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Cardiovascular Death (cardiovascular + death)
Selected AbstractsInsulin resistance, diabetes and cardiovascular risk: approaches to treatmentDIABETES OBESITY & METABOLISM, Issue 6 2005Daniel E. Rosenberg Abstract:, The prevalence of diabetes is increasing worldwide. Insulin resistance and diabetes mellitus are major predictors of cardiovascular ischaemic disease. Other risk factors for cardiovascular death including hypertension, dyslipidaemia, smoking and visceral obesity are especially lethal in diabetics. C-reactive protein, plasminogen activator inhibitor-1, matrix metalloproteinases and other emerging risk factors and their roles are continually being researched and discovered. Treatment of this syndrome must be aimed at lifestyle modification, glycaemic control and management of concomitant risk factors. Diet and exercise play a vital role in the treatment of diabetes and the metabolic syndrome. Weight reduction and increased physical activity will improve insulin resistance, hyperglycaemia, hypertension and dyslipidaemia. Hypertension management has been shown to be especially important in diabetics to prevent cardiovascular events. Likewise, multiple clinical trials show that reduction of cholesterol is even more vital in diabetics than the general population for risk reduction of coronary disease. There is a great deal of evidence that tight control of glycaemia is essential to treatment of this condition. There are a variety of available pharmacological agents available including metformin, insulin secretagogues, alpha-glucosidase inhibitors, thiazolidinediones and insulin. The mechanisms and side effects of these medications are discussed. As macrovascular disease is the major cause of morbidity and mortality, an early, aggressive, multi-factorial approach to treatment of the metabolic syndrome and diabetes is vital to prevent adverse cardiac outcomes. [source] Nephropathy, but not retinopathy, is associated with the development of heart disease in Type 1 diabetes: a 12-year observation study of 462 patientsDIABETIC MEDICINE, Issue 6 2005O. Torffvit Abstract Aims To study the occurrence of heart disease and death in Type 1 diabetic patients and evaluate whether presence of microangiopathy, i.e. nephropathy and retinopathy, was associated with the outcome. Methods A 12-year observation study of 462 Type 1 diabetic patients without a previous history of heart disease at baseline who were treated under routine care in a hospital out-patient clinic. Results A total of 85 patients developed signs of heart disease, i.e. myocardial infarction (n = 41), angina (n = 23), and heart failure (n = 17) and 56 patients died. The mortality for patients without signs of heart disease during the observation period was 7.6% compared with 51% in patients with myocardial infarction (P < 0.001), 26% in patients with angina (P < 0.01) and 65% in patients with heart failure (P < 0.001). The relative risk for death was 9.0 (P < 0.001) and 2.5 (P < 0.05) times higher in patients with macroalbuminuria and microalbuminuria, respectively. The risk for cardiovascular death was 18.3 times (P < 0.001) higher in patients with macroalbuminuria compared with patients with normoalbuminuria. In patients with sight-threatening retinopathy, the relative risk for death was 7.0 times higher (P < 0.01) and the risk for coronary heart disease events 4.4 times higher (P < 0.05) compared with patients with no retinopathy. However, when retinopathy was adjusted for presence of macroalbuminuria, this association disappeared. Conclusion This study shows a high incidence of heart disease in patients with Type 1 diabetes. The worse prognosis was seen in patients with sight-threatening retinopathy and macroalbuminuria and microalbuminuria at baseline. Macroalbuminuria and microalbuminuria were independently associated with a high risk for heart disease and death while the association with sight-threatening retinopathy only occurred in the presence of nephropathy. [source] Osteopontin as a novel prognostic marker in stable ischaemic heart disease: a 3-year follow-up studyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2010Panagiota Georgiadou Eur J Clin Invest 2010; 40 (4): 288,293 Abstract Objectives, Osteopontin (OPN) is a glycoprotein, which may play a major role in the regulation of biological phenomena. Increased levels of OPN have been linked to the presence and to the severity of atherosclerosis. This study was undertaken to assess the prognostic significance of plasma OPN levels in patients with stable ischaemic heart disease (IHD). Methods, In 101 patients with stable IHD and angiographically documented significant coronary artery stenosis, plasma OPN levels were measured at baseline (time of coronary arteriography). Patients were prospectively followed for a median time of 3 years (minimum 2·25, maximum 3·9 years). The primary study endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, need for revascularization and hospitalization for cardiovascular reasons. Results, Baseline lnOPN levels were directly related to age (r = 0·27, P < 0·001) and inversely to left ventricular ejection fraction (r = ,0·32, P < 0·01). Left ventricular ejection fraction was an independent predictor of plasma OPN levels after adjustment for age and gender (, = ,0·013, P = 0·02). Median OPN value was 55 ng mL,1. In the univariate Cox-regression analysis, OPN levels > 55 ng mL,1 (n = 50) were significantly related to adverse cardiac outcome (HR = 2·40, 95% CI: 1·11,5·23, P = 0·027). In multivariate model, OPN levels > 55 ng mL,1 remained statistically significant independent predictor of adverse outcome after adjustment for age, gender, left ventricular ejection fraction and the number of diseased coronary arteries (HR = 2·88, 95% CI: 1·09,7·58, P = 0·032). Conclusion, OPN may provide significant prognostic information independent of other traditional prognostic markers in patients with stable IHD. [source] Uremic pruritus: A reviewHEMODIALYSIS INTERNATIONAL, Issue 2 2005Jocemir R. Lugon Abstract Pruritus is a major disorder among the skin derangements in advanced renal failure. Its prevalence seems to be diminishing perhaps because of improvements in dialysis treatment. Recent information suggests that interactions between dermal mast cells and distal ends of nonmyelinated C fibers may be important in the precipitation and regulation of the sensory stimuli. The knowledge as to the control of pruritus transmission to cortex areas is still incomplete but endogenous opioid and opioid receptors may have a role in this regard. A recent classification was proposed for pruritus based on the level of its origin. Uremic pruritus, however, seems to be too complex to fit perfectly in any of the suggested modalities. Inflammation and malnutrition are recognized risk factors for cardiovascular death in end-stage renal disease patients, which may be related to the genesis of pruritus. Consistent with this concept, lower serum levels of albumin and higher serum levels of ferritin were found in pruritic patients when compared to nonpruritic ones. Newer treatments for this difficult clinical problem are being developed and tested. [source] Enhanced Predictive Power of Quantitative TWA during Routine Exercise Testing in the Finnish Cardiovascular StudyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2009MIKKO MINKKINEN B.M.S. Introduction: We examined whether quantification of T-wave alternans (TWA) enhances this parameter's capacity to evaluate the risk for total and cardiovascular mortality and sudden cardiac death (SCD). Methods and Results: The Finnish Cardiovascular Study (FINCAVAS) enrolled consecutive patients (n = 2,119; 1,342 men and 777 women) with a clinically indicated exercise test with bicycle ergometer. TWA (time domain-modified moving average method) was analyzed from precordial leads, and the results were grouped in increments of 10 ,V. Hazard ratios (HR) for total and cardiovascular mortality and SCD were estimated for preexercise, routine exercise, and postexercise stages. Cox regression analysis was performed. During follow-up of 47.1 ± 12.9 months (mean ± standard deviation [SD]), 126 patients died: 62 were cardiovascular deaths, and 33 of these deaths were sudden. During preexercise, TWA , 20 ,V predicted the risk for total and cardiovascular mortality (maximum HR >4.4 at 60 ,V, P < 0.02 for both). During exercise, HRs of total and cardiovascular mortality were significant when TWA measured ,50 ,V, with 90 ,V TWA yielding maximum HRs for total and cardiovascular death of 3.1 (P = 0.03) and 6.4 (P = 0.002), respectively. During postexercise, TWA ,60 ,V indicated risk for total and cardiovascular mortality, with maximum HR of 3.4 at 70 ,V (P = 0.01) for cardiovascular mortality. SCD was strongly predicted by TWA levels ,60 ,V during exercise, with maximum HR of 4.6 at 60 ,V (P = 0.002), but was not predicted during pre- or postexercise. Conclusion: Quantification of TWA enhances its capacity for determination of the risk for total and cardiovascular mortality and SCD in low-risk populations. Its prognostic power is superior during exercise compared to preexercise or postexercise. [source] Novel Measures of Heart Rate Variability Predict Cardiovascular Mortality in Older Adults Independent of Traditional Cardiovascular Risk Factors: The Cardiovascular Health Study (CHS)JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2008PHYLLIS K. STEIN Ph.D. Background: It is unknown whether abnormal heart rate turbulence (HRT) and abnormal fractal properties of heart rate variability identify older adults at increased risk of cardiovascular death (CVdth). Methods: Data from 1,172 community-dwelling adults, ages 72 ± 5 (65,93) years, who participated in the Cardiovascular Health Study (CHS), a study of risk factors for CV disease in people ,65 years. HRT and the short-term fractal scaling exponent (DFA1) derived from 24-hour Holter recordings. HRT categorized as: normal (turbulence slope [TS] and turbulence onset [TO] normal) or abnormal (TS and/or TO abnormal). DFA1 categorized as low (,1) or high (>1). Cox regression analyses stratified by Framingham Risk Score (FRS) strata (low = <10, mid = 10,20, and high >20) and adjusted for prevalent clinical cardiovascular disease (CVD), diabetes, and quartiles of ventricular premature beat counts (VPCs). Results: CVdths (N = 172) occurred over a median follow-up of 12.3 years. Within each FRS stratum, low DFA1 + abnormal HRT predicted risk of CVdth (RR = 7.7 for low FRS; 3.6, mid FRS; 2.8, high FRS). Among high FRS stratum participants, low DFA1 alone also predicted CVdth (RR = 2.0). VPCs in the highest quartile predicted CVdth, but only in the high FRS group. Clinical CV disease predicted CVdth at each FRS stratum (RR = 2.9, low; 2.6, mid; and 1.9, high). Diabetes predicted CVdth in the highest FRS group only (RR = 2.2). Conclusions: The combination of low DFA1 + abnormal HRT is a strong risk factor for CVdth among older adults even after adjustment for conventional CVD risk measures and the presence of CVD. [source] New Considerations Relating to Class Effect With Angiotensin-Converting