Uric acid: role in cardiovascular disease and effects of losartan

A substantial body of epidemiological and experimental evidence suggests that serum uric acid is an important, independent risk factor for cardiovascular and renal disease especially in patients with hypertension, heart failure, or diabetes. Elevated serum uric acid is highly predictive of mortality in patients with heart failure or coronary artery disease and of cardiovascular events in patients with diabetes. Further, patients with hypertension and hyperuricemia have a 3- to 5-fold increased risk of experiencing coronary artery disease or cerebrovascular disease compared with patients with normal uric acid levels. Although the mechanisms by which uric acid may play a pathogenetic role in cardiovascular disease is unclear, hyperuricemia is associated with deleterious effects on endothelial dysfunction, oxidative metabolism, platelet adhesiveness, hemorheology, and aggregation. Xanthine oxidase inhibitors (e.g., allopurinol) or a variety of uricosuric agents (e.g., probenecid, sulfinpyrazone, benzbromarone, and benziodarone) can lower elevated uric acid levels but it is unknown whether these agents reversibly impact cardiovascular outcomes. However, the findings of the recent LIFE study in patients with hypertension and left ventricular hypertrophy suggest the possibility that a treatment-induced decrease in serum uric acid may indeed attenuate cardiovascular risk. LIFE showed that approximately 29% (14% to 107%, p = 0.004) of the treatment benefit of a losartan-based versus atenolol-based therapy on the primary composite endpoint (death, myocardial infarction, or stroke) may be ascribed to differences in achieved serum uric acid levels. Overall, serum uric acid may be a powerful tool to help stratify risk for cardiovascular disease. At the very least, it should be carefully considered when evaluating overall cardiovascular risk.     

The concentration of uric acid in patients with metabolic syndrome and cardiovascular diseases

The association of elevated serum uric acid (hyperuricemia, gout) with the presence of classical coronary risk factors and coronary artery disease (CAD) or myocardial infarction (MI) has been analysed in many epidemiological studies. Numerous studies have revealed that hypertension, high body mass index (BMI), lipid disorders (especially raised triglyceride (TG) levels and low high dense lipoprotein cholesterol (HDL-C) level), and increased creatinine or insulin levels have caused hyperuricemia. Gout has often occurred with typical disorders for the metabolic syndrome X. Significant correlation of the serum uric level and the CAD presence and severity of coronary atherosclerosis confirmed by coronary angiography has been observed in women. Hyperuricemia has also indirect influence on progress of CAD by physical activity restriction, what causes sedentary mode of life and lead to obesity. Therefore, we conducted our study in order to estimate uric acid levels in patients with metabolic syndrome and coexisting cardiovascular system diseases.     

Hyperuricemia,the kidneys,and the spectrum of associated diseases: a narrative review

Hyperuricemia (elevated serum uric acid) is prevalent, and an important mediator of gout, an increasingly common condition. In addition, hyperuricemia is associated with metabolic syndrome, diabetes, hypertension, and kidney and cardiovascular diseases. Although it remains controversial whether hyperuricemia is a causal factor for kidney disease, the kidneys play a major role in the regulation of serum uric acid levels. Approximately two-thirds of the uric acid produced in humans is excreted by the kidneys. The handling of urate in the renal proximal tubule is extensive, as uric acid undergoes filtration, reabsorption, and secretion. Variations in renal urate handling have been shown to influence the risk of gout. In observational studies, hyperuricemia has been shown to predict kidney disease onset and progression, with a variety of mechanisms implicated. Because of this close association between hyperuricemia and kidney disease, and due to limited studies on the topic, it is important to conduct future studies on the treatment of hyperuricemia to slow kidney disease progression and improve cardiovascular survival in patients with chronic kidney disease. Furthermore, it is important to monitor for gout in patients with kidney disease and to follow the guidelines for treatment of hyperuricemia in this group of patients. This narrative review provides an in-depth discussion of the link between serum uric acid levels, renal handling of uric acid, and diseases associated with dysfunction in uric acid homeostasis.     

