IL-18- 心血管事件独立危险因素

心血管疾病为一种慢性炎症性疾病,大部分证据显示IL-18与代谢综合征及它的后果有关。有报道循环中IL-18水平在心血管疾病患者中升高,与心血管疾病有显著的相关性,并且能够预测心血管疾病患者的心血管事件和死亡率,促进2型糖尿病的发展。在不稳定斑块、脂肪组织、肌肉组织中存在IL-18,通过caspase-1等调控,与IL-18结合蛋白结合而失活,与IL-18受体结合影响其因子的转录。这篇综述的的目的在于描述心血管疾病患者中IL-18总的大概作用,尤其强调心血管危险和生活方式干预的潜在效应。     

IL-18-心血管事件独立危险因素

心血管疾病为一种慢性炎症性疾病,大部分证据显示IL-18与代谢综合征及它的后果有关。有报道循环中IL-18水平在心血管疾病患者中升高,与心血管疾病有显著的相关性,并且能够预测心血管疾病患者的心血管事件和死亡率,促进2型糖尿病的发展。在不稳定斑块、脂肪组织、肌肉组织中存在IL-18,通过caspase-1等调控,与IL-18结合蛋白结合而失活,与IL-18受体结合影响其因子的转录。这篇综述的的目的在于描述心血管疾病患者中IL-18总的大概作用,尤其强调心血管危险和生活方式干预的潜在效应。     

C-reactive protein as a risk factor versus risk marker

PURPOSE OF REVIEW: C-reactive protein (CRP) is consistently associated with cardiovascular disease in prospective and cross-sectional clinical and epidemiological studies. Inflammation is an important mechanism in cardiovascular disease, and the plasma level of CRP is considered to reflect the inflammatory condition of the patient and/or the vessel wall. In addition, there are also a number of indications for a causal role of CRP in cardiovascular disease. RECENT FINDINGS: A number of new publications show potential causal effects of CRP on cardiovascular disease, and evidence from human-CRP transgenic animals also indicates a causal contribution of CRP to cardiovascular disease. On the other hand, a new large prospective study and an updated meta-analysis indicate that the contribution of CRP to cardiovascular disease is less impressive than reported earlier (odds ratio, 1.58; 95% confidence interval, 1.48-1.68). SUMMARY: We review here the most recent evidence on mechanisms by which CRP is involved as a causal factor in the precipitation of cardiovascular disease. Evidence for such a role is accumulating.     

血浆游离DNA检测在心血管系统疾病诊断中的应用

心血管疾病发病率和病死率居高不下,寻求敏感性高的生物学指标帮助早期诊断和改善预后意义重大.血浆游离DNA(cell-free DNA,cfDNA)是一类存在于血浆、尿液及其他体液中游离于细胞之外的双链DNA片段.血浆cfDNA水平在心血管疾病的早期明显升高,提示其可能是心血管疾病的潜在生物标志物.为了更深入理解cfDN...     

Doppler echocardiographic reference values for healthy rhesus monkeys under ketamine hydrochloride sedation

Cardiac ultrasound is a noninvasive technique that is commonly used to serially evaluate cardiac structure and function. Recent advances in Doppler-Echocardiography enable the ultrasonographer to perform a sophisticated noninvasive assessment of cardiovascular physiology. The Rhesus monkey is a frequently used non-human primate animal model of human cardiovascular disease because this species closely models human anatomy and physiology. However, while this species is frequently used in cardiovascular research, standardized echocardiographic values generated from large numbers of normal Rhesus are not available. In the present study, we performed cardiac ultrasound imaging on 28 healthy Rhesus monkeys to obtain normal reference values of cardiovascular structure and function in this species. Nomograms were generated from these data by plotting parameters of cardiovascular geometry and function with body weight. These normal reference data were compared to previously reported values obtained from prior studies that used noninvasive, invasive, and morphometric techniques. Cardiac ultrasound is a noninvasive technique that is commonly used to serially evaluate cardiac structure and function. Recent advances in Doppler-Echocardiography enable the ultrasonographer to perform a sophisticated noninvasive assessment of cardiovascular physiology. The Rhesus monkey is a frequently used non-human primate animal model of human cardiovascular disease because this species closely models human anatomy and physiology. However, while this species is frequently used in cardiovascular research, standardized echocardiographic values generated from large numbers of normal Rhesus are not available. In the present study, we performed cardiac ultrasound imaging on 28 healthy Rhesus monkeys to obtain normal reference values of cardiovascular structure and function in this species. Nomograms were generated from these data by plotting parameters of cardiovascular geometry and function with body weight. These normal reference data were compared to previously reported values obtained from prior studies that used noninvasive, invasive, and morphometric techniques.     

