Risk Stratification and Risk Modification in Patients with Acute Coronary Syndromes

When patients are suffering an acute coronary syndrome (ACS) it is important to know, for themselves, but also for their treating physicians and for allocation of available resources, what their risk will be for developing a new cardiovascular event not only at short-term but also during long-term follow-up. Risk assessment may help to select the optimal management to reduce the risk of untoward events. In this thesis the different aspects of this subject are evaluated

Scaling and trends of hourly precipitation extremes in two different climate zones – Hong Kong and the Netherlands

Hourly precipitation extremes in very long time series from the Hong Kong Observatory and the Netherlands are investigated. Using the 2 m dew point temperature from 4 h before the rainfall event as a measure of near surface absolute humidity, hourly precipitation extremes closely follow a 14% per degree dependency – a scaling twice as large as following from the Clausius-Clapeyron relation. However, for dew point temperatures above 23 °C no significant dependency on humidity was found. Strikingly, in spite of the large difference in climate, results are almost identical in Hong Kong and the Netherlands for the dew point temperature range where both observational sets have sufficient data. Trends in hourly precipitation extremes show substantial increases over the last century for both De Bilt (the Netherlands) and Hong Kong. For De Bilt, not only the long term trend, but also variations in hourly precipitation extremes on an inter-decadal timescale of 30 yr and longer, can be linked very well to the above scaling; there is a very close resemblance between variations in dew point temperature and precipitation intensity with an inferred dependency of hourly precipitation extremes of 10 to 14% per degree. For Hong Kong there is no connection between variations in humidity and those in precipitation intensity in the wet season, May to September. This is consistent with the found zero-dependency of precipitation intensity on humidity for dew points above 23 °C. Yet, outside the wet season humidity changes do appear to explain the positive trend in hourly precipitation extremes, again following a dependency close to twice the Clausius-Clapeyron relation

Differential effects of tissue plasminogen activator and streptokinase on infarct size and on rate of enzyme release: influence of early infarct related artery patency: The GUSTO Enzyme Substudy

Background The recent international GUSTO trial of 41 021 patients with acute myocardial infarction demonstrated improved 90-mm infarct related artery patency as well as reduced mortality in patients treated with an accelerated regimen of tissue plasminogen activator, compared to patients treated with streptokinase. A regimen combining tissue plasminogen activator and streptokinase yielded intermediate results. The present study investigated the effects of treatment on infarct size and enzyme release kinetics in a subgroup of these patients. Methods A total of 553 patients from 15 hospitals were enrolled in the study. Four thrombolytic strategies were compared: streptokinase with subcutaneous heparin, streptokinase with intravenous (iv.) heparin, tissue plasminogen activator with iv. heparin, and streptokinase plus tissue plasminogen activator with i.v. heparin. The activity of alpha-hydroxybutyrate dehydrogenase (HBDH) in plasma was centrally analysed and infarct size was defined as cumulative HBDH release per litre of plasma within 72 h of the first symptoms (Q(72)). Patency of the infarct-related vessel was determined by angiography in 159 patients, 90 mm after treatment. Results Infarct size was 3·72 g-eq . 1−1 in patients with adequate coronary perfusion (TIMI-3) at the 90 mm angi-ogram and larger in patients with TIMI-2 (4·35 g-eq . 1−1) or TIMI 0-1 (5·07 g-eq . 1−1)flow (P=0·024). In this subset of the GUSTO angiographic study, early coronary patency rates (TIMI 2+3) were similar in the two streptokinase groups (53 and 46%). Higher, but similar, patency rates were observed in the tissue plasminogen activator and combination therapy groups (87 and 90%). Median infarct size for the four treatment groups, expressed in gram- equivalents (g-eq) of myocardium, was 4·4, 4·5, 3·9 and 3·9 g-eq per litre of plasma (P=0·04 for streptokinase vs tissue plasminogen activator). Six hours after the first symptoms, respectively 5·3, 6·6, 14·0 and 13·6% of total HBDH release was complete (P<0·000l for streptokinase vs tissue plasminogen activator). Conclusions Rapid and complete coronary reperfusion salvages myocardial tissue, resulting in limitation of infarct size and accelerated release of proteins from the myocardium. Treatment with tissue plasminogen activator, resulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differences in survival between treatment groups in the GUSTO tria

Reduction of recurrent ischemia with abciximab during continuous ECG-ischemia monitoring in patients with unstable angina refractory to standard treatment (CAPTURE)

