. CONCLUSIONS: Serum cystatin C detects rapid GFR decreases one to two days earlier than creatinine. Cystatin C is an early and accurate marker to detect rapid GFR decreases as in ARF.

Cardiovascular risk factors and probability for cardiovascular events in HIV-infected patients - part III: age differences.

OBJECTIVE: In recent years, concerns have been growing about an elevated rate of cardiovascular diseases in HIV-infected patients due to side effects of antiretroviral therapy. The present study analyses the cardiovascular risk profile and the probability of cardiovascular events with regard to the age of HIV-infected patients. METHODS: Cardiovascular risk factors of 309 HIV-infected adults were analysed. Patients were divided into four groups: 18-30 years (group 1), 31-40 years (group 2), 41-50 years (group 3), > 50 years (group 4). Overall 10-years probability for cardiovascular events was evaluated by the Framingham algorithm. RESULTS: Differences between the groups were detected in cardiovascular risk factors including changes in lipid- and glucose metabolism. Lipid values increased with elevated age, such as total cholesterol concentration (Mean +/- SEM in group 1 vs. group 4: 4.71 +/- 0.20 to 6.36 +/- 0.21 mmol/L, p < 0.05), LDL-cholesterol concentration (2.86 +/- 0.17 vs. 4.17 +/- 0.21 mmol/L, p < 0.05) and triglyceride concentration (1.56 +/- 0.14 vs. 3.48 +/- 0.40 mmol/L, p < 0.05). HDL-cholesterol concentration did not show a significant difference (1.15 +/- 0.03 mmol/L). Glucose concentration increased with elevated age in HIV-infected patients (5.28 +/- 0.19 vs. 6.46 +/- 0.24 mmHg, p < 0.05), but there was no significant difference in HbA1c - concentration, blood pressure and smoking rate between the groups. The overall 10-years probability for cardiovascular events was higher in group 1 (median: 1.9%) than in group 4 (20.5%; p < 0.01). CONCLUSIONS: The risk of cardiovascular events is related to the age in HIV-infected patients. Therefore, an increased duration of life due to a more effective antiretroviral therapy will have a significant impact on the rate of cardiovascular events in this patient population. In the future, further increase of cardiovascular events in HIV-infected patients may be expected.

Cardiovascular risk factors and probability for cardiovascular events in HIV-infected patients. Part II: gender differences.

OBJECTIVE: Due to the side effects of antiretroviral therapy and long term survival there is an increasing concern of an elevated rate of cardiovascular diseases in HIV-infected patients. The present study analysed the cardiovascular risk profile and the probability of cardiovascular events in HIV-infected patients, due to differences of gender. METHODS: Cardiovascular risk factors of 309 HIV-infected adults, including 240 males were analysed. Overall 10-years probability for cardiovascular events was evaluated by the Framingham algorithm. RESULTS: Gender differences were detected in cardiovascular risk factors such as lipid values, blood pressure and the rate of smoking. Tobacco use was much more common in HIV-infected males compared with HIV-infected females (67.5% vs. 49.3%; p<0.001). Although no significant difference was noticed in total cholesterol (5.49 +/- 0.09 vs. 5.53 +/- 0.19 mmol/L, p = 0.84), the HDL-cholesterol concentration was significantly lower (1.09 +/- 0.03 vs. 1.36 +/- 0.06 mmol/L, p < 0.001) and the triglyceride concentration higher (3.01 +/- 0.21 vs. 2.06 +/- 0.26 mmol/L, p = 0.02) in HIV-infected males compared to HIV-infected females. Additionally, systolic blood pressure was higher in HIV-infected males compared with HIV-infected females (123.1 +/- 1.1 vs. 115.4 +/- 2.1 mmHg, p < 0.01). No significant differences were detected in HbA1c concentrations between both groups (5.15 +/- 0.07 vs. 5.31 +/- 0.11, p = 0.26). The overall 10-years probability for cardiovascular events was 8.7% (median) in HIV-infected males and 1.7% in HIV-infected females (p < 0.0001). CONCLUSIONS: In the present study, we observed gender differences in the cardiovascular risk profile of HIV-infected individuals. The risk of premature atherosclerosis and associated cardiovascular events was significantly higher in HIV-infected males.

Cardiovascular risk factors and probability for cardiovascular events in HIV-infected patients: part I. Differences due to the acquisition of HIV-infection.

