Detailed data on patients admitted for acute myocardial infarction (AMI) on a European-wide basis are lacking. The Euro Heart Survey 2009 Snapshot was designed to assess characteristics, management, and hospital outcomes of AMI patients throughout European Society of Cardiology (ESC) member countries in a contemporary ‘real-world’ setting, using a methodology designed to improve the representativeness of the survey.
Member countries of the ESC were invited to participate in a 1-week survey of all patients admitted for documented AMI in December 2009. Data on baseline characteristics, type of AMI, management, and complications were recorded using a dedicated electronic form. In addition, we used data collected during the same time period in national registries in Sweden, England, and Wales. Data were centralized at the European Heart House.
Overall, 4236 patients (mean age 66±13 years; 31% women) were included in the study in 47 countries. Sixty per cent of patients had ST-segment elevation myocardial infarction, with 50% having primary percutaneous coronary intervention and 21% fibrinolysis. Aspirin and thienopyridines were used in >90%. Unfractionated and low-molecular-weight heparins were the most commonly used anticoagulants. Statins, beta-blockers, and angiotensin-converting enzyme inhibitors were used in >80% of the patients. In-hospital mortality was 6.2%. Regional differences were observed, both in terms of population characteristics, management, and outcomes.
In-hospital mortality of patients admitted for AMI in Europe is low. Although regional variations exist in their presentation and management, differences are limited and have only moderate impact on early outcomes.
Acute myocardial infarction; Europe; hospital outcomes; survey
To describe the characteristics, treatment, and mortality in patients with ST-elevation myocardial infarction (STEMI) by use of chronic oral anticoagulant (OAC) therapy.
Using data from the Global Registry of Acute Coronary Syndromes (GRACE), patient characteristics, treatment, and reperfusion strategies of STEMI patients on chronic OAC are described, and relevant variables compared with patients not on chronic OAC. Six-month post-discharge mortality rates were evaluated by Cox proportional hazard models.
Of 19,094 patients with STEMI, 574 (3.0%) were on chronic OAC at admission. Compared with OAC non-users, OAC users were older (mean age 73 vs. 65 years), more likely to be female (37 vs. 29%), were more likely to have a history of atrial fibrillation, prosthetic heart valve, venous thromboembolism, or stroke/transient ischaemic attack, had a higher mean GRACE risk score (166 vs. 145), were less likely to be Killip class I (68 vs. 82%), and were less likely to undergo catheterization/percutaneous coronary intervention (52 vs. 66%, respectively). Of the patients who underwent catheterization, fewer OAC users had the procedure done within 24 h of admission (56.5 vs. 64.5% of OAC non-users). In propensity-matched analyses (n=606), rates of in-hospital major bleeding and in-hospital and 6-month post-discharge mortality were similar for OAC users and OAC non-users (2.7 and 3.7%, p=0.64; 15 and 13%, p=0.56; 15 and 12%, p=0.47, respectively), rates of in-hospital recurrent myocardial infarction (8.6 and 2.0%, p<0.001) and atrial fibrillation (32 and 22%, p=0.004) were higher in OAC patients, and rates of 6-month stroke were lower (0.6 and 4.3%, p=0.038). Patients in both groups who underwent catheterization had lower mortality than those who did not undergo catheterization.
This is the largest study to describe the characteristics and treatment of STEMI patients on chronic OAC. The findings suggest that patients on chronic OAC are less likely to receive guideline-indicated management, but have similar adjusted rates of in-hospital and 6-month mortality.
Acute coronary syndrome; anticoagulant; guidelines; myocardial infarction
To investigate whether a hospital-specific opportunity-based composite score (OBCS) was associated with mortality in 136,392 patients with acute myocardial infarction (AMI) using data from the Myocardial Ischaemia National Audit Project (MINAP) 2008–2009.
