Towards the prevention of acute lung injury: a population based cohort study protocol

<p>Abstract</p> <p>Background</p> <p>Acute lung injury (ALI) is an example of a critical care syndrome with limited treatment options once the condition is fully established. Despite improved understanding of pathophysiology of ALI, the clinical impact has been limited to improvements in supportive treatment. On the other hand, little has been done on the prevention of ALI. Olmsted County, MN, geographically isolated from other urban areas offers the opportunity to study clinical pathogenesis of ALI in a search for potential prevention targets.</p> <p>Methods/Design</p> <p>In this population-based observational cohort study, the investigators identify patients at high risk of ALI using the prediction model applied within the first six hours of hospital admission. Using a validated system-wide electronic surveillance, Olmsted County patients at risk are followed until ALI, death or hospital discharge. Detailed in-hospital (second hit) exposures and meaningful short and long term outcomes (quality-adjusted survival) are compared between ALI cases and high risk controls matched by age, gender and probability of developing ALI. Time sensitive biospecimens are collected for collaborative research studies. Nested case control comparison of 500 patients who developed ALI with 500 matched controls will provide an adequate power to determine significant differences in common hospital exposures and outcomes between the two groups.</p> <p>Discussion</p> <p>This population-based observational cohort study will identify patients at high risk early in the course of disease, the burden of ALI in the community, and the potential targets for future prevention trials.</p

Coronary endothelial function testing provides superior discrimination compared with standard clinical risk scoring in prediction of cardiovascular events

BACKGROUND Endothelial dysfunction is regarded as the early stage of atherosclerosis and is associated with cardiovascular (CV) events. This study was designed to determine whether assessment of coronary endothelial function (CEF) is safe and can reclassify risk in patients with early coronary artery disease beyond the Framingham risk score (FRS). METHODS AND RESULTS CEF was evaluated using intracoronary acetylcholine in 470 patients who presented with chest pain and nonobstructive coronary artery disease. CV events were assessed after a median follow-up of 9.7 years. The association between CEF and CV events was examined, and the net reclassification improvement index (NRI) was used to compare the incremental contribution of CEF when added to FRS.The mean age was 53 years, and 68% of the patients were women with a median FRS of 8. Complications (coronary dissection) occurred in three (0.6%) and CV events in 61 (13%) patients. In univariate analysis, microvascular CEF [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.72-0.97, P=0.032] and epicardial CEF (HR 0.73, 95% CI 0.59-0.90, P=0.01) were found to be significant predictors of CV events, whereas FRS was not (HR 1.05, 95% CI 0.85-1.26, P=0.61). When added to FRS, microvascular CEF correctly reclassified 11.3% of patients [NRI 0.11 (95% CI 0.019-0.21)], epicardial CEF correctly reclassified 12.1% of patients [NRI 0.12 (95% CI -0.02 to 0.26)], and the combined microvascular and epicardial CEF correctly reclassified 22.8% of patients [NRI 0.23 (95% CI 0.08-0.37)]. CONCLUSION CEF testing is safe and adds value to the FRS, with superior discrimination and risk stratification compared with FRS alone in patients presenting with chest pain or suspected ischemia

Coronary endothelial function testing may improve long-term quality of life in subjects with microvascular coronary endothelial dysfunction

Aim Angina pectoris in the absence of obstructive coronary artery disease (CAD) is common and is associated with poor quality of life (QOL). Coronary microvascular endothelial dysfunction is associated with myocardial ischaemia and is a common cause of angina. We hypothesise that evaluation of coronary endothelial function, its diagnosis and treatment will favourably impact QOL in patients with angina symptoms and non-obstructive CAD. Methods and results Follow-up was done on 457 patients with chest pain and non-obstructive coronary arteries who had undergone coronary vascular reactivity evaluation by administration of intracoronary acetylcholine at the time of diagnostic study. After a mean follow-up of 8.4±4.7 years, QOL was assessed by administration of the SF-36 QOL survey. Patients diagnosed and treated for microvascular endothelial dysfunction had a higher (better) overall mental composite score (44.8 vs 40.9, p=0.036) and mental health score (44.2 vs 40.7, p=0.047), and a trend towards higher vitality scores (39.1 vs 35.9, p=0.053) and role emotional scores (43.6 vs 40.4, p=0.073), compared with patients with normal endothelial function. Conclusion Among patients with chest pain and normal coronaries, diagnosis and treatment of coronary microvascular endothelial dysfunction in those with angina pectoris and non-obstructive CAD are associated with better QOL compared with patients with normal endothelial function