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Biomedical subjects

K A Fox

Publications and source records attributed to K A Fox.

At least 37 records · Page 2Linked to original sources
PubMed2000

The ENACT study: a pan-European survey of acute coronary syndromes. European Network for Acute Coronary Treatment.

AIM: The European Network for Acute Coronary Treatment (ENACT) study was designed to collect prospective information across Europe on the relative frequency, diagnosis and management of the whole spectrum of acute coronary syndromes. METHODS: Cardiologists, who were respondents to mailings sent out to 17 European countries with the target of reaching one centre per million inhabitants, completed a prospective patient record, each physician providing information on 10 consecutive patients with a working diagnosis on admission of acute coronary syndrome, and a questionnaire. RESULTS: A total of 390 responses were received (0.91/10(6)population) with data on 3092 patients in 29 countries. The patient population comprised 1431 (46%) with an initial working diagnosis of unstable angina/non-ST-segment elevation myocardial infarction, 1205 (39%) with myocardial infarction and 445 (14%) with suspected acute coronary syndrome. The ratio of unstable angina to myocardial infarction was 1.2:1 and this was similar across Europe. An initial diagnosis of myocardial infarction was more likely to be confirmed than unstable angina or suspected acute coronary syndrome. There were wide variations in the rates of angiography and percutaneous coronary intervention across Europe. Most unstable angina patients received aspirin, nitrates and heparin (unfractionated heparin 44% intravenous, 16% subcutaneous; low-molecular-weight heparin 50%). Overall, 50% of unstable angina patients and 34% of myocardial infarction patients received low-molecular-weight heparin and 6% and 8% respectively received a glycoprotein IIb/IIIa inhibitor, but there were large inter-country differences. There were also national differences in the use of calcium antagonists, angiotensin-converting enzyme inhibitors and beta-blockers. CONCLUSION: The ENACT study provides robust data, for the first time, on the relative frequency of unstable angina and acute myocardial infarction across Europe. It provides insight into differences in management across Europe and a reference benchmark of current treatment.

Acute Disease↗
PubMed2000

Memory function in patients with stable, moderate to severe cardiac failure.

BACKGROUND: Psychologic dysfunction is common in patients with heart disease. Patients with end-stage cardiac failure have cognitive dysfunction that can affect their ability to comply with complex treatment regimes. The prevalence of cognitive dysfunction in patients with stable, moderately severe cardiac failure is not known. The purpose of this study was to evaluate the prevalence of memory dysfunction in that population. METHODS: Twenty patients with previous myocardial infarction (MI), New York Heart Association class III or IV cardiac failure symptoms, and left ventricular ejection fraction (LVEF) <40% were studied. Twenty patients with previous MI, no heart failure symptoms, and LVEF >50% were studied as a control group. Memory function was assessed with the Rivermead Behavioural Memory Test and digit span test. Results were controlled for affective state and estimated premorbid intellectual function with the National Adult Reading Test. RESULTS: Patients with cardiac failure performed as well as controls in the memory test (mean [95% confidence intervals] score 18.2 [16.5-19.9] versus 19.7 [18.1-21.4] points, P =.20) and digit span test (10.1 [9.2-11.0] versus 11.0 [9.9-12.2] points). Affective symptoms were more prevalent among patients with cardiac failure. Estimated premorbid intellectual function appeared poorer in patients with cardiac failure (reading test score 24 [7-36] versus 32 [11-46] points). Memory test outcomes were not significantly affected after adjustment for these variables. CONCLUSIONS: Patients with prior MI and stable, moderately severe cardiac failure do not have significantly memory impairment. Memory dysfunction is not likely to interfere with rehabilitation or compliance with treatment regimes. Anxiety and depression, however, are relatively common in this group.

Aged↗
PubMed2000

Predictors of recurrent ischemic events and death in unstable coronary artery disease after treatment with combination antithrombotic therapy.

