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Biomedical subjects

Stuart M Cobbe

Publications and source records attributed to Stuart M Cobbe.

At least 19 recordsLinked to original sources
PubMed2007

Cost-effectiveness of automated external defibrillators in public places: con.

PURPOSE OF REVIEW: To discuss the clinical effectiveness, public health impact and cost-effectiveness of public access defibrillation. RECENT FINDINGS: High rates of survival from prehospital ventricular fibrillation have been documented in patients treated by first responders using automated external defibrillators. The recent Public Access Defibrillation trial demonstrated a doubling of cardiac arrest survival in community units where volunteers trained in cardiopulmonary resuscitation were additionally equipped with automated external defibrillators. The cost-effectiveness analysis of the Public Access Defibrillation trial has not yet been published, and previous analyses have lacked full data on cost, outcome, or both. Data from many sources indicate that automated external defibrillator placement at sites with an expected rate of one cardiac arrest per defibrillator per 5 years, as recommended by the American Heart Association, addresses only around 1-2% of prehospital arrests, and will have a minimal impact on population survival. SUMMARY: While highly targeted provision of automated external defibrillators in areas of greatest risk, such as casinos and airports, may be cost-effective, it will have little impact at a population level. Provision of more widespread public access defibrillation to sites with lower incidence of cardiac arrest is unlikely to be cost-effective, and may represent poorer value for money than alternative healthcare interventions in coronary artery disease.

Cost-Benefit Analysis↗
PubMed2006

Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: This study sought to determine whether metformin improves vascular function or myocardial ischemia in nondiabetic subjects. BACKGROUND: Metformin prevents diabetes and may reduce coronary events in patients with diabetes, but effects on microvascular function and angina are not clear. METHODS: We conducted an 8-week double-blind, randomized, placebo-controlled study of metformin 500 mg twice a day in 33 nondiabetic women with a prior history of normal coronary angiography but two consecutive positive (ST-segment depression > or =1 mm) exercise tolerance tests. All parameters were measured at baseline and at 8 weeks, together with an in vivo assessment of forearm (skin) microvascular function using laser Doppler imaging combined with iontophoresis. RESULTS: In comparison with placebo (n = 17), metformin recipients (n = 16) showed significant reductions in weight and in homeostatic model assessment for insulin resistance (p < 0.05, intention to treat). Endothelium-dependent microvascular responses improved significantly with metformin (2-way repeated analysis of variance, p = 0.0003), but responses with placebo were unchanged (p = 0.50). A comparison of change in acetylcholine responses between metformin and placebo recipients was significant, whether analyzed by a 2-way analysis of variance (p < 0.0001) or change in area under curves (mean change +392 perfusion units, 95% confidence interval [CI] 20 to 764). Endothelium-independent responses were not altered. Maximal ST-segment depression (-0.84 mm, 95% CI -1.49 to -0.20, p = 0.013), Duke score (6.1 U, 95% CI 1.8 to 10.5, p = 0.008), and chest pain incidence (-0.11 episodes/day, 95% CI -0.22 to 0.00, p = 0.056) improved in metformin relative to placebo recipients. CONCLUSIONS: Metformin may improve vascular function and decrease myocardial ischemia in nondiabetic women with chest pain and angiographically normal coronary arteries. Larger controlled trials of longer duration are warranted.

Adult↗
PubMed2006

Microvascular function, metabolic syndrome, and novel risk factor status in women with cardiac syndrome X.

To characterize microvascular function, candidate risk pathways, and metabolic syndrome prevalence in women with cardiac syndrome X, 52 nondiabetic women with angiographically normal epicardial arteries but >1 mm of planar ST depression during exercise testing (patients) and 24 healthy controls of similar age were recruited. In addition to fasting blood samples and anthropometric measurements, forearm cutaneous microvascular function after iontophoresis of acetylcholine and sodium nitroprusside was assessed by laser Doppler imaging. Despite body mass index correction and a larger proportion on statin therapy, patients had high levels of insulin (p=0.016), triglycerides (p=0.018), intercellular adhesion molecule-1 (p=0.021), von Willebrand factor (p=0.005), and leptin (p=0.005) and lower levels of high-density lipoprotein cholesterol (p=0.042) compared with controls. Consistent with these data, 30% of patients but only 8% of controls fulfilled criteria for the metabolic syndrome as defined by the National Cholesterol Education Program (p=0.015). Endothelium-dependent and -independent microvascular functions were markedly impaired in patients (p<0.001), and the odds ratio for cardiac syndrome X was 7.38 (95% confidence interval 2.2 to 24.7) if the acetylcholine response was <8,710 flux units. In conclusion, women with cardiac syndrome X more commonly have metabolic syndrome and related adiposity, metabolic, and inflammatory derangements. They also have significantly impaired skin microvascular function as assessed by laser Doppler imaging, consistent with generalized vascular dysfunction, a finding with potential diagnostic implications.

