Angina pectoris unstable
411
samples and was more strongly correlated with %LV (r=0.52, p<0.01) and %FV
(r=-0.51, p<0.01). Plasma miR-126 was negatively correlated with %LV (r=-0.37,
p<0.05). Furthermore, plasma miR-126 tended to be lower in the coronary sinus
and more strongly correlated with %LV (r=-0.43, p<0.05). There are no significant
correlation between %LV or %FV and plasma levels of other miRNAs.
Conclusions: These results suggest that miR-100 might be released into the
coronary circulation from vulnerable coronary plaque, while miR-126 might be
decreased during transcoronary passage, providing interesting insight into the
role of miRNAs in coronary atherosclerotic diseases.
P2256 | BEDSIDE
Supersilent myocardial ischemia and risk of all-cause mortality in
elderly patients
A. Bouzas Mosquera, J. Peteiro, F.J. Broullon Molanes, N. Alvarez Garcia,
M.M. Garcia Guimaraes, D. Martinez Ruiz, J.C. Yanez Wonenburger, B. Bouzas
Zubeldia, R. Fabregas Casal, A. Castro Beiras. Hospital Universitario A Coruña,
A Coruña, Spain
P2257 | BEDSIDE
Beta trace protein and Cystatin C add complementary information
to CRUSADE bleeding score for predicting bleeding risk in non ST
segment elevation acute coronary syndromes
J.M. Andreu-Cayuelas 1 , A.A. Lopez-Cuenca 2 , F. Marin 1 , A. Mateo-Martinez 1 ,
M. Sanchez-Martinez 1 , M. Quintana-Giner 1 , A.I. Romero-Aniorte 1 , J.A. Vilchez 1 ,
M. Valdes 3 , S. Manzano Fernandez 3 . 1 University Hospital Virgen De La Arrixaca,
Murcia, Spain; 2 Hospital de la Vega Lorenzo Guirao, Cieza, Murcia, Spain;
3 University of Murcia, School of Medicine, Department of Cardiology, Murcia,
Spain
Aims: To evaluate whether Beta trace protein (BTP) and cystatin C (CysC) provide information to the CRUSADE bleeding score for predicting major bleeding
(MB); and to compare them to other renal function parameters in non-ST-segment
elevation acute coronary syndromes (NSTE-ACS).
Methods and results: We included 273 pts with NSTE-ACS. NSTE-ACS was
defined as ischemic symptoms lasting ≥10 min and occurring ≤72-h before admission and either ST-segment deviation of ≥1 mm or elevated levels of a cardiac
biomarker of necrosis. All blood samples were obtained before coronary angiography within 24-h of admission. The study endpoint was MB (BARC definition
criteria: bleeding type 3 to type 5). During a follow-up of 760 days [411-1098], 25
pts (9.2%) had MB. Pts with MB had higher BTP (0.98 [0.71-1.16] vs 0.72 mg/L
[0.60-0.91], p=0.002), CysC (1.05 [0.91-1.30] vs 0.90 mg/L [0.75-1.08], p=0.003)
and lower eGFR (66±27 vs 80±30 mL/min/1.73m2 , p=0.02) than pts without MB;
there were no differences in creatinine levels between both groups (p=0.14). In
multivariate analyses, a BTP>0.97 mg/L (HR=3.4, 95% CI=1.5-7.9, p=0.004) and
CysC>0.96 mg/L (HR=3.1, 95% CI=1.2-7.5, p=0.02) were significant predictors
of MB, while eGFR using MDRD equations and creatinine were not. Among subjects with eGFR>60ml/min/1.73m2 , those with elevated BTP or CysC had a significantly higher risk for MB (Fig. 1). NRI from the addition of BTP and CysC to
CRUSADE were 38% and 21% respectively, while the relative IDI were 12% and
4%.
Figure 1A, B
Conclusion: BTP and CysC were superior to conventional renal parameters for
predicting MB, and provide complementary information to the CRUSADE score
in NSTE-ACS. Future studies should assess the potential role of incorporating
these renal function biomarkers into the bleeding risk scales.
