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1.  Polyvascular Disease and Long-term Cardiovascular Outcomes in Older Patients with Non–ST-segment Elevation Myocardial Infarction 
Background
The impact of polyvascular disease (peripheral arterial disease [PAD] and/or cerebrovascular disease [CVD]) on long-term cardiovascular outcomes among older patients with acute myocardial infarction (MI) has not been well studied.
Methods
Non–ST-elevation MI (NSTEMI) patients aged ≥65 years from the CRUSADE registry who survived to hospital discharge were linked to longitudinal data from the Centers for Medicare and Medicaid Services (n=34,205). All patients were presumed to have coronary artery disease (CAD) and were classified into 4 groups: 10.7% had prior CVD (CAD+CVD group); 11.5% had prior PAD (CAD+PAD); 3.1% had prior PAD and CVD (CAD+PAD+CVD); and 74.7% had no polyvascular disease (CAD alone). Cox proportional hazard modeling was used to examine the hazard of long-term mortality and the composite of death, readmission for MI, or readmission for stroke (median follow-up 35 months, IQR 17–49) among the 4 groups.
Results
Compared with the CAD-alone group, patients with polyvascular disease had a greater comorbidity burden, were less likely to undergo revascularization, and less often received recommended discharge interventions. Three-year mortality rates increased with a greater number of arterial beds involved: 33% for CAD alone, 49% for CAD+PAD, 52% for CAD+CVD, and 59% for CAD+PAD+CVD. Relative to the CAD-alone group, patients with all 3 arterial beds involved had the highest risk of long-term mortality (adjusted HR [95% CI]: 1.49 [1.38–1.61], with a lower risk for those with CAD+CVD, 1.38 [1.31–1.44], and those with CAD+PAD, 1.29 [1.23–1.35]). Similarly, the adjusted risk of long-term composite ischemic events was highest among the CAD+PAD+CVD group.
Conclusions
Older NSTEMI patients with polyvascular disease have substantially higher long-term risk, such that the 3-year mortality rate is >50%. Future studies targeting greater adherance to secondary prevention strategies and novel therapies are needed to help reduce long-term cardiovascular events in this vulnerable population.
doi:10.1161/CIRCOUTCOMES.111.964379
PMCID: PMC3707283  PMID: 22715460
2.  Should patients with acute coronary disease be stratified for management according to their risk? Derivation, external validation and outcomes using the updated GRACE risk score 
BMJ Open  2014;4(2):e004425.
Objectives
Risk scores are recommended in guidelines to facilitate the management of patients who present with acute coronary syndromes (ACS). Internationally, such scores are not systematically used because they are not easy to apply and some risk indicators are not available at first presentation. We aimed to derive and externally validate a more accurate version of the Global Registry of Acute Coronary Events (GRACE) risk score for predicting the risk of death or death/myocardial infarction (MI) both acutely and over the longer term. The risk score was designed to be suitable for acute and emergency clinical settings and usable in electronic devices.
Design and setting
The GRACE risk score (2.0) was derived in 32 037 patients from the GRACE registry (14 countries, 94 hospitals) and validated externally in the French registry of Acute ST-elevation and non-ST-elevation MI (FAST-MI) 2005.
Participants
Patients presenting with ST-elevation and non-ST elevation ACS and with long-term outcomes.
Outcome measures
The GRACE Score (2.0) predicts the risk of short-term and long-term mortality, and death/MI, overall and in hospital survivors.
Results
For key independent risk predictors of death (1 year), non-linear associations (vs linear) were found for age (p<0.0005), systolic blood pressure (p<0.0001), pulse (p<0.0001) and creatinine (p<0.0001). By employing non-linear algorithms, there was improved model discrimination, validated externally. Using the FAST-MI 2005 cohort, the c indices for death exceeded 0.82 for the overall population at 1 year and also at 3 years. Discrimination for death or MI was slightly lower than for death alone (c=0.78). Similar results were obtained for hospital survivors, and with substitutions for creatinine and Killip class, the model performed nearly as well.
Conclusions
The updated GRACE risk score has better discrimination and is easier to use than the previous score based on linear associations. GRACE Risk (2.0) performed equally well acutely and over the longer term and can be used in a variety of clinical settings to aid management decisions.
doi:10.1136/bmjopen-2013-004425
PMCID: PMC3931985  PMID: 24561498
ACCIDENT & EMERGENCY MEDICINE
3.  Pentraxin 3 as a Novel Marker Predicting Congestive Heart Failure in Subjects With Acute Coronary Syndrome 
Korean Circulation Journal  2010;40(8):370-376.
Background and Objectives
Pentraxin 3 (PTX3) was shown to be elevated in the acute phase of acute myocardial infarction (AMI) and to have prognostic significance in AMI patients. The aim of this study was to estimate whether the value of PTX3 could be used as a prognostic biomarker, with the global registry of acute coronary events (GRACE) risk assessment tool, in patients with acute coronary syndrome (ACS).
Subjects and Methods
Between July 2007 and June 2008, 137 patient subjects (mean age : 61±12 years, M : F=108 : 29) with ACS who underwent coronary intervention, but did not have a prior percutaneous coronary intervention (PCI) and/or follow-up coronary angiogram, were enrolled. We estimated the all-cause mortality or death/MI, in-hospital and to 6 months, using the GRACE risk scores and compared these estimates with serum PTX3 concentrations.
Results
The serum PTX3 concentration showed a significant increase in ST segment elevation myocardial infarction (STEMI) greater than the unstable angina pectoris (UAP) group (2.4±2.1 ng/mL vs. 1.3±0.9 ng/mL, p= 0.017, respectively), but did not show a significant difference between non-ST segment elevation myocardial infarction (NSTEMI) and the UAP group (1.9±1.4 ng/mL vs. 1.3±0.9 ng/mL, p=0.083, respectively). The serum PTX3 concentration was closely related to death/MI in-hospital (r=0.242, p=0.015) and death/MI to 6 months (r=0.224, p=0.023), respectively. The serum PTX3 concentration was not related to all-cause mortality in-hospital (r=0.112, p=0.269) and to 6 months (r=0.132, p=0.191), respectively. Among the parameters determining the GRACE risk scores, the degree of Killip class in congestive heart failure (CHF) was independently associated with the supramedian PTX3 concentration [odds ratio: 2.229 (95% confidence interval: 1.038-4.787), p=0.040].
