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Biomedical subjects

A D Timmis

Publications and source records attributed to A D Timmis.

At least 37 records · Page 2Linked to original sources
PubMed2001

Interaction between smoking and the glycoprotein IIIa P1(A2) polymorphism in non-ST-elevation acute coronary syndromes.

OBJECTIVES: The goal of this study was to determine the interaction between smoking and the glycoprotein IIIa P1(A2) polymorphism in patients admitted with non-ST-elevation acute coronary syndromes (ACS). BACKGROUND: An increased incidence of the P1(A2) polymorphism in smokers presenting with ST-elevation acute myocardial infarction (AMI) has recently been reported. We, therefore, postulated that, as a consequence of this interaction, fewer smokers with the P1(A2) polymorphism would present with non-ST-elevation ACS. METHODS: We performed a prospective cohort analysis of 220 white Caucasoid patients admitted with non-ST-elevation ACS fulfilling Braunwald class IIIb criteria for unstable angina who were stratified by smoking status. RESULTS: There were twice as many nonsmokers as smokers. Nonsmokers compared with smokers were older (mean [SD]; 63.9 [11.2] vs. 57.6 [10.3]; p < 0.0001), more likely to have had a previous admission with unstable angina (24.3% vs. 13.2%; p = 0.051) and AMI (45.8% vs. 30.3%; p < 0.026), more likely to have undergone revascularization (24.3% vs. 1.8%; p = 0.028) and were more likely to be on aspirin on admission (60.4% vs. 44.7%; p = 0.026). The proportion of nonsmokers positive for the P1(A2) polymorphism was equivalent to that expected for this population but was significantly reduced in smokers (28.7% vs. 10%; Pearson chi-square = 9.09, p = 0.0026). In a logistic regression model, the odds ratio (OR) for being positive for the P1(A2) polymorphism was significantly reduced by smoking (OR [interquartile range]: 0.26 [0.11 to 0.62]; p = 0.0026). CONCLUSIONS: There is a significant reduction in the P1(A2) polymorphism in smokers admitted with non-ST-elevation ACS compared with nonsmokers, which suggests an interaction between smoking and this polymorphism.

Acute Disease↗
PubMed2001

Underuse of coronary revascularization procedures in patients considered appropriate candidates for revascularization.

BACKGROUND: Ratings by an expert panel of the appropriateness of treatments may offer better guidance for clinical practice than the variable decisions of individual clinicians, yet there have been no prospective studies of clinical outcomes. We compared the clinical outcomes of patients treated medically after angiography with those of patients who underwent revascularization, within groups defined by ratings of the degree of appropriateness of revascularization in varying clinical circumstances. METHODS: This was a prospective study of consecutive patients undergoing coronary angiography at three London hospitals. Before patients were recruited, a nine-member expert panel rated the appropriateness of percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) on a nine-point scale (with 1 denoting highly inappropriate and 9 denoting highly appropriate) for specific clinical indications. These ratings were then applied to a population of patients with coronary artery disease. However, the patients were treated without regard to the ratings. A total of 2552 patients were followed for a median of 30 months after angiography. RESULTS: Of 908 patients with indications for which PTCA was rated appropriate (score, 7 to 9), 34 percent were treated medically; these patients were more likely to have angina at follow-up than those who underwent PTCA (odds ratio, 1.97; 95 percent confidence interval, 1.29 to 3.00). Of 1353 patients with indications for which CABG was considered appropriate, 26 percent were treated medically; they were more likely than those who underwent CABG to die or have a nonfatal myocardial infarction--the composite primary outcome (hazard ratio, 4.08; 95 percent confidence interval, 2.82 to 5.93)--and to have angina (odds ratio, 3.03; 95 percent confidence interval, 2.08 to 4.42). Furthermore, there was a graded relation between rating and outcome over the entire scale of appropriateness (P for linear trend=0.002). CONCLUSIONS: On the basis of the ratings of the expert panel, we identified substantial underuse of coronary revascularization among patients who were considered appropriate candidates for these procedures. Underuse was associated with adverse clinical outcomes.

Angina Pectoris↗
PubMed2001

The effect of aspirin on C-reactive protein as a marker of risk in unstable angina.

