Elderly heart failure patients and the role of beta-blocker therapy

In this article different aspects of chronic heart failure in old age are described. We mainly focus on the place of beta-blocker therapy in chronic heart failure. Beta-blockers are recommended for the treatment of stable chronic heart failure with left ventricular systolic dysfunction. There is additional information from recent studies that there is proven efficacy for beta-blocker therapy in patients with heart failure up to the age of 80 years. For patients with heart failure aged 80 and over the evidence to prescribe beta-blockers is limited. However, it is known that also in very elderly patients beta-blocker therapy is well tolerated. In patients with heart failure with preserved systolic ventricular function there is still no evidence that there is a beneficial effect of beta-blockers. It is still not clear if there are differences between beta-blocking agents. Of all beta-blockers, only bisoprolol, carvedilol, nebivolol and metoprolol CR are proven effective in stable chronic heart failure with impaired left ventricular systolic function and can be recommended in elderly patients on standard treatment with diuretics and ACE inhibition.     

Long-Term Use of Angiotensin Receptor Blockers and the Risk of Cancer

The association between angiotensin receptor blockers (ARBs) and cancer is controversial with meta-analyses of randomized controlled trials and observational studies reporting conflicting results. Thus, the objective of this study was to determine whether ARBs are associated with an overall increased risk of the four most common cancers, namely, lung, colorectal, breast and prostate cancers, and to explore these effects separately for each cancer type. We conducted a retrospective cohort study using a nested case-control analysis within the United Kingdom (UK) General Practice Research Database. We assembled a cohort of patients prescribed antihypertensive agents between 1995, the year the first ARB (losartan) entered the UK market, and 2008, with follow-up until December 31, 2010. Cases were patients newly-diagnosed with lung, colorectal, breast and prostate cancer during follow-up. We used conditional logistic regression to estimate adjusted rate ratios (RRs) and 95% confidence intervals (CIs) of cancer incidence, comparing ever use of ARBs with ever use of diuretics and/or beta-blockers. The cohort included 1,165,781 patients, during which 41,059 patients were diagnosed with one of the cancers under study (rate 554/100,000 person-years). When compared to diuretics and/or beta-blockers, ever use of ARBs was not associated with an increased rate of cancer overall (RR: 1.00; 95% CI: 0.96–1.03) or with each cancer site separately. The use of angiotensin-converting enzyme inhibitors and calcium channel blockers was associated with an increased rate of lung cancer (RR: 1.13; 95% CI: 1.06–1.20 and RR: 1.19; 95% CI: 1.12–1.27, respectively). This study provides additional evidence that the use of ARBs does not increase the risk of cancer overall or any of the four major cancer sites. Additional research is needed to further investigate a potentially increased risk of lung cancer with angiotensin-converting enzyme inhibitors and calcium channel blockers.     

Prediction of all-cause mortality with hypoalbuminemia in patients with heart failure: a meta-analysis

Abstract

Objective: The prognostic utility of serum albumin level for mortality in heart failure patients has received considerable attention. This meta-analysis sought to examine the prognostic significance of hypoalbuminemia for prediction of all-cause mortality in patients with heart failure.

Materials and methods: Pubmed and Embase databases were systematically searched up to 10 March 2019 to identify eligible studies. Epidemiological studies reporting a multivariable-adjusted risk estimate of all-cause mortality associated with hypoalbuminemia in acute or chronic heart failure patients were included.

Results: Nine studies from 10 articles involving 16,763 heart failure patients were included in the final analysis. Hypoalbuminemia was associated with an increased in-hospital mortality (risk ratio [RR] 4.90; 95% confidence interval [CI] 2.96–8.10) and long-term all-cause mortality (RR 1.75; 95% CI 1.35–2.27) in acute heart failure patients. Chronic heart failure patients with hypoalbuminemia exhibited a 3.5-fold (95% CI 1.29–9.73) higher risk for long-term all-cause mortality.

