Long-term follow-up of intensive glycaemic control on renal outcomes in the Veterans Affairs Diabetes Trial (VADT)

Aims/hypothesis

We conducted an analysis of data collected during the Veterans Affairs Diabetes Trial (VADT) and the follow-up study (VADT-F) to determine whether intensive (INT) compared with standard (STD) glycaemic control during the VADT resulted in better long-term kidney outcomes.

Methods

VADT randomly assigned 1791 veterans from 20 Veterans Affairs (VA) medical centres who had type 2 diabetes mellitus and a mean HbA_1c of 9.4 ± 2% (79.2 mmol/mol) at baseline to receive either INT or STD glucose control for a median of 5.6 years (randomisation December 2000 to May 2003; intervention ending in May 2008). After the trial, participants received routine care through their own physicians within the VA. This is an interim analysis of the VADT-F (June 2008 to December 2013). We collected data using VA and National databases and report renal outcomes based on serum creatinine, eGFR and urine albumin to creatinine ratio (ACR) in 1033 people who provided informed consent to participate in the VADT-F.

Results

By the end of the VADT-F, significantly more people who received INT treatment during the VADT maintained an eGFR >60 ml min^?1 1.73 m^?2 (OR 1.34 [95% CI 1.05, 1.71], p = 0.02). This benefit was most evident in those who were classified as at moderate risk (INT vs STD, RR 1.3, p = 0.03) or high risk (RR 2.3, p = 0.04) of chronic kidney disease on the Kidney Disease Improving Global Outcomes (KDIGO-CKD) at the beginning of VADT. At the end of VADT-F, significantly more people from the INT group improved to a low KDIGO risk category (RR 6.1, p = 0.002). During the VADT-F there were no significant differences between INT and STD for average HbA_1c, blood pressure or lipid levels.

Conclusions/interpretation

After just over 11 years of follow-up, there was a 34% greater odds of maintaining an eGFR of >60 ml min^?1 1.73 m^?2 and of improving the KDIGO category in individuals with type 2 diabetes who had received INT for a median of 5.6 years.VADT clinical trials.gov number: NCT 00032487.

     

肾动脉支架置入术对老年肾动脉粥样硬化性高血压的长期影响及临床相关因素

目的探讨肾动脉支架置入术对老年肾动脉粥样硬化性高血压的长期影响及临床相关因素。 方法选取2013年5月至2015年7月淄博市人民医院收治的85例老年肾动脉粥样硬化性高血压患者作为研究对象,所有患者均接受肾动脉支架置入术治疗。术后随访3～48个月,观察研究对象舒张压(DBP)、收缩压(SBP)、血肌酐(Scr),并对肾功能恶化、全因死亡的影响因素进行分析。 结果随访结束时患者DBP、SBP水平较术前降低,Scr水平较术前升高,差异有统计学意义(P<0.05)。18例(21.18%)出现肾功能恶化。Logistic多因素分析显示,合并糖尿病、年龄≥60岁、Scr≥133.3 μmol/L是导致肾功能恶化的独立危险因素(P<0.05)。10例(11.76%)死亡,其中5例死于肾功能衰竭,4例心力衰竭,1例病因尚未明确。Logistic多因素分析显示,年龄≥60岁是导致全因死亡的独立危险因素(P<0.05)。 结论肾动脉支架置入术治疗老年肾动脉粥样硬化性高血压可长期保持血压稳定,Scr≥133.3 μmol/L、年龄≥60岁、合并糖尿病是导致肾动脉支架置入术预后不良的危险因素。     

Safety of sirolimus-eluting stenting and its effect on restenosis in patients with unstable angina pectoris (a SIRIUS substudy)

The SIRIUS study was a double-blinded, randomized trial of the sirolimus-eluting stent (SES) to evaluate its effect on the rate of restenosis. The present report is a retrospective analysis of short- and long-term outcomes of SESs compared with bare metal stents (BMSs) in a subgroup of patients with unstable angina enrolled in the trial. Of 1,058 patients randomized in SIRIUS, 533 (50.4%) had unstable angina pectoris and 490 had stable angina. In the unstable angina group, patients treated with SESs and BMSs had similar clinical and angiographic characteristics. The stenting procedure was highly successful in the 2 groups (95.9% and 97.4%, respectively) with similar immediate angiographic results and short-term (in-hospital) clinical event rates. At 1-year follow-up, compared with BMSs, patients with unstable angina treated with SESs had significantly lower rates of target lesion revascularization (5.5% vs 22.3%, p <0.0001), target vessel failure (10.9% vs 26.3%, p <0.0001), and major adverse cardiac events (8.4% vs 24.8%, p <0.0001). Stent thrombosis was a rare event, with only 1 patient (0.4%) in each group during the first 30 days. Late thrombosis occurred in 2 patients (0.7%) in the BMS group but in none of the SES group. In conclusion, in the higher risk subgroup of patients with unstable angina, SESs are as safe as BMSs in decreasing restenosis and the need for repeat revascularization. This is reflected by a significant decrease in major adverse cardiac events and target vessel failure. Patients with unstable angina undergoing percutaneous coronary intervention who meet the entry criteria of the SIRIUS study should be preferentially treated with SESs.     