Methods and results:
For 199 hospitals a multidimensional hospital OBCS was calculated on the number of times that aspirin, thienopyridine, angiotensin-converting enzyme inhibitor (ACEi), statin, β-blocker, and referral for cardiac rehabilitation was given to individual patients, divided by the overall number of opportunities that hospitals had to give that care. OBCS and its six components were compared using funnel plots. Associations between OBCS performance and 30-day and 6-month all-cause mortality were quantified using mixed-effects regression analysis. Median hospital OBCS was 95.3% (range 75.8–100%). By OBCS, 24.1% of hospitals were below funnel plot 99.8% CI, compared to aspirin (11.1%), thienopyridine (15.1%), β-blockers (14.7%), ACEi (19.1%), statins (12.1%), and cardiac rehabilitation (17.6%) on discharge. Mortality (95% CI) decreased with increasing hospital OBCS quartile at 30 days [Q1, 2.25% (2.07–2.43%) vs. Q4, 1.40% (1.25–1.56%)] and 6 months [Q1, 7.93% (7.61–8.25%) vs. Q4, 5.53% (5.22–5.83%)]. Hospital OBCS quartile was inversely associated with adjusted 30-day and 6-month mortality [OR (95% CI), 0.87 (0.80–0.94) and 0.92 (0.88–0.96), respectively] and persisted after adjustment for coronary artery catheterization [0.89 (0.82–0.96) and 0.95 (0.91–0.98), respectively].
Multidimensional hospital OBCS in AMI survivors are high, discriminate hospital performance more readily than single performance indicators, and significantly inversely predict early and longer-term mortality.
Acute myocardial infarction; composite performance indicators; mortality; performance; quality of care
Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial.
Methods and Results
TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals.
Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing.
Clinical Trial Registration
URL: ClinicalTrials.gov. Unique identifier: NCT00403767.
anticoagulants; arrhythmia; embolism; prevention; risk factors
Platelet activation is central to the pathogenesis of acute coronary syndromes. Surface expression of P‐selectin on activated platelets induces formation of platelet–monocyte aggregates and promotes vascular inflammation and thrombosis. P‐selectin antagonism may represent a novel therapeutic strategy in vascular disease. We aimed to investigate the effects of the novel P‐selectin antagonist PSI‐697 on platelet–monocyte aggregate formation in humans.
Methods and Results
In a double‐blind, randomized, placebo‐controlled crossover study, healthy smokers were randomized to receive either oral PSI‐697 600 mg or matched placebo. The sequence of treatment was also randomized, with all subjects receiving both PSI‐697 and placebo. Platelet–monocyte aggregates were measured by flow cytometry at 4 and 24 hours in the presence and absence of thrombin receptor‐activating peptide (TRAP; 0.1 to 1.0 μm/L). The ex vivo addition of TRAP caused a concentration‐dependent increase in platelet–monocyte aggregates from 8.2% to 94.8% (P<0.001). At 4 and 24 hours, plasma concentrations of PSI‐697 increased to 1906 and 83 ng/mL, respectively (P<0.001). PSI‐697 had no demonstrable effect on either stimulated or unstimulated platelet–monocyte aggregates at 4 or 24 hours (P>0.05). P‐selectin‐blocking antibody (CLB‐Thromb6), but not PSI‐697, inhibited both stimulated and unstimulated platelet–monocyte aggregate formation in vitro (P<0.001).
The novel small‐molecule P‐selectin antagonist PSI‐697 did not inhibit basal or stimulated platelet–monocyte aggregate formation in humans at the dose tested. Its clinical efficacy remains to be established.
Clinical Trial Registration
URL: http://EudraCT.ema.europa.eu Unique identifier: 2007‐005695‐14.
platelets; P‐selectin; thrombosis
Atrial fibrillation (AF) is the most common form of cardiac arrhythmia and associated with significant mortality and morbidity. It is a powerful predictor of future embolic stroke, such that anticoagulation is recommended in the majority of patients. For many years this has predominantly been in the form of vitamin K antagonists. However, there are well-documented difficulties with their administration that result in poor compliance and high discontinuation rates. Over recent years several oral alternative anticoagulant agents have become available with the potential to overcome many of these pitfalls. In this review, we discuss current recommendations for anticoagulant therapy in AF and how these may change in the future with the introduction of novel therapeutic options.
Pyrrolobenzodiazepine (PBD) dimers, tethered through inert propyldioxy or pentyldioxy linkers, possess potent bactericidal activity against a range of Gram-positive bacteria by virtue of their capacity to cross-link duplex DNA in sequence-selective fashion. Here we attempt to improve the antibacterial activity and cytotoxicity profile of PBD-containing conjugates by extension of dimer linkers and replacement of one PBD unit with phenyl-substituted or benzo-fused heterocycles that facilitate non-covalent interactions with duplex DNA.
DNase I footprinting was used to identify high-affinity DNA binding sites. A staphylococcal gene microarray was used to assess epidemic methicillin-resistant Staphylococcus aureus 16 phenotypes induced by PBD conjugates. Molecular dynamics simulations were employed to investigate the accommodation of compounds within the DNA helix.
