1 Introduction Major and profound changes have taken place in China over the past 30 years. An epidemic of cardiovascular diseases （CVD） in China is emerging as a result of lifestyle changes, urbanization, and the accelerated process of aging. The incidence of CVD is continuously increasing and will remain an upward trend in the next decade. Since 2005,
Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Iuflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction （AMI）, Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes （such as death, recurrent myocardial in- farction, and heart failure） in patients with AMI.
Background Liraglutide is glucagon-like peptide-1 receptor agonist for treating patients with type 2 diabetes mellitus. Our previous studies have demonstrated that liraglutide protects cardiac function through improving endothelial function in patients with acute myocardial infarction undergoing percutaneous coronary intervention. The present study will investigate whether liraglntide can perform direct protective effects on cardiomyocytes against reperfusion injury. Methods In vitro experiments were performed using H9C2 cells and neonatal rat ventricular cadiomyocytes undergoing simulative hypoxia/reoxygenation （H/R） induction. Cardiomyocytes apoptosis was detected by fluorescence TUNEL. Mitochondrial membrane potential （AWm） and intracellular reactive oxygen species （ROS） was assessed by JC-1 and DHE, respectively. Fura-2/AM was used to measure intracellular Ca2＋ concentration and calcium transient. Immtmofluorescence staining was used to assess the expression level of sarcoplasmic reticulum Ca2＋-ATPase （SERCA2a）. In vivo experiments, myocardial apoptosis and expression of SERCA2a were detected by colorimetric TUNEL and by immunofluorescence staining, respectively. Results In vitro liraglutide inhibited cardiomyotes apoptosis against H/R. △mψ of cardiomyocytes was higher in liraglntide group than H/R group. H/R increased ROS production in H9C2 cells which was attenuated by liraglutide. Liraglutide significantly lowered Ca2＋ overload and improved calcium transient compared with H/R group, lmmunofluorescence staining results showed liraglutide promoted SERCA2a expression which was decreased in H/R group. In ischemia/reperfusion rat hearts, apoptosis was significantly attenuated and SERCA2a expression was increased by liraglutide compared with H/R group. Conclusions Liraglutide can directly protect cardiomyocytes against reperfusion injury which is possibly through modulation of intracellular calcium homeostasis.
Cardiovascular disease （CVD） is the leading cause of death and disability worldwide. The primary prevention of CVD is dependent upon the ability to identify high-risk individuals long before the development of overt events. This highlights the need for accurate risk strati- fication. An increasing number of novel biomarkers have been identified to predict cardiovascular events. Biomarkers play a critical role in the definition, prognostication, and decision-making regarding the management of cardiovascular events. This review focuses on a variety of promising biomarkers that provide diagnostic and prognostic information. The myocardial tissue-specific biomarker cardiac troponin, high- sensitivity assays for cardiac troponin, and heart-type fatty acid binding proteinall help diagnose myocardial infarction （MI） in the early hours following symptoms. Inflammatory markers such as growth differentiation factor-15, high-sensitivity C-reactive protein, fibrinogen, and uric acid predict MI and death. Pregnancy-associated plasma protein A, myeloperoxidase, and matrix metalloproteinases predict the risk of acute cor- onary syndrome. Lipoprotein-associated phospholipase A2 and secretory phospholipase A2 predict incident and recurrent cardiovascular events. Finally, elevated natriuretic peptides, ST2, endothelin-1, mid-regional-pro-adrenomedullin, copeptin, and galectin-3 have all been well validated to predict death and heart failure following a MI and provide risk stratification information for heart failure. Rapidly develop- ing new areas, such as assessment ofmicro-RNA, are also explored. All the biomarkers reflect different aspects of the development ofather- osclerosis.
Cognitive damage in heart failure （HF） involves different domains thus interfering with the ability for single patient to self-care and to cope with treatment regimens, modifying symptoms and health behaviours. Many cerebral and functional changes were detected in brain imaging, involving areas of both grey and white matter deputed to cognition. Although various instruments are available to explore cognition, no consensus was obtained on better tools to be used in HF population. Reduction in cerebral blood flow, decreased cardiac output, altera-tions of cerebrovascular reactivity and modification of blood pressure levels are the main features involved in the etiopathogenetic mecha-nisms of cognitive deficit. Several cardiac variables, laboratory parameters, demographic and clinical elements were studied for their possible relation with cognition and should be properly evaluated to define patients at increased risk of impairment. The present review gathers avail-able data pointing out assured information and discussing possible areas of research development.
