HEART score performance in Asian and Caucasian patients presenting to the emergency department with suspected acute coronary syndrome.

BACKGROUND: The HEART score is a simple and effective tool to predict short-term major adverse cardiovascular events in patients suspected of acute coronary syndrome. Patients are assigned to three risk categories using History, ECG, Age, Risk factors and Troponin (HEART). The purpose is early rule out and discharge is considered safe for patients in the low risk category. Its performance in patients of Asian ethnicity is unknown. We evaluated the performance of the HEART score in patients of Caucasian, Chinese, Indian and Malay ethnicity. METHODS: The HEART score was assessed retrospectively in 3456 patients presenting to the emergency department with suspected acute coronary syndrome (1791 Caucasians, 1059 Chinese, 344 Indians, 262 Malays), assigning them into three risk categories. RESULTS: The incidence of major adverse cardiovascular events within six weeks after presentation was similar between the ethnic groups. A smaller proportion of Caucasians was in the low risk category compared with Asians (Caucasians 35.8%, Chinese 43.5%, Indians 45.3%, Malays 44.7%, p<0.001). The negative predictive value of a low HEART score was comparable across the ethnic groups, but lower than previously reported (Caucasians 95.3%, Chinese 95.0%, Indians 96.2%, Malays 96.6%). Also the c-statistic for the HEART score was not significantly different between the groups. CONCLUSIONS: These results show that the overall performance of the HEART score is equal among Caucasian and Asian ethnic groups. The event rate in the low risk group, however, was higher than reported in previous studies, which queries the safety of early discharge of patients in the low risk category.

Identification of CD163 as an antiinflammatory receptor for HMGB1-haptoglobin complexes.

Secreted by activated cells or passively released by damaged cells, extracellular HMGB1 is a prototypical damage-associated molecular pattern (DAMP) inflammatory mediator. During the course of developing extracorporeal approaches to treating injury and infection, we inadvertently discovered that haptoglobin, the acute phase protein that binds extracellular hemoglobin and targets cellular uptake through CD163, also binds HMGB1. Haptoglobin-HMGB1 complexes elicit the production of antiinflammatory enzymes (heme oxygenase-1) and cytokines (e.g., IL-10) in WT but not in CD163-deficient macrophages. Genetic disruption of haptoglobin or CD163 expression significantly enhances mortality rates in standardized models of intra-abdominal sepsis in mice. Administration of haptoglobin to WT and to haptoglobin gene-deficient animals confers significant protection. These findings reveal a mechanism for haptoglobin modulation of the inflammatory action of HMGB1, with significant implications for developing experimental strategies targeting HMGB1-dependent inflammatory diseases.

Routinely analyzed leukocyte characteristics improve prediction of mortality after coronary angiography.

BACKGROUND: Inflammation and leukocyte infiltration are hallmarks of atherosclerosis. Clinically routine hematology analyzers mostly perform an entire differential blood count by default, irrespective of the requested parameter. We hypothesize that these normally unreported leukocyte characteristics associate with coronary artery disease (CAD) severity and can improve prediction of mortality in coronary angiography patients. METHODS: We studied coronary angiography patients suspected of CAD (n = 1015) from the Utrecht Coronary Biobank cohort. Leukocyte characteristics were routinely assessed in blood drawn directly prior to angiography using an automated hematology analyzer and extracted from the Utrecht patient oriented database (UPOD) database. Patients were followed up for a median duration of 805 days, during which 65 patients died. We evaluated the association of leukocyte characteristics with synergy between PCI with taxus and cardiac surgery (SYNTAX) score as a measure of CAD severity, all-cause and cardiovascular mortality and major adverse cardiovascular events (MACEs). In order to determine the improvement of risk prediction, we calculated continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI). RESULTS: Monocyte percentage showed strong independent predictive value for all-cause mortality (hazard ratio (HR) 1.44 (1.19-1.74), p < 0.001), and the monocyte-to-lymphocyte ratio performed best for cardiovascular mortality (HR 1.42 (1.11-1.81), p = 0.005). The cNRIs and IDIs of leukocyte characteristics for all-cause mortality confirmed the improvement in mortality risk prediction. No significantly predictive leukocyte characteristics were found for MACEs. CONCLUSION: Readily available yet unreported leukocyte characteristics from routine hematology analyzers significantly improved prediction of mortality in coronary angiography patients on top of clinical characteristics.