Conclusion
The serum PTX3 level provides important information for the risk stratification of CHF among the parameters determining the GRACE risk scores in subjects with ACS.
doi:10.4070/kcj.2010.40.8.370
PMCID: PMC2933461  PMID: 20830250
Pentraxin 3; Myocardial infarction; Acute coronary syndrome; Heart failure
4.  Peripheral Arterial Disease in Patients Presenting with Acute Coronary Syndrome in Six Middle Eastern Countries 
To describe prevalence and impact of peripheral arterial disease (PAD) in patients with acute coronary syndrome (ACS), data were collected over 5 months from 6 Middle Eastern countries. Patients were divided into 2 groups (with and without PAD). Out of 6705 consecutive ACS patients, PAD was reported in 177 patients. In comparison to non-PAD, PAD patients were older and more likely to have cardiovascular risk factors. They were more likely to have high Killip class, high GRACE risk score, and non-ST elevation ACS (NSTEACS) at presentation. Thrombolytics, antiplatelet use, and coronary intervention were comparable in both groups. When presented with ST-elevation myocardial infarction (STEMI), patients with PAD had worse outcomes, while in NSTEACS; PAD was associated with higher rate of heart failure in comparison to non-PAD patients. In diabetics, PAD was associated with 2-fold increase in mortality when compared to non-PAD (P = 0.028). After adjustment, PAD was associated with high mortality in STEMI (adjusted OR 2.6; 95% CI 1.23–5.65, P = 0.01). Prevalence of PAD in ACS in the Gulf region is low. Patients with PAD and ACS constitute a high risk group and require more attention. PAD in patients with STEMI is an independent predictor of in-hospital death.
doi:10.1155/2011/815902
PMCID: PMC3246760  PMID: 22220279
5.  In-hospital Major Clinical Outcomes in Patients With Chronic Renal Insufficiency Presenting With Acute Coronary Syndrome: Data From a Registry of 8176 Patients 
Mayo Clinic Proceedings  2010;85(4):332-340.
OBJECTIVE: To assess the impact of chronic renal insufficiency (CRI) on in-hospital major adverse cardiac events across the acute coronary syndrome (ACS) spectrum.
PATIENTS AND METHODS: From January 29, 2007, through July 29, 2007, 6 adjacent Middle Eastern countries participated in the Gulf Registry of Acute Coronary Events, a prospective, observational registry of 8176 patients. Patients were categorized according to estimated glomerular filtration rate into 4 groups: normal (≥90 mL/min), mild (60-89 mL/min), moderate (30-59 mL/min), and severe CRI (<30 mL/min). Patients' characteristics and in-hospital major adverse cardiac events in the 4 groups were analyzed.
RESULTS: Of 6518 consecutive patients with ACS, 2828 (43%) had mild CRI, 1304 (20%) had moderate CRI, and 345 (5%) had severe CRI. In CRI groups, patients were older and had a higher prevalence of hypertension, diabetes mellitus, and dyslipidemia. On admission, these patients had a higher resting heart rate and frequently had atypical and delayed presentations. Compared with the normal estimated glomerular filtration group, CRI groups were less likely to receive antiplatelet drugs, β-blockers, angiotensin-converting enzyme inhibitors, and statins and were less likely to undergo coronary angiography. In-hospital heart failure, cardiogenic shock, and major bleeding episodes were significantly higher in all CRI groups. In multivariate analysis, mild, moderate, and severe CRI were associated with a higher adjusted odds ratio (OR) of death (mild: OR, 2.1; 95% confidence interval [CI], 1.2-3.7; moderate: OR, 6.7; 95% CI, 3.9-11.5; and severe: OR, 12.0; 95% CI, 6.6-21.7).
CONCLUSION: Across the ACS spectrum, patients with CRI had a worse risk profile, had more atypical and delayed presentations, and were less likely to receive evidence-based therapy. Chronic renal insufficiency of varying stages is an independent predictor of in-hospital morbidity and mortality.
Across the acute coronary syndrome spectrum, patients with chronic renal insufficiency had a worse profile, had more atypical and delayed presentations, and were less likely to receive evidence-based therapy; chronic renal insufficiency of varying stages is an independent predictor of in-hospital morbidity and mortality.
doi:10.4065/mcp.2009.0513
PMCID: PMC2848421  PMID: 20360292
6.  Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: findings from the global registry of acute coronary events (GRACE) 
Heart  2003;89(9):1003-1008.
Objective: To determine whether creatinine clearance at the time of hospital admission is an independent predictor of hospital mortality and adverse outcomes in patients with acute coronary syndromes (ACS).
Design: A prospective multicentre observational study, GRACE (global registry of acute coronary events), of patients with the full spectrum of ACS.
Setting: Ninety four hospitals of varying size and capability in 14 countries across four continents.
Patients: 11 774 patients hospitalised with ACS, including ST and non-ST segment elevation acute myocardial infarction and unstable angina.
Main outcome measures: Demographic and clinical characteristics, medication use, and in-hospital outcomes were compared for patients with creatinine clearance rates of > 60 ml/min (normal and minimally impaired renal function), 30–60 ml/min (moderate renal dysfunction), and < 30 ml/min (severe renal dysfunction).
Results: Patients with moderate or severe renal dysfunction were older, were more likely to be women, and presented to participating hospitals with more comorbidities than those with normal or minimally impaired renal function. In comparison with patients with normal or minimally impaired renal function, patients with moderate renal dysfunction were twice as likely to die (odds ratio 2.09, 95% confidence interval 1.55 to 2.81) and those with severe renal dysfunction almost four times more likely to die (odds ratio 3.71, 95% confidence interval 2.57 to 5.37) after adjustment for other potentially confounding variables. The risk of major bleeding episodes increased as renal function worsened.
Conclusion: In patients with ACS, creatinine clearance is an important independent predictor of hospital death and major bleeding. These data reinforce the importance of increased surveillance efforts and use of targeted intervention strategies in patients with acute coronary disease complicated by renal dysfunction.
PMCID: PMC1767853  PMID: 12923009
creatinine clearance; renal dysfunction; acute coronary syndromes; prognosis
7.  Microalbuminuria indicates long-term vascular risk in patients after acute stroke undergoing in-patient rehabilitation 
BMC Neurology  2012;12:102.
Background
Patients in neurologic in-patient rehabilitation are at risk of cardio- and cerebrovascular events. Microalbuminuria (MAU) is frequent and an important risk predictor but has not been validated in in-patient rehabilitation. We therefore aimed to examine MAU as an indicator of risk and predictor of vascular events in a prospective study.
Methods
The INSIGHT (INvestigation of patients with ischemic Stroke In neuroloGic reHabiliTation) registry is the first to provide large scale data on 1,167 patients with acute stroke (< 3 months) that survived the initial phase of high risk and were undergoing neurologic in-patient rehabilitation. MAU was determined by dipstick-testing and correlated to baseline clinical variables (stroke-origin, functional impairment, co-morbidity, ankle-brachial-index, intima-media-thickeness) as well as vascular events after one year of follow-up. Comparisons were made with the χ2 or Mann–Whitney-U Test. Relative risks (RR) with 95% confidence intervals (CI) were estimated using log-binominal models. To evaluate the association between MAU and new vascular events as well as mortality, we calculated hazard ratios (HR) using Cox proportional hazard regression.