Enzyme Inhibitors-The PEACE StudyJOURNAL OF CLINICAL HYPERTENSION, Issue 3 2005Domenic A. Sica MD Angiotensin-converting enzyme inhibitor therapy provides positive outcome benefits in a number of cardiac scenarios including congestive heart failure, postmyocardial infarction, as well as in the hypertensive patient at cardiac risk. This benefit exists both in normotensive and hypertensive individuals and is present in those with various grades of cardiovascular risk. This beneficial cardiovascular effect has now been observed with several angiotensin-converting enzyme inhibitors, suggesting a class effect. The Prevention of Events with Angiotensin-Converting Enzyme Inhibition trial studied the effect of adding the angiotensinconverting enzyme inhibitor trandolapril to a contemporary therapeutic regimen of patients with stable coronary artery disease and preserved left ventricular function. In this study, the addition of trandolapril did not confer any additional benefit in terms of reducing the incidence of cardiovascular death, myocardial infarction, or coronary revascularization. The neutral findings in this trial add a new wrinkle to the concept of class effect for cardiovascular protection with angiotensin-converting enzyme inhibitors in patients with coronary artery disease. [source] Lung function, insulin resistance and incidence of cardiovascular disease: a longitudinal cohort studyJOURNAL OF INTERNAL MEDICINE, Issue 5 2003G. Engström Abstract., Engström G, Hedblad B, Nilsson P, Wollmer P, Berglund G, Janzon L (University of Lund, Malmö University Hospital, Malmö, Sweden). Lung function, insulin resistance and incidence of cardiovascular disease: a longitudinal cohort study. J Intern Med 2003; 253: 574,581. Objectives., To explore whether a reduced lung function is a risk factor for developing diabetes and insulin resistance (IR), and whether such relationship contributes to the largely unexplained association between lung function and incidence of cardiovascular disease (CVD). Design., Forced vital capacity (FVC) was assessed at baseline. Incidence of diabetes and IR [according to the homeostasis model assessment (HOMA) model] was assessed in a follow-up examination after 13.9 ± 2.6 and 9.4 ± 3.6 years for men and women, respectively. After the follow-up examination, incidence of CVD (stroke, myocardial infarction or cardiovascular death) was monitored over 7 years. Setting., Populations-based cohort study. Subjects., Initially nondiabetic men (n = 1436, mean age 44.6 years) and women (n = 896, mean age 49.8 years). Results., Prevalence of IR at the follow-up examination was 34, 26, 21 and 21%, respectively, for men in the first (lowest), second, third and fourth quartile of baseline FVC (P for trend <0.0001). The corresponding values for women were 30, 29, 25 and 17%, respectively (P for trend <0.001). Adjusted for potential confounders, the odds ratio (OR) for IR (per 10% increase in FVC) was 0.91 (CI: 0.84,0.99) for men and 0.89 (CI: 0.80,0.98) for women. FVC was similarly significantly associated with the incidence of diabetes (OR = 0.90, CI: 0.81,1.00), adjusted for sex and other confounders. The incidence of CVD after the follow-up examination was significantly increased only amongst subjects with low FVC who had developed IR (RR = 1.7, CI: 1.02,2.7). Conclusion., Subjects with a moderately reduced FVC have an increased risk of developing IR and diabetes. This relationship seems to contribute to the largely unexplained association between reduced lung function and incidence of CVD. [source] Inflammatory bio-markers and cardiovascular risk predictionJOURNAL OF INTERNAL MEDICINE, Issue 4 2002G. J. Blake Abstract.,Blake GJ, Ridker PM (Harvard Medical School, Boston, MA, USA). Inflammatory bio-markers and cardiovascular risk prediction (Review). J Intern Med 2002; 252: 283,294. Inflammatory processes are now recognized to play a central role in the pathogenesis of atherosclerosis and its complications. Plasma levels of several markers of inflammation have been found to be associated with future cardiovascular risk in a variety of clinical settings. These markers include cell adhesion molecules, cytokines, pro-atherogenic enzymes and C-reactive protein (CRP). Initially thought of as an inactive downstream marker of the inflammatory cascade, emerging evidence suggests that CRP may be directly involved in atherogenesis, and that arterial plaque can produce CRP, independent of traditional hepatic pathways. In addition to being a strong predictor of future cardiovascular risk amongst patients presenting with acute coronary syndromes, numerous studies have found that baseline levels of CRP are associated with risk of future myocardial infarction, stroke, peripheral vascular disease and cardiovascular death amongst apparently healthy populations. The combination of measurement of a marker of inflammation with lipid testing may improve upon risk stratification based on lipid testing alone, and intensification of programmes for exercise, weight loss, and smoking cessation is recommended for those with elevated CRP levels. Further trials are needed to confirm the potential benefits of statins amongst individuals with elevated CRP levels. [source] Alcohol-Induced Endothelial Changes Are Associated With Oxidative Stress and Are Rapidly Reversed After WithdrawalALCOHOLISM, Issue 10 2005Giorgio Soardo Abstract: Background: Although heavy alcohol drinkers are at an increased risk of developing cardiovascular events, moderate alcohol intake is associated with reduced incidence of cardiovascular death. This paradox might reflect a dose-related effect of different alcohol intakes on endothelial function and this, in turn, might depend on changes in oxidative stress Methods: We tested the effects of alcohol withdrawal in heavy alcohol consumers and compared the plasma levels of endothelin-1, nitric oxide, plasminogen activator inhibitor-1, von Willebrand factor, malondialdehyde, and intracellular glutathione with those of alcoholics that did not modify their alcohol intake and teetotalers. In human endothelial cells that had been cultured for 2 weeks in the presence of different concentrations of ethanol, we assessed the same parameters after withdrawal of ethanol exposure Results: Alcohol increased the levels of endothelin-1, nitric oxide, and plasminogen activator inhibitor-1 and decreased the levels of von Willebrand factor both in vivo and in vitro. These changes were dose dependent, rapidly reversed after withdrawal of exposure, and associated with the presence of increased oxidative stress as indicated by increased levels of both malondialdehyde and intracellular glutathione. Blockade of oxidative stress by incubation of endothelial cells in the presence of oxidants' scavengers prevented the alcohol-induced functional modifications of the endothelium Conclusions: Alcohol affects endothelial function with an effect that is mediated by an activated oxidative stress and is rapidly reversed after withdrawal. Dose-related endothelial responses to different alcohol intakes might translate in either vascular protection or vascular damage. [source] Glycated albumin levels predict long-term survival in diabetic patients undergoing haemodialysisNEPHROLOGY, Issue 4 2008KOUSUKE FUKUOKA SUMMARY: Aim: Glycated albumin (GA) is recognized as a reliable marker for monitoring glycemic control particularly in patients with end-stage renal disease (ESRD). Here, we investigated the impact of GA levels on long-term survival in diabetic patients with ESRD. Methods: We enrolled ESRD patients with diabetic nephropathy into our single-centre prospective follow-up study (n = 98, 66 men and 32 women; age 68.2 12.3 years) with a mean follow-up period of 47.7 months. All patients had started haemodialysis between December 1992 and November 2003. They were categorized into two groups according to their GA levels at the initiation of haemodialysis; GA < 29% (low-GA group; n = 54) and GA 29% (high-GA group; n = 44). Results: Between low-GA and high-GA groups, there were no significant differences in various clinical parameters except GA and HbA1c levels. The cumulative survival rate of low-GA group was significantly higher than that of high-GA group (P = 0.034, log,rank test). After adjustment for age, sex, total cholesterol, C-reactive protein and albumin, high-GA was a significant predictor of survival (hazard ratio 1.042 per 1.0% increment of GA, 95% CI 1.014,1.070, P < 0.05), but not in the case with HbA1c. Cox proportional hazard model demonstrated that high-GA group was a significant predictor for cardiovascular death (hazard ratio 2.971 (1.064,8.298), P = 0.038). Conclusion: We conclude that poor glycemic control (GA 29%) before starting haemodialysis is associated with increased cardiovascular morbidity and shortened survival in diabetic patients with ESRD. [source] Cardiac Resynchronization Therapy in Patients with Mildly Impaired Left Ventricular FunctionPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2009PAUL W.X. FOLEY M.R.C.P. Aims: We sought to determine the unknown effects of cardiac resynchronization therapy (CRT) in patients with a left ventricular ejection fraction (LVEF) >35%. Because of its technical limitations, echocardiography (Echo) may underestimate LVEF, compared with cardiovascular magnetic resonance (CMR). Methods: Of 157 patients undergoing CRT (New York Heart Association [NYHA] functional class III or IV, QRS , 120 ms), all of whom had a preimplant Echo-LVEF ,35%, 130 had a CMR-LVEF ,35% (Group A, 19.7 ± 7.0%[mean ± standard deviation]) and 27 had a CMR-LVEF >35% (Group B, 43.6 ± 7.7%). All patients underwent a CMR scan at baseline and a clinical evaluation, including a 6-minute walk test and a quality of life questionnaire, at baseline and after CRT. Results: Both groups derived similar improvements in NYHA functional class (A =,1.3, B =,1.2, [mean]), quality of life scores (A =,21.6, B =,33.0; all P < 0.0001 for changes from baseline), and 6-minute walking distance (A = 64.5, B = 70.1 m; P < 0.001 and P < 0.0001, respectively). Symptomatic response rates (increase by ,1 NYHA classes or 25% 6-minute walking distance) were 79% in group A and 92% in group B. Over a maximum follow-up period of 5.9 years for events, patients in group A were at a higher risk of death from any cause, hospitalization for major cardiovascular events (P = 0.0232), or cardiovascular death (P = 0.0411). There were borderline differences in the risk of death from any cause (P = 0.0664) and cardiovascular death or hospitalization for heart failure (P = 0.0526). Conclusions: This observational study suggests that the benefits of CRT extend to patients with a LVEF > 35%. [source] Latest news and product developmentsPRESCRIBER, Issue 19 2008Article first published online: 16 OCT 200 ARBs less effective than ACE inhibitors? The efficacy of angiotensin-II receptor blockers (ARBs) in preventing cardiovascular events in high-risk patients has been challenged by the findings of a large randomised trial (Lancet 2008 published online; doi 10.1016/ S0140-6736(08)61242-8). In the TRANSCEND trial, 5926 patients with cardiovascular disease or diabetes with end-organ damage who could not tolerate ACE inhibitor therapy were randomised to placebo or telmisartan (Micardis) 80mg per day in addition to standard therapies. After 56 months, mean blood pressure was lower with telmisartan (by 4.0/2.2mmHg) but there were no significant differences between telmisartan and placebo in the risk of cardiovascular events , a composite of cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure. Hospitalisation for cardiovascular reasons were slightly but significantly reduced by telmisartan (33 vs 30 per cent). MHRA: fentanyl patch errors potentially fatal Errors in dosing, accidental exposure and enhanced absorption from heat exposure have resulted in life-threatening and fatal incidents with transdermal fentanyl, warns the MHRA in its latest Drug Safety Update (September 2008). There is also evidence that fentanyl patches are being prescribed for nonlicensed indications, including treatment of opioid-naive patients. Other topics in this issue include managing adverse reactions to HPV vaccine and an update on new cases of progressive multifocal leucoencephalopathy associated with natalizumab (Tysabri). Call for DURG research The Drug Utilisation Research Group is inviting abstracts for oral and poster presentations at its 20th annual meeting on 5 February 2009. The theme of the morning session is ,Whose prescribing budget is it anyway?'