Significant Increase In All-cause Mortality Research Articles

Right ventricular systolic function in patients undergoing transcatheter aortic valve implantation: A systematic review and meta-analysis

BackgroundRight ventricular (RV) systolic dysfunction is associated with worse survival in patients undergoing surgical aortic valve replacement (SAVR), yet it is not included in traditional risk scores of transcatheter aortic valve implantation (TAVI) candidates. We aimed to evaluate the prognostic value of RV systolic function on clinical outcomes in patients undergoing TAVI at one year follow-up; and, echocardiographic changes of RV systolic function up to 12 months after TAVI and compared with SAVR when possible. Methods and resultsThis systematic review and meta-analysis is registered in PROSPERO (CRD42017065761). Studies investigating RV systolic function with echocardiography in TAVI cohorts were identified from Medline, Embase and Cochrane databases. We used random-effects models to assess differences in primary outcomes. Twenty-one studies were identified, where RV systolic function and clinical outcomes were assessed in eight (4016 patients) and RV systolic function changes were evaluated in 14 (1709 patients). For the primary outcome of all-cause death at one year, RV systolic dysfunction was associated with a significant 78% relative risk increase (risk ratio[95% confidence interval (CI)]) = 1.78[1.37, 2.31], P < 0.01), albeit significant heterogeneity (I2 = 64%, P < 0.01). RV systolic function was unchanged after TAVI throughout follow-up as shown with tricuspid annular plane systolic excursion (TAPSE)(mean difference[95% CI]pre-discharge = 0.03 [−0.92,0.99]mm,1–3 months = −0.09[−0.89,0.71]mm,6–12 months = 0.52 [−0.29,1.32] mm, all P = NS), while TAPSE was significantly reduced after SAVR (pre-discharge = −10.17[−13.11,−7.24]mm, P < 0.01;1–3 months = −7.3[−8.17,−6.44]mm, P < 0.01;6–12 months = −5.99[−7.95,−4.03]mm, P < 0.01). ConclusionsRV systolic dysfunction was associated with a significant increase in all-cause mortality at one year after TAVI. RV systolic function was unchanged after TAVI up to 12 months, whereas deteriorated significantly after SAVR.

Guideline-Adherent Antithrombotic Treatment Improves Outcomes in Patients With Atrial Fibrillation: Insights From the Community-Based Darlington Atrial Fibrillation Registry

ObjectiveTo assess the influence of guideline-adherent vs nonadherent antithrombotic treatment (ATT) on stroke and mortality rates in an atrial fibrillation (AF) primary care population. Patients and MethodsWe used the Darlington Registry cohort, which included 105,000 patients from March 31, 2012, through March 31, 2013. Guideline adherence in ATT was assessed against 2014 National Institute for Health and Care Excellence guidelines, which recommend oral anticoagulation for stroke prevention as a default management unless a truly low risk of stroke (CHA2DS2-VASc=0 in men and 1 in women) is evident. ResultsOf 2259 patients with AF (2.15%), 36.1% were undertreated, 50.8% were guideline adherent, and 13.1% were overtreated. Oral anticoagulation was declined by 5.0% and contraindicated in 8.3%. Of 67 incident strokes (3.0%), 66 (98.5%) occurred in high-risk patients (CHA2DS2-VASc ≥2). For the high-risk cohort, 1-year stroke rates were 4.5% (95% CI, 3.2%-6.3%) for undertreatment, 1.9% (95% CI, 1.2%-2.9%) for guideline adherence, and 7.2% (95% CI, 4.4%-11.6%) for overtreatment; corresponding mortality rates were 16.1% (95% CI, 13.6%-19.0%), 8.0% (95% CI, 6.5%-9.8%), and 8.2% (95% CI, 5.2%-12.7%), respectively. On multivariable analysis, both undertreatment and overtreatment of high-risk patients were associated with significant increases in stroke rates (odds ratio [OR]=2.32; 95% CI, 1.30-3.14; P=.005 and OR=2.28; 95% CI, 1.12-4.63; P=.02, respectively). Undertreatment was also associated with a significant increase in all-cause mortality (OR=1.59; 95% CI, 1.14-2.21; P=.006). ConclusionOnly half of all eligible patients with AF are prescribed oral anticoagulation in accordance with guideline recommendations. Guideline-adherent ATT significantly reduces the risk of stroke and improves survival.