OBJECTIVE: Due to side effects, such as hyperlipidaemia and insulin resistance, there is an increasing concern that antiretroviral drugs lead to an epidemic of cardiovascular diseases in HIV-infected patients. The present study characterizes the cardiovascular risk profile of HIV-infected individuals, due to the acquisition of HIV-infection. METHODS: Cardiovascular risk factors of 309 HIV-infected adults (HIV-acquisition: 59.2% by homosexual contact (group 1), 28.5% by heterosexual contact (group 2), 9.1% by intravenous drug abuse (group 3) and 3.2% by blood transfusion (group 4)) were analysed. Overall 10-years probability for cardiovascular events was analysed by the Framingham algorithm. RESULTS: Tobacco use was more common in group 1 subjects compared with group 2 subjects (67% vs. 52%; p<0.05). Additionally, group 1 subjects exhibited elevated total cholesterol (5.6 +/- 0.1 mmol/L vs. 4.8 +/- 0.3), LDL-cholesterol (3.6 +/- 0.1 mmol/L vs. 2.8 +/- 0.2) and triglyceride concentrations (3.2 +/- 0.3 mmol/L vs. 1.7 +/- 0.2) compared with group 3 (all p<0.05). No significant differences between the groups were detected in glucose metabolism. The overall 10-years probability for cardiovascular events was significantly higher in group 1 compared with group 2 and group 3 (12.2 +/- 0.8% vs. 6.6 +/- 0.9% and 7.9 +/- 1.6%, p<0.05). CONCLUSIONS: The cardiovascular risk profile differs between subgroups of HIV-infected individuals, leading to significant higher probability of cardiovascular events in group 1 subjects. The risk of premature atherosclerosis by HIV-infected individuals and therapeutic options remains to be established.

Prognostic implication of cardiac troponin T increase following stent implantation.

OBJECTIVE: To identify the incidence and clinical significance of myocardial injury following elective stent implantation. DESIGN: Prospective clinical study with 278 consecutive patients undergoing stenting of de novo coronary or saphenous vein graft lesions. Incidence of periprocedural myocardial injury was assessed by analysis of 12 lead ECG, creatine kinase (CK; upper limit of normal (ULN) 70 IU/l for women, 80 IU/l for men), and cardiac troponin T (cTnT; point of care test; threshold 0.1 ng/ml) before and 6, 12, and 24 hours after the intervention. Major adverse cardiac events (MACE: acute myocardial infarction, bypass surgery, and cardiac death) were recorded during clinical follow up (mean (SD) 7.8 (5.3) months). RESULTS: Following elective stenting, the rate of a positive cTnT status was 17.3%, the rate of CK increase of 1-3x ULN 14.7%, the rate of CK increase of > 3x ULN 1.4%, and the rate of Q wave myocardial infarction 0.4%. Cardiac mortality during follow up was higher in patients with postprocedurally increased CK (7.1% v 1.3%, p = 0.01, log rank) and cTnT (9.1% v 0.9%, p < 0.001, log rank). In addition, postprocedurally increased cTnT was associated with a higher overall incidence of MACE (13.1% v 4.0%, p < 0.01, log rank) and was identified as an independent factor for MACE during follow up (hazard ratio 3.27, 95% confidence interval 1.14 to 9.41, p = 0.028). CONCLUSIONS: Following elective stent implantation, a positive cTnT status identified patients at risk of a worse long term outcome. Treatment strategies have to be developed that lead to prognostic improvement by reducing periprocedural myocardial injury.

Abnormal coronary flow velocity reserve after coronary intervention is associated with cardiac marker elevation.

BACKGROUND: Residual reduction of relative coronary flow velocity reserve (rCVR) after successful coronary intervention has been related to microvascular impairment. However, the incidence of cardiac enzyme elevation as a surrogate marker of an underlying embolic myocardial injury in these cases has not been studied. METHODS AND RESULTS: A series of 55 consecutive patients with successful coronary stenting, periprocedural intracoronary Doppler analysis, and determination of creatine kinase (CK; upper limit of normal [ULN] for women 70 IU/L, for men 80 IU/L) and cardiac troponin T (cTnT; bedside test, threshold 0.1 ng/mL) before and 6, 12, and 24 hours after intervention were studied. Postprocedural rCVR was the only intracoronary Doppler parameter that independently correlated with cTnT (r=-0.498, P<0.001) and CK outcome (r=-0.406, P=0.002). Receiver operating characteristic analysis identified a postprocedural rCVR of 0.78 as the best discriminating value, with a sensitivity of 83.3% and 69.2% and a specificity of 79.1% and 76.2% for detection of cTnT and CK elevation, respectively. Stratified according to this cutoff value, the incidence of cTnT elevation was 52.6% in patients with (n=19) and 5.6% in patients without (n=36) a postprocedural rCVR <0.78 (P<0.001), associated with a CK elevation >1 times the ULN in 36.8% and 5.6% (P=0.005) of patients, respectively. CONCLUSIONS: Cardiac marker elevation can frequently be found after coronary procedures that are associated with a persistent reduction of rCVR, indicating procedural embolization of atherothrombotic debris with microvascular impairment and myocardial injury as a potential underlying mechanism.