Results
A substantial proportion of patients was MAU positive at baseline (33.1%). Upon univariate analysis these patients were about 4 years older (69 vs. 65 years; p < 0.0001), had a slightly higher body mass index (27.8 vs. 27.1 kg/m2; p = 0.03) and increased waist circumference (79.5 vs. 50.4% for women [p < 0.0001] and 46.8 vs. 43.2% for men [p = 0.04]) and twice as often had diabetes mellitus (41.8 vs. 20.1%; p < 0.0001). Patients with MAU had a similar NIH stroke scale score (median 3 vs. 3; p = 0.379) but had lower values on the Barthel Index (median 75 vs. 90; p < 0.001). They had higher rates of atrial fibrillation (RR 1.38; 95% CI 1.09-1.75), coronary artery disease (RR 1.54; 95% CI 1.18-2.00), heart failure (RR 1.70; 95% CI 1.10-2.60) symptomatic peripheral artery disease (RR 2.30; 95% CI 1.40-3.80) and atherosclerotic stroke etiology (53.7 vs. 35.4%; p < 0.0001). MAU was associated with an increased intima-media-thickness, decreased ankle-brachial-index and polyvascular disease (RR 1.56; 95%CI 1.31-1.99). The event rate after a median follow-up of 13 months was 6.7% for fatal or nonfatal stroke, 4.7% for death, and 10.9% for combined vascular events (stroke, MI, vascular death). The presence of MAU was predictive for vascular events during the following year (HR for total mortality 2.2; 95% CI 1.3-3.7; HR for cardiovascular events 2.3; 95% 1.2 - 4.4).
Conclusions
INSIGHT demonstrated a significant association between MAU and polyvascular disease and further supports previous findings that MAU predicts cardio-/cerebrovascular events in patients recovering from ischemic stroke. This biomarker may also be used in patients during neurologic in-patient rehabilitation, opening a window of opportunity for early intervention in this patient group at increased risk for recurrent events.
doi:10.1186/1471-2377-12-102
PMCID: PMC3517490  PMID: 23007013
8.  IS DEPRESSION AFTER AN ACUTE CORONARY SYNDROME SIMPLY A MARKER OF KNOWN PROGNOSTIC FACTORS FOR MORTALITY? 
Psychosomatic medicine  2009;71(7):697-703.
Objective
Controversy remains over whether the association between depression and mortality in patients with acute coronary syndromes (ACS) is confounded by incomplete adjustment for measures of known prognostic markers. We assessed whether depression was associated with the most comprehensive empirically derived index of clinical mortality predictors: the Global Registry of Acute Coronary Events (GRACE) risk score for predicting 6-month mortality after discharge for ACS. We also assessed whether depression remained an independent predictor of all-cause mortality after adjustment for the GRACE score and left ventricular dysfunction.
Methods
We prospectively surveyed 457 ACS patients (aged 25–92 years; 41% women, 13% black, and 11% Hispanic), hospitalized between May 2003 and June 2005. Depressive symptoms were assessed with the Beck Depression Inventory (BDI) and diagnosis of major depressive disorder (MDD) by a structured psychiatric interview, within one week of hospitalization.
Results
Despite differences in individual components of the GRACE score between depressed and non-depressed participants, neither depression measure was associated with overall GRACE score. For participants with MDD, the mean (SD) GRACE score was 84 (33), compared to 92 (31) for those without MDD (p=0.09). Using Cox proportional hazardsregression analysis, MDD and depressive symptom severity each predicted mortality after controlling for GRACE score and left ventricular dysfunction (adjusted hazard ratio for MDD, 2.51; 95% CI 1.45–4.37).
Conclusion
Depression is not simply a marker of clinical indicators that predict all-cause mortality after ACS. This strengthens the assertion that there is something unique in the association between depression and post-ACS prognosis, independent of known prognostic markers.
doi:10.1097/PSY.0b013e3181ad2abd
PMCID: PMC2908084  PMID: 19592517
depression; myocardial infarction; unstable angina; prognosis
9.  Elevated Rho-Kinase Activity as a Marker Indicating Atherosclerosis and Inflammation Burden in Polyvascular Disease Patients With Concomitant Coronary and Peripheral Arterial Disease 
Clinical cardiology  2013;36(6):347-351.
Background
Recent evidence suggests that Rho-kinase (ROCK) plays an important role in the pathogenesis of atherosclerosis and a marker of atherosclerotic burden. Polyvascular disease with concomitant peripheral arterial disease (PAD) and coronary artery disease (CAD) is common and associated with a worse prognosis. The aim of this study was to evaluate ROCK activity as a marker of polyvascular disease.
Hypothesis
Methods
We retrospectively analyzed patients undergoing coronary angiography at our institution between February 2009 and May 2009. Patients with only CAD (n = 40) defined by coronary artery stenosis of ≥50% by angiography, only PAD (n = 40) defined by an ankle brachial index (ABI) <0.9, and combined CAD/PAD (n = 40) were matched by age and sex to control patients (n = 40) without CAD or PAD. ROCK activity was determined by phosphorylation of the myosin binding subunit in leukocytes and then compared between each group. Multivariate analysis was used to determine independent predictors of polyvascular disease. Discriminative ability of elevated ROCK activity was assessed using receiver operator characteristics (ROC) curves.
Results
Patients (age 68 ± 12 years, 79% male) with CAD, PAD, and CAD/PAD had a mean ABI of 1.08, 0.62, and 0.65, respectively, compared to 1.08 in the control group. There was an incremental increase in ROCK activity in patients with CAD (4.61 ± 2.11), PAD (4.27 ± 1.39), and CAD/PAD (5.96 ± 1.94) compared to control (2.40 ± 0.43) (all P < 0.05). ROCK activity (odds ratio: 4.53, 95% confidence interval: 1.26–6.30) was an independent predictor of polyvascular disease. The ROCK cutoff value of 4.85 had a sensitivity of 72.7% and a specificity of 65.7%, with an area under ROC curve of 0.71 for polyvascular disease.
Conclusions
Patients with concomitant peripheral and coronary arterial disease are associated with increased Rho-kinase activity. Rho-kinase activity may be a potential marker of atherosclerotic burden for patients with polyvascular disease.
doi:10.1002/clc.22118
PMCID: PMC3807086  PMID: 23553913
10.  Validation of the GRACE score for prognosis in Indian patients with acute coronary syndromes 
Indian Heart Journal  2012;64(3):263-269.
Aim
To validate the global registry of acute coronary events (GRACE) score in acute coronary syndromes (ACS) patients and study its angiographic correlation.
Methods and results
Two-hundred and thirty-five ACS patients were studied for the combined endpoint of all-cause in-hospital mortality and non-fatal infarction/reinfarction. We tested the predictive accuracy of the composite GRACE score using the receiver operating characteristics (ROC) curve.
Lower systolic blood pressure (SBP) (odds ratio [OR] 7.93, P=0.005), ST-segment deviation (OR 7.79, P=0.02) and cardiac biomarker positivity (OR > 6.52, P=0.01) were significantly associated with events. Serum creatinine > 1.4 mg/dL showed a trend towards statistical significance (OR 4.14, P=0.05), whereas age > 50 years (OR 3.62, P=not significant [NS]) and Killips class 4 (OR 2.71, P=NS) showed good association. The best value for predicting events was a GRACE score of > 217 and these patients were more likely to have double/triple vessel disease (P = 0.0009). The C statistic for the GRACE score was 0.75.