BACKGROUND: Patients with non-Q-wave acute coronary syndromes (ACS) have substantial rates of recurrent ischemic events, but prognostic studies have been small or preceded the routine use of aggressive combination antithrombotic therapy. We sought to identify predictors of these events after antithrombotic treatment of non-Q-wave ACS. METHODS: We assessed 30-day rates of a composite triple end point (death, infarction, or refractory angina) and double end point (death or infarction) among 3171 patients with non-ST-segment elevation ACS randomly assigned to enoxaparin or heparin, plus aspirin, for 2 to 8 days. We created multivariable regression models to predict these end points from baseline factors. RESULTS: Overall, 682 patients (21%) reached the triple end point and 220 (6.8%) reached the double end point. Independent predictors of the triple end point were admission with myocardial necrosis, ST-segment depression, prior angina severity, symptom duration, and allocation to enoxaparin treatment in patients with ST-segment depression (significant interaction). Independent predictors of the double end point were admission with myocardial necrosis, ST-segment depression, enrollment region, age >75 years, prior angina severity, and rales. By deciles, the average predicted risk for the double end point ranged from 2% to 20%: a patient aged <75 years with no risk factors had a 3.5% risk, whereas a patient aged >75 years with 2 additional high-risk features (myonecrosis and ST depression) had a risk of death or reinfarction of 26%. CONCLUSIONS: Patients with non-ST-segment elevation ACS exhibit a broad range of risk of adverse recurrent ischemic events. The predictive power of the model for the triple end point, using baseline variables, was modest. However, a subgroup at very low risk of the double end point (average 2%) can be identified with baseline variables.

Aged↗
PubMed2000

Vitamin C and the risk of acute myocardial infarction.

BACKGROUND: Low-fat soluble-antioxidant status is associated with an increased risk of heart disease. OBJECTIVE: The aim of this study was to examine whether low plasma concentrations of vitamin C confer an independent risk of acute myocardial infarction (AMI). DESIGN: Male patients (n = 180) aged <65 y with a first AMI and without an existing diagnosis of angina (>6 mo) who were admitted within 12 h after onset of symptoms were compared with apparently healthy volunteers (n = 177). Plasma concentrations and dietary intakes of vitamin C were determined during hospitalization and 3 mo later. RESULTS: Compared with the control subjects, the patients had higher total cholesterol and lower HDL-cholesterol concentrations and more of them smoked. The relative risk of AMI for the lowest compared with the highest quintile of plasma vitamin C during hospitalization (14.5 and >60.5 micromol/L, respectively) was 8.37 (95% CI: 3.28, 21. 4) after adjustment for classic risk factors. At 3 mo, mean (+/-SEM) plasma vitamin C concentrations in patients had increased significantly, from 19.6 +/- 1.2 to 35.1 +/- 1.9 micromol/L (P < 0. 001) and no longer conferred a risk of AMI [relative risk: 1.02 (95% CI: 0.51, 2.03)]. Habitual dietary vitamin C intake of patients (before AMI) did not differ significantly from that of control subjects. The increase in plasma vitamin C after recovery from the infarction could not be explained by a similarly large increase in dietary vitamin C. CONCLUSIONS: A low plasma concentration of vitamin C was not associated with an increased risk of AMI, irrespective of smoking status. The apparent risk of AMI due to a low plasma vitamin C concentration was distorted by the acute phase response.

Adult↗
PubMed2000

Memory impairment in out-of-hospital cardiac arrest survivors is associated with global reduction in brain volume, not focal hippocampal injury.

BACKGROUND AND PURPOSE: More than 30% of out-of-hospital cardiac arrest (OHCA) survivors suffer significant memory impairment. The hippocampus may be vulnerable to hypoxic injury during cardiac arrest. The purpose of this study was to determine whether selective hippocampal injury is the substrate for this memory impairment. METHODS: Seventeen OHCA survivors and 12 patients with uncomplicated myocardial infarction were studied. OHCA survivors were divided into those with impaired and intact memory. Memory was assessed by use of the Rivermead Behavioural Memory Test and Doors and People Test. MRI was used to determine intracranial, whole-brain, amygdala-hippocampal complex, and temporal lobe volumes. Brain structure was also examined by statistical parametric mapping. RESULTS: Left amygdala-hippocampal volume was reduced in memory-impaired OHCA victims compared with control subjects (mean 3. 93 cm(3) and 95% CI 3.50 to 4.36 cm(3) versus mean 4.65 cm(3) and 95% CI 4.37 to 4.93 cm(3); P=0.002). Left temporal lobe and whole-brain volumes were also reduced. There were no differences in amygdala-hippocampal volume indexed against ipsilateral temporal lobe volume. Significant correlations were observed between total brain volume and Rivermead Behavioural Memory Test (r=0.56, P<0.05) and Doors and People Test (r=0.67, P<0.01) scores in OHCA survivors. Both recall and recognition were compromised in memory-impaired subjects. Statistical parametric mapping did not detect focal brain abnormalities in these subjects. Global cerebral atrophy was confirmed by qualitative assessment. CONCLUSIONS: Memory impairment in OHCA survivors is associated with global cerebral atrophy, not selective hippocampal damage. Rehabilitation protocols need to account for the global nature of the brain injury.