Prognostic Impact of Low-Flow Severe Aortic Stenosis in Small-Body Patients Undergoing TAVR: The OCEAN-TAVI Registry

ObjectivesThis study aimed to analyze the prognostic impact of low-flow (LF) severe aortic stenosis in small-body patients undergoing transcatheter aortic valve replacement (TAVR). BackgroundWestern literature demonstrates a poor prognosis with paradoxical LF and low-flow low-gradient (LF-LG) severe aortic stenosis (AS), as defined by stroke volume index (SVi) <35 ml/m2 and mean pressure gradient <40 mm Hg with preserved left ventricular ejection fraction (LVEF). However, this poor prognosis is contested in Japan owing to the smaller body size of Japanese patients relative to that of Western patients. Additionally, there are no reports of the prognostic implication of paradoxical LF or LF-LG severe AS in small-body patients undergoing TAVR. MethodsThis was a retrospective analysis of 723 consecutive Japanese patients (median age 85 years; 32.6% male; median body surface area 1.4 m2) who underwent TAVR for severe AS at 9 sites in Japan. The primary and secondary endpoints were cumulative all-cause and cardiovascular mortality after TAVR, respectively. ResultsNinety-seven (13.4%) patients had paradoxical LF severe AS whereas 38 (5.3%) had paradoxical LF-LG with severe AS. PLF was associated with a significant increase in all-cause (hazard ratio [HR]: 3.00; 95% confidence interval [CI]: 1.34 to 6.72; p < 0.001) and cardiovascular mortality (HR: 5.58; 95% CI: 1.19 to 26.2; p < 0.01), as compared with patients’ normal flow and preserved LVEF. PLF-LG was associated with a significant increase in all-cause mortality (HR: 3.76; 95% CI: 1.09 to 13.73; p < 0.01), as compared with normal flow high gradient with preserved LVEF. SVi was an independent predictor of cardiovascular mortality on multivariate analysis after adjustments for age, sex, clinically relevant variables, and other echocardiographic parameters (HR: 1.96; 95% CI: 1.19 to 3.23; p < 0.01). ConclusionsAmong Japanese small-body patients with severe AS, both paradoxical LF and LF-LG severe AS were associated with poor outcomes following TAVR. SVi was an independent predictor of cardiovascular mortality after TAVR. (Optimised Transcatheter Valvular Intervention registry [OCEAN-TAVI]; UMIN000020423)

Body Mass Index and Mortality.

Although the prevalence of obesity, a well-known risk factor for various chronic diseases such as hypertension, type 2 diabetes and dyslipidemia, is rapidly increasing worldwide, the association of obesity with all-cause mortality remains controversial. Many previous epidemiologic studies have demonstrated a U-shaped relationship between obesity and mortality, suggesting that there is an obesity paradox. However, recent large-scale meta-analyses found contradictory results that both overweight and obese subjects exhibited a significant increase in all-cause mortality. This review summarizes the key epidemiologic studies on the association of obesity with mortality and thoroughly examines the causes of the obesity paradox and the precautions needed in the interpretation of this clinical evidence.