[Biochemical markers of ischemic and non-ischemic myocardial damage]. / Biochemische Marker bei ischämischen und nicht ischämischen Myokardschädigungen.

BACKGROUND: Biochemical markers have been an integrative part of non-invasive diagnostic strategies in cardiology for nearly 50 years, experiencing a renascence by the recently acknowledged prognostic potential of cardiac troponins in acute coronary syndromes. DIAGNOSIS: According to the guidelines of the National Academy of Clinical Biochemistry and the International Federation of Clinical Chemistry cardiac troponin T and cardiac troponin I should be considered as the new "gold markers" of ischemic myocardial injury. One characteristic feature of these new markers is the improved diagnostic potential, reflected by the choice of two cut-off values to distinguish minor myocardial injury from acute myocardial infarction. In addition, cardiac troponins allow risk stratification in the clinical setting of acute coronary syndromes: approximately threefold higher mortality rate for patients with rest angina or ST segment elevation and cardiac troponin elevation on admission. Other indications for cardiac marker analysis are monitoring of therapeutic success in case of invasive and non-invasive reperfusion strategies and non-invasive diagnosis of non-ischemic myocardial injury (myocarditis, cardiac contusion and chemotherapy). CONCLUSION: Biochemical cardiac markers are a useful tool in the diagnosis of both ischemic and non-ischemic myocardial injury. Among these, cardiac troponins seem to become the gold markers for the new millennium.

Elevation of intracranial pressure in acute AIDS-related cryptococcal meningitis.

Prior to the AIDS-era, elevation of intracranial pressure was known to be a typical complication of cryptococcal meningitis associated with an increased risk of early death. In AIDS-patients, however, the prevalence and clinical significance of this complication are as yet unclear. We analysed clinical features and courses, CSF findings, serological results and neuroimaging scans in acute cryptococcal meningitis in eight patients with AIDS. Five showed symptoms and signs compatible with raised intracranial pressure, which was life-threatening in one and the most probable cause of death in another. Serial monitoring of intracranial pressure together with repeated CSF analysis revealed that severe intracranial pressure elevation in AIDS related cryptococcal meningitis can occur in spite of effective antimycotic treatment, does not depend on an increased CSF/serum osmolality ratio or CSF overproduction and can be associated with normal cranial computed tomography and magnetic resonance imaging findings. Our data support the hypothesis that CSF reabsorption failure plays the crucial role in the pathophysiological mechanism. External lumbar drainage may be of benefit in selected cases of acute AIDS related cryptococcal meningitis with persisting life threatening elevation in intracranial pressure and normal computed tomogram.

Oleic acid inhibition of Na+/D-glucose transport in isolated renal brush-border membranes: role of lipid physical parameters and trans Na(+)-inhibition.

UNLABELLED: Inhibition of Na+/D-glucose transport by oleic acid was investigated in renal brush-border membrane vesicles (BBMV). Lipid physical parameters were determined by spectrofluorometry. cis-Unsaturated C16-C22 long-chain fatty acids (LCFA) as oleic acid reduced nonzero limiting anisotropy r infinity with DPH and 12-AS as probes and decreased rotational correlation time phi of 12-AS. At 8 s and 15 s Na+/D-glucose transport was competitively inhibited. A positive correlation existed between decrease in r infinity (acyl chain order) or decrease in rotational correlation time phi (= increase in 'fluidity') and inhibition of Na+/D-glucose transport. Except elaidic acid trans unsaturated and saturated LCFA had no effect on fluorescence anisotropy and Na+/D-glucose transport. Per cent transport inhibition was unaffected by 0 voltage clamping and by FCCP. Ki for trans Na(+)-inhibition of D-glucose transport was 29 mmol/l. Na(+)-transport was stimulated by oleic acid, exceeding the Ki value for trans Na+ inhibition. CONCLUSION: oleic acid inhibits Na+/D-glucose transport by a decrease in lipid acyl chain order and an increase in 'fluidity', by trans Na(+)-inhibition and presumably by a third unknown mechanism.