Acetylcholine↗
PubMed2005

Plasma lipoproteins and apolipoproteins as predictors of cardiovascular risk and treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).

BACKGROUND: Statins are important in vascular disease prevention in the elderly. However, the best method of selecting older patients for treatment is uncertain. We assessed the role of plasma lipoproteins as predictors of risk and of treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). METHOD AND RESULTS: The association of LDLc and HDLc with risk was examined in the 5804 70- to 82-year-old subjects of PROSPER. Baseline LDLc showed no relation to risk of the primary end point in the placebo group (P=0.27), nor did on-treatment LDLc in the pravastatin group (P=0.12). HDLc was inversely associated with risk in subjects on placebo (P=0.0019) but not in those on pravastatin (P=0.24). Risk reduction on pravastatin treatment was unrelated to baseline LDLc (P=0.38) but exhibited a significant interaction with HDLc (P=0.012). Subjects in the lowest 2 quintiles of HDLc (<1.15 mmol/L) had a risk reduction of 33% (hazard ratio, 0.67; 95% confidence limits, 0.55, 0.81; P<0.0001), whereas those with higher HDLc showed no benefit (RR, 1.06; 95% confidence limits, 0.88, 1.27; P=0.53). During follow-up, there was no relation between achieved level of LDLc or HDLc and risk. However, the change in the LDLc/HDLc ratio on statin treatment appeared to account for the effects of therapy. CONCLUSIONS: In people >70 years old, HDLc appears to be a key predictor of risk and of treatment benefit. Findings in PROSPER suggest that statin therapy could usefully be targeted to those with HDLc <1.15 mmol/L or an LDLc/HDLc ratio >3.3.

Aged↗
PubMed2005

Post-discharge survival following pre-hospital cardiopulmonary arrest due to cardiac aetiology: temporal trends and impact of changes in clinical management.

AIMS: To determine whether survival after discharge following pre-hospital cardiopulmonary arrest has improved. METHODS AND RESULTS: The Heartstart Register was used to identify all 1659 patients discharged alive from Scottish hospitals during 1991-01 following pre-hospital arrest due to cardiac aetiology. The cohort was split into tertiles using year of arrest. A Cox proportional hazards model was used to determine risk of death relative to 1991-93. Patients who survived cardiopulmonary arrest in 1997-01 were less likely to die from any cause (unadjusted HR 0.60, 95% CI 0.48-0.75, P<0.001) or cardiac disease (unadjusted HR 0.50, 95% CI 0.38-0.65, P<0.001). After adjustment for case-mix, there remained significant declines in all-cause (adjusted HR 0.62, 95% CI 0.50-0.78, P<0.001) and cardiac death (adjusted HR 0.52, 95% CI 0.39-0.68, P<0.001). Clinical management had improved, with increased use of thrombolysis (47-63%, chi2 trend, P<0.001), beta-blockers (28-53%, chi2 trend, P<0.001), ACE-inhibitors (48-69%, chi2 trend, P<0.001), and anti-thrombotics (79-88%, chi2 trend, P<001). Adjustment for recorded changes in management attenuated the decline in all-cause death (adjusted HR 0.77, 95% CI 0.60-0.98, P=0.03). CONCLUSION: Survival following cardiopulmonary arrest has improved after adjusting for changes in case-mix. Better clinical management has contributed to this improvement.

Aged↗
PubMed2005

Effect of pravastatin on rate of kidney function loss in people with or at risk for coronary disease.