Conclusion
Higher GRACE score predicts in-hospital events and more severe angiographic coronary artery disease (CAD).
doi:10.1016/S0019-4832(12)60084-4
PMCID: PMC3861059  PMID: 22664808
Acute coronary syndromes; Prognosis
11.  Adjustment of the GRACE score by growth differentiation factor 15 enables a more accurate appreciation of risk in non-ST-elevation acute coronary syndrome 
European Heart Journal  2011;33(9):1095-1104.
Aims
The aim of the study was to evaluate whether knowledge of the circulating concentration of growth differentiation factor 15 (GDF-15) adds predictive information to the Global Registry of Acute Coronary Events (GRACE) score, a validated scoring system for risk assessment in non-ST-elevation acute coronary syndrome (NSTE-ACS). We also evaluated whether GDF-15 adds predictive information to a model containing the GRACE score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), a prognostic biomarker already in clinical use.
Methods and results
The GRACE score, GDF-15, and NT-proBNP levels were determined on admission in 1122 contemporary patients with NSTE-ACS. Six-month all-cause mortality or non-fatal myocardial infarction (MI) was the primary endpoint of the study. To obtain GDF-15- and NT-proBNP-adjusted 6-month estimated probabilities of death or non-fatal MI, statistical algorithms were developed in a derivation cohort (n = 754; n = 66 reached the primary endpoint) and applied to a validation cohort (n = 368; n = 33). Adjustment of the GRACE risk estimate by GDF-15 increased the area under the receiver-operating characteristic curve (AUC) from 0.79 to 0.85 (P < 0.001) in the validation cohort. Discrimination improvement was confirmed by an integrated discrimination improvement (IDI) of 0.055 (P = 0.005). A net 31% of the patients without events were reclassified into lower risk, and a net 27% of the patients with events were reclassified into higher risk, resulting in a total continuous net reclassification improvement [NRI(>0)] of 0.58 (P = 0.002). Addition of NT-proBNP to the GRACE score led to a similar improvement in discrimination and reclassification. Addition of GDF-15 to a model containing GRACE and NT-proBNP led to a further improvement in model performance [increase in AUC from 0.84 for GRACE plus NT-proBNP to 0.86 for GRACE plus NT-proBNP plus GDF-15, P = 0.010; IDI = 0.024, P = 0.063; NRI(>0) = 0.42, P = 0.022].
Conclusion
We show that a single measurement of GDF-15 on admission markedly enhances the predictive value of the GRACE score and provides moderate incremental information to a model including the GRACE score and NT-proBNP. Our study is the first to provide simple algorithms that can be used by the practicing clinician to more precisely estimate risk in individual patients based on the GRACE score and a single biomarker measurement on admission. The rigorous statistical approach taken in the present study may serve as a blueprint for future studies exploring the added value of biomarkers beyond clinical risk scores.
doi:10.1093/eurheartj/ehr444
PMCID: PMC3888120  PMID: 22199121
GDF-15; NT-proBNP; GRACE score; Acute coronary syndrome; Risk stratification
12.  Age and clinical outcomes in patients presenting with acute coronary syndromes☆ 
Context
Elderly patients have more cardiovascular risk factors and a greater burden of ischemic disease than younger patients.
Aims
To examine the impact of age on clinical presentation and outcomes in patients presenting with acute coronary syndrome (ACS).
Methods and material
Collected data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2), which is a prospective multicenter study from six adjacent Arab Middle Eastern Gulf countries. Patients were divided into 3 groups according to their age: ≤50 years, 51–70 years and >70 years and their clinical characteristics and outcomes were analyzed. Mortality was assessed at one and 12 months.
Statistical analysis used
One-way ANOVA test for continuous variables, Pearson chi-square (X2) test for categorical variables and multivariate logistic regression analysis for predictors were performed.
Results
Among 7930 consecutive ACS patients; 2755 (35%) were ≤50 years, 4110 (52%) were 51–70 years and 1065 (13%) >70 years old. The proportion of women increased with increasing age (13% among patients ≤50 years to 31% among patients > 70 years). The risk factor pattern varied with age; younger patients were more often obese, smokers and had a positive family history of CAD, whereas older patients more likely to have diabetes mellitus, hypertension, and dyslipidemia. Advancing age was associated with under-treatment evidence-based therapies. Multivariate logistic regression analysis after adjusting for relevant covariates showed that old age was independent predictors for re-ischemia (OR 1.29; 95% CI 1.03–1.60), heart failure (OR 2.8; 95% CI 2.17–3.52) and major bleeding (OR 4.02; 95% CI 1.37–11.77) and in-hospital mortality (age 51–70: OR 2.67; 95% CI 1.86–3.85, and age >70: OR 4.71; 95% CI 3.11–7.14).
Conclusion
Despite being higher risk group, elderly are less likely to receive evidence-based therapies and had worse outcomes. Guidelines adherence is highly recommended in elderly.
doi:10.1016/j.jcdr.2012.08.005
PMCID: PMC3770118  PMID: 24027372
Acute coronary syndrome; Age; Elderly
13.  Does Simplicity Compromise Accuracy in ACS Risk Prediction? A Retrospective Analysis of the TIMI and GRACE Risk Scores 
PLoS ONE  2009;4(11):e7947.
Background
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.
Methodology/Principal Findings
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.
Conclusions/Significance
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.
doi:10.1371/journal.pone.0007947
PMCID: PMC2776353  PMID: 19956773
14.  Gender-related differences in the presentation, management, and outcomes among patients with acute coronary syndrome from Oman 
Objective
To assess gender-related differences in the presentation, management, and in-hospital outcomes among acute coronary syndrome (ACS) patients from Oman.
Methods
Data were analyzed from 1579 consecutive ACS patients from Oman during May 8, 2006 to June 6, 2006 and January 29, 2007 to June 29, 2007, as part of Gulf RACE (Registry of Acute Coronary Events). Analyses were conducted using univariate and multivariate statistical techniques.
Results
In this study, 608 (39%) patients were women with mean age 62 ± 12 vs. 57 ± 13 years (p < 0.001). More women were seen in the older age groups (age <55 years: 25% vs. 43%, 55–74 years: 60% vs. 49% and >75 years: 15% vs. 8%; p < 0.001). Women had higher frequencies of diabetes, hypertension, hyperlipidemia, obesity, angina, and aspirin use, but less history of smoking. Women were significantly less likely to have ischemic chest pain, ST-elevation myocardial infarction (STEMI), non-STEMI and were more likely to have dyspnea, unstable angina, ST depression and left bundle branch block. Both groups received ACS medications and cardiac catheterization equally; however, women received anticoagulants (88% vs. 79%; p < 0.001), angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) (70% vs. 65%; p = 0.050) more and clopidogrel less (20% vs. 29%; p < 0.001). Women experienced more recurrent ischemia and heart failure but with similar in-hospital mortality (4.6% vs. 4.3%) even after adjusting for age (p = 0.500).
