HRT and the primary prevention of cardiovascular disease

Observational studies have consistently shown a benefit of hormone replacement therapy (HRT) on coronary heart disease (CHD), but some randomised studies have not shown any significant effect. Thus questions still remains as to whether HRT is beneficial for CHD, and in whom this benefit might be achieved. The biological effects of oestrogen on the cardiovascular system have been extensively studied, and beneficial effects on metabolic CHD risk factors, as well as on arterial function and on surrogate clinical markers of CHD, have been demonstrated. Thus it seems implausible that HRT should not benefit CHD in postmenopausal women. Most randomised trials using clinical outcomes have studied just one dose of one HRT regimen, a dose inappropriately high with the average starting age of the participants being in their mid-60s. The observational population studies largely comprise women starting on HRT at appropriate dose around the age of menopause, i.e. early 50s. In fact, it was the older women in the randomised trials that failed to show benefit, whereas there was a trend to benefit in the younger ones for whom the starting dose of HRT was appropriate. Furthermore, a pilot study of lower dose HRT in older women did not show any cardiovascular harm. Inappropriately high doses of oestrogen could cause cardiovascular harm due to transient disturbances in thrombogenesis and vascular remodelling. Whilst the greatest CHD benefit may be seen by starting HRT in the early postmenopause, this does not exclude benefit in older women given appropriate low dose therapy.     

Automated electronic reminders to facilitate primary cardiovascular disease prevention: randomised controlled trial

Background

Primary care databases contain cardiovascular disease risk factor data, but practical tools are required to improve identification of at-risk patients.

Aim

To test the effects of a system of electronic reminders (the ‘e-Nudge’) on cardiovascular events and the adequacy of data for cardiovascular risk estimation.

Design of study

Randomised controlled trial.

Setting

Nineteen general practices in the West Midlands, UK.

Method

The e-Nudge identifies four groups of patients aged over 50 years on the basis of estimated cardiovascular risk and adequacy of risk factor data in general practice computers. Screen messages highlight individuals at raised risk and prompt users to complete risk profiles where necessary. The proportion of the study population in the four groups was measured, as well as the rate of cardiovascular events in each arm after 2 years.

Results

Over 38 000 patients'' electronic records were randomised. The intervention led to an increase in the proportion of patients with sufficient data who were identifiably at risk, with a difference of 1.94% compared to the control group (95% confidence interval [CI] = 1.38 to 2.50, P<0.001). A corresponding reduction occurred in the proportion potentially at risk but requiring further data for a risk estimation (difference = –3.68%, 95% CI = –4.53 to –2.84, P<0.001). No significant difference was observed in the incidence of cardiovascular events (rate ratio = 0.96, 95% CI = 0.85 to 1.10, P = 0.59).

Conclusion

Automated electronic reminders using routinely collected primary care data can improve the adequacy of cardiovascular risk factor information during everyday practice and increase the visibility of the at-risk population.     

Drug treatments in the secondary prevention of ischaemic stroke

Stroke is an important cause of death and disability. However, about two thirds of cerebrovascular events are initially minor. They carry a high risk of potentially severe recurrent events, but they also offer an opportunity for secondary prevention to avoid such recurrences. As most recurrent events occur within a short time after the initial presentation, secondary prevention has to be started as soon as possible. Dramatic risk reduction can be achieved with well-established drugs if used in a timely manner. A standard secondary preventive regimen will address multiple vascular risk factors and will usually consist of an antiplatelet agent, a lipid lowering drug, and an antihypertensive agent. Depending on the risk factor profile of each patient, this will have to be adjusted individually, for example, taking into account the presence of cardioembolism or of stenotic disease of the brain-supplying arteries. In recent years, the approach to treating these risk factors has evolved. In addition to absolute blood pressure, blood pressure variability has emerged as an important contributing factor to stroke risk, which is affected differently by different antihypertensive agents. New oral anticoagulants reduce the risk of cerebral haemorrhage and the need for regular blood checks. The best antiplatelet regimen for stroke prevention is still uncertain, and treatment of dyslipidaemia may change if trials with cholesteryl ester transfer protein (CETP) inhibitors, which increase levels of HDL-cholesterol, are successful. This article reviews the current evidence for drug treatments in the secondary prevention of ischaemic stroke.     