Increasing the length of the linker in PBD dimers led to a progressive reduction in antibacterial activity, but not in their cytotoxic capacity. Complex patterns of DNA binding were noted for extended PBD dimers. Modelling of DNA strand cross-linking by PBD dimers indicated distortion of the helix. A majority (26 of 43) of PBD-biaryl conjugates possessed potent antibacterial activity with little or no helical distortion and a more favourable cytotoxicity profile. Bactericidal activity of PBD-biaryl conjugates was determined by inability to excise covalently bound drug molecules from bacterial duplex DNA.
PBD-biaryl conjugates have a superior antibacterial profile compared with PBD dimers such as ELB-21. We have identified six PBD-biaryl conjugates as potential drug development candidates.
pyrrolobenzodiazepine dimers; pyrrolobenzodiazepine-biaryl conjugates; DNA adduct formation; MRSA
Acute coronary syndrome (ACS) is common in patients approaching the end-of-life (EoL), but these patients rarely receive palliative care. We compared the utility of a palliative care prognostic tool (Gold Standards Framework (GSF)) and the Global Registry of Acute Coronary Events (GRACE) score, to help identify patients approaching EoL.
Methods and Findings
172 unselected consecutive patients with confirmed ACS admitted over an eight-week period were assessed using prognostic tools and followed up for 12 months. GSF criteria identified 40 (23%) patients suitable for EoL care while GRACE identified 32 (19%) patients with ≥10% risk of death within 6 months. Patients meeting GSF criteria were older (p = 0.006), had more comorbidities (1.6±0.7 vs. 1.2±0.9, p = 0.007), more frequent hospitalisations before (p = 0.001) and after (0.0001) their index admission, and were more likely to die during follow-up (GSF+ 20% vs GSF- 7%, p = 0.03). GRACE score was predictive of 12-month mortality (C-statistic 0.75) and this was improved by the addition of previous hospital admissions and previous history of stroke (C-statistic 0.88).
This study has highlighted a potentially large number of ACS patients eligible for EoL care. GSF or GRACE could be used in the hospital setting to help identify these patients. GSF identifies ACS patients with more comorbidity and at increased risk of hospital readmission.
In order to enhance DNA triple helix stability synthetic oligonucleotides have been developed that bear amino groups on the sugar or base. One of the most effective of these is bis-amino-U (B), which possesses 5-propargylamino and 2′-aminoethoxy modifications. Inclusion of this modified nucleotide not only greatly enhances triplex stability, but also increases the affinity for related sequences. We have used a restriction enzyme protection, selection and amplification assay (REPSA) to isolate sequences that are bound by the heavily modified 9-mer triplex-forming oligonucleotide B6CBT. The isolated sequences contain An tracts (n = 6), suggesting that the 5′-end of this TFO was responsible for successful triplex formation. DNase I footprinting with these sequences confirmed triple helix formation at these secondary targets and demonstrated no interaction with similar oligonucleotides containing T or 5-propargylamino-dU.
Adherence to evidence-based treatments and its consequences after acute myocardial infarction (MI) are poorly defined. We examined the extent to which clopidogrel treatment initiated in hospital is continued in primary care; the factors predictive of clopidogrel discontinuation and the hazard of death or recurrent MI.
Methods and results
We linked the Myocardial Ischaemia National Audit Project registry and the General Practice Research Database to examine adherence to clopidogrel in primary care among patients discharged from hospital after MI (2003–2009). Hospital Episode Statistics and national mortality data were linked, documenting all-cause mortality and non-fatal MI. Of the 7543 linked patients, 4650 were prescribed clopidogrel in primary care within 3 months of discharge. The adjusted odds of still being prescribed clopidogrel at 12 months were similar following non-ST-elevation myocardial infarction (NSTEMI) 53% (95% CI, 51–55) and ST-elevation myocardial infarction (STEMI) 54% (95% CI, 52–56), but contrast with statins: NSTEMI 84% (95% CI, 82–85) and STEMI 89% (95% CI, 87–90). Discontinuation within 12 months was more frequent in older patients [>80 vs. 40–49 years, adjusted hazard ratio (HR) 1.50 (95% CI, 1.15–1.94)] and with bleeding events [HR 1.34 (95% CI, 1.03–1.73)]. 18.15 patients per 100 person-years (95% CI, 16.83–19.58) died or experienced non-fatal MI in the first year following discharge. In patients who discontinued clopidogrel within 12 months, the adjusted HR for death or non-fatal MI was 1.45 (95% CI, 1.22–1.73) compared with untreated patients, and 2.62 (95% CI, 2.17–3.17) compared with patients persisting with clopidogrel treatment.
