尿酸代谢失衡与心血管疾病及药物干预

尿酸是体内嘌呤代谢的终末产物,与各类心血管疾病的发生发展密切相关,是心血管疾病的重要危险因子之一。综述尿酸的代谢及生理病理意义,尿酸代谢失衡与急性心肌梗死、高血压、胰岛素抵抗、肥胖症等心血管疾病的关联以及尿酸代谢失衡的药物干预与心血管保护作用。     

Efficacy and Safety of a Urate Lowering Regimen in Primary Gout

Background and Objectives. Pharmacologic urate lowering therapy (ULT), at full maintenance doses, has been associated with acute gout arthritis (in up to 80% of patients). The American College of Rheumatology has recently advocated gradually titrating the maintenance dose upward to chosen serum urate target. Few studies have examined the efficacy and safety of a ULT in primary gout. Patients and Methods. The ULT regimen examined included allopurinol (50 mg/day, with increases of 50 mg/month up to 300 mg/day) and colchicine, as prophylaxis to prevent acute gouty attacks. The efficacy and safety of this regimen was examined in 42 patients in whom allopurinol was withheld for ≥3 months and restarted after this assessment and followed up for 12 months. The efficacy and safety of the ULT regimen was related to the serum urate decrease and to the incidence of acute gout flares, respectively. Results. Fifty-nine patients (mean age 59 years, 56 men) with primary gout received the gradually titrated ULT regimen. Baseline serum urate was (mean ± SD) 8.4 ± 0.8 mg/dL. At 3, 6, 9, and 12 months serum urate fell by a mean of 1.8, 2.5, 2.7, and 2.5 mg/dL, respectively (p < 0.001). A serum urate level <6.0 mg/dL was achieved by 38/59 (64%) patients. During the 12 months following the start of the ULT we documented 10 acute arthritis episodes (17% of patients). Conclusions. A gradually titrated hypouricemic regimen for 6 months in patients with primary gout appears to be effective and safe.     

非布司他对痛风合并高尿酸血症患者血清sICAM-1, ET-1 及尿酸水平的影响

目的:探讨非布司他对痛风合并高尿酸血症患者血清内皮素-1(ET-1)、细胞间粘附分子-1(ICAM-1)及尿酸水平的影响。方法:收集在我院就诊或住院治疗的80例痛风合并高尿酸血症患者,随机分为实验组和对照组,每组40例。对照组患者给予别嘌呤醇片治疗;实验组患者给予非布司他片治疗。观察并比较两组患者治疗前后血尿酸、s ICAM-1、ET-1水平及临床疗效。结果:与治疗前相比,两组患者治疗后的血尿酸、s ICAM-1、ET-1水平均显著降低(P0.05);与对照组相比,实验组患者的血尿酸、s ICAM-1、ET-1水平较低(P0.05),临床治疗总有效率较高(P0.05)。结论:非布司他能够降低痛风合并高尿酸血症的s ICAM-1、ET-1及尿酸水平,且临床疗效较好。     

Metabolic Syndrome in Primary Gout

Background and Objectives. Primary gout has traditionally been associated with obesity, arterial hypertension, and abnormal lipid and glucose homeostasis, but we do not know the prevalence of these vascular risk factors in patients with primary gout from a Mediterranean country. Patients and Method. All patients with primary gout and 2 or more acute arthritis episodes documented by a physician were selected for the study. The diagnosis of MS required ≥3 criteria (ATP III). Patients were classified in two groups: decreased (underexcretors) and normal (normoexcretors) uric acid excretion related to serum urate levels. Results. One hundred and four patients (mean age, 59 years; 100 males) with primary gout were included in the study. MS was diagnosed in 38 subjects (37%). The most frequent triad defining MS was an increased waist circumference, blood pressure, and trygliceride levels. The prevalence of type 2 diabetes mellitus (T2D) was significantly higher in patients with the MS (21/38, 55%) as compared with subjects without the MS (3/66, 5%; p < 0.001). Mean serum urate level in patients with and without MS was identical (8.1 mg/dL), but mean 24-hour uric acid excretion was significantly lower in the former than in the latter (444 ± 110 mg/24-hour/1,73 m² versus 546 ± 221 mg/day/1,73 m²; p = 0.009). Conclusions. The condition of the MS occurs in about one-third of the patients with primary gout. Increased waist circumference, blood pressure, and triglycerides levels is the most frequent MS triad. Diminished urinary uric acid excretion is more severe in gout patients with the MS.     

