Showing papers by "Stuart M. Cobbe published in 2009"

Rosuvastatin and cardiovascular events in patients undergoing hemodialysis

Abstract: BACKGROUND: Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not bee ...

Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events

Abstract: Background Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke. Methods and Findings In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70–82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44–2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04–1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p<0.0001) improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20). Conclusions In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance. Please see later in the article for Editors' Summary

Adipocytokines and risk of stroke in older people: a nested case–control study

Abstract: Background Inflammation may play an important role in atherothrombosis and in promoting cerebral damage after stroke. We hypothesized that plasma adipocytokine concentrations would be associated with risk of stroke in older people. Methods Nested case-control study from the Prospective Study of Pravastatin in the Elderly ( PROSPER). Subjects were aged 70-82 years and followed up for a mean of 3.2 years: 266 incident stroke cases ( 179 confirmed as ischaemic) were compared with 532 controls matched for age, gender and treatment allocation ( pravastatin or placebo). Adipocytokines [ adiponectin, interleukin- (IL-)18 and tumour necrosis factor (TNF)alpha] were measured on stored baseline plasma samples. Results Elevated plasma adiponectin was associated with lower risk of ischaemic stroke on univariate analysis: odds ratio ( OR) 0.78 per 1 SD increase (95% CI 0.62-0.97). There were no associations of IL- 18 or TNF alpha with risk for ischaemic or total strokes. In multivariate models the independent predictors of ischaemic stroke were prior cerebrovascular accident ( OR 2.68, 95% CI 1.60-4.50), any alcohol use (1.98, 1.33-2.94), triglycerides (1.40, 1.11-1.77), Barthel score (0.75, 0.58-0.96) and known diabetes (1.72, 1.04-2.83); adiponectin, IL- 18 and TNFa did not contribute. A similar pattern of risk was seen for total stroke. Conclusions Reduced adiponectin may have a modest role in the aetiology of ischaemic stroke in older people, however IL- 18 and TNFa are unlikely to play any important part. These adipocytokines do not have clinical predictive utility; history of prior cerebrovascular accident, known diabetes mellitus, prior disability and higher alcohol intake explain much of the stroke risk.

Red cell distribution width has incremental prognostic value to B-type natriuretic peptide in acute heart failure.

Abstract: Background Red blood cell distribution width (RDW) is a measure of the variation in cell volume within the circulating erythrocyte population. Red blood cell distribution width is available routinely with every complete blood count (CBC) test and is most commonly used for differentiating between different types of anaemia. In recent years, an alternative role for this haematological parameter has emerged—as a potential prognostic marker. The independent prognostic significance of RDW in acute heart failure has recently . been reported. 1 This novel biomarker has previously been shown to be a strong, independent predictor of prognosis in patients with chronic heart failure. 2 However, neither of these studies included the B-type natriuretic peptides (BNP S ) in their respective multivariable analyses. It remains unknown whether or not RDW provides incremental prognostic information to these 'gold standard' bio-markers in acute or chronic heart failure. Aims Our aim was to evaluate the prognostic value of RDW in patients with acute heart failure. In particular, we studied whether or not this novel biomarker provides additional prognostic information to BNP. Methods Patient selection All admissions to the Royal and Western Infirmaries in Glasgow with acute heart failure were screened prospectively from 1 December 2006-20 July 2008. Patients were eligible if they were at least 18 years of age and able to provide written informed consent. Both acute decompensation of chronic heart failure and new onset acute heart failure were included. Patients with reduced and preserved systolic function heart failure were included. Inclusion criteria included satisfying the European Society of Cardiology (ESC) definition of acute heart failure 3 and having an elevated BNP (> 100 pg/mL). Exclusion criteria included acute coronary syndromes complicated by pulmonary oedema, cognitive impairment, and serious concurrent systemic disease resulting in reduced life expectancy. The study protocol was approved by the Local Research Ethics Committee, and all patients provided written informed consent. Blood sampling Blood samples were obtained on the first day of admission and processed immediately. Plasma BNP was measured using the Architect Assay (Abbott Laboratories, Abbott Park, IL, USA). Components of the CBC (RDW, haemoglobin, white cell count, and lymphocytes) were measured using the XE-2100 analyser (Sysmex, Japan). Anaemia was identified using the World Health Organization criteria 4 Statistical analysis Categorical variables are expressed as number with the percentage. Continuous variables are expressed as mean with standard deviation (SD) and median with inter-quartile range (IQR) when the distribution is normal and non-normal, respectively. B-type natriuretic peptide was positively skewed and analysed as log[concentration] in a continuous fashion. A Kaplan-Meier survival curve was drawn, stratifying patients into two groups depending on whether their RDW was elevated (defined as RDW ≥14.5%) and a log-rank value was calculated to assess statistical significance. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals (Cls) for individual components of the CBC univariately and then together in a multivariable analysis with age, sex, and BNP. A P-value of <0.05 was considered statistically significant.