PCSK9 inhibitors for prevention of atherosclerotic cardiovascular disease

The discovery of proprotein convertase subtilisin kexin-type 9 (PCSK9) and the development of inhibitors of PCSK9 function appear to mark an epochal advance in clinical lipidology. PCSK9 is a circulating protein that binds to low-density lipoprotein (LDL) receptors and facilitates their lysosomal degradation following internalization in cells. Blocking PCSK9 thus increases the recycling of LDL receptors and results in more receptors on the cell surface, particularly in the liver, thereby lowering LDL levels. In this Roundtable, we discuss the recent large cardiovascular outcomes trials in which evolocumab and alirocumab, monoclonal antibodies directed against PCSK9, successfully reduced major cardiovascular events. We discuss the safety of these drugs as well as the safety of maintaining very low LDL cholesterol levels. Finally, we address pragmatic considerations affecting the use of PCSK9 inhibitors in clinical practice.     

Patients' responsiveness to a decision support tool for primary prevention of cardiovascular diseases in primary care

OBJECTIVE: Assessment of patients' responsiveness to a decision support tool for primary prevention of cardiovascular diseases (CVDs). The booklet focuses on barriers at patient level. METHODS: Process evaluation of an intervention in primary care. Patients at high or potentially high-cardiovascular risk were asked by their GP to prepare themselves for a second consultation in order to participate in decisions on risk management. OUTCOMES: Patients' actually having read the booklet and returning for the second consultation; comprehension and perceived relevance of the information; perceived reassurance. RESULTS: 17 GPs, in the intervention arm of a cluster RCT, issued 276 decision support tools during the first consultation and were instructed to ask them to return for a second consultation to discuss their CVD risk. Patients had a mean age of 54 years, 47% were male and 19% actually had a high cardiovascular risk. Data on 239 patients, a mixture of returnees and non-returnees, showed that they all read the booklet; comprehension was fair to good; 85% perceived the information as relevant; 68% of the patients felt reassured by the information. Satisfaction with the first consultation was higher in the non-returnees. CONCLUSIONS: Cardiovascular prevention spread over two consultations with use of a decision support tool for patients is not easily applicable for GPs. However, based on the findings of good patients' responsiveness, we recommend further development and implementation of decision support tools in primary care. PRACTICE IMPLICATIONS: Decision support for primary CV-prevention is welcomed by patients but needs further adjustment of both the GP and the organization of CV-prevention in primary care. Sharing information between professional and patient on a personal CV-risk management plan is difficult, more training is needed.     

HRT and heart disease: problems and prospects

The divergent findings of hormone replacement therapy (HRT) from observational and randomized clinical studies are summarized and reasons for the different results are postulated. Chronic use of HRT since menopause has no harmful effects on CHD event rate, while the initiation of therapy after a recent cardiovascular event causes an early increase in recurrent CHD events. Once endothelial dysfunction and atherosclerotic disease has developed, the starting of HRT promotes plaque instability, vascular inflammation and prothrombotic effects. The timing of HRT use since menopause is therefore crucial in the effectiveness and safety of HRT on the vascular system.     

Self-management support in cardiovascular consultations by advanced practice nurses trained in motivational interviewing: An observational study

ObjectiveThis observational study explores advanced practice nurses’ (APN) performance in secondary prevention and self-management support in patients with cardiovascular disease.MethodsReal-life consultations in three outpatient clinics were recorded on audio and analysed. First, discussed (sub)categories were determined using five categories of self-management: symptom management, treatment, biomedical cardiovascular risk factors, psychosocial consequences, and lifestyle changes. Second, the extent in which motivational interviewing aspects were applied was determined using the Behaviour Change Counselling Index (BECCI).ResultsIn total, 49 consultations performed by five female APNs were analysed. Physical topics were discussed in 98% and psychological subthemes in 41% of the consultations. Although not all components of motivational interviewing were applied, talking about current behaviour and behaviours that should change were discussed, and information was provided. Especially setting targets and exchanging ideas on how to reach behavioural goals were applied to a small extent.ConclusionWell-trained APNs in the current study do not carry out motivational interviewing in a structural and complete manner according to BECCI and do not discuss all self-management categories.Practice implicationsPsychological topics should be more integrated in providing self-management support by APNs and the application of motivational interviewing should be enhanced by regularly and repeated training.     

