Carbonyl-scavenging drugs & protection against carbonyl stress-associated cell injury.

This mini-review highlights the chemical and cytoprotective properties of various hydralazine analogues that block the induction of cell death by acrolein, a highly toxic contributor to "carbonyl stress" during a diverse range of human diseases. Recent work on the action of hydralazine against various carbonyl-mediated pathologies is also reviewed.

Sudden, unexpected cardiac or unexplained death in England: a national survey.

BACKGROUND: Post-mortem examinations of adults who were apparently healthy but died suddenly and unexpectedly sometimes reveal no morphological abnormalities to explain their deaths. The frequency of such unexplained deaths in relation to other causes of sudden cardiac death is not known. AIM: To estimate the frequency of sudden unexpected cardiac or unexplained death in England. DESIGN: Prospective survey using a stratified random sample of 83 of the 132 H.M. Coroner's jurisdictions in England. METHODS: Consecutive White Caucasians, aged 16-64 years, with no medical history of cardiac disease, seen alive within 12 h of death, on whom autopsy found either a cardiac or no identifiable cause of death, were included. The coroner's officer sent a copy of the post-mortem report and a completed case registration form to the investigators, with tissue samples. RESULTS: Sixty-seven (81%) coroners participated, each maintaining prospective surveillance for 4 months. Of 692 ascertained cases, case registration forms were received for 650 (94%), post-mortem reports for 682 (99%), blood samples for 569 (82%), myocardial slices for 517 (75%) and whole hearts for 47 (7%). In cases with myocardial tissue, death was ascribed to ischaemic heart disease in 465 (82.4%). In 43.1% the ischaemia was acute, in 19.1% there was myocardial scarring but no acute ischaemia, and 20.2% had coronary atheroma only. Death was due to left ventricular hypertrophy in 32 (5.7%), to other cardiac causes in 30 (5.3%) and in 23 (4.1%) there was no clear cause. Those with cardiac causes were 81% male, median ages 55.9 (male) and 56.6 (female) years. The 23 unexplained deaths were 57% female, median ages 40.5 (male) and 54.9 (female) years. The estimated annual frequency of sudden unexpected death due to cardiac or unidentified causes, in English adults of employment age, was 11/100,000 (3481 annual deaths). DISCUSSION: In 4.1% of sudden unexpected deaths under 65 years, no cause was found. Until it becomes accepted practice to identify these cases by a name, such as Sudden Adult Death Syndrome (SADS), it will not be possible to study their aetiology systematically.

Mechanistic investigations on the reaction between 1,2-dioxines and bulky stabilized phosphorus ylides: an efficient route to closely related cyclopropane stereoisomers.

The bulky stabilized ylides (2a-d) react with a range of 1,2-dioxines (1a-d) to afford the diversely functionalized cyclopropanes 7 in excellent yield and diastereomeric excess. This is in direct contrast to the situation when nonbulky ester ylides are utilized which results in a completely different cyclopropyl series. Through a combination of isolation, spectroscopic, temperature, and deuterium and additive effects studies, the mechanism of cyclopropane formation from this second pathway can be proposed. Importantly, enolate quenching of the intermediate 1-2lambda(5)-oxaphospholanes 4 prior to collapse results in an equilibrium mixture of intermediates 10 and 11 which have been fully characterized, and their formation is primarily a result of the steric bulk of the stabilized ester ylide. These intermediates (10/11) then collapse further and result in formation of the observed closely related cyclopropyl stereoisomers 7 and 8. Moreover, the addition of LiBr to these reactions allows for the control of which of the two possible cyclopropanation pathways will be dominant. Finally, optimal protocols that demonstrate the potential of this new cyclopropanation methodology for the ready construction of closely related cyclopropyl stereoisomers are presented.

In vitro antiviral activity of the anthraquinone chrysophanic acid against poliovirus.