OBJECTIVES: This study was designed to assess the interaction between aspirin and C-reactive protein (CRP) release in unstable angina. BACKGROUND: C-reactive protein release in acute coronary syndromes may be a response to myocardial necrosis or may reflect the inflammatory process that drives atherogenesis. Aspirin has the potential to influence CRP release, either by its anti-inflammatory activity or by reducing myocardial necrosis. The clinical significance of this potential interaction has not previously been tested. METHODS: We conducted a prospective cohort study of 304 consecutive patients admitted with non-ST-elevation acute coronary syndromes. Serial blood samples were obtained for CRP and troponin I assay. End points were cardiac death and nonfatal myocardial infarction during follow-up for 12 months. RESULTS: A total of 174 patients (57%) were taking aspirin before admission. Patients taking aspirin had lower troponin I concentrations throughout the sampling period, only 45 (26.0%) having concentrations >0.1 mg/l compared with 48 (37.8%) patients not taking aspirin (p = 0.03). Maximum CRP concentrations were also lower in patients taking aspirin (8.16 mg/l [3.24 to 24.5]) than in patients not taking aspirin (11.3 mg/l [4.15 to 26.1]), although the difference was not significant. However, there was significant interaction (p = 0.04) between prior aspirin therapy and the predictive value of CRP concentrations for death and myocardial infarction at 12 months. Thus, odds ratios (95% confidence intervals) for events associated with an increase of 1 standard deviation in maximum CRP concentration were 2.64 (1.22-5.72) in patients not pretreated with aspirin compared with 0.98 (0.60-1.62) in patients pretreated with aspirin. CONCLUSIONS: The association between CRP and cardiac events in patients with unstable angina is influenced by pretreatment with aspirin. Modification of the acute-phase inflammatory responses to myocardial injury is the major mechanism of this interaction.

Aged↗
PubMed2001

Angiotensin-converting enzyme inhibition is associated with reduced troponin release in non-ST-elevation acute coronary syndromes.

OBJECTIVES: This study was done to determine the effects of angiotensin-converting enzyme (ACE) inhibition and other clinical factors on troponin release in non-ST-elevation acute coronary syndrome (ACS). BACKGROUND: Troponin is now widely used as a marker of risk in ACS, but determinants of its release have not been defined. METHODS: This was a prospective cohort study of 301 consecutive patients admitted with non-ST-elevation ACS. Baseline clinical data were recorded, ACE gene polymorphism was determined and serial blood samples were obtained for troponin-I assay. RESULTS: Significant troponin-I release (>0.1 microg/l) was detected in 93 (31%) patients. Pretreatment with ACE inhibitors, recorded in 53 patients (17.6%), independently reduced the odds of troponin-I release (odds ratio 0.25; 95% confidence intervals 0.10 to 0.64) and was associated with lower maximum troponin-I concentrations (median [interquartile range]) compared with patients not pretreated with ACE inhibitors (0.44 microg/l [0.19 to 2.65 microg/l] vs. 4.18 microg/l [0.91 to 12.41 microg/l], p = 0.01). Pretreatment with aspirin, recorded in 173 patients (57.5%), did not significantly reduce the odds of troponin-I release after adjustment but was associated with lower maximum troponin-I concentrations compared with patients not pretreated with aspirin (2.31 microg/l [0.72 to 8.02 microg/l] vs. 5.85 microg/l [1.19 to 12.79 microg/l], p = 0.05). The ACE genotyping (n = 268) showed 81 patients (30%) DD homozygous and 77 (29%) II homozygous. There was no association between ACE genotype and troponin release. CONCLUSIONS: We conclude that ACE inhibition reduces troponin release in non-ST-elevation ACS. This is likely to be mediated by the beneficial effects of treatment on vascular reactivity and the coagulation system.

Aged↗
PubMed2001

Diabetes.

