A multicentre analysis of troponin use in clinical practice.

BACKGROUND: The role of troponin quantification in evaluation of patients with suspected acute coronary syndrome is established, but with cost implications. Emerging high-sensitivity troponin and novel multi-marker assays herald further resource implications. AIMS: The objective of this study was to quantify recent trends in troponin usage and costs in a cross-section of hospitals. METHODS: A cross-sectional survey seeking data on troponin usage and costs from six tertiary referral, public access teaching hospitals for consecutive years between 2003 and 2009 was carried out. RESULTS: A median annual increase in the volume of troponin assays requested was identified in all six hospitals, with an average median annual increase of 6.9 % across hospitals (interquartile range 3.4, 10.1 %). This annual increase was not accompanied by a corresponding increase in volume of patients presenting to the Emergency Department (ED) with chest pain. The majority (44-67 %) of troponin requests originated in the ED of hospitals. The median annual spend on troponins per hospital was 115,612 (interquartile range 80,452, 140,918). An analysis of results of assays performed in one centre found that the majority (91 %) of troponin assays performed were in the normal range. CONCLUSIONS: An annual increase in troponin requests without a corresponding increase in patient activity raises the possibility of increasingly indiscriminate troponin testing. The cumulative direct and indirect costs of inappropriate testing are significant. Corrective strategies are necessary to improve patient selection and testing protocols, particularly in the advent of the high-sensitivity troponin assays and novel multi-marker strategies.

Inflammatory bio-markers and cardiovascular risk prediction.

Inflammatory processes are now recognized to play a central role in the pathogenesis of atherosclerosis and its complications. Plasma levels of several markers of inflammation have been found to be associated with future cardiovascular risk in a variety of clinical settings. These markers include cell adhesion molecules, cytokines, pro-atherogenic enzymes and C-reactive protein (CRP). Initially thought of as an inactive downstream marker of the inflammatory cascade, emerging evidence suggests that CRP may be directly involved in atherogenesis, and that arterial plaque can produce CRP, independent of traditional hepatic pathways. In addition to being a strong predictor of future cardiovascular risk amongst patients presenting with acute coronary syndromes, numerous studies have found that baseline levels of CRP are associated with risk of future myocardial infarction, stroke, peripheral vascular disease and cardiovascular death amongst apparently healthy populations. The combination of measurement of a marker of inflammation with lipid testing may improve upon risk stratification based on lipid testing alone, and intensification of programmes for exercise, weight loss, and smoking cessation is recommended for those with elevated CRP levels. Further trials are needed to confirm the potential benefits of statins amongst individuals with elevated CRP levels.

Mutation in the promoter region of the beta-fibrinogen gene and the risk of future myocardial infarction, stroke and venous thrombosis.

AIM: Polymorphisms in the promoter region of the beta-fibrinogen gene are associated with increased plasma fibrinogen levels. We investigated whether the distribution of the C148T polymorphism is associated with an increase in cardiovascular risk. METHODS AND RESULTS: In a nested case-control design, the distribution of the C148T polymorphism was investigated among 751 participants in the Physicians' Health Study who subsequently developed myocardial infarction, stroke or venous thromboembolism (cases) and among 751 age- and smoking-matched controls over follow-up of 8.6 years. Frequency of the T allele was similar among men who had myocardial infarction (22.7%, P=0.5), stroke (18.4%, P=0.2) or venous thromboembolism (17.0%, P=0.1) compared with those with no cardiovascular events (21.5%). The relative risk for any vascular event among men homozygous or heterozygous for the T allele compared with men homozygous for the C allele was 0.94 (95% CI 0.76-1.16). We found no evidence of an association between the T allele and myocardial infarction (relative risk 1.06; 95% CI 0.82-1.36), stroke (0.87, 0.63-1.21) or venous thromboembolism (0.75; 0.51-1.08). Analysis adjusted for aspirin use and traditional cardiovascular risk factors had no significant effect on these findings. CONCLUSION: In a large prospective cohort, carriage of the T allele for the C148T mutation in the beta-fibrinogen promoter gene was not associated with an increased subsequent risk of cardiovascular events.

A prospective evaluation of lipoprotein-associated phospholipase A(2) levels and the risk of future cardiovascular events in women.

OBJECTIVES: We sought to determine prospectively whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) was a predictor of future cardiovascular risk in women. BACKGROUND: Inflammatory markers may help predict cardiovascular risk. Lp-PLA(2) levels have recently been hypothesized to be an independent predictor of cardiovascular risk in hypercholesterolemic men. METHODS: We conducted a prospective, nested case-control study among 28,263 apparently healthy middle-aged women to assess the risk of death from coronary heart disease, non-fatal myocardial infarction, and stroke associated with baseline levels of Lp-PLA(2) over a mean follow-up of three years. RESULTS: In univariate analysis, mean levels of Lp-PLA(2) correlated strongly with low-density lipoprotein cholesterol (r = 0.51; p = 0.0001), were lower among women currently using hormone replacement therapy (mean 0.98 mg/l vs. 1.23 mg/l; p = 0.0001) and were significantly higher at baseline among cases (n = 123) than controls (n = 123) (mean 1.20 mg/l vs. 1.05 mg/l; p = 0.016). However, the predictive value of Lp-PLA(2) was markedly attenuated after adjustment for these and other cardiovascular risk factors. Specifically, the multivariate relative risks of future cardiovascular events for women in the lowest (referent) to highest quartiles of Lp-PLA(2) were 1.00, 0.75, 0.64 and 1.17, respectively (all p values non-significant). In contrast, the adjusted relative risks of future cardiovascular events for each increasing quartile of C-reactive protein (another marker of low-grade inflammation) were 1.00, 1.78, 2.02 and 4.66, respectively (p-value for trend = 0.002). Inclusion of Lp-PLA(2) levels did not significantly attenuate this latter observation. CONCLUSIONS: In contrast to prior data among hyperlipidemic men, the current data suggest that Lp-PLA(2) is not a strong predictor of future cardiovascular risk among unselected women.