This is the first study to use linked registries to determine persistence of clopidogrel treatment after MI in primary care. It demonstrates that discontinuation is common and associated with adverse outcomes.
ACS; Myocardial infarction; Clopidogrel; Anti-platelet; Observational
To examine the extent of delay from initial hospital presentation to fibrinolytic therapy or primary percutaneous coronary intervention (PCI), characteristics associated with prolonged delay, and changes in delay patterns over time in patients with ST-segment elevation myocardial infarction (STEMI).
Methods and results
We analysed data from 5170 patients with STEMI enrolled in the Global Registry of Acute Coronary Events from 2003 to 2007. The median elapsed time from first hospital presentation to initiation of fibrinolysis was 30 min (interquartile range 18–60) and to primary PCI was 86 min (interquartile range 53–135). Over the years under study, there were no significant changes in delay times to treatment with either strategy. Geographic region was the strongest predictor of delay to initiation of fibrinolysis >30 min. Patient's transfer status and geographic location were strongly associated with delay to primary PCI. Patients treated in Europe were least likely to experience delay to fibrinolysis or primary PCI.
These data suggest no improvements in delay times from hospital presentation to initiation of fibrinolysis or primary PCI during our study period. Geographic location and patient transfer were the strongest predictors of prolonged delay time, suggesting that improvements in modifiable healthcare system factors can shorten delay to reperfusion therapy even further.
Percutaneous coronary intervention; ST-segment elevation myocardial infarction; Reperfusion; Fibrinolysis
Recent genetic studies identified the rs1333049 variant on chromosome 9p21 as a major susceptibility locus for coronary artery disease and myocardial infarction (MI). Here, we evaluated whether this variant also contributes to recurrent MI or cardiac death following an acute coronary syndrome (ACS).
Methods and results
A total of 3247 patients with ACS enrolled in the Global Registry of Acute Coronary Events (GRACE) in three distinct populations (UK, Belgium and Poland) were prospectively followed for 6 months and genotyped for rs1333049, in addition to 3004 and 2467 healthy controls from the UK and Belgium. After having confirmed that the at-risk C allele of rs1333049 was associated with index ACS in the UK and Belgian populations, we found that the rs1333049 at-risk C allele was significantly and independently associated with recurrent MI [age- and gender-adjusted hazard ratio (HR) 1.48, CI = 1.00–2.19, P = 0.048; and multivariable-adjusted HR 1.47, CI = 0.99–2.18; P = 0.053] and with recurrent MI or cardiac death (age- and gender-adjusted HR 1.58, CI = 1.00–2.48; P = 0.045; and multivariable adjusted HR 1.49, CI = 1.03–1.98; P = 0.028) within 6 months after an index ACS. Inclusion of rs1333049 into the GRACE risk score significantly improved classification for recurrent MI or cardiac death (P = 0.040), as calculated by the integrated discrimination improvement method.
In this large observational study, the 9p21 variant was independently associated with adverse cardiac outcome after ACS.
Chromosome 9p21; Rs1333049; Genetics; Acute coronary syndrome; Myocardial infarction; Plaque rupture
Smoking increases platelet aggregability, and the degree of platelet inhibition by clopidogrel on ex vivo platelet function tests. Whether smoking status affects the relationship between clopidogrel and clinical outcomes is unknown.
Methods and Results
We evaluated the relationship between smoking status (current smoker (CS), former smoker (FS), and never smoker (NS)) and treatment with clopidogrel on the risk of all-cause, cardiovascular, and cancer mortality among the 12,152 participants from the CHARISMA trial with established cardiovascular disease. Current smoking was associated with an increase in all-cause (adjusted hazard ratio [HR] 2.58, [1.85–3.60]), cardiovascular (HR 2.26, [1.48–3.45]), and cancer mortality (HR 4.16, [2.46–7.03]) compared to NS. The impact of clopidogrel and mortality differed by smoking status (P for interaction = 0.018 for current smokers). Among CS, clopidogrel was associated with a reduction in all-cause mortality (HR 0.68, [0.49–0.94]); clopidogrel did not reduce all cause mortality among FS (HR 0.95, [0.75–1.19]) or NS (HR 1.14, [0.83–1.58]). A similar pattern was noted for cardiovascular mortality. As expected, no relationship was observed between clopidogrel and cancer mortality by smoking status. The risk of bleeding seemed to differ according to smoking status; randomized clopidogrel was associated with a significantly increased hazard of severe or moderate bleeding (HR 1.62, P=0.04) among CS, but a smaller and nonsignificant increase among NS (HR 1.31, P=0.15).