Aged↗
PubMed2000

Management of unstable angina.

Unstable angina is a common condition that presents a challenge to physicians because of its complex pathophysiology, and because of the high incidence of associated death and myocardial infarction. This article summarizes key strategies that can be employed in managing unstable angina and describes their interaction with the mechanisms that underpin the condition.

Adrenergic beta-Antagonists↗
PubMed2000

Local and systemic effects of intra-arterial desmopressin in healthy volunteers and patients with type 3 von Willebrand disease. Role of interleukin-6.

Intra-arterial desmopressin caused dose and time dependent increases (p <0.001 for all) in forearm blood flow (all doses) and plasma tissue plasminogen activator (t-PA) concentrations (desmopressin > or = 70 ng/min). Although plasma t-PA concentrations rose in both forearms, there was a modest local release of t-PA in the infused forearm (14 ng/100 mL of tissue/min, p <0.05). At desmopressin doses > or = 300 ng/min, plasma von Willebrand factor (vWf) and Factor VIII:C concentrations rose in both forearms (p <0.001) and correlated with the rise in interleukin-6 concentrations (r = 0.92, p <0.001: r = 0.85, p = 0.002 respectively). Neither desmopressin nor substance P caused t-PA, vWf or Factor VIII:C release in the patients, although desmopressin increased plasma interleukin-6 concentrations as in healthy volunteers. We conclude that desmopressin releases t-PA, vWf and Factor VIII:C predominantly via systemic mechanisms, possibly mediated by cytokine release. Patients with type 3 vWD appear to have a generalised failure to release t-PA acutely despite a normal interleukin-6 response to desmopressin infusion.

Adult↗
PubMed1999

Implications of the Organization to Assess Strategies for Ischemic Syndromes-2 (OASIS-2) study and the results in the context of other trials.

Although unfractionated heparin is widely used for thrombin inhibition in the management of unstable coronary artery disease, clinical and experimental evidence suggests that it is suboptimal. Recent pharmaceutical strategies to improve upon unfractionated heparin's efficacy profile have centered on the development of 2 major classifications of thrombin inhibition medications: the naturally occurring leech protein hirudin (and synthetic analogs) and low-molecular-weight (LMW) heparins. In the Organisation to Assess Strategies for Ischaemic Syndromes-2 (OASIS-2) trial, hirudin was demonstrably more effective than heparin in diminishing rates of death, myocardial infarction (MI), and angina at both 72 hours and 7 days after unstable coronary artery disease index events, with risk ratios on the order of 0.8. Similarly, in the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) study, the LMW heparin enoxaparin emerged superior to unfractionated heparin in attenuating rates of unstable coronary artery disease at 14 days, 30 days, and 1 year. On the other hand, findings involving other LMW heparins (dalteparin sodium, Fragmin, and fraxaparin) are equivocal. Although the Fragmin During Instability in Coronary Artery Disease (FRISC) study demonstrated statistically significant superiority of this LMW heparin over aspirin/placebo in driving down death/MI/revascularization rates, the Fragmin in Unstable Coronary Artery Disease (FRIC) trial showed no such superiority, but had wide confidence intervals. Similarly, the Fraxaparin Versus Unfractionated Heparin in Acute Coronary Syndromes (FRAXIS) trial with fraxaparin failed to show superiority over unfractionated heparin. The favorable efficacy findings associated with hirudin and enoxaparin regimens, compared with unfractionated heparin, accrued without significant increases in the incidences of life-threatening bleeding events (e.g., hemorrhagic stroke), but did include more frequent lesser bleeding events. In summary, both hirudin and enoxaparin have demonstrated clinically important improvements in outcome compared with standard treatments in unstable coronary artery disease.