Shift work and overall and cause-specific mortality in the Danish nurse cohort

Objectives Evidence of an effect of shift work on all-cause and cause-specific mortality is inconsistent. This study aims to examine whether shift work is associated with increased all-cause and cause-specific mortality. Methods We linked 28 731 female nurses (age ≥44 years), recruited in 1993 or 1999 from the Danish nurse cohort where they reported information on shift work (night, evening, rotating, or day), to the Danish Register of Causes of Death to identify deaths up to 2013. We used Cox regression models with age as the underlying scale to examine the associations between night, evening, and rotating shift work (compared to day shift work) and all-cause and cause-specific mortality in models adjusted for potentially confounding variables. Results Of 18 015 nurses included in this study, 1616 died during the study time period from the following causes: cardiovascular disease (N=217), cancer (N= 945), diabetes (N=20), Alzheimer's disease or dementia (N=33), and psychiatric diseases (N=67). We found that working night [hazard ratio (HR) 1.26, 95% confidence interval 95% CI) 1.05-1.51] or evening (HR 1.29, 95% CI 1.11-1.49) shifts was associated with a significant increase in all-cause mortality when compared to working day shift. We found a significant association of night shift work with cardiovascular disease (HR 1.71, 95% CI 1.09-2.69) and diabetes (HR 12.0, 95% CI 3.17-45.2, based on 8 cases) and none with overall cancer mortality (HR 1.05, 95% CI 0.81-1.35) or mortality from psychiatric diseases (HR 1.17, 95% CI 0.47-2.92). Finally, we found strong association between evening (HR 4.28, 95% CI 1.62-11.3) and rotating (HR 5.39, 95% CI 2.35-12.3) shift work and mortality from Alzheimer's disease and dementia (based on 8 and 14 deaths among evening and rotating shift workers, respectively). Conclusions Women working night and evening shifts have increased all-cause, cardiovascular, diabetes, and Alzheimer's and dementia mortality.

Nonselective β-Blockers and Survival in Patients With Cirrhosis and Ascites: A Systematic Review and Meta-analysis.

Nonselective β-blockers (NSBBs), given to reduce the risk of variceal bleeding, have been associated with increased mortality in patients with cirrhosis and refractory ascites in some, but not all, studies. We performed a systematic review and meta-analysis to evaluate the effect of NSBBs on all-cause mortality in patients with cirrhosis and refractory ascites. We performed a comprehensive search of MEDLINE, Embase, Web of Science, and Scopus databases through January 2015, supplemented with a manual search. Trial-specific risk ratios (RRs) were pooled using the random-effects model. Our analysis included 3 randomized control trials and 8 observational studies of propranolol, carvedilol, nadolol, and metoprolol, reporting 1206 deaths among 3145 patients with ascites. The control groups received other interventions to prevent variceal bleeding. NSBB use was not associated with increased all-cause mortality in all patients with ascites (RR, 0.95; 95% confidence interval [CI], 0.67-1.35); nonrefractory ascites alone (RR, 0.96; 95% CI, 0.50-1.82), or refractory ascites alone (RR, 0.95; 95% CI, 0.57-1.61). Results were similar in randomized controlled trials and observational studies. Use of NSBBs was not associated with increased mortality at 6, 12, 18, and 24 months. Overall, the included studies had a medium to high risk of bias, except for 3 clinical trials in which the risk of biased was determined to be low. The use of NSBBs was not associated with a significant increase in all-cause mortality in patients with cirrhosis and ascites or refractory ascites. Certainty in the available estimates is low; a randomized trial of only patients with ascites is needed to answer this question. This meta-analysis does not support the position that NSBBs routinely be withheld from patients with ascites.

Target Blood Pressure in Patients with Diabetes: Asian Perspective.

Recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) trial enrolled 4733 participants with type 2 diabetes and randomized them to a target systolic blood pressure (SBP) of less than 120 mm Hg or 140 mm Hg. Despite the significant difference in the achieved SBP, there was no significant difference in the incidence of primary outcomes. Based on this evidence, the target SBP for diabetics has been revised in the majority of major guidelines. However, there is a steeper association between SBP and stroke in Asians than other ethnicities, with stroke being the leading cause of cardiovascular mortality. This suggests that target BP in the Asian region should be tailored towards prevention of stroke. In the ACCORD study, the intensive BP treatment was associated with significant reductions in both total stroke and non-fatal stroke. The results from the ACCORD study are supported by a subgroup analysis from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study, which showed that, in diabetic patients, the risk of stroke continues to decrease to a SBP value of 115 mm Hg with no evidence of J curve. As diabetes is highly associated with underlying coronary artery disease, there is a justified concern for adverse effects resulting from too much lowering of BP. In a post hoc analysis of 6400 diabetic subjects enrolled in the International Verapamil SR-Trandolapril (INVEST) study, subjects with SBP of less than 110 mm Hg were associated with a significant increase in all-cause mortality. In the ONTARGET study, at any levels of achieved SBP, diastolic blood pressure (DBP) below 67 mm Hg was associated with increased risk for cardiovascular outcomes. As such, a prudent approach would be to target a SBP of 130–140 mm Hg and DBP of above 60 mm Hg in diabetics with coronary artery disease. In conclusion, hypertension, in association with diabetes, has been found to be significantly correlated with an elevated risk for cardiovascular events. As the association between stroke and BP is stronger in Asians, compared to other ethnicities, consideration should be given for a target BP of 130/80 mm Hg in Asians.

Increased All-Cause Mortality Associated With Digoxin Therapy in Patients With Atrial Fibrillation: An Updated Meta-Analysis.

Digoxin is still commonly used in atrial fibrillation (AF) patients with and without heart failure (HF) for heart rate control. Studies concerning the detrimental effects of digoxin therapy in AF patients are inconsistent. This updated meta-analysis examined the association of digoxin therapy with all-cause mortality in AF patients, stratified by heart function status. We included observational studies with multivariate-adjusted data on digoxin and all-cause mortality in the analysis. The relative risks (RRs) of all-cause mortality were calculated and reported with 95% confidence intervals (95% CIs). Seventeen studies comprising 408,660 patients were included. Overall, in AF patients, digoxin treatment was associated with a significant increase in all-cause mortality after multivariate-adjustment (RR = 1.22; 95% CI 1.15-1.30). When stratified by heart function status, digoxin treatment was associated with a 14% increase in all-cause mortality in AF patients with HF (RR = 1.14, 95% CI 1.04-1.24), and a 36% increase in those without HF (RR = 1.36, 95% CI 1.18-1.56). The increased risk of all-cause mortality was significantly higher in AF patients without HF compared with those with HF (P for interaction = 0.04). This meta-analysis demonstrates that digoxin therapy was associated with a significant increase in all-cause mortality in AF patients, especially in those without HF. Given other available options, digoxin should be avoided as a first-line agent for heart rate control in AF patients.

ROCKET AF adds more concerns about Digoxin safety in patients with atrial fibrillation

In a recent article in the Journal, we have reviewed the adverse cardiovascular outcomes observed with digoxin use in the PALLAS study.1 The PALLAS study was designed to determine if dronedarone would reduce major vascular events in patients with permanent atrial fibrillation (AF).2 However the study was stopped early because of safety reasons, as a significant number of patients on the dronedarone arm reached the co-primary end point composite of stroke, myocardial infarction, systemic embolism, or cardiovascular death. Data sub-analyses suggested that digoxin-dronedarone interaction was responsible for the higher arrhythmic death rate observed in the trial. These observations are consistent with several other studies that demonstrate the potential hazard of the use of digoxin in heart failure and/or atrial fibrillation.A more recent article published in the Lancet studied the use and outcomes of digoxin in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism in Atrial Fibrillation (ROCKET AF) trial.3 The investigators concluded that digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF.

Associations of Metabolic Syndrome and its Components With Mortality in the Elderly: A Cohort Study of 73,547 Taiwanese Adults.