Conclusions
Women admitted with ACS were older than men, had more risk factors, presented differently with no difference in hospital mortality. This is similar to Gulf RACE study except for mortality. Women received anticoagulants/ACEIs /ARBs more but were under-treated with clopidogrel.
doi:10.1016/j.jsha.2010.09.003
PMCID: PMC3727510  PMID: 23960630
Gender-related differences; Women; Acute coronary syndrome; Oman
15.  ACHTUNG-Rule: a new and improved model for prognostic assessment in myocardial infarction 
Background:
Thrombolysis In Myocardial Infarction (TIMI), Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (PURSUIT) and Global Registry of Acute Coronary Events (GRACE) scores have been developed for risk stratification in myocardial infarction (MI). The latter is the most validated score, yet active research is ongoing for improving prognostication in MI.
Aim:
Derivation and validation of a new model for intrahospital, post-discharge and combined/total all-cause mortality prediction – ACHTUNG-Rule – and comparison with the GRACE algorithm.
Methods:
1091 patients admitted for MI (age 68.4 ± 13.5, 63.2% males, 41.8% acute MI with ST-segment elevation (STEMI)) and followed for 19.7 ± 6.4 months were assigned to a derivation sample. 400 patients admitted at a later date at our institution (age 68.3 ± 13.4, 62.7% males, 38.8% STEMI) and followed for a period of 7.2 ± 4.0 months were assigned to a validation sample. Three versions of the ACHTUNG-Rule were developed for the prediction of intrahospital, post-discharge and combined (intrahospital plus post-discharge) all-cause mortality prediction. All models were evaluated for their predictive performance using the area under the receiver operating characteristic (ROC) curve, calibration through the Hosmer–Lemeshow test and predictive utility within each individual patient through the Brier score. Comparison through ROC curve analysis and measures of risk reclassification – net reclassification improvement index (NRI) or Integrated Discrimination Improvement (IDI) – was performed between the ACHTUNG versions for intrahospital, post-discharge and combined mortality prediction and the equivalent GRACE score versions for intrahospital (GRACE-IH), post-discharge (GRACE-6PD) and post-admission 6-month mortality (GRACE-6).
Results:
Assessment of calibration and overall performance of the ACHTUNG-Rule demonstrated a good fit (p value for the Hosmer–Lemeshow goodness-of-fit test of 0.258, 0.101 and 0.550 for ACHTUNG-IH, ACHTUNG-T and ACHTUNG-R, respectively) and high discriminatory power in the validation cohort for all the primary endpoints (intrahospital mortality: AUC ACHTUNG-IH 0.886 ± 0.035 vs. AUC GRACE-IH 0.906 ± 0.026; post-discharge mortality: AUC ACHTUNG-R 0.827 ± 0.036 vs. AUC GRACE-6PD 0.811 ± 0.034; combined/total mortality: AUC ACHTUNG-T 0.831 ± 0.028 vs. AUC GRACE-6 0.815 ± 0.033). Furthermore, all versions of the ACHTUNG-Rule accurately reclassified a significant number of patients in different, more appropriate, risk categories (NRI ACHTUNG-IH 17.1%, p (2-sided) = 0.0021; NRI ACHTUNG-R 22.0%, p = 0.0002; NRI ACHTUNG-T 18.6%, p = 0.0012). The prognostic performance of the ACHTUNG-Rule was similar in both derivation and validation samples.
Conclusions:
All versions of the ACHTUNG-Rule have shown excellent discriminative power and good calibration for predicting intrahospital, post-discharge and combined in-hospital plus post-discharge mortality. The ACHTUNG version for intrahospital mortality prediction was not inferior to its equivalent GRACE model, and ACHTUNG versions for post-discharge and combined/total mortality demonstrated apparent superiority. External validation in wider, independent, preferably multicentre, registries is warranted before its potential clinical implementation.
doi:10.1177/2048872612466536
PMCID: PMC3760564  PMID: 24062923
Myocardial infarction; prognosis; risk assessment; GRACE risk score
16.  Clinical Profile and Mortality of ST-Segment Elevation Myocardial Infarction Patients Receiving Thrombolytic Therapy in the Middle East 
Objective:
Little is known about thrombolytic therapy patterns in patients with ST-elevation myocardial infarction (STEMI) in the Middle East. The objective of this study was to evaluate the clinical profile and mortality of STEMI patients who arrived in hospital within 12 hours from pain onset and received thrombolytic therapy.
Patients and Methods:
This was a prospective, multinational, multi-centre, observational survey of consecutive acute coronary syndrome patients admitted to 65 hospitals in six Middle Eastern countries during the period between October 2008 and June 2009, as part of Gulf RACE-II (Registry of Acute Coronary Events). Analyses were performed using univariate statistics.
Results:
Out of 2,465 STEMI patients, 66% (n = 1,586) were thrombolysed with namely: streptokinase (43%), reteplase (44%), tenecteplase (10%), and alteplase (3%). 22.7% received no reperfusion. Median age of the study cohort was 50 (45-59) years with majority being males (91%). The overall median symptom onset-to-presentation and door-to-needle times were 165 (95- 272) minutes and 38 (24-60) minutes, respectively. Generally, patients presenting with higher GRACE risk scores were treated with newer thrombolytic agents (reteplase and tenecteplase) (P < 0.001). The use of newer thrombolytic agents was associated with a significantly lower mortality at both 1-month (0.8% vs. 1.7% vs. 4.2%; P = 0.014) and 1-year (0% vs. 1.7% vs. 3.4%; P = 0.044) compared to streptokinase use.
Conclusions:
Majority of STEMI patients from the Middle East were thrombolysed with streptokinase and reteplase in equal numbers. Nearly one-fifth of patients did not receive any reperfusion therapy. There was inappropriately long symptom-onset to hospital presentation as well as door-to-needle times. Use of newer thrombolytic agents in high risk patients was appropriate. Newer thrombolytic agents were associated with significantly lower mortality at 1-month and 1-year compared to the older agent, streptokinase.
doi:10.4103/1995-705X.99224
PMCID: PMC3424777  PMID: 22919446
Acute coronary syndrome; GRACE score; Middle East; mortality; reteplase; STEMI; streptokinase; tenecteplase; thrombolytic therapy
17.  GRACE and TIMI risk scores but not stress imaging predict long-term cardiovascular follow-up in patients with chest pain after a rule-out protocol 
Netherlands Heart Journal  2011;19(7-8):324-330.
Objective
To determine the long-term prognostic value of stress imaging and clinical risk scoring for cardiovascular mortality in chest pain patients after ruling out acute coronary syndrome (ACS).