Research to date indicates that the number of coronary artery bypass graft （CABG） surgery patients affected by depression （i.e., major, minor, dysthymia） approximates between 30% and 40% of all cases. A longstanding empirical interest on psychosocial factors in CABG surgery patients highlights an association with increased risk of morbidity in the short and longer term. Recent evidence suggests that both depression and anxiety increase the risk for mortality and morbidity after CABG surgery independent of medical factors, although the behavioral and biological mechanisms are poorly understood. Though neither depression nor anxiety seem to markedly affect neuropsy- chological dysfunction, depression confers a risk for incident delirium. Following a comprehensive overview of recent literature, practical advice is described for clinicians taking into consideration possible screening aids to improve recognition of anxiety and depression among CABG surgery patients. An overview of contemporary interventions and randomized, controlled trials are described, along with suggestions for future CABG surgery research.
The flow properties of blood play significant roles in tissue perfusion by contributing to hydrodynamic resistance in blood vessels. These properties are influenced by pathophysiological processes, thereby increasing the clinical relevance of blood rheology information. There is well-established clinical evidence for impaired blood fluidity in humans of advanced age, including enhanced plasma and whole blood viscosity, impaired red blood cell (RBC) deformability and enhanced RBC aggregation. Increased plasma fibrinogen concentration is a common finding in many studies owing to the pro-inflammatory condition of aged individuals; this finding of increased fibrinogen concentration explains the higher plasma viscosity and RBC aggregation in elderly subjects. Enhanced oxidant stress in advanced age is also known to contribute to altered blood fluidity, with RBC deformability being an important determinant of blood viscosity. Several studies have shown that physical activity may improve the hemorheological picture in elderly subjects, yet well-designed observational and mechanistic studies are required to determine the specific effects of regular exercise on hemorheological parameters in healthy and older individuals.
A sensitive and selective liquid chromatography mass spectrometry method was developed for the determination of rhynchophylline in rat plasma. After the addition of estazolam as the internal standard (IS), protein precipitation by acetonitrile was used for sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 column (2.1 × 150 mm, 5 µm) with acetonitrile–0.1% formic acid as the mobile phase with gradient elution. The electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification by using target fragment ions m/z 385 for rhynchophylline and m/z 295 for the IS. Calibration plots were linear over the range of 5–500 ng/mL for rhynchophylline in plasma. The lower limit of quantification for rhynchophylline was 5 ng/mL. The mean recovery of rhynchophylline from plasma was in the range of 87.7–92.6%. The coefficients of variation of intra-day and inter-day precision were both less than 11%. This method is sensitive and selective enough to be used in pharmacokinetic research for the determination of rhynchophylline in rat plasma.
