心血管疾病临床药学论文

Chronic kidney disease is a risk factor for cardiovascular diseaseChronic kidney disease (CKD) is a widespread concern of public health, the incidence increased gradually, at the same time brought about serious consequences and problems. We note that the patient's renal failure is dialysis and kidney transplantation, but few scholars concerned about CKD and cardiovascular disease (CVD) relationship. Now that CKD with CVD-related, and progress than acute renal failure more likely die of cardiovascular disease, CVD is the most common CKD the cause of death [1]. Recognized that CKD is a risk factor for CVD that is very important. Only in this way will it be possible to conduct an in-depth, and then search for the prevention and treatment of related measures to ensure greater benefits for these patients. CKD is defined as biopsy or the markers of renal damage confirmed> 3 months, or GFR <60ml / ()> 3 months. Cause of disease and the general based on credits for the diabetic and non-diabetic renal disease and transplantation. Renal dysfunction by renal biopsy or related markers such as proteinuria, abnormal urinary sediment, abnormal imaging to diagnose and so on. Proteinuria is not only to prove the existence of CKD, renal disease may also become an important basis for the type of diagnosis and the severity of kidney disease and cardiovascular disease-related. Urinary albumin and creatinine ratio or total protein and creatinine ratio can be used to assess proteinuria. GFR <60ml / () renal damage as a critical value, which indicates the level of GFR is often the beginning of renal failure, including increased incidence of cardiovascular disease and the degree of risk. GFR <15ml / () will need dialysis treatment. GKD especially terminal kidney disease (ESRD) patients, CVD risk of a marked increase in general through the vascular tree to achieve. ESRD with atherosclerosis may be a causal relationship to each other, on the one hand, accelerated atherosclerosis in kidney disease progress, on the other hand, ESRD is the deterioration of many of the traditional atherosclerotic risk factors [2]. In general, CVD is the basic types of vascular disease and cardiomyopathy, the two subtypes of vascular disease is atherosclerosis and vascular remodeling, and CKD are the role of these two subtypes. Atherosclerotic plaque formation and the main obstruction in the main, CKD in atherosclerosis and the high incidence of a much wider range of diffuse atherosclerosis in a marked increase in cardiovascular disease mortality and accelerated deterioration of renal function. Atherosclerosis can lead to arterial wall thickening and myocardial ischemia matrix. In CKD patients, ischemic heart disease such as angina, myocardial infarction and sudden death, and cerebrovascular disease, peripheral vascular disease and heart failure are more common. Initially that the dialysis patients may be secondary to ischemic heart disease in easy to overload, left ventricular hypertrophy and small artery disease, resulting in reduced oxygen supply. However, studies have found that EPO in the former region, the low level of hemoglobin that also may be associated with ischemia-related. CKD patients the incidence of major vascular remodeling is higher, can lead to vascular remodeling in pressure overload, through the wall and the cavity wall thickening and increased the ratio of traffic overload, or to achieve, but mainly to increase the diameter and the wall thickness of main. Vascular remodeling in arterial compliance often dropped, resulting in increased systolic blood pressure, pulse pressure increased, left ventricular hypertrophy and reduced coronary perfusion [3,4]. Decreased arterial compliance and increased pulse pressure in dialysis patients are cardiovascular disease (CVD) risk factors independent [5].