Effects of early intracoronary streptokinase on infarct size estimated from cumulative enzyme release and on enzyme release rate: A randomized trial of 533 patients with acute myocardial infarction

The effects of early intracoronary streptokinase (SK) on enzymatic infarct size and rate of enzyme release were studied in a randomized multicenter trial. A total of 533 patients with acute myocardial infarction (AMI) were allocated to either the SK treatment group (n = 269) or the conventional (control) treatment group (n = 264). Enzymatic infarct size was represented by the cumulative quantity of alpha-hydroxybutyrate dehydrogenase (HBDH) released by the heart per liter of plasma in the first 72 hours. Rate of enzyme release was represented by the ratio of HBDH quantities released in 24 hours and 72 hours. On an "intention to treat" basis, the SK group had a smaller (by 30%; p = 0.0001) median enzymatic infarct size and a higher (by 35%; p = 0.0001) median rate of enzyme release than the control group. Limitation of infarct size was less apparent in patients tre

Extended Theories of Gravity and their Cosmological and Astrophysical Applications

We review Extended Theories of Gravity in metric and Palatini formalism pointing out their cosmological and astrophysical application. The aim is to propose an alternative approach to solve the puzzles connected to dark components.Comment: 44 pages, 11 figure

Vroege trombolyse verbetert de prognose op lange termijn voor patienten met een hartinfarct

In a previously reported clinical study treatment of myocardial infarction with intracoronary streptokinase (269 patients) was compared with conventional therapy (264 patients). To determine the long-term effects of thrombolytic therapy patient data were collected from 3 to 7 years after admission. Three-year survival rates were 87% after thrombolysis and 79% after conventional therapy. Bypass surgery was done in 19% versus 16%, and PTCA in 9% versus 6% of patients. Patients treated with thrombolysis also had a better prognosis after discharge. The difference in survival between the two treatment groups was 6% after 1 year and 10% after 5 years. Benefit was largest in patients with an anterior infarction, patients with extensive myocardial ischaemia and patients treated shortly after onset of infarction. Left ventricular function appeared to be the best determinant predicting survival after discharge. The findings show that early thrombolysis after acute myocardial infarction also results in improved long-term survival

Long term benefit of early thrombolytic therapy in patients with acute myocardial infarction

Patients (n = 533) who participated in the Interuniversity Cardiology Institute of the Netherlands Trial were followed up for 3 to 7 years. The 5 year survival rate after thrombolytic therapy with intracoronary streptokinase was 81% (269 patients) compared with 71% after conventional therapy (264 patients). The greatest improvement in survival was observed in patients with anterior infarction (81% versus 64% with thrombolytic therapy or conventional therapy, respectively), in those with heart failure on admission or a previous infarction and in those with extensive myocardial ischemia on admission. Left ventricular ejection fraction at the time of hospital discharge was better after thrombolytic therapy. In the hospital survivors, long-term outcome was related to left ventricular function at the time of discharge and, to a lesser extent, to the underlying coronary artery disease. The initial therapy (thrombolysis or conventional) was not an independent additional determinant of long-term survival when left ventricular function and coronary status at the time of hospital discharge were taken into account. Thus, the salutary effects of thrombolytic therapy appear to be the result of myocardial salvage. Reinfarction within 3 years was observed more frequently after thrombolytic therapy, particularly in patients with inferior wall infarction and those with greater than or equal to 90% stenosis of the infarct-related vessel at discharge. Coronary bypass surgery and coronary angioplasty were performed more frequently after thrombolytic therapy than in conventionally treated patients. At 5 years, approximately 40% of patients in both groups had an uneventful course without reinfarction or additional revascularization procedures. These observations demonstrate that the benefits of thrombolytic therapy are maintained throughout 5 years of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS

Postprandial triglyceride response in young adult men and familial risk for coronary atherosclerosis

Setting: Coronary angiography departments of four central general hospitals in the Netherlands. Patients: 80 sons (mean age, 24.8 years) of men with severe coronary artery disease and 55 sons (mean age, 23.2 years) of controls. Measurements: Postprandial levels of serum triglycerides, retinyl palmitate, and total cholesterol were measured during a 12-hour period after a standardized oral lipid load. Results: Both groups showed a marked increase in levels of serum triglyceride and retinyl palmitate after lipid loading, reaching a maximum 4 to 6 hours postprandially. No changes in postprandial total cholesterol levels were observed in either group. Sons of men with coronary artery disease had prolonged postprandial hypertriglyceridemia when compared with sons of controls. Significant differences in postprandial triglyceride levels were found at 8 hours (difference, 0.35 mmol/L; 95% CI, 0.07 to 0.62 mmol/L), at 10 hours (difference, 0.21 mmol/L; CI, 0.06 to 0.36 mmol/L), and at 12 hours after lipid loading (difference, 0.13 mmol/L; CI, 0.01 to 0.26 mmol/L). Levels of postprandial retinyl palmitate were also slightly, but not statistically, different (mainly after 6 hours). Conclusions: Healthy young adult sons, whose fathers have established coronary artery disease, have prolonged postprandial hypertriglyceridemia. Changes in postprandial lipoprotein metabolism appear to be associated with familial risk for coronary atherosclerosis