Conclusions: Hypoalbuminemia is possibly an independent predictor of all-cause mortality in patients with acute or chronic heart failure. However, the current findings should be further confirmed in future prospective studies. Moreover, future well-designed randomized controlled trials would be required to investigate whether correcting hypoalbuminemia in heart failure patients has potential to improve survival outcome.     

Heart Failure Care in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis

Background

Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs.

Methods and Findings

Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval [CI]: 49%–64%) of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%–41%) with beta-blockers, and 32% (95% CI: 25%–39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%–7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%–10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified.

Conclusions

The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed. Please see later in the article for the Editors'' Summary     

Cardioprotection by aldosterone receptor antagonism in heart failure. Part I. The role of aldosterone in heart failure

In recent years understanding of the role of aldosterone has expanded beyond the known classic effects of promoting renal sodium retention and potassium and magnesium loss. It is now well documented that aldosterone causes myocardial and perivascular fibrosis, blocks the myocardial uptake of norepinephrine, and increases plasminogen activator inhibitor levels. In conjunction with angiotensin II, aldosterone causes vascular damage, endothelial dysfunction, and decreased vascular compliance. Therefore, the renin-angiotensin-aldosterone system (RAAS) plays a major role in the development of both hypertension and heart failure and is therefore, a key target for therapeutic interventions. Commonly prescribed medications for control of hypertension and congestive heart failure are inhibitors of the RAAS, including angiotensin converting enzyme inhibitors (ACE-I) and Angiotensin II (A-II) receptor antagonists. There is a well-documented increase in aldosterone levels that occurs over several months during chronic treatment with an ACE-I or A-II receptor antagonist. Such suppression of circulating aldosterone however, is transient, as exemplified by the term "escape" used to describe the phenomenon. This rebound of aldosterone even occurs when patients receive both an ACE-I and A-II receptor antagonist. In addition, ACE-I and A-II receptor antagonists are less effective in controlling BP in the estimated 60% of hypertensive patients who are salt (volume) sensitive and more prone to hypertension-associated morbidity such as black patients and type 2 diabetics. Thus chronic and complete blockade of aldosterone action requires an aldosterone receptor antagonist. The "Randomized Aldactone Evaluation Study" (RALES) trial results in patients with severe heart failure NYHA class III or IV and a left ventricular ejection fraction of no more than 35 percent showed that administration of a sub-hemodynamic dose of spironolactone (25 mg a day) as an add on therapy to ACE-I plus standard treatment resulted in a significant mortality reduction due both to decreased death from progressive heart failure and sudden cardiac death. These findings support the pivotal role of aldosterone in the pathophysiology of progressive heart failure. Although it is an effective antialdosterone agent, widespread use of spironolactone in humans is limited by its tendency to produce undesirable sexual side effects. At standard doses, impotence and gynaecomastia can be induced in men, whereas pre-menopausal women may experience menstrual disturbances. Data on a selective aldosterone receptor antagonist, eplerenone, appear promising for the effective blockade of aldosterone and its harmful effects without the sexual disturbances of spironolactone. Recently Eplerenone was successfully introduced for the treatment of hypertension and heart failure. Growing number of experimental studies are finding a broader role for Aldosterone in driving the pathophysiology of both heart failure and hypertension. When added to conventional therapy aldosterone receptor blockers show benefits which are in addition to those conferred by ACE-I and/or AII receptor blockers.     

Prevalence,incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large‐scale meta‐analysis of 3,211,768 patients and 113,383,368 controls