BACKGROUND: In the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina) trial, 1265 patients with refractory unstable angina were treated with abciximab or placebo, in addition to standard treatment from 16 to 24 hours preceding coronary intervention through 1 hour after intervention. To investigate the incidence of recurrent ischemia and the ischemic burden, a subset of 332 patients (26%) underwent continuous vector-derived 12-lead ECG-ischemia monitoring. METHODS and RESULTS: Patients were monitored from start of treatment through 6 hours after coronary intervention. Ischemic episodes were detected in 31 (18%) of the 169 abciximab and in 37 (23%) of the 163 placebo patients (NS). Only 9 (5%) of abciximab versus 22 (14%) of placebo patients had >/=2 ST episodes (P<0.01). In patients with ischemia, abciximab significantly reduced total ischemic burden (P<0.02), which was calculated alternatively as the total duration of ST episodes per patient, the area under the curve of the ST vector magnitude during episodes, or the sum of the areas under the curves of 12 leads during episodes. Twenty-one patients (6%) suffered a myocardi

Comparison of usefulness of computer assisted continuous 48-h 3-lead with 12-lead ECG ischaemia monitoring for detection and quantitation of ischaemia in patients with unstable angina

AIMS: The selection of ECG leads used for ST monitoring may influence detection and quantitation of ischaemia. METHODS: We compared on-line continuous 48-h 12-lead against 3-lead ST monitoring in 130 unstable angina patients (Mortara. ELI-100). Onset and offset of ST episodes were defined by the lead with the first > or = 100 microV ST change relative to baseline and the lead with the latest return to baseline ST level, respectively. ST episodes were calculated for 12 leads and 3 leads (V2, V5, III) separately. RESULTS: ST episodes were detected in 88 patients (77%) by 12-lead and in 71 patients (62%) by 3-lead ST monitoring (P < 0.02). The median number (25.75%) of episodes/patient was 1 (0.3) for 3-lead and 2 (1.6) for 12-lead (P < 0.0001). The total duration of ischaemia detected during 12-lead far exceeded 3-lead monitoring: 12.3 (1, 58.2) and 1.7 (0, 23.3) min respectively (P < 0.0001). The probability of recurrent ischaemia declined most during the first 24 h of monitoring. After a period without ST changes of 1, 12, 24 and 36 h, the probabilities of recurrent ischaemia were 63, 31, 14 and 9%, respectively. CONCLUSIONS: Continuous 12-lead ST monitoring increases detection rate and duration of ST episodes compared to 3-lead ST monitoring. The use of continuous 12-lead ECG monitoring devices on emergency wards and coronary care units is recommended

Relation of Iron Status to Prognosis After Acute Coronary Syndrome

Iron deficiency has been extensively researched and is associated with adverse outcomes in heart failure. However, to our knowledge, the temporal evolution of iron status has not been previously investigated in patients with acute coronary syndrome (ACS). Therefore, we aimed to explore the temporal pattern of repeatedly measured iron, ferritin, transferrin, and transferrin saturation (TSAT) in relation to prognosis post-ACS. BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective, multicenter, observational cohort study conducted in The Netherlands between 2008 and 2015. A total of 844 patients with post-ACS were enrolled and underwent high-frequency (median 17) blood sampling during 1 year follow-up. Biomarkers of iron status were measured batchwise in a central laboratory. We analyzed 3 patient subsets, including the case-cohort (n = 187). The primary endpoint (PE) was a composite of cardiovascular mortality and repeat nonfatal ACS, including unstable angina pectoris requiring revascularization. The association between iron status and the PE was analyzed using multivariable joint models. Mean age was 63 years; 78% were men, and >50% had iron deficiency at first sample in the case-cohort. After adjustment for a broad range of clinical variables, 1 SD decrease in log-iron was associated with a 2.2-fold greater risk of the PE (hazard ratio 2.19, 95% confidence interval 1.34 to 3.54, p = 0.002). Similarly, 1 SD decrease in log-TSAT was associated with a 78% increased risk of the PE (hazard ratio 1.78, 95% confidence interval 1.17 to 2.65, p = 0.006). Ferritin and transferrin were not associated with the PE. Repeated measurements of iron and TSAT predict risk of adverse outcomes in patients with post-ACS during 1 year follow-up. Trial Registration: The Netherlands Trial Register. Unique identifiers: NTR1698 and NTR1106. Registered at https://www.trialregister.nl/trial/1614 and https://www.trialregister.nl/trial/1073