Available evidence shows that metabolic syndrome (Mets) has clear adverse effects for middle-aged and pre-elderly adults; however, the effect of Mets on mortality among elderly adults remains unclear. In addition, the comparative utility of Mets and its component for predicting mortality among the elderly has not been clearly established. Using data from a large Taiwanese cohort, we evaluated the effect of Mets and its components on subsequent all-cause and cause-specific mortality overtime among the elderly.A total of 73,547 elders (age ≥65 years) participated in the Taipei Elderly Health Examination Program from 2007 to 2010. Mets was diagnosed using the adult treatment panel III criteria, and mortality was ascertained by using national death records. Time-dependent analysis was used to evaluate associations of Mets and its components with all-cause mortality, cardiovascular disease (CVD) mortality, and expanded CVD mortality.This retrospective cohort study found that 42.6% of elders had Mets. During 194,057 person-years of follow-up, 2944 deaths were observed. After adjusting for sociodemographic characteristics and comorbidities, Mets was associated with increased risk of expanded CVD mortality (hazard ratio [HR], 1.27; 95% CI, 1.10–1.46) but not all-cause or CVD mortality. Among Mets components, decreased high-density lipoprotein cholesterol (HDL-C, HR 1.25, 95% CI 1.13–1.37) and hyperglycemia (HR 1.21, 95% CI 1.12–1.31) were associated with a significant increase in all-cause mortality. Hypertension and low HDL-C were predictors of CVD mortality and expanded CVD mortality, and, as compared with Mets, were associated with a higher risk of expanded CVD mortality.The present findings indicate that, in elderly adults, individual components of Mets are better predictors of all-cause and cause-specific mortality than is Mets as a whole. Our results suggest that future efforts should focus on preventing and managing individual risk factors (particularly hypertension, low HDL-C, and hyperglycemia) rather than on “diagnosing” Mets in elders.

Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)

Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767. In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076). Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed. Janssen Research & Development and Bayer HealthCare AG.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

All-cause mortality and serious cardiovascular events in people with hip and knee osteoarthritis: a population based cohort study

Background Because individuals with osteoarthritis (OA) avoid physical activities that exacerbate symptoms, potentially increasing risk for cardiovascular disease (CVD) and death, we assessed the relationship between OA disability and these outcomes. Methods In a population cohort aged 55+ years with at least moderately severe symptomatic hip and/or knee OA, OA disability (Western Ontario McMaster Universities (WOMAC) OA scores; Health Assessment Questionnaire (HAQ) walking score; use of walking aids) and other covariates were assessed by questionnaire. Survey data were linked to health administrative data to determine the relationship between baseline OA symptom severity to all-cause mortality and occurrence of a composite CVD outcome (acute myocardial infarction, coronary revascularization, heart failure, stroke or transient ischemic attack) over a median follow-up of 13.2 and 9.2 years, respectively. Results Of 2156 participants, 1,236 (57.3%) died and 822 (38.1%) experienced a CVD outcome during follow-up. Higher (worse) baseline WOMAC function scores and walking disability were independently associated with a higher all-cause mortality (adjusted hazard ratio, aHR, per 10-point increase in WOMAC function score 1.04, 95% confidence interval, CI 1.01–1.07, p = 0.004; aHR per unit increase in HAQ walking score 1.30, 95% CI 1.22–1.39, p<0.001; and aHR for those using versus not using a walking aid 1.51, 95% CI 1.34–1.70, p<0.001). In survival analysis, censoring on death, risk of our composite CVD outcome was also significantly and independently associated with greater baseline walking disability ((aHR for use of a walking aid = 1.27, 95% CI 1.10–1.47, p = 0.001; aHR per unit increase in HAQ walking score = 1.17, 95% CI 1.08–1.27, p<0.001). Conclusions Among individuals with hip and/or knee OA, severity of OA disability was associated with a significant increase in all-cause mortality and serious CVD events after controlling for multiple confounders. Research is needed to elucidate modifiable mechanisms.

