Ethnic differences in arterial responses, inflammation, and metabolic profiles: possible insights into ethnic differences in cardiovascular disease and stroke.
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Biomedical subjects
Publications and source records attributed to Christopher J Boos.
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Atrial fibrillation is the most common sustained cardiac arrhythmia and the most frequently encountered cause of embolic stroke. Vitamin K antagonists (such as warfarin) have represented the cornerstone of anticoagulation practice for the last 60 years. Although highly effective in preventing thromboembolic events among patients with atrial fibrillation, warfarin therapy is limited by a multitude of potential problems. Hence, warfarin is significantly underused in clinical practice, with only half of warfarin-treated patients actually achieving therapeutic anticoagulation in routine clinical practice. Consequently, there is an overwhelming need for an alternative oral anticoagulant for patients with atrial fibrillation that is safer, more practical and effective. Ximelagatran (Exanta, AstraZeneca) is a novel oral direct thrombin inhibitor that is rapidly converted to the active compound melagatran after oral absorption. It has a low potential for drug interactions, anticoagulation monitoring is not required, and it is administered at a fixed twice-daily dose. The Stroke Prevention using the ORal Thrombin Inhibitor in patients with nonvalvular atrial Fibrillation (SPORTIF) III and V trials have together demonstrated the noninferiority of ximelagatran relative to warfarin for the prevention of stroke and embolic events in atrial fibrillation. Unfortunately, initial optimism has been tempered by serious concerns over its safety data in view of its propensity to cause elevation in liver enzymes.
Cancer is a disease largely dependent on neoangiogenesis. Cancer neoangiogenesis is often disordered and abnormal, with evidence of coexisting vascular endothelial dysfunction. A novel method of assessing vascular endothelial function in cancer is via the quantification of circulating endothelial cells (CEC). Unusual in healthy individuals, their presence in elevated numbers often indicates substantial vascular endothelial perturbation. Another interesting cell type is the endothelial progenitor cell (EPC), whose numbers increase in the presence of vascular damage. Recent research suggests that EPCs have an important role in tumor vasculogenesis. Another marker being investigated in the context of vascular dysfunction and coagulopathy is the endothelial microparticle (EMP). Thus, CECs, EPCs and EMPs may represent potentially novel methods for evaluating the vascular status of cancer patients. This review will summarize the current position of CECs, EPCs and EMPs in cell biology terms, with particular emphasis on their relationship to malignant disease.
Gastroenteritis affected many British military personnel during the war in Iraq. In the first month, 1,340 cases were seen; 73% of patients required hospital admission and 36% were hospital staff. In a survey of 500 hospital staff, 76% reported gastroenteritis, which was more likely in clinical workers. Investigations showed only caliciviruses.
OBJECTIVES: Ximelagatran is a novel oral direct thrombin inhibitor. It has favorable pharmacodynamic properties, with a broad therapeutic range without the need for anticoagulation monitoring. We aimed to discover whether ximelagatran offers a genuine future replacement to warfarin for patients in persistent atrial fibrillation (AF). MATERIALS AND METHODS: We provide an evidence-based review of the relative merits and disadvantages of warfarin and aspirin. We subsequently present an overview of the evidence for the utility of ximelagatran in the treatment of AF. RESULTS: Adjusted dose warfarin is recommended over aspirin for patients in AF at high risk of future stroke. Some of this benefit is partially offset by the higher bleeding risks associated with warfarin therapy. The SPORTIF III and V studies have shown that ximelagatran is not inferior to warfarin in the prevention of all strokes in patients with AF (both persistent and paroxysmal). This benefit was partially offset by the finding of a significant elevation of liver transaminases (>3 x normal) in 6% of patients. CONCLUSIONS: Current data would suggest that ximelagatran might represent a future alternative to warfarin. The lack of need for anticoagulant monitoring has been partially offset by a need for regular monitoring of liver function. Further data from randomized clinical trials is clearly needed.
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Cardiac troponins are invaluable tools for the detection of minimal myocardial injury. No study to date has analyzed the effect of permanent cardiac pacing on minimal myocardial injury detection by cardiac troponin I (cTnI) measurement. We investigated 76 clinically stable patients (mean age 75 years, range 31-93 years, 59% men) listed for elective endocardial permanent pacemaker insertion. Patients were required to have normal levels of cardiac cTnI, aspartate transaminase (AST) and creatinine kinase (CK) on a venous blood sample taken immediately prior to elective pacemaker implantation. Repeat measurements of AST, CK, and cTnI were performed at a mean of 19.2 post implantation. There was a detectable small rise in cTnI levels above normal in 21% of patients in a second blood sample taken 18-21 hours later (mean cTnI 0.39 +/- 0.37 microg/L, normal < 0.15 microg/L). The only factor that correlated with this rise was prolonged x ray screening time for lead implantation.
The health and economic burden of stroke to society is enormous. Pharmacological therapies remain the primary stroke prevention strategy for the vast majority. Several existing and newer pharmacological agents aimed at the treatment of hypertension and lowering cholesterol are proving to be effective. For example, the antiplatelet agent clopidogrel has reduced end points in the secondary prevention of stroke, as have combinations of aspirin with traditional therapies, including dipyramidole. The direct oral thrombin inhibitor ximelagatran is a novel oral anticoagulant that has shown significant potential as a possible replacement to warfarin therapy, for the prevention of stroke for patients with non-valvular atrial fibrillation. Additional novel agents with hypothetical, although not yet proven, benefits in stroke prevention include fish oils, homocysteine-lowering therapy and anti-inflammatory agents. Finally, a controversial novel polypill, which would include fixed combinations of several pharmacological agents, may yet become a realistic and promising stroke prevention option.
BACKGROUND: Treatment with angiotensin converting enzyme (ACE) inhibitors reduces mortality and morbidity among patients with heart failure, left-ventricular dysfunction after myocardial infarction and with hypertension. In addition, they have been shown to slow the progression of chronic kidney disease and reduce the recurrence of stroke and vascular events. MATERIAL/METHODS: There has been an enormous interest in the potential cardioprotective effects of ACE inhibitors. This principle has been assessed in two landmark double blind placebo controlled clinical trials, HOPE and EUROPA. This article seeks to review and compare the important findings of these two clinical studies. RESULTS: In the HOPE study, ramipril once daily produced a 22% reduction in the primary composite endpoint of myocardial infarction, stroke, or cardiovascular death (P < 0.001) among an older cohort (>55 years) of patients at high risk of future cardiovascular complications. The EUROPA study assessed the effects of the ACE inhibitor perindopril in a larger group of lower risk patients with established stable cardiovascular disease. In EUROPA, once daily treatment with perindopril lead to a significant 20% relative risk reduction in the combined primary endpoint (cardiovascular mortality, non-fatal myocardial infarction, and resuscitated cardiac arrest; p = 0.0003). CONCLUSIONS: HOPE and EUROPA provide compelling evidence to suggest that all patients with evidence of stable cardiovascular disease or diabetes (plus one additional risk factor) should be treated with an ACE inhibitor.
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