Value of admission electrocardiogram in predicting outcome of thrombolytic therapy in acute myocardial infarction

To determine the value of the admission 12-lead electrocardiogram to predict infarct size limitation by thrombolytic therapy, data were analyzed in 488 of 533 patients with acute myocardial infarction (AMI) from a randomized multicenter study. All patients had typical electrocardiographic changes diagnostic for an AMI and were admitted within 4 hours after the onset of chest pain; 245 patients were allocated to thrombolytic treatment and 243 to conventional treatment. Cumulative 72-hour release into plasma of myocardial alpha-hydroxybutyrate dehydrogenase (HBDH) was used as a measure of infarct size. In general, the amount of infarct limitation due to thrombolytic therapy was proportional to the size of the area at risk. Patients with new Q waves, high QRS score and high ST-segment elevation or depression had the largest enzymatic infarct size in both treatment groups, irrespective of location of the AMI. Compared with conventionally treated patients, patients with anterior AMI treated with streptokinase had significant infarct size limitation (480 U/liter HBDH, 37%), and limitation was most prominent in those with Q waves (820 U/liter HBDH) or high ST elevation (750 U/liter HBDH). Infarct size limitation in inferior AMI was less impressive (330 U/liter HBDH, 33%) and patients with high ST-segment elevation (460 U/liter HBDH) or marked contralateral ST-segment depression (430 U/liter HBDH) had the most notable infarct limitation.(ABSTRACT TRUNCATED AT 250 WORDS

Verbeterde prognose voor patienten met een acuut hartinfarct door vroege thrombolyse

Twee behandelingen werden vergeleken in een gerandomiseerd onderzoek waaraan 533 patiënten met een acuut infarct deelnamen, 264 patiënten werden conventioneel behandeld (groep 1) en 269 kregen een behandeling die gericht was op snelle rekanalisatie van de veelal afgesloten coronairarterie (groep 2). Bij de eerste 152 patiënten in groep 2 werd uitsluitend intracoronair streptokinase gegeven (250.000 eenheden), onmiddellijk na coronariografie. Bij de volgende 117 patiënten werd deze intracoronaire behandeling voorafgegaan door intraveneuze toediening van streptokinase (500.000 eenheden). Bij 198 van de 234 patiënten bij wie angiografie werd verricht in de acute fase van het infarct, was de met het infarct samenhangende coronairarterie doorgankelijk aan het eind van de ingreep (85). De sterfte was lager bij patiënten uit groep 2 gedurende de gehele follow-up-periode. De éénjaarsoverleving was 91 bij patiënten in groep 2 en 84 in groep 1. Het voorkomen van ventrikelfibrilleren, pericarditis en card

The pharmacogenetics of Statin Therapy on clinical events: no evidence that genetic variation affects statin response on myocardial infarction

Background: The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association study (GWAS) analysis within the Genomic Investigation of Statin Therapy (GIST) consortium, we investigated whether genetic variation was associated with the response of statins on cardiovascular disease risk reduction.Methods: The investigated endpoint was incident myocardial infarction (MI) defined as coronary heart disease death and definite and suspect non-fatal MI. For imputed single nucleotide polymorphisms (SNPs), regression analysis was performed on expected allelic dosage and meta-analysed with a fixed-effects model, inverse variance weighted meta-analysis. All SNPs with p-values <5.0 x 10(-4) in stage 1 GWAS meta-analysis were selected for further investigation in stage-2. As a secondary analysis, we extracted SNPs from the Stage-1 GWAS meta-analysis results based on predefined hypotheses to possibly modifying the effect of statin therapy on MI.Results: In stage-1 meta-analysis (eight studies, n = 10,769, 4,212 cases), we observed no genome-wide significant results (p < 5.0 x 10(-8)). A total of 144 genetic variants were followed-up in the second stage (three studies, n = 1,525, 180 cases). In the combined meta-analysis, no genome-wide significant hits were identified. Moreover, none of the look-ups of SNPs known to be associated with either CHD or with statin response to cholesterol levels reached Bonferroni level of significance within our stage-1 meta-analysis.Conclusion: This GWAS analysis did not provide evidence that genetic variation affects statin response on cardiovascular risk reduction. It does not appear likely that genetic testing for predicting effects of statins on clinical events will become a useful tool in clinical practice.Pathophysiology, epidemiology and therapy of agein