. Abstracts will be accepted on any drug utilisation research studies and will be published in the Journal of Pharmacoepidemiology and Drug Safety. Information is available at www.durg.org.uk the deadline for submissions is 1 December. Early bromocriptine no benefit in Parkinson's Initiating treatment of Parkinson's disease with the dopamine agonist bromocriptine offers no long-term benefit compared with levodopa, the UK Parkinson's Disease Research Group trial has shown (Neurology 2008;71:474-80). After 14 years' follow-up of 166 patients, there were no differences in the prevalence of motor complications, dementia or mortality, but levodopa was associated with superior scores of disability and physical functioning. The authors say the belief that early dopamine agonist treatment is neuroprotective in Parkinson's disease should be abandoned. Ezetimibe with statin cancer risk ,not credible' Analysis of data pooled from two large trials provides ,no credible evidence' that ezetimibe (Ezetrol) is associated with an increased risk of cancer when added to statin therapy (N Engl J Med 2008 published online; doi 10.1056/NEJMsa0806603). A possible link with increased risk of cancer with ezetimibe plus simvastatin was suggested by the SEAS trial (N Engl J Med 2008 published online; doi 10.1056/NEJMoa 0804602). This hypothesis was tested in two trials involving more than 20 500 patients over 1.0-2.7 years. There was no excess of cancer overall or at particular sites; cancer deaths were more numerically but not significantly higher with ezetimibe and there was no evidence of increased risk with duration of treatment. Telmisartan provides no advantage after stroke Adding telmisartan (Micardis) to standard treatment after ischaemic stroke does not reduce morbidity, US investigators report (N Engl J Med 2008 published online; doi 10.1056/NEJMoa 0804593). A total of 20 332 patients with recent ischaemic stroke were randomised to placebo or telmisartan 80mg per day in addition to antiplatelet therapy and antihypertensive agents. After 2.5 years, blood pressure was 3.8/2.0mmHg lower in patients taking telmisartan but there were no significant differences from placebo in the risks of recurrent stroke, cardiovascular events or new-onset diabetes. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 8 2008Article first published online: 12 MAY 200 Glargine preferred to lispro as type 2 add-on Basal insulin glargine (Lantus) and insulin lispro (Humalog) at mealtimes improved glycaemic control equally well in patients with type 2 diabetes poorly controlled by oral agents, but patient satisfaction was greater with basal insulin (Lancet 2008;371:1073-84). The 44-week APOLLO trial, funded by Sanofi Aventis, was a nonblinded randomised comparison of basal and prandial insulin regimens added to oral treatment in 418 patients. It found similar reductions in HbA1C (,1.7 vs ,1.9 per cent respectively). Fasting and nocturnal glucose levels were lower with insulin glargine and postprandial levels were lower with insulin lispro. The basal regimen was associated with fewer hypoglycaemic events (5.2 vs 24 per patient per year), less weight gain (3.01 vs 3.54kg) and greater improvement in patient satisfaction scores. Treating hypertension cuts mortality in over-80s Treating hypertension in the over-80s reduces all-cause mortality by 21 per cent, the HYVET study has shown (N Engl J Med online: 31 March 2008; doi: 10.1056/NEJMoa 0801369). Compared with placebo, treatment with indapamide alone or with perindopril for an average of 1.8 years also reduced the incidence of fatal stroke by 39 per cent, cardiovascular death by 23 per cent and heart failure by 64 per cent. The incidence of stroke was reduced by 30 per cent but this was of borderline statistical significance. Fewer serious adverse events were reported with treatment than with placebo. New work for NICE The DoH has announced the 18th work programme for NICE. Seven public health interventions include preventing skin cancer, smoking by children and excess weight gain during pregnancy. Public health guidance will include the provision of contraceptive services for socially disadvantaged young people. Two new clinical guidelines are sedation in young people and management of fractured neck of femur. New technology appraisals may include eight therapies for cancer, two new monoclonal antibodies for psoriasis and rheumatoid arthritis, an oral retinoid for severe chronic hand eczema and methylnaltrexone for opioid-induced bowel dysfunction. Combinations no better against CV disease Taking ezetimibe and simvastatin (Inegy) does not appear to slow the progression of atherosclerosis more than high-dose simvastatin alone, say researchers from The Netherlands (N Engl J Med 2008;358: 1431-43). In patients with hypercholesterolaemia, there was no difference in regression or progression of atherosclerosis after two years' treatment with simvastatin 80mg per day alone or combined with ezetimibe 10mg per day. Adverse event rates were similar. In patients with vascular disease or high-risk diabetes, there was no difference between the ACE inhibitor ramipril 10mg per day or the ARB telmisartan (Micardis) 80mg per day as monotherapy, or their combination, in the risk of a composite outcome of cardiovascular death, MI, stroke and admission for heart failure (N Engl J Med 2008;358:1547-59). Combined treatment was associated with higher risks of hypotensive symptoms, syncope and renal dysfunction. Twice-daily celecoxib increases CV risk Taking celecoxib (Celebrex) twice daily carries a higher risk of cardiovascular events than the same total dose taken once daily, a metaanalysis suggests (Circulation 2008; doi: 10.1161/ CIRCULATIONAHA.108. 764530). The analysis of six placebo-controlled trials involving a total of 7950 patients taking celecoxib for indications other than rheumatoid arthritis found that the combined risk of cardiovascular death, myocardial infarction, stroke, heart failure or thromboembolic event increased with dose over the range 400-800mg per day. The risk was significantly greater with 200mg twice daily (HR 1.8) than 400mg once daily (HR 1.1). Patients at greatest baseline risk were at disproportionately increased risk from celecoxib. Long-term etanercept effective in AS An open-label study suggests that etanercept (Enbrel) remains effective in the treatment of ankylosing spondylitis in the long term (Ann Rheum Dis 2008;67:346-52). Of 257 patients who completed six months' treatment with etanercept and who entered the nonblinded extension study, 126 completed a total of 168-192 weeks' treatment. The commonest adverse events were injection-site reactions (22 per cent), headache (20 per cent) and diarrhoea (17.5 per cent). The annual rate of serious infections was 0.02 per person. Response and partial remission rates after 192 weeks were similar to those reported after 96 weeks. Metformin reduces risk Metformin reduces the risk of developing diabetes in individuals at increased risk, a meta-analysis suggests (Am J Med 2008;121:149-57.e2). The study included 31 mostly small, randomised, controlled trials involving a total of 4570 participants and lasting at least eight weeks (8267 patient-years of treatment). Metformin was associated with reductions in body mass (,5.3 per cent), fasting glucose (,4.5 per cent) and insulin resistance (,22.6 per cent); lipid profiles also improved. The odds of developing diabetes were reduced by 40 per cent,an absolute risk reduction of 6 per cent over 1.8 years. MHRA clarifies cough and colds advice Press reports mistakenly suggested that the MHRA had banned some cough and cold remedies when it issued new guidance on treating young children, the MHRA says. The Agency's advice followed a review of over-thecounter cough and cold medicines for children by the Commission on Human Medicines. Children under two are at increased risk of adverse reactions and should no longer be treated with products containing antihistamine (chlorphenamine, brompheniramine, diphenhydramine), antitussives (dextromethorphan, pholcodine), expectorants (guaifenesin, ipecacuanha) and decongestants (phenylephrine, pseudoephedrine, ephedrine, oxymetazoline and xylometazoline). The MHRA said these products, which are classified as general sale medicines, should be removed from open shelves until available in new packaging that complies with the advice. They may still be supplied by a pharmacist for the treatment of older children. Coughs and colds should be treated with paracetamol or ibuprofen for fever, a simple glycerol, honey or lemon syrup for cough, and vapour rubs and inhalant decongestants for stuffy nose. Saline drops can be used to thin and clear nasal secretions in young babies. Parents are being urged not to use more than one product at a time to avoid inadvertently administering the same constituent drug twice. Perindopril brand switch Servier Laboratories is replacing its current formulations of perindopril (Coversyl, Coversyl Plus) with a new product that is not bioequivalent. The current Coversyl brand contains perindopril erbumine (also known as tert -butylamine). The new formulation contains perindopril arginine; it will be distinguished by new brand names (Coversyl Arginine, Coversyl Arginine Plus) and new packaging. Coversyl 2, 4 and 8mg tablets are equivalent to Coversyl Arginine 2.5, 5 and 10mg. Servier says the change is part of the simplification and harmonisation of global manufacturing; the arginine salt is already used in other countries and offers greater stability and a longer shelf-life. Both Coversyl and Coversyl Arginine will be in the supply chain for the next few weeks. Generic perindopril will continue to be the erbumine salt and prescriptions for generic perindopril are not affected. New from