All-Cause Mortality and Serious Cardiovascular Events in People with Hip and Knee Osteoarthritis: A Population Based Cohort Study

BackgroundBecause individuals with osteoarthritis (OA) avoid physical activities that exacerbate symptoms, potentially increasing risk for cardiovascular disease (CVD) and death, we assessed the relationship between OA disability and these outcomes.MethodsIn a population cohort aged 55+ years with at least moderately severe symptomatic hip and/or knee OA, OA disability (Western Ontario McMaster Universities (WOMAC) OA scores; Health Assessment Questionnaire (HAQ) walking score; use of walking aids) and other covariates were assessed by questionnaire. Survey data were linked to health administrative data to determine the relationship between baseline OA symptom severity to all-cause mortality and occurrence of a composite CVD outcome (acute myocardial infarction, coronary revascularization, heart failure, stroke or transient ischemic attack) over a median follow-up of 13.2 and 9.2 years, respectively.ResultsOf 2156 participants, 1,236 (57.3%) died and 822 (38.1%) experienced a CVD outcome during follow-up. Higher (worse) baseline WOMAC function scores and walking disability were independently associated with a higher all-cause mortality (adjusted hazard ratio, aHR, per 10-point increase in WOMAC function score 1.04, 95% confidence interval, CI 1.01–1.07, p = 0.004; aHR per unit increase in HAQ walking score 1.30, 95% CI 1.22–1.39, p<0.001; and aHR for those using versus not using a walking aid 1.51, 95% CI 1.34–1.70, p<0.001). In survival analysis, censoring on death, risk of our composite CVD outcome was also significantly and independently associated with greater baseline walking disability ((aHR for use of a walking aid = 1.27, 95% CI 1.10–1.47, p = 0.001; aHR per unit increase in HAQ walking score = 1.17, 95% CI 1.08–1.27, p<0.001).ConclusionsAmong individuals with hip and/or knee OA, severity of OA disability was associated with a significant increase in all-cause mortality and serious CVD events after controlling for multiple confounders. Research is needed to elucidate modifiable mechanisms.

Impact of hypertension and renin–angiotensin system inhibitors in aortic stenosis

Experimental studies revealed that renin-angiotensin system (RAS) could play a crucial role in the pathophysiology of aortic stenosis (AS). The objectives of this study were to examine (i) the impact of hypertension on AS progression and clinical events and (ii) the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs). In this observational study, we retrospectively analysed clinical and Doppler echocardiographic data prospectively collected in 338 patients with AS. Patients were separated into four groups: patients without hypertension and not treated by RAS medication (Ctrl group), patients with hypertension but not treated by RAS medication (HTN group), patients treated with ACEIs, and patients treated with ARBs. AS progression rate was assessed by the annualized increase in peak aortic jet velocity. Compared with Ctrl group, patients in HTN group had faster stenosis progression (P=0·01). Patients on ARBs had slower AS progression compared with Ctrl (trend P=0·10) and HTN (P=0·002) groups, whereas patients on ACEIs had similar progression rate compared with Ctrl group (P=NS) but lower compared with HTN group (P=0·02). On multivariable analysis, compared with Ctrl group, HTN group was associated with faster AS progression rate (P=0·002), whereas ARBs with slower progression (P=0·0008). During a mean follow-up of 6·2±2·4years, HTN (hazard ratio [HR]=2·45; P=0·006) and ACEI (HR=2·30; P=0·01) groups were associated with a significant increase in all-cause mortality compared with Ctrl group, whereas ARB group (HR: 0·89; P=0·80) not. In multivariable analysis, HTN and ACEI groups remained associated with increased mortality. Hypertension is associated with significantly faster stenosis progression and higher incidence of clinical events in patients with AS. ARBs but not ACEs were found to abolish the increased risk of mortality associated with hypertension.