People with severe mental illness (SMI) – schizophrenia, bipolar disorder and major depressive disorder – appear at risk for cardiovascular disease (CVD), but a comprehensive meta‐analysis is lacking. We conducted a large‐scale meta‐analysis assessing the prevalence and incidence of CVD; coronary heart disease; stroke, transient ischemic attack or cerebrovascular disease; congestive heart failure; peripheral vascular disease; and CVD‐related death in SMI patients (N=3,211,768) versus controls (N=113,383,368) (92 studies). The pooled CVD prevalence in SMI patients (mean age 50 years) was 9.9% (95% CI: 7.4‐13.3). Adjusting for a median of seven confounders, patients had significantly higher odds of CVD versus controls in cross‐sectional studies (odds ratio, OR=1.53, 95% CI: 1.27‐1.83; 11 studies), and higher odds of coronary heart disease (OR=1.51, 95% CI: 1.47‐1.55) and cerebrovascular disease (OR=1.42, 95% CI: 1.21‐1.66). People with major depressive disorder were at increased risk for coronary heart disease, while those with schizophrenia were at increased risk for coronary heart disease, cerebrovascular disease and congestive heart failure. Cumulative CVD incidence in SMI patients was 3.6% (95% CI: 2.7‐5.3) during a median follow‐up of 8.4 years (range 1.8‐30.0). Adjusting for a median of six confounders, SMI patients had significantly higher CVD incidence than controls in longitudinal studies (hazard ratio, HR=1.78, 95% CI: 1.60‐1.98; 31 studies). The incidence was also higher for coronary heart disease (HR=1.54, 95% CI: 1.30‐1.82), cerebrovascular disease (HR=1.64, 95% CI: 1.26‐2.14), congestive heart failure (HR=2.10, 95% CI: 1.64‐2.70), and CVD‐related death (HR=1.85, 95% CI: 1.53‐2.24). People with major depressive disorder, bipolar disorder and schizophrenia were all at increased risk of CVD‐related death versus controls. CVD incidence increased with antipsychotic use (p=0.008), higher body mass index (p=0.008) and higher baseline CVD prevalence (p=0.03) in patients vs. controls. Moreover, CVD prevalence (p=0.007), but not CVD incidence (p=0.21), increased in more recently conducted studies. This large‐scale meta‐analysis confirms that SMI patients have significantly increased risk of CVD and CVD‐related mortality, and that elevated body mass index, antipsychotic use, and CVD screening and management require urgent clinical attention.     

The Association of Cardioprotective Medications with Pneumonia-Related Outcomes

Introduction

Little research has examined whether cardiovascular medications, other than statins, are associated with improved outcomes after pneumonia. Our aim was to examine the association between the use of beta-blockers, statins, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) with pneumonia-related outcomes.

Materials and Methods

We conducted a retrospective population-based study on male patients ≥65 years of age hospitalized with pneumonia and who did not have pre-existing cardiac disease. Our primary analyses were multilevel regression models that examined the association between cardiovascular medication classes and either mortality or cardiovascular events.

Results

Our cohort included 21,985 patients: 22% died within 90 days of admission, and 22% had a cardiac event within 90 days. The cardiovascular medications studied that were associated with decreased 90-day mortality included: statins (OR 0.70, 95% CI 0.63–0.77), ACE inhibitors (OR 0.82, 95% CI 0.74–0.91), and ARBs (OR 0.58, 95% CI 0.44–0.77). However, none of the medications were significantly associated with decreased cardiovascular events.

Discussion

While statins, ACE inhibitors, and ARBs, were associated with decreased mortality, there was no significant association with decreased CV events. These results indicate that this decreased mortality is unlikely due to their potential cardioprotective effects.     

Case-control study of factors associated with chronic Chagas heart disease in patients over 50 years of age

A case-control study on chronic Chagas heart disease (CCHD) was carried out between 1997 and 2005. Ninety patients over 50 years of age were examined for factors related to (CCHD). Fourty-six patients (51.1%) with Chagas heart disease (anomalous ECG) were assigned to the case group and 44 (48.9%) were included in the control group as carriers of undetermined forms of chronic disease. Social, demographic (age, gender, skin color, area of origin), epidemiological (permanence within an endemic zone, family history of Chagas heart disease or sudden death, physical strain, alcoholism, and smoking), and clinical (systemic hypertension) variables were analyzed. The data set was assessed through single-variable and multivariate analysis. The two factors independently associated with heart disease were age--presence of heart disease being three times higher in patients over 60 years of age (odds ratio, OR: 2.89; confidence interval of 95%: 1.09-7.61)--and family history of Chagas heart disease (OR: 2.833, CI 95%: 1.11-7.23). Systemic hypertension and gender did not prove to hold any association with heart disease, as neither did skin color, but this variable showed low statistical power due to reduced sample size.     