Chrysophanic acid (1,8-dihydroxy-3-methylanthraquinone), isolated from the Australian Aboriginal medicinal plant Dianella longifolia, has been found to inhibit the replication of poliovirus types 2 and 3 (Picornaviridae) in vitro. The compound inhibited poliovirus-induced cytopathic effects in BGM (Buffalo green monkey) kidney cells at a 50% effective concentration of 0.21 and 0.02 microgram/ml for poliovirus types 2 and 3, respectively. The compound inhibited an early stage in the viral replication cycle, but did not have an irreversible virucidal effect on poliovirus particles. Chrysophanic acid did not have significant antiviral activity against five other viruses tested: Coxsackievirus types A21 and B4, human rhinovirus type 2 (Picornaviridae), and the enveloped viruses Ross River virus (Togaviridae) and herpes simplex virus type 1 (Herpesviridae). Four structurally-related anthraquinones--rhein, 1,8-dihydroxyanthraquinone, emodin and aloe-emodin were also tested for activity against poliovirus type 3. None of the four compounds was as active as chrysophanic acid against the virus. The results suggested that two hydrophobic positions on the chrysophanic acid molecule (C-6 and the methyl group attached to C-3) were important for the compound's activity against poliovirus.

Designing bronchial biopsy studies.

Bronchial biopsy provides valuable information about the inflammatory processes in lung tissue, but optimal results are only achieved if the design of intervention studies is sufficiently rigorous. The parallel-group design has merit, but the cross-over design is statistically superior, providing the wash-out period is effective. Heterogeneity of contributing pathologies in asthma patients results in large inter-patient variability which must be controlled for, for example by using strict inclusion criteria, which should ideally relate to the specific inflammatory marker being studied. The inclusion of a placebo group helps to quantify sample variability. The study must have sufficient statistical power to detect inter-group differences for each variable; appropriate adjustments should be made when multiple tests are used. Studies with larger patient numbers are best performed using a multi-centre design, with one centre analysing all tissue samples to reduce variability. Study duration depends on the type of investigation, but should ideally be short. Longer studies are necessary to evaluate chronic changes such as tissue remodelling. Changes in clinical status and cellular events may follow different time courses after intervention. Biopsy measurements are less reproducible than physiological tests, and diurnal variation in the number and function of inflammatory cells can further complicate measurement. The timing of clinical trial assessments needs to allow for these idiosyncrasies. Finally, a balance must be maintained between the risk, albeit small, and the benefit of performing bronchial biopsies.

Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA).

OBJECTIVE: To examine the benefits of adding salmeterol compared with increasing dose of inhaled corticosteroids. DESIGN: Systematic review of randomised, double blind clinical trials. Independent data extraction and validation with summary data from study reports and manuscripts. Fixed and random effects analyses. SETTING: EMBASE, Medline, and GlaxoWellcome internal clinical study registers. MAIN OUTCOME MEASURES: Efficacy and exacerbations. RESULTS: Among 2055 trials of treatment with salmeterol, there were nine parallel group trials of >/=12 weeks with 3685 symptomatic patients aged >/=12 years taking inhaled steroid in primary or secondary care. Compared with response to increased steroids, in patients receiving salmeterol morning peak expiratory flow was greater at three months (difference 22.4 (95% confidence interval 15.0 to 30.0) litre/min, P<0.001) and six months (27.7 (19.0 to 36.4) litre/min, P<0.001). Forced expiratory volume in one second (FEV(1)) was also increased at three months (0.10 (0.04 to 0.16) litres, P<0.001) and six months (0.08 (0.02 to 0.14) litres, P<0.01), as were mean percentage of days and nights without symptoms (three months: days-12% (9% to 15%), nights-5% (3% to 7%); six months: days-15% (12% to 18%), nights-5% (3% to 7%); all P<0.001) and mean percentage of days and nights without need for rescue treatment (three months: days-17% (14% to 20%), nights-9% (7% to 11%); six months: days-20% (17 to 23%), nights-8% (6% to 11%); all P<0.001). Fewer patients experienced any exacerbation with salmeterol (difference 2.73% (0.43% to 5.04%), P=0. 02), and the proportion of patients with moderate or severe exacerbations was also lower (2.42% (0.24% to 4.60%), P=0.03). CONCLUSIONS: Addition of salmeterol in symptomatic patients aged 12 and over on low to moderate doses of inhaled steroid gives improved lung function and increased number of days and nights without symptoms or need for rescue treatment with no increase in exacerbations of any severity.