Methods
A standard rule-out protocol was performed in emergency room patients with a normal or non-diagnostic admission electrocardiogram (ECG) within 6 h of chest pain onset. ACS patients were identified by troponin T, recurrent angina and serial ECG. Dobutamine stress echocardiography (DSE) was performed after ACS was ruled out. Myocardial perfusion scintigraphy (MPS) was performed within 6 months in an outpatient setting according to the physician’s discretion.
Results
524 patients were included. GRACE and TIMI risk scores were 75 (57–96) and 1 (0–2) in the rule-out ACS group, and 89 (74–107) and 2 (1–3) in the ACS group, respectively (median, interquartile range). Follow-up (median 9.4 (8.9–10.0) years) was complete in 96%. 350 of 379 rule-out ACS patients had an interpretable DSE and 52 patients underwent an MPS. 21 of the rule-out ACS patients (6%) died of a cardiovascular cause compared with 24 (17%) ACS patients (p < 0.001). For rule-out ACS patients, C-statistics were 0.829 and 0.803 for the GRACE and TIMI scores. In these patients, DSE and MPS outcome did not predict long-term cardiovascular mortality. In multivariate analysis, known chronic heart failure, ACE inhibitor use, and GRACE score were independent predictors of cardiovascular mortality.
Conclusions
TIMI and GRACE score but not DSE and MPS are accurate predictors of long-term cardiovascular mortality, even in chest pain patients with a normal or non-diagnostic electrocardiogram undergoing a rule-out protocol.
doi:10.1007/s12471-011-0154-9
PMCID: PMC3144333  PMID: 21584800
Chest pain; Echocardiography; Stress imaging; Cardiovascular mortality; GRACE risk score; TIMI risk score
18.  GRACE and TIMI risk scores but not stress imaging predict long-term cardiovascular follow-up in patients with chest pain after a rule-out protocol 
Netherlands Heart Journal  2011;19(7-8):324-330.
Objective
To determine the long-term prognostic value of stress imaging and clinical risk scoring for cardiovascular mortality in chest pain patients after ruling out acute coronary syndrome (ACS).
Methods
A standard rule-out protocol was performed in emergency room patients with a normal or non-diagnostic admission electrocardiogram (ECG) within 6 h of chest pain onset. ACS patients were identified by troponin T, recurrent angina and serial ECG. Dobutamine stress echocardiography (DSE) was performed after ACS was ruled out. Myocardial perfusion scintigraphy (MPS) was performed within 6 months in an outpatient setting according to the physician’s discretion.
Results
524 patients were included. GRACE and TIMI risk scores were 75 (57–96) and 1 (0–2) in the rule-out ACS group, and 89 (74–107) and 2 (1–3) in the ACS group, respectively (median, interquartile range). Follow-up (median 9.4 (8.9–10.0) years) was complete in 96%. 350 of 379 rule-out ACS patients had an interpretable DSE and 52 patients underwent an MPS. 21 of the rule-out ACS patients (6%) died of a cardiovascular cause compared with 24 (17%) ACS patients (p < 0.001). For rule-out ACS patients, C-statistics were 0.829 and 0.803 for the GRACE and TIMI scores. In these patients, DSE and MPS outcome did not predict long-term cardiovascular mortality. In multivariate analysis, known chronic heart failure, ACE inhibitor use, and GRACE score were independent predictors of cardiovascular mortality.
Conclusions
TIMI and GRACE score but not DSE and MPS are accurate predictors of long-term cardiovascular mortality, even in chest pain patients with a normal or non-diagnostic electrocardiogram undergoing a rule-out protocol.
doi:10.1007/s12471-011-0154-9
PMCID: PMC3144333  PMID: 21584800
Chest pain; Echocardiography; Stress imaging; Cardiovascular mortality; GRACE risk score; TIMI risk score
19.  Immediate and one-year outcome of patients presenting with Acute Coronary Syndrome complicated by stroke: Findings from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2) 
Background
Stroke is a potential complication of acute coronary syndrome (ACS). The aim of this study was to identify the prevalence, risk factors predisposing to stroke, in-hospital and 1-year mortality among patients presenting with ACS in the Middle East.
Methods
For a period of 9 months in 2008 to 2009, 7,930 consecutive ACS patients were enrolled from 65 hospitals in 6 Middle East countries.
Results
The prevalence of in-hospital stroke following ACS was 0.70%. Most cases were ST segment elevation MI-related (STEMI) and ischemic stroke in nature. Patients with in-hospital stroke were 5 years older than patients without stroke and were more likely to have hypertension (66% vs. 47.6%, P = 0.001). There were no differences between the two groups in regards to gender, other cardiovascular risk factors, or prior cardiovascular disease. Patients with stroke were more likely to present with atypical symptoms, advanced Killip class and less likely to be treated with evidence-based therapies. Independent predictors of stroke were hypertension, advanced killip class, ACS type –STEMI and cardiogenic shock. Stroke was associated with increased risk of in-hospital (39.3% vs. 4.3%) and one-year mortality (52% vs. 12.3%).
Conclusion
There is low incidence of in-hospital stroke in Middle-Eastern patients presenting with ACS but with very high in-hospital and one-year mortality rates. Stroke patients were less likely to be appropriately treated with evidence-based therapy. Future work should be focused on reducing the risk and improving the outcome of this devastating complication.
doi:10.1186/1471-2261-12-64
PMCID: PMC3480946  PMID: 22894647
Acute coronary syndrome; Myocardial infarction; Stroke; Risk factors; Prognosis
20.  Cardiac Complications in Patients with Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Observational Studies 
PLoS Medicine  2011;8(6):e1001048.
Vicente Corrales-Medina and colleagues report estimates of the risk of cardiac complications among patients with community-acquired pneumonia from a systematic review and meta-analysis.
Background
Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality. CAP can trigger acute cardiac events. We sought to determine the incidence of major cardiac complications in CAP patients to characterize the magnitude of this problem.
Methods and Findings
Two investigators searched MEDLINE, Scopus, and EMBASE for observational studies of immunocompetent adults with clinical and radiological evidence of CAP that reported any of the following: overall cardiac complications, incident heart failure, acute coronary syndromes (ACS), or incident cardiac arrhythmias occurring within 30 days of CAP diagnosis. At a minimum, studies had to establish enrolment procedures and inclusion and exclusion criteria, enrol their patients sequentially, and report the incidence of cardiac complications as a function of their entire cohorts. Studies with focus on nosocomial or health care–associated pneumonia were not included. Review of 2,176 citations yielded 25 articles that met eligibility and minimum quality criteria. Seventeen articles (68%) reported cohorts of CAP inpatients. In this group, the pooled incidence rates for overall cardiac complications (six cohorts, 2,119 patients), incident heart failure (eights cohorts, 4,215 patients), acute coronary syndromes (six cohorts, 2,657 patients), and incident cardiac arrhythmias (six cohorts, 2,596 patients), were 17.7% (confidence interval [CI] 13.9–22.2), 14.1% (9.3–20.6), 5.3% (3.2–8.6), and 4.7% (2.4–8.9), respectively. One article reported cardiac complications in CAP outpatients, four in low-risk (not severely ill) inpatients, and three in high-risk inpatients. The incidences for all outcomes except overall cardiac complications were lower in the two former groups and higher in the latter. One additional study reported on CAP outpatients and low-risk inpatients without discriminating between these groups. Twelve studies (48%) asserted the evaluation of cardiac complications in their methods but only six (24%) provided a definition for them. Only three studies, all examining ACS, carried out risk factor analysis for these events. No study analyzed the association between cardiac complications and other medical complications or their impact on other CAP outcomes.