BACKGROUND: Limited data suggest that HMG-CoA reductase inhibitors (statins) reduce rates of kidney function loss. We performed this analysis to determine whether pravastatin reduced the rate of kidney function loss over approximately 5 years in people with or at high risk for coronary disease. METHODS AND RESULTS: This was a post hoc subgroup analysis of data from 3 randomized double-blind controlled trials comparing pravastatin 40 mg/d and placebo in subjects with a previous acute coronary syndrome or who were at high cardiovascular risk. The primary outcome was the rate of change in estimated glomerular filtration rate (GFR; in mL/min per 1.73 m2/y). The Modified Diet and Renal Disease Study (MDRD) and Cockcroft-Gault equations were used to estimate GFR. We studied 18,569 participants, 3402 (18.3%) of whom had moderate chronic kidney disease as defined by an estimated GFR of 30 to 59.9 mL/min per 1.73 m2 body surface area. In subjects with moderate chronic kidney disease at baseline, pravastatin reduced the adjusted rate of kidney function loss by approximately 34%, although the absolute reduction in the rate of loss was small (0.22 mL/min per 1.73 m2/y by MDRD-GFR; 95% CI, 0.07 to 0.37). Pravastatin did not reduce the frequency of > or =25% decreases in kidney function in this group when MDRD-GFR was used to estimate GFR (relative risk [RR], 0.84; 95% CI, 0.66 to 1.06). When all 18,569 subjects were considered, pravastatin reduced the adjusted rate of kidney function loss by 8% (0.08 mL/min per 1.73 m2/y by MDRD-GFR; 95% CI, 0.01 to 0.15) and the risk of acute renal failure (RR, 0.60; 95% CI, 0.41 to 0.86) but did not significantly reduce the frequency of a > or =25% decline in kidney function by MDRD-GFR (RR, 0.94; 95% CI, 0.88 to 1.01). CONCLUSIONS: Pravastatin modestly reduced the rate of kidney function loss in people with or at risk for cardiovascular disease. However, the primary indication for the use of statins in people with or at risk for coronary events remains the reduction in mortality that results from their use.

Aged↗
PubMed2005

Junctional rhythm--a suitable surrogate endpoint in catheter ablation of atrioventricular nodal reentry tachycardia?

INTRODUCTION: Current AHA/ACC guidelines state that junctional rhythm (JR) is an acceptable endpoint in patients undergoing radiofrequency ablation (RFA) for narrow complex tachycardia in the presence of dual AV nodal physiology, but in the absence of inducible AVNRT. Only limited data are available on the utility of JR as a marker of successful slow pathway ablation. We sought to further characterize the sensitivity, specificity, and predictive value of JR in AVNRT ablation. METHODS: A retrospective analysis was performed of 387 consecutive patients with documented narrow complex tachycardia referred for ablation, with dual AV nodal physiology and inducible AVNRT at electrophysiological study. RFA of slow pathway was performed, with the presence or absence of JR recorded for each application and inducibility tested using atrial stimulation protocol and isoproterenol. RESULTS: Successful ablation was achieved in 385 of 387 patients using a total of 1,861 applications of radiofrequency energy. JR occurred in 692 applications, giving a sensitivity and specificity of JR as an indicator of successful ablation of 99.5% and 79.1% and a positive predictive value of 55.5%. CONCLUSIONS: This study confirms that successful ablation of slow pathway seldom occurs in the absence of JR. Although JR almost invariably occurs with successful ablation, its lack of specificity and low positive predictive value questions the use of it as an endpoint in AVNRT ablations, and the guidelines should reflect this.

Adolescent↗
PubMed2004

Effect of pravastatin on cardiovascular events in people with chronic kidney disease.