P2258 | BEDSIDE
Prognosis assesment of estimated glomerular filtration rate by the
new CKD-EPI equations in comparison with the modification in diet
of renal disease in non-ST elevation acute coronary syndromes
M. Navarro-Penalver 1 , A. Lopez-Cuenca 2 , P.J. Flores-Blanco 1 , F. Marin 1 ,
M. Sanchez-Galian 1 , S. Montalban-Larrea 1 , M. Quintana-Giner 1 , S. ParraPallares 1 , M. Valdes 3 , S. Manzano Fernandez 3 . 1 University Hospital Virgen De
La Arrixaca, Murcia, Spain; 2 Hospital de la Vega Lorenzo Guirao, Cieza, Murcia,
Spain; 3 University of Murcia, School of Medicine, Department of Cardiology,
Murcia, Spain
Aims: The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equations estimate glomerular filtration rate (eGFR) more accurately than Modification Diet for Renal Disease (MDRD) formula. The aim of the present study is
to evaluate whether CKD-EPI equations predict risk for mortality more accurately
than MDRD in patients with non-ST elevation acute coronary syndromes (ACS)
Methods and results: 314 subjects (age 66±12 years, male 70%) with nonST elevation ACS were studied. Non-ST elevation ACS was defined as ischemic
symptoms lasting 10 minutes or more and occurring within 72 hours before randomization and either ST-segment deviation of 1 mm or more or elevated levels of a cardiac biomarker of necrosis. All blood samples were obtained before
coronary angiography within 24 hours of hospital admission. Estimated GFR was
calculated using CKD-EPI and MDRD equations. Patients were clinically followed
and the occurrence of death was recorded in all. Over the study period (median
648 days [interquartile range 236 to 1042], 29 patients (9.2%) died. Decedents
had poorer renal function parameters (p<0.001). After multivariate adjustment,
CKD-EPI equations and MDRD equation were independent predictors of adverse
outcomes (CKD-EPI creatinine, per ml/min/1.73m2 : HR 0.974 [95% CI 0.954 to
0.994], p = 0.012; CKD-EPI cystatin C, per ml/min/1.73m2 : HR 0.953 [95% CI
0.958 to 0.992], p = 0.004; CKD-EPI creatinine-cystatin C, per ml/min/1.73m2 :
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Purpose: Elderly patients have a higher prevalence of coronary artery disease
but also a higher probability of abnormal perception of angina, and the Duke
Treadmill Score failed to show significant prognostic value in these patients. The
prevalence and clinical significance of echocardiographic evidence of myocardial
ischemia in elderly patients with negative exercise electrocardiograms (i.e., supersilent myocardial ischemia [SSMI]) has not been investigated. Our aim was to
evaluate the prevalence, predictors and outcome of SSMI, as assessed by exercise echocardiography, in elderly patients with known or suspected coronary
artery disease.
Methods: SSMI was defined as the development of exercise-induced wall motion abnormalities in the absence of chest pain or ischemic electrocardiographic
changes. A total of 1497 consecutive patients aged ≥65 years (50.8% males) with
baseline interpretable electrocardiograms underwent treadmill exercise echocardiography and did not develop chest pain or ischemic electrocardiographic
changes during the tests. The increase in wall motion score index from rest to
peak exercise (WMSI) was used as a quantifier of the degree of SSMI. The
end-point was all-cause mortality.
Results: SSMI was evident in 318 patients (20%). In logistic regression analysis,
male sex (odds ratio [OR] 2.30, 95% CI 1.73-3.06, p <0.001), diabetes mellitus
(OR 1.61, 95% CI 1.17-2.21, p = 0.004), prior myocardial infarction (OR 4.07,
95% CI 3.04-5.46, p <0.001), and resting left ventricular ejection fraction <55%
(OR 1.44, IC 1.03-2.03, p = 0.036) remained predictors of SSMI in elderly patients. During an average follow-up of 4.3±3.2 years, 197 patients died. Five-year
mortality rate was 16.9% in patients with SSMI vs 11% in those without SSMI
(p=0.016). In Cox regression analysis, WMSI remained an independent predictor of mortality (hazard ratio 2.58, 95% CI 1.07-6.23, p=0.03).
Conclusions: A significant proportion of elderly patients with known or suspected
coronary artery disease have echocardiographic evidence of SSMI in the absence of exercise-induced chest pain or ischemic electrocardiographic changes,
which in turn identifies a subgroup of patients at a significantly higher risk of mortality.
412
Angina pectoris unstable
HR 0.972 [95% CI 0.953 to 0.992], p=0.005 and MDRD, per ml/min/1.73m2 : HR
0.978 [95% CI 0.959 to 0.997], p=0.025). Reclassification analyses showed that
all CKD-EPI equations more accurately categorized the risk for mortality than
MDRD (Table 1).