Heart failure and angiotensin converting enzyme inhibition: problems and perspectives.

Heart failure has become the most widely studied syndrome in cardiology over the recent years. Despite the encouraging achievements by angiotensin converting enzyme (ACE) inhibitors, the mortality of patients with chronic heart failure remains high. There are several factors which can potentially be responsible for the fact that about 80% of patients with a failing heart defy protection by ACE inhibitors: different activation of tissue and systemic renin-angiotensin system (RAS) in a particular heart disease and the distinct ability of various ACE inhibitors to block cardiac ACE, alternative pathways for angiotensin II formation (chymase), genetic polymorphism of the RAS system and the complexity of neuroendocrine activation. Moreover, chronic heart failure can provoke disturbances in the reactivity of peripheral vessels and metabolism of striated muscles. These factors may then potentiate the vicious circle of heart failure. New therapeutic approaches, which could further reduce the mortality in patients with heart failure involve angiotensin II type 1 receptor antagonists, beta-blockers, aldosterone antagonists and blockers of the endothelin receptor. A number of questions associated with functions of the RAS still remain open and their solution could be of substantial benefit for patients with a failing heart.     

Meta-Analysis of Combined Therapy with Angiotensin Receptor Antagonists versus ACE Inhibitors Alone in Patients with Heart Failure

Background

There is insufficient evidence whether the benefit of adding angiotensin II receptor blockers (ARBs) to angiotensin-converting enzyme (ACE) inhibitors outweighs the increased risk of adverse effects in patients with heart failure.

Methodology/Principal Findings

Two independent reviewers searched and abstracted randomized controlled trials of ARBs and ACE inhibitors compared to ACE inhibitor therapy alone in patients with heart failure reporting mortality and hospitalizations having a follow-up of at least 6 months identified by a systematic literature search. Eight trials including a total of 18,061 patients fulfilled our inclusion criteria. There was no difference between patients treated with combination therapy and ACE inhibitor therapy alone for overall mortality, hospitalization for any reason, fatal or nonfatal MI. Combination therapy was, however, associated with fewer hospital admissions for heart failure (RR 0.81, 95%CI 0.72–0.91), although there was significant heterogeneity across trials (p-value for heterogeneity = 0.04; I² = 57% [95%CI 0–83%]). Patients treated with combination therapy had a higher risk of worsening renal function and symptomatic hypotension, and their trial medications were more often permanently discontinued. Lack of individual patient data precluded the analysis of time-to-event data and identification of subgroups which potentially benefit more from combination therapy such as younger patients with preserved renal function and thus at lower risk to experience worsening renal function or hyperkalemia.

Conclusions/Significance

Combination therapy with ARBs and ACE inhibitors reduces admissions for heart failure in patients with congestive heart failure when compared to ACE inhibitor therapy alone, but does not reduce overall mortality or all-cause hospitalization and is associated with more adverse events. Thus, based on current evidence, combination therapy with ARBs and ACE inhibitors may be reserved for patients who remain symptomatic on therapy with ACE inhibitors under strict monitoring for any signs of worsening renal function and/or symptomatic hypotension.     

Outcomes and Characteristics of Patients Undergoing Percutaneous Angioplasty Followed by Below-Knee or Above-Knee Amputation for Peripheral Artery Disease

Objective

Little is known about long-term outcomes among patients who receive percutaneous angioplasty (PTA) for peripheral artery disease (PAD) then undergo below-knee or above-knee amputations. We sought to determine clinical outcomes associated with below-knee or above-knee amputation, along with possible explanatory factors and treatment strategies.

Methods

Using data from Taiwan’s National Health Insurance Research Database from 1997 to 2010, 7,568 adult patients were divided into three groups: lower extremity preserved (LE), below-knee amputation (BK) and above-knee amputation (AK). We assessed outcomes including major adverse cardiovascular events (MACE) and associated risk factors.

