高脂血症患者血尿酸、瘦素、脂联素水平的变化

目的观察不同临床类型的高脂血症患者血尿酸（uA）、瘦素、脂联素水平,探讨其在高脂血症发病中的作用。方法选择不同临床类型的高脂血症患者336例,分为高胆固醇血症组（高TC组）、高甘油三酯血症组（高TG组）、混合型高脂血症组（混合组）和低高密度脂蛋白血症组（低HDL—C组）组;另选择正常对照组204人。检测各组患者的血尿酸、血清瘦素和脂联素水平,并分析其在脂代谢中的作用。结果与正常对照组相比,高TG组、混合组及低HDL—C组UA水平有不同程度的升高（P〈0．05）,其中高TG组uA水平升高最明显。与正常对照组比较,除低HDL—C组脂联素水平明显升高外（P〈0．05）,其余各高脂血症组无论是血清瘦素水平,还是脂联素水平差异均无统计学意义（P〉0．05）。高脂血症各组之间两两比较,高TG组瘦素水平低于低HDL—C组（P〈0．05）,高TC组脂联素水平低于低HDL—C组（P〈0．05）。结论高脂血症患者存在尿酸代谢紊乱,可能与血清瘦素、脂联素共同参与有关。血清瘦素、脂联素将来有可能成为判定代谢综合征的严重程度及预后的指标。     

Study on uric acid metabolism in patients with primary aldosteronism]

This study was conducted to elucidate renal uric acid metabolism in patients with primary aldosteronism (PA;16 cases) as compared with normotensive subjects (NT;25 cases) and essential hypertensives (EHT;51 cases). All subjects were hospitalized and received a regular diet(Na;120 mEq,K;75 mEq,daily) for more than two weeks, after which renal clearance tests were performed, and serum uric acid(SUA), fractional excretions of uric acid(FEUA), sodium(FENa), and inorganic phosphorus(FEP) were evaluated. Plasma aldosterone concentration(PAC) was measured in 16 patients with PA before treatment and in 8 patients after adrenalectomy. SUA was lower in PA than in either NT or EHT, and this lowering was more obvious in male subjects. In NT, PA and EHT, FEUA, an index of renal excretion of uric acid, correlated negatively with SUA and positively with FENa and FEP, which reflected sodium reabsorption at the renal total tubules and proximal tubules, respectively. Although FENa was nearly the same in all the three groups, FEUA and FEP were significantly higher in PA than in EHT or NT. However, no significant correlation was found between PAC and SUA or FEUA in PA. In PA a significant increase of SUA, and decreases of FEUA and FEP were observed after the removal of adenoma compared to before the surgery. These results suggest that uric acid transport might be closely related to sodium transport in the renal tubules, particularly at the proximal site, and also lead to the conclusion that the lower SUA in PA resulted from the suppression of reabsorption and/or an enhancement of secretion of uric acid in the proximal tubules, being related to the so-called escape phenomenon.     

Effects of azelnidipine on uric acid metabolism in patients with essential hypertension

Purpose: To examine effects of a long-acting calcium channel blocker (CCB) azelnidipine on uric acid metabolism in hypertensive patients.

Methods: Azelnidipine was administered to 72 patients at a daily dose of 8?mg or 16?mg. In 22 cases out of the 72 patients, a different CCB was switched to azelnidipine. Blood pressure was measured and biochemical parameters of blood and urine were evaluated before and 2–3 months after the administration.

Results: Azelnidipine significantly decreased both systolic and diastolic blood pressure and the heart rate. It decreased both serum urate levels and the urinary uric acid to creatinine ratio (Uur/Ucr), but did not affect the uric acid clearance to creatinine clearance ratio (Cur/Ccr). Azelnidipine decreased both Uur/Ucr and Cur/Ccr in patients with Uur/Ucr ≥0.5 or ≥0.34, although it did not change these clearance parameters in patients with Uur/Ucr <0.5 or <0.34. Azelnidipine decreased the serum urate levels and Uur/Ucr in hyperuricemic patients with uric acid levels ≥7.0?mg/dL in males and ≥6.0?mg/dL in females. It did not change these parameters in normouricemic patients with serum urate levels <7.0?mg/dL in males and <6.0?mg/dL in females. Azelnidipine decreased Uur/Ucr and Cur/Ccr in hyperuricemic patients with normal or overexcretion of uric acid, although it did not change these clearance parameters in hyperuricemic patients with uric acid hypoexcretion.