Novel clinical markers of vascular wall inflammation.

Inflammatory processes play a pivotal role in the pathogenesis of atherosclerosis and mediate many of the stages of atheroma development from initial leukocyte recruitment to eventual rupture of the unstable atherosclerotic plaque. Elevated plasma levels of several markers of the inflammatory cascade have been shown to predict future risk of plaque rupture. These markers include P-selectin, interleukin-6, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, and C-reactive protein (CRP). Produced in the liver in response to interleukin-6, CRP has emerged as the most powerful inflammatory marker of future cardiovascular risk. Initially considered an innocent bystander in the atherosclerotic process, recent evidence suggests that CRP may have direct proinflammatory effects. Numerous large-scale, prospective studies have found that elevated baseline levels of CRP are a strong independent predictor of future vascular risk. Furthermore, aspirin and statin therapy appear to be particularly effective among individuals with high CRP levels. The addition of CRP screening to traditional lipid testing has the potential to identify individuals at high risk for future cardiovascular events who may benefit from targeted preventive interventions.

Vascular closure devices and the risk of vascular complications after percutaneous coronary intervention in patients receiving glycoprotein IIb-IIIa inhibitors.

Vascular closure devices offer advantages over traditional means of obtaining hemostasis after percutaneous coronary intervention (PCI) in terms of patient comfort and time to ambulation. We investigate whether such devices also reduce the risk of vascular complications in selected patient populations. We conducted a retrospective analysis of all patients who underwent PCI at our institution between January 1998 and December 1999. Of 3,151 consecutive patients, 3,027 were eligible to receive vascular closure devices. Of these, 1,485 received a closure device and 1,409 received glycoprotein IIb-IIIa antagonists. The overall vascular complication rate, as defined by the need for surgical repair or transfusion, or the development of arteriovenous fistula, pseudoaneurysm, or large hematoma, was 4.20%. By univariate analysis, the use of closure devices was associated with a lower vascular complication rate (3.03% vs 5.52%; p = 0.002) and a shorter length of hospital stay (2.77 vs 3.97 days, p <0.001). Multivariate analysis showed a significant reduction in vascular complications with closure devices (odds ratio 0.59, p = 0.007). For the subgroup of patients receiving glycoprotein IIb-IIIa antagonists, the use of closure devices was associated with an even more pronounced reduction in the risk of vascular complications (odds ratio 0.45, p <0.008). Thus, the use of closure devices in selected patients undergoing PCI is associated with a low rate of vascular complications and decreased length of stay. This benefit was most marked for patients receiving glycoprotein IIb-IIIa antagonists.

Rheolytic thrombectomy for in-stent thrombosis: creating a diagnostic window.

Acute-stent thrombosis is a relatively uncommon complication of coronary artery stenting, however, it is a potentially catastrophic event. In this case report of stent thrombosis, rheolytic thrombectomy is used to reestablished flow within the artery and, thereby, facilitate intravascular ultrasound. This documented that inadequate stent expansion, residual disease, and tissue prolapse through the stent at an angulated segment of the artery are factors that may underlie thrombosis. This case illustrates that rheolytic thrombectomy is feasible in subacute thrombosis, and that this approach facilitates diagnostic evaluation and treatment of underlying factors involved in stent thrombosis.

Inflammatory mechanisms in atherosclerosis: from laboratory evidence to clinical application.

From the initial stages of leukocyte recruitment to diseased endothelium, to eventual rupture of unstable atheromatous plaque, pro-inflammatory mechanisms mediate key steps in atherogenesis and its complications. Lipid lowering, both with diet and statin therapy, has been shown to have favorable effects on inflammatory processes in atheromatous plaque. Several plasma markers of inflammation have been found to predict future cardiovascular risk, both among patients with acute coronary syndromes and myocardial infarction, and among healthy men and women. C-reactive protein (CRP), a pattern recognition molecule linked to the innate immune system, is a sensitive marker of low-grade vascular inflammation, which may also have direct pro-inflammatory actions. Recent studies have shown that statin therapy may lower CRP levels independent of lipid-lowering effects. Statin therapy may also be highly effective for the prevention of cardiovascular events among individuals with elevated CRP levels. The role of statin therapy for plaque stabilization in acute coronary syndromes, and for prevention of future plaque rupture among healthy individuals with evidence of vascular inflammation, is an area of active research.

Pathophysiology of atherosclerosis: development, regression, restenosis.

There is now a very large number of patients with coronary artery disease who have also undergone percutaneous interventions such as coronary angioplasty. Atherosclerosis and restenosis are two distinct pathologic processes with different underlying pathophysiologic mechanisms, different natural histories, different clinical presentations, and treatment strategies. Management strategies to target both processes are currently poorly applied in clinical practice. The development of integrated management strategies to target atherosclerosis, as well as restenosis in the postprocedural period remains a priority.

Atherogenic lipids and endothelial dysfunction: mechanisms in the genesis of ischemic syndromes.

Atherogenic lipids, particularly oxidized low-density lipoprotein, are responsible for a wide range of cellular dysfunctions within the vessel wall. The effects on endothelial cells disrupt normal control of vasomotion, with a reduction of effective nitric oxide activity, the development of a procoagulant surface, chronic low-grade inflammation, and abnormal cell growth. These changes are central not only in the development of atherosclerosis but also in the evolution of both stable and unstable ischemic syndromes. There is growing evidence that these abnormal changes in cell function respond rapidly to changes in the atherogenic lipids. Certain cell functions can improve within hours or days of cholesterol lowering.