Objective Coronary artery ectasia (CAE) refers to abnormal dilation of coronary artery segments to 1.5 times of adjacent normal ones. Epicardial fat is associated with cardiovascular risk factors. The relationship between CAE and epicardial fat has not yet been investigated. This study aimed to assess the relationship between CAE and epicardial fat volume (EFV) in older people by dual-source computed tomography coronary angiography (CTCA). Methods We prospectively enrolled 1400 older adults who were scheduled for dual-source CTCA. Under reconstruction protocols, patients with abnormal segments 1.5 times larger than the adjacent segments were accepted as CAE. EFV was measured by semi-automated software. Traditional risk factors in CAE patients, as well as the extent of EFV, were analyzed and compared to non-CAE group. Results A total of 885 male and 515 female older patients were enrolled. CAE was identified by univariable analysis in 131 patients and significantly correlated to hypertension, smoking, hyperlipidemia, prior percutaneous coronary intervention and ascending aorta aneurysm. EFV was shown to be significantly higher in CAE patients than patients without ectasia. In multivariable analyses, EFV (P = 0.018), hypertension (P < 0.001) and hyperlipidemia (P < 0.001) were significantly correlated to CAE. There was a significant negative correlation between EFV and Markis classification. Conclusions CAE can be reliably recognized by dual-source CTCA. Epicardial fat might play a role in etiopathogenesis and progression of CAE, providing a new target for treating ectasia. J Geriatr Cardiol 2013; 10: 10-15. doi: 10.3724/SP.J.1263.2012.12191
Heart failure （HF） with preserved ejection fraction （HFpEF） is the most common form of HF in older adults, and is increasing in preva- lence as the population ages. Furthermore, HFpEF is increasing out of proportion to HF with reduced EF （HFrEF）, and its prognosis is worsening while that of HFrEF is improving. Despite the importance of HFpEF, our understanding of its pathophysiology is incomplete, and optimal treatment remains largely undefined. A cardinal feature of HFpEF is reduced exercise tolerance, which correlates with symptoms as well as reduced quality of life. The traditional concepts of exercise limitations have focused on central dysfimction related to poor cardiac pump function. However, the mechanisms are not exclusive to the heart and lungs, and the understanding of the pathophysiology of this dis- ease has evolved. Substantial attention has focused on defining the central versus peripheral mechanisms underlying the reduced functional capacity and exercise tolerance among patients with HF. In fact, physical training can improve exercise tolerance via peripheral adaptive mechanisms even in the absence of favorable central hemodynamic function. In addition, the drug trials performed to date in HFpEF that have focused on influencing cardiovascular function have not improved exercise capacity. This suggests that peripheral limitations may play a significant role in HF limiting exercise tolerance, a hallmark feature of HFpEF.
Objective To perform a systematic review and meta-analysis of the predictive abilities of CHADS(2) and CHA(2)DS(2)-VASc in stroke and thromboembolism risk stratification of atrial fibrillation (AF) patients. Methods We searched PubMed and EMBASE for English- language literature on comparisons of the diagnostic performance between CHADS(2) and CHA2DS(2)-VASc in predicting stroke, or systemic embolism, in AF. We then assessed the quality of the included studies and pooled the C-statistics and 95% confidence intervals (95% CI). Results Eight studies were included. It was unsuitable to perform a direct meta-analysis because of high heterogeneity. When analyzed as a continuous variable, the C-statistic ranged from 0.60 to 0.80 (median 0.683) for CHADS(2) and 0.64-0.79 (median 0.673) for CHA2DS2-VASc. When analyzed as a continuous variable in anticoagulation patients, the subgroup analysis showed that the pooled C-statistic (95% CI) was 0.660 (0.655-0.665) for CHADS2 and 0.667 (0.651-0.683) for CHA2DS(2)-VASc (no significant difference). For non-anticoagulation patients, the pooled C-statistic (95% CI) was 0.685 (0.666-0.705) for CHADS(2) and 0.675 (0.656-0.694) for CHA2DS2-VASc (no significant difference). The average ratio of endpoint events in the low-risk group of CHA2DS(2)-VASc was less than CHADS(2) (0.41% vs. 0.94%, P < 0.05). The average proportion of the moderate-risk group of CHA2DS(2)-VASc was lower than CHADS(2) (11.12% vs. 30.75%, P < 0.05). Conclusions The C-statistic suggests a similar clinical utility of the CHADS(2) and CHA2DS(2)-VASc scores in predicting stroke and thromboembolism, but CHA2DS(2)-VASc has the important advantage of identifying extremely low-risk patients with atrial fibrillation, as well as classifying a lower proportion of patients as moderate risk.
Atrial fibrillation （AF） is the most common arrhythmia diagnosed in clinical practice. The consequences of AF have been clearly estab- lished in multiple large observational cohort studies and include increased stroke and systemic embolism rates if no oral anticoagulation is prescribed, with increased morbidity and mortality. With the worldwide aging of the population characterized by a large influx of ＂baby boomers＂ with or without risk factors for developing AF, an epidemic is forecasted within the next 10 to 20 years. Although not all studies support this evidence, it is clear that AF is on the rise and a significant amount of health resources are invested in detecting and managing AF This review focuses on the worldwide burden of AF and reviews global health strategies focused on improving detection, prevention and risk stratification of AF, recently recommended by the World Heart Federation.
