Low serum bilirubin concentration is a novel risk factor for the development of albuminuria in patients with type 2 diabetes

Objective

Bilirubin has been recognized as an important endogeneous antioxidant. Previous studies reported that bilirubin could prevent atherosclerosis. The aim of this study was to investigate if serum bilirubin concentration could be a predictor for the development of albuminuria in patients with type 2 diabetes.

Materials and Methods

We measured serum bilirubin in 320 consecutive patients with normoalbuminuria. We performed follow-up study to assess the development of albuminuria, mean interval of which was 3.2 ± 0.9 years. Cox proportional hazards regression was used to examine the relationship between serum bilirubin concentration and the development of albuminuria.

Results

During follow-up duration, 43 patients have developed albuminuria. In multivariate analysis, after adjusting for comprehensive risk factors, the risk of developing albuminuria was higher in the lowest quartile of serum bilirubin concentrations than that in the highest quartile of serum bilirubin concentrations (Hazard ratio, 5.76; 95% CI, 1.65 to 24.93).

Conclusions

Low serum bilirubin concentration could be a novel risk factor for the development of albuminuria in patients with type 2 diabetes.     

Effect of Renin–Angiotensin System Inhibition on Cardiovascular Events in Older Hypertensive Patients with Metabolic Syndrome

Objective

Metabolic syndrome (MetS) is associated with cardiovascular disease (CVD). Insulin resistance has been hypothesized as the underlying feature of MetS. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are widely used antihypertensives that may improve insulin sensitivity. The aim of the study is to evaluate the effect of ACEI/ARB on incident CVD events in older hypertensive patients with MetS.

Materials/Methods

We used the Cardiovascular Health Study, a prospective cohort study of individuals > 65 years of age to evaluate ACEI/ARB use and time to CVD events (including coronary and cerebrovascular events). The study included 777 subjects who had hypertension and ATP III-defined MetS, but free of CVD and diabetes at baseline. Cox regression models were used to evaluate the effect of ACEI/ARB as compared to other antihypertensives on the time to the first CVD events.

Results

ACEI/ARB use was associated with a decreased risk of CVD events (adjusted HR = 0.658, 95 % C.I. [0.436–0.993]) compared to other antihypertensives. When CVD endpoints were evaluated separately, use of ACEI/ARB was associated with lower rates of angioplasty and coronary events (HR of 0.129 and 0.530 respectively, with 95 % CI [0.017–0.952] and [0.321–0.875]).

Conclusions

ACEI/ARB use was associated with a lower risk of CVD events in older hypertensive patients with MetS, primarily due to a reduction in coronary events. The potential protective effect of ACEI/ARB on CVD events in older individuals with MetS will need further confirmation from prospective studies.     

The effect of enzyme replacement therapy on clinical outcomes in female patients with Fabry disease – A systematic literature review by a European panel of experts

BackgroundHeterozygous females with Fabry disease have a wide range of clinical phenotypes depending on the nature of their mutation and their X-chromosome inactivation pattern; it is therefore important to examine outcomes of enzyme replacement therapy (ERT) in the female patient population specifically. This paper presents the findings of a systematic literature review of treatment outcomes with ERT in adult female patients.MethodsA comprehensive systematic literature review was conducted through January 2017 to retrieve published papers with original data on ERT in the treatment of Fabry disease. The review included all original articles that presented ERT outcomes data on patients with Fabry disease, irrespective of the study type.ResultsClinical evidence for the efficacy of ERT in female patients was available from 67 publications including six clinical trial publications, and indicates significant reductions in plasma and urine globotriaosylceramide (GL-3) accumulation (in female patients with elevated pre-treatment levels) and improvements in cardiac parameters and quality of life (QoL). To date, data are insufficient to conclude on the effects of ERT on the nervous system, gastrointestinal manifestations, and pain in female patients with Fabry disease.ConclusionsThis review of available literature data demonstrates that ERT in adult female patients with Fabry disease has a beneficial effect on GL-3 levels and cardiac outcomes. The current evidence also suggests that ERT may improve QoL in this patient population, though further studies are needed to examine these results.     

ACEI、ARB联合多巴胺及速尿持续泵入解除心肾综合征患者利尿剂抵抗的临床分析

目的探讨血管紧张素转换酶抑制剂（ACEI）、血管紧张素受体拮抗剂（ARB）联合多巴胺及速尿持续泵入解除心肾综合征患者利尿剂抵抗的标准及方法。方法选择慢性心力衰竭合并肾功能不全及利尿剂抵抗患者100例（心功能Ⅲ~Ⅳ级,肌酐〈3mg/dl）,随机分为ACEI、ARB联合多巴胺及速尿持续泵入治疗组和对照组,每组50例。全部患者在入院时均进行心脏超声、胸片、肾功能、心电图等检查。2组患者的发病年龄、心功能分级、肾功能水平、浮肿及少尿程度差异无统计学意义（P〉0.05）。结果治疗组患者症状明显改善,左心室射血分数增加,体重降低,尿量增加（P〈0.05）。结论 ACEI、ARB联合多巴胺及速尿持续泵入治疗心肾综合征合并利尿剂抵抗,无论对心功能或肾功能的改善都十分有益。     

Angiotensin-Converting Enzyme Inhibitors in Hypertension: To Use or Not to Use?

