Values underlying the National Service Framework for coronary heart disease in England : a discourse analysis

OBJECTIVES: The National Service Framework (NSF) for Coronary Heart Disease--published by the English Department of Health in 2000--sets out how those within the health service should seek to prevent and treat coronary heart disease and care for people with the disease. Its prescriptions are partly based on what is known about coronary heart disease and partly on its underlying 'values'. This paper seeks to identify those values.

METHODS:An analysis of the discourses within the text of the NSF based on critical discourse analysis.

RESULTS: Three different discourses can be identified: the managerial, the clinical and the political. The managerial discourse is dominant. Each discourse has its own values. The main 'aspirational' values within the NSF are efficiency, effectiveness, autonomy (choice), universalism and equity. Some aspirational values--particularly equity--appear to be largely rhetorical and lead to few recommendations or prescriptions. Some values that might have been expected to underlie the framework, such as compassion and democracy, are largely absent.

CONCLUSIONS: Discourse analysis provides a more systematic and transparent method of describing the values behind health care policy than the methods that have been used previously.

An index of unhealthy lifestyle is associated with coronary heart disease mortality rates for small areas in England after adjustment for deprivation

Indices of socio-economic deprivation are often used as a proxy for differences in the health behaviours of populations within small areas, but these indices are a measure of the economic environment rather than the health environment. Sets of synthetic estimates of the ward-level prevalence of low fruit and vegetable consumption, obesity, raised blood pressure, raised cholesterol and smoking were combined to develop an index of unhealthy lifestyle. Multi-level regression models showed that this index described about 50% of the large-scale geographic variation in CHD mortality rates in England, and substantially adds to the ability of an index of deprivation to explain geographic variations in CHD mortality rates.

Novel therapeutics for cononary artery disease from genome-wide association study data

Abstract
Background: Coronary artery disease (CAD), one of the leading causes of death globally, is influenced by both environmental and genetic risk factors. Gene-centric genome-wide association studies (GWAS) involving cases and controls have been remarkably successful in identifying genetic loci contributing to CAD. Modern in silico platforms, such as candidate gene prediction tools, permit a systematic analysis of GWAS data to identify candidate genes for complex diseases like CAD. Subsequent integration of drug-target data from drug databases with the predicted candidate genes can potentially identify novel therapeutics suitable for repositioning towards treatment of CAD.
Methods: Previously, we were able to predict 264 candidate genes and 104 potential therapeutic targets for CAD using Gentrepid (www.gentrepid.org), a candidate gene prediction platform with two bioinformatic modules to reanalyze Wellcome Trust Case-Control Consortium GWAS data. In an expanded study, using five bioinformatics modules on the same data, Gentrepid predicted 647 candidate genes and successfully replicated 55% of the candidate genes identified by the more powerful CARDIoGRAMplusC4D consortium meta-analysis. Hence, Gentrepid was capable of enhancing lower quality genotype-phenotype data, using an independent knowledgebase of existing biological data. Here, we used our methodology to integrate drug data from three drug databases: the Therapeutic Target Database, PharmGKB and Drug Bank, with the 647 candidate gene predictions from Gentrepid. We utilized known CAD targets, the scientific literature, existing drug data and the CARDIoGRAMplusC4D meta-analysis study as benchmarks to validate Gentrepid predictions for CAD.
Results: Our analysis identified a total of 184 predicted candidate genes as novel therapeutic targets for CAD, and 981 novel therapeutics feasible for repositioning in clinical trials towards treatment of CAD. The benchmarks based on known CAD targets and the scientific literature showed that our results were significant (p < 0.05).
Conclusions: We have demonstrated that available drugs may potentially be repositioned as novel therapeutics for the treatment of CAD. Drug repositioning can save valuable time and money spent on preclinical and phase I clinical studies.

Frequency and clinical predictors of coronary artery disease in chronic renal failure renal transplant candidates

Background/aims: Cardiovascular diseases are major causes of mortality in chronic renal failure patients before and after renal transplantation. Among them, coronary disease presents a particular risk; however, risk predictors have been used to diagnose coronary heart disease. This study evaluated the frequency and importance of clinical predictors of coronary artery disease in chronic renal failure patients undergoing dialysis who were renal transplant candidates, and assessed a previously developed scoring system. Methods: Coronary angiographies conducted between March 2008 and April 2013 from 99 candidates for renal transplantation from two transplant centers in Sao Paulo state were analyzed for associations between significant coronary artery diseases (>= 70% stenosis in one or more epicardial coronary arteries or >= 50% in the left main coronary artery) and clinical parameters. Results: Univariate logistic regression analysis identified diabetes, angina, and/or previous infarction, clinical peripheral arterial disease and dyslipidemia as predictors of coronary artery disease. Multiple logistic regression analysis identified only diabetes and angina and/or previous infarction as independent predictors. Conclusion: The results corroborate previous studies demonstrating the importance of these factors when selecting patients for coronary angiography in clinical pretransplant evaluation.