脑血管疾病患者血尿酸和纤维蛋白原的测定与分析

目的:为了解脑血管疾病患者血尿酸、血浆纤维蛋白原水平及相互关系。方法:对81例脑梗死患者、77例脑出血患者和55例时照者采血测定血尿酸、血浆纤维蛋白原,并分析二者的相关性。结果:脑梗死疾病组和脑出血疾病组UA和Fib水平均高于时照组(P＜0．05);脑血管疾病组组间无差异(P□0．05);血尿酸和血浆纤维蛋白原二者间无相关性。结论:血尿酸、血浆纤维蛋白原作为脑血管疾病的危险因素可能是独立存在的。     

Effects of Losartan/Hydrochlorothiazide on Serum Uric Acid Levels and Blood Pressure in Hypertensive Patients

The effect of a mixed formulation of 50 mg losartan (LOS) and 12.5 mg hydrochlorothiazide (HCTZ) on blood pressure and the uric acid metabolism was analyzed in 73 patients who switched to this formulation from other antihypertensive drugs. Eight patients who switched to the formulation from the regular dose of renin-angiotensin (RA) inhibitor (angiotensin receptor blocker [ARB] or angiotensin-converting enzyme [ACE] inhibitor) only showed a significant decrease in blood pressure, from 156.9 ± 14.1/88.6 ± 9.7 mmHg to 128.3 ± 16.0/76.1 ±10.7 mmHg (p = 0.007), and a significant increase in serum uric acid levels, from 5.2 ± 1.1 mg/dL to 6.8 ± 0.7 mg/dL (p = 0.02). In the other 50 patients who switched from a combination of the regular dose of RA inhibitor and calcium channel blocker (CCB), their blood pressure significantly increased, from 126.0 ± 13.8/72.0 ± 10.0 mmHg to 132.5 ± 16.4/76.5 ± 11.3 mmHg (p = 0.02), and their serum uric acid levels also significantly increased, from 5.6 ± 1.1 mg/dL to 6.1 ± 1.3 mg/dL (p = 0.0002). Considering that guidelines recommend using antihypertensive therapies that do not lead to an increase in serum uric acid levels, we conclude that using the ARB/HCTZ combination is less suitable than the regular dose of the ARB/CCB combination due to its effect on hypertension and serum uric acid levels.     

The Treatment of Gout and Disorders of Uric Acid Metabolism with Allopurinol

Allopurinol (4-hydroxypyrazolo (3,4-d)-pyrimidine) is a potent xanthine oxidase inhibitor which inhibits the oxidation of naturally occurring oxypurines, thus decreasing uric acid formation. The clinical and metabolic effects of this agent were studied in 80 subjects with primary and secondary gout and other disorders of uric acid metabolism. Allopurinol has been universally successful in lowering the serum uric acid concentration and uric acid excretion to normal levels, while not significantly affecting the clearance of urate or other aspects of renal function. Oxypurine excretion increased concomitantly with the fall in urine uric acid. The agent is particularly valuable in the management of problems of gout with azotemia, acute uric acid nephropathy and uric acid urolithiasis. The minor side effects, clinical indications and theoretical complications are discussed.     