Sudden cardiac death （SCD） affects approximately 800,000 individuals per annum globally. It is most frequently due to cardiac tachy-arrhythmias, which include mono-morphic or polymorphic ventricular tachycardia （VT）, torsade de pointes and ventricular fibrillation （VF）. Risk stratification for SCD remains a challenging problem in clinical practice.
Chronic heart failure （CHF） is a highly prevalent condition among the elderly and is associated with considerable morbidity, institution-alization and mortality. In its advanced stages, CHF is often accompanied by the loss of muscle mass and strength. Sarcopenia is a geriatric syndrome that has been actively studied in recent years due to its association with a wide range of adverse health outcomes. The goal of this review is to discuss the relationship between CHF and sarcopenia, with a focus on shared pathophysiological pathways and treatments. Mal- nutrition, systemic inflammation, endocrine imbalances, and oxidative stress appear to connect sarcopenia and CHF. At the muscular level, alterations of the ubiquitin proteasome system, myostatin signaling, and apoptosis have been described in both sarcopenia and CHF and could play a role in the loss of muscle mass and function. Possible therapeutic strategies to impede the progression of muscle wasting in CHF patients include protein and vitamin D supplementation, structured physical exercise, and the administration of angiotensin-converting enzyme inhibitors and β-blockers. Hormonal supplementation with growth hormone, testosterone, and ghrelin is also discussed as a potential treatment.
The elderly population is increasing worldwide, with subjects 〉 65 years of age constituting the fastest-growing age group. Furthermore, the elderly face the greatest risk and burden of cardiovascular disease mortality and morbidity. Although elderly patients, particularly those older 〉 75, have not been well represented in randomized clinical trials evaluating lipid-lowering therapy, the available evidence supporting the use of statin therapy in primary prevention in older individuals is derived mainly from subgroup analyses and post-hoc data. On the other hand, elderly patients often have multiple co-morbidities that require a high number of concurrent medications; this may increase the risk for drug-drug interactions, thereby reducing the potential benefits of statin therapy. The aim of this review was to present the relevant literature regarding statin use in the elderly for theft primary cardiovascular disease, with the associated risks and benefits of treatment.
Coronary artery calcification （CAC） is highly prevalent in patients with coronary heart disease （CHD） and is associated with major adverse cardiovascular events. There are two recognized type of CACintimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcification is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary interven- tion have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD pa- tients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC.
Chronic heart failure （CHF） is the leading cause of hospitalization for those over the age of 65 and represents a significant clinical and economic burden. About half of hospital re-admissions are related to co-morbidities, polypharmacy and disabilities associated with CHF. Moreover, CHF also has an enormous cost in terms of poor prognosis with an average one year mortality of 33%–35%. While more than half of patients with CHF are over 75 years, most clinical trials have included younger patients with a mean age of 61 years. Inadequate data makes treatment decisions challenging for the providers. Older CHF patients are more often female, have less cardiovascular diseases and associated risk factors, but higher rates of non-cardiovascular conditions and diastolic dysfunction. The prevalence of CHF with reduced ejection fraction, ischemic heart disease, and its risk factors declines with age, whereas the prevalence of non-cardiac co-morbidities, such as chronic renal failure, dementia, anemia and malignancy increases with age. Diabetes and hypertension are among the strongest risk factors as predictors of CHF particularly among women with coronary heart disease. This review paper will focus on the specific consideration for CHF assessment in the older population. Management strategies will be reviewed, including non-pharmacologic, pharmacologic, quality care indicators, quality improvement in care transition and lastly, end-of-life issues. Palliative care should be an integral part of an interdiscipli-nary team approach for a comprehensive care plan over the whole disease trajectory. In addition, frailty contributes valuable prognostic in-sight incremental to existing risk models and assists clinicians in defining optimal care pathways for their patients.