Conclusions: Azelnidipine decreased the serum urate acid levels and Uur/Ucr, and this response was most prominent in hyperuricemic patients or patients with normal and overexcretion of uric acid.     

Related factors of serum uric acid in patients with primary hypertension and hyperhomocysteinemia

Objective: To investigate the related factors of serum uric acid in patients with primary hypertension and hyperhomocysteinemia. Methods: One hundred and ten patients with primary hypertension and hyperhomocysteinemia (homocysteine levels >10 μmol/L) were enrolled into this study, ages from 18 years to 75 years. They were divided into the normal serum uric acid group which contained 74 cases patients (41 cases of male and 33 cases of female) and the hyperuricemia group which contained 36 cases patients (20 cases of male and 16 cases of female). Plasma concentrations of homocysteine, serum uric acid, serum folic acid, blood sugar, triglyceride, total cholesterol, serum low density lipoprotein cholesterol, serum high density lipoprotein cholesterol, blood urea nitrogen, and creatinine were detected in these patients, and the deference of them between the two groups was compared. And then the risk factors of serum uric acid with univariate analysis and multivariate analysis by logistic regression analysis were analyzed. Results: The result of multivariate analysis showed that the incidence of serum uric acid in patients with primary hypertension and hyperhomocysteinemia had significant relationships with systolic blood pressure (OR [odds ratio]: 1.132, 95%CI [confidence interval]: 1.003~1.290, p = 0.043), diastolic blood pressure (OR: 1.353 95%CI: 1.023~1.789, p = 0.034, homocysteine (OR: 1.264, 95%CI: 1.016~1.573, p = 0.035), triglyceride (OR: 9.726, 95%CI: 1.288~73.466, p = 0.027), and creatinine (OR: 1.031, 95%CI: 1.005~1.508, p = 0.018). Conclusion: The indices of systolic blood pressure, diastolic blood pressure, homocysteine, triglyceride, and creatinine were important risk factors of serum uric acid in patients with primary hypertension and hyperhomocysteinemia. It is of great significance to measure multiple risk factors in patients with primary hypertension and hyperhomocysteinemia.     

伊贝沙坦对高血压病伴高尿酸血症的干预作用

目的：探讨伊贝沙坦对高血压病伴高尿酸血症患者的干预作用。方法：高血压病伴高尿酸血症患者80例，随机分成伊贝沙坦组40例，给予伊贝沙坦300mg／d；常规治疗组40例，给予钙拮抗剂或B受体阻滞剂等，排除对血尿酸代谢有影响的药物ACEI及利尿剂等。治疗6周后观察收缩压（SBP）、舒张压（DBP）、血尿酸（UA）、尿素氮（BUN）、肌酐（Cr）、尿微量白蛋白（MA）变化。结果：伊贝沙坦组和常规治疗组SBP、DBP和治疗前比均显著下降（P〈0．01）。伊贝沙坦治疗组血UA、BUN、Cr及尿MA水平分别由治疗前（448．1±50．8）μmol／L、（10．7±1．3）mmol／L、（149．1±13．8）μmol／L、（57．1±17．4）mg／L下降至（367．9±42．9）μmol／L、（8．2±1．0）mmol／L、（120．9±11．5）μmol／L、（44．6±13．7）mg／L（P均〈0．01），而常规治疗组血UA、BUN、Cr及尿MA水平下降无显著性差异（P〉0．05）。结论：伊贝沙坦能有效地降低高血压病患者的血压同时还具有降血尿酸及肾脏保护作用。     

慢性心力衰竭患者血尿酸水平与左室重构程度关系的探讨

目的:探讨慢性心力衰竭(CHF)患者不同血尿酸(UA)水平和左室重构程度的关系.方法:565例CHF患者,按NYHA心功能分级分为Ⅰ、Ⅱ、Ⅲ、Ⅳ级,分别为236、138、132、59例;按照AHA/ACC的CHF分期法分为B、C、D期,分别为236、270、59例;健康体检者105例作为对照组.所有入选者入院后急诊或常规检查UA、肝肾功能、电解质等项目;超声心动图测定心脏左室舒张末期内径(LVEDd)、室间隔厚度(IVSd)、左室后壁厚度(LVPWd),计算左室质量(LVM)和左室质量指数(LVMI).结果:CHF患者UA水平较对照组明显增加(P<0.05),排除利尿剂的影响后仍随心功能分级和分期增高而增加;CHF组中UA增高者LVM、LVMI、LVEDd、LVPWd及左室肥厚发生率均显著高于UA正常者(P<0.01);直线相关分析显示LVM、LVMI与UA呈明显的正相关,分别为r=0 406,P<0.01;r=0 388,P<0.01.结论:UA异常是CHF患者代谢障碍的早期信号,是左室重构的促进因素.     

