早期纠正贫血对慢性肾衰竭心血管病变影响的多中心临床研究

目的观察早期使用促红细胞生成素治疗贫血对透析前慢性肾衰竭(CRF)患者心血管病变的影响.方法采用多中心、前瞻性、对照临床研究.血肌酐(Scr)在147～400 μmol/L的CRF患者158例,按基线Hb水平分组.将Hb<110 g/L的患者分为2组,(1)治疗组86例,每周接受α-促红细胞生成素100～135 U/kg皮下注射;(2)对照Ⅰ组40例,未接受α-促红细胞生成素治疗;将Hb≥110 g/L的32例患者作为对照Ⅱ组,未接受α-促红细胞生成素治疗.行超声心动图检查,测左心室质量指数(LVMI)、血压等,随访时间2年.结果 3组患者基线临床资料(年龄、性别、原发病、营养状况、高血压的发生率、使用降压药物的种类和数量等)无明显差异(均P>0.05);治疗组、对照Ⅰ组、对照Ⅱ组患者左心室肥厚(LVH)的发生率分别为72.1%、72.5%、59.4%;LVMI与Hb水平呈负相关(r=-0.70, P<0.01),与Scr呈正相关(r=0.64, P<0.05).治疗24个月后,治疗组患者Hb水平较基线时明显上升(P<0.05),LVMI较基线时明显下降(P<0.05),LVH的发生率(55.8%)较治疗前降低16.3%,但平均动脉压、使用降压药物的数量与基线相比无明显差异.对照Ⅰ组与对照Ⅱ组患者Hb逐渐下降,LVMI明显增加,LVH发生率与基线相比明显增高(P<0.05).随访期间,Scr较基线增高1倍的患者比率,治疗组(3.4%)与对照Ⅰ组(15.0%)相比差异有统计学意义(P<0.05),而对照Ⅰ组与对照Ⅱ组(9.4%)相比无明显差异(P>0.05).结论轻中度CRF患者存在LVH,贫血是导致透析前CRF患者LVH的重要原因.用促红细胞生成素早期治疗贫血能使部分患者LVH逆转.透析前CRF患者用促红细胞生成素治疗并不加重高血压,并可能有助于延缓肾衰竭的进程.     

老年男性血清25羟维生素D水平与左心室肥厚的相关性研究

目的探讨老年男性血清25羟维生素D水平对于心脏左心室肥厚(LVH)的预测意义。方法选取333例老年男性患者,根据是否合并LVH分为非LVH组208例,LVH组125例,2组行超声心动检查,采用ELISA法检测血清25羟维生素D,采用多因素多元逐步回归分析。结果与非LVH组比较,LVH组血清肌酐水平明显升高,差异有统计学意义(P<0.05);血清25羟维生素D明显降低[(35.5±14.8)nmol/L vs(30.7±10.8)nmol/L,P<0.05],左心室重量指数(LVMI)明显增高(P<0.01)。体重指数和25羟维生素D与LVMI独立相关(β=0.216,-0.155,P<0.01)。结论在老年男性患者中,较低的25羟维生素D水平可能是LVH的独立危险因素。     

原发性高血压患者血压变异性与左心室质量指数的相关性分析

目的探讨原发性高血压患者血压变异性(blood pressure variability,BPV)与左心室质量指数(left ventricular mass index,LVMI)的相关性。方法选择我院住院的原发性高血压患者95例,根据心电图、彩色超声心动图检查确定是否伴有左心室肥厚(left ventricular hypertrophy,LVH)分为LVH组42例及无LVH组53例,另选择血压正常且无LVH的健康体检者40例为对照组,收集3组一般临床资料,检测同型半胱氨酸(Hcy)水平,进行24 h动态血压监测,比较3组24 h、夜间、昼间平均血压、收缩压标准差和舒张压标准差及LVMI。结果3组年龄、体质量指数、吸烟、尿酸、血红蛋白、血脂、糖化血红蛋白及各时间段内平均血压比较,差异无统计学意义(P>0.05);3组性别、糖尿病比例、Hcy、肌酐、LVMI及24 h、夜间、昼间收缩压标准差和舒张压标准差比较,差异有统计学意义(P<0.05,P<0.01)。LVH组男性比例、Hcy、LVMI及24 h、夜间、昼间收缩压标准差和舒张压标准差明显高于无LVH组和对照组(P<0.05),LVH组和无LVH组糖尿病比例和肌酐水平明显高于对照组,差异有统计学意义[59.5%和56.6%vs 7.5%,(92.0±4.8)μmol/L和(81.3±15.9)μmol/L vs(65.4±13.2)μmol/L,P<0.05]。无LVH组与对照组LVMI及24 h、夜间、昼间收缩压标准差和舒张压标准差比较,差异无统计学意义(P>0.01)。LVH组非杓型高血压比例明显高于无LVH组和对照组(85.7%vs 34.0%、5.0%,P=0.000)。结论BPV与高血压患者的LVH关系密切,其可能作为靶器官损伤最新的独立预测因素。     