Clopidogrel therapy may be more effective, but with a greater bleeding risk in CS than in patients who are not smokers. Further studies are needed to investigate this possibility.
Smoking; Clopidogrel; Mortality; Cardiovascular disease
More than 50% of patients initially resuscitated from out‐of‐hospital cardiac arrest die in hospital.
To investigate the prognostic value of serum protein S‐100 and neuron‐specific enolase (NSE) concentrations for predicting (a) memory impairment at discharge; (b) in‐hospital death, after resuscitation from out‐of‐hospital cardiac arrest.
In a prospective study of 143 consecutive survivors of out‐of‐hospital cardiac arrest, serum samples were obtained within 12, 24–48 and 72–96 hours after the event. S‐100 and NSE concentrations were measured. Pre‐discharge cognitive assessment of patients (n = 49) was obtained by the Rivermead Behavioural Memory Test (RBMT). The relationship between biochemical brain marker concentrations and RBMT scores, and between marker concentrations and the risk of in‐hospital death was examined.
A moderate negative relationship was found between S‐100 concentration and memory test score, at all time points. The relationship between NSE and memory test scores was weaker. An S‐100 concentration >0.29 μg/l at time B predicted moderate to severe memory impairment with absolute specificity (42.8% sensitivity). S‐100 remained an independent predictor of memory function after adjustment for clinical variables and cardiac arrest timing indices. NSE and S‐100 concentrations were greater in patients who died than in those who survived, at all time points. Both NSE and S‐100 remained predictors of in‐hospital death after adjustment for clinical variables and cardiac arrest timing indices. The threshold concentrations yielding 100% specificity for in‐hospital death were S‐100: 1.20 μg/l (sensitivity 44.8%); NSE 71.0 μg/l (sensitivity 14.0%).
Estimation of serum S‐100 concentration after out‐of‐hospital cardiac arrest can be used to identify patients at risk of significant cognitive impairment at discharge. Serum S‐100 and NSE concentrations measured 24–48 hours after cardiac arrest provide useful additional information.
cardiac arrest; hypoxia–ischaemia (brain); cognitive function
ELB-21 is a pyrrolo[2,1-c][1,4]benzodiazepine dimer with potent anti-staphylococcal activity; it binds covalently to guanine residues on opposing strands of duplex DNA, interfering with regulatory proteins and transcription elongation in a sequence selective manner. Transcriptional and proteomic alterations induced by exposure of Staphylococcus aureus clinical isolate EMRSA-16 to ELB-21 were determined in order to define more precisely the bactericidal mechanism of the drug.
DNase I footprinting was used to identify high affinity DNA binding sites. Microarrays and gel electrophoresis were used to assess the ELB-21-induced phenotype.
High affinity interstrand binding sites in which guanine residues were separated by four base pairs, and also some intrastrand cross-linking sites of variable length were identified. Exposure of EMRSA-16 to 0.015 mg/L ELB-21 elicited a twofold or greater up-regulation of 168 genes in logarithmic phase and 181 genes in stationary phase; the majority of genes affected were associated with resident prophages φSa2 and φSa3, pathogenicity island SaPI4 and DNA damage repair. ELB-21 induced a marked increase in the number of viable phage particles in culture supernatants. The expression of only a limited number of genes showed more than 50% reduction. Sixteen extracellular and four intracellular proteins were differentially expressed during logarithmic and stationary phases, including RecA, proteins associated with staphylococcal pathogenesis (IsaA, CspA), cell division and wall synthesis.
ELB-21 kills S. aureus by forming multiple interstand and intrastrand DNA cross-links, resulting in induction of the DNA damage response, derepression of resident prophages and modulation of a limited number of genes involved with cell wall synthesis.
Staphylococcus aureus; pyrrolobenzodiazepine dimers; DNA cross-linking; DNA damage response; sequence-selective DNA binding
The objective of this study was to evaluate the diagnostic value of heart-type fatty acid-binding protein (H-FABP) in patients with acute chest pain and compare it with standard cardiac markers.
We undertook a prospective evaluation of 100 consecutive patients admitted with acute chest pain suggestive of acute coronary syndromes (ACS). Serum cardiac troponin I (cTnI), cardiac troponin T (cTnT), creatine kinase-MB (CK-MB) mass, myoglobin, and H-FABP were determined at presentation and 2, 4, 8–10, and 16–24 hours after presentation. The main outcome measure was the best sensitivity value within 6 hours after symptom onset.