To assess and synthesize the prospective cohort studies published so far on the association between atrial fibrillation (AF) and dementia incidence. We searched PubMed, Web of Science, and the Cochrane Library for potential studies published in English previous to April 2018. Two independent reviewers screened the search results for prospective cohort studies reporting the association between AF and dementia incidence in patients with normal cognitive function at baseline and not suffering from an acute stroke. The Newcastle-Ottawa Scale was adopted to evaluate the quality of the included studies. The pooled hazard ratio (HR) of AF for dementia was calculated with the Comprehensive Meta-Analysis software, version 2. Heterogeneity and publication bias were assessed with the test and funnel plot, respectively. We finally identified 11 prospective cohort studies covering 112,876 patients. All the included studies reported an adjusted HR obtained in multiple Cox regression models. The qualities of the included studies ranged from moderate to high. In pooled analysis with a fixed-effects model, AF was independently associated with dementia incidence (HR = 1.34, 95% CI: 1.24-1.44). Subgroup analysis of studies considering anticoagulation as an important confounding factor achieved a similar result. Based on the test and funnel plot, we did not detect obvious heterogeneity and publication bias in our study. Meta-regression on age did not find significant results. The results of our meta-analysis further confirmed that AF was an independent risk factor for dementia in patients with normal baseline cognitive function not suffering from acute stroke. Screening for dementia in AF patients and including dementia as an independent outcome in large AF treatment trials is warranted.
To investigate the rate of anticoagulant use, the reasons for not prescribing anticoagulant, and the factors associated with non-prescription of anticoagulant in older Thai adults with non-valvular atrial fibrillation. A multicenter registry of patients with non-valvular atrial fibrillation was conducted during 2014 to 2017 in Thailand. Demographic, medical history, antithrombotic medication, non-antithrombotic medication, and laboratory data were collected and analyzed. Data were compared between the older adult (≥ 65 years) and younger adult (< 65 years) groups. The reasons why anticoagulant was not prescribed were collected, and predictive factors were identified. A total of 3218 patients (1873 males) with an average age of 67.3 ± 11.3 years were included. Almost two-thirds (61.0%) of patients were in the older adult group. Anticoagulant was prescribed in 2422 patients (75.3%): 81.4% in the older adult group and 65.7% in the younger adult group. The three main reasons for not prescribing anticoagulant were already taking antiplatelets, patient refusal, and bleeding risk. These reasons were more common in older adults as compared to younger adults. Multivariate analysis revealed current use of antiplatelets to be the most important factor that predict the non-prescription of anticoagulant in older population. The prevalence of anticoagulant prescription among older Thai adults with atrial fibrillation is 81.4%. Taking antiplatelet drugs was found to be the strongest reason that predicts the non-prescription of anticoagulant in this patient population. A guideline should be developed to optimize the use of anticoagulant and antiplatelet in older adults.
To evaluate the PR to RR interval ratio (PR/RR, heart rate-adjusted PR) as a prognostic marker for long-term ventricular arrhythmias and cardiac death in patients with implantable cardioverter defibrillator (ICDs) and cardiac resynchronization therapy with defibrillators (CRT-D). We retrospectively analyzed data from 428 patients who had an ICD/CRT-D equipped with home monitoring. Baseline PR and RR interval data prior to ICD/CRT-D implantation were collected from standard 12-lead electrocardiograph, and the PR/RR was calculated. The primary endpoint was appropriate ICD/CRT-D treatment of ventricular arrhythmias (VAs), and the secondary endpoint was cardiac death. During a mean follow-up period of 38.8 ± 10.6 months, 197 patients (46%) experienced VAs, and 47 patients (11%) experienced cardiac death. The overall PR interval was 160 ± 40 ms, and the RR interval was 866 ± 124 ms. Based on the receiver operating characteristic curve, a cut-off value of 18.5% for the PR/RR was identified to predict VAs. A PR/RR ≥ 18.5% was associated with an increased risk of VAs [hazard ratio (HR) = 2.243, 95% confidence interval (CI) = 1.665-3.022, < 0.001) and cardiac death (HR = 2.358, 95%CI = 1.240-4.483, = 0.009) in an unadjusted analysis. After adjustment in a multivariate Cox model, the relationship remained significant among PR/RR ≥ 18.5%, VAs (HR = 2.230, 95%CI = 1.555-2.825, < 0.001) and cardiac death (HR = 2.105, 95%CI = 1.101-4.025, = 0.024. A PR/RR ≥ 18.5% at baseline can serve as a predictor of future VAs and cardiac death in ICD/CRT-D recipients.