水钠潴留period as a result of dialysis treatment by ultrafiltration, dialysis patients with the diagnosis of heart failure more difficult, but the decline in blood pressure, fatigue, loss of appetite and other signs of heart failure diagnosis can be used as an important clue; On the other hand, more水钠潴留inappropriate to reflect the ultrafiltration rather than heart failure or heart failure combined ultrafiltration inappropriate. In fact, during dialysis ultrafiltration is inappropriate for one of the reasons why high blood pressure, heart failure often prompts. Therefore, dialysis patients with heart failure is an important indicator of poor prognosis, which often prompts the patient is in progress of cardiovascular disease. 1 chronic kidney disease risk factors of cardiovascular disease Is well known that patients suffering from kidney disease increase in cardiovascular disease mortality, largely attributable to high blood pressure caused by kidney disease, dyslipidemia, and anemia, but may lead to the causes of plaque rupture is not clear. Light to moderate CKD patients significantly increased the risk of vascular events, and when GFR <45ml / () at the risk greater. Recent studies suggest that due to ACEI (such as captopril, etc.) can reduce chronic kidney disease patients after myocardial infarction risk, if there is no clear contraindication, it is recommended conventional [6]. In normal circumstances, the application of chronic kidney disease treatment of ACEI or ARBs should be careful, it is necessary to understand the benefits of the application, but also take into account blood pressure, renal function, blood electrolyte changes, and possible interactions between drugs, such as the decline in renal function occur, increased serum potassium, etc. must be stopped [1]. In CKD in CVD risk factors to be divided into two types of traditional and non-traditional, traditional risk factors are the main means used to assess symptoms of ischemic heart disease factors such as age, diabetes, systolic blood pressure, left ventricular hypertrophy, and low HDL - C and so on, these factors and the relationship between cardiovascular disease and most people are the same. And define the non-traditional risk factors need to meet the following conditions: (1) to promote the development of CVD rationality biology; (2) the risk factors increased with the severity of kidney disease-related evidence; (3) reveals the CKD and the risk of CVD factors relevant evidence; (4) risk factors in the control group after treatment to reduce CVD evidence. Has been identified in non-traditional risk factors are mainly Hyperhomocysteinemia, oxidative stress, abnormal lipid levels, and atherosclerosis-related increase in markers of inflammation [7]. Recent study found that dialysis patients with oxidative stress and inflammatory markers significantly higher than the general population. Oxidative stress and inflammation may