Coronary plaque rupture in patients with myocardial infarction after noncardiac surgery: Frequent and dangerous

Purpose: The pathophysiology of acute coronary syndromes (ACS) after noncardiac surgery is not established yet. Thrombosis over a vulnerable plaque or decreased oxygen supply secondary to anemia or hypotension may be involved. The purpose of this study was to investigate the pathophysiology of ACS complicating noncardiac surgery. Methods: Clinical and angiographic data were prospectively recorded into a database for 120 consecutive patients that had an ACS after noncardiac surgery (PACS), for 120 patients with spontaneous ACS (SACS), and 240 patients with stable coronary artery disease (CAD). Coronary lesions with obstructions greater than 50% were classified based on two criteria: Ambrose's classification and complex morphology. The presence of Ambrose's type II or complex lesions were compared between the three groups. Results: We analyzed 1470 lesions in 480 patients. In PACS group, 45% of patients had Ambrose's type II lesions vs. 56.7% in SACS group and 16.4% in stable CAD group (P < 0.001). Both PACS and SACS patients had more complex lesions than patients in stable CAD group (56.7% vs. 79.2% vs. 31.8%, respectively; P < 0.001). Overall, the independent predictors of plaque rupture were being in the group PACS (P < 0.001, OR 2.86; CI, 1.82-4.52 for complex lesions and P < 0.001, OR 3.43; CI, 2.1-5.6 for Ambrose's type II lesions) or SACS (P < 0.001, OR 8.71; CI, 5.15-14.73 for complex lesions and P < 0.001, OR 5.99; CI, 3.66-9.81 for Ambrose's type II lesions). Conclusions: Nearly 50% of patients with perioperative ACS have evidence of coronary plaque rupture, characterizing a type 1 myocardial infarction. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Adaptive immunity is related to coronary artery disease severity after acute coronary syndrome in subjects with metabolic syndrome

Metabolic syndrome (MetS) is an inflammatory state associated with high coronary disease risk. Inflammation and adaptive immunity modulate atherosclerosis and plaque instability. We examined early changes in anti-oxidized lowdensity lipoprotein (LDL) (anti-oxLDL) autoantibodies (Abs) in patients with MetS after an acute coronary syndrome (ACS). Patients of both genders (n=116) with MetS were prospectively included after an acute yocardial infarction (MI) or hospitalization due to unstable angina. Anti-oxLDL Abs (IgG class) were assayed at baseline, three and six weeks after ACS. The severity of coronary disease was evaluated by the Gensini score. We observed a decrease in anti-oxLDL Abs titers (p<0.002 vs. baseline), mainly in males (p=0.01), in those under 65 y (p=0.03), and in subjects with Gensini score above median (p=0.04). In conclusion, early decrease in circulating anti-oxLDL Abs is associated with coronary disease severity among subjects with MetS.

Computed tomographic coronary angiography in patients with surgically treated type A aortic dissection: preliminary results

Acute type A aortic dissection is a serious emergency with a mortality rate of up to 40% within the first 24 h when left untreated. Surgical therapy needs to be initiated promptly. Due to this urgent situation, preoperative evaluation of the coronary arteries is not routinely performed in these patients. The aim of this study was to evaluate the accuracy of 64-slice computed tomography angiography (CTA) for postoperative coronary artery assessment in these patients. Ten consecutive patients with two or more cardiovascular risk factors were prospectively enrolled. Patients had type A aortic dissection treated surgically with a supracoronary graft of the ascending aorta. Performance of CTA to exclude significant stenosis (>50% lumen narrowing) and/or coronary artery dissection was compared with quantitative coronary angiography. A total of 147 segments were evaluated. Three segments (2%) were excluded from analysis. CTA correctly assessed one of three significant stenoses in three patients and correctly excluded coronary artery disease (CAD) in six of ten patients. One patient was rated false positive. Overall accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CT for identifying coronary artery disease by segment was 98%, 33%, 99%, 50%, and 99%, respectively (P<0.05). By patient, it was 70%, 33%, 86%, 50%, and 75%, respectively. No coronary artery dissection was found. Noninvasive CTA may be a viable alternative to conventional angiography for postoperative coronary artery evaluation in patients with surgically treated type A aortic dissection and cardiovascular risk factors. An NPV of 99% should allow for reliable exclusion of CAD. Further studies with higher patient numbers are warranted.