H-FABP peak concentration occurred at 8 hours after symptoms onset and was the most sensitive early marker with 79.9% and 98% of patients with AMI identified at presentation and 2 hours after presentation respectively. The sensitivity of all other cardiac markers (CK-MB mass, cTnI, cTnT, and myoglobin) at presentation was < 62%. The negative predictive value of H-FABP (94%) was also superior to other markers within the first 2 hours of presentation. Myoglobin was the second most sensitive early marker at presentation. Peak sensitivity of cTnI, CK-MB mass, and cTnT were present at 4, 8–10, and 8–10 hours respectively after presentation.
Combined measurement of H-FABP and cTnI on two occasions during the first 8 hours after symptom onset was sufficiently sensitive and specific for the early diagnosis of most patients with acute MI and may provide advantages over other cardiac marker combinations.
Acute myocardial infarction; Acute coronary syndromes; Heart-type fatty acid-binding protein; Cardiac markers
The aim of this study was to assess the diagnostic and prognostic value of heart-type fatty acid-binding protein (H-FABP) in elective percutaneous coronary intervention (PCI) and compare it with standard cardiac markers.
A prospective evaluation was done of 80 consecutive patients admitted for elective PCI. Serum cardiac troponin T (cTnT), cardiac troponin I (cTnI), creatine kinase-MB (CK-MB mass), myoglobin, and H-FABP were determined pre-angioplasty and 1, 2, 4, and 16–24 hrs post-angioplasty. Elevated cardiac markers were correlated with demographic, angiographic and procedural variables. Patients were followed up for 20–26 months.
H-FABP peaked early at 2 hours and was useful for the early detection of evolving AMI within 1–3 hours after angioplasty. Cardiac-TnI, myoglobin, H-FABP, CK-MB mass, and cTnT concentrations were elevated in 46.25%, 17.5%, 13.3%, 11.25%, and 7.5% respectively. Cardiac-TnI was the most sensitive marker for detecting all complications and was superior to all other markers. Elevated cardiac markers were correlated with old age (P < 0.02); chest pain ± ECG changes of ischaemia (P < 0.003); use of stents (P < 0.019) and major complications such as major dissection (P < 0.004); transient vessel closure (P < 0.022); bail out stent (P < 0.003), and AMI (P < 0.042). Elevated cardiac markers were associated with a reduction of event-free survival (16.92 versus 20.67 months, P < 0.03).
Heart-type-FABP measurements at 1 hour (or thereafter) post-PCI may offer an early chance of detecting evolving AMI; cTnI was the most sensitive marker for the detection of major complications in patients undergoing PCI. Measurements of cTnI 16–24 hours post-PCI should be part of the routine management of patients following elective PCI.
Percutaneous coronary intervention; PCI; Acute coronary syndrome; Heart-type fatty acid-binding protein; Cardiac markers; Cardiac troponins; Complications
To determine whether changes in practice, over time, are associated with altered rates of major bleeding in acute coronary syndromes (ACS).
Methods and results
Patients from the Global Registry of Acute Coronary Events were enrolled between 2000 and 2007. The main outcome measures were frequency of major bleeding, including haemorrhagic stroke, over time, after adjustment for patient characteristics, and impact of major bleeding on death and myocardial infarction. Of the 50 947 patients, 2.3% sustained a major bleed; almost half of these presented with ST-elevation ACS (44%, 513). Despite changes in antithrombotic therapy (increasing use of low molecular weight heparin, P < 0.0001), thienopyridines (P < 0.0001), and percutaneous coronary interventions (P < 0.0001), frequency of major bleeding for all ACS patients decreased (2.6 to 1.8%; P < 0.0001). Most decline was seen in ST-elevation ACS (2.9 to 2.1%, P = 0.02). The overall decline remained after adjustment for patient characteristics and treatments (P = 0.002, hazard ratio 0.94 per year, 95% confidence interval 0.91–0.98). Hospital characteristics were an independent predictor of bleeding (P < 0.0001). Patients who experienced major bleeding were at increased risk of death within 30 days from admission, even after adjustment for baseline variables.
Despite increasing use of more intensive therapies, there was a decline in the rate of major bleeding associated with changes in clinical practice. However, individual hospital characteristics remain an important determinant of the frequency of major bleeding.