不同负荷量他汀对急性心肌梗死直接PCI术后心肌细胞的影响◆

目的 比较不同负荷剂量的他汀对急性心肌梗死直接PCI术后心肌细胞的影响。方法 纳入我院急性心肌梗死行急诊PCI术患者共140例,随机分为4组,负荷剂量组A(阿托伐他汀80mg,35例),负荷剂量组B(瑞舒伐他汀20mg,35例),常规剂量组C(阿托伐他汀20mg ,35例),常规剂量组D(瑞舒伐他汀5mg,35例),检测PCI前后hs-CRP、血清淀粉样蛋白(SAA)、CK-MB、cTnI、内皮素(ET-1)、一氧化氮(NO)、纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物(PAI-1),记录术后2小时18导联心电图,计算ST段回落指数(STR),比较PCI术后心肌梗死校正TIMI帧计数(CTFC),术后30天随访,测定LVEF并复查肝肾功能,记录主要心血管不良事件(MACE)。结果 PCI术后2小时 hs-CRP、SAA、CK-MB、cTnI、NO、t-PA各组均升高,但hs-CRP、SAA、CK-MB、cTnI负荷剂量组低于常规剂量组(P<0.05),NO、t-PA负荷剂量组高于常规剂量组(P<0.05); ET-1、PAI-1均降低,但负荷剂量组低于常规剂量组(P<0.05),各项指标两负荷剂量组比较未见统计学差异(P>0.05);术后2小时STR、CTFC、术后30天LVEF及主要心血管不良事件发生率,负荷剂量组均优于常规剂量组(P<0.05),两负荷剂量组比较未见统计学差异(P>0.05)。结论 急性心肌梗死患者行直接PCI术前联合应用负荷量他汀能够改善术后心肌微循环灌注,进一步减少心肌细胞的坏死,改善患者短期临床预后,阿托伐他汀与瑞舒伐他汀相比较临床疗效无显著差异。     

Prognostic value of uric acid in patients with ST-elevated myocardial infarction undergoing primary coronary intervention

Elevated uric acid (UA) levels have been associated with cardiovascular disease in epidemiologic studies. The relation between UA levels and long-term outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention is not known. Data from 2,249 consecutive patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention were evaluated. Patients were divided into 2 groups with high or low UA using upper limits of normal of 6 mg/dl for women and 7 mg/dl for men. There were 1,643 patients in the low-UA group (mean age 55.9 ± 11.6 years, 85% men) and 606 patients in the high-UA group (mean age 60.5 ± 12.6 years, 76% men). Serum UA levels were 8.0 ± 1.5 mg/dl in the high-UA group and 5.2 ± 1.0 mg/dl in the low-UA group (p <0.001). The in-hospital mortality rate was significantly higher in patients with high UA levels (9% vs 2%, p <0.001), as was the rate of adverse outcomes in patients with high UA. The mean follow-up time was 24.3 months. Cardiovascular mortality, reinfarction, target vessel revascularization, heart failure, and major adverse cardiac events were all significantly higher in the high-UA group. In a multivariate analyses, high plasma UA levels were an independent predictor of major adverse cardiac events in the hospital (odds ratio 2.03, 95% confidence interval 1.25 to 3.75, p = 0.006) and during long-term follow-up (odds ratio 1.64, 95% confidence interval 1.05 to 2.56, p = 0.03). In conclusion, high UA levels on admission are independently associated with in-hospital and long-term adverse outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention.     