Most guidelines for the management of patients with cardiovascular disease recommend angiotensin-converting enzyme (ACE) inhibitors as first-choice therapy, whereas angiotensin receptor blockers (ARBs) are merely considered an alternative for ACE inhibitor–intolerant patients. The aim of this review was to compare outcomes and adverse events between ACE inhibitors and ARBs in patients. In patients with hypertension and hypertension with compelling indications, we found no difference in efficacy between ARBs and ACE inhibitors with regard to the surrogate endpoint of blood pressure and outcomes of all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. However, ACE inhibitors remain associated with cough and a very low risk of angioedema and fatalities. Overall withdrawal rates because of adverse events are lower with ARBs than with ACE inhibitors. Given the equal outcome efficacy but fewer adverse events with ARBs, risk-to-benefit analysis in aggregate indicates that at present there is little, if any, reason to use ACE inhibitors for the treatment of hypertension or its compelling indications.     

联合应用氯沙坦和氨氯地平治疗单纯收缩期高血压的疗效

目的观察氨氯地平单用或与氯沙坦联合应用治疗单纯收缩期高血压的疗效及其对靶器官的保护作用。方法将60例中老年原发性高血压病患者随机分为氨氯地平组（A组）和氨氯地平加氯沙坦组（B组），分别予以氨氯地平5mg／d口服和氨氯地平5mg／d加氯沙坦50mg／d口服，观察治疗前、后尿微量蛋白、血钾、血尿素氮、血肌酐、血尿酸及血压的变化。结果治疗8周，两组血压均有明显下降，A组总有效率为53．33％，B组总有效率为83．33％。两组差异有统计学意义（P〈0．05）。两组治疗前、后的尿微量蛋白，肾功能的差异有统计学意义（P〈0．05）。结论CCB（氨氯地平）和ARB（氯沙坦）联合应用可用于单纯收缩期高血压的治疗。     

葛根素联合ACEI／ARB治疗早期糖尿病肾病疗效的Meta分析

目的:评价葛根素制荆联合ACEI/ARB出对早期糖尿病肾病微量白蛋白尿的治疗效应.方法:检索中国生物医学文献数据库自1989年1月至2007年10月期间,发表的有关ACEI或ARB类药物联合葛根素对早期DN作用的随机对照临床试验研究文献,采用随机效应模型法对符合纳入标准的文献中尿微量白蛋白的差值进行Meta分析.结果:6项共322例纳入研究,联合治疗组与对照组患者尿微量白蛋白比较,标准化均数的合并值为-3.27,其95%可信区间为(-4.77,-1.77),合并效应量的假设检验结果示,P＜0.05;葛根素联合ACEI治疗亚组与对照组患者尿微量白蛋白比较的5项研究,标准化均数的合并值为-3.47,其95%可信区间为(-5.21,-1.72),合并效应量的假设检验结果示,P＜0.05.结论:葛根素联合ACEI/ARB有明显减少DN患者尿微量白蛋白排泄率的作用,亚组分析发现,葛根素联合ACEI的治疗效应优于单纯ACEI对照组.     

RETRACTED ARTICLE: Dual blockade of the renin-angiotensin system in chronic renal disease: <Emphasis Type="Italic">to do or not to do</Emphasis>

The renin-angiotensin-aldosterone system has an important role in the progression of both diabetic and nondiabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin-II receptor blocker can effectively retard or halt this progression. However, their renoprotective effect is not enough, because approximately 20% of patients have a progressive course to endstage renal disease. There is now clear evidence that combination therapy of two agents is more antiproteinuric and, likely renoprotective, than each agent alone. However, several critical issues should be addressed before recommending it as standard treatment in chronic renal disease.     

Effect of valsartan on erythropoietin and hemoglobin levels in stage III-IV chronic kidney disease patients

Angiotensin-converting enzyme inhibitors (ACEIs) were accepted as a potential cause of inadequate epoetin response in chronic kidney disease (CKD) patients. We aimed to determine the effects of valsartan, an angiotensin receptor blocker (ARB), on serum ertyhropoietin levels and on certain biochemical and haematological parameters in hypertensive CKD patients. Twenty-two stage III-IV CKD patients (mean age; 56.8 +/- 8.9 years, 12 male 10 female) were included in the study. Before initiating the treatment, current anti-hypertensive treatments (if any) were discontinued, and blood samples were collected after a washout period of 3 weeks. Valsartan 80 mg/day was started, and additional anti-hypertensive agents were given according to study protocol if needed. One way Anova and paired t-tests were used for statistical comparisons. Serum blood urea nitrogen (BUN), creatinine, uric acid, potassium, haemoglobin and erythropoietin values were measured, and glomerular filtration rates were calculated before and 3, 6 and 90 days after valsartan treatment, a significant reduction in EPO level was observed at 3rd (19.6 +/- 24.0 vs. 13.8 +/- 8.5, p = 0.010), 6th (12.1 +/- 7.6, p = 0.009), and 90th days (8.3 +/- 5.4, p = 0.007). When pre-treatment values were compared with 90th day results, no significant change was observed in terms of hgb, htc, serum BUN, creatinine, uric acid, potassium, and GFR values. In conclusion, valsartan, an ARB, did not decrease haemoglobin levels in stage III-IV CKD patients despite significant reduction in serum erythropoietinlevels, so ARBs may be preferred to ACEIs in CKD patients when indicated.