老年患者血清护骨素水平与左心室结构和功能的相关性研究

目的探讨老年患者血清护骨素水平对于心脏左心室结构与功能的预测意义。方法选择51 7例老年患者,根据护骨素水平按3分位数分组:护骨素<1.50μg/L组(A组,171例)护骨素1.50～2.72μg/L组(B组,176例),护骨素>2.72μg/L组(C组,1 70例)。ELISA法检测血清护骨素水平;多因素采用多元逐步回归及logistic回归分析。结果随护骨素水平升高,3组LVEF逐渐下降(P<0.01),左心室质量指数逐渐升高(P<0.01),以左心室肥厚为因变量,以性别、年龄、收缩压、舒张压、空腹血糖、血肌酐、TC,LDL-C.HDL-C、TG、sqrt护骨素为自变量,logistic回归分析显示,左心室肥厚与性别、年龄、收缩压、sqrt护骨素独立相关。结论在老年心血管病患者中,血清护骨素水平可能是左心室肥厚的独立危险因素,并且老年女性发生左心室肥厚的风险高于男性。     

Validity of the ECG diagnosis of left ventricular hypertrophy in normotensive and moderately hypertensive men when using the echocardiographic assessment of left ventricular mass index as reference.

The diagnostic validity of ECG criteria for left ventricular hypertrophy (LVH) was assessed in 100 men aged 22-64 (mean 47) years with moderate hypertension (Group 1) and 95 age-matched normotensive men (Group 2) using echocardiographic recordings of LV mass index (MI) as reference. A diagnosis of LVH was made in subjects with LVMI greater than or equal to 125 g/m2. Mean LVMI was 126 +/- 34 g/m2 in Group 1 vs. 100 +/- g/m2 in Group 2 (P less than 0.001), and the prevalence of LVH was 48% and 11% respectively (P less than 0.001). The mean ECG voltage according to Sokolow-Lyon (S-L) was 28 +/- 8 mm in Group 1 and 27 +/- 7 mm in Group 2 (NS); with 19% having LVH in Group 1 and 14% in Group 2 (NS). Using the Cornell criterion Group 1 had on average 15 +/- 6 mm vs. 12 +/- 5 mm in Group 2 (P less than 0.001), but only two Group 1 patients had LVH. In Group 2 a significant negative correlation between age and S-L voltage was found (r = 0.33, P less than 0.001). LVMI was not correlated with any of the two voltage criteria using linear regression analysis whereas multiple regression analysis revealed a weak, but significant correlation between LVMI and S-L voltage in Group 1 (t = 2.06, P = 0.04). No subject had LV strain pattern or LVH according to the Romhilt Estes point score system. In the assessment of possible LVH in normal or moderately hypertensive men less than 65-70 years of age, ECG has limited value.     

老年高血压患者动脉僵硬度与左心室肥厚关系

目的探讨老年高血压患者动脉僵硬度与左心室肥厚的关系。方法选择原发性老年高血压患者68例,以左心室重量指数(LVMI)作为评价左心室肥厚指标,将患者分为左心室肥厚组(32例)和非左心室肥厚组(36例)。以颈动脉-股动脉肢体动脉搏动波(cfPWV)和脉压作为评价动脉僵硬度指标,进行24 h动态血压监测、cfPWV及超声心动图检测,并进行多因素相关分析。结果左心室肥厚组较非左心室肥厚组患者cfPWV高[(14.45±1.83)m/s vs(10.89±1.94)m/s]、脉压大[(78.66±9.05)mm Hg(1 mm Hg=0.133 kPa)vs(60.39±7.74)mm Hg],两组比较,差异有统计学意义(P<0.01),logistic回归分析显示,LVMI与cfPWV、脉压呈正相关。结论动脉僵硬度增加是老年高血压患者左心室肥厚的重要危险因素。     