Serum C‐reactive protein in the prediction of cardiovascular diseases: Overview of the latest clinical studies and public health practice

Cardiovascular disease is the most common cause of morbidity and mortality globally. Epidemiological studies using high‐sensitivity assays for serum C‐reactive protein have shown a consistent association between cardiovascular disease risk and serum C‐reactive protein concentrations. C‐reactive protein is a biomarker for inflammation, and has been established in clinical practice as an independent risk factor for cardiovascular disease events. There is evidence that serum C‐reactive protein is an excellent biomarker of cardiovascular disease and is also an independent and strong predictor of adverse cardiovascular events. Further characterization of the impact and influence of lifestyle exposures and genetic variation on the C‐reactive protein response to cardiovascular disease events may have implications for the therapeutic approaches to reduce cardiovascular disease events. This review summarizes the studies that have examined the association between serum C‐reactive protein and the risk of cardiovascular disease. We also discuss the impact of independent factors and C‐reactive protein genetic polymorphisms on baseline plasma C‐reactive protein levels.     

Non-high-density lipoprotein cholesterol and cardiovascular disease

PURPOSE OF REVIEW: Non-HDL cholesterol was designated a secondary target of therapy in the recent Adult Treatment Panel III report. This paper reviews correlates of non-HDL cholesterol levels and summarizes the available data on non-HDL cholesterol as a predictor of cardiovascular events as well as data linking treatment-induced changes in non-HDL cholesterol to cardiovascular outcomes. RECENT FINDINGS: Non-HDL cholesterol levels in the population vary by age, sex, and race and are closely linked to measures of adiposity, especially visceral adiposity. Several reports in populations with and without cardiovascular disease have recently been published that document the prognostic utility of non-HDL cholesterol levels. Preliminary data are also available to suggest that pharmacologically induced changes in non-HDL cholesterol levels relate to prognosis. SUMMARY: Non-HDL cholesterol is a potent predictor of cardiovascular risk among a broad range of individuals with and without cardiovascular disease and is prognostic over a wide range of follow-up periods. The impact of pharmacologically induced changes in non-HDL cholesterol on cardiovascular outcomes is less clear and requires further study.     

Mitochondrial dysfunction in cardiovascular disease

Whereas the pathogenesis of atherosclerosis has been intensively studied and described, the underlying events that initiate cardiovascular disease are not yet fully understood. A substantial number of studies suggest that altered levels of oxidative and nitrosoxidative stress within the cardiovascular environment are essential in the development of cardiovascular disease; however, the impact of such changes on the subcellular or organellar components and their functions that are relevant to cardiovascular disease inception are less understood. In this regard, studies are beginning to show that mitochondria not only appear susceptible to damage mediated by increased oxidative and nitrosoxidative stress, but also play significant roles in the regulation of cardiovascular cell function. In addition, accumulating evidence suggests that a common theme among cardiovascular disease development and cardiovascular disease risk factors is increased mitochondrial damage and dysfunction. This review discusses aspects relating mitochondrial damage and function to cardiovascular disease risk factors and disease development.     

我国心血管专科临床科研数据中心的建设与思考

中国是心血管疾病的数据大国,但是从数据质量和临床科研上讲,并非强国。为了提高心血管数据在临床质量评估和科研中的应用,我院心内科开始了心血管专科临床科研数据中心的尝试和建设。通过借鉴美国相关经验,以及对我国心血管临床质量评估以及科研需求的深入调研,我们建设了以心血管专科临床数据仓库以及心血管注册数据中心为核心的心血管专科临床科研数据中心。在此基础上,进一步探索并建设了自定义科研表单,多维度组合筛选,基于随访策略的心血管随访管理,基于个性化诊疗计划的心血管病人院后管理,相关性分析及不良心血管事件模式发现等应用和工具,有助于提升心血管专科的临床流程效率,临床质量评估和科研水平,同时为建立全国性的心血管疾病注册数据库打下了基础。     

GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data

Patients with type 2 diabetes (T2DM) have a substantial risk of developing cardiovascular disease. The strong connection between the severity of hyperglycaemia, metabolic changes secondary to T2DM and vascular damage increases the risk of macrovascular complications. There is a challenging demand for the development of drugs that control hyperglycaemia and influence other metabolic risk factors to improve cardiovascular outcomes such as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina and heart failure (major adverse cardiovascular events). In recent years, introduction of the new drug class of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has changed the treatment landscape as GLP-1RAs have become well-established therapies in T2DM. The benefits of GLP-1RAs are derived from their pleiotropic effects, which include appetite control, glucose-dependent secretion of insulin and inhibition of glucagon secretion. Importantly, their beneficial effects extend to the cardiovascular system. Large clinical trials have evaluated the cardiovascular effects of GLP-1RAs in patients with T2DM and elevated risk of cardiovascular disease and the results are very promising. However, important aspects still require elucidation, such as the specific mechanisms involved in the cardioprotective effects of these drugs. Careful interpretation is necessary because of the heterogeneity across the trials concerning the definition of cardiovascular risk or cardiovascular disease, baseline characteristics, routine care and event rates. The aim of this review is to describe the main clinical aspects of the GLP-1RAs, compare them using data from both the mechanistic and randomized controlled trials and discuss potential reasons for improved cardiovascular outcomes observed in these trials. This review may help clinicians to decide which treatment is most appropriate in reducing cardiovascular risk in patients with T2DM.     

Role of estrogen receptor-alpha in pharmacogenetics of estrogen action

PURPOSE OF REVIEW: To summarize recent data regarding the role of estrogen receptor-alpha polymorphisms in determining the response to estrogen therapy or the risk of clinical cardiovascular events. RECENT FINDINGS: Recent clinical trials of hormone replacement therapy for cardiovascular disease have yielded surprisingly negative results, shifting clinical opinions from a position of presumed cardiovascular benefit to one of confirmed harm. Understanding why hormone replacement therapy has beneficial effects on intermediate risk markers for cardiovascular disease, but produces an increase in cardiovascular events, is an important public health question with the potential to elucidate fundamentally important aspects on atherogenesis, cardiovascular disease, and the biology of estrogen action. One question concerning the cardiovascular effects of hormone replacement therapy is whether genetic factors can substantially modify individual responses to estrogen treatment. New clinical trial evidence is emerging that links the presence of particular variants in the estrogen receptor to the response of HDL and other intermediate endpoints to hormone replacement therapy. SUMMARY: One or more common variants in estrogen receptor-alpha are associated with a differential response to hormone replacement therapy in several domains of estrogen action. However, the effect of these variants on the risk of clinical cardiovascular events in the setting of hormone replacement therapy is not yet known. Additional research focusing on the clinical impact of common variants in estrogen receptor-alpha, estrogen receptor-beta and the progesterone receptor promise to improve clinical decision-making concerning the use of hormone replacement therapy and other novel estrogen agonists.     

From a static to a dynamic concept of risk: the circadian epidemiology of cardiovascular events

A growing body of evidence substantiates that the occurrence of cardiovascular events in unevenly distributed in time, especially during the 24 h. These temporal patterns are indicative of temporal variation in the (1) pathophysiological mechanisms that trigger cardiovascular events and (2) physiological status of the cardiovascular system, which combine to give rise to 24 h and other periodicities in the susceptibility to disease. The classic assumption of epidemiologic studies is constancy (or homeostasis) in one's risk to disease during the 24 h, as well as other, time domains. However, we propose a new concept, that of chronorisk since it takes into account the temporal variability in the pathophysiological mechanisms and their reciprocal temporal interactions that lead to day-night and other time-dependent patterns in cardiovascular events. This chronobiological approach, which is expected to contribute new insight into the prognostic and therapeutic assessment of cardiovascular events, is worthy of broader application in cardiovascular and other fields of medicine and warrants further investigation.     

Targeting the redox system for cardiovascular regeneration in aging

Cardiovascular aging presents a formidable challenge, as the aging process can lead to reduced cardiac function and heightened susceptibility to cardiovascular diseases. Consequently, there is an escalating, unmet medical need for innovative and effective cardiovascular regeneration strategies aimed at restoring and rejuvenating aging cardiovascular tissues. Altered redox homeostasis and the accumulation of oxidative damage play a pivotal role in detrimental changes to stem cell function and cellular senescence, hampering regenerative capacity in aged cardiovascular system. A mounting body of evidence underscores the significance of targeting redox machinery to restore stem cell self-renewal and enhance their differentiation potential into youthful cardiovascular lineages. Hence, the redox machinery holds promise as a target for optimizing cardiovascular regenerative therapies. In this context, we delve into the current understanding of redox homeostasis in regulating stem cell function and reprogramming processes that impact the regenerative potential of the cardiovascular system. Furthermore, we offer insights into the recent translational and clinical implications of redox-targeting compounds aimed at enhancing current regenerative therapies for aging cardiovascular tissues.     