Table 1. Evaluating added predictive ability of adding CKD-EPI equations to MDRD for prediction
of mortality using recalssification indexes
MDRD + CKD-EPI creatinine
MDRd + CKD-EPI cystatin C
MDRD + CKD-EPI creatinine–
cystatin C
IDI
P
NRI
p
% no events
correctly
reclassified
% events
correctly
reclassified
5.2%
7.7%
<0.001
0.003
17%
18%
0.014
0.051
14%
18%
3%
0%
8.2%
0.003
19%
0.037
19%
0%
Conclusion: In patients with non-ST elevation ACS, CKD-EPI equations based
provide more acurate risk stratification than MDRD for the prediction of mortality.
P2259 | BEDSIDE
Routine invasive strategy is of most benefit in trials that did not
specify positive cardiac biomarker status as an inclusion criterion:
a meta-analysis
L. Santarella 1 , E. Agushi 1 , E. Cenko 1 , A. Dormi 2 , B. Xhyheri 1 , C. Pizzi 1 ,
O. Manfrini 1 , R. Bugiardini 1 . 1 University of Bologna, Department of Internal
Medicine, Section of Cardiology, Bologna, Italy; 2 University of Bologna, Bologna,
Italy
P2261 | BEDSIDE
Genetic polymorphisms on chromosome 9p21 and 6p24 and
long-term follow-up after acute coronary syndrome
M. Kiliszek 1 , M. Franaszczyk 2 , R. Ploski 2 , G. Opolski 1 . 1 Medical University of
Warsaw, 1st Department of Cardiology, Warsaw, Poland; 2 Department of Medical
Genetics, Medical University of Warsaw, Poland, Warsaw, Poland
Purpose: Several single nucleotide polymorpshisms (SNPs) were found in
genome-wide studies to correlate with coronary artery disease. So far little is
known about the prognostic value of those genetic markers. We tested the prognostic value of rs12526453 (SNP located in an intron of phophastase and actin
regulator 1 (PHACTR1) on chromosome 6p24) and rs10757278 (from 9p21 locus) in patients (pts) with acute coronary syndrome (ACS).
Methods: Consecutive pts with ACS (myocardial infarction or unstable angina)
were included in the registry in the years 2008-2010. The endpoint was all-cause
death. Median follow up was 1252 (IQR 1068-1401) days. All pts were genotyped
with rs10757278 and rs12526453.
Results: 551 consecutive pts were included (493 were treated with primary
angioplasty). Major allele frequency was 0.49 for rs10757278 and 0.70 for
rs12526453. During follow up 102 pts has died. In univariate Cox-regression
analysis both polymorphisms were significantly linked with prognosis [HR
(CI)]: rs10757278: 0,67 (0,51-0,89), p=0.006 and rs12526453: 0,72 (0,55-0,95),
p=0.021. In multivariate Cox-regression analysis only 9p21 was significantly
linked with prognosis after ACS. The other factors significantly correlated with
prognosis were: age, heart rate at admission, previous myocardial infarction and
history of heart failure. Kaplan-Meyers curves for 9p21 are shown on the figure 1.
P2260 | BEDSIDE
Prognostic assessment in non-ST elevation acute coronary
syndrome with negative troponin levels: a multimarker approach
A. Tello Montoliu 1 , J.M. Garcia-Salas 2 , T. Casas 2 , A. Lopez Cuenca 1 ,
P. Perez-Berbel 3 , S. Manzano-Fernandez 1 , F. Marin 1 , M. Valdes 1 . 1 University
Hospital Virgen de la Arrixaca, Department of Cardiology, Murcia, Spain;
2 University Hospital Virgen de la Arrixaca, Department of Clinical Analysis,
Murcia, Spain; 3 General University Hospital of Alicante, Department of
Cardiology, Alicante, Spain
Purpose: Non-ST elevation acute coronary syndrome (nSTEACS) patients with
negative troponin (-Tn) levels and low or moderate risk show a non-negligible adverse events rate. The use of a multimarker approach to improve the prognosis
assessment performed by the TIMI risk score has not been evaluated yet. Thus
the purpose of this study was s to investigate the prognostic value of a multimarker approach in addition to TIMI risk score in this setting.
Methods: This is a prospective, observational study in which nSTEACS patients
with -Tn (<0.035 μg/L) with low or moderate (≤4 points) TIMI risk score admitted to a tertiary institution were included. Blood samples were drawn within the
first 48 hours of the admittance for biomarker assessment. Levels of interleukin 6
Figure 1
Conclusions: 9p21 polymorphsim is linked with prognosis after myocardial infarction. Polymorphic allele seems to have protective effect.