BACKGROUND: Limited data describe the cardiovascular benefit of HMG-CoA reductase inhibitors (statins) in people with moderate chronic kidney disease (CKD). The objective of this analysis was to determine whether pravastatin reduced the incidence of cardiovascular events in people with or at high risk for coronary disease and with concomitant moderate CKD. METHODS AND RESULTS: We analyzed data from the Pravastatin Pooling Project (PPP), a subject-level database combining results from 3 randomized trials of pravastatin (40 mg daily) versus placebo. Of 19 700 subjects, 4491 (22.8%) had moderate CKD, defined by an estimated glomerular filtration rate of 30 to 59.99 mL/min per 1.73 m2 body surface area. The primary outcome was time to myocardial infarction, coronary death, or percutaneous/surgical coronary revascularization. Moderate CKD was independently associated with an increased risk of the primary outcome (adjusted HR 1.26, 95% CI 1.07 to 1.49) compared with those with normal renal function. Among the 4491 subjects with moderate CKD, pravastatin significantly reduced the incidence of the primary outcome (HR 0.77, 95% CI 0.68 to 0.86), similar to the effect of pravastatin on the primary outcome in subjects with normal kidney function (HR 0.78, 95% CI 0.65 to 0.94). Pravastatin also appeared to reduce the total mortality rate in those with moderate CKD (adjusted HR 0.86, 95% CI 0.74 to 1.00, P=0.045). CONCLUSIONS: Pravastatin reduces cardiovascular event rates in people with or at risk for coronary disease and concomitant moderate CKD, many of whom have serum creatinine levels within the normal range. Given the high risk associated with CKD, the absolute benefit that resulted from use of pravastatin was greater than in those with normal renal function.

Adult↗
PubMed2004

Comparison of femoral bleeding complications after coronary angiography versus percutaneous coronary intervention.

Vascular complications arising after coronary angiography (CA) and percutaneous coronary intervention (PCI) may be under-reported. Access site complications were studied after consecutive CA and PCI in the investigators' center (an urban university hospital) from October to December 2002. Three hundred eleven consecutive procedures (237 CA studies and 74 PCIs) were included, of which 309 (99%) involved femoral arterial access. Seventy percent of all arterial punctures were closed by manual pressure, 28% by C-pressure clamps, and 2% with closure devices. Femoral hematomas occurred in 22% and 41% of CA studies and PCIs, respectively. Hematoma >5 cm occurred in 6% and 11% of CA studies and PCIs, respectively. Nineteen patients (23%) with access site complications had prolonged hospital admission. Increased body mass index and hematoma development within the catheter laboratory were predictors of prolonged admission.

Age Distribution↗
PubMed2004

Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the west of Scotland coronary prevention study.

We examined the association of serum alanine aminotransferase (ALT) with features of the metabolic syndrome and whether it predicted incident diabetes independently of routinely measured factors in 5,974 men in the West of Scotland Coronary Prevention Study. A total of 139 men developed new diabetes over 4.9 years of follow-up. ALT, but not aspartate aminotransferase, levels increased progressively with the increasing number of metabolic syndrome abnormalities from (means +/- SD) 20.9 +/- 7.6 units/l in those with none to 28.1 +/- 10.1 units/l in those with four or more (P < 0.001). In a univariate analysis, men with ALT in the top quartile (ALT >/=29 units/l) had an elevated risk for diabetes (hazard ratio 3.38 [95% CI 1.99-5.73]) versus those in the bottom quartile (<17 units/l). ALT remained a predictor with adjustment for age, BMI, triglycerides, HDL cholesterol, systolic blood pressure, glucose, and alcohol intake (2.04 [1.16-3.58] for the fourth versus first quartile). In stepwise regression, incorporating ALT and C-reactive protein (CRP) together with metabolic syndrome criteria, elevated ALT (>/=29 units/l), and CRP (>/=3 mg/l) predicted incident diabetes, but low HDL cholesterol and hypertension did not. Thus, elevated ALT levels within the "normal" range predict incident diabetes. The simplicity of ALT measurement and its availability in routine clinical practice suggest that this enzyme activity could be included in future diabetes prediction algorithms.

Alanine Transaminase↗
PubMed2003

Cost effectiveness and cost utility model of public place defibrillators in improving survival after prehospital cardiopulmonary arrest.