糖尿病合并高尿酸血症相关因素分析

目的分析2型糖尿病（T2DM）合并高尿酸血症的原因及防治效果。方法选择2006年3月至2010年2月收治162例T2DM患者,将合并有高尿酸血症者作为观察组,非高尿酸血症者作为对照组,比较两组患者在年龄、病程、空腹血糖（FBS）、糖化血红蛋白（HbAle）、总三酰甘油（TG）、总胆固酵（TC）、肌酐（Cr）、冠心病、高血压、脑血管意外等方面上的差异。结果高尿酸血症者发生率49.72%,与血肌酐、血脂代谢相关,与空腹血糖、糖化血红蛋白无关;合并冠心病、高血压、脑血管意外较多。结论糖尿病合并高尿酸血症的发病率较高,预后欠佳,对T2DM高尿酸血症者综合防治的基础上,要树立良好的生活方式。     

脑梗死患者血清尿酸及胱抑素C水平与颅内动脉狭窄关系的临床分析

目的 分析脑梗死患者血清尿酸及胱抑素C(Cystatin C,CysC)水平与颅内动脉狭窄的关系.方法 收集107例住院脑梗死患者的临床资料,均完成头颅CTA及常规生化检查,根据颅内大血管近端狭窄程度分为无狭窄组、轻度狭窄组和中重度狭窄组,分别比较三组间性别、年龄、吸烟、饮酒、高血压、糖尿病、三酰甘油、总胆固醇、低密度脂蛋白、尿酸、CysC水平和高尿酸、高CysC的发生率.结果 三组分别在年龄、性别、吸烟、饮酒、三酰甘油、低密度脂蛋白、总胆固醇方面比较,均差异无统计学意义(P＞0.05),轻度狭窄及中重度狭窄组的血清尿酸、CysC水平和高血压、糖尿病、高尿酸、高CysC发生率均显著高于无狭窄组(P＜0.05),且中重度狭窄组血清尿酸、CysC水平显著高于轻度狭窄组(P＜0.05),Logistic回归分析显示高尿酸、高CysC均是颅内动脉狭窄的独立危险因素(OR=3.200,P=0.035,95％CI:1.088 ～9.414;OR=3.446,P=0.030,95％ CI:1.250～9.498).结论 高尿酸、高CysC是脑梗死患者颅内动脉狭窄的独立危险因素,其狭窄程度可能与血清尿酸、CysC水平相关,两者之间可能存在协同作用.     

高尿酸血症与冠心病关系的研究

目的探讨高尿酸血症与冠心病的关系。方法选择临床确诊的冠心病患者43例及同期健康查体者50例,分别检测两组对象的血尿酸、血脂以及血糖。结果冠心病患者的血尿酸、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）与健康人相比较,差异具有统计学意义（P〈0.01）;2、3支冠脉病变与单支病变者相比较,差异具有统计学意义。结论冠心病患者的血尿酸明显升高,高尿酸血症很可能是冠心病发生的另一大危险因素。     

高血压合并高尿酸血症与冠心病关系的研究

目的 观察评价高血压(EH)合并高尿酸血症(HUA)与冠心病(CAD)关系.方法 选取2016年3月至12月本院门诊及住院EH病人117例,随机对照试验(Randomized Controlled Trial,RCT)分为3组:单纯EH病人39例设为对照组,EH伴HUA病人39例设为观察A组,EH伴CAD病人39例设为观察B组;并总结3组之间的关系.结果 观察组TC、GLU、UA、Cr等指标均显著高于对照组(均P＜0.05);观察B组血尿酸浓度、HUA并发率均显著高于对照组(均P＜0.05);随冠状动脉病变血管支数的增加,血尿酸浓度与HUA患病率均明显升高,呈线性趋势(均P＜0.05).结论 EH合并HUA与CAD之间存在着必然的内在联系,HUA可能与EH和CAD的发生发展有一定的相关性,对其预后也产生一定影响,因此,显著控制患者血压、血清尿酸值,才能够有效防治和延缓CAD的发生.     

Management of hypertension and dyslipidaemia in patients presenting with hyperuricaemia: case histories

A number of studies have shown that hyperuricaemia is associated with an increased incidence of coronary heart disease. It has been proposed that the elevated serum uric acid levels are linked to other risk factors, such as hypertension, dyslipidaemia and diabetes. Hyperuricaemia is commonly encountered in patients with essential hypertension and is considered as a risk factor for morbidity and mortality associated with hypertension. In addition, lipid abnormalities (mainly hypertriglyceridaemia) are also found more frequently in hypertensive patients than in normotensives. There is evidence that the angiotensin II receptor antagonist, losartan, increases urate excretion by reducing reabsorption of urate in the renal proximal tubule. It is also known that fibric acid derivatives (fibrates) have several beneficial actions in addition to their lipid-lowering capacity. Fenofibrate administration is associated with a uric acid lowering effect. In this respect, we present two patients with hypertension and dyslipidaemia together with elevated serum uric acid levels. We also discuss (in the format of questions and answers) the pathophysiological mechanisms underlying the association of serum uric acid with cardiovascular disease, and we review the relevant literature to justify an evidence-based decision to choose an antihypetensive agent (losartan) or a lipid-lowering drug (fenofibrate) with an additional hypouricaemic effect.     