Diabetes mellitus associated cardiovascular signalling alteration: A need for the revisit

Diabetes mellitus, a chronic metabolic disorder, is recognized as a root cause of cardiovascular disorders. A long-term and uncontrolled diabetes mellitus coincides with the cardiovascular signalling alteration, resulting in inadequacy of maintaining the cardiovascular physiology. Nitric oxide (NO) is an imperative mediator of cardiovascular physiology as its signalling is known to mediate vasodilatory, anti-platelet, anti-proliferative, and anti-inflammatory actions in vessels. In 1998, Robert Furchgott, Louis Ignarro and Ferid Murad received the Nobel Prize in Medicine or Physiology for their great discoveries concerning the role of NO (originally identified as endothelium-derived relaxing factor, EDRF) as a key signalling molecule in regulating cardiovascular physiology. The activation of phosphatidylinositol 3-kinase (PI3-K) further activates protein kinase B (PKB/Akt), which subsequently enhances eNOS activation and vascular NO generation. However, in recent studies a marked impairment in PI3-K/Akt–eNOS–NO signalling has been demonstrated in the condition of diabetes mellitus. Therefore, the defective PI3-K–Akt–eNOS–NO signalling pathways could make diabetic patients more vulnerable to cardiovascular disease pathology concerning the key functions of NO. Adenosine produced by cardiac cells has abilities to attenuate the proliferation of cardiac fibroblasts, inhibit collagen synthesis, and defend the myocardium against ischemia–reperfusion injury. However, diabetes mellitus is associated with enhanced unidirectional uptake of interstitial adenosine and reduced ability to release adenosine by cardiac cells during ATP deprivation. The reduced myocardial extracellular availability and increased uptake of adenosine could make diabetic subjects more susceptible to myocardial abnormalities. This review throws lights on diabetes mellitus-associated cardiovascular signalling alterations and their possible contribution to cardiovascular disease pathology.     

Cardiovascular protective effects of 17beta-estradiol metabolites.

17beta-estradiol (estradiol), the most abundant endogenous estrogen, affords cardiovascular protection. However, in a given cohort of postmenopausal women, estradiol replacement therapy provides cardiovascular protection in only a subset. The reasons for this variable action can only be understood once the mechanisms by which estradiol induces its cardiovascular protective effects are known. Because most biological effects of estradiol are mediated via estrogen receptors (ERs) and the heart and blood vessels contain both ER-alpha and ER-beta, the prevailing view is that ERs mediate estradiol-induced cardiovascular protection. However, recent findings that estradiol protects against vascular injury in arteries of mice lacking either ER-alpha or ER-beta seriously challenges this concept. Thus other non-ER mechanisms may be operative. Endogenous estradiol is enzymatically converted to several nonestrogenic metabolites, and some of these metabolites induce potent biological effects via ER-independent mechanisms. Therefore, it is conceivable that the cardiovascular protective effects of estradiol are mediated via its endogenous metabolites. On the basis of the evidence cited in this review, the cardiovascular protective effects of estradiol are both ER dependent and independent. The purpose of this article is to review the evidence regarding the cardiovascular protective effects of estradiol metabolites and to discuss the cellular, biochemical, and molecular mechanisms involved.     

A computerized test battery for the assessment of cardiovascular reactivity

Recent evidence has suggested a possible relationship between the tendency to exhibit excessive cardiovascular reactions during psychological challenge and the risk of cardiovascular disease. Valid techniques for reliably assessing such reactions are, however, minimally available. A test battery for the assessment of cardiovascular reactivity to experimental challenge is currently being developed at the University of Pittsburgh in conjunction with the University of Miami and Duke University. An IBM-AT compatible microcomputer is being used for the concurrent collection of physiological data and presentation of the laboratory stressors. Digitized cardiovascular data being collected include EKG, Impedance Cardiogram (ICG), phonocardiogram, and a peripheral pulse wave measure. Blood pressure readings are also being collected and stored on disk. The computer presents three challenging video games, each designed to elicit cardiovascular reactions. Processing programs are being used and developed for the standardized scoring of the digitized signals. To assist in epidemiological research a mobile testing unit has been assembled for the easy administration of the test battery in varying geographical locations. The test battery being developed will increase the feasibility of epidemiological and clinical assessment of stress-induced cardiovascular responses which may substantiate a link between reactivity and cardiovascular disease.     