Clinical effectiveness on an acute in-patient psychiatric unit.

The paper outlines a model for addressing clinical effectiveness, and an illustration of how this is practically implemented through team working in a multidisciplinary in-patient environment. This is particularly relevant given the number of recent reports that highlight the need to develop and invest in the in-patient services. The difficulty in implementing evidence-based practice for mental health interventions is also addressed and initiatives being developed to enable a realistic approach in such an environment are described. The paper describes a structure and a process, using examples from audit, research and other initiatives particular to the unit, in providing accessible evidence based interventions for ward based staff, and improved clinical effectiveness generally.

Antiviral flavonoid from Pterocaulon sphacelatum, an Australian Aboriginal medicine.

The antipicornaviral activity of an ethanolic extract of the green aerial parts of the Australian plant Pterocaulon sphacelatum (Labill.) Benth. & Hook. f. ex F. Muell. has been investigated. This plant has been a favoured traditional medicine, used for the treatment of colds by the Australian Aboriginal people. Antiviral activity-guided fractionation of the extract of P. sphacelatum using an inhibition of poliovirus-induced cytopathic effect assay, has yielded the antiviral flavonoid chrysosplenol C (3,7,3'-trimethoxy-5,6,4'-trihydroxyflavone). This compound is a 4'-hydroxy-3-methoxyflavone, one of a group of compounds known to be potent and specific inhibitors of picornaviral replication. These compounds inhibit the replication of rhinoviruses, the most frequent causative agent of the common cold. The coumarin 6,7,8-trimethoxycoumarin was also isolated from the ethanolic extract.

Characterisation and in vitro cytotoxicity of triorganophosphinegold(i) 2-mercaptobenzoate complexes.

The preparation and full NMR ((1)H, (13)C and (31)P) characterisation of three [R(3)PAu(2mba)] complexes, Where R = Et, Ph and Cy, and 2mba is the anion derived from 2-mercaptobenzoic acid is reported. An interesting solvent dependence in the (1)H spectra is rationalised in terms of competing intra- and inter-molecular hydrogen bonding. An X-ray analysis of the [Ph(3) PAu(2mba)] species reveals a linear P-Au-S arrangement and association in the lattice via the familar carboxylic acid dimer motif. The in Vitro cytotoxicity against seven human tumout lines is also described. The complexes display moderate to very high activity. Particularly noteworthy is their greater activity against the H226 cell line (non-small cell lung cancer) compared with that displayed by a range of cytotoxic drugs.

Functional disability and end organ damage in patients with systemic lupus erythematosus (SLE), SLE and Sjögren's syndrome (SS), and primary SS.

OBJECTIVE: To determine the accumulated end organ damage and health status in patients with SS and to compare with patients with SLE (with or without SS). METHODS: Thirty-seven patients with primary SS were studied and compared with 120 patients with SLE and 21 patients with SLE and SS. The Medical Outcome Survey Short Form 20 with an additional question for fatigue was used to assess health status. The SLICC/ACR damage index with a supplementary oral section was used to assess end organ damage. For statistical analysis, logistic regression analysis, Fisher's exact test, and Kruskal-Wallis rank tests were applied. RESULTS: Patients in all 3 groups had reduced quality of life with respect to all aspects of functional status and well being. There was no difference between the groups. In the primary SS group, the greatest damage was in the oral section (62% of patients). The patients with SLE and SS had the greatest renal, peripheral vascular, and musculoskeletal damage (24, 19, 38% of patients, respectively) followed by the SLE group. Ocular damage was more common in the primary SS group, but that was due to older age in this group. Malignancy was most common in the primary SS group (11%). Other organ damage scores did not differ between groups. CONCLUSION: End organ damage is uncommon in primary SS (with the exception of oral damage), but the degree of functional ability is as great as in SLE.