Instantaneous coronary collateral function during supine bicycle exercise

The instantaneous response of the collateral circulation to isometric physical exercise in patients with non-occlusive coronary artery disease (CAD) is not known.

The human coronary collateral circulation

Coronary collaterals are an alternative source of blood supply to myocardium jeopardized by ischaemia. Well-developed coronary collateral arteries in patients with coronary artery disease (CAD) mitigate myocardial infarcts and improve survival.

Cause or effect of arteriogenesis: compositional alterations of microparticles from CAD patients undergoing external counterpulsation therapy

Recently, a clinical study on patients with stable coronary artery disease (CAD) showed that external counterpulsation therapy (ECP) at high (300 mmHg) but not at low inflation pressure (80 mmHg) promoted coronary collateral growth, most likely due to shear stress-induced arteriogenesis. The exact molecular mechanisms behind shear stress-induced arteriogenesis are still obscure. We therefore characterized plasma levels of circulating microparticles (MPs) from these CAD patients because of their ambivalent nature as a known cardiovascular risk factor and as a promoter of neovascularization in the case of platelet-derived MPs. MPs positive for Annexin V and CD31CD41 were increased, albeit statistically significant (P<0.05, vs. baseline) only in patients receiving high inflation pressure ECP as determined by flow cytometry. MPs positive for CD62E, CD146, and CD14 were unaffected. In high, but not in low, inflation pressure treatment, change of CD31CD41 was inversely correlated to the change in collateral flow index (CFI), a measure for collateral growth. MPs from the high inflation pressure group had a more sustained pro-angiogenic effect than the ones from the low inflation pressure group, with the exception of one patient showing also an increased CFI after treatment. A total of 1005 proteins were identified by a label-free proteomics approach from MPs of three patients of each group applying stringent acceptance criteria. Based on semi-quantitative protein abundance measurements, MPs after ECP therapy contained more cellular proteins and increased CD31, corroborating the increase in MPs. Furthermore, we show that MP-associated factors of the innate immune system were decreased, many membrane-associated signaling proteins, and the known arteriogenesis stimulating protein transforming growth factor beta-1 were increased after ECP therapy. In conclusion, our data show that ECP therapy increases platelet-derived MPs in patients with CAD and that the change in protein cargo of MPs is likely in favor of a pro angiogenic/arteriogenic property.

Coronary collateral function long after drug-eluting stent implantation

OBJECTIVES: This study was designed to compare coronary collateral function in patients after bare-metal stent (BMS) or drug-eluting stent (DES) implantation. BACKGROUND: Drug-eluting stents have an inhibitory effect on the production of cytokines, chemotactic proteins, and growth factors, and may therefore negatively affect coronary collateral growth. METHODS: A total of 120 patients with long-term stable coronary artery disease (CAD) after stent implantation were included. Both the BMS group and the DES group comprised 60 patients matched for in-stent stenosis severity of the vessel undergoing collateral flow index (CFI) measurement at follow-up and for the duration of follow-up. The primary end point of the investigation was invasively determined coronary collateral function 6 months after stent implantation. Collateral function was assessed by simultaneous aortic, coronary wedge, and central venous pressure measurements (yielding CFI) and by intracoronary electrocardiogram during balloon occlusion. RESULTS: There were no differences between the groups regarding age, gender, body mass index, frequency of cardiovascular risk factors, use of cardiovascular drugs, severity of CAD, or site of coronary artery stenoses. Despite equal in-stent stenosis severity (46 +/- 34% and 45 +/- 36%) and equal follow-up duration (6.2 +/- 10 months and 6.5 +/- 5.4 months), CFI was diminished in the DES versus BMS group (0.154 +/- 0.097 vs. 0.224 +/- 0.142; p = 0.0049), and the rate of collaterals insufficient to prevent ischemia during occlusion (intracoronary electrocardiographic ST-segment elevation > or =0.1 mV) was higher with 50 of 60 patients in the DES group and 33 of 60 patients in the BMS group (p = 0.001). CONCLUSIONS: Collateral function long after coronary stenting is impaired with DES (sirolimus and paclitaxel) when compared with BMS. Considering the protective nature of collateral vessels, this could lead to more serious cardiac events in the presence of an abrupt coronary occlusion.

