Evaluating sex specific differences in dilated cardiomyopathy

背景心力衰竭影响着全球2600万人。它是导致住院和过早死亡的主要原因，也是一个主要的经济负担，占NHS预算的1-2%。第二个最常见的原因是扩张型心肌病，这是一种心肌疾病，在英国，每250人中就有1人受到影响，即24万人。不幸的是，尽管进行了最好的治疗，但这一相对年轻的人口(中位年龄40岁)的死亡率仍然很高。在50岁的扩张型心肌病和心脏疤痕患者中，大约有一半在10年内死亡或接受心脏移植。我们迫切需要改善对患有这种疾病的患者的护理方式。性别(男性或女性)可能在疾病进展中起关键作用。我的研究表明：(I)扩张型心肌病影响的男性是女性的两倍。要么男性风险更高，要么女性受到保护。(Ii)扩张型心肌病男性和女性的心脏不同。与男性相比，女性的心脏更小，心脏功能更好。(Iii)尽管如此，女性患并发症的风险是男性的两倍。女性50岁以上的并发症是男性的两倍，而男性无论年龄大小，并发症的数量都相同。这表明，尽管女性的病情较轻，但她们患并发症的风险更高，而且这种风险在绝经后会增加。尽管有这些观察，我们目前对待男性和女性是完全相同的。目的和目的在本研究计划中，我将研究扩张型心肌病对男性和女性一生的不同影响，以期改善所有扩张型心肌病患者的诊断、治疗和预后。我将做三项主要研究：1.女性经历了许多独特的生活事件，这些事件与怀孕和更年期等主要荷尔蒙变化有关。然而，我们不知道它们对扩张型心肌病或其并发症的影响。我将利用一个大型的全科医学研究数据库，在我们的专科研究中心和普通人群中研究这些药物对患者的影响。2.扩张型心肌病尚无性别特异性治疗建议。我开展了一项国际研究，整理了约6500名患者的数据。我将开发一个在女性身上运行良好的风险预测模型。风险预测模型使用患者的风险因素来预测预后。我还将研究是否应该对男性和女性的风险因素采用不同的界限。3.虽然我们知道男性和女性在心脏结构上存在差异，但我们不知道原因。其中一个原因可能是男性和女性心脏基因的启动方式不同。我将寻找扩张型心肌病患者和健康心脏患者心脏组织中基因信号的变化。谁参与了这项研究？我将领导这项研究，并与拥有成功完成这项研究所需专业知识的人合作。我在国际上和英国都有一个合作团队，他们来自不同的学科，包括流行病学、内分泌学、生物统计学和遗传学。潜在影响这项研究将对患者、临床医生和政策制定者产生直接影响。确定扩张型心肌病在男性和女性中的不同之处和原因将有助于我们理解患者经历的健康结果的范围。这项研究的结果可以应用于诊断和风险分层(即患者是否处于并发症的高风险或低风险)，并可能导致针对性别的治疗建议。这将导致所有扩张型心肌病患者健康状况的实际改善，重新评估我们目前治疗男性和女性相同的模式。患者和国家患者组(英国心肌病，Pump Marvellous)参与了这项研究的所有阶段。他们说，这是一个非常重要的以患者为中心的项目，目标是一个主要的未得到满足的需求。

Context Heart failure affects 26 million people globally. It is a leading cause of hospitalisations and early deaths and is a major economic burden, making up 1-2% of the NHS budget. The second commonest cause is dilated cardiomyopathy, a heart muscle condition that affects up to 1 in 250 people, or 240,000 people in the UK. Unfortunately, despite best treatment, mortality for this relatively young population (median age 40) remains high. Approximately half of patients aged 50 with dilated cardiomyopathy and scarring in the heart die or have a heart transplant within 10 years. We urgently need to improve how we care for patients with this condition. Sex (being male or female) may play a critical role in disease progression. My research shows that:(i) Dilated cardiomyopathy affects twice as many men as women. Either men are more at risk or women are protected.(ii) The hearts of men and women with dilated cardiomyopathy differ. Compared to men, women have smaller hearts and better heart function. (iii) Despite this, women have a two-fold increased risk of complications compared to men. Women get twice as many complications after 50 whilst men have the same number of complications regardless of age. This suggests that women are more at risk of complications despite a 'milder' disease and this risk increases after menopause. Despite these observations, we currently treat men and women exactly the same. Aims and objectives In this research programme, I will study how dilated cardiomyopathy affects men and women differently across their lifespan with the aim of improving diagnosis, treatment and prognosis for all patients with dilated cardiomyopathy. I will do three main studies: 1. Women experience a number of unique life events linked to major hormonal changes such as pregnancy and menopause. However, we do not know their impact on dilated cardiomyopathy or its complications. I will study the effect of these on patients in our specialist research centre and in the general population using a large general practice research database. 2. There are no sex specific treatment recommendations in dilated cardiomyopathy. I have developed an international study collating data on ~6500 patients. I will develop a risk prediction model which works well in women. Risk prediction models use patient risk factors to predict prognosis. I will also study whether we should apply different cut offs for risk factors in men and women. 3. Whilst we know there are differences in heart structure between men and women, we do not know why. One reason could be due to differences in how the heart genes are switched on in men versus women. I will look for changes in gene signals in heart tissue from men and women with dilated cardiomyopathy compared to healthy hearts. Who is involved in this research? I will lead this research and collaborate with people with the expertise needed to successfully complete this research. I have a team of collaborators internationally and in the UK from different disciplines including epidemiology, endocrinology, biostatistics, and genetics. Potential impact This study will have immediate impact for patients, clinicians and policy makers. Identifying how and why dilated cardiomyopathy differs in men and women will help us to make sense of the range of health outcomes that patients experience.The results of this study can be applied to diagnosis and risk stratification (i.e. whether patients are at high or low risk of complications) and could lead to sex-specific treatment recommendations. This would lead to realistic improvements in the health of all patients with dilated cardiomyopathy, re-evaluating our current model of treating men and women the same.Patients and national patient groups (Cardiomyopathy UK, Pumping Marvellous) have been engaged in all stages of this study. They say this is an incredibly important patient centred project targeting a major unmet need.