NICE Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Clinical Guidance No. 63, March 2008 This clinical guideline focuses on additional aspects of care for women with gestational diabetes (88 per cent of cases) or pre-existing diabetes (of which about 40 per cent is type 2 diabetes) and their babies. To date, insulin aspart (NovoRapid) is the only drug in the guideline specifically licensed for use in pregnancy and NICE advises obtaining informed consent to implement its recommendations for using other insulins and oral hypoglycaemic agents. As with other guidelines, NICE begins by stressing the importance of patient-centred care and involving women in decisions about their treatment. The guideline is divided into six sections, dealing with consecutive periods of pregnancy. Preconceptual planning should include empowering women to help them reduce risks, optimising glycaemic control (after retinal assessment) and increasing monitoring intensity, and providing information about the effects of pregnancy on diabetes. Metformin may be recommended as an adjunct or alternative to insulin, but other oral hypoglycaemic agents should be replaced with insulin, although glibenclamide is an option during pregnancy. Isophane insulin is the preferred long-acting insulin; lispro (Humalog) and aspart are considered safe to use. ACE inhibitors and angiotensin-II receptor blockers should be replaced with other antihypertensive agents and statins should be discontinued. Recommendations for screening and treatment of gestational diabetes build on previous guidance (CG62). Drug treatment will be needed by 10-20 per cent , this includes insulin (soluble, aspart or lispro) and/or metformin or glibenclamide, tailored to individual need. Antenatal care includes optimising glycaemic control. Insulin lispro or aspart should be considered in preference to soluble insulin. If glycaemic control cannot be achieved with insulin injections, an insulin pump may be indicated. The guideline includes a timetable for appointments and the care that should offered after each interval. Recommendations for intrapartum care, which supplement those in CG55, include frequent monitoring of blood glucose. Neonatal care includes recommendations for monitoring and screening the infant and the management of hypoglycaemia. Postnatal care (supplementing CG37) involves adjusting maternal treatment to avoid hypoglycaemia and recommendations for returning to community care. Metformin and glibenclamide are the only oral agents suitable for breastfeeding women. Women with gestational diabetes need advice about glycaemic control and planning for future pregnancies. Lifestyle advice and measurement of annual fasting plasma glucose should be offered. Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. Technology Appraisal No. 138, March 2008 The latest technology appraisal of asthma treatments covers inhaled steroids for adults and children over 12 with chronic asthma. It makes only two recommendations. First, the cheapest appropriate option is recommended. Second, when a steroid and a long-acting beta2-agonist are indicated, the decision to prescribe a combined inhaler or separate devices should take into account therapeutic need and likely adherence. Combined inhalers are currently less expensive than separate devices, though they may not remain so. When a combined inhaler is chosen it should be the cheapest. NICE concludes that, at equivalent doses, there is little difference in the effectiveness or adverse event profile of the available steroids or the fixed-dose combinations. According to specialist advice, choosing the best device for an individual remains the overriding concern. Continuous positive airway pressure for the treatment of obstructive sleep apnoea/hypopnoea syndrome. Technology Appraisal No. 139, March 2008 NICE recommends continuous positive airway pressure (CPAP) for adults with moderate or severe obstructive sleep apnoea, and for those with a milder disorder if quality of life and functioning are impaired and alternative strategies such as lifestyle change have failed. Diagnosis and treatment is the responsibility of a specialist team. A CPAP device costs £250-£550 and lasts for seven years. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 4 2008Article first published online: 20 MAR 200 Suicide warning for all antidepressants All antidepressants are to include a warning of the risk of suicide in their product information, the MHRA says. The requirement formerly applied only to SSRIs but, following a US review of safety data, the Agency says the risk is similar for all classes of antidepressants. Patients at increased risk include young people with psychiatric morbidity and those with a history of suicidal ideation. Patients are at increased risk of suicide until remission occurs, and clinical experience shows that the risk is increased during the early stages of recovery. Confusion over type 2 diabetes management Contradictory findings have been reported from two studies of intensive management of type 2 diabetes. The STENO-2 study (N Engl J Med 2008;358:580-91) found that tight control of blood glucose, blood pressure and lipids plus low-dose aspirin in 160 patients with type 2 diabetes and microalbuminuria significantly reduced all-cause mortality, cardiovascular events, cardiovascular death and microvascular complications by 40-60 per cent. The US National Heart, Blood and Lung Institute has announced the end of the intensive treatment arm of the ACCORD study (unpublished). This study was comparing intensive lowering of blood glucose below currently recommended levels (target HbA1C <6 per cent) with conventional management in adults with type 2 diabetes at especially high risk for heart attack and stroke. Although mortality was reduced in both arms compared with other populations, intensive treatment was associated with increased mortality equivalent to three deaths per 1000 patients per year over four years. Another antibiotics campaign The Government has launched another campaign to promote public awareness that antibiotics are not appropriate for viral infections causing coughs, colds and sore throats. Get Well Soon , Without Antibiotics is supported by a national advertising campaign and leaflets and posters encouraging the public to ask advice rather than demand a prescription. Details are available at www.dh.gov.uk. Episenta: once-daily sodium valproate Following a launch to specialists last year, a new once-daily modified-release formulation of sodium valproate is being promoted more widely to GPs. Episenta is licensed for the treatment of all forms of epilepsy and is formulated as modified-release capsules of 150mg and 300mg and sachets of modified-release granules of 500mg and 1000mg. The dose may be administered once or twice daily. Patients may be switched from enteric-coated tablets of valproate to the same dose given as Episenta. Episenta costs £5.70 or £10.90 for 100 × 150mg or 300mg capsules, and £18 or £35.50 for 100 × 500mg or 1000mg sachets. Latest NICE agenda The Department of Health has referred a new batch of topics for appraisal by NICE. Six of seven technology appraisals are for cancer drugs; the last is for dabigatran etexilate for venous thromboembolism. There will be four new clinical guidelines: autism spectrum disorders, hypertension in pregnancy, bed-wetting in children and severe mental illness with substance abuse. Two combined public health and clinical guidelines will address alcohol misuse. Varenicline vs NRT Varenicline (Champix) offers slightly greater smoking cessation rates than nicotine replacement therapy (NRT) in the long term and better symptom improvement, an international study has shown (Thorax 2008; published online:10.1136/ thx.2007.090647). A total of 746 smokers were randomised to treatment with varenicline 1mg twice daily for 12 weeks or transdermal NRT (21mg reducing to 7mg per day) for 10 weeks. Continuous abstinence rates for the last four weeks of treatment were 56 vs 43 per cent. The corresponding rates for one year were 26 and 20 per cent. Varenicline was associated with greater reductions in cravings, withdrawal symptoms and smoking satisfaction, but more nausea (37 vs 10 per cent). Adverse reactions class effect of statins The MHRA has identified several adverse effects that it says are class effects of the statins (Drug Safety Update 2008;1:Issue 7). Following a review of clinical trials and spontaneous reports, it is now apparent that any statin may be associated with sleep disturbance, depression, memory loss and sexual dysfunction; interstitial lung disease has been reported rarely. Product information is being updated to include the new information. Depression, including suicidal ideation, has also been associated with varenicline (Champix), the MHRA says; affected patients should stop treatment immediately. The combination of transdermal nicotine replacement therapy (NRT) and varenicline appears to be associated with a higher incidence of nausea, headache, vomiting, dizziness, dyspepsia and fatigue than NRT alone. The MHRA has also announced that, following the suspension of marketing authorisation for carisoprodol (Carisoma), it is considering a phased withdrawal of the closely-related meprobamate , the main active metabolite of carisoprodol. Following a successful pilot study, the public are being encouraged to report adverse reactions on yellow cards; the MHRA notes that health professionals provide more complete reports but patients include more information about quality of life. The scheme will be promoted via community pharmacies throughout the UK from February 2008. Cochrane: evidence on back pain interventions The latest release of Cochrane reviews includes three meta-analyses assessing interventions for back pain. Overall, NSAIDs were found to be effective as short-term treatment for acute or chronic back pain but the effect size was small. They were comparable with paracetamol but associated with more adverse effects; COX-2 selective NSAIDs were similarly effective, with slightly fewer adverse effects. There was no evidence that antidepressants reduced back pain but intensive individual patient education (lasting 2.5 hours) was effective for acute and subacute back pain and comparable with manipulation and physiotherapy; its effects on chronic pain were unclear. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 20 2007Article first published online: 26 NOV 200 GPs and pharmacists to work more closely Closer working between GPs and community and primary-care pharmacists ,could further improve prescribing quality and therapeutic outcomes for patients', according to a report by the London School of Pharmacy and Alliance Boots. The report suggests that the expansion of primary-care centres and the increasing complexity of care they offer mean that community pharmacists will increasingly need to take on some GP roles. It foresees an increase in shared premises and calls for closer interdisciplinary working between GPs, pharmacists and nurses. Variation in PCT commissioning of enhanced services from pharmacies has resulted in ,a fragmented system of postcode pharmaceutical care rationing'. Full read-write access to patients' records will be essential if the benefits of electronic prescribing are to be realised. How pharmacists can support commissioners The NHS Alliance and Primary Care Pharmacists' Association have published a guide for practice-based commissioners on making the most of primary-care pharmacists. Prescribing Support and Prescribing Advice for Practice Based Commissioners , A Guide for Commissioning Groups and GPs illustrates how pharmacists can support commissioners at all levels of medicines use. Copies are free to NHS Alliance members and cost £10 for others. Directory website aids diabetes management The National Diabetes Support Team is developing a website that brings together different datasets and tools for diabetes management. The Diabetes Data Directory (www.yhpho.org.uk/diabetesdatadirectory/introddd.asp) summarises what other online databases can provide and lists the tools that can be used to answer specific questions. The first edition is now online, providing direct links to the appropriate sites. Flu vaccine efficacy in older people challenged US reviewers have questioned the effectiveness of flu vaccine in older people (Lancet Infect Dis online: 24 September; doi: 10.1016/ S1473-3099(07)70236-0). They were unable to confirm a reduction in flu mortality since 1980, concluding that biased patient selection and nonspecific end-points such as all-cause mortality may have exaggerated the benefits of vaccination in clinical trials. The Department of Health is encouraging younger people in at-risk groups to be vaccinated against flu this winter; last year, 58 per cent of under-65s at risk were not vaccinated. OC cervical cancer risk probably overestimated Recent evidence that oral contraceptives may be associated with a small increase in the incidence of cervical cancer probably overestimates the risk, says the Clinical Effectiveness Unit of the Faculty of Family Planning and Reproductive Health Care (www.ffprhc.org.uk). A recent study in the BMJ reported a 12 per cent reduced overall risk of cancer associated with oral contraceptives but an increased risk of cervical cancer of 38 per 100 000 woman-years after at least eight years' use. The FFPRHC says this study was conducted before the UK cervical screening programme was established, and at a time when the average Inhaled insulin ,unlikely to be cost effective' Inhaled insulin (Exubera) is safe and effective but costs so much more than injected insulin that it is unlikely to be cost effective, according to a new Health Technology Assessment (2007;11:No.33.www.hta.nhsweb.nhs.uk). The review included nine trials (seven of Exubera), in which the only significant difference between inhaled and injected soluble insulin was in patient preference. However, most of the trials used syringes for insulin injection rather than pens. The extra cost of inhaled insulin is put at between £600 and £1000 per year. New topics for NICE The Secretary of State for Health has referred the novel antihypertensive aliskiren (Rasilez) for appraisal by NICE; aliskiren is the first direct renin inhibitor to be introduced. Other referrals to NICE include five clinical guidelines (multiple pregnancy, transient loss of consciousness, lower UTI in men, post-ITU rehabilitation and colorectal and anal cancer). Topics for technology appraisals include cetuximab (Erbitux) for colorectal and head and neck cancers. QOF statistics for 06/07 GPs in England averaged 96.3 per cent of the maximum points available for the clinical domain of the Quality and Outcomes Framework in 2006/07 compared with 97.1 per cent previously, official statistics show. Mean practice scores for most clinical areas were in the mid-90 per cent range, but highest for obesity (100 per cent) and lowest for depression (81 per cent), palliative care (90 per cent), mental health and epilepsy (<95 per cent). NICE consulting on type 2 diabetes guideline NICE is consulting on its draft clinical guideline for the management of type 2 diabetes. Comments should be submitted online by 22 November; publication is scheduled for April 2008. The drug of first choice for glycaemic control is metformin, which should be considered even for patients who are not overweight; a sulphonylurea is an alternative or adjunctive agent if glycaemic control is not achieved with metformin alone. If these regimens fail, a glitazone may be added. Exenatide (Byetta) is recommended only for obese patients for whom other oral treatments have failed. The guidance will update and replace clinical guidelines E, F, G and H, and technology appraisals 53, 60 and 63. Glitazones increase risk of HF but not CV death A new meta-analysis , this time of seven trials involving a total of 20 191 patients with type 2 diabetes or impaired glucose tolerance treated with a glitazone , has concluded that these agents are associated with an increased risk of heart failure but not cardiovascular death (Lancet 2007;370:1129,36). Compared with comparator drugs, glitazones were associated with an increased risk of congestive heart failure (2.3 vs 1.4 per cent; relative risk, RR, 1.72; number needed to harm over 30 months, 107). There was no heterogeneity between studies, showing that this is a class effect. However, the risk of cardiovascular death was not increased for either rosiglitazone (Avandia) or pioglitazone (Actos). Copyright © 2007 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 12 2007Article first published online: 4 OCT 200 NAO: GPs still not prescribing efficiently The National Audit Office (NAO) says NHS funds are being wasted through inefficient GP prescribing and patients not taking their medicines. The NAO's long-awaited report, Prescribing Costs in Primary Care (www.nao.org.uk), found large variations between PCTs in generic prescribing of statins, ACE inhibitors and angiotensin-II antagonists, and protonpump inhibitors; PCTs were also paying widely differing prices for these products. There was a five-fold variation in prescribing volume for clopidogrel between PCTs. These four drugs accounted for only 19 per cent of total spending but, if all practices matched the performance of the best 25 per cent, the NHS would save £200 million annually. PCTs should do more to rationalise prescribing and support their GPs, the NAO concludes. The NAO says that the cost of medicines dispensed for but not taken by patients lies somewhere in the range £100-£800 million annually. Strategies to reduce waste include public awareness campaigns and restricting supplies to four weeks (or two weeks for new medicines). Rosiglitazone may increase CV death risk A meta-analysis of 42 clinical trials has suggested that rosiglitazone is associated with increased risks of myocardial infarction (MI) and cardiovascular death (N Engl J Med 2007; published online 21 May: doi 10.1056/ NEJMoa072761). Like the COX-2 inhibitors, rosiglitazone was licensed without determining its possible effects on long-term cardiovascular outcomes, and interpretation of the latest findings is complicated by the multiple comparisons involved. For risk of MI, there was no significant difference between rosiglitazone and placebo (though this was of borderline statistical signifi-cance , p=0.07), metformin, sulphonylureas or insulin. Rosiglitazone was associated with a statistically significant 43 per cent increased risk compared with all comparators combined but the absolute increase in risk was very small (0.02 per cent). The trends were similar for risk of cardiovascular death, though rosiglitazone was associated with a 64 per cent increased risk compared with all comparators combined that was of borderline statistical significance (p=0.06). The authors acknowledge that their analysis pooled short-term studies that excluded patients at risk of heart disease and was not designed to determine cardiovascular outcomes, and they had no access to patientlevel data; as a result, there is uncertainty about their findings. Nevertheless, they say there is now an urgent need to clarify the risk associated with rosiglitazone. GlaxoSmithKline has rebutted the findings, stating that the cardiovascular risk profile of rosiglitazone is comparable with that of other oral antidiabetic drugs. The MHRA says warnings in the current SPCs for Avandia and Avandamet already reflect most of the data in the latest US review. The possible effects of rosiglitazone on cardiovascular events is currently being evaluated in the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycaemia in Diabetes (RECORD) study. Good management tool The Department of Health has published a disease management tool to enable PCTs to model local interventions that could reduce emergency admissions. The web-based ,voluntary good practice tool' will demonstrate how interventions in primary care and social care settings can improve the management of long-term conditions including cardiovascular disease, asthma and COPD, and dementia and depression. Counterfeit medicines The MHRA has issued an unprecedented three alerts about fake medicines in the legitimate supply chain, recalling all affected lot numbers. Three batches of Zyprexa 10mg tablets (olanzapine) were withdrawn after a company printing labels became suspicious and alerted Eli Lilly. Two of the batches, which contained 60 per cent of the stated active ingredient, had reached patients but no adverse events were reported. Two lots of parallel-imported Plavix 75mg tablets (clopidogrel) have been withdrawn after counterfeit packs were identified. The lots were in French original packaging but will have been overlabelled for the UK market. The counterfeits were mixed with genuine packs from Sanofi-Aventis. Fake Casodex 50mg tablets (bicalutamide) have been identified in a parallel import from France. The Royal Pharmaceutical Society reports that the fake contains 75 per cent of the stated dose of bicalutamide. Alcohol-free mometasone Schering-plough has introduced an alcohol-free formulation of mometasone furoate nasal spray (Nasonex) for hay fever. The company says that an alcohol vehicle causes nasal irritation and leaves an unpleasant aftertaste, adding that over 40 per cent of patients cite this as the main reason for stopping treatment, and over 50 per cent state a preference for an alcohol-free product. Aid to improve statin adherence Adherence to statin therapy can be improved if patients use a decision aid when they are offered treatment,US investigators say (Arch Intern Med 2007;167:1076-82). The decision aid estimated the individual's 10-year cardiovascular risk and the risk reduction from treatment, and summarised the disadvantages of statins.Patients with diabetes who used the aid knew more about their risk and were less indecisive about treatment than those who did not. The odds of having missed a dose over three months were three times higher for patients who had not used the aid. Online tool calculates switch savings A new online tool can help GPs estimate the savings achievable from switching patients to cheaper medicines. The Switch Saving Calculator, developed by the Prescribing Analysis & Support Team at the NHS Regional Drug and Therapeutics Centre in