整合素与心血管疾病

细胞 -细胞之间以及细胞 -细胞外基质蛋白之间的正常粘附是细胞生长 ,分化以及迁移的基础 ,负责细胞内、外信号的传递 ,也是心血管系统所有组成成分维持功能正常的前提条件。因此 ,粘附功能异常在心血管疾病发病机制中也起着关键作用。目前为止 ,总共有 6个粘附分子家族 ,整合素 (ｉｎｔｅｇｒｉｎ)是细胞表面介导细胞 -细胞间以及细胞与细胞外基质粘附作用的粘附分子之一 ,与细胞的迁移、增殖和分化密切相关 ,是细胞信息传递的一个重要组成部分。整合素在维持血管正常结构和血管壁的通透性 ,防止血小板沉积和血栓形成 ,促进创伤愈合 ,以及…     

外泌体miRNA在心血管疾病中的研究进展

<正>心血管疾病(cardiovascular diseases,CVD)是全球高发性疾病,其中冠心病(coronary heart disease,CHD)是世界范围内的主要死亡原因,在老年人群中死亡率和发病率不断上升[1],与微小RNA(microRNA,miRNA,miR)的调节密切相关[2]。研究报道,miRNA调节大量信号通路,可通过外泌体(exosome)实现细胞间传递,参与细胞间的信息交流[3],其严格     

Hysterectomy prevalence and cardiovascular disease risk factors in American Indian women

OBJECTIVES: We investigated hysterectomy prevalence and associated demographic and reproductive factors among American Indian women. The association between hysterectomy and cardiovascular disease (CVD) risk factors was also examined. METHODS: Data were from 2689 American Indian women who participated in the first examination of the Strong Heart Study from 1989 to 1992. Odds ratios were estimated for factors related to hysterectomy adjusting for other covariates. The association between hysterectomy and CVD risk factors was examined among 1726 eligible women using analysis of covariance. RESULTS: Hysterectomy prevalence ranged from 24% to 34% across differing age groups and the percent with oophorectomy among those with a hysterectomy ranged from 43% to 63%. Geographic area, more prior pregnancy losses, more education, and less speaking of the native language were associated with increased hysterectomy prevalence. After adjustment for age, the women who had a hysterectomy with intact ovaries had higher total cholesterol and low-density lipoprotein cholesterol levels than those with a natural menopause. CONCLUSIONS: American Indian women have comparable hysterectomy prevalence as non-Hispanic white women. Education and native language speaking related to hysterectomy in this population. Hysterectomy alone may relate to unfavorable changes of lipid profile.     

HIBISCUS: Hydroxychloroquine for the secondary prevention of thrombotic and obstetrical events in primary antiphospholipid syndrome

The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%–21% at 5?years in thrombotic APS and 20–28% in obstetrical APS [2, 3].Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4–16].Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency.Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial.This trial consists in two parts: a retrospective and a prospective study.The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.     

表没食子儿茶素没食子酸酯对心血管疾病防治作用的研究进展

中国在公元前3 000年以前就有饮用绿茶的记载。现代技术发现绿茶含有大量的茶多酚,儿茶素是茶多酚的主要成分,包括4种单体物质,即表没食子儿茶素没食子酸酯[(-)-epigallocatechin gallate, EGCG]、表儿茶素没食子酸酯(epicatechin gallate,ECG)、表没食子儿茶素(epigallocatechin,EGC)和表儿茶素(epicatechin,EC),其中最主要的活性成分EGCG被认为具有抗癌、减肥、抗糖尿病、抗菌、抗病毒、预防龋齿等作用^[1]。大量研究发现饮茶也会减少心血管疾病的发生风险,对心脏具有明确的保护作用,本文就EGCG对心血管疾病的预防作用研究进展进行综述。     