Benefits of a beta-blocking agent (carvedilol) on bilateral atherosclerotic renal artery stenosis. A case report

A 77 year old man with coronary artery disease was referred to our institution for recurrent (flash) episodes of pulmonary edema due to malignant hypertension. A selective contrast-enhanced angiography showed severe bilateral renal artery stenosis. We also found a high level of plasma renin production identifying intense renin-angiotensin system activation. We first considered revascularisation. Percutaneous intervention initially failed and thereafter the patient denied surgical revascularisation. We have then recommended medical therapy, namely a beta-blocker after adequate correction of fluid retention. We used CARVEDILOL which has no nephrotoxicity and effectively inhibit the renin-angiotensin system. The patient feels significant functional and clinical improvement with no fluid retention relapse with a follow-up of more than 18 months.     

Effect of losartan versus atenolol on aortic valve sclerosis (a LIFE substudy)

Neither losartan- nor atenolol-based antihypertensive regimens could prevent the progression of aortic valve (AV) sclerosis in elderly, high-risk hypertensive patients, and the regression of AV sclerosis did not translate into reduced cardiovascular risk.     

Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes

Aims/hypothesis

In diabetes, advanced glycation end-products (AGEs) and the AGE precursor methylglyoxal (MGO) are associated with endothelial dysfunction and the development of microvascular complications. In this study we used a rat model of diabetes, in which rats transgenically overexpressed the MGO-detoxifying enzyme glyoxalase-I (GLO-I), to determine the impact of intracellular glycation on vascular function and the development of early renal changes in diabetes.

Methods

Wild-type and Glo1-overexpressing rats were rendered diabetic for a period of 24 weeks by intravenous injection of streptozotocin. Mesenteric arteries were isolated to study ex vivo vascular reactivity with a wire myograph and kidneys were processed for histological examination. Glycation was determined by mass spectrometry and immunohistochemistry. Markers for inflammation, endothelium dysfunction and renal dysfunction were measured with ELISA-based techniques.

Results

Diabetes-induced formation of AGEs in mesenteric arteries and endothelial dysfunction were reduced by Glo1 overexpression. Despite the absence of advanced nephrotic lesions, early markers of renal dysfunction (i.e. increased glomerular volume, decreased podocyte number and diabetes-induced elevation of urinary markers albumin, osteopontin, kidney-inflammation-molecule-1 and nephrin) were attenuated by Glo1 overexpression. In line with this, downregulation of Glo1 in cultured endothelial cells resulted in increased expression of inflammation and endothelium dysfunction markers. In fully differentiated cultured podocytes incubation with MGO resulted in apoptosis.

Conclusions/interpretation

This study shows that effective regulation of the GLO-I enzyme is important in the prevention of vascular intracellular glycation, endothelial dysfunction and early renal impairment in experimental diabetes. Modulating the GLO-I pathway therefore may provide a novel approach to prevent vascular complications in diabetes.     

Long-term clinical outcomes of the Drug-Eluting Stents in the Real World (DESIRE) Registry

Background: Recently, cardiologists have treated more complex patients and lesions with drug-eluting stents (DES). However, long-term efficacy and safety of the off-label use of these new devices is yet to be demonstrated.
Methods: The Drug-Eluting Stents in the Real World (DESIRE) registry is a prospective, nonrandomized single-center registry with consecutive patients treated solely with DES between May 2002 and May 2007. The primary end-point was long-term occurrence of major adverse cardiac events (MACE). Patients were clinically evaluated at 1, 3, and 6 months and then annually up to 5 years.
Results: A total of 2,084 patients (2,864 lesions and 3,120 DES) were included. The mean age was 63.8 ± 11.5 years. Diabetes was detected in 28.9% and 40.7% presented with acute coronary syndrome. Cypher™ was the predominant DES in this registry (83.5%). Mean follow-up time was 2.6 ± 1.2 years and was obtained in 96.5% of the eligible patients. Target lesion revascularization (TLR) was performed in 3.3% of the patients. Q wave myocardial infarction (MI) occurred in only 0.7% of these patients and total stent thrombosis rate was 1.6% (n = 33). Independent predictors of thrombosis were PCI in the setting of MI (HR 11.2; 95% CI, 9.6–12.4, P = 0.001), lesion length (HR 4.6; 95% CI, 3.2–5.3, P = 0.031), moderate to severe calcification at lesion site (HR 13.1; 95% CI, 12.1–16.7, P < 0.001), and in-stent residual stenosis (HR 14.5; 95% CI, 10.2–17.6, P < 0.001).
Conclusion: The use of DES in unselected population is associated with long-term safety and effectiveness with acceptable low rates of adverse clinical events.     