痛风与单纯性高尿酸血症人群高脂血症的对比分析

目的:对比分析痛风与单纯高尿酸血症合并高脂血症的情况。方法:收集青岛大学附属医院痛风专病门诊2009年5月至2016年1月收治的痛风患者7207例(男性6759例,女性448例),单纯高尿酸血症患者2095例(男性1852例,女性243例)。测量受试者身高、体重、腰围、臀围、血压、空腹血糖(FPG)、血甘油三酯(TG)、血胆固醇(TC)及血尿酸(UA),计算并比较两组高甘油三脂血症、高胆固醇血症的患病率,并分析其在痛风发生中的独立作用。结果:痛风组高甘油三酯血症和高胆固醇血症的患病率分别为57.8%、47.5%;单纯高尿酸血症组为51.8%、52.9%;两组率相比的比值比,高甘油三脂血症1.274[95%CI(1.155,1.404)],胆固醇血症0.805[95%CI(0.730,0.887)]。按性别分层分析,男性痛风组高甘油三脂血症、高胆固醇血症患病率分别为56.2%,46.8%;单纯高尿酸血症组分别为52.3%,52.6%。两组率相比的比值比,高甘油三脂血症1.25[95CI%(1.13,1.39)],高胆固醇血症0.80[95CI%(0.72,0.89)]。女性中痛风组高甘油三脂血症、高胆固醇血症患病率分别为52.2%,58.90%;单纯高尿酸血症组分别为46.6%,58.0%;两组差异无统计学意义。高甘油三脂血症与痛风的发生正相关OR=1.29,95%CI(1.12,1.48),高胆固醇血症与痛风的发生负相关OR=0.80,95%CI(0.73,0.89)。结论:痛风与单纯高尿酸血症患者存在不同的脂代谢状态,高甘油三酯血症可能是单纯高尿酸血症发展为痛风的危险因素。     

脑小血管病患者血清尿酸水平和步态障碍之间的相关性

目的:探讨脑小血管病(Cerebral small vessel disease,CSVD)患者血清尿酸(Uric acid,UA)水平和步态障碍之间的相关性。方法:将我院自2018年1月至2019年1月收治的CSVD患者172例作为研究对象,根据患者血清尿酸水平分为研究组87例,对照组85例。收集和比较两组的临床资料,使用Logistic回归分析血清尿酸和CSVD患者脑室旁、深部白质高信号、步态障碍之间的相关性。结果:两组的年龄、性别、体质指数、血糖指标、血脂指标水平,合并高血压、糖尿病病史和吸烟情况比较差异无统计学意义(P0.05)。研究组血清尿酸水平、饮酒患者比例明显高于对照组(P0.05),脑室旁高信号和深部白质高信号中重度比例均明显高于对照组(P0.05);将步态障碍、脑室旁高信号与深部白质高信号作为影响因素带入相关分析,结果显示血清尿酸水平与步态障碍、脑室旁高信号与深部白质高信号比较存在正相关(P0.05)。结论:CSVD患者血清高尿酸水平与脑室旁、深部白质高信号病变程度呈明显的正相关性,也是患者步态障碍的影响因素。     

血脂与血尿酸浓度变化在老年脂肪肝患者诊断中的价值

目的：研究血脂与血尿酸浓度变化在老年脂肪肝患者诊断中的价值。方法：选取我院三年来健康体检时确诊为脂肪肝患者 的80 例为观察组,体检结果为健康正常人的80 例为对照组。测定两组总胆固醇、甘油三酯、血尿酸、高密度脂蛋白胆固醇、低密 度脂蛋白胆固醇的值,将检测结果进行对比。结果：两组检测结果对比,观察组的总胆固醇高于对照组的(x2=11.358,P=0.015);观 察组的甘油三酯值高于对照组（x2=7.456,P=0.035）;观察组中的血尿酸,高于对照组值（x2=9.875,P=0.029）、低密度脂蛋白胆固醇 的值,高于对照组（x2=12.037,P=0.013）,高密度脂蛋白胆固醇低于对照组（x2=5.149,P=0.041）。在轻、中、重度三组脂肪肝患者中, 中度脂肪肝患者的总胆固醇、甘油三酯、血尿酸、低密度脂蛋白含量高于轻度脂肪肝患者,高密度脂蛋白含量低于轻度脂肪肝患 者,P＜0.05,差异有统计学意义;重度脂肪肝患者的总胆固醇、甘油三酯、血尿酸、低密度脂蛋白含量高于中度脂肪肝患者,高密度 脂蛋白含量低于中度脂肪肝患者,P＜0.05,差异有统计学意义。结论：脂肪肝病变程度越大,脂肪肝患者总胆固醇、甘油三酯、血尿 酸、低密度脂蛋白胆固醇的值越高,高密度脂蛋白胆固醇的值越低,血脂与血尿酸浓度变化可作为诊断脂肪肝疾病的依据,可实 现早发现、早治疗,值得应用。     