Newcastle, calculates potential savings based on past, current or projected use of the target drug. It can be applied to individual prescribers or scaled up to practice, commissioning group, PCT, health authority or even national level. Separate calculators are available for primary and secondary care. The current version calculates potential savings by switching from atorvastatin to simvastatin. The Newcastle team says other drugs will be added and they will update prices regularly. The calculator is at www.nyrdtc.nhs.uk:80/Services/presc_supp/ switch_saving_calculator/switch_saving_calculator.html. No improvement in drug information for patients leaving hospital The information given to patients discharged from hospital is not improving, according to the Healthcare Commission's annual patient survey (www.healthcare commission.org.uk). The 2006 survey found that the commonest reason patients were kept waiting for at least four hours to leave hospital was the delay in providing discharge medicines. Provision of written information increased from 62 per cent of patients in 2005 to 65 per cent in 2006. However, only 76 per cent said they had been told about their medicines in a way they could ,completely' understand (79 per cent in 2002). The proportion of patients reporting complete information about sideeffects also fell (from 40 per cent in 2005 to 37 per cent). Aspirin in preeclampsia A new meta-analysis has found that primary prevention with low-dose aspirin modestly but consistently reduces the risk of preeclampsia (Lancet 2007; published online 18 May). The study of 31 trials involving 32 217 women at low to moderate risk found that antiplatelet agents (mostly aspirin) reduced the risk of pre-eclampsia and preterm birth by 10 per cent without an increased risk of bleeding. The benefit was similar across subgroups. There were also nonsignificant reductions in the risk of small for age, stillborn and death before discharge. New from NICE NICE approves varenicline for NHS NICE has endorsed the use of varenicline (Champix) as an aid to smoking cessation within the NHS for England and Wales; it has already been approved for use in Scotland by the Scottish Medicines Consortium. Varenicline is a partial agonist at the ,4,2 nicotinic receptor. It alleviates craving and withdrawal symptoms, and reduces the rewarding and reinforcing effects of smoking. The commonest adverse effect is mild to moderate nausea, which improves with time.1 Varenicline is licensed for smoking cessation in adults; NICE says it should be offered as an option for smokers who say they want to quit as part of a programme of behavioural support. However, treatment should not be withheld if counselling and support are not available. NICE was critical of manufacturer Pfizer's economic arguments in favour of varenicline, which inappropriately included US data, assumed a single quit attempt and may have overestimated its efficacy. It nonetheless concluded that varenicline is more effective than nicotine replacement therapy (NRT) or bupropion (Zyban) in achieving continuous abstinence. NICE estimated that, compared with NRT, the odds of abstinence at one year with varenicline were 54 per cent greater. A Cochrane review1 concluded that abstinence was 66 per cent more likely with varenicline than with bupropion, and three times more likely than with placebo. There was also a benefit from offering smokers a wider choice of treatments. A 12-week course of varenicline costs £163.80; it is also licensed for an additional 12-week course and dose tapering may be considered for those at high risk of relapse. The final appraisal determination does not state which is the treatment of first choice for smoking cessation. NICE is currently preparing guidance on smoking cessation in pri-mary care, pharmacies and workplaces. Copyright © 2007 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 8 2007Article first published online: 23 JUL 200 Lamotrigine for partial, valproate for generalised A large UK trial has shown that lamotrigine is the most effective choice in the treatment of partial epilepsy (Lancet 2007;369: 1000-15). The SANAD trial, commissioned by the National Institute for Health Research's Health Technology Assessment programme, randomised 1721 patients (for whom carbamazepine monotherapy would have been the treatment of choice) to treatment with carbamazepine, gabapentin, lamotrigine, oxcarbazepine (Trileptal) or topiramate (Topamax). Lamotrigine was associated with a longer time to treatment failure, though time to 12-month remission favoured carbamazepine. Over four years' follow-up, lamotrigine was numerically but not significantly superior. The authors concluded lamotrigine is clinically superior to carbamazepine for partial epilepsy A second arm of the trial, yet to be published, evaluated the treatment of generalised epilepsy and found valproate to be clinically most effective, though topiramate was cost effective for some patients. Chronic pain common in nursing homes Most residents in nursing homes say they have long- term pain but only one in seven say a health professional has ever discussed its treatment with them, according to a report by the Patients' Association (www.patients-association.org.uk). Pain in Older People ,A Hidden Problem was a qualitative study of 77 older residents in care homes in England. Most were frail and suffered long-term illness. The study found that 85 per cent of residents said they were often troubled by aches or pains and these lasted over a year in 74 per cent. Most described their pain as moderate (33 per cent) or severe (38 per cent) but 8 per cent said it was excruciating. Many reported limitations on mobility and social activities despite a high level of stoicism. All but one were taking medication to relive pain; one-third experienced adverse effects but 78 per cent believed drugs offered the most effective treatment. One-quarter said a doctor or nurse had discussed how to stop their pain worsening, and 15 per cent said they had discussed how to treat their pain. Visits from GPs appeared to be uncommon. Atherothrombotic events despite treatment Between one in five and one in seven of high-risk patients experience atherothrombotic events despite evidence-based treatment, the REACH study has shown (J Am Med Assoc 2007;297:1197-1206). REACH (REduction of Atherothrombosis for Continued Health) is an international observational study involving 68 236 patients with atherothrombotic disease or at least three risk factors. Most were taking conventional evidence-based medication. After one year, the incidence of the combined endpoint of cardiovascular death, myocardial infarction, stroke or hospitalisation for atherothrombotic events was approximately 15 per cent for patients with coronary artery disease or cardiovascular disease, and 21 per cent in patients with peripheral artery disease and established coronary disease. Event rates increased with the number of vascular beds affected, rising to 26 per cent in patients with three symptomatic arterial disease locations. Extended CD prescribing by nurses and pharmacists The Medicines and Healthcare products Regulatory Agency (MHRA) is consulting on expanding the prescribing of controlled drugs (CDs) by nonmedical prescribers. Currently, nurse independent prescribers can prescribe 12 CDs, including diamorphine and morphine, but pharmacist independent prescribers may not prescribe any CDs. The proposal is to allow both professions to prescribe any CDs within their competence, with the exception of cocaine, diamorphine or dipipanone for the management of addiction. The closing date for consultation is 15 June. Consultation is also underway on expanding the range of CDs nurses and pharmacists can prescribe under a patient group direction (PGD), and their use for pain relief. The closing date for consultation is 20 April. Intrinsa: transdermal testosterone for women A transdermal formulation of testosterone has been introduced for the treatment of low sexual desire associated with distress in women who have experienced an early menopause following hysterectomy involving a bilateral oophorectomy and are receiving concomitant oestrogen therapy. Manufacturer Procter & Gamble says that Intrinsa, a twice-weekly patch, delivers testosterone 300µg every 24 hours, achieving premenopausal serum testosterone levels. Clinical trials showed that Intrinsa reduced distress in 65-68 per cent and increased satisfying sexual activity in 51-74 per cent of women. A month's treatment (eight patches) costs £28.00. Fish oil for secondary ,not primary ,prevention of CHD Supplementing statin therapy with eicosapentaenoic acid (EPA) reduces the risk of major coronary events in patients with coronary heart disease (CHD) ,but not in patients with no history of CHD Lancet 2007;369:1090-8). The five-year study in 18 645 patients with total cholesterol levels of 6.5mmol per litre or greater found that the incidence of sudden cardiac death, fatal and nonfatal myocardial infarction in CHD patients treated with EPA plus a statin was 8.7 per cent compared with 10.7 per cent with a statin alone (relative risk reduction 19 per cent). A similar relative risk reduction in patients with no CHD was not statistically significant. There was no difference in mortality between the groups but EPA did reduce unstable angina and nonfatal coronary events. Department pilots information prescriptions The Department of Health has announced 20 sites to pilot information prescriptions prior to a nationwide roll-out in 2008. The prescriptions will guide people with long-term conditions such as diabetes and cancer to sources of support and information about their condition. The Department hopes the project will increase patients' understanding of their discussions with health professionals, empower them to locate the information they need, and provide long-term support. NPSA guidelines for safer prescribing The National Patient Safety Agency (www.npsa.nhs.uk) has published five guidelines to improve medication safety in the NHS. Targeting ,high-risk issues', the guidance covers anticoagulant prescribing, liquid medicines for oral or enteral administration, injectable medicines, epidural injections and infusions, and paediatric intravenous infusions. The implementation of each guide is supported by additional tools and resources. Better adherence not matched to outcomes A systematic review has found that interventions can increase adherence to prescribed medication but there is no evidence that clinical outcomes also improve (Arch Intern Med 2007;167:540-9). The review of 37 trials identified 20 reporting increased adherence. The most effective interventions were behavioural changes to reduce dose demands and those involving monitoring and feedback. Improvements in clinical outcomes were variable and did not correspond to changes in adherence. Antidepressant plus mood stabiliser no better US investigators have found that combining a mood stabiliser with an antidepressant is no more effective than a mood stabiliser alone in preventing mood changes (N Engl J Med 2007; published online 28 March, doi.10.1056/NEJMoa064135). The study found durable