The design and analysis of paired cluster randomized trials: an application of meta-analysis techniques.

The statistical issues in clinical trials where clusters, communities or groups rather than individuals are randomized are often not fully appreciated. In this paper we discuss the design and analysis of trials in which pairs of clusters are randomized in the context of one recent trial, the British Family Heart Study. Both sample size calculations and the analysis strategy need to take account of the between-cluster component of variance. The analysis can be considered as a random effects meta-analysis across cluster pairs, and can usefully be presented as such. Techniques developed in the context of meta-analysis can then be used in the analysis, for example using a profile likelihood method to derive a confidence interval for the overall treatment effect which takes into account the variability in the estimate of the between-cluster variance. The methods presented here are contrasted with previously published methods for cluster randomized trials.

Change in coronary risk and coronary risk factor levels in couples following lifestyle intervention. The British Family Heart Study.

OBJECTIVES: To measure the extent to which changes in cardiovascular risk factors were correlated among married couples following a 1-year primary care, family-centered, cardiovascular lifestyle intervention program and to identify couples who benefited most from this prevention program. DESIGN: Observational study. SETTING: Thirteen primary care centers in 13 towns in Britain. PARTICIPANTS: A total of 1477 men aged 40 to 59 years and their female partners who attended a family health checkup in 1991 to 1992 from randomly ordered invitations to registered families. After 1 year, 1204 (82%) partner pairs were rescreened. MAIN OUTCOME MEASURES: One-year changes in cigarette smoking, systolic blood pressure, serum cholesterol level, blood glucose level, and a total coronary risk score. RESULTS: Comparing men and women partners, baseline values and 1-year changes in overall coronary risk score (Pearson r = 0.27 and r = 0.20, respectively), cigarette smoking, body mass index, systolic blood pressure, cholesterol levels, and glucose levels were all positively correlated (all P < .001 except smoking cessation, P = .03). Changes in cholesterol levels and systolic blood pressure were also associated with partner's baseline measurement (P < or = .01 in both men and women). CONCLUSIONS: Men and women who benefit most from risk factor reductions have partners who also tend to benefit most. Conversely, men and women who enjoy little or no benefit have partners who tend to have similarly small benefits. It is likely that lifestyle intervention targeted at men and women as couples rather than as individuals may result in a greater reduction in cardiovascular risk factors, possibly through mutual reinforcement of lifestyle changes.

Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.

BACKGROUND: Inflammation is an important feature of atherosclerotic lesions, and increased production of the acute-phase reactant. C-reactive protein (CRF), is associated with a poor prognosis in severe unstable angina. We have investigated the existence and possible significance of the acute-phase responses of CRP and another sensitive reactant, serum amyloid A protein (SAA), in patients with unstable or stable angina. METHODS: We used new ultrasensitive immunoassays to measure CRP and SAA concentrations in plasma from 2121 outpatients with angina (1030 unstable, 743 stable, the rest atypical) enrolled in the European Concerted Action on Thrombosis and Disabilities (ECAT) Angina Pectoris Study. All patients underwent coronary angiography and extensive clinical and laboratory assessment at study entry, and were then followed up for 2 years. All suspected coronary events during follow-up were reviewed by an independent endpoint committee. FINDINGS: 75 individuals (41 with unstable, 29 with stable, and 5 with atypical angina) had a coronary event during follow-up. Concentrations of CRP at study entry were associated with coronary events in patients with stable or unstable angina: there was about a two-fold increase in the risk of a coronary event in patients whose CRP concentration was in the fifth quintile (> 3.6 mg/L), compared with the first four quintiles. A third of the events occurred among patients who had a CRP concentration of more than 3.6 mg/L. CRP concentrations were positively correlated with age, smoking, body-mass index, triglycerides, extent of coronary stenosis, history of myocardial infarction, and lower ejection fraction. By contrast, concentrations of SAA were not associated with risk of a coronary event. INTERPRETATION: We found that raised circulating concentrations of CRP are predictors of coronary events in patients with stable or unstable angina. The modest acute-phase responses of CRP were probably not the result of myocardial necrosis. Whatever the underlying mechanisms, the sensitive measurement of CRP as a prognostic marker may be useful in the management of coronary heart disease.