Secondhand smoke exposure and survival following acute coronary syndrome: prospective cohort study of 1261 consecutive admissions among never-smokers

Abstract: Objective: To determine whether exposure to secondhand smoke is associated with early prognosis following acute coronary syndrome. Design, setting and participants: We interviewed consecutive patients admitted to nine Scottish hospitals over 23 months. Information was obtained, via questionnaire, on age, sex, smoking status, postcode of residence and admission serum cotinine concentration was measured. Follow-up data were obtained from routine hospital admission and death databases. Results: Of the 5815 participants, 1261 were never-smokers. Within 30 days, 50 (4%) had died and 35 (3%) had a non-fatal myocardial infarction. All-cause deaths increased from 10 (2.1%) in those with cotinine ⩽0.1 ng/ml to 22 (7.5%) in those with cotinine >0.9 ng/ml (χ 2 test for trend p 0.9 ng/ml: adjusted OR 4.80, 95% CI 1.95 to 11.83, p = 0.003). The same dose response was observed for cardiovascular deaths and death or myocardial infarction. Conclusions: Secondhand smoke exposure is associated with worse early prognosis following acute coronary syndrome. Non-smokers need to be protected from the harmful effects of secondhand smoke.

Paroxysmal bidirectional ventricular tachycardia with tachycardiomyopathy in a pregnant woman

Abstract: Palpitations in pregnancy are not an uncommon complaint. We present a case of palpitations in the third trimester related to bidirectional ventricular tachycardia with evidence, of left ventricular systolic dysfunction. The case was successfully managed with flecainide therapy and urgent elective caesarean section. The rhythm stabilised to sinus rhythm and left ventricular systolic function normalised. We discuss the possible underlying diagnosis of catecholaminergic polymorphic ventricular tachycardia with resultant tachycardiomyopathy. A literature review of bidirectional ventricular tachycardia is presented. This is the first reported case of bidirectional VT producing LV systolic dysfunction, which normalised following stabilisation of rhythm. The complex issues of management of this case in particular with regard to the pregnancy are discussed.

Isoprenaline increases Excursive Restitution Slope in the Conscious Rabbit with Ischaemic Heart Failure

Abstract: Background: An increased QT/RR slope is hypothesized to be predictive of sudden cardiac death after myocardial infarction. Previous studies have shown that beta-adrenergic stimulation increases QT/RR slope, but the effects of beta-adrenergic stimulation on QT/RR slope in heart failure are unknown. Methods: New Zealand White rabbits underwent coronary ligation (n=15) or sham surgery (n=11), and implantation of a pediatric pacemaker lead in the right ventricle for chronic ECG recording. Eight weeks after surgery, unsedated rabbits were given intravenous administrations of 0.25 to 2.0 ml of 1 micromol/l isoprenaline, while peak QRS to QRS (RR) and Q to T peak (QT) intervals were measured. Results: Ligated rabbits (n=6) had lower LVEF than sham rabbits (n=7, p 1 in ligated rabbits (1.27 +/- 0.66) and <1 in sham rabbits (0.35 +/- 0.14, p=.004). Absolute value of the negative slope was greater in ligated rabbits (-0.81 +/- 0.52 vs -0.35 +/- 0.14, p=.04). Conclusion: Ischaemic heart failure produces steeper restitution slopes during beta-adrenergically induced QT/TQ hysteresis. This could underlie the propensity of failing hearts to arrhythmias.