Angina, Unstable↗
PubMed1999

Endothelial dysfunction, impaired endogenous fibrinolysis, and cigarette smoking: a mechanism for arterial thrombosis and myocardial infarction.

BACKGROUND: Effective endogenous fibrinolysis requires rapid release of tissue plasminogen activator (tPA) from the vascular endothelium. Smoking is a known risk factor for arterial thrombosis and myocardial infarction, and it causes endothelial dysfunction. We therefore examined the effects of cigarette smoking on substance P-induced tPA release in vivo in humans. METHODS AND RESULTS: Blood flow and plasma fibrinolytic factors were measured in both forearms of 12 smokers and 12 age- and sex-matched nonsmokers who received unilateral brachial artery infusions of substance P (2 to 8 pmol/min). In both smokers and nonsmokers, substance P caused dose-dependent increases in blood flow and local release of plasma tPA antigen and activity (P<0.001 for all) but had no effect on the local release of plasminogen activator inhibitor type 1. Compared with nonsmokers, increases in forearm blood flow (P=0.03) and release of tPA antigen (P=0.04) and activity (P<0.001) caused by substance P were reduced in smokers. The area under the curve for release of tPA antigen and activity decreased by 51% and 53%, respectively. CONCLUSIONS: Cigarette smoking causes marked inhibition of substance P-induced tPA release in vivo in humans. This provides an important mechanism whereby endothelial dysfunction may increase the risk of atherothrombosis through a reduction in the acute fibrinolytic capacity.

Adult↗
PubMed1999

Have we reached the limit with thrombolytic therapy?

In the 13 years since the publication of the GISSI-1 study in 1986, and the incorporation of thrombolysis into the standard management of myocardial infarction, this treatment has, apparently, fulfilled its promise. Short-term mortality gains are accompanied by improvements in ventricular function and a reduction in major cardiovascular complications. Follow-up studies have demonstrated that these short-term gains, following a single thrombolytic administration, are sustained for at least 8 years with persistent separation of the survival curves. In terms of cost effectiveness, this is a remarkable success. Streptokinase and accelerated tPA administration are the most widely used thrombolytic agents, and yet only about 50% of patients achieve unrestricted flow (TIMI 3) within 90 minutes of administration. Newer agents, including genetically modified tPA and a much older agent, staphylokinase, appear to offer superior patency rates and simpler administration. However, bleeding risks remain a concern and cannot be predicted from smaller scale studies. This lesson has been learned from the attempts to augment heparin or other antithrombotic treatment in conjunction with thrombolysis, resulting in increased rates of major and cerebral bleeding. We have not reached the limit in applying thrombolysis to all potentially eligible patients. By doing so, with a minimum of delay, more lives would be saved than by substitution of thrombolytic agents or by using adjunctive treatments with marginal survival advantages.

Fibrinolytic Agents↗
PubMed1999

The relationship between QT intervals and mortality in ambulant patients with chronic heart failure. The united kingdom heart failure evaluation and assessment of risk trial (UK-HEART)