丹红注射液对急性脑梗死患者血尿酸与胆红素水平的影响

目的:探究丹红注射液对急性脑梗死患者血尿酸与胆红素水平的影响。方法:选取2015年2月到2016年2月我院神经内科收治的急性脑梗死患者96例,根据随机数字对照表分为对照组与试验组,每组各48例。对照组给予患者钙离子拮抗剂尼莫地平缓释片和抗血小板凝集剂阿斯匹林肠溶片治疗,试验组采用常规药物治疗联合给予丹红注射液治疗。观察并比较两组患者的临床疗效以及治疗前后血尿酸与胆红素水平的变化情况。结果:治疗后,两组患者的NIHSS评分及血尿酸与胆红素水平均较治疗前显著降低(P0.05),且与对照组相比,试验组的NIHSS评分及血尿酸与胆红素水平更低(P0.05)。结论:丹红注射液对急性脑梗死患者具有显著的治疗效果,推测可能与降低血尿酸与胆红素的水平有关。     

血清尿酸水平与老年轻度高血压患者的内皮功能相关性分析

目的:探讨血清尿酸水平与老年轻度高血压患者的内皮功能相关性。方法:选取我院2020年1月到2020年12月共收治的200例老年轻度高血压患者作为研究对象,所有患者均为未使用过降压药物治疗,将其分为轻度高血压组。另选取同期收治的200例高血压常规药物治疗患者作为重度高血压组与200名健康者作为对照组,对比三组患者血清尿酸水平与血管内皮功能。对观察组所有患者依照血清尿酸水平进行分组,将血清尿酸水平208-360μmol/L的患者分为低尿酸组,共计136例,将血清尿酸水平≥360μmol/L的患者分为高尿酸组,共计64例。对比两组患者的一般临床指标、血管内皮功能与氧化应激指标,并分析血清尿酸水平与老年轻度高血压患者的内皮功能相关性。结果:重度、轻度高血压组与对照组患者NO、ET-1、SUA水平对比差异显著,具有统计学意义(P<0.05);高尿酸组与低尿酸组患者TG、TC、DBP、SBP水平对比无明显差异(P>0.05),高尿酸组患者Cr水平高于低尿酸组,组间对比,差异具有统计学意义(P<0.05);高尿酸组与低尿酸组患者T-AOC、GSH-Px、LHP、MDA、NO、ET-1水平对比差异显著,高尿酸组患者LHP、MDA和ET-1水平明显高于低尿酸组,高尿酸组患者T-AOC、GSH-Px、NO水平明显低于低尿酸组,组间对比,差异具有统计学意义(P>0.05);Spearman相关分析结果显示:TG、TC、Cr、DBP、SBP与血尿酸水平无明显相关性(P>0.05),T-AOC、GSH-Px、NO与血清尿酸水平呈负相关(P<0.05),LHP、MDA、ET-1与血清尿酸水平呈正相关(P<0.05)。结论:血清尿酸水平与老年轻度高血压患者的内皮功能具有明显相关性,而且证明血尿酸水平的升高可能由患者氧化应激导致,因此氧化应激水平也是引起血管内皮功能障碍的一种潜在机制,希望本研究结果能够为高血压患者的疾病控制提供参考意见。     