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Purpose: We further explored the hypothesis of fewer cardiac deaths among Unstable Angina and Non-ST-Elevation Myocardial Infarction (UA/NSTEMI) patients
undergoing early angiography, attempting to address previous concerns on baseline risk of patients as assessed by troponin status.
Methods: Only randomized controlled clinical trials reporting data on cardiac
biomarkers were considered for inclusion in this meta-analysis. Routine invasive
and selective invasive strategies were compared as follows: analysis 1: trials only
recruiting participants with positive cardiac biomarkers (NSTEMI) versus those
that recruited participants with positive and negative cardiac biomarkers as an
inclusion criterion (UA/NSTEMI), regardless of stents use; analysis 2: trials selected as above, with stents deployed during procedures. The primary end-points
were mortality, recurrent non fatal MI and their combination.
Results: For analysis 1, a total of 8 trials (10,411 patients) were eligible for our
study: 3 with NSTEMI (VINO, VANQWISH and ICTUS) and 5 with UA/NSTEMI
(TIMI IIIB, MATE, FRISC II, TACTIS-TIMI 18 and RITA 3). For analysis 2, three
of the eight selected trials (MATE; TIMI-3B and VANQWISH) were excluded because they were undertaken in the pre-stent era. Duration of the follow-up periods
ranged from 6 to 24 months. In the period of time from randomization to the end
of follow-up, the use of routine invasive strategy was associated with a significant
reduction for the composite ischemic events with 21% lower odds (RR 0.79; CI,
0.70-0.90) in UA/NSTEMI. In contrast, there was no benefit of the use of such
strategy (RR 1.19; CI, 1.03-1.38) in NSTEMI. The observed effects were consistent among most evaluated trials except for the case of MATE in UA/NSTEMI and
VINO in NSTEMI. Regarding the period of time from randomization to discharge,
a routine invasive strategy was associated with significantly higher odds of the
endpoint in both UA/NSTEMI (RR 1.28; CI, 1.11-1.46) and NSTEMI (RR 1.85;
CI, 1.49-2.29). Changing the methods for analysis from all randomized studies to
studies that were undertaken in the post-stent era (analysis 2) did not alter the
interpretation of the data.
Conclusions: Contrary to expectations, a routine invasive strategy is of most
benefit in trials recruiting a large number of UA patients, whereas it cannot be
proven to reduce deaths or nonfatal myocardial infarction in NSTEMI patients.
Potential clinical benefits from PCI do not seem to favorably affect the overall
prognosis of the index myocardial infarction.
(IL-6); placental grown factor (PIGF); Soluble fms-Like Tyrosine Kinase 1 (sFlt1);
N-terminal pro brain natriuretic peptide (NT proBNP); copeptin; and high sensitivity C-reactive protein (hs-CRP) were determined in blood samples. The composite
primary end-point of cardiovascular death, non-fatal ACS, non-elective coronary
revascularization, or acute heart failure was recorded during 6-month follow-up
period. Cut-off points were defined as the highest product of sensitivity and specificity for each biomarker level in those statistical associated with prognosis.
Results: A total of 212 patients with a mean age of 63.7±11.4 years old were
included. Using the TIMI risk score 69.7% and 30.3% were classified as low (0-2
points) and moderate risk (3-4 points) respectively. The primary end-point occurred in 13.5% of patients at 6-month follow-up. Only raised IL-6 (>12.40 ng/L);
PIGF (>21.34 ng/L); and hs-CRP (>0.76 mg/dL) were associated with the occurrence of adverse outcomes. The simultaneous elevation of 2 to 3 biomarker
levels was an independent predictor for the primary end-oint after adjusts with
TIMI risk score (HR: 7.36; 3.10-17.50, p<0.0001). A multimarker approach consinting in 2-3 biomarkers, and prior ischemic heart disease in addition to TIMI risk
scale showed an area under curve of 0.814 (p<0.0001) with a high discrimination
for adverse events (IDI: 0.184, p=0.002). A total of 46.2% patients with events
were re-classified from moderate to high risk, whereas 32.6% of patients without
events were re-classified to low risk ((p=0.034 y p=0.001, respectively) showing
a high Clinical Net reclassification improvement (CNRI) index (35.6%; p=0.029).
Conclusions: A multimarker approach in addition to the TIMI risk score improves
the prognostic assesment in nSTEACS patients with –Tn levels at 6 month followup.