AIMS: Mortality in patients with heart failure remains high and is difficult to predict. QT interval parameters on a 12-lead ECG have been shown to predict arrhythmic events in patients with a variety of myocardial diseases. There is some, but not consistent, evidence that QT interval parameters may act as predictors of mortality, in particular sudden death, in patients with heart failure. In an adequately powered prospective study we have studied QT interval parameters in patients with stable chronic heart failure in order to determine whether they are predictive of all-cause mortality or mode of death. METHODS AND RESULTS: Five hundred and fifty-four ambulant outpatients with chronic heart failure were recruited. A 12-lead ECG, chest radiograph, echocardiogram, 24 h ambulatory electrocardiogram and serum for biochemical analysis were obtained at baseline. Patients were followed for 471+/-168 days. QT intervals were measured in all leads blinded to patient's characteristics and outcome, were corrected for heart rate, and the maximum QT intervals, and QT dispersion (range of QT intervals) were determined. The same parameters were determined for JT intervals. The primary end-point was all-cause mortality, secondary end-points were sudden cardiac death and death due to progressive heart failure. Multivariate analysis with the Cox's proportional hazards model was used to determine which variables were independently related to outcome. Four hundred and ninety-five patients had analysable ECGs at study entry and of these 71 died during follow-up. The heart rate corrected QT dispersion and maximum QT interval were significant univariate predictors of all-cause mortality (P=0.026 and <0.0001 respectively), and also of sudden death and progressive heart failure death, but were not related to outcome in the multivariate analysis. The independent predictors of all-cause mortality were cardiothoracic ratio (P=0.0003), creatinine (P=0.0009), heart rate (P=0.007), echocardiographically derived left ventricular end-diastolic dimension (P=0.007) and ventricular couplets on 24 h electrocardiographic monitoring (P=0.015). CONCLUSION: In an adequately powered prospective study none of the QT or JT parameters were shown to be independent predictors of outcome in patients with mild to moderate congestive heart failure. These variables do not therefore add to the prognostic information which can be gained from simple radiographic, biochemical, echocardiographic and Holter data in this group of patients.

Death, Sudden, Cardiac↗
PubMed1999

In vitro analysis of coronary atheromatous lesions by intravascular ultrasound; reproducibility and histological correlation of lesion morphology.

AIM: To determine the reproducibility and histological correlation of qualitative intravascular ultrasound imaging of atheromatous coronary arteries using the recently proposed European Society of Cardiology classification of plaque composition in conditions approximating the clinical setting. METHODS: Atheromatous lesions (n=21), identified from 30 post-mortem human coronary arteries, were imaged using intravascular ultrasound in a pulsatile flow system which simulates coronary flow. Fifty sites (21 x minimum lumen area and 29 x distal reference sites) were selected independently by two observers from continuous video recordings. Atheromatous plaque was classified as echodense, echolucent, heterogeneous or calcified by each observer and by one observer on separate occasions. Arterial specimens were histologically sectioned at these sites and similarly analysed by a third observer blinded to the intravascular ultrasound appearances. RESULTS: Overall inter- and intra-observer reproducibility for plaque-type (Kappa 0.87[0.80-0.94] and 0.89[0. 85-0.93 respectively]) and focal calcification (0.78[0.74-0.82] and 0.88[0.84-0.92]) was high. Differences in site selection significantly influenced reproducibility particularly at reference sites. Agreement for overall plaque type between intravascular ultrasound and histology occurred in 89% of sites (Kappa 0.73[0.69-0. 77]). Specificity and positive predictive values for individual plaque types were greater than 90%. CONCLUSION: Using modern intravascular ultrasound technology in an in vitro system which approximates the clinical setting the proposed ESC classification of plaque composition by intravascular ultrasound is reproducible and correlates well with histology. It should therefore perform reliably in diagnostic intravascular ultrasound examinations and in the guidance of percutaneous coronary interventions.

Aged↗
PubMed1999

Group psychological treatment for chest pain with normal coronary arteries.

We used a psychological treatment package (education, relaxation, breathing training, graded exposure to activity and exercise, and challenging automatic thoughts about heart disease) to treat 60 patients who had continuing chest pain despite cardiological reassurance following haemodynamically normal angiography. The treatment was delivered in six sessions over eight weeks to groups of up to six patients. The patients kept daily records of chest pain episode frequency and nitrate use. Questionnaires were used to assess anxiety, depression and disability. Exercise tolerance was tested by treadmill electrocardiography, with capnographic assessment of hyperventilation. The results were compared with waiting-list controls. Treatment significantly reduced chest pain episodes (p < 0.01) from median 6.5 to 2.5 per week. There were significant improvements in anxiety and depression scores (p < 0.05), disability rating (p < 0.0001) and exercise tolerance (p < 0.05), and these were maintained at six month follow-up. Treatment reduced the prevalence of hyperventilation from 54% to 34% (p < 0.01) but not the prevalence of ECG-positive exercise tests. Patients continuing to attribute their pain to heart disease had poorer outcomes. Group psychological treatment for non-cardiac chest pain is feasible, reduces pain, psychological morbidity and disability, and improves exercise tolerance.

Breathing Exercises↗