Acute coronary syndrome; Bleeding; Unstable angina; Myocardial infarction
Heart-type fatty acid binding-protein (H-FABP) has been reported to be a potential novel biochemical marker for the early diagnosis of acute myocardial infarction (AMI). The effect of kidney diseases on the renal handling of H-FABP has not yet been fully evaluated. The aim of this study was to compare the effect of renal failure on the level of H-FABP and cardiac troponin (cTnT) concentrations.
The study population was a small group of 16 patients with renal failure (6 females, 10 males aged 30–70 years) on routine regular haemodialysis or peritoneal dialysis.
The mean ±SD of serum urea and creatinine concentration in this group of patients was 19 ±9.6 mmol/L and 531.3 ±231.2 mmol/L respectively. H-FABP was increased in all 16 patients (81 ±53.3μg/L). The cTnT was increased ≥ 0.1μg/L in 8 patients (50%), ≥ 0.2μg/L in 5 patients (31.3%), and ≥ 0.3μg/L in 1 patient (6%).
The diagnostic efficiency of H-FABP and cTnT for the diagnosis of AMI in the presence of renal failure may be limited and such patients may have high levels even in the absence of AMI.
Heart-type fatty acid-binding protein; Cardiac troponin T; Renal failure
Chest pain is a non-specific complaint and is the most frequent reason for patients seeking urgent medical attention. A small group of these patients will have acute coronary syndromes (ACS). The current diagnostic and triage systems based on clinical history and electrocardiograms are insufficient. They may result in some of these patients being misdiagnosed and being admitted to the wrong units or receiving inappropriate care, treatment and investigations. In some patients, the diagnosis is delayed resulting in the late administration (or no administration) of essential early treatment. A few patients with ACS may be inadvertently discharged from the emergency department leading to serious health and legal implications. These systems also result in the unnecessary admission of a substantial number of patients without ACS. The triage and management of patients with chest pain can be considerably improved by implementation of serial cardiac markers testing that can identify ACS in the very early stages of presentation. This review article will discuss the currently available markers of myocardial damage such as creatine kinase (CK), creatine kinase muscle and brain (CK-MB) (mass and activity), CK-MB isoforms, heart-type fatty acid-binding protein, myoglobin, cardiac troponin T, and cardiac troponin I.
Cardiac markers; Acute coronary syndromes; ACS; Acute myocardial infarction; AMI; Non-ST elevation myocardial infarction; NSTEMI; Chest pain
The Thrombolysis in Myocardial Infarction (TIMI) risk scores for Unstable Angina/Non-ST–elevation myocardial infarction (UA/NSTEMI) and ST-elevation myocardial infarction (STEMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores for in-hospital and 6-month mortality are established tools for assessing risk in Acute Coronary Syndrome (ACS) patients. The objective of our study was to compare the discriminative abilities of the TIMI and GRACE risk scores in a broad-spectrum, unselected ACS population and to assess the relative contributions of model simplicity and model composition to any observed differences between the two scoring systems.
ACS patients admitted to the University of Michigan between 1999 and 2005 were divided into UA/NSTEMI (n = 2753) and STEMI (n = 698) subpopulations. The predictive abilities of the TIMI and GRACE scores for in-hospital and 6-month mortality were assessed by calibration and discrimination. There were 137 in-hospital deaths (4%), and among the survivors, 234 (7.4%) died by 6 months post-discharge. In the UA/NSTEMI population, the GRACE risk scores demonstrated better discrimination than the TIMI UA/NSTEMI score for in-hospital (C = 0.85, 95% CI: 0.81–0.89, versus 0.54, 95% CI: 0.48–0.60; p<0.01) and 6-month (C = 0.79, 95% CI: 0.76–0.83, versus 0.56, 95% CI: 0.52–0.60; p<0.01) mortality. Among STEMI patients, the GRACE and TIMI STEMI scores demonstrated comparably excellent discrimination for in-hospital (C = 0.84, 95% CI: 0.78–0.90 versus 0.83, 95% CI: 0.78–0.89; p = 0.83) and 6-month (C = 0.72, 95% CI: 0.63–0.81, versus 0.71, 95% CI: 0.64–0.79; p = 0.79) mortality. An analysis of refitted multivariate models demonstrated a marked improvement in the discriminative power of the TIMI UA/NSTEMI model with the incorporation of heart failure and hemodynamic variables. Study limitations included unaccounted for confounders inherent to observational, single institution studies with moderate sample sizes.