Association of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index with measures of disease activity and health status in patients with systemic lupus erythematosus.

OBJECTIVE: To examine the internal consistency and validity of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) with respect to disease activity, health status, and medication score. METHODS: A prospective cross sectional study of patients with systemic lupus erythematosus (SLE) attending a specialist lupus outpatient clinic between July 1994 and February 1995. The internal consistency of the SDI components was examined using Cronbach's coefficient alpha. The associations of the SDI components with disease activity measured by the British Isles Lupus Assessment Group (BILAG) index, health status measured by the Medical Outcomes Study (MOS) Short Form 20, and with a medication score were analyzed using Spearman's rank correlation coefficient (p). RESULTS: 133 women and 8 men ranging in age from 20.1 to 88.7 years (mean 41.1, SD 12.5) were studied. With few exceptions, the components of the SDI that reflect damage in different organ systems were not associated with each other. We found a significant although weak relationship between some related SDI and BILAG components (p 0.25 to 0.28; p < 0.01). While damage to the musculoskeletal system was associated with limitations in physical functioning measured with the MOS Short Form 20 (p-0.30; p < 0.01) and renal damage inversely with fatigue (p-0.23; p < 0.01) there was no significant relationship of other SDI components with the MOS Short Form 20. Renal and neuropsychiatric damage were associated significantly with the medication score (p 0.27 and 0.23; p < 0.01). CONCLUSION: The components of the SDI are valid in that they are associated with disease activity in the respective organ systems and some of them with a medication score. However, damage in different organ systems in SLE does not follow a common pattern. It is thus suggested that the SDI profile be used in addition to the SDI total score as an endpoint in clinical and epidemiological studies.

Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities.

BACKGROUND: Disturbances of the fibrinolytic system that lead to decreased removal of fibrin deposits may be important risk factors for coronary thrombosis. There is as yet no consensus on the prognostic value of fibrinolytic parameters, which may be attributed in part to the choice of confounding variables controlled for. METHODS AND RESULTS: The ECAT study is a prospective multicenter study of 3043 patients with angina pectoris followed for 2 years. Baseline measurements included 10 fibrinolytic variables. The results were analyzed in relation to the subsequent incidence of myocardial infarction or sudden coronary death. They are presented before and after adjustment for clusters of confounding variables that are markers of different mechanisms: insulin resistance (body mass index, triglyceride, and HDL cholesterol), inflammation (fibrinogen and C-reactive protein), and endothelial cell damage (von Willebrand factor). An increased incidence of events was associated with higher baseline concentrations of tissue plasminogen activator (TPA) antigen (P = .0002), plasminogen activator inhibitor-1 (PAI-1) activity (P = .02), and PAI-1 antigen (P = .001). The associations of PAI-1 activity and PAI-1 antigen with risk of events disappeared after adjustment for parameters reflecting insulin resistance but were not affected by other adjustments. TPA antigen was affected to a similar extent by adjustment for parameters reflecting insulin resistance. Inflammation, or endothelial cell damage, but the risk association disappeared only after combined adjustments. CONCLUSIONS: The prognostic role of PAI-1 in predicting coronary events is related principally to insulin resistance, whereas that of TPA antigen could be explained only by its relationship with different mechanisms, including insulin resistance, inflammation and endothelial cell damage.

The psychological impact of cardiovascular screening and intervention in primary care: a problem of false reassurance? British Family Heart Study Group.

