Pharmacokinetic and pharmacodynamic properties of eptifibatide in subjects with normal or impaired renal function

BACKGROUND: Previous studies of the glycoprotein IIb-IIIa inhibitor eptifibatide have included patients with moderate renal impairment (serum creatinine concentrations, 2.0-4.0 mg/dL). In these patients, adjustment of the standard infusion dose (2.0 microg/kg.min) to 1.0 microg/kg.min was recommended on empiric grounds because approximately 50% of eptifibatide is cleared renally. OBJECTIVE: The present study was designed to assess teh pharmacokinetic and pharmacodynamic properties of eptifibatide in subjects with various levels of creatinine clearance (CrCl), a parameter that is a more accurate indicator of renal function than serum creatinine concentration to determine the appropriate dose adjustment in patients with reduced renal function. A secondary objective was to determine the tolerability of eptifibatide when administered to patients with decreased renal function. METHODS: This open-label study was concluded at 3 US sites experienced in conducting similar studies. Subjects with differing renal function (normal [group 1, CrCl > 80 mL/min], mild renal impairment [group 2, CrCl 51-80 mL/min], moderate renal impairment [group 3, CrCl 30-50 mL/min], or severe renal impairment [group 4, CrCl <30 mL/min]) received a 24-hour eptifibatide infusion of 2.0 microg/kg.min (groups 1, 2, and 3) or 1.0 microg/kg.min (group 4). The primary end point was the eptifibatide steady-state plasma concentration; the secondary end points included inhibition of platelet aggregation and eptifibatide clearance, terminal plasma half-life, and area under the plasma concentration-time curve. In addition to analyses performed for each group, pharmacokinetic models were estimated and eptifibatide clearance was related to CrCl as a continuous variable by linear regression. All adverse events were recorded, with particular attention to bleeding. RESULTS: Thirty-one subjects (21 men, 10 women; mean age, 58.5 years [range, 44-73 years]; mean body weight, 81.6 kg [range, 51.5-105.1 kg]; mean height, 162.9 cm [range, 150-183 cm]) were included in the study. A strong correlation was found between eptifibatide clearance and CrCl. A tree-based analytic model indicated that the optimal discrete break point for the purpose of dose adjustment was a CrCl of 55.85 mL/min, which was rounded to 50 mL/min for practical clinical reasons. In patients with moderate or severe renal impairment (CrCl < or = 50 mL/min), clearance rates and steady-state concentrations of eptifibatide were approximately 50% lower and almost 2-fold higher, respectively, than in patients with normal renal function or mild renal impairment (CrCl > 50 mL/min). Inhibition of platelet aggregation exceeded the clinically significant threshold of 80% in all groups. Five subjects had a mild bleeding event and 4 subjects experienced mild to moderate nonbleeding events, 2 of which were considered drug-related by the investigator. None of the events required intervention. CONCLUSIONS: In this study, moderate to severe renal impairment was associated with an approximately 50% reduction in total eptifibatide clearance and a corresponding doubling of plasma eptifibatide concentration. Based on these findings, in patients with moderately or severely impaired renal function (calculated CrCl < or =50 mL/min) who are scheduled for percutaneous coronary intervention or who have non-ST-segment elevation acute coronary syndromes, it is appropriate to reduce the infusion dose of eptifibatide by 50% (from 2 to 1 microg/kg.min). Because the bolus dose(s) is (are) used to establish the initial targeted plasma eptifibatide concentrations, which are independent of clearance, and given that the volume of distribution did not correlate with renal function, no adjustment of the bolus dose(s) is required.     

Use of dipeptidyl peptidase-4 inhibitors for the treatment of patients with type 2 diabetes mellitus and chronic kidney disease

Choices of antidiabetic agents for patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) are limited. Available data suggest that the use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be safe in patients at various stages of renal insufficiency. However, except for linagliptin, dosage adjustment is necessary. The efficacy of DPP-4 inhibitors in patients with renal insufficiency is generally similar to that of the general population with T2DM, with reductions in mean glycated hemoglobin (HbA1c) levels of 0.7% to 1.0% compared with baseline, and 0.4% to 0.7% compared with placebo. The frequency of moderate hypoglycemia is 21% to 80% higher with DPP-4 inhibitors compared with placebo, but the frequency of severe hypoglycemia is similar to that with placebo. The use of DPP-4 inhibitors in patients with renal insufficiency is associated with a slight weight loss of < 1 kg. Dipeptidyl peptidase-4 inhibitors may be used as monotherapy in patients with CKD and HbA1c levels < 8.5% as an alternative to insulin, glipizide, or pioglitazone. They can also be used as add-on therapy to glipizide and/or pioglitazone in patients with HbA1c levels < 9%, but studies are needed to evaluate these combinations in patients with renal insufficiency. Long-term and large-scale clinical trials are