Management of Hypertension and Dyslipidaemia in Patients Presenting with Hyperuricaemia: Case Histories

Summary

A number of studies have shown that hyperuricaemia is associated with an increased incidence of coronary heart disease. It has been proposed that the elevated serum uric acid levels are linked to other risk factors, such as hypertension, dyslipidaemia and diabetes. Hyperuricaemia is commonly encountered in patients with essential hypertension and is considered as a risk factor for morbidity and mortality associated with hypertension. In addition, lipid abnormalities (mainly hypertriglyceridaemia) are also found more frequently in hypertensive patients than in normotensives. There is evidence that the angiotensin II receptor antagonist, losartan, increases urate excretion by reducing reabsorption of urate in the renal proximal tubule. It is also known that fibric acid derivatives (fibrates) have several beneficial actions in addition to their lipidlowering capacity. Fenofibrate administration is associated with a uric acid lowering effect. In this respect, we present two patients with hypertension and dyslipidaemia together with elevated serum uric acid levels. We also discuss (in the format of questions and answers) the pathophysiological mechanisms underlying the association of serum uric acid with cardiovascular disease, and we review the relevant literature to justify an evidence-based decision to choose an antihypetensive agent (losartan) or a lipidlowering drug (fenofibrate) with an additional hypouricaemic effect.     

糖尿病合并冠心病患者血清尿酸水平分析

目的探讨糖尿病合并冠心病患者尿酸水平与冠状动脉病变的关系。方法2型糖尿病患者108例，经冠状动脉造影检查确诊为冠心病患者52例，为冠心病组；56例确诊为未合并冠心病患者，为非冠心病组；根据冠状动脉受累情况，分为1支、2支、3支病变组，并测定血尿酸（SUA）水平。结果冠心病组尿酸水平高于非冠心病组。结论血清尿酸水平是糖尿病合并冠心病患者冠状动脉病变的危险因素。     

老年女性高尿酸血症与冠状动脉病变程度的相关性

目的 探讨老年女性高尿酸血症(Hyperuricemia,HUA)与冠状动脉造影确诊的冠心病的冠脉病变程度的关系.方法 回顾性分析400例老年女性,根据冠状动脉造影结果分为两组,冠心病组260例,非冠心病组即对照组140例,观察两组吸烟、高血压病、2型糖尿病、高脂血症、冠心病家族史、体重指数及高尿酸血症与冠心病发病的关系.再将老年女性按血尿酸浓度>360 μmol/L的标准诊断高尿酸血症分为HUA组与非HUA组,观察HUA与冠脉病变支数及Gensini积分的关系.结果 ①老年女性冠心病组高尿酸血症的比例(23.1%)高于对照组(12.1%),差异有统计学意义(P<0.05).②HUA为老年女性冠心病发生的影响因素(OR=2.171,95%CI:1.223~3.853,Wald χ2=6.99),但对其他指标进行校正采用多因素Logisitic逐步回归进行危险因素筛选,HUA并不是老年女性冠心病发生的独立危险因素.③老年女性病变血管支数的分布在HUA 组与非 HUA组之间差异有统计学意义(Z=2.78,P<0.05).老年女性HUA患者的Gensini 积分高于非HUA患者(Z=2.08 P<0.05),且在女性的全组、HUA 组及非HUA 组Gensini 积分与血尿酸水平均呈正相关(rs =0.177,0.213,0.152,P<0.05).结论 老年女性HUA与冠心病发生有一定关联,但不是独立危险因素,HUA是反应冠心病病情程度的一个重要指标.老年女性高尿酸血症患者在冠心病诊治上应引起重视.     