BACKGROUND: There have been many reports of the adverse psychological effects of screening. Here we discuss the results of a randomized controlled study--one of the first to address this issue. AIM: To determine the extent to which participation in a population-based intervention programme that aims to reduce the risk of cardiovascular diseases raises concerns about health, or undermines a belief in the ability to reduce that risk. METHOD: A randomized controlled trial involving 13 general practices in England, Wales and Scotland was conducted. Two thousand, nine hundred and eighty-four middle-aged men and women undergoing cardiovascular risk-screening and intervention, and a randomized comparison group of 3,576 men and women from the same practices, who were not offered the intervention, were compared on three outcomes: perception of current health, perceived risk of suffering a heart attack, and perceived ability to reduce the risk of suffering a heart attack. RESULTS: We found no evidence to suggest that participation in this one-year, population-based intervention programme, to reduce the risk of cardiovascular disease raised concerns about health or risk of a heart attack; indeed, those in the intervention group were slightly more optimistic about their health. Alterations in perceptions of current health and the risk of suffering a heart attack were associated directly with true alterations in risk factors. A more noticeable effect on participants in this intervention programme was a reduction in their perceived ability to further reduce their risks of a heart attack. This was associated with a decrease in weight and with quitting smoking. CONCLUSION: Contemporary screening and intervention programmes in primary care, aimed at reducing risk of cardiovascular disease, do not necessarily lead to raised anxiety or concern about health. A more subtle effect of screening would appear to be one of reassurance in the face of continuing, albeit reduced, risk.

Further validation of the BILAG disease activity index in patients with systemic lupus erythematosus.

OBJECTIVE: To examine the association among the BILAG disease activity index components and their relations with global assessments, health status, and laboratory tests with regard to the validity of the BILAG index. METHODS: A cross sectional study of consecutive patients with systemic lupus erythematosus (SLE) attending a specialist lupus outpatient clinic between July 1994 and February 1995. The internal consistency of the British Isles Lupus Assessment Group (BILAG) index-a disease activity assessment system for SLE patients, based on the principle of the physician's intention to treat-was examined using Cronbach's coefficient alpha. The association of the components of the BILAG index with health status as measured with the MOS Short Form 20 (SF-20), with patients' and doctors' global assessments of patient wellbeing and with laboratory tests was analysed with Spearman rank correlations. RESULTS: 133 female and eight male patients, age 20.1 to 88.7 years (mean 41.1, SD 12.5), were included. With few exceptions, the components of the BILAG index which reflect disease activity in different organ systems were not associated with each other. With the exception of the mucocutaneous component, we found a significant relation between all components of BILAG and global assessment of patient wellbeing, health status, erythrocyte sedimentation rate, or serum C3 level. CONCLUSIONS: The study confirms the validity of all but the mucocutaneous component of the BILAG index. However, disease activity in different organ systems in SLE does not follow a common pattern. Thus the individual BILAG components should be used rather than the total BILAG score as a primary endpoint in clinical and epidemiological studies. To capture the total effect of SLE on an individual measures of disease activity, damage, and health status are all needed.

Using a coronary risk score for screening and intervention in general practice. British Family Heart Study.

AIM: To investigate whether a risk score proposed by the British Regional Heart Study (BRHS), derived from data collected in 1978-1980, provides an appropriate basis for current coronary risk factor screening and intervention in general practice. METHODS: The BRHS risk score was applied to 1993 men aged 40-59 years and 1353 women aged 35-59 years, from 13 general practices in England, Wales and Scotland, who had health checks during 1991-1992 in the British Family Heart Study (FHS). Modifications to the BRHS risk score were made in order to identify subjects with a current high risk compared with others of the same age and sex. These were validated on 3272 men and 2229 women recruited from different general practices during 1992-1994 in the FHS. RESULTS: Only 9% of men in the FHS fell into the published top (highest risk) quintile of the BRHS score, versus an expected 20%, and 44% fell into the bottom quintile. Scores were, on average, substantially lower in the FHS men than in the BRHS men, principally because of lower measured cholesterol levels (using a Reflotron) and a lower prevalence of cigarette-smoking. The BRHS scores also tended to increase with age, disproportionately identifying older subjects, and were substantially lower in women than in men. Simple age-related modifications to the risk score were therefore devised to overcome these problems. These modifications performed well in the validation. CONCLUSIONS: The substantial difference in risk scores between the BRHS and FHS men may reflect both a real reduction in risk and changes in calibration and methodology. Current use of the BRHS risk score may therefore mislead doctors and patients in the direction of complacency. In addition, the published BRHS risk score has an age-dependence that is undesirable in terms of guiding the intensity of lifestyle intervention which should be offered to an individual patient. The simple modifications proposed provide a more appropriate basis for coronary risk factor screening and intervention in general practice, and one that can be used both for men and for women.