Conclusions
Major cardiac complications occur in a substantial proportion of patients with CAP. Physicians and patients need to appreciate the significance of this association for timely recognition and management of these events. Strategies aimed at preventing pneumonia (i.e., influenza and pneumococcal vaccination) in high-risk populations need to be optimized. Further research is needed to understand the mechanisms underlying this association, measure the impact of cardiac complications on other CAP outcomes, identify those patients with CAP at high risk of developing cardiac complications, and design strategies to prevent their occurrence in this population.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Community-acquired pneumonia (CAP), that is, pneumonia infections contracted outside of hospital or health care settings, is a common condition and can be fatal, particularly to older people. For example, every year, an estimated 5–6 million people contract this form of pneumonia in the US, leading to 1.1 million people being admitted to hospitals and causing 60,000 deaths—the most frequent cause of infectious disease-related mortality. In the US for example, more than half of older patients who present to the hospital with CAP have preexisting chronic cardiac conditions—an important fact given that acute infections, such as CAP, can affect the cardiovascular system in various ways and precipitate acute cardiac events, such as heart failure, heart attacks, and cardiac arrhythmias.
Why Was This Study Done?
Although it is bio-medically plausible that a considerable proportion of patients with CAP have cardiac complications, systematic data on the scale of this potential problem are lacking—a concerning omission given the important implications for health policy-making and direct patient care. Therefore, in this study, the researchers conducted a systematic review to examine the published literature on cardiac complications in patients with CAP in order to characterize the nature and significance of this association, and to identify areas that require further research and investigation.
What Did the Researchers Do and Find?
The researchers searched MEDLINE, Scopus, and EMBASE for all relevant articles published in English, French, or Spanish languages until June 2010. The researchers used strict criteria to select appropriate articles (such as radiographic evidence of CAP) and only selected studies that had outcomes of the incidence of cardiac complications, such as incident (new or worsening) heart failure, acute coronary syndromes (acute myocardial infarction or unstable angina), and incident cardiac arrhythmias within 30 days of diagnosis of CAP.
Using these methods, the researchers identified 2,176 articles for review and selected 25 eligible papers for their analysis. Seventeen articles (68%) reported cohorts of CAP inpatients. In this group, the pooled incidence rates of overall cardiac complications (six cohorts, 2,119 patients), incident heart failure (eight cohorts, 4,215 patients), acute coronary syndromes (six cohorts, 2,657 patients), and incident cardiac arrhythmias (six cohorts, 2,596 patients), were 17.7%, 14.1%, 5.3%, and 4.7% respectively. Only three studies, (all of acute coronary syndromes) did risk factor analysis for these events. Possible risk factors identified included older age, preexisting congestive heart failure, severity of pneumonia, and the use of insulin by glucose sliding scales in hospitalized patients. No study analyzed the association between cardiac complications and other medical complications (such as acute renal failure, respiratory failure, shock, etc.) or their impact on other outcomes, such as death, in patients with CAP.
What Do These Findings Mean?
Although limited to a mostly descriptive analysis, these findings clearly show that major cardiac complications occur in a significant proportion of patients with CAP, especially in those admitted to hospital. These findings have important clinical and public health implications. Clinicians should be more aware of the significance of the association between CAP and cardiac complications to better inform, treat, and manage patients. Physicians and health officials need to increase efforts to optimize the rates of influenza and pneumococcal vaccination among older people and those with chronic cardiac conditions to reduce the incidence of CAP in these high-risk populations. There needs to be more consideration given to the potential impact of cardiac complications on mortality and costs associated with CAP. Finally, these findings highlight the need for prospective, well-designed, and adequately powered studies of cardiac complications in patients with CAP. More research attention should be given to this important area in order to improve the outcomes for patients with CAP and to decrease the consequent burden on health care systems through recognition of risk, prevention, and intervention on acute cardiac complications.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001048.
Information can be found on Wikipedia on community-acquired pneumonia (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The US Centers for Disease Control provide patient information on community-acquired pneumonia
The American Heart Association provides information on heart failure, acute coronary syndromes, and arrhythmias
doi:10.1371/journal.pmed.1001048
PMCID: PMC3125176  PMID: 21738449
21.  Characteristics and in-hospital outcomes of patients with acute coronary syndromes and heart failure in the United Arab Emirates 
BMC Research Notes  2012;5:534.
Background
Heart failure (HF) is a serious complication of acute coronary syndromes (ACS), and is associated with high in-hospital mortality and poor long-term survival. The aims of this study were to describe the clinical characteristics, management and in-hospital outcomes of coronary syndrome (ACS) patients with HF in the United Arab Emirates.
Findings
The study was selected from the Gulf Registry of Acute Coronary Events (Gulf RACE), a prospective multi-national, multicenter registry of patients hospitalized with ACS in six Middle East countries. The present analysis was focused on participants admitted to various hospitals in the UAE with a diagnosis of ACS in 2007 and were analyzed in terms of HF (Killip class II/III and IV) on admission. Of 1691 patients (mean age: 52.6 ± 11.7 years; 210 Females, 1481 Males) with ACS, 356 (21%) had an admission diagnosis of HF (Killip class II/III and IV). HF patients were less frequently males (19.2% vs. 34.3%; P < 0.001). HF was more frequently associated with hypertension (64.3% vs. 43.9%; P < 0.001), hyperlipidemia (49.4% vs. 31.8%; P < 0.001) and diabetes mellitus (DM) (51.1% vs. 36.2%; P < 0.001). HF was significantly associated with in-hospital mortality (OR = 11.821; 95% CI: 5.385-25.948; P < 0.001). In multivariate logistic regression, age, hyperlipidemia, heart rate and DM were associated with higher in-hospital HF.
Conclusions
HF is observed in about 1 in 5 patients with ACS in the UAE and is associated with a significant increase in in-hospital mortality and other adverse outcomes.
doi:10.1186/1756-0500-5-534
PMCID: PMC3527184  PMID: 23014157
Heart failure; Acute coronary syndrome; United Arab Emirates
22.  Temporal trends in the use of invasive cardiac procedures for non-ST segment elevation acute coronary syndromes according to initial risk stratification 
The Canadian Journal of Cardiology  2009;25(11):e370-e376.