500例老年体检人群的尿酸水平及护理措施

目的探讨老年体检人群的尿酸水平及其护理措施。方法将2012年4月至2013年4月在我院进行健康体检的500例老年人作为研究对象,观察研究对象检出的尿酸水平,总结高尿酸血症的发病因素以及相关护理措施。结果 66⁶9岁组的高尿酸血症发生率显著低于7069岁组的高尿酸血症发生率显著低于70⁷8岁组,P<0.05;高尿酸血症组的并发疾病(冠心病、高血脂症、糖尿病、高血压等)的发生率显著高于尿酸正常组,P<0.05。结论高尿酸血症在老年人群中的发生率较高,其发生还可诱发相关并发症,加重病情,预后不良。老年人应定时参加健康体检,以便尽早发现高尿酸血症,早期进行治疗,对于体检检出尿酸水平升高的老年人,尤其要引起重视,应及时到医院就医。     

高血压病患者冠状动脉病变与血清尿酸水平的相关性

目的探讨高血压病患者血清尿酸水平与冠状动脉病变程度的相关性。方法对于经过冠状动脉造影的368例高血压病患者,测定血清尿酸及其它临床生化指标。根据冠状动脉造影结果分为冠心病组(n=240)和正常冠脉对照组(n=128)进行回顾性分析。结果冠心病组的血清尿酸水平(448.32± 115.12)μmol／L明显高于正常冠脉对照组(371.36±98.98)μmol／L(P＜0.001)；多因素逐步回归分析显示高血压病患者的冠状动脉狭窄程度与血清尿酸水平呈显著线性回归关系(P＜0.001)。结论高血压病患者的血清尿酸水平与冠状动脉狭窄程度密切相关。降低血清尿酸水平能否延缓或减轻冠脉病变程度,有待于进一步大规模前瞻性研究加以论证。     

急性冠脉综合征患者冠脉介入术后对比剂肾损伤的危险因素

目的探究急性冠脉综合征(ACS)患者行冠脉介入操作后发生对比剂损伤(CI-AKI)的危险因素。方法回顾性分析2018年宣武医院全年经皮冠状动脉造影术1 007例次,资料完整的ACS患者206例次。根据KDIGO标准将患者分为对照组(非CI-AKI组)(195例)和CI-AKI组(11例)。观察指标:年龄、性别、体重指数、既往病史(高血压,糖尿病,脑血管疾病,心功能不全,高尿酸血症/痛风,慢性肾脏病)、术前尿酸、血肌酐和尿素(术前、术后48 h内或7 d内)、手术类型、病变血管数、水化和血容量。通过进行单因素和多因素分析,筛选出ACS患者PCI术后CI-AKI的危险因素。结果 206例次患者中11例次(5.34%)发生CI-AKI。单因素分析显示,年龄、术前肌酐清除率和高尿酸血症病史等差异有统计学意义(P<0.05)。多因素分析显示,急诊手术(OR=4.881)和高尿酸血症病史(OR=5.916)是CI-CKI的独立危险因素(P<0.05)。结论临床对于CI-AKI的认识不足导致CI-AKI的发病率较低且漏诊率高,PCI术后水化不足。急诊PCI和既往诊断高尿酸血症是CI-AKI的独立危险因素。与术前尿酸水平相比,既往诊断高尿酸血症对于CI-AKI的发生有更强的预测作用。     

Serum uric acid and risk of coronary heart disease

Many large epidemiological studies confirmed a positive association between raised serum uric acid (SUA) levels and risk of coronary heart disease (CHD) or cardiovascular disease (CVD) in the general population, among hypertensive patients and those with established CHD, stroke, diabetes and heart failure. There is much controversy concerning the role of SUA as an independent risk factor for CHD as SUA is related to many of the established risk factors for cardiovascular disease including hypertension, dyslipidaemia, obesity and pre-existing disease. The epidemiological evidence suggests that SUA is an independent predictor of CVD in subjects with hypertension and established vascular disease but not in healthy subjects. This evidence suggests that the influence of SUA on CHD is explained by the secondary association of SUA with other established etiological risk factors (hypertension, dyslipidaemia, hyperinsulinaemia, obesity and pre-existing disease). There is no evidence so far to indicate that lowering SUA levels with drug treatment has a beneficial effect on CVD outcome. In summary, there is little support for an independent causal role for SUA in the development of CHD. However, SUA may provide useful prognostic information in subjects with hypertension and vascular disease.     