Transforming growth factor <Emphasis Type="Italic">beta</Emphasis> signaling in adult cardiovascular diseases and repair

The majority of children with congenital heart disease now live into adulthood due to the remarkable surgical and medical advances that have taken place over the past half century. Because of this, adults now represent the largest age group with adult cardiovascular diseases. It includes patients with heart diseases that were not detected or not treated during childhood, those whose defects were surgically corrected but now need revision due to maladaptive responses to the procedure, those with exercise problems and those with age-related degenerative diseases. Because adult cardiovascular diseases in this population are relatively new, they are not well understood. It is therefore necessary to understand the molecular and physiological pathways involved if we are to improve treatments. Since there is a developmental basis to adult cardiovascular disease, transforming growth factor beta (TGFβ) signaling pathways that are essential for proper cardiovascular development may also play critical roles in the homeostatic, repair and stress response processes involved in adult cardiovascular diseases. Consequently, we have chosen to summarize the current information on a subset of TGFβ ligand and receptor genes and related effector genes that, when dysregulated, are known to lead to cardiovascular diseases and adult cardiovascular deficiencies and/or pathologies. A better understanding of the TGFβ signaling network in cardiovascular disease and repair will impact genetic and physiologic investigations of cardiovascular diseases in elderly patients and lead to an improvement in clinical interventions.     

Erectile dysfunction in patients with cardiovascular disease

Erectile dysfunction is a highly prevalent disease, especially in cardiovascular-compromised men. Many of the well-established risk factors for cardiovascular disease are also risk factors for erectile dysfunction. A correlation between erectile dysfunction and endothelial dysfunction is well established. It is postulated that erectile dysfunction with an arteriovascular aetiology can predate and be an indicator of potential coronary artery disease. In this paper we will attempt to increase awareness among cardiologists for the predictive value of erectile dysfunction for future cardiovascular disease in order to optimise cardiovascular risk management. The treatment of erectile dysfunction and cardiovascular interactions is also discussed in detail.     

Effect of rosuvastatin on outcomes in chronic haemodialysis patients – design and rationale of the AURORA study

Background

Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population. In contrast to patients with normal renal function, the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospective randomised trials. A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events (AURORA) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis.

Methods

More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been randomised (1:1), irrespective of baseline lipid levels, to treatment with rosuvastatin 10 mg or placebo. The primary study endpoint is the time to a major cardiovascular event (first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Secondary endpoints include all-cause mortality, major cardiovascular event-free survival time, time to cardiovascular death, time to non-cardiovascular death, cardiovascular interventions, tolerability of treatment and health economic costs per life-year saved. Study medication will be given until 620 subjects have experienced a major cardiovascular event.

Conclusion

Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this expanding population.     

Teaching cardiovascular physiology with equivalent electronic circuits in a practically oriented teaching module

Here, we report on a new tool for teaching cardiovascular physiology and pathophysiology that promotes qualitative as well as quantitative thinking about time-dependent physiological phenomena. Quantification of steady and presteady-state (transient) cardiovascular phenomena is traditionally done by differential equations, but this is time consuming and unsuitable for most undergraduate medical students. As a result, quantitative thinking about time-dependent physiological phenomena is often not extensively dealt with in an undergraduate physiological course. However, basic concepts of steady and presteady state can be explained with relative simplicity, without the introduction of differential equation, with equivalent electronic circuits (EECs). We introduced undergraduate medical students to the concept of simulating cardiovascular phenomena with EECs. EEC simulations facilitate the understanding of simple or complex time-dependent cardiovascular physiological phenomena by stressing the analogies between EECs and physiological processes. Student perceptions on using EEC to simulate, study, and understand cardiovascular phenomena were documented over a 9-yr period, and the impact of the course on the students' knowledge of selected basic facts and concepts in cardiovascular physiology was evaluated over a 3-yr period. We conclude that EECs are a valuable tool for teaching cardiovascular physiology concepts and that EECs promote active learning.