recovery occurred in 23.5 per cent of patients treated with a mood stabiliser and adjunctive antidepressant therapy for six months compared with 27.3 per cent of those taking a mood stabiliser plus placebo. [source] Early Low-Grade Proteinuria: Causes, Short-Term Evolution and Long-Term Consequences in Renal TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2005Jean-Michel Halimi Proteinuria 1 year after transplantation is associated with poor renal outcome. It is unclear whether low-grade (<1 g/24 h) proteinuria earlier after transplantation and its short-term change affect long-term graft survival. The effects of proteinuria and its change on long-term graft survival were retrospectively assessed in 484 renal transplant recipients. One- and 3-month proteinuria correlated with donor age, donor cardiovascular death, prolonged cold and warm ischemia times and acute rejection. One- and 3-month proteinuria (per 0.1 g/24 h, hazard ratio (HR): 1.07 and 1.15, p < 0.0001),especially low-grade proteinuria (HR: 1.20 and 1.26, p < 0.0001),were powerful, independent predictors of graft loss. Its short-term reduction correlated with arterial pressure (AP) (the lower the 3-month diastolic and 12-month systolic AP, the lower the risk of increasing proteinuria during 1,3 months and 3,12 months periods, respectively: Odds ratio (OR) per 10 MmHg: 0.78, p = 0.01 and 0.85, respectively, p = 0.02), and was associated with decreased long-term graft loss (per 0.1 g/24 h: HR: 0.88 and 0.98, respectively, p < 0.0001), independently of initial proteinuria. Early low-grade proteinuria due to pre-transplant renal lesions, ischemia-reperfusion and immunologic injuries is a potent predictor of graft loss. Short-term reduction in proteinuria is associated with improved long-term graft survival. [source] One-year Outcomes Following Coronary Computerized Tomographic Angiography for Evaluation of Emergency Department Patients with Potential Acute Coronary SyndromeACADEMIC EMERGENCY MEDICINE, Issue 8 2009Judd E. Hollander MD Abstract Objectives:, Coronary computerized tomographic angiography (CTA) has high correlation with cardiac catheterization and has been shown to be safe and cost-effective when used for rapid evaluation of low-risk chest pain patients from the emergency department (ED). The long-term outcome of patients discharged from the ED with negative coronary CTA has not been well studied. Methods:, The authors prospectively evaluated consecutive low- to intermediate-risk patients who received coronary CTA in the ED for evaluation of a potential acute coronary syndrome (ACS). Patients with cocaine use, known cancer, and significant comorbidity reducing life expectancy and those found to have significant disease (stenosis , 50% or ejection fraction < 30%) were excluded. Demographics, medical and cardiac history, labs, and electrocardiogram (ECG) results were collected. Patients were followed by telephone contact and record review for 1 year. The main outcome was 1-year cardiovascular death or nonfatal acute myocardial infarction (AMI). Results:, Of 588 patients who received coronary CTA in the ED, 481 met study criteria. They had a mean (±SD) age of 46.1 (±8.8) years, 63% were black or African American, and 60% were female. There were 53 patients (11%) rehospitalized and 51 patients (11%) who received further diagnostic testing (stress or catheterization) over the subsequent year. There was one death (0.2%; 95% confidence interval [CI] = 0.01% to 1.15%) with unclear etiology, no AMI (0%; 95% CI = 0 to 0.76%), and no revascularization procedures (0%; 95% CI = 0 to 0.76%) during this time period. Conclusions:, Low- to intermediate-risk patients with a Thrombosis In Myocardial Infarction (TIMI) score of 0 to 2 who present to the ED with potential ACS and have a negative coronary CTA have a very low likelihood of cardiovascular events over the ensuing year. [source] Antiplatelet therapy after endovascular intervention: Does combination therapy really work and what is the optimum duration of therapy?,,CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue S1 2009Richard V. Milani MD Abstract The number of patients undergoing peripheral interventions has increased in recent years, highlighting the need for a safe and effective protective antithrombotic therapy. Platelet inhibition following coronary intervention is associated with a significantly reduced risk of graft occlusion, and has been acknowledged to be safe and effective in patients with peripheral arterial disease. Monotherapy with either aspirin or clopidogrel, reduces the rate of stroke, myocardial infarction, and cardiovascular death in patients suffering from peripheral arterial disease. Limited data from clinical trials investigating combination therapy of aspirin with ticlopidine or clopidogrel in patients undergoing endovascular interventions, have suggested the potential for a reduction in cardiovascular events. Nevertheless, the optimal duration of postintervention antiplatelet therapy remains to be defined. © 2009 Wiley-Liss, Inc. [source] Omega-3 Dietary Supplements and the Risk of Cardiovascular Events: A Systematic ReviewCLINICAL CARDIOLOGY, Issue 7 2009FCCM, Paul E. Marik MD Background Epidemiologic data suggest that omega-3 fatty acids derived from fish oil reduce cardiovascular disease. The clinical benefit of dietary fish oil supplementation in preventing cardiovascular events in both high and low risk patients is unclear. Objective To assess whether dietary supplements of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease cardiovascular events across a spectrum of patients. Data Sources MEDLINE, Embase, the Cochrane Database of Systematic Reviews, and citation review of relevant primary and review articles. Study Selection Prospective, randomized, placebo-controlled clinical trials that evaluated clinical cardiovascular end points (cardiovascular death, sudden death, and nonfatal cardiovascular events) and all-cause mortality in patients randomized to EPA/DHA or placebo. We only included studies that used dietary supplements of EPA/DHA which were administered for at least 1 year. Data Extraction Data were abstracted on study design, study size, type and dose of omega-3 supplement, cardiovascular events, all-cause mortality, and duration of follow-up. Studies were grouped according to the risk of cardiovascular events (high risk and moderate risk). Meta-analytic techniques were used to analyze the data. Data Synthesis We identified 11 studies that included a total of 39 044 patients. The studies included patients after recent myocardial infarction, those with an implanted cardioverter defibrillator, and patients with heart failure, peripheral vascular disease, and hypercholesterolemia. The average dose of EPA/DHA was 1.8 ± 1.2 g/day and the mean duration of follow-up was 2.2 ± 1.2 years. Dietary supplementation with omega-3 fatty acids significantly reduced the risk of cardiovascular deaths (odds ratio [OR]: 0.87, 95% confidence interval [CI]: 0.79,0.95, p = 0.002), sudden cardiac death (OR: 0.87, 95% CI: 0.76,0.99, p = 0.04), all-cause mortality (OR: 0.92, 95% CI: 0.85,0.99, p = 0.02), and nonfatal cardiovascular events (OR: 0.92, 95% CI: 0.85,0.99, p = 0.02). The mortality benefit was largely due to the studies which enrolled high risk patients, while the reduction in nonfatal cardiovascular events was noted in the moderate risk patients (secondary prevention only). Meta-regression failed to demonstrate a relationship between the daily dose of omega-3 fatty acid and clinical outcome. Conclusions Dietary supplementation with omega-3 fatty acids should be considered in the secondary prevention of cardiovascular events. Copyright © 2009 Wiley Periodicals, Inc. [source] Reassessing the Cardiovascular Risks and Benefits of ThiazolidinedionesCLINICAL CARDIOLOGY, Issue 9 2008Andrew Zinn MD Abstract This article is designed for the general cardiologist, endocrinologist, and internist caring for patients with diabetes and coronary artery disease. Despite the burden of coronary disease in diabetics, little is known about the impact of commonly used oral hypoglycemic agents on cardiovascular outcomes. As the untoward effects of insulin resistance (IR) are increasingly recognized, there is interest in targeting this defect. Insulin resistance contributes to dyslipidemia, hypertension, inflammation, hypercoagulability, and endothelial dysfunction. The aggregate impact of this process is progression of systemic atherosclerosis and an increased risk of adverse cardiovascular outcomes. As such, much attention has been paid to the peroxisome-proliferator-activated receptor gamma (PPARg) agonists rosiglitazone and pioglitazone (thiazolidinediones [TZDs]). Many studies have demonstrated a beneficial effect on the atherosclerotic process; specifically, these agents have been shown to reduce markers of inflammation, retard progression of carotid intimal thickness, prevent restenosis after coronary stenting, and prevent cardiovascular death and myocardial infarction in 1 large trial. Such benefits come at the risk of fluid retention and heart failure (HF) exacerbation, and the net effect on plasma lipids is still poorly understood. Thus, the aggregate risk-benefit ratio is poorly defined. A recent meta-analysis has raised significant concerns regarding the overall cardiovascular safety of 1 particular PPARg agonist (rosiglitazone), prompting international debate and regulatory changes. This review scrutinizes the clinical evidence regarding the cardiovascular risks and benefits of PPARg agonists. Future studies of PPARg agonists, and other emerging drugs that treat IR and diabetes, must be designed to look at cardiovascular outcomes. Copyright © 2008 Wiley Periodicals, Inc. [source] Assessment of cardiovascular risk in waiting-listed renal transplant patients: a single center experience in 558 casesCLINICAL TRANSPLANTATION, Issue 5 2009G. Leonardi Abstract:, Cardiac screening is recommended to prevent cardiovascular death after renal transplantation. This retrospective observational study illustrates the results of application of a cardiac assessment algorithm in a series of 558 renal transplant candidates at a single center in Turin, Italy. A dipyridamole-stress sestamibi myocardial scintiscan (DMS) performed in 302/558 (54.1%) cases was positive in 52 (17.2%), negative in 200 (66.2%), borderline in 16 (5.3%), and with signs of previous necrosis in 34 (11.4%). Coronary lesions detected by angiography in 48.1% of the 52 positives were treated medically (13.5%) or by percutaneous/surgical procedure (34.6%). Coronary lesions were detected in 14.1% of asymptomatic population subgroup. The minor and major cardiovascular event rates and the cardiovascular death rate were 1.9%, 0%, and 0%, respectively, in positive DMS group (high-cardiological risk) vs. 10%, 4.5%, and 3.5% in the negatives (p > 0.5; n.s.). It is suggested that not increased cardiovascular event or deaths rates in the high-risk group reflect early coronary lesion detection and correction. Since 55.9% of cardiovascular events or deaths occurred in the negative group more than 24 months after the DMS, its mandatory