早期慢性肾脏病患者胰岛素抵抗与左心室肥厚的关系

目的 探讨早期慢性肾脏病(CKD)患者胰岛素抵抗(IR)与左心室肥厚(LVH)的关系.方法 采用稳态模型方法检测108例早期CKD患者和25例正常对照者胰岛素抵抗指数(HomaIR)及其他有关指标;采用超声心动图检测早期CKD患者LVH有关指标,分析IR与LVH的关系.结果 IR及LVH在CKD早期即已存在,且随着内生肌酐清除率(Ccr)的下降,IR和LVH患病率均显著增加(P值均<0.01).与非IR组相比,IR组LVMI(左心室质量指数)水平及LVH患病率均显著增加(P值均<0.05).与非LVH组相比,LVH组空腹胰岛素(FIns)、餐后2 h血糖(2hPG)和Homa-IR水平及IR患病率均显著增高(P值均<0.05),Ccr、Hb和夜间血压下降率(nDPD)均显著下降(P值均<0.05),24 h动态血压值、甲状旁腺激素(PTH)均显著增高(P值均<0.05).单因素相关性分析显示,LVMI与FIns、Homa-IR和PTH等呈显著正相关(P值均<0.05),与Ccr和Hb呈显著负相关(P值均<0.01).多因素逐步回归分析显示,Hb、Homa-IR和Ccr可进入回归方程.结论 IR存在于早期CKD患者且随肾功能减退而愈加严重,与早期CKD患者业已存在的LVH有关,可能是LVH发生的重要机制.贫血和肾功能减退本身也与早期CKD患者LVH发生有关.     

Positive outcomes of high hemoglobin target in patients with chronic kidney disease not on dialysis: a randomized controlled study

Correcting anemia in patients with chronic kidney disease (CKD) to higher hemoglobin (Hb) levels may be associated with increased risk. No optimal target for Hb has been established. This controlled study examined 321 patients with CKD who were not on dialysis, had a Hb level of <10g/dL, and a serum creatinine of 2.0 to 6.0mg/dL. They were randomized into two target Hb groups: 161 to high Hb (11.0-13.0g/dL) to receive darbepoetin alfa and low Hb to 160 (9.0-11.0g/dL) to receive recombinant erythropoietin. The study lasted 48weeks. Of 154 and 153 patients with adverse events, cardiovascular adverse events developed in 42 and 51 patients in the high and low Hb groups, respectively, with no significant difference in the incidence. All quality of life scores improved in the high Hb group and vitality improved significantly more with high Hb (P=0.025). The left ventricular mass index (LVMI) remained stable in the low Hb group, but there was a significant decrease in LVMI in the high group (P<0.001). There were no safety concerns with targeting a higher Hb level during the 48weeks of this study. Patients with a higher Hb target had comparatively better outcomes with respect to quality of life and LVMI.     

Nandrolone decanoate is a good alternative for the treatment of anemia in elderly male patients on hemodialysis

Objective: To assess the efficiency of nandrolone decanoate (ND) in the control of anemia in elderly male patients on hemodialysis (HD), and to determine its influence on nutritional parameters. Design: A prospective 6-month study with randomization of patients on recombinant human erythropoietin (rHuEPO) therapy into two groups. Group A: rHuEPO was stopped before starting treatment with ND. Group E: rHuEPO was continued. Setting: Renal unit, tertiary-care center. Patients: 14 male patients in Group A and 19 patients, 12 males and 7 females, in Group E. Interventions: In Group A rHuEPO was stopped and ND 200 mg/I.M. weekly was given over six months. Results: The increase in hemoglobin and hematocrit levels was progressive with ND, and significant differences (p < 0.003) were evident after six months (9.6 ± 1.0 vs 11.0 ± 1.4 and 28.9 ± 4.7 vs 33.0 ± 4.7, respectively), which remained unmodified in Group E. Group A showed a significant increase in serum creatinine, total protein, transferrin and anthropometric parameters. These parameters remained stable and even presented a tendency to decrease in Group E. There was a significant rise in the concentration of triglycerides and a significant decrease in both HDL-cholesterol and apolipoprotein A-1 in Group A. However, lipoprotein (a) decreased significantly. No significant changes were detected in Group E. Conclusions: The use of ND would allow us an acceptable treatment of anemia as well as a better nutritional condition in elderly male patients on dialysis.     