Prehypertension is associated with insulin resistance state and not with an initial renal function impairment. A Metabolic Syndrome in Active Subjects in Spain (MESYAS) Registry substudy

BACKGROUND: The aim of this study was to assess the prevalence of metabolic syndrome (MS) and other surrogate markers of insulin resistance, and whether these markers are better for defining the prehypertensive state than is renal dysfunction. METHODS: Data from 19,041 healthy active workers, mean age 42.2 (10.7) years, from three health insurance companies, were prospectively collected. Presence of MS, assessed according to the modified criteria of the National Cholesterol Education Program Third Adult Treatment Panel, and the ratio of triglycerides to high-density lipoprotein were considered as surrogate markers of insulin resistance. Renal function was assessed by the Modification of Diet in Renal Disease Study equation. Blood pressure was classified as normotension (NT), prehypertension (PHT), or hypertension (HT) according to the guidelines of the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. RESULTS: The global presence of MS was 11.8% The higher prevalence was found in subjects with hypertension (30%), followed by those with PHT (9.6%). The prevalence in normotensive subjects was very low (0.9%). The presence of MS and hypertension increased in parallel with age. Metabolic syndrome (odds ratio [OR] 4.3), obesity (OR 2.2), overweight (OR 1.7), impaired fasting glucose (OR 1.3), and elevated triglycerides to HDL ratio (OR 1.2), but no degree of renal dysfunction, were independent risk factors for the progression from NT to PHT. CONCLUSIONS: Prehypertension is associated with markers of insulin resistance, assessed by the presence of MS and other surrogate markers, and not with an initial renal dysfunction. In this study, MS was found to be present in almost one third of hypertensive but asymptomatic and otherwise healthy workers.     

分肾功能测量评估单侧粥样硬化性肾动脉狭窄支架术对肾功能的影响

目的 应用肾动态显像评估单侧动脉硬化性肾动脉狭窄患者腔内治疗效果,并对可能改善分肾功能的影响因素进行分析.方法 回顾性分析北京安贞医院2016年1月-2018年4月收治的60例单侧动脉硬化性肾动脉狭窄患者,均行肾动脉支架成形术.收集患者的一般资料,术前及术后肾功能检查结果,肾动脉彩色多普勒超声(彩超)及肾动态显像结果,...     

The effect of anemia and white matter hyperintensities (WMH) on cognitive impairment in patients with amnestic mild cognitive impairment (MCI)

Anemia and subcortical ischemic change might be associated with increased risks for cognitive impairment among the elderly. This study examined the associations among anemia, WMH and cognitive function in patients with amnestic MCI. We recruited 278 subjects with amnestic MCI from the Clinical Research Center for Dementia of South Korea (CREDOS), a hospital-based cohort study. A standardized neuropsychological battery, containing tests of language, visuospatial function, verbal memory and executive function, was used for all patients. Anemia was defined as a hemoglobin concentration below 12 g/dl for women and below 13 g/dl for men. The severity of WMH was also examined using brain magnetic resonance imaging (MRI). After multivariable adjustments, anemia and WMH were associated with poorer performance on cognitive function tests (anemia: Stroop test, F=4.17, p=0.042; WMH: Stroop test, F=6.45, p=0.002; Rey-complex figure test-copy, F=4.08, p=0.018). Moreover, a significant interaction between anemia and the severity of WMH was observed in performance on the Go/no go test (F=4.50, p=0.012) and the Stroop test (F=3.36, p=0.037). In post hoc analysis, anemic patients with severe WMH had significantly worse scores on measure of executive function (Go/no go test, p=0.011; Stroop test, p=0.001). Anemia and WMH had interactive effects on executive function impairment among the elderly with amnestic MCI.