Results

Overall MACE was significantly higher in the AK group compared to the LE and BK groups, over a mean follow-up of 2.45 years (hazard ratio [HR]: 1.81; 95% confidence interval [CI]: 1.50–2.18 for AK vs. LE; HR: 1.67; 95% CI: 1.36–2.06 for AK vs. BK). However MACE were similar for the BK and LE groups (HR: 1.08; 95% CI: 0.98–1.20). Overall mortality was highest in the AK group (HR: 1.65, 95% CI: 1.34–2.04 for AK vs. BK). As for patient characteristics, atrial fibrillation was more prevalent in the AK group than in the BK group (17% vs. 7%). Independent risk factors associated with death after above- or below-knee amputation included advanced age, heart failure, dialysis, male gender and high patient volume.

Conclusion

The MACE rate was highest in the AK group, whereas the LE and BK groups were similar in this regard. Furthermore, overall mortality increased with larger area of amputation.     

Mortalidad y factores pronósticos asociados en pacientes ancianos y muy ancianos hospitalizados con infección respiratoria COVID-19

IntroductionElderly patients with COVID-19 has a worse clinical evolution, being more susceptible to develop serious manifestations. The differences between the elderly and very elderly population, mortality and associated prognostic factors of SARS-CoV-2 infection have not been enough studied yet.MethodsAn observational study of 416 elderly patients admitted consecutively to Hospital General Universitario de Ciudad Real for COVID-19 respiratory infection from March 1st to April 30th, 2020. Data were collected including patient demographic information, medical history, clinical characteristics, laboratory data, therapeutic interventions and clinical outcomes during the hospitalization and after discharge, until June 15, 2020 with the aim of analyzing mortality, and associated prognostic factors.ResultsThe mean age was 84.43 ± 5.74 years old; elderly patients (75-84 years) were 50.2% of the sample and very elderly (≥ 85 years) the remaining 49.8%. In Cox regression model, mortality rate was higher in very elderly group (HR = 2.58; 95% CI: 1.23-5.38; P = .01), hypertensive (HR = 3, 45; 95% CI: 1.13-10.5; P = .03) and chronic kidney disease patients (HR = 3.86; 95% CI: 1.3-11.43; P = .02). In contrast, calcium antagonists (HR = 0.27; 95% CI: 0.12-0.62; P = .002) and anticoagulant therapy during hospitalization (HR = 0.26; 95% CI: 0.08 0, 83; P = .02) were associated with a longer time free of mortality.ConclusionsMortality rate was higher in very eldery patients compared with eldery; and in hypertensive and chronic kidney disease patients. Anticoagulation therapy and calcium chanel bloquers treatment during hospitalization were associated with a higher survival in the short-term follow-up in patients hospitalized with COVID-19.     

Identification of a metabolic signature for multidimensional impairment and mortality risk in hospitalized older patients

A combination of several metabolic and hormonal adaptations has been proposed to control aging. Little is known regarding the effects of multiple deregulations of these metabolic and hormonal systems in modulating frailty and mortality in hospitalized elderly patients. We measured 17 biological serum parameters from different metabolic/hormonal pathways in 594 hospitalized elderly patients followed up to 1 year who were stratified into three groups according to their multidimensional impairment, evaluated by a Comprehensive Geriatric Assessment (CGA)‐based Multidimensional Prognostic Index (MPI). The mortality incidence rates were 7% at 1 month and 21% at 1 year. Our data show that frailty and mortality rate were positively associated with chronic inflammation and with a down‐regulation of multiple endocrine factors. Of the 17 biomarkers examined, blood levels of IGF‐1, triiodothyronine, C‐reactive protein, erythrocyte sedimentation rate, white blood cell and lymphocyte counts, iron, albumin, total cholesterol, and LDL‐c were significantly associated with both MPI severity grade and mortality. In multivariate Cox proportional hazard model, the following biomarkers most strongly predicted the risk of mortality (adjusted hazard ratio (HR) per 1 quintile increment in predictor distribution): IGF‐1 HR = 0.71 (95% CI: 0.63–0.80), CRP HR = 1.48 (95% CI: 1.32–1.65), hemoglobin HR = 0.82 (95% CI: 0.73–0.92), and glucose HR = 1.17 (95% CI: 1.04–1.30). Multidimensional impairment assessed by MPI is associated with a distinctive metabolic ‘signature’. The concomitant elevation of markers of inflammation, associated with a simultaneous reduction in multiple metabolic and hormonal factors, predicts mortality in hospitalized elderly patients.     