原发性肾小球肾炎患者血浆高同型半胱氨酸水平的变化及与钙磷乘积和血尿酸的相关性分析

目的:分析原发性肾小球肾炎患者血浆高同型半胱氨酸(Hcy)水平的变化及其与钙磷乘积、血尿酸(UA)的相关性。方法:选择2016年3月至2018年3月在我院就诊的80例原发性肾小球肾炎患者作为观察组,另选取同期于我院接受体检的50例健康者作为对照组。采用循环酶法测定受检者血浆Hcy水平,通过比色法测定血清UA,采用离子选择电极法测定血清钙离子(Ca^2+)、磷离子(P3+),对比两组各项血液指标水平及阳性检出率,并通过Pearson分析法分析血浆Hcy与钙磷乘积、UA的相关性。结果:观察组血浆Hcy、P^3+、钙磷乘积及UA水平高于对照组,Ca^2+低于对照组,差异有统计学意义(P<0.05)。观察组Hcy、Ca^2+、P^3+、UA阳性检出率高于对照组,差异有统计学意义(P<0.05)。血浆Hcy水平与Ca^2+呈负相关(r=-2.208,P<0.05),与P3+、钙磷乘积、UA呈正相关(r=0.102、0.592、0.703,P均<0.05)。结论:原发性肾小球肾炎患者血浆Hcy水平较高,且其水平与钙磷乘积、UA水平呈正相关,故监测三项指标变化可为临床防治该病提供科学依据。     

Effects of Three Strong Statins (Atorvastatin,Pitavastatin, and Rosuvastatin) on Serum Uric Acid Levels in Dyslipidemic Patients

We have retrospectively investigated the effects of three strong statins, atorvastatin, pitavastatin, and rosuvastatin, on serum uric acid (SUA) levels. SUA levels after a few months of statin treatment were compared with those before treatment in 150 outpatients with dyslipidemia. In the atorvastatin (n = 62) and rosuvastatin (n = 45) groups, the SUA levels were reduced by 6.5% (p < 0.0001) and 3.6% (p = 0.03) respectively, but in the pitavastatin group (n = 43), the SUA level increased by 3.7% (p = 0.38). Because uric acid is considered a risk factor for cardiovascular disorders, atorvastatin or rosuvastatin treatment may be recommended when statins are used in patients at high risk for cardiovascular disorders complicated with hyperuricemia.     

Determinants of the Clinical Outcomes of Gout During the First Year of Urate-Lowering Therapy

Clinical benefit early in urate-lowering treatment of gout is difficult to document. We examined data from 1,832 gouty subjects treated with either urate-lowering agents or placebo to identify determinants of gout flare incidence and tophus size during year 1 of treatment. Reductions from pretreatment serum urate levels influenced flare frequency and tophus size, but the effect of urate level on flare incidence was biphasic. Lower urate levels were associated with higher flare incidence early in treatment but lower incidence by one year. The complex relationship between urate-lowering and clinical outcome early in treatment has implications for both clinical and investigative approaches to urate-lowering management.     

血尿酸水平与冠状动脉病变程度的关系探讨

目的:探讨血尿酸(SUA)水平与冠状动脉病变程度的关系。方法:将268例疑似冠心病(CHD)患者,经冠状动脉造影分为冠心病组198例和非冠心病组70例;冠心病组又分为单支病变组80例,双支病变组56例,三支病变组62例。分别检测各组研究对象血尿酸含量,同时记录年龄、性别、吸烟、高血压、糖尿病、血尿酸及冠状动脉造影结果,分析血尿酸与已知冠心病主要危险因素、冠状动脉病变程度的相关性。结果:冠心病组血尿酸水平(395.35±84.40)μmol/L,显著高于非冠心病组(282.20±66.68)μmol/L(P<0.05)。单支病变组(338.48±77.36)μmol/L、双支病变组(399.62±84.36)μmol/L、三支病变组(445.16±92.20)μmol/L,血尿酸水平呈递增趋势,各组之间的差异有统计学意义。结论:血尿酸水平可反映冠状动脉病变严重程度。降尿酸治疗有望成为心血管疾病防治的一种新途径。     