Costs and cost effectiveness of cardiovascular screening and intervention: the British family heart study.

OBJECTIVE: To measure costs and cost effectiveness of the British family heart study cardiovascular screening and intervention programme. DESIGN: Cost effectiveness analysis of randomised controlled trial. Clinical and resource use data taken from trial and unit cost data from external estimates. SETTING: 13 general practices across Britain. SUBJECTS: 4185 men aged 40-59 and their 2827 partners. INTERVENTION: Nurse led programme using a family centered approach, with follow up according to degree of risk. MAIN OUTCOME MEASURES: Cost of the programme it self; overall short term cost to NHS; cost per 1% reduction in coronary risk at one year. RESULTS: Estimated cost of putting the programme into practice for one year was 63 pounds per person (95% confidence interval 60 pounds to 65 pounds). The overall short term cost to the health service was 77 pounds per man (29 pounds to 124 pounds) but only 13 pounds per woman (-48 pounds to 74 pounds), owing to differences in utilisation of other health service resources. The cost per 1% reduction in risk was 5.08 pounds per man (5.92 pounds including broader health service costs) and 5.78 pounds per woman (1.28 pounds taking into account wider health service savings). CONCLUSIONS: The direct cost of the programme to a four partner practice of 7500 patients would be approximately 58,000 pounds. Annually, 8300 pounds would currently be paid to a practice of this size working to the maximum target on the health promotion bands, plus any additional reimbursement of practice staff salaries for which the practice qualified. The broader short term costs to the NHS may augment these costs for men but offset them considerably for women.

A British Cardiac Society survey of the potential for the secondary prevention of coronary disease: ASPIRE (Action on Secondary Prevention through Intervention to Reduce Events).

OBJECTIVE: To measure the potential for secondary prevention of coronary disease in the United Kingdom. DESIGN: Cross sectional survey of a representative sample of coronary patients from a retrospective review of hospital medical records and patient interview and examination. SETTING: Stratified random sample of 12 specialist cardiac centres and 12 district general hospitals drawn from 34 specialist cardiac centres and 261 district general hospitals in 12 geographic areas in the United Kingdom. SUBJECTS: 2583 patients < or = 70 yr; 25 consecutive males and 25 consecutive females identified retrospectively in each of four diagnostic categories: coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, acute myocardial infarction, and acute myocardial ischaemia without evidence of infarction. MAIN OUTCOME MEASURES: Risk factor recording and management in medical records; the prevalence and control of risk factors at interview six months after the procedure or event. RESULTS: Recording of coronary risk factors in patient's records was incomplete and this varied by risk factor. Smoking habit and blood pressure were most completely recorded, whereas a history of hyperlipidaemia and blood cholesterol concentrations were least complete. Risk factor records were more likely to be complete in cardiac centres than in district hospitals. At interview 10% to 27% of patients were still smoking cigarettes and 75% remained overweight, females more severely so. Up to a quarter of patients remained hypertensive, males more severely so than females. Over three quarters had a total cholesterol > 5.2 mmol/l. In patients on medication for blood pressure, cholesterol or glucose, risk factor profiles were little better than in those who were not. Only about one patient in three was taking a beta blocker after infarction. Up to a fifth of patients who had had acute myocardial ischaemia were not taking aspirin at follow up. CONCLUSIONS: There is considerable potential to reduce the risk of a further major ischaemic event in patients with established coronary disease. This can be achieved by effective lifestyle intervention, the rigorous management of blood pressure and cholesterol, and the appropriate use of prophylactic drugs.