血清NLR、GDF-15及TRPC1与老年心力衰竭患者相关性分析

摘要 目的：探讨血清中性粒细胞与淋巴细胞比值（NLR）、生长分化因子-15（GDF-15）及瞬时受体电位通道1（TRPC1）与老年心力衰竭患者相关性。方法：选取我院2020年1月到2022年10月收治的100例老年慢性心力衰竭患者作为研究对象,将其分为心力衰竭组,另选取同期来我院体检的101名健康老年人作为对照组,98例心律失常老年患者作为心律失常组,对比三组受检者血清NLR、GDF-15及TRPC1水平,并应用受试者工作（ROC）曲线分析血清NLR、GDF-15及TRPC1对老年慢性心力衰竭的诊断价值。并依照NYHA心功能分级标准对100例心力衰竭患者进行评价,其中Ⅱ级23例,Ⅲ级38例,Ⅳ级39例,对比不同心功能分级患者血清NLR、GDF-15及TRPC1表达水平,应用Spearman相关分析分析血清NLR、GDF-15及TRPC1与老年心力衰竭患者心功能的相关性。结果：三组受检者血清NLR、GDF-15及TRPC1水平对比差异显著,心力衰竭组明显高于心律失常组和对照组（P＜0.05）;通过绘制ROC曲线,分析表1中组间具有明显差异的指标,确定其对老年心力衰竭的诊断效能,结果显示,曲线下面积（AUC）从依次为NLR（0.688）、GDF-15（0.667）、TRPC1（0.656）、三者联合（0.671）。NLR诊断灵敏度为67.61 %,特异度为66.85 %,GDF-15诊断灵敏度为60.03 %,特异度为67.53 %,TRPC1诊断灵敏度为61.24 %,特异度为66.53 %,三者联合诊断灵敏度为74.58 %,特异度为86.32 %;不同级别心功能的心力衰竭患者血清NLR、GDF-15及TRPC1水平对比差异显著,Ⅳ级心功能明显高于Ⅲ级、Ⅱ级（P＜0.05）;Spearman相关分析结果显示：NLR、GDF-15及TRPC1水平与老年心力衰竭患者心功能呈正相关（P＜0.05）。结论：血清NLR、GDF-15及TRPC1三者联合对于老年心力衰竭诊断灵敏度和特异度较高,且与患者心功能具有明显相关性,临床可考虑应用NLR、GDF-15及TRPC1作为超声心动图补充诊断手段,为临床诊断提供参考意见。     

Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study

Background

Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI).

Methods

Population-based cohort study of patients diagnosed with incident heart failure during 2000–2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease.

Results

39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08–1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35–1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86–1.15 and 0.94, 95% CI: 0.89–1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes.

Conclusions

Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.     

Predictors for Stroke and Death in Non-Anticoagulated Asian Patients with Atrial Fibrillation: The Fushimi AF Registry

Background

Atrial fibrillation (AF) increases the risk of stroke and death. Data on the predictors for stroke and death in ‘real-world’ AF patients are limited, especially from large prospective Asian cohorts.

Methods

The Fushimi AF Registry is a community-based prospective survey designed to enroll all AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,304 patients (median follow-up period 741 days). We explored the predictors for ‘death, stroke, and systemic embolism (SE)’ during follow-up in 1,541 patients not receiving oral anticoagulants (OAC) at baseline.