尿酸通过诱导线粒体钙稳态失衡介导内皮细胞炎症反应

目的探讨线粒体钙稳态失衡在高尿酸（UA）导致的血管内皮细胞炎症中的病理生理机制。方法采用Fluo-3 AM及Rhod-2 AM分别对UA刺激后的人脐静脉内皮细胞（HUVEC-C）进行胞质钙离子浓度（[Ca2＋]i）和线粒体钙离子浓度（[Ca2＋]mito）的特异性染色;RT-PCR法检测其C反应蛋白（CRP）和细胞间黏附分子1（ICAM-1）的mRNA表达变化;Western blot检测ICAM-1的蛋白变化;ELISA法检测其培养液上清白细胞介素6（IL-6）的释放变化情况。结果HUVEC-C经600μmol/L的UA刺激后,其[Ca2＋]i未见明显变化,而[Ca2＋]mito呈波浪式升高（P〈0.05）,并在24 h内保持较高的状态;CRP、ICAM-1、IL-6均在UA刺激后升高（P〈0.05）。结论UA可导致内皮细胞炎症反应,[Ca2＋]mito的升高与之相关,提示线粒体钙稳态失衡在UA导致的内皮炎症反应中起一定的介导作用。     

Effects of statin treatment in patients with coronary artery disease and chronic kidney disease

Statins reduce cardiovascular morbidity and mortality from coronary artery disease (CAD). However, the effects of statin therapy in patients with CAD and chronic kidney disease (CKD) remain unclear. Within a single hospital-based cohort in the Shinken Database 2004–2010 comprising all patients (n = 15,227) who visited the Cardiovascular Institute, we followed patients with CKD and CAD after percutaneous coronary intervention (PCI). A major adverse cardiovascular and cerebrovascular event (MACCE) was defined by composite end points, including death, myocardial infarction, cerebral infarction, cerebral hemorrhage, and target lesion revascularization. A total of 391 patients were included in this study (median follow-up time 905 ± 679 days). Of these, 209 patients used statins. Patients with statin therapy were younger than those without. Obesity and dyslipidemia were more common, and the glomerular filtration rate (GFR) was significantly higher, in patients undergoing statin treatment. MACCE and cardiac death tended to be less common, and all-cause death was significantly less common, in patients taking statins. Multivariate analysis showed that low estimated GFR, poor left ventricular ejection fraction, and the absence of statin therapy were independent predictors for all-cause death of CKD patients after PCI. Statin therapy was associated with reduced all-cause mortality in patients with CKD and CAD after PCI.     

Effects of carbohydrates on uric acid metabolism

The rapid infusion of fructose, but not of glucose or galactose, to normal male volunteers produced a 30% rise in serum uric acid. All three hexoses increased the renal excretion of uric acid, phosphate, bicarbonate, and glucose. While only fructose clearly increased uric acid production, all three hexoses appeared to diffusely inhibit renal proximal tubular function. Data are presented that suggest that fructose infusions may concomitantly stimulate the conversion of preformed adenine nucleotides to uric acid while inhibiting de novo uric acid synthesis. Chronic ingestion of a fructose-rich diet did not alter serum or urinary uric acid.     

Renal underexcretion of uric acid is present in patients with apparent high urinary uric acid output

OBJECTIVE: To compare renal handling of uric acid in patients with primary gout with that of a control group. METHODS: A case-control study of 100 patients with primary gout and 72 healthy controls was undertaken. Creatinine clearance, uric acid clearance, 24-hour uric acid urinary excretion, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, urinary uric acid to creatinine ratio, and glomerular uric acid filtered load were calculated using 24-hour urine samples. After treatment with allopurinol to achieve similar glomerular filtered load of uric acid, patients were again compared with controls. RESULTS: Patients with gout showed lower uric acid clearance, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, and urinary uric acid to creatinine ratio than controls at baseline, when patients showed hyperuricemia. Although the glomerular uric acid filtered load was much higher in patients with gout than controls, 24-hour uric acid excretion was not statistically different. After treatment with allopurinol, and achieving similar uric acid filtered loads, patients still showed lower figures than controls. When patients with 24-hour urinary uric acids levels >700 mg/day were compared with controls, they had lower uric acid clearance and fractional excretion of uric acid than controls, both at baseline and after achieving similar filtered loads with allopurinol therapy. CONCLUSIONS: Renal underexcretion is the main mechanism for the development of primary hyperuricemia in gout, but even patients showing apparent high 24-hour uric acid output show lower uric acid clearance than controls, indicating that relative, low-grade underexcretion of uric acid is at work.     