become the basic medium, while other factors such as anemia and cardiac disease, and calcium and phosphorus metabolic abnormalities and vascular remodeling and a decline in vascular compliance. Failure cardiovascular disease CVD mortality in dialysis patients than the general population 10 to 30 times, and the emergence of heart failure after acute myocardial infarction and high mortality rates, myocardial infarction within 1 to 2 years up to 59% mortality ~ 73%, significantly higher than the general crowd, and the Worcester heart Attack Study found that 3 / 4 males and 2 / 3 of women suffering from acute myocardial infarction in diabetic patients still alive after 2 years. At the same time hemodialysis patients atherosclerosis, heart failure and left ventricular hypertrophy abnormally high incidence of nearly 40% of the patients of ischemic heart disease or heart failure. Cardiovascular disease after renal transplantation Renal transplant patients, 35% ~ 50% of CVD death, CVD mortality than the general population of high 2-fold, but was significantly lower than that in hemodialysis patients. The most likely reason is acceptable from a kidney transplant and dialysis-related hemodynamic abnormalities and abnormal toxins. CVD after renal transplantation is the multiple risk factors, and not only include traditional factors such as hypertension, diabetes, hyperlipidemia, left ventricular hypertrophy, and have a decline in GFR of the non-traditional factors such as hyperhomocysteinemia, as well as immune suppression and exclusion. of cardiovascular disease in diabetic nephropathy Early diabetic nephropathy is mainly expressed in microalbuminuria, and progression of cardiovascular disease. Although type 1 diabetes patients with normal blood pressure, but was found in 24h at night to monitor the existence of "Nondipping" mode, may lead to microalbuminuria. "Nondipping" is identified the risk factors of cardiovascular disease, microalbuminuria with the diabetic patients are more vulnerable to dyslipidemia, blood glucose and blood pressure difficult to control. The study has confirmed that microalbuminuria with CVD have a clear relationship between the two types of diabetes in both the presence, but because of the age factor in type 2 diabetes in the more significant. Microalbuminuria is now considered that the prognosis of diabetic patients with cardiovascular disease and other factors in the risk of death indicators point of view can be explained as follows: (1) traditional microalbuminuria individual a higher incidence of risk factors; (2) micro - proteinuria can reflect the endothelial dysfunction, increased vascular permeability, abnormal coagulation and fibrinolysis system; (3) and inflammatory markers related; (4) are more vulnerable to end-organ damage. Prior studies suggest that the recent high blood pressure and vascular endothelial dysfunction, and therefore these patients may further aggravate the endothelial damage. However, the mechanism is not entirely clear at present that may be related to L-arginine transport by endothelial cells to damage, which led to the cell matrix of the lack of NO synthesis. Non-diabetic renal disease cardiovascular disease We mainly albuminuria and decreased GFR as a sign of chronic kidney disease, proteinuria than at the same time that microalbuminuria is more important, because whether or not