Company closure and mortality in a Greek bus company

Previous studies strongly support an association between unemployment and an increased risk of morbidity and mortality. To assess the impact of company closure on the mortality of redundant employees. The mortality of a cohort of male ex-employees of the Athens Bus Transportation Company Epixirisi Astikon Siginonion (EAS) was followed from September 1992 to October 1993. Information on causes of death was obtained from death certificates and classified according to the ninth revision of the International Classification of Diseases. The expected number of deaths was calculated based on 5 year age groups. Cause-specific mortality rates for the Greek population were obtained from the Greek National Statistics Service, and standardized mortality rates (SMRs) were calculated using population census data for 1991. The cohort consisted of 4400 subjects. Thirty deaths were recorded. Crude mortality was significantly elevated (SMR = 1.75; 95% confidence interval (CI) 1.18-2.5; Table 1). A statistically significant excess in mortality from ischaemic heart disease was shown (18 deaths observed; SMR = 4.83; 95% CI 2.86-7.64). One year before the privatization and closure of EAS (1991), nine deaths were recorded among its 7400 employees (SMR = 0.34). Our study found a significant increase in all-cause mortality and death from ischaemic heart disease in male workers who were made redundant and suggested a significant negative impact of unemployment resulting from company closure on mortality. These results may signal future mortality patterns in Greece if the current climate of austerity and recession continues.

Increased mortality among patients taking digoxin--analysis from the AFFIRM study

Digoxin is frequently used for rate control of atrial fibrillation (AF). It has, however, been associated with increased mortality. It remains unclear whether digoxin itself is responsible for the increased mortality (toxic drug effect) or whether it is prescribed to sicker patients with inherently higher mortality due to comorbidities. The goal of our study was to determine the relationship between digoxin and mortality in patients with AF. The association between digoxin and mortality was assessed in patients enrolled in the AF Follow-Up Investigation of Rhythm Management (AFFIRM) trial using multivariate Cox proportional hazards models. Analyses were conducted in all patients and in subsets according to the presence or absence of heart failure (HF), as defined by a history of HF and/or an ejection fraction <40%. Digoxin was associated with an increase in all-cause mortality [estimated hazard ratio (EHR) 1.41, 95% confidence interval (CI) 1.19-1.67, P < 0.001], cardiovascular mortality (EHR 1.35, 95% CI 1.06-1.71, P = 0.016), and arrhythmic mortality (EHR 1.61, 95% CI 1.12-2.30, P = 0.009). The all-cause mortality was increased with digoxin in patients without or with HF (EHR 1.37, 95% CI 1.05-1.79, P = 0.019 and EHR 1.41, 95% CI 1.09-1.84, P = 0.010, respectively). There was no significant digoxin-gender interaction for all-cause (P = 0.70) or cardiovascular (P = 0.95) mortality. Digoxin was associated with a significant increase in all-cause mortality in patients with AF after correcting for clinical characteristics and comorbidities, regardless of gender or of the presence or absence of HF. These findings call into question the widespread use of digoxin in patients with AF.

Is liver transplantation a risk factor for cardiovascular disease? a meta-analysis of observational studies

Up to two-thirds of patients develop metabolic syndrome within the first 5 years after orthotopic liver transplantation (OLT). However, data on overall cardiovascular (CV) morbidity and mortality among OLT recipients and particularly those who develop metabolic syndrome remain elusive. A literature search using MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and meeting abstracts (along with their bibliographies) was performed to identify studies. Data on ischemic CV events were extracted from each study and were used for pooled analyses. Overall pooled estimates and 95% confidence intervals (CIs) for the incidence of CV events and deaths were obtained with a random effects model. Twelve observational studies reporting CV outcomes for 4792 post-OLT recipients who were followed for 28,783 person-years were included. Pooled estimates showed that the 10-year risk of developing CV events among the post-OLT recipients was 13.6% (95% CI = 9%-8.1%). Pooled estimates from case-control studies showed that the post-OLT group had an approximately 64% greater risk of experiencing CV events than controls (standardized incidence ratio = 1.64, 95% CI = 1.18-2.20). Among OLT recipients, those with metabolic syndrome were approximately 4 times more likely to have a CV event [odds ratio (OR) = 4.01, 95% CI = 1.94-8.32] without any significant increase in all-cause mortality (OR = 1.15, 95% CI = 0.63-2.10). In conclusion, this systematic review suggests that OLT recipients and particularly those with metabolic syndrome have a high risk for CV events. However, the literature is limited and lacks high-quality studies. Future prospective studies are warranted to confirm these findings and determine whether aggressive risk-reduction strategies can attenuate the increased CV risk seen in this population.