高尿酸血症与冠心病危险因素相关性的研究

目的探讨高尿酸血症与血压、脂代谢紊乱、血糖等冠心病危险因素的关系。方法收集5304例检测者分为高尿酸组及正常酸组,将各种临床资料分析。结果高尿酸血症的患病率为19．8％,其中血尿酸高于均数者,男性更多,更加肥胖,收缩压和舒张压增高,甘油二三酯升高,血糖更高。男性、体重指数、舒张压、甘油三酯、血糖是预测血尿酸升高的主要因素。结论血尿酸水平的升高与肥胖,脂代谢紊乱,血压升高,糖尿病密切相关,高尿酸血症是冠心病的危险因素之一,可能成为预测冠心病严重程度的生化指标。     

Vascular and metabolic effects of angiotensin II receptor blockers

Angiotensin II receptor blockers (ARBs) are widely used in patients with hypertension, heart failure and type 2 diabetes mellitus (T2DM). Several large clinical trials have demonstrated that these agents are effective in reducing cardiovascular mortality and morbidity. These benefits are partly independent of the degree of blood pressure reduction and most likely related to ARBs' anti-inflammatory, metabolic and vascular effects. Clinical studies showed that the anti-inflammatory effect of ARBs could be related to the dosage and/or the length of the treatment. In large clinical trials, ARBs have inconsistently reduced the risk of new-onset T2DM. Among ARBs, only losartan significantly reduced serum uric acid levels. Moreover, it has been demonstrated that ARBs improve endothelial dysfunction in patients with hypertension and/or coronary artery disease (CAD), while all but one of the studies proved that these agents could usually, after 6 – 12 months of therapy, induce regression of vascular hypertrophy in hypertensive patients. These positive effects could be relevant to vascular protection and, together with the blood pressure reduction, constitute the background of the improved outcome observed in clinical studies on mortality and/or morbidity in hypertensive, high-risk and CAD patients. The clinical significance of the different potency of ARBs needs to be investigated further in specific and adequately powered trials.     

冠心病患者血清胆红素与尿酸的检验价值分析

目的观察血清胆红素与尿酸对冠心病患者的检验价值。方法从我院收治入院的冠心病患者中抽取35例组成观察组,另从同期正常体检人群中抽取35例作为对照组,对两组患者进行血常规检测,并对比其血尿酸与血清总胆红素、血清直接胆红素的水平。结果观察组患者的血尿酸水平明显高于对照组,而血清胆红素水平则明显低于对照组;多支动脉出现病变患者相较单支病变患者血尿酸水平明显升高,而血清胆红素水平明显下降,以上差异均有统计学意义(P<0.05);两组患者血清直接胆红素水平相近,差异不具有统计学意义(P>0.05)。结论冠心病患者的血清总胆红素和尿酸水平与正常人差异较大,且这两项指标对冠状动脉病情的发展有一定的提示作用,因此可以在临床上作为冠心病患者的检查指标。     

高尿酸血症与糖尿病心脑血管并发症的关系

目的 探讨高尿酸血症对2型糖尿病(T2DM)心脑血管并发症的影响.方法 对430例T2DM患者,根据血尿酸水平分成高尿酸组(观察组)和正常血尿酸组(对照组),比较两组UA、Cr、TC、TG、FBS、HbA1c、BMI的差别及冠心病、高血压、急性脑血管意外发生情况.结果 两组患者FBS、HbA1c间差异均无统计学意义(P＞0.05);高尿酸组BMI、TG、TC、Cr高于对照组(P＜0.05);高血压、冠心病、脑血管病发病率也高(P＜0.05).结论 高尿酸血症与肥胖、血脂异常明显相关;加重T2DM患者的代谢紊乱,并促进心脑血管并发症的发生和发展.     

高尿酸血症与缺血性卒中及其药物治疗

全球多项研究显示,高尿酸血症是缺血性脑卒中的独立危险因素之一,血尿酸水平升高可增加脑卒中的发生率和死亡率。高尿酸血症与缺血性卒中的危险因素(高血压、糖尿病、高血脂、动脉粥样硬化等)共同促进缺血性脑卒中的发生。对高尿酸血症的治疗已经从急性期治疗转变为强调长期控制血尿酸达标,预防各种合并症。高尿酸血症的治疗包括调整饮食结构、改变生活方式、积极控制与血尿酸升高相关的危险因素、避免应用血尿酸升高的药物、碱化尿液等。降低血尿酸的药物包括增加尿酸排泄的药物、抑制尿酸合成药物、辅助降尿酸药。如果引起血尿酸增高的原因不能去除,需要长期降尿酸治疗。