Detection of circulating antierythropoietin antibodies in patients with end stage renal disease on regular hemodialysis

Recombinant human erythropoietin (rHuEPO) has been successfully and safely used to treat anemia in patients with end stage renal disease (ESRD). The safety profile of rHuEPO had been considered to be excellent with possible exception of hypertension and increased risk of dialysis access thrombosis. Recently, antibody-mediated pure red cell aplasia associated with administration of rHuEPO has been identified as a cause of major concern; we aimed to detect and evaluate the presence of anti-EPO antibodies in patients with ESRD on regular dialysis who are using rHuEPO. Serum anti-EPO antibodies were detected by enzyme-linked immunosorbant assay technique in a total of 90 patients who are currently on regular hemodialysis and using rHuEPO alpha subcutaneously for more than 6 months. All patients were subjected to full history taking and clinical examination. Complete blood count, reticulocytes count, serum creatinine, blood urea, serum albumin, serum ferritin, and hepatitis markers were performed for all patients. Our results showed that 35 patients (38.9%) had the anti-EPO antibodies in their blood, while 55 patients (61.1%) did not have the circulating antibodies. The mean hemoglobin (Hb) level was significantly lower in the antibody positive group (8.8 g/dl ± 1.35) than in the antibody negative group (9.42 g/dl ± 1.32) (P = 0.000). The reticulocytes count was also significantly much lower in the patients who had anti-EPO antibodies with mean of (1.99 ± 1.14) vs. (3.15 ± 0.89) in the antibody negative (P = 0.000). The dose of EPO administrated in both studied groups was insignificantly different. The incidence of anti-EPO antibodies is high in ESRD patients on maintenance hemodialysis. Its presence is associated with increased incidence of anemia possibly due to immune-mediated inhibition of erythropoiesis as evidenced by reticulocytopenia.     

Erythropoietin Administration May Potentiate Mobilization of Storage Iron in Patients on Oral Iron Chelation Therapy

Five, repeatedly transfused, patients with refractory anemia (RA) or RA with ringed sideroblast (RARS) subtypes of myelodysplastic syndrome (MDS), with serum ferritin (SF) levels of >2,000 μg/L, and one female with Hb E [β26(B8)Glu→Lys]/β⁰-thalassemia (thal) with an SF level of 1,760 μg/L, were treated with deferiprone (L1) at the dose of 4–6 g per day for at least 26 months. Beginning in the second month, all patients received recombinant human erythropoietin (rHuEPO) at the dose of 150 IU/kg thrice weekly, subcutaneously for 24 months. A significant increase in iron excretion after combined administration of L1 and rHuEPO compared to treatment with L1 as a single agent, was observed in all patients. The amount of excreted iron in urine ranged from 7.5 to almost 20 mg per day. In one patient, a response to rHuEPO resulted in transfusion independence and her SF decreased from 2086 to 879 μg/L. In four MDS patients, who remained dependent on red blood cell (RBC) transfusions, simultaneous administration of L1 and rHuEPO enabled the stabilization of SF levels, despite continuing iron load from the transfusions. Combined administration of rHuEPO and oral iron chelators may potentiate mobilization of storage iron and maintain iron balance in transfusion-dependent iron overloaded early MDS patients.     

Proven strategies to reduce cardiovascular mortality in hemodialysis patients

BACKGROUND: In hemodialysis patients, left ventricular hypertrophy (LVH) correlates with mortality. The reason for LVH in uremics is multifactorial. The primary objective of our study was to investigate the effects of a multi-interventional treatment strategy on LVH. METHODS: In 230 ambulatory patients, including patients with coronary artery disease, diabetes, diastolic and systolic dysfunction, we continued optimized cardiac therapy (beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) with full anemia correction by intravenous epoetin-beta. The dose of epoetin-beta for maintaining target hemoglobin (Hb) was 68 +/- 23 IU/kg/week. Serial echocardiograms were recorded every 3-6 months. The mean observation period was 4.8 +/- 1.2 years. RESULTS: Mean Hb at baseline was 11.2 +/- 2.0 versus 14.1 +/- 1.4 g/dl (p < 0.001) at study end. There was a significant reduction in left ventricular mass index (LVMI: 159 +/- 50.4 vs. 130.2 +/- 42.7 g/m(2); p < 0.001). In a subgroup of 2/3 of the patients, LVMI returned to normal (169 +/- 33 vs. 114 +/- 14 g/m2; p < 0.001). CONCLUSION: Baseline LVMI (p < 0.001), Hb increase (p < 0.03), and triple cardiac therapy (p < 0.03) were significant and independent prognostic factors for a reduction in LVMI. The annual cardiovascular mortality was 5%. Even anemia correction from 12 to 14 g/dl results in further (p < 0.001) regression of LVMI.     