Diagnostic accuracy of 64-slice computed tomography for detecting angiographically significant coronary artery stenosis in an unselected consecutive patient population: comparison with conventional invasive angiography

BACKGROUND: Multislice computed tomography (MSCT) is a promising noninvasive method of detecting coronary artery disease (CAD). However, most data have been obtained in selected series of patients. The purpose of the present study was to investigate the accuracy of 64-slice MSCT (64 MSCT) in daily practice, without any patient selection. METHODS AND RESULTS: Using 64-slice MSCT coronary angiography (CTA), 69 consecutive patients, 39 (57%) of whom had previously undergone stent implantation, were evaluated. The mean heart rate during scan was 72 beats/min, scan time 13.6 s and the amount of contrast media 72 mL. The mean time span between invasive coronary angiography (ICAG) and CTA was 6 days. Significant stenosis was defined as a diameter reduction of > 50%. Of 966 segments, 884 (92%) were assessable. Compared with ICAG, the sensitivity of CTA to diagnose significant stenosis was 90%, specificity 94%, positive predictive value (PPV) 89% and negative predictive value (NPV) 95%. With regard to 58 stented lesions, the sensitivity, specificity, PPV and NPV were 93%, 96%, 87% and 98%, respectively. On the patient-based analysis, the sensitivity, specificity, PPV and NPV of CTA to detect CAD were 98%, 86%, 98% and 86%, respectively. Eighty-two (8%) segments were not assessable because of irregular rhythm, calcification or tachycardia. CONCLUSION: Sixty-four-MSCT has a high accuracy for the detection of significant CAD in an unselected patient population and therefore can be considered as a valuable noninvasive technique.

Does the beta-blocker nebivolol increase coronary flow reserve?

INTRODUCTION: Nebivolol, a highly selective beta1-adrenergic receptor-blocker, increases basal and stimulated endothelial nitric oxide (NO)-release. It is unknown, whether coronary perfusion is improved by the increase in NO availability. Therefore, we sought to evaluate the effect of nebivolol on coronary flow reserve (CFR) and collateral flow. METHODS: Doppler-flow wire derived coronary flow velocity measurements were obtained in ten controls and eight patients with coronary artery disease (CAD) at rest and after intracoronary nebivolol. CFR was defined as maximal flow during adenosine-induced hyperemia divided by resting flow. In the CAD group, collateral flow was determined after dilatation of a flow-limiting coronary stenosis. Collateral flow index (CFI) was defined as the ratio of flow velocity during balloon inflation divided by resting flow. RESULTS: CFR at rest was 3.0+/-0.6 in controls and 2.1+/-0.4 in CAD patients. After intracoronary doses of 0.1, 0.25, and 0.5 mg nebivolol, CFR increased to 3.4+/-0.7, 3.9+/-0.9, and 4.0+/-0.1 (p<0.01) in controls, and to 2.3+/-0.7, 2.6+/-0.9, and 2.6+/-0.5 (p<0.05) in CAD patients. CFI decreased significantly with intracoronary nebivolol and correlated to changes in heart rate (r=0.75, p<0.001) and rate-pressure product (r=0.59, p=0.001). DISCUSSION: Intracoronary nebivolol is associated with a significant increase in CFR due to reduction in resting flow (controls), or due to an increase in maximal coronary flow (CAD patients). CFI decreased with nebivolol parallel to the reduction in myocardial oxygen consumption.

Myeloid-related protein 8/14 complex is released by monocytes and granulocytes at the site of coronary occlusion: a novel, early, and sensitive marker of acute coronary syndromes

AIMS: We investigated whether myeloid-related protein 8/14 complex (MRP8/14) expressed by infiltrating monocytes and granulocytes may represent a mediator and early biomarker of acute coronary syndromes (ACS). METHODS AND RESULTS: Immunohistochemistry of coronary thrombi was done in 41 ACS patients. Subsequently, levels of MRP8/14 were assessed systemically in 75 patients with ACS and culprit lesions, with stable coronary artery disease (CAD), or with normal coronary arteries. In a subset of patients, MRP8/14 was measured systemically and at the site of coronary occlusion. Macrophages and granulocytes, but not platelets stained positive for MRP8/14 in 76% of 41 thrombi patients. In ACS, local MRP8/14 levels [22.0 (16.2-41.5) mg/L] were increased when compared with systemic levels [13.4 (8.1-14.7) mg/L, P = 0.03]. Systemic levels of MRP8/14 were markedly elevated [15.1 (12.1-21.8) mg/L, P = 0.001] in ACS when compared with stable CAD [4.6 (3.5-7.1) mg/L] or normals [4.8 (4.0-6.3) mg/L]. Using a cut-off level of 8 mg/L, MRP8/14 but not myoglobin or troponin, identified ACS presenting within 3 h from symptom onset. CONCLUSION: In ACS, MRP8/14 is markedly expressed at the site of coronary occlusion by invading phagocytes. The occurrence of elevated MRP8/14 in the systemic circulation prior to markers of myocardial necrosis makes it a prime candidate for the detection of unstable plaques and management of ACS.