Results

The mean age was 73.1 ± 12.5 years, and 673 (44%) patients were female. The mean CHADS₂ and CHA₂DS₂-VASc scores were 1.76 and 3.08, respectively. Cumulative events were as follows: stroke/SE in 61 (4%) and death in 230 (15%), respectively. On multivariate analysis, advanced age (hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.24–2.29), underweight (body mass index <18.5 kg/m²) (HR: 1.71, 95% CI: 1.25–2.32), previous stroke/SE/transient ischemic attack (HR: 1.70, 95% CI: 1.25–2.30), heart failure (HR: 1.59, 95% CI: 1.17–2.15), chronic kidney disease (HR: 1.53, 95% CI: 1.16–2.02), and anemia (HR: 2.41, 95% CI: 1.78–3.28) were independent predictors for death/stroke/SE. Cumulative numbers of these 6 risk predictors could stratify the incidence of death/stroke/SE in patients without OAC, as well as those with OAC in our registry.

Conclusions

Advanced age, underweight, previous stroke/SE/transient ischemic attack, heart failure, chronic kidney disease, and anemia were independently associated with the risk of death/stroke/SE in non-anticoagulated Japanese AF patients.     

Reappraisal of Metformin Efficacy in the Treatment of Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials

Background

The UK Prospective Diabetes Study showed that metformin decreases mortality compared to diet alone in overweight patients with type 2 diabetes mellitus. Since then, it has been the first-line treatment in overweight patients with type 2 diabetes. However, metformin-sulphonylurea bitherapy may increase mortality.

Methods and Findings

This meta-analysis of randomised controlled trials evaluated metformin efficacy (in studies of metformin versus diet alone, versus placebo, and versus no treatment; metformin as an add-on therapy; and metformin withdrawal) against cardiovascular morbidity or mortality in patients with type 2 diabetes. We searched Medline, Embase, and the Cochrane database. Primary end points were all-cause mortality and cardiovascular death. Secondary end points included all myocardial infarctions, all strokes, congestive heart failure, peripheral vascular disease, leg amputations, and microvascular complications. Thirteen randomised controlled trials (13,110 patients) were retrieved; 9,560 patients were given metformin, and 3,550 patients were given conventional treatment or placebo. Metformin did not significantly affect the primary outcomes all-cause mortality, risk ratio (RR) = 0.99 (95% CI: 0.75 to 1.31), and cardiovascular mortality, RR = 1.05 (95% CI: 0.67 to 1.64). The secondary outcomes were also unaffected by metformin treatment: all myocardial infarctions, RR = 0.90 (95% CI: 0.74 to 1.09); all strokes, RR = 0.76 (95% CI: 0.51 to 1.14); heart failure, RR = 1.03 (95% CI: 0.67 to 1.59); peripheral vascular disease, RR = 0.90 (95% CI: 0.46 to 1.78); leg amputations, RR = 1.04 (95% CI: 0.44 to 2.44); and microvascular complications, RR = 0.83 (95% CI: 0.59 to 1.17). For all-cause mortality and cardiovascular mortality, there was significant heterogeneity when including the UK Prospective Diabetes Study subgroups (I ² = 41% and 59%). There was significant interaction with sulphonylurea as a concomitant treatment for myocardial infarction (p = 0.10 and 0.02, respectively).

Conclusions

Although metformin is considered the gold standard, its benefit/risk ratio remains uncertain. We cannot exclude a 25% reduction or a 31% increase in all-cause mortality. We cannot exclude a 33% reduction or a 64% increase in cardiovascular mortality. Further studies are needed to clarify this situation. Please see later in the article for the Editors'' Summary     

National assessment of recommendations from healthcare providers for smoking cessation among adults with cancer

Cancer survivors benefit from evidence-based smoking cessation treatment. A crucial first step in this process is a clinician recommending that the patient quit smoking. However, contemporary delivery of advice to quit among patients with cancer is not well known. In a cross-sectional analysis of all adult smokers included in a prospective population-representative study of US adults, we analyzed the frequency that patients reported receiving advice to quit smoking from a healthcare professional according to reported cancer history (no cancer, tobacco-related cancer, non-tobacco related cancer history). Among an estimated 28.3 million smokers, 9.3% reported a history of cancer, 48.8% of which were tobacco-related cancers. In general, advice to quit was reported by more (67.8%) cancer survivors than those adults without any cancer (56.0%). After adjustment for sociodemographic factors, smokers with a non tobacco-related cancer (0.51, 95% CI 0.32–0.83) and those without any cancer history (0.43, 95% CI 0.30–0.63) were both less likely to report being advised to quit smoking than patients with a tobacco-related cancer history.     