Ethnic differences in clinical outcome of patients presenting to the emergency department with chest pain.

BACKGROUND: Ethnicity, although known to influence cardiovascular outcome in assorted clinical settings, has not been investigated previously as a risk factor in patients presenting to the emergency department with suspected acute myocardial infarction. METHODS: In this multi-ethnic cohort study conducted in Singapore and The Netherlands, 2784 patients presenting to the emergency department with chest pain were enrolled (788 Caucasians, 1281 Chinese, 404 Indians and 311 Malays) and were followed up for 1 year. RESULTS: Although Caucasian patients on average were older and had incurred more cardiovascular adverse events, the Asian ethnic groups carried a greater burden of cardiovascular risk factors. Caucasian and Malay patients were most frequently diagnosed with acute myocardial infarction (Caucasians 11.2%, Chinese and Indians 6.4%, Malays 10.6%, P<0.001), also after correction for baseline differences. Chinese and Indian patients, however, more often had unstable angina. Asian patients had strikingly more extensive coronary artery disease than Caucasian patients (triple-vessel disease: Caucasians 6.5%, Chinese 22.8%, Indians 32.4%, Malays 32.8%, P<0.001) and Chinese patients with myocardial infarction more frequently underwent coronary revascularisation compared with Caucasian patients (Caucasians 41.4%, Chinese 67.5%, Indians 62.5%, Malay 46.7%, P=0.005). Ethnicity was not an independent predictor of major adverse cardiovascular events during 1-year follow-up in all chest pain patients. CONCLUSIONS: The prevalence of myocardial infarction and unstable angina, revascularisation rate and extent of coronary artery disease differ significantly among chest pain patients of different ethnic groups. These findings have important clinical implications and support consideration of ethnicity in risk stratification and determination of the patient management strategy in patients with symptoms suggestive of myocardial infarction.

Suspected acute coronary syndrome in the emergency room: Limited added value of heart type fatty acid binding protein point of care or ELISA tests: The FAME-ER (Fatty Acid binding protein in Myocardial infarction Evaluation in the Emergency Room) study.

BACKGROUND: Timely recognition of acute coronary syndrome remains a challenge as many biomarkers, including troponin, remain negative in the first hours following the onset of chest pain. We assessed the diagnostic accuracy of heart-type fatty acid binding protein (H-FABP), a cardiac biomarker with potential value immediately post symptom onset. METHODS AND RESULTS: Prospective monocentre diagnostic accuracy study of H-FABP bedside point of care (CardioDetect®) and ELISA tests in acute coronary syndrome suspected patients presenting within 24 hours of symptom onset to the emergency department, in addition to clinical findings, electrocardiography and the currently recommended biomarker high sensitivity troponin-T (hs-cTnT). The final diagnosis of acute coronary syndrome was adjudicated by two independent cardiologists, blinded to H-FABP results. Acute coronary syndrome was diagnosed in 149 (32.9%) of 453 unselected patients with suspected acute coronary syndrome (56% men, mean age 62.6 years). Negative predictive values were similar for H-FABP point of care and ELISA tests (79% vs. 78% respectively), but inferior to initial hs-cTnT (negative predictive value 86%). The addition of H-FABP point of care results to hs-cTnT increased the negative predictive value to 89%. In a multivariable logistic regression model, H-FABP point of care and ELISA tests yielded relevant diagnostic information in addition to clinical findings and ECG (likelihood ratio test p<0.001) and increased area under the receiver operating characteristics curve (AUC; 0.82 vs. 0.84 and 0.84). This added value attenuated, however, after inclusion of hs-cTnT in the diagnostic model (AUC 0.88). CONCLUSIONS: In patients suspected of acute coronary syndrome presenting to the emergency department, H-FABP testing improves diagnostic accuracy in addition to clinical findings and electrocardiography. H-FABP, however, has no additional diagnostic value when hs-cTnT measurements are also available.