The causes of accelerated atherogenesis in diabetes are unclear but the consequences in terms of cardiovascular morbidity and mortality are profound. Thus diabetes not only increases the risk of coronary heart disease but also increases the case fatality rate, ensuring that the majority of patients die of cardiovascular causes, often before the age of 50 years. The problem is compounded by autonomic neuropathy which alters the perception of cardiac pain, attenuating symptoms which are often atypical or absent. This may delay presentation or lead to inappropriate triage decisions such that access to defibrillators and specific treatment is denied. Central to the cardiovascular management of diabetes is vigorous risk factor modification although clear evidence that this leads to extra protection against coronary heart disease beyond that achieved in non-diabetic individuals has not been forthcoming. In other respects too, the management of diabetic patients with heart disease is underpinned by the same evidence-base as applies to non-diabetic patients, and it is noteworthy that 15-20% of the patients in most of the landmark clinical trials have been diabetic. Recently, however, trials such as the United Kingdom Prospective Diabetes Study (UKPDS), the Heart Outcomes Prevention Evaluation (HOPE) study, and the Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study have identified novel strategies for reducing cardiovascular risk in diabetes. These trials have already had a major impact on cardiological practice, emphasising the prime importance of blood pressure control and converting enzyme inhibition for reducing cardiovascular risk in diabetes as well as the value of insulin therapy for reducing mortality in diabetic myocardial infarction. Additional trials, already in progress, are expected to refine further the cardiovascular management of patients with diabetes in order to provide an effective challenge for a problem that shows no signs of going away.

Angina Pectoris↗
PubMed2001

Socioeconomic differentials in recurrent ischaemia and mortality after acute myocardial infarction.

OBJECTIVE: To examine the influence of socioeconomic deprivation on case fatality following acute myocardial infarction. DESIGN: Prospective cohort observational study. SETTING: General hospital. PATIENTS: 1417 white and south Asian patients admitted with acute myocardial infarction between January 1988 and December 1996, and classified by the Carstairs socioeconomic deprivation score of the enumeration district of residence. MAIN OUTCOME MEASURES: 30 day and one year survival. RESULTS: There was little variation across deprivation groups in age, sex, or smoking status, though a higher proportion of patients from more deprived enumeration districts were diabetic and of south Asian origin, and a higher proportion of them developed Q wave infarction and left ventricular failure. There was no appreciable variation in clinical treatment with deprivation. Patients from more deprived enumeration districts had a higher risk of recurrent ischaemic events (death, recurrent myocardial infarction, or unstable angina) over the first 30 days: event free survival (95% confidence interval (CI)) of the most deprived quartile was 0.79 (95% CI 0.74 to 0.83) compared with 0.85 (95% CI 0.80 to 0.88) in the least deprived quartile. The unadjusted hazard ratio corresponding to an increase from the 5th to 95th centile of the deprivation distribution was 1.54 (95% CI 1.02 to 2.32), and 1.59 (95% CI 1.03 to 2.44) after adjustment for age, sex, racial group, diabetes, acute treatment with thrombolysis and aspirin, and left ventricular failure. Survival from 30 days to one year, however, did not show a socioeconomic gradient (hazard ratio adjusted for the same variables was 1.07 (95% CI 0.68 to 1.70)). CONCLUSIONS: In patients hospitalised with acute myocardial infarction, there is a strong association between early recurrent ischaemic events and socioeconomic deprivation that is not accounted for by clinical presentation or treatment. This association appears to be attenuated over time.

Adult↗
PubMed2000

Magnitude and consequences of error in coronary angiography interpretation (the ACRE study).

In the routine reporting of coronary angiograms, there are no contemporary estimates of the magnitude and consequences of interobserver variability. We therefore measured the agreement beyond chance between (1) the number of narrowed arteries on an angiographic report extracted from case notes and independent assessments by 2 cardiologists, and (2) actual patient management over an 18-month follow-up period and each cardiologist's hypothetical management proposal based on abstracted clinical details. Two hundred nine angiograms were randomly selected from 4,121 patients in a prospective study (Appropriateness of Coronary Revascularisation [ACRE study]). The number of narrowed arteries was defined using Coronary Artery Surgery Study (CASS) criteria. For the number of narrowed arteries, cardiologists A and B agreed with the angiographic report in 126 patients (60%, weighted kappa = 0.64) and 124 patients (59%, weighted kappa = 0.63), respectively. In a subset of 92 patients (44%) there was unanimous agreement on the number of narrowed arteries (both cardiologists agreed with the angiographic report). Comparing actual management (34 percutaneous transluminal coronary angioplasty and 39 coronary artery bypass grafting procedures on follow-up) with each of the cardiologist's management recommendations showed agreement in 150 patients (72%, kappa = 0.46) and 154 patients (74%, kappa = 0.48) for cardiologists A and B, respectively. These agreements on management improved (p = 0.05) for cardiologist B (but not A) when analysis was confined to the subset of 92 patients, showing agreement in 73 patients (79%, kappa = 0.60). Thus, in routine clinical practice, the agreement beyond chance in interpretation of the number of narrowed arteries was good. Disagreements on subsequent patient management arose as a result of, and independent of, errors in angiographic interpretation.