Baseline Q waves as a prognostic modulator in patients with ST-segment elevation: insights from the PLATO trial

Baseline Q waves may provide additional value compared with time from the onset of symptoms in predicting outcomes for patients with ST-segment elevation. We evaluated whether baseline Q waves superseded time from symptom onset as a prognostic marker of one-year mortality in patients with ST-segment elevation acute coronary syndrome. Our study was derived from data from patients undergoing primary percutaneous coronary intervention within 24 hours in the PLATelet inhibition and patient Outcomes trial Q waves on the baseline electrocardiogram were evaluated by a blinded core laboratory. We assessed the associations between baseline Q waves and time from symptom onset to percutaneous coronary intervention with peak biomarkers, ST-segment resolution on the discharge electrocardiogram, and one-year all-cause and vascular mortality. Of 4341 patients with ST-segment elevation, 46% had baseline Q waves. Compared to those without Q waves, those with baseline Q waves were older, more frequently male, had higher heart rates, more advanced Killip class and had a longer time between the onset of symptoms and percutaneous coronary intervention. They also had higher one-year all-cause mortality than patients without baseline Q waves (baseline Q waves: 4.9%; no baseline Q waves: 2.8%; hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.29-2.45, p < 0.001). Complete ST-segment resolution was greatest and all-cause mortality lowest among those with symptom onset three hours or less before percutaneous coronary intervention and no baseline Q waves. After multivariable adjustment, baseline Q waves, but not time from symptom onset, were associated with a significant increase in all-cause mortality (adjusted HR 1.42, 95% CI 1.10-2.01, p = 0.046) and vascular mortality (adjusted HR 1.58, 95% CI 1.09-2.28, p = 0.02). The presence of baseline Q waves provides useful additional prognostic insight into the clinical outcome of patients with ST-segment elevation. Clinical Trials.gov registration no. NCT00391872.

The impact of prosthesis–patient mismatch on long-term survival after aortic valve replacement: a systematic review and meta-analysis of 34 observational studies comprising 27 186 patients with 133 141 patient-years

Numerous studies have linked prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) to adverse outcomes. Its correlation with long-term survival has been described but with contradicting results. This systematic review and meta-analysis of observational studies aims to determine the hazard of PPM after AVR. The Medline and EMBase databases were searched for English-language original publications. Two researchers independently screened studies and extracted data. Pooled estimates were obtained by random effects model. Subgroup analyses were performed to detect sources of heterogeneity. The search yielded 348 potentially relevant studies; 34 were included comprising 27 186 patients and 133 141 patient-years. Defined by the universally accredited indexed effective orifice area <0.85 cm(2)/m(2), 44.2% of patients were categorized as having PPM. In 34.2 and 9.8% of patients moderate (0.65-0.85 cm(2)/m(2)) and severe (<0.65 cm(2)/m(2)) PPM was present, respectively. Prosthesis-patient mismatch was associated with a statistically significant increase in all-cause mortality (HR = 1.34, 95% CI: 1.18-1.51), but only a trend to an increase in cardiac-related mortality (HR = 1.51, 95% CI: 0.88-2.60) was recognized. Analysis by severity of PPM demonstrated that both moderate and severe PPM increased all-cause mortality (HR = 1.19, 95% CI: 1.07-1.33 and HR = 1.84, 95% CI: 1.38-2.45) and cardiac-related mortality (HR = 1.32, 95% CI: 1.02-1.71 and HR = 6.46, 95% CI: 2.79-14.97). Further analyses showed a consistent effect over separate time intervals during follow-up. Prosthesis-patient mismatch is associated with an increase in all-cause and cardiac-related mortality over long-term follow-up. We recommend that current efforts to prevent PPM should receive more emphasis and a widespread acceptance to improve long-term survival after AVR.