Symptomatic carotid atherosclerotic disease: correlations between plaque composition and ipsilateral stroke risk.

BACKGROUND AND PURPOSE: For symptomatic patients with carotid artery stenosis, the risk benefit for surgical intervention may vary among patient groups. Various modalities of plaque imaging have been promoted as potential tools for additional risk stratification, particularly in patients with moderate stenosis. However, it remains uncertain to what extent carotid plaque components predict risk of future ipsilateral ischemic stroke. METHODS: In 2 large atherosclerotic carotid plaque biobank studies, we related histological characteristics of 1640 carotid plaques with a validated risk model for the prediction of individual 1- and 5-year stroke risk. RESULTS: No significant heterogeneity between the studies was found. Predicted 5-year stroke risk (top versus bottom quartile) was related to plaque thrombus (odds ratio, 1.42; 95% confidence interval, 1.11-1.89; P=0.02), fibrous content (0.65; 0.49-0.87; P=0.004), macrophage infiltration (1.41; 1.05-1.90; P=0.02), high microvessel density (1.49; 1.05-2.11; P=0.03), and overall plaque instability (1.40; 1.05-1.87; P=0.02). This association was not observed for cap thickness, calcification, intraplaque hemorrhage, or lymphocyte infiltration. Plaques removed within 30 days of most recent symptomatic event were most strongly correlated with predicted stroke risk. CONCLUSIONS: Features of the vulnerable carotid plaque, including plaque thrombus, low fibrous content, macrophage infiltration, and microvessel density, correlate with predicted stroke risk. This study provides a basis for plaque imaging studies focused on stroke risk stratification.

Serum extracellular vesicle protein levels are associated with acute coronary syndrome.

AIMS: Biomarkers are essential in the early detection of acute coronary syndromes (ACS). Serum extracellular vesicles are small vesicles in the plasma containing protein and RNA and have been shown to be involved in ACS-related processes like apoptosis and coagulation. Therefore, we hypothesized that serum extracellular vesicle protein levels are associated with ACS. METHODS AND RESULTS: Three serum extracellular vesicle proteins potentially associated with ACS were identified with differential Q-proteomics and were evaluated in 471 frozen serum samples of ACS-suspected patients presenting to the emergency department (30% of whom had an ACS). Protein levels were measured after vesicle isolation using ExoQuick. Mean serum extracellular vesicle concentration of the different proteins was compared between ACS and non-ACS patients. Selected proteins were tested in a univariate logistic regression model, as well as in a multivariate model to adjust for cardiovascular risk factors. A separate analysis was performed in men and women. In the multivariate logistic regression analysis, polygenic immunoglobulin receptor, (pIgR; OR 1.630, p=0.026), cystatin C (OR 1.641, p=0.021), and complement factor C5a (C5a, OR 1.495, p=0.025) were significantly associated with ACS, while total vesicle protein concentration was borderline significant. The association of the individual proteins with ACS was markedly stronger in men. CONCLUSIONS: These data show that serum extracellular vesicle pIgR, cystatin C, and C5a concentrations are independently associated with ACS and that there are pronounced gender differences. These observations should be validated in a large, prospective study to assess the potential role of vesicle content in the evaluation of patients suspected of having an ACS.

Past, current and future concepts in atherosclerotic biobanking.

Knowledge on the pathogenesis of atherosclerotic disease mainly originates from observations made by pathologists who systemically collected vascular tissue. Biobanking of human tissues has become a professionalized joint effort, including the expertise of epidemiologists, pathologists and biologists. Mostly, biobanks are used for cross-sectional studies and the obtained specimens often represent later stages of disease. Technical improvements in high-throughput genetic and proteomic screening lead to important new insights into pathophysiological processes. Atherosclerotic disease progression is a major killer in the Western society. Pathological biobanking studies revealed insights in plaque progression and destabilization. However, atherosclerotic disease is a typical example where insights into progression of the disease may be hampered by the cross-sectional design of the biobanks. This article will focus on the accomplishments that have been made through biobanking of atherosclerotic tissues in the past and the present. In addition, future potentials of atherosclerotic plaque biobanks will be discussed.