Adult↗
PubMed2000

Autonomic dysfunction is related to impaired pancreatic beta cell function in patients with coronary artery disease.

OBJECTIVE: To assess the role of beta cell failure in the development of autonomic dysfunction in patients with coronary artery disease. DESIGN: Autonomic function was measured by standard clinical methods and by heart rate variability in 24 type II diabetic and 24 non-diabetic subjects with coronary artery disease. Quantitative estimates of pancreatic beta cell function (%beta) and insulin resistance were made from basal plasma glucose and insulin concentrations using a computer solved model. Fasting proinsulin levels provided an independent measure of beta cell function. RESULTS: The circadian rhythm of sympathovagal balance (ratio of low to high frequency spectral components of heart rate variability) was significantly attenuated in patients with below median (%beta </= 63. 3) compared with above median pancreatic beta cell function. Multiple measures of autonomic function showed positive associations with %beta (low frequency: r = 0.41, p = 0.004; high frequency: r = 0.27, p = 0.07; lying/standing fall in systolic pressure: r = -0.30, p = 0.04) and negative associations with proinsulin (low frequency: r = -0.35, p = 0.03; high frequency: r = -0.36, p = 0.02; standard deviation of RR intervals: r = -0.43, p = 0.007). Associations tended to be stronger in non-diabetic than diabetic patients. In contrast, there was no association between insulin resistance and either autonomic function or the circadian rhythm of sympathovagal balance, regardless of diabetes status. CONCLUSIONS: The data are consistent with the hypothesis that beta cell failure plays a pathogenic role in the development of autonomic dysfunction in patients with coronary artery disease.

Adult↗
PubMed2000

Influence of previous aspirin treatment and smoking on the electrocardiographic manifestations of injury in acute myocardial infarction.

OBJECTIVE: To examine demographic and clinical characteristics of patients with acute myocardial infarction in order to identify factors affecting the electrocardiographic evolution of injury. METHODS: Prospective cohort study of 1399 consecutive patients with a first myocardial infarction. Baseline clinical data associated with ST elevation and Q wave development were identified and 12 month survival was estimated. RESULTS: Smoking had complex effects on the evolution of injury, increasing the odds of ST elevation (odds ratio (OR) 1.61; 95% confidence interval (CI) 1.08 to 2.36), but reducing the odds of Q wave development (OR 0.69, 95% CI 0.49 to 0.96). The effects of previous aspirin treatment were more consistent with reductions in the odds of ST elevation (OR 0.57, 95% CI 0.35 to 0.94) and Q wave development (OR 0.53, 95% CI 0.34 to 0. 84). ST elevation and Q wave development were both associated with an adverse prognosis, with estimated 12 month survival rates of 80. 6% (95% CI 78.2% to 83.1%) and 80.0% (95% CI 77.5% to 82.5%), respectively, compared with 86.5% (95% CI 81.2% to 91.9%) and 89.9% (95% CI 86.2% to 93.7%) for patients without these ECG changes. CONCLUSIONS: The thrombogenicity of the blood may be a major determinant of infarct severity. Smoking increases thrombogenicity and the likelihood of ST elevation, but because coronary occlusion is relatively more thrombotic in smokers, responses to both endogenous and exogenous thrombolysis are better, reducing the risk of Q wave development. Previous aspirin treatment reduces thrombogenicity, protecting against ST elevation and Q wave development.

Aged↗
PubMed2000

Prognostic implications of ventricular fibrillation in acute myocardial infarction: new strategies required for further mortality reduction.