OBJECTIVE: To determine the cost effectiveness and cost utility of locating defibrillators in all major airports, railway stations, and bus stations throughout Scotland. DESIGN: Economic modelling exercise with data from Heartstart (Scotland). Parameters used in economic model included direct costs derived for increased accident and emergency attendances, increased hospital bed days, purchase and maintenance of defibrillators, and training in their use; life years gained calculated from increased discharges from hospital and mean survival after discharge; utility (quality of life) obtained from published data. Sensitivity analyses tested the robustness of model. Future gains discounted at 1.5% a year and future costs at 6%. SETTING: Whole of Scotland. SUBJECTS: Records of all prehospital cardiac arrests due to presumed heart disease that occurred in a major airport, railway, or bus station between May 1991 and March 1998 and were not witnessed by ambulance or medical staff. MAIN OUTCOME MEASURES: Observed survival to hospital admission and observed survival to discharge. Predicted survival calculated by applying observed survival in patients attended by ambulance staff within three minutes to those who waited longer. RESULTS: The total discounted direct costs were 18 325 pounds sterling a year. The cost per life year gained was 29 625 pounds sterling (49 625 dollars, 43 151 Euros) and the cost per quality adjusted life year (QALY) gained was pound 41 146 (68 924 dollars, 59 932 Euros). More widespread provision of public place defibrillators would increase these figures. CONCLUSIONS: The cost per QALY calculated for public place defibrillators represents poorer value for money than some alternative strategies for improving survival after prehospital cardiopulmonary arrest, such as the use of other trained first responders. The figure exceeds the commonly discussed cut off levels for funding in the United Kingdom and United States of pound 30 000 and 50 000 dollars per QALY, respectively.

Cost-Benefit Analysis↗
PubMed2003

Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study.

BACKGROUND: The National Cholesterol Education Program (NCEP) recently proposed a simple definition for metabolic syndrome. Information on the prospective association of this definition for coronary heart disease (CHD) and type 2 diabetes is currently limited. METHODS AND RESULTS: We used a modified NCEP definition with body mass index in place of waist circumference. Baseline assessments in the West of Scotland Coronary Prevention Study were available for 6447 men to predict CHD risk and for 5974 men to predict incident diabetes over 4.9 years of follow-up. Mean LDL cholesterol was similar but C-reactive protein was higher (P<0.0001) in the 26% of men with the syndrome compared with those without. Metabolic syndrome increased the risk for a CHD event [univariate hazard ratio (HR)=1.76 (95% CI, 1.44 to 2.15)] and for diabetes [univariate HR=3.50 (95% CI 2.51 to 4.90)]. Metabolic syndrome continued to predict CHD events (HR=1.30, 95% CI, 1.00 to 1.67, P=0.045) in a multivariate model incorporating conventional risk factors. Men with 4 or 5 features of the syndrome had a 3.7-fold increase in risk for CHD and a 24.5-fold increase for diabetes compared with men with none (both P<0.0001). C-reactive protein enhanced prognostic information for both outcomes. With pravastatin, men with the syndrome had similar risk reduction for CHD as compared with those without (HR, 0.73 and 0.69; pravastatin versus placebo). CONCLUSIONS: A modified NCEP metabolic syndrome definition predicts CHD events, and, more strikingly, new-onset diabetes, and thus helps identify individuals who may receive particular benefit from lifestyle measures to prevent these diseases.

Body Mass Index↗
PubMed2002

Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.

BACKGROUND: Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals, their efficacy and safety in elderly people is not fully established. Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with, or at high risk of developing, cardiovascular disease and stroke. METHODS: We did a randomised controlled trial in which we assigned 5804 men (n=2804) and women (n=3000) aged 70-82 years with a history of, or risk factors for, vascular disease to pravastatin (40 mg per day; n=2891) or placebo (n=2913). Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke. Analysis was by intention-to-treat. FINDINGS: Pravastatin lowered LDL cholesterol concentrations by 34% and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo (hazard ratio 0.85, 95% CI 0.74-0.97, p=0.014). Coronary heart disease death and non-fatal myocardial infarction risk was also reduced (0.81, 0.69-0.94, p=0.006). Stroke risk was unaffected (1.03, 0.81-1.31, p=0.8), but the hazard ratio for transient ischaemic attack was 0.75 (0.55-1.00, p=0.051). New cancer diagnoses were more frequent on pravastatin than on placebo (1.25, 1.04-1.51, p=0.020). However, incorporation of this finding in a meta-analysis of all pravastatin and all statin trials showed no overall increase in risk. Mortality from coronary disease fell by 24% (p=0.043) in the pravastatin group. Pravastatin had no significant effect on cognitive function or disability. INTERPRETATION: Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals. PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people.

Aged↗