there is diabetes, nephrotic syndrome and cardiovascular disease are related to the existence of the abnormal changes, such as serious hyperlipidemia and high blood coagulation status, etc. This explains the importance of reducing proteinuria. At present, we risk groups were divided into 3 groups, has been suffering from CVD, other vascular disease or diabetes as a high-risk groups; with traditional CVD risk factors such as high blood pressure, age, etc., as the crowd in danger; the community known as the low-risk group members 翻译.. 慢性肾病是心血管疾病的危险因素慢性肾病（CKD）是值得广泛关注的公共健康，发病率逐渐上升，同时带来了严重的后果和问题。我们注意到肾衰病人的主要是透析和肾移植，但是很少有学者关注CKD与心血管疾病（CVD）的关系。现已认为CKD也与CVD有关，且比急性进展中的肾功能衰竭更容易死于心血管疾病，CVD是 CKD最常见的死亡原因〔1〕。认识到CKD是CVD的高危因素这一点，是很重要的。只有这样，才有可能进行深入，进而寻求相关的预防和治疗措施，使这些病人获得更大益处。 CKD是指由肾活检或有关的标志物证实的肾功损害＞3个月，或GFR＜60ml/（）＞3个月。一般依据病和病因学分为糖尿病性、非糖尿病性和移植后肾病。肾功能损害可通过肾活检或相关的标志物如蛋白尿、异常尿沉积物、影像学异常等来诊断。蛋白尿不仅可以证明CKD的存在，亦可成为肾病类型诊断的重要依据，并与肾脏疾病的严重程度和心血管疾病的有关。尿白蛋白与肌酐比率或总蛋白与肌酐比率可用于评估蛋白尿。GFR＜60ml/（）作为肾功损害的临界值，该水平GFR往往预示肾衰的开始，其中也包括增加心血管疾病的发生及危险程度。GFR＜15ml/（）则需要透析治疗。 GKD尤其是终末肾病（ESRD）患者，CVD危险明显增加，一般通过血管树来实现的。ESRD与动脉粥样硬化可能互为因果关系，一方面粥样硬化加速肾病进展，另一方面ESRD恶化是许多传统粥样硬化的危险因素〔2〕。一般而言，CVD的基本类型是血管疾病和心肌病，血管疾病的两种亚型是动脉粥样硬化和大血管重塑，而CKD对这两种亚型均有作用。动脉粥样硬化主要以斑块形成和闭塞为主，CKD中动脉粥样硬化发生率很高而且范围更广，弥漫的粥样硬化明显增加心血管疾病死亡率和加速肾功能恶化。动脉粥样硬化可导致动脉壁基质增厚和心肌缺血。在CKD病人中，缺血性心脏病如心绞痛、心梗和猝死，以及脑血管疾病、外周血管疾病和心衰都是比较常见的。最初认为透析病人出现缺血性心脏病可能继发于容易超载、左室肥厚和小动脉病变，导致氧供减少。但是后来的研究发现，在前促红素区域，血红蛋白水平低，说明亦可能与缺血有关。CKD病人大血管重塑发生率亦较高，血管重塑可导致压力超载，通过管壁增厚和管壁与内腔比值增高或者流量超载来实现，但主要以增加的管壁直径和厚度为主。血管重塑常常使动脉顺应性下降，导致收缩压增加、脉压增大、左室肥厚和冠脉灌注减少〔3，4〕。动脉顺应性下降和脉压增大均为透析病人心血管疾病（CVD）的独立危险因素〔5〕。由于透析期间水钠潴留可通过超滤得到治疗，透析病人心衰的诊断比较困难，但血压下降、疲劳、食欲减退等征象，可作为心衰诊断的重要线索；另一方面，水钠潴留更能反映超滤不合适，而不是心衰或心衰合并超滤不恰当。实际上，透析期间超滤不合适的原因之一就是高血压，往往提示心衰。因此，心衰是透析病人预后不良的重要指标，这往往提示病人心血管疾病正在进展。 1 慢性肾病的心血管疾病危险因素 众所周知，患肾脏疾病的病人心血管病死亡率增加，很大程度上归因于肾病所致的高血压、血脂异常和贫血，但可能导致粥样斑块破裂的原因还不是很清楚。轻到中度CKD病人血管事件危险明显增高，而当GFR＜45ml/（）时这种危险更大。近期有关研究认为因 ACEI（如卡托普利等）可降低慢性肾病病人心梗后的危险，如没有明显禁忌证，建议常规〔6〕。而在一般情况下，慢性肾病应用ACEI或ARBs治疗要慎重，既要了解应用的益处，又要考虑到血压、肾功能、血电解质变化和可能的药物间相互作用，如出现肾功能下降、血钾增高等就必须停药〔1〕。 在CKD中把CVD的危险因素分为传统和非传统两种，传统的危险因素主要指用于评估有症状缺血性心脏病的因素，如年龄、糖尿病、收缩性高血压、左室肥厚、低HDL-C等，这些因素与心血管疾病的关系与一般人是一致的。 而界定非传统危险因素需要满足如下条件：（1）促进CVD发展的生物学方面的合理性；（2）危险因素升高与肾病严重程度相关的证据；（3）揭示CKD中CVD与危险因素关系的相关证据；（4）有对照组中危险因素经治疗后CVD降低的证据。目前已确定的非传统危险因素主要有高同型半胱氨酸血症、氧化应激、异常脂血症、与粥样硬化有关的增高的炎症标志物〔7〕。近来研究发现，透析病人氧化应激和炎症标志物水平明显高于一般人群。氧化应激和炎症有可能成为基本的介质，而其他因素如贫血与心肌病有关，钙磷代谢异常与血管重塑和血管顺应性下降有关。 肾衰中心血管疾病 透析病人中CVD死亡率比普通人群高10～30倍，而出现急性心梗和心衰后致死率很高，心梗后1～2年死亡率达59%～73%，明显高于一般人群，而Worcester heart Attack研究发现，有3/4男性和2/3女性糖尿病病人患急性心梗后仍存活2年以上。同时血液透析病人动脉粥样硬化、心衰和左室肥厚发生率异常增高，有接近40%的病人出现缺血性心脏病或心衰。 肾移植后心血管疾病 肾移植病人中有35%～50%因CVD死亡，CVD死亡率比普通人群高2倍，但明显低于血液透析病人。最可能的原因是接受肾移植后免除了与透析有关的血流动力学异常和毒素异常。肾移植后CVD的危险因素是多重的，既包括传统因素如高血压、糖尿病、高脂血症、左室肥厚，亦有与GFR 下降有关的非传统因素如高同型半胱氨酸血症以及免疫抑制和排斥。 糖尿病肾病的心血管疾病 糖尿病肾病的早期主要表现为微量白蛋白尿，与心血管疾病进展有关。尽管1型糖尿病病人血压正常，但在24h监测中发现夜间存在 “Nondipping”模式，可能导致微量白蛋白尿。“Nondipping”是已确认的心血管疾病的危险因素，伴有微量白蛋白尿的糖尿病病人也更易出现血脂异常、血糖难以控制和血压升高。有关研究已证实微量白蛋白尿与CVD有明确关系，在两种类型糖尿病中均存在，但由于年龄因素在2型糖尿病中更显著。现已认为微量白蛋白尿是糖尿病病人心血管疾病预后和其他致死因素的危险指标，可通过如下观点来解释：（1）微量白蛋白尿个体传统危险因素发生率更高；（2）微量白蛋白尿能反映内皮功能异常、血管渗透性增加、凝血纤溶系统异常；（3）与炎症标志物有关；（4）更易出现终末器官损害。最近Prior研究认为高血压与血管内皮功能异常有关，因此在这类病人中可能进一步加重内皮损害。但有关机制不完全清楚，目前认为可能与L-精氨酸转运至内皮细胞受到损害有关，进而导致细胞内合成NO的基质缺乏。 非糖尿病性肾病的心血管疾病 我们主要把蛋白尿和GFR下降作为慢性肾病的标志，同时认为蛋白尿比微量白蛋白尿更重要，因为无论是否存在糖尿病，肾病综合征均存在与心血管疾病有关的异常改变，如严重高脂血症和高凝血状态等，这就说明降低蛋白尿具有重要意义。目前我们把危险人群分为3组，已经患CVD、其他血管病或糖尿病作为高危人群；具有CVD传统的易患因素如高血压、年龄等作为中危人群；将社区人员称为低危人群