血红蛋白水平对急性心肌梗死患者近期预后的影响

目的探讨急性心肌梗死患者入院时血红蛋白水平与30d心性死亡和并发症之间的关系。方法在解放军总医院住院的660例急性心肌梗死患者，依据血红蛋白水平将其分为A（〈100g／L）、B（100～119g／L）、C（120～139g／L）、D（140～159g／L）、E（≥160g／L）5组。分析不同血红蛋白水平对急性心肌梗死30d病死率及并发症的影响并探讨其相关因素。结果30d病死率分别为25．0％，20．4％，10．6％，4．3％和8．5％（P〈0．001）；心力衰竭为36．1％，25．5％，20．9％，8．6％和5．1％（P〈0．001）；肺炎为33．3％，23．5％，8．5％，2．2％和5．1％（P〈0．001）；消化道出血为19．4％，5．1％，0．9％，0．9％和1．7％（P〈0．001）；但是，心源性休克和室速／室颤的发生率5组间差异无统计学意义。偏相关分析显示急性心肌梗死患者的血红蛋白水平与患者年龄呈负相关（P〈0．001）；与血浆白蛋白和载脂蛋白A1正相关（P〈0．001和P=0．001）。结论依据急性心肌梗死患者血红蛋白水平，其近期死亡和（或）严重并发症的发生率呈J型曲线，血红蛋白水平越低，近期死亡和（或）严重并发症的风险越大；较多的老年急性心肌梗死患者血红蛋白水平低于非老年患者。     

老年高血压左心室肥厚患者左心室重构和冠状动脉病变分析

目的老年高血压左心室肥厚(left ventricular hypertrophy,LVH)患者左心室重构和冠状动脉病变发生及严重程度分析。方法选择高血压患者553例,根据年龄以及是否合并LVH,分为非老年非LVH组(A组,1 41例),非老年LVH组(B组,86例),老年非LVH组(C组,196例),老年LVH组(D组,130例),比较各组危险因素伴发情况、生化指标、冠心病发生、冠状动脉病变严重程度及心脏超声结果。结果与A组比较,其余3组的冠状动脉造影阳性率明显升高;B组和D组高血压3级比例、冠状动脉3支病变率明显升高(P<0.05,P<0.01);C组和D组的二尖瓣舒张早期血流峰值速度和舒张晚期血流峰值速度的比值明显降低;B组和D组的左心房内径、左心室舒张末内径、左心室收缩末内径、左心室重量指数明显增加,LVEF明显降低(P<0.01)。C组心脏超声指标较D组变化明显,差异有统计学意义(P<0.01)。结论老年高血压LVH患者高血压病程长,高血压程度严重,冠状动脉狭窄发生率高且病变程度更严重,心脏收缩与舒张功能显著降低。     

Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial

In myelodysplastic syndromes (MDS), anemia responds to recombinant human erythropoietin (rHuEPO) alone and in combination with recombinant human granulocyte-colony-stimulating factor (rHuGCSF) in 10% to 20% and in 35% to 40% of patients, respectively. We randomly divided 60 patients with low-grade anemic MDS and serum EPO levels lower than 500 IU/L (500 mU/mL) into 2 groups: rHuEPO + rHuG-CSF (arm A) and supportive care (arm B). After 12 weeks, those who had erythroid responses were given rHuEPO alone for 40 additional weeks. They were also given rHuG-CSF if they had relapses. A response was considered major if the hemoglobin (Hb) level was 115 g/L (11.5 g/dL) or higher and minor Hb increase was 15 g/L (1.5 g/dL) or more or if it remained stable without transfusion. Ten of 24 patients responded in arm A, and 0 of 26 responded in arm B (P =.01). Eight patients in arm A continued rHuEPO therapy alone, and 6 had relapses. Responses were always restored when rHuG-CSF was reintroduced. Mean direct costs per patient were 26,723 euros (arm A) and 8,746 euros (arm B). Quality of life was assessed with a Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale. Similar percentages of patients from both arms showed significant clinical improvement. rHuEPO plus rHuG-CSF led to responses in 41.7% of MDS patients. This treatment was expensive. No effect on quality of life was demonstrated.     