OBJECTIVE: To determine the changing risk of ventricular fibrillation, the prognostic implications, and the potential long term prognostic benefit of earlier hospital admission, after acute myocardial infarction. DESIGN: Prospective observational study. SETTING: A district general hospital in east London. PATIENTS: 1225 consecutive patients admitted to a coronary care unit with acute myocardial infarction. MAIN OUTCOME MEASURES: Time of onset of pain and ventricular fibrillation, and long term survival of patients admitted with acute myocardial infarction. RESULTS: The rate of ventricular fibrillation in these hospital inpatients was high in the first hour from onset of pain (118 events/1000 persons/h; 95% confidence interval (CI) 50.7 to 231) and fell rapidly to an almost constant low level by six hours; 27.4% of patients with early ventricular fibrillation died in hospital, compared with 11.6% of those without (p < 0.0001), but mortality in patients who survived to hospital discharge was not altered by early ventricular fibrillation (five year survival: 75.0% (95% CI 60.0% to 84.8%) with ventricular fibrillation v 73.3% (95% CI 69.6% to 76.6%) without ventricular fibrillation). CONCLUSIONS: Patients successfully resuscitated from early ventricular fibrillation have the same prognosis as those without ventricular fibrillation after acute myocardial infarction. Faster access to facilities for resuscitation must be achieved if major improvements in the persistently high case fatality of patients after acute myocardial infarction are to be made.

Aged↗
PubMed1999

Rating the appropriateness of coronary angiography, coronary angioplasty and coronary artery bypass grafting: the ACRE study. Appropriateness of Coronary Revascularisation study.

BACKGROUND: Previous studies investigating the appropriateness of invasive management of coronary disease had not reported the internal consistency of their ratings and may now be out of date. The aim of this study was to measure the influence of clinical factors on contemporary ratings of the appropriateness of coronary angiography, percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft (CABG) in the Appropriateness of Coronary Revascularisation (ACRE) study. METHODS: The Delphi-RAND technique was used, in which an expert panel (four cardiologists, three cardiothoracic surgeons, a general physician and a general practitioner), meeting in 1995, rated mutually exclusive indications (n = 2178 for angiography, n = 995 for PTCA and n = 984 for CABG). The main outcome measures were the appropriateness category (inappropriate, uncertain or appropriate) for each of the three procedures and treatment preference. RESULTS: For revascularization, the strongest determinant of inappropriateness was coronary anatomy. The odds ratio (OR) for inappropriate PTCA was 10.6 (95 per cent confidence interval (CI) 4.8-23.5) for the effect of left main stem or three-vessel disease versus single-vessel disease, and for CABG it was 0.06 (95 per cent CI 0.03-0.15). The number of diseased vessels was strongly related to preference for medical, PTCA or CABG treatment (p for linear trend <0.001). Mild versus severe anginal symptoms were associated with inappropriate angiography (OR 2.0 (95 per cent CI 0.9-9.8), although this effect was stronger when only the cardiologists' ratings were considered (OR 10.1 (95 per cent CI 2.4-42.6)). CONCLUSION: These are the first UK ratings of appropriateness covering all three procedures. The associations with clinical factors provide evidence of the internal consistency of these ratings. Prospective validation of these ratings against clinical outcomes is under way in the ACRE study.

Aged↗
PubMed1999

Modification of coronary artery disease progression by cholesterol-lowering therapy: the angiographic studies.

Large randomized placebo-controlled trials have demonstrated that cholesterol lowering with statin therapy reduces the incidence of adverse cardiac events. Smaller angiographic studies have shown that coronary artery disease progression can be slowed and, in some cases, reversed by cholesterol-lowering interventions. These anatomical changes, however, are small and occur too slowly to account for the early clinical benefit. Current evidence suggests that plaque stabilization is the most important mechanism, by which cholesterol-lowering therapy reduces both the incidence of adverse cardiac events and coronary artery disease progression.

Anticholesteremic Agents↗
PubMed1999

Diabetes and the heart.

Diabetes mellitus adversely affects the pathology, presentation and outcome of patients with coronary artery disease. Knowledge of the risks and benefits of medical and mechanical therapies particular to diabetic patients is useful in the optimal management of diabetic heart disease.

Coronary Disease↗