微粒化非诺贝特调节老年代谢综合征患者血脂及尿酸代谢的研究

目的观察微粒化非诺贝特(非诺贝特)对老年代谢综合征患者血脂及尿酸代谢的影响,并探讨其潜在机制。方法入选131例老年代谢综合征患者,同时伴有高TG及高尿酸血症,每日顿服非诺贝特胶囊200 mg,疗程为4周。观察治疗前和治疗4周后主要血脂参数、血尿酸、24 h尿尿酸的变化及不良反应。结果非诺贝特治疗4周后:(1)患者血清TG下降最为显著,与基线比较下降49%,血清HDL-C水平升高18%,此外患者血清TC和LDL-C水平也有一定程度的下降(分别为11%和14%);(2)患者血尿酸水平由(472.5±74.8)μmol/L降至(325.0±82.1)μmol/L,下降幅度为31.2%。其中男性患者血尿酸水平下降32.6%,女性患者下降29.7%,差异均有统计学意义(P<0.01)。(3)患者24 h尿尿酸排泄明显增多,由(2 885.2±502.7)μmol/L增加至(3 701.7±768.2)μmol/L,排泄增加28.8%,其中男性24 h尿尿酸排泄高于女性(P<0.01)。结论非诺贝特具有同时改善老年代谢综合征患者的血脂及尿酸代谢异常的双重疗效,能明显促进尿尿酸排泄,且该作用与性别无关。     

高血压患者中尿酸对心血管事件的影响

随着人们饮食条件及生活方式的改善,高尿酸血症（hyperuricemia,HUA）的发生率逐渐升高。众所周知,高水平血尿酸（serum uric acid,SUA）促进高血压的发生发展。降尿酸治疗对血压的影响也显而易见。近来,高血压患者中尿酸对心血管事件（冠心病、心力衰竭、脑卒中、房颤）的影响逐渐被证实,已成为目前关注的重点。现就高血压患者中尿酸对心血管事件的影响及治疗做一综述。     

Effects of lipid-lowering therapy with strong statin on serum polyunsaturated fatty acid levels in patients with coronary artery disease

Residual risk of cardiovascular events after treatment with stain might be explained in part because patients have low levels of n?3 polyunsaturated fatty acids (PUFA). We examined how lipid-lowering therapy with strong statin affected serum PUFA levels in patients with coronary artery disease. The study population consisted of 46 patients with coronary artery disease whose low-density lipoprotein (LDL) cholesterol was more than 100 mg/dl. Lipid-lowering therapy was performed with a strong statin including atorvastatin (n = 22), rosuvastatin (n = 9) or pitavastatin (n = 15). Serum PUFA levels were determined by gas chromatography. The treatment with strong statin decreased the sum of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) levels (195 ± 41 to 184 ± 44 μg/ml, P < 0.05) as well as the sum of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels (233 ± 71 to 200 ± 72 μg/ml, P < 0.001). These effects of strong statin resulted in a significant decrease in ratio of the sum of EPA and DHA levels to the sum of DGLA and AA levels (1.20 ± 0.27 to 1.10 ± 0.35, P < 0.05). The percent decrease in the LDL cholesterol level correlated significantly with that in the sum of EPA and DHA levels (r = 0.38, P < 0.01). In conclusion, our results showed that lipid-lowering therapy with strong statin mainly reduced n?3 PUFAs in proportion to the decrease in the LDL cholesterol level in patients with coronary artery disease.     

Effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia in Chinese population

Therapy with losartan compared to irbesartan was performed in a Chinese sample of hypertensive patients with elevated serum uric acid (SUA) levels. After 1 week of screening and a 2 week single-blinded placebo baseline period, patients were treated for 4 weeks with losartan 50 mg or irbesartan 150 mg. After 4 weeks, patients with SiDBP <90 mmHg and SiSBP <140 mmHg continued the same dose regimen for another 4 weeks. If blood pressure was not controlled after 4 weeks of treatment, the dose of either regimen was doubled to losartan 100 mg and irbesartan 300 mg. There were 351 patients randomized (176 to losartan and 175 to irbesartan), and of these, 325 patients completed the study (162 in the losartan group and 163 in the irbesartan group). At baseline, the median SUA level in the losartan group was 422 and 420 micromol/l in the irbesartan group. At 8 weeks of therapy, SUA decreased by 63 mumol/l in the losartan group compared to 12 mumol/l in the irbesartan group (P < 0.0001). Blood pressure declined comparably in both groups from 151/92 mmHg at baseline to 137/83 and 135/83 (losartan and irbesartan, respectively, NS). No severe AEs were found for either treatment group. Therapy with losartan decreased SUA levels significantly more than irbesartan in Chinese patients with hypertension and elevated SUA levels, demonstrating the unique uricosuric effect of this ARB in this ethnic group.