系统性红斑狼疮患者左室肥厚发生率及其相关因素分析

目的探讨系统性红斑狼疮(systemic lupus erythematosus,SLE)患者左室肥厚(left ventricular hypertrophy,LVH)发生率及其相关因素。方法初诊SLE患者92例,女性84例,男性8例,平均年龄35.8±8.3岁,应用彩超测定心脏各参数,计算左室质量指数(LVMI),判断有无LVH,并比较阳性组(LVH+)和阴性组(LVH-)有关参数。结果92例初诊SLE患者中,39例(42.39%)存在LVH;LVMI与平均动脉压(MABP)、C反应蛋白(CRP)成正相关(P<0.01和P<0.05),与Hb负相关(P<0.01),r值分别为3.164、2.303和-2.848。结论部分SLE患者早期可出现LVH,MABP、Hb和CRP是SLE伴LVH的危险因素,宜及早干预相关危险因素,以减轻或逆转SLE患者的LVH,减少心血管事件。     

A Pilot Evaluation of the Long-term Effect of Combined Therapy With Intravenous Iron Sucrose and Erythropoietin in Elderly Patients With Advanced Chronic Heart Failure and Cardio-Renal Anemia Syndrome: Influence on Neurohormonal Activation and Clinical Outcomes

BackgroundThe prognosis in elderly patients with advanced chronic heart failure (CHF) and cardio-renal anemia syndrome (CRAS) is ominous, and treatment alternatives in this subset of patients are scarce.Methods and ResultsTo assess the long-term influence of combined therapy with intravenous (IV) iron and erythropoietin (rHuEPO) on hemoglobin (Hb), natriuretic peptides (NT-proBNP), and clinical outcomes in elderly patients with advanced CHF and mild-to-moderate renal dysfunction and anemia (CRAS) who are not candidates for other treatment alternatives, 487 consecutive patients were evaluated. Of them, 65 fulfilling criteria for entering the study were divided into 2 groups and treated in an open-label, nonrandomized fashion: intervention group (27, combined anemia therapy) and control group (38, no treatment for anemia). At baseline, mean age was 74 ± 8 years, left ventricular ejection fraction was 34.5 ± 14.1, Hb was 10.9 ± 0.9 g/dL, creatinine was 1.5 ± 0.5 mg/dL, NT-proBNP was 4256 ± 4952 pg/mL, and 100% were in persistent New York Heart Association (NYHA) Class III or IV. At follow-up (15.3 ± 8.6 months), patients in the intervention group had higher levels of hemoglobin (13.5 ± 1.5 vs. 11.3 ± 1.1; P < .0001), lower levels of natural log of NT-proBNP (7.3 ± 0.8 vs. 8.0 ± 1.3, P = .016), better NYHA functional class (2.0 ± 0.6 vs. 3.3 ± 0.5; P < .001), and lower readmission rate (25.9% vs. 76.3%; P < .001). In the multivariate Cox proportional hazards model, combined therapy was associated with a reduction of the combined end point all-cause mortality or cardiovascular hospitalization (HR 95%CI 0.2 [0.1-0.6]; P < .001).ConclusionLong-term combined therapy with IV iron and rHuEPO may increase Hb, reduce NT-proBNP, and improve functional capacity and cardiovascular hospitalization in elderly patients with advanced CHF and CRAS with mild to moderate renal dysfunction.     

Erythropoietin administration may potentiate mobilization of storage iron in patients on oral iron chelation therapy

Five, repeatedly transfused, patients with refractory anemia (RA) or RA with ringed sideroblast (RARS) subtypes of myelodysplastic syndrome (MDS), with serum ferritin (SF) levels of > 2,000 microg/L, and one female with Hb E [beta26(B8)Glu --> Lys]/beta0-thalassemia (thal) with an SF level of 1,760 microg/ L, were treated with deferiprone (L1) at the dose of 4-6 g per day for at least 26 months. Beginning in the second month, all patients received recombinant human erythropoietin (rHuEPO) at the dose of 150 IU/kg thrice weekly, subcutaneously for 24 months. A significant increase in iron excretion after combined administration of L1 and rHuEPO compared to treatment with L1 as a single agent, was observed in all patients. The amount of excreted iron in urine ranged from 7.5 to almost 20 mg per day. In one patient, a response to rHuEPO resulted in transfusion independence and her SF decreased from 2086 to 879 microg/L. In four MDS patients, who remained dependent on red blood cell (RBC) transfusions, simultaneous administration of L1 and rHuEPO enabled the stabilization of SF levels, despite continuing iron load from the transfusions. Combined administration of rHuEPO and oral iron chelators may potentiate mobilization of storage iron and maintain iron balance in transfusion-dependent iron overloaded early MDS patients.     