BACKGROUND:
Current guidelines support an early invasive strategy in the management of high-risk non-ST elevation acute coronary syndromes (NSTE-ACS). Although studies in the 1990s suggested that high-risk patients received less aggressive treatment, there are limited data on the contemporary management patterns of NSTE-ACS in Canada.
OBJECTIVE:
To examine the in-hospital use of coronary angiography and revascularization in relation to risk among less selected patients with NSTE-ACS.
METHODS:
Data from the prospective, multicentre Global Registry of Acute Coronary Events (main GRACE and expanded GRACE2) were used. Between June 1999 and September 2007, 7131 patients from across Canada with a final diagnosis of NSTE-ACS were included the study. The study population was stratified into low-, intermediate- and high-risk groups, based on their calculated GRACE risk score (a validated predictor of in-hospital mortality) and according to time of enrollment.
RESULTS:
While rates of in-hospital death and reinfarction were significantly (P<0.001) greater in higher-risk patients, the in-hospital use of cardiac catheterization in low- (64.7%), intermediate- (60.3%) and high-risk (42.3%) patients showed an inverse relationship (P<0.001). This trend persisted despite the increase in the overall rates of cardiac catheterization over time (47.9% in 1999 to 2003 versus 51.6% in 2004 to 2005 versus 63.8% in 2006 to 2007; P<0.001). After adjusting for confounders, intermediate-risk (adjusted OR 0.80 [95% CI 0.70 to 0.92], P=0.002) and high-risk (adjusted OR 0.38 [95% CI 0.29 to 0.48], P<0.001) patients remained less likely to undergo in-hospital cardiac catheterization.
CONCLUSION:
Despite the temporal increase in the use of invasive cardiac procedures, they remain paradoxically targeted toward low-risk patients with NSTE-ACS in contemporary practice. This treatment-risk paradox needs to be further addressed to maximize the benefits of invasive therapies in Canada.
PMCID: PMC2776566  PMID: 19898699
Acute coronary syndromes; Cardiac catheterization; Guidelines; Risk stratification
23.  Gender Disparities in the Presentation, Management and Outcomes of Acute Coronary Syndrome Patients: Data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2) 
PLoS ONE  2013;8(2):e55508.
Background
Gender-related differences in mortality of acute coronary syndrome (ACS) have been reported. The extent and causes of these differences in the Middle-East are poorly understood. We studied to what extent difference in outcome, specifically 1-year mortality are attributable to demographic, baseline clinical differences at presentation, and management differences between female and male patients.
Methodology/Principal Findings
Baseline characteristics, treatment patterns, and 1-year mortality of 7390 ACS patients in 65 hospitals in 6 Arabian Gulf countries were evaluated during 2008–2009, as part of the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2). Women were older (61.3±11.8 vs. 55.6±12.4; P<0.001), more overweight (BMI: 28.1±6.6 vs. 26.7±5.1; P<0.001), and more likely to have a history of hypertension, hyperlipidemia or diabetes. Fewer women than men received angiotensin-converting enzyme inhibitors (ACE), aspirin, clopidogrel, beta blockers or statins at discharge. They also underwent fewer invasive procedures including angiography (27.0% vs. 34.0%; P<0.001), percutaneous coronary intervention (PCI) (10.5% vs. 15.6%; P<0.001) and reperfusion therapy (6.9% vs. 20.2%; P<0.001) than men. Women were at higher unadjusted risk for in-hospital death (6.8% vs. 4.0%, P<0.001) and heart failure (HF) (18% vs. 11.8%, P<0.001). Both 1-month and 1-year mortality rates were higher in women than men (11% vs. 7.4% and 17.3% vs. 11.4%, respectively, P<0.001). Both baseline and management differences contributed to a worse outcome in women. Together these variables explained almost all mortality disparities.
Conclusions/Significance
Differences between genders in mortality appeared to be largely explained by differences in prognostic variables and management patterns. However, the origin of the latter differences need further study.
doi:10.1371/journal.pone.0055508
PMCID: PMC3566183  PMID: 23405162
24.  Management and outcomes of patients presenting with STEMI by use of chronic oral anticoagulation: results from the GRACE registry 
Aims:
To describe the characteristics, treatment, and mortality in patients with ST-elevation myocardial infarction (STEMI) by use of chronic oral anticoagulant (OAC) therapy.
Methods:
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.
Results:
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.
Conclusions:
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.
doi:10.1177/2048872613483019
PMCID: PMC3821815  PMID: 24222840
Acute coronary syndrome; anticoagulant; guidelines; myocardial infarction
25.  High Lipoprotein(a) Levels are Associated With Long-Term Adverse Outcomes in Acute Myocardial Infarction Patients in High Killip Classes 
Korean Circulation Journal  2010;40(10):491-498.
Background and Objectives
An elevated concentration of lipoprotein(a) {Lp(a)} is associated with an increased prevalence and increased severity of coronary artery disease. However, the relationship between Lp(a) levels and outcomes after acute myocardial infarction (AMI) is unclear.
Subjects and Methods
Between October 2005 and June 2007, we measured serum Lp(a) levels in 832 consecutive AMI patients (age, 62.8±12.4 years, 600 men) on admission. They were divided into tertiles according to their serum Lp(a) levels {Tertile 1 (n=276), Lp(a)<13.8 mg/dL; Tertile 2 (n=279), Lp(a)=13.8-30.6 mg/dL; Tertile 3 (n=277), Lp(a)>30.6 mg/dL}.
Results
There were no differences in baseline clinical characteristics among Tertiles 1, 2, and 3, except for proportions of Killip class III-IV patients (5.8% vs. 10.0% vs. 18.8%, respectively, p<0.001). There were significant differences in left ventricular ejection fractions (57.3±11.4% vs. 55.9±12.3% vs. 53.1±13.1%, p<0.001). Among the laboratory findings, there were significant differences in total cholesterol (173.3±37.2 vs. 183.5±38.9 vs. 185.3±43.8 mg/dL, p=0.001), low density lipoprotein-cholesterol (111.3±34.3 vs. 122.9±34.7 vs. 123.3±39.4 mg/dL, p<0.001), apolipoprotein B (92.8±25.4 vs. 100.8±26.0 vs. 101.9±28.8 mg/dL, p<0.001), and amino-terminal pro-brain natriuretic peptide levels (1805.2±4343.3 vs. 2607.9±5216.3 vs. 3981.5±7689.7 pg/mL, p<0.001). After adjusting for multiple variables in the high Killip class (III-IV) subgroup, the risk estimate for major adverse cardiovascular events (MACE) at 1-year follow-up was significantly higher in Tertile 3 than in Tertiles 1 or 2 (hazard ratio 6.723, 95% confidence interval 1.037-43.593, p=0.046).
Conclusion
In patients in high Killip classes, high serum levels of Lp(a) were significantly associated with long-term adverse outcomes after AMI.
doi:10.4070/kcj.2010.40.10.491
PMCID: PMC2978291  PMID: 21088752
Myocardial infarction; Lipoproteins; Prognosis

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