线粒体功能障碍与心血管疾病

 线粒体是真核细胞能量产生的重要细胞器,并在细胞钙稳态、信号传导和细胞凋亡调节中也发挥着举足轻重的作用。导致线粒体功能障碍的可能原因有氧化应激、Ca2+紊乱、线粒体生物合成减少以及线粒体DNA突变等,这些因素也与心血管疾病的发生发展密切相关。认识和研究线粒体功能障碍及其在心血管疾病中的重要作用,对阐明心血管疾病的发病机制、开拓其临床防治和药物研发新思路都具有重要意义。     

G蛋白偶联受体激酶在心血管疾病中的作用

G-protein-coupled receptors (GPCRs) are hitherto the largest family of membrane receptors. They activate associated heterotrimeric G-proteins and participate in the regulation of intracellular signaling pathways, which are accomplished via ligand binding to them. G-protein-coupled receptor kinases (GRKs) are key modulators of GPCR signaling. GRKs, in concert with β-arrestins, classically lead to desensitization and internalization of GPCR, thus preventing hyperactivation of GPCR second messenger cascades. Changes in the GRKs expression and regulation have featured prominently in many cardiovascular diseases, including heart failure, myocardial infarction, cardiac hypertrophy, and hypertension. Intensively studying the role of GRKs in cardiovascular diseases contributes to expounding the mechanism of correlated diseases. Herein, we review the role of GRKs in cardiovascular pathophysiology.     

Isoflavones and cardiovascular disease

The specific profile of estrogens on cardiovascular risk, with limiting action on atherogenesis but a less clear protection on cardiovascular episodes, might be improved by other agonists of the estrogen receptor, such as isoflavones. By using a systematic search based on the electronic Medline database plus a hand-search of reference lists of selected review papers, we reviewed the rapidly growing body of experimental and clinical data that, on average, follow a pattern of benefit rather similar to estrogens. Experimental models have used endothelial and vascular smooth muscle cells, isolated arteries, and live animals, including monkeys. The clinical evidence arises from studies on the lipid profile and lipid oxidation, insulin resistance, hemostasis, changes in the inflammatory factors, and indicators of endothelial function, including metabolites of nitric oxide and prostacyclin. There are not randomized trials investigating the action of isoflavones on the incidence of clinical episodes, but a few recent, well-designed studies have suggested the association of the ingestion of isoflavones with a reduction in the atherosclerotic burden, as indicated by the measurement of the intima-media thickness in carotid vessels.     

Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease

Chronic inflammation is being shown to be increasingly involved in the onset and development of several pathological disturbances such as arteriosclerosis, obesity, diabetes, neurodegenerative diseases and even cancer. Treatment for chronic inflammatory disorders has not been solved, and there is an urgent need to find new and safe anti-inflammatory compounds. Flavonoids belong to a group of natural substances occurring normally in the diet that exhibit a variety of beneficial effects on health. The anti-inflammatory properties of flavonoids have been studied recently, in order to establish and characterize their potential utility as therapeutic agents in the treatment of inflammatory diseases. Several mechanisms of action have been proposed to explain in vivo flavonoid anti-inflammatory actions, such as antioxidant activity, inhibition of eicosanoid generating enzymes or the modulation of the production of proinflammatory molecules. Recent studies have also shown that some flavonoids are modulators of proinflammatory gene expression, thus leading to the attenuation of the inflammatory response. However, much work remains to be done in order to achieve definitive conclusions about their potential usefulness. This review summarizes the known mechanisms involved in the anti-inflammatory activity of flavonoids and the implications of these effects on the protection against cancer and cardiovascular disease.     

外泌体在心血管疾病中的研究进展*

AIM: Exosomes are bi-lipid membrane originated in the cell endocytosis system and secreted into the extracellular matrix. The cells secrete exosomes into extracellular matrix to impact target cells with the significant functions of cell-cell information transmission and immunological regulation. Recent studies show that cell-cell communication regulated by exosomes can be found in both physiological and pathological conditions of cardiovascular diseases (CVD). Exosomes derived from many types of cells (such as myocardial cells, endothelial cells and stem cells) play an important regulatory role in the pathogenetic mechanism of CVD. Meanwhile, exosome-based investigations have shown huge potential for the treatment of CVD. This review will focus on the biological characteristics and functions of exosomes in the diagnosis and treatment of CVD.