C-reactive protein, left ventricular mass index, and risk of cardiovascular disease in essential hypertension.

We examined the association between C-reactive protein (CRP) and left ventricular mass index (LVMI), and investigated prospectively the incidence of cardiovascular disease (CVD) in asymptomatic subjects with essential hypertension. A total of 629 subjects (mean age 62 years, 51% female) free of prior CVD were included in this study. In cross-sectional analysis at baseline, patients were divided into three groups according to serum CRP levels: <1, 1 to 2, and >2 mg/L. In multivariate analysis, LVMI increased in a stepwise fashion with increasing CRP levels in both men (127.2+/-2.9, 138.7+/-4.1, 141.8+/-3.5 g/m(2), respectively; F=6.85, p=0.001) and women (119.5+/-3.6, 129.2+/-4.9, 130.2+/-4.8 g/m(2); F=4.23, p=0.031). During follow-up (mean 32 months), 52 subjects (19 female) developed CVD. Kaplan-Meier analysis with log-rank tests showed a significantly poorer event-free survival rate in the group with elevated CRP levels (> or =1 mg/L) (chi(2)=8.22, p<0.01) and that with left ventricular hypertrophy (LVH) (chi(2)=19.91, p<0.01). When participants were divided into four groups on the basis of CRP level (<1 or > or =1 mg/L) and the absence or presence of LVH, the group with LVH/CRP> or =1 mg/L showed markedly poorer event-free survival (chi(2)=28.02, p<0.01), and the adjusted hazard ratio by multivariate Cox regression analysis was 2.65 (95% confidence interval [CI]=1.55-5.46, p<0.01). In the subgroup with LVH (n=362), a significantly lower event-free survival rate of CVD was also observed in the group with CRP> or =1 mg/L (hazard ratio [HR] 1.37, 95% CI: 1.02-1.85, p=0.025). Our findings demonstrate that the CRP level is independently associated with LVMI, and suggest that measurement of CRP may provide clinically important prognostic information to supplement LVH.     

代谢综合征患者过氧化物酶体增殖物激活受体δ+294T/C基因多态性与血脂、肥胖和左室肥厚的关系

目的探讨代谢综合征(MS)患者过氧化物酶体增殖物激活受体δ(PPARδ)+294T/C基因多态性与血脂、肥胖和左室肥厚的关系。方法检测300例MS、174例高血压病(EH)和143例2型糖尿病(DM)患者的体重指数(BMI)、腰围、血压、血脂、空腹血糖(FBG)和空腹血浆胰岛素(FINS)。MS诊断根据1999年WHO亚太诊断标准,其中389例患者行超声心动图检测心脏结构改变,应用聚合酶链反应-限制性片段长度多态性方法测定PPARδ+294T/C基因多态性。结果PPARδ+294T/C基因多态性各基因型频率分布组间比较差异无统计学意义。MS组血浆总胆固醇、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平和BMI明显高于DM组。MS组和EH组的左室重量(LVM)、左室重量指数(LVMI)和左室肥厚罹患率均明显高于DM组。MS组CC型血浆总胆固醇和LDL-C水平明显高于TT型和TC型[总胆固醇:CC型(6.13±1.86)mmol/L比TC型(5.14±1.10)mmol/L或TT型(4.99±1.42mmol/L),P<0.05或P<0.01;LDL-C:CC型(3.82±1.52)mmol/L比TC型(3.14±0.88)mmol/L或TT型(2.90±0.87)mmol/L,P<0.05或P<0.01]。分析PPARδ各基因型与LVMI和BMI的关系,发现MS组C等位基因携带者(CC+TC)LVMI和BMI明显高于TT型[LVMI:CC+TC(46±10)g/m2.7比TT(44±10)g/m2.7;BMI:CC+TC(26±3)kg/m2比TT(25±3)kg/m2,P<0·05]。结论MS患者PPARδ+294T/C基因多态性与肥胖和脂质紊乱关系密切,C等位基因携带者较TT基因型患者左室重构明显。