Showing papers by "Stuart M. Cobbe published in 2011"

Obesity is associated with fatal coronary heart disease independently of traditional risk factors and deprivation

Abstract: Background The effect of body mass index (BMI) on coronary heart disease (CHD) risk is attenuated when mediators of this risk (such as diabetes, hypertension and hyperlipidaemia) are accounted for. However, there is now evidence of a differential effect of risk factors on fatal and non-fatal CHD events, with markers of inflammation more strongly associated with fatal than non-fatal events. Objective To describe the association with BMI separately for both fatal and non-fatal CHD risk after accounting for classical risk factors and to assess any independent effects of obesity on CHD risk. Methods and results In the West of Scotland Coronary Prevention Study BMI in 6082 men (mean age 55 years) with hypercholesterolaemia, but no history of diabetes or CVD, was related to the risk of fatal and non-fatal CHD events. After excluding participants with any event in the first 2 years, 1027 non-fatal and 214 fatal CHD events occurred during 14.7 years of follow-up. A minimally adjusted model (age, sex, statin treatment) and a maximally adjusted model (including known CVD risk factors and deprivation) were compared, with BMI 25–27.4 kg/m 2 as referent. The risk of non-fatal events was similar across all BMI categories in both models. The risk of fatal CHD events was increased in men with BMI 30.0–39.9 kg/m 2 in both the minimally adjusted model (HR=1.75 (95% CI 1.12 to 2.74)) and the maximally adjusted model (HR=1.60 (95% CI 1.02 to 2.53)). Conclusions These hypothesis generating data suggest that obesity is associated with fatal, but not non-fatal, CHD after accounting for known cardiovascular risk factors and deprivation. Clinical trial registration WOSCOPS was carried out and completed before the requirement for clinical trial registration.

Slowing of Electrical Activity in Ventricular Fibrillation is Not Associated with Increased Defibrillation Energies in the Isolated Rabbit Heart.

Abstract: Prolonged out-of-hospital ventricular fibrillation (VF) arrests are associated with reduced ECG dominant frequency (DF) and diminished defibrillation success. Partial reversal of ischaemia increases ECG DF and improves defibrillation outcome. We have investigated the metabolic components of ischaemia responsible for the decline in ECG DF and defibrillation success. Isolated Langendorff-perfused rabbit hearts were loaded with the voltage-sensitive dye RH237. Using a photodiode array, epicardial membrane potentials were recorded at 252 sites (15x15mm) on the anterior surface of the left & right ventricles. Simultaneously, a global ECG was recorded. VF was induced by burst pacing, and after 60s, perfusion was either reduced to 6ml/min or the perfusate composition changed to impose hypoxia (95%N2/5%CO2), pH 6.7 (80%O2/20%CO2), or hyperkalaemia (8mM). Using Fast Fourier Transform, power spectra were created from the optical signals and the global ECG. The optical power spectra were summated to give a global power spectrum (pseudoECG). At 600s the minimum defibrillation voltage (MDV) was determined by step-up protocol. During VF, the ECG and pseudoECG DF were reduced by low-flow ischaemia (9.0±1.0Hz, p<0.01, n=5) and raised [K+]o (12.2±1.3 Hz, p<0.05, n=7) compared to control (19.2±1.5 Hz, n=20), but were unaffected by acidic pHo (16.7±1.1 Hz, n=11) and hypoxia (14.0±1.2 Hz, n=10). In contrast, the MDV was raised by acidic pH (156.1±26.4V, p<0.001) and hypoxia (154.1±22.1V, p<0.01) compared to control (65.6±2.3V), but comparable changes were not observed in low-flow ischaemia (61.0±0.5V) or raised [K+]o (56±3V). In summary, different metabolites are responsible for the reduction in DF and the increase in defibrillation energy during ischaemic VF.

Microvolt T-Wave Alternans in End-Stage Renal Disease Patients—Associations with Uremic Cardiomyopathy

Abstract: Summary Background and objectives Premature cardiovascular (CV) events, especially sudden cardiac death, are common in ESRD patients and associated with uremic cardiomyopathy. Identification of high-risk patients is difficult. Microvolt T-wave alternans (MTWA) is a noninvasive method of detecting variability in electrocardiogram (ECG) T-wave morphology and is a promising technique for identifying patients at high risk of ventricular tachyarrhythmias. MTWA results of ESRD and hypertensive left ventricular hypertrophy (LVH) patients were assessed to determine the prevalence of abnormal results and associations with uremic cardiomyopathy. Design, setting, participants, & measurements In this single-center observational study, 200 ESRD and 30 LVH patients underwent assessment including CV history, ECG, cardiac magnetic resonance imaging, and an MTWA exercise test. MTWA results were classified as “negative” or “abnormal” on the basis of previously published reports. Results An abnormal MTWA result was more common in ESRD compared with LVH patients (57.5% versus 26.7%, respectively; P = 0.002). In ESRD patients, MTWA was significantly associated with uremic cardiomyopathy, clinical history of atherosclerosis (coronary, cerebral, peripheral) and diabetes mellitus, older age, and hemodialysis therapy. Independent associations with an abnormal MTWA result were older age, macrovascular disease, increased left ventricle (LV) mass, and LV dilation. Conclusions Features of uremic cardiomyopathy are associated with an abnormal MTWA result.