repetition every two yr after a negative finding is recommended. [source] Mycophenolate mofetil vs. azathioprine is associated with decreased acute rejection, late acute rejection, and risk for cardiovascular death in renal transplant recipients with pre-transplant diabetesCLINICAL TRANSPLANTATION, Issue 2 2005Kristin M David Abstract:, Outcomes specifically in mycophenolate mofetil (MMF)-treated diabetic renal transplant patients have not been previously reported. This study compared acute rejection (AR), late acute rejection (LAR), patient survival [and specifically death from cardiovascular (CV), infectious and malignant causes], incidence of post-transplant malignancies, and graft loss in MMF- or azathioprine (AZA)-treated renal transplant patients with pre-transplant diabetes. Outcomes were compared between MMF- (n = 14 144) and AZA- (n = 3001) treated diabetic patients using the Scientific Registry of Transplant Recipients data on all U.S. adult renal transplants performed between 1995 and 2002. Statistical analyses included Kaplan,Meier survival analysis, Cox multivariable regression and chi-square tests. MMF patients had less AR compared with AZA-treated patients (23.5% vs. 28.3%, p < 0.001) and less risk for LAR over 4 yr [hazard ratio (HR): 0.64, 95% CI 0.44, 0.92; p = 0.02]. While time to any-cause death did not differ between the groups, MMF treatment was associated with a 20% decreased risk of CV death (HR: 0.80, 95% CI 0.67, 0.97; p = 0.020) compared with AZA treatment. MMF patients also had a lower incidence of malignancies than AZA patients (2.2% vs. 3.7%, p < 0.001). These results suggest treatment with MMF compared with treatment with AZA in diabetic transplant patients is associated with less AR, less risk of LAR, a decreased risk of CV death, and a lower incidence of malignancies. [source] Prediction of cardiovascular and total mortality in Chinese type 2 diabetic patients by the WHO definition for the metabolic syndromeDIABETES OBESITY & METABOLISM, Issue 1 2006G. T.-C. Aim:, The aim of this study is to investigate the prevalence of metabolic syndrome (MES) in type 2 diabetic patients and the predictive values of the World Health Organization (WHO) and National Cholesterol Education Programme (NCEP) definitions and the individual components of the MES on total and cardiovascular mortality. Methods:, A prospective analysis of a consecutive cohort of 5202 Chinese type 2 diabetic patients recruited between July 1994 and April 2001. Results:, The prevalence of the MES was 49.2,58.1% depending on the use of various criteria. There were 189 deaths (men: 100 and women: 89) in these 5205 patients during a median (interquartile range) follow-up period of 2.1 (0.3,3.6 years). Of these, 164 (87%) were classified as cardiovascular deaths. Using the NCEP criterion, patients with MES had a death rate similar to those without (3.51 vs. 3.85%). By contrast, based on the WHO criteria, patients with MES had a higher mortality rate than those without (4.3 vs. 2.4%, p = 0.002). Compared to patients with neither NCEP- nor WHO-defined MES, only the group with MES defined by the WHO, but not NCEP, criterion had significantly higher mortality rate (2.6 vs. 6.8%, p < 0.001). Using Cox regression analysis, only age, duration of diabetes and smoking were identified as independent factors for cardiovascular or total death. Among the various components of MES, hypertension, low BMI and albuminuria were the key predictors for these adverse events. Conclusions:, In Chinese type 2 diabetic patients, the WHO criterion has a better discriminative power over the NCEP criterion for predicting death. Among the various components of the MES defined either by WHO or NCEP, hypertension, albuminuria and low BMI were the main predictors of cardiovascular and total mortality. [source] HOPE for patients with Type 2 diabetes: an application of the findings of the MICRO-HOPE substudy in a British hospital diabetes clinicDIABETIC MEDICINE, Issue 8 2001S. C. Jones Abstract Aims, The MICRO-HOPE substudy demonstrated that when ramipril treatment was added to people with Type 2 diabetes and additional cardiovascular risk factors cardiovascular events were reduced by 25% in 4.5 years. We wished to determine the proportion of people with Type 2 diabetes and additional cardiovascular risk factors registered with a hospital diabetes service. Methods, Non-proteinuric people (n = 1370) with Type 2 diabetes identified on our diabetes register were subject to analysis. Anticipated reductions in cardiovascular events due to ramipril treatment were based on reductions observed in the MICRO-HOPE substudy. Results, Non-proteinuric people (n = 1075 (78%)) with Type 2 diabetes had at least one additional cardiovascular risk factor. Twenty-nine percent were already taking an angiotensin-converting enzyme inhibitor. The remaining 764 patients were similar to ramipril-treated participants in the MICRO-HOPE substudy. Treatment with ramipril for 4.5 years would be anticipated to reduce cardiovascular deaths by 26, revascularization procedures by 19 and admissions for myocardial infarction and stroke by 18 and 26, respectively. Conclusions, Of non-proteinuric people with Type 2 diabetes, 78% have additional cardiovascular risk factors. Only a small proportion currently receive treatment with an angiotensin-converting enzyme inhibitor. The incidence of cardiovascular events could be reduced if more patients were treated with ramipril and other cardiovascular risk factors were addressed. Diabet. Med. 18, 667,670 (2001) [source] Enhanced Predictive Power of Quantitative TWA during Routine Exercise Testing in the Finnish Cardiovascular StudyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2009MIKKO MINKKINEN B.M.S. Introduction: We examined whether quantification of T-wave alternans (TWA) enhances this parameter's capacity to evaluate the risk for total and cardiovascular mortality and sudden cardiac death (SCD). Methods and Results: The Finnish Cardiovascular Study (FINCAVAS) enrolled consecutive patients (n = 2,119; 1,342 men and 777 women) with a clinically indicated exercise test with bicycle ergometer. TWA (time domain-modified moving average method) was analyzed from precordial leads, and the results were grouped in increments of 10 ,V. Hazard ratios (HR) for total and cardiovascular mortality and SCD were estimated for preexercise, routine exercise, and postexercise stages. Cox regression analysis was performed. During follow-up of 47.1 ± 12.9 months (mean ± standard deviation [SD]), 126 patients died: 62 were cardiovascular deaths, and 33 of these deaths were sudden. During preexercise, TWA , 20 ,V predicted the risk for total and cardiovascular mortality (maximum HR >4.4 at 60 ,V, P < 0.02 for both). During exercise, HRs of total and cardiovascular mortality were significant when TWA measured ,50 ,V, with 90 ,V TWA yielding maximum HRs for total and cardiovascular death of 3.1 (P = 0.03) and 6.4 (P = 0.002), respectively. During postexercise, TWA ,60 ,V indicated risk for total and cardiovascular mortality, with maximum HR of 3.4 at 70 ,V (P = 0.01) for cardiovascular mortality. SCD was strongly predicted by TWA levels ,60 ,V during exercise, with maximum HR of 4.6 at 60 ,V (P = 0.002), but was not predicted during pre- or postexercise. Conclusion: Quantification of TWA enhances its capacity for determination of the risk for total and cardiovascular mortality and SCD in low-risk populations. Its prognostic power is superior during exercise compared to preexercise or postexercise. [source] Bone marrow stem cells regenerate infarcted myocardiumPEDIATRIC TRANSPLANTATION, Issue 2003Donald Orlic Abstract: Heart disease is the leading cause of death in the United States for both men and women. Nearly 50% of all cardiovascular deaths result from coronary artery disease. Occlusion of the left coronary artery leads to ischemia, infarction, necrosis of the affected myocardial tissue followed by scar formation and loss of function. Although myocytes in the surviving myocardium undergo hypertrophy and cell division occurs in the border area of the dead tissue, myocardial infarcts do not regenerate and eventually result in the death of the individual. Numerous attempts have been made to repair damaged myocardium in animal models and in humans. Bone marrow stem cells (BMSC) retain the ability throughout adult life to self-renew and differentiate into cells of all blood lineages. These adult BMSC have recently been shown to have the capacity to differentiate into multiple specific cell types in tissues other than bone marrow. Our research is focused on the capacity of BMSC to form new cardiac myocytes and coronary vessels following an induced myocardial infarct in adult mice. In this paper we will review the data we have previously published from studies on the regenerative capacity of BMSC in acute ischemic myocardial injury. In one experiment donor BMSC were injected directly into the healthy myocardium adjacent to the injured area of the left ventricle. In the second experiment, mice were treated with cytokines to mobilize their BMSC into the circulation on the theory that the stem cells would traffic to the myocardial infarct. In both experimental protocols, the BMSC gave rise to new cardiac myocytes and coronary blood vessels. This BMSC-derived myocardial regeneration resulted in improved cardiac function and survival. [source] Added Value of a Resting ECG Neural Network That Predicts Cardiovascular MortalityANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2009Marco V. Perez M.D. Background: The resting 12-lead electrocardiogram (ECG) remains the most commonly used test in evaluating patients with suspected cardiovascular disease. Prognostic values of individual findings on the ECG have been reported but may be of limited use. Methods: The characteristics of 45,855 ECGs ordered by physician's discretion were first recorded and analyzed using a computerized system. Ninety percent of these ECGs were used to train an artifical neural network (ANN) to predict cardiovascular mortality (CVM) based on 132 ECG and four demographic characteristics. The ANN generated a Resting ECG Neural Network (RENN) score that was then tested in the remaining ECGs. The RENN score was finally assessed in a cohort of 2189 patients who underwent exercise treadmill testing and were followed for CVM. Results: The RENN score was able to better predict CVM compared to individual ECG markers or a traditional Cox regression model in the testing cohort. Over a mean of 8.6 years, there were 156 cardiovascular deaths in the treadmill cohort. Among the patients who were classified as intermediate risk by Duke Treadmill Scoring (DTS), the third tertile of the RENN score demonstrated an adjusted Cox hazard ratio of 5.4 (95% CI 2.0,15.2) compared to the first RENN tertile. The 10-year CVM was 2.8%, 8.6% and 22% in the first, second and third RENN tertiles, respectively. Conclusions: An ANN that uses the resting ECG and demographic variables to predict CVM was created. The RENN score can further risk stratify patients deemed at moderate risk on exercise treadmill testing. [source] | ||||||||||||||||||||||||||||