Serum Uric Acid Levels and Risk of Metabolic Syndrome in Healthy Adults

ObjectiveTo investigate the relationship between hyperuricemia and metabolic syndrome in a population of healthy subjects.MethodsWe studied 1,573 healthy adults (25 to 64 years old) in the population laboratory of the Tehran University of Medical Sciences. The study was designed according to the World Health Organization MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) project with use of the National Cholesterol Education Program Adult Treatment Panel III criteria for metabolic syndrome.ResultsThe crude prevalence of the metabolic syndrome was 29.9% (age-adjusted, 27.5%). The rate of metabolic syndrome significantly increased in higher quartiles of serum uric acid in both sexes but especially in women (P < .0001 versus P = .026). The bivariate correlation was significant between uric acid levels and age, total serum cholesterol, high-density lipoprotein cholesterol, triglycerides, body mass index, waist and hip circumferences, waist-to-hip ratio, and systolic and diastolic blood pressures; however, there was not a significant correlation between serum uric acid concentrations and fasting plasma glucose.ConclusionThese data indicate that an independent relationship exists between hyperuricemia and the metabolic syndrome. Moreover, hyperuricemia is significantly correlated with hypertriglyceridemia, hypertension, and visceral obesity. Early detection of hyperuricemia seems to be essential for prevention of the metabolic syndrome. (Endocr Pract. 2008;14:298-304)     

Terahertz Time-Domain Spectroscopy of Glucose and Uric Acid

We report the use ofterahertz time-domain spectroscopy for thestudy of two therapeutic bio-molecules:glucose and uric acid. Terahertztransmission spectra of crystalline samplesof both molecules were measured between 0.1–3.0 THz using an evacuated spectroscopysystem. We propose that the stereo-isomersof glucose show spectral featuresoriginating from intermolecular vibrationalmodes, as do uric acid and its derivativemolecule, allantoin. In addition, wepresent a full temperature dependence ofthe terahertz absorption of L-glucose.     

高血压患者颈动脉粥样硬化与血脂、血压和血尿酸水平的相关性分析

目的:探讨高血压患者颈动脉粥样硬化(CAS)与血脂、血压以及血尿酸水平的相关性。方法:选择2017年2月至2018年8月在我院就诊的高血压患者117例作为研究组,另选择同期在我院进行体检的健康志愿者50例作为对照组。采用彩色多普勒超声诊断仪测定所有受试者的颈动脉内中膜厚度(IMT),并根据研究组患者的颈动脉IMT将其分为斑块组(IMT≥1.3 mm,33例)、IMT增厚组(1.0 mm≤IMT1.3 mm,49例)和IMT正常组(IMT1.0 mm,35例)。比较研究组与对照组受试者IMT,同时分别比较研究组与对照组受试者以及不同IMT高血压患者平均收缩压(SBP)、平均舒张压(DBP)、血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)以及尿酸水平,并采用Pearson相关性分析法分析高血压患者IMT与各指标的相关性。结果:与对照组比较,研究组IMT、SBP、DBP、TC、TG、LDL-C、血尿酸水平升高,HDL-C水平降低,差异均有统计学意义(P0.05)。斑块组患者SBP、DBP、TC、TG、LDL-C、血尿酸水平高于IMT增厚组和IMT正常组,HDL-C水平低于IMT增厚组和IMT正常组,差异均有统计学意义(P0.05);IMT增厚组患者SBP、DBP、TC、TG、LDL-C、血尿酸水平高于IMT正常组,HDL-C水平低于IMT正常组,差异均有统计学意义(P0.05)。Pearson相关性分析显示,高血压患者的IMT与SBP、DBP、TC、TG、LDL-C、血尿酸均呈正相关,与HDL-C呈负相关(P0.05)。结论:高血压患者IMT与血脂、血压和血尿酸水平均有明显相关性,血压、血脂、血尿酸参与了高血压患者CAS的发生与发展。