The predictive value of plasma catestatin for all-cause and cardiac deaths in chronic heart failure patients

Catestatin (CST) is a proteolytic fragment of Chromogranin A with a broad spectrum of activities in the cardiovascular system. The level of plasma CST increases in chronic heart failure patients, but its potential relationship to patient prognosis is unknown. In this study, we measured plasma CST levels in 202 chronic heart failure patients and followed them for a median of 52.5 months. The plasma CST level was higher in patients with all-cause death and cardiac death than in survivors. According to univariate COX regression, higher plasma CST levels predicted increased risk of all-cause and cardiac death. After adjustment for other confounding factors, plasma CST was an independent risk factor for both outcomes, and the hazard ratios (HRs) were 1.84 (95% CI: 1.02–3.32, p = 0.042) and 2.41 (95% CI: 1.26–4.62, p = 0.008) for all-cause death and cardiac death, respectively. The new risk-predictive model considering CST was superior to the previous model for both outcomes by ANOVA and likelihood ratio tests (p = 0.040 and p = 0.008, respectively). Concurrent increases in plasma BNP (B-type natriuretic peptide) and CST levels predicted the highest risk for both all-cause and cardiac deaths [HR = 5.18 (95% CI: 1.94–13.87, p = 0.001) and HR = 9.19 (95% CI: 2.75–30.78, p < 0.001), respectively]. Large-scale studies are needed to further assess the value of plasma CST in predicting heart failure prognosis.     

Pre-existing diseases of patients increase susceptibility to hypoxemia during gastrointestinal endoscopy

Hypoxemia is the most common adverse event that happened during gastrointestinal endoscopy. To estimate risk of hypoxemia prior to endoscopy, American Society of Anesthesiology (ASA) classification scores were used as a major predictive factor. But the accuracy of ASA scores for predicting hypoxemia incidence was doubted here, considering that the classification system ignores much information about general health status and fitness of patient that may contribute to hypoxemia. In this retrospective review of clinical data collected prospectively, the data on 4904 procedures were analyzed. The Pearson's chi-square test or the Fisher exact test was employed to analyze variance of categorical factors. Continuous variables were statistically evaluated using t-tests or Analysis of variance (ANOVA). As a result, only 245 (5.0%) of the enrolled 4904 patients were found to present hypoxemia during endoscopy. Multivariable logistic regressions revealed that independent risk factors for hypoxemia include high BMI (BMI 30 versus 20, Odd ratio: 1.52, 95% CI: 1.13-2.05; P?=?0.0098), hypertension (Odd ratio: 2.28, 95% CI: 1.44-3.60; P?=?0.0004), diabetes (Odd ratio: 2.37, 95% CI: 1.30-4.34; P?=?0.005), gastrointestinal diseases (Odd ratio: 1.77, 95% CI: 1.21-2.60; P?=?0.0033), heart diseases (Odd ratio: 1.97, 95% CI: 1.06-3.68; P?=?0.0325) and the procedures that combined esophagogastroduodenoscopy (EGD) and colonoscopy (Odd ratio: 4.84, 95% CI: 1.61-15.51; P?=?0.0292; EGD as reference). It is noteworthy that ASA classification scores were not included as an independent predictive factor, and susceptibility of youth to hypoxemia during endoscopy was as high as old subjects. In conclusion, some certain pre-existing diseases of patients were newly identified as independent risk factors for hypoxemia during GI endoscopy. High ASA scores are a confounding predictive factor of pre-existing diseases. We thus recommend that youth (≤18 yrs), obese patients and those patients with hypertension, diabetes, heart diseases, or GI diseases should be monitored closely during sedation endoscopy.