The GRACE scores provided superior discrimination as compared with the TIMI UA/NSTEMI score in predicting in-hospital and 6-month mortality in UA/NSTEMI patients, although the GRACE and TIMI STEMI scores performed equally well in STEMI patients. The observed discriminative deficit of the TIMI UA/NSTEMI score likely results from the omission of key risk factors rather than from the relative simplicity of the scoring system.
Heart-type fatty acid binding-protein (H-FABP) has been reported to be a potential novel biochemical marker for the early diagnosis of acute myocardial infarction (AMI). The presence of H-FABP in the liver has not been reported. The aim of this study was to compare the effect of chronic liver diseases on the level of H-FABP concentrations.
The effects of chronic liver diseases including infective hepatitis and cirrhosis on the concentration of H-FABP was studied in a small group of patients (n=10, mean age ±SD = 58.33 ± 7.19 years). The serum concentrations of the following markers were measured: H-FABP, alanine aminotransferase (ALT) and bilirubin and compared with a reference control group (20 healthy blood donors, mean age ±SD = 63.8 ±8.01).
The serum concentrations of these markers in the control group as compared to patients with chronic liver disease were as follows (mean ± SD): H-FABP = 6.86 ±2.21 μg/L versus 6.44 ±3.06 μg/L (p = NS); ALT = 29.8 ±14.7 U/L versus ALT = 198.67 ±122.89 U/L (p < 0.0005) and bilirubin = 9.6 ±4.0 μmol/L versus bilirubin = 100.89 ±87.85 μmol/L (p < 0.0001).
These data illustrate clearly that there is no significant interference with the normal concentration of H-FABP in the presence of liver diseases, despite the significant elevation of liver enzymes and proteins. These data may support a useful role of H-FABP for the diagnosis of myocardial injury in patients with liver diseases.
Heart-type fatty acid-binding protein (H-FABP); Chronic liver diseases; Bilirubin; Alanine aminotransferase
We have prepared triplex-forming oligonucleotides containing the nucleotide analogue 5-dimethylaminopropargyl deoxyuridine (DMAPdU) in place of thymidine and examined their ability to form intermolecular triple helices by thermal melting and DNase I footprinting studies. The results were compared with those for oligonucleotides containing 5-aminopropargyl-dU (APdU), 5-guanidinopropargyl-dU (GPdU) and 5-propynyl dU (PdU). We find that DMAPdU enhances triplex stability relative to T, though slightly less than the other analogues that bear positive charges (T << PdU < DMAPdU < APdU < GPdU). For oligonucleotides that contain multiple substitutions with DMAPdU dispersed residues are more effective than clustered combinations. DMAPdU will be especially useful as a nucleotide analogue as, unlike APdU and GPdU, the base does not require protection during oligonucleotide synthesis and it can therefore be used with other derivatives that require mild deprotection conditions.
Abdominal adiposity is a growing clinical and public health problem. It is not known whether it is similarly associated with cardiovascular disease (CVD) and diabetes in different regions around the world, and thus whether measuring waist circumference (WC) in addition to body mass index (BMI) is useful in primary care practice.
Methods and Results
Randomly chosen primary care physicians (PCPs) in 63 countries recruited consecutive patients aged 18 to 80 years, on two pre-specified half-days. WC and BMI were measured and the presence of CVD and diabetes recorded. Of the patients consulting the PCPs, 97% agreed to participate in this study. Overall, 24% of 69,409 men and 27% of 98,750 women were obese (BMI ≥ 30 kg/m2). A further 40% and 30% of men and women, respectively, were overweight (BMI 25 to 30 kg/m2). In men and women, respectively, increased WC (>102/88cm, men/women) was recorded in 29% and 48%, CVD in 16% and 13%, and diabetes in 13% and 11%. There was a statistically significant graded increase in the frequency of CVD and diabetes with both BMI and WC, with a stronger relationship for WC than for BMI across regions, for both genders. This relationship between WC, CVD and particularly diabetes was seen even in lean patients (BMI <25 kg/m2).
Among men and women consulting PCPs, BMI and particularly WC were both strongly linked to CVD and especially to diabetes. Strategies to address this global problem are required to prevent an epidemic of these major causes of morbidity and mortality.
cardiovascular disease; diabetes mellitus; epidemiology; obesity; risk factors; Abdominal Fat; Adiposity; Adolescent; Adult; Aged; 80 and over; Body Mass Index; Cardiovascular Diseases; epidemiology; etiology; Diabetes Mellitus; Female; Humans; International Cooperation; Male; Middle Aged; Obesity; complications; Physicians; Family; Primary Health Care; Random Allocation; World Health