Influence of pre-existing inflammation on the outcome of acute coronary syndrome: a cross-sectional study.

OBJECTIVES: Inflammation is a well-established risk factor for the development of coronary artery disease (CAD) and acute coronary syndrome (ACS). However, less is known about its influence on the outcome of ACS. The aim of this study was to determine if blood biomarkers of inflammation were associated specifically with acute myocardial infarction (MI) or unstable angina (UA) in patients with ACS. DESIGN: Cross-sectional study. SETTING: Patients admitted to the coronary care unit, via the emergency room, at a central county hospital over a 4-year period (1992-1996). PARTICIPANTS: In a substudy of Carlscrona Heart Attack Prognosis Study (CHAPS) of 5292 patients admitted to the coronary care unit, we identified 908 patients aged 30-74 years, who at discharge had received the diagnosis of either MI (527) or UA (381). MAIN OUTCOME MEASURES: MI or UA, based on the diagnosis set at discharge from hospital. RESULTS: When adjusted for smoking, age, sex and duration of chest pain, concentrations of plasma biomarkers of inflammation (high-sensitivity C reactive protein>2 mg/L (OR=1.40 (1.00 to 1.96) and fibrinogen (p for trend=0.035)) analysed at admission were found to be associated with MI over UA, in an event of ACS. A strong significant association with MI over UA was found for blood cell markers of inflammation, that is, counts of neutrophils (p for trend<0.001), monocytes (p for trend<0.001) and thrombocytes (p for trend=0.021), while lymphocyte count showed no association. Interestingly, eosinophil count (p for trend=0.003) was found to be significantly lower in patients with MI compared to those with UA. CONCLUSIONS: Our results show that, in patients with ACS, the blood cell profile and degree of inflammation at admission was associated with the outcome. Furthermore, our data suggest that a pre-existing low-grade inflammation may dispose towards MI over UA.

The influence of smoking and impaired glucose homoeostasis on the outcome in patients presenting with an acute coronary syndrome: a cross-sectional study.

OBJECTIVES: Smoking, diabetes, male sex, hypercholesterolaemia and hypertension are well-established risk factors for the development of coronary artery disease (CAD). However, less is known about their role in influencing the outcome in the event of an acute coronary syndrome (ACS). The aim of this study was to determine if these risk factors are associated specifically with acute myocardial infarction (MI) or unstable angina (UA) in patients with suspected ACS. DESIGN: Cross-sectional study. SETTING: Patients admitted to the coronary care unit, via the emergency room, at a central county hospital over a 4-year period (1992-1996). PARTICIPANTS: From 5292 patients admitted to the coronary care unit, 908 patients aged 30-74 years were selected, who at discharge had received the diagnosis of either MI (527) or UA (381). A control group consisted of 948 patients aged 30-74 years in whom a diagnosis of ACS was excluded. MAIN OUTCOME MEASURES: MI or UA. RESULTS: Current smoking (OR 2.42 (1.61 to 3.62)), impaired glucose homoeostasis defined as glycated haemoglobin ≥5.5% + blood glucose ≥7.5 mM (OR 1.78 (1.19 to 2.67)) and male sex (OR 1.71 (1.21 to 2.40)) were significant factors predisposing to MI over UA, in the event of an ACS. Compared with the non-ACS group, impaired glucose homoeostasis, male sex, cholesterol level and age were significantly associated with development of an ACS (MI and UA). Interestingly, smoking was significantly associated with MI (OR 2.00 (1.32 to 3.02)), but not UA. CONCLUSIONS: Smoking or impaired glucose homoeostasis is an acquired risk factor for a severe ACS outcome in patients with CAD. Importantly, smoking was not associated with UA, suggesting that it is not a risk factor for all clinical manifestations of CAD, but its influence is important mainly in the acute stages of ACS. Thus, on a diagnosis of CAD, the cessation of smoking and management of glucose homoeostasis are of upmost importance to avoid severe subsequent ACS consequences.

Comparison of PrASE and Pyrosequencing for SNP Genotyping.

BACKGROUND: There is an imperative need for SNP genotyping technologies that are cost-effective per sample with retained high accuracy, throughput and flexibility. We have developed a microarray-based technique and compared it to Pyrosequencing. In the protease-mediated allele-specific extension (PrASE), the protease constrains the elongation reaction and thus prevents incorrect nucleotide incorporation to mismatched 3'-termini primers. RESULTS: The assay is automated for 48 genotyping reactions in parallel followed by a tag-microarray detection system. A script automatically visualizes the results in cluster diagrams and assigns the genotypes. Ten polymorphic positions suggested as prothrombotic genetic variations were analyzed with Pyrosequencing and PrASE technologies in 442 samples and 99.8 % concordance was achieved. In addition to accuracy, the robustness and reproducibility of the technique has been investigated. CONCLUSION: The results of this study strongly indicate that the PrASE technology can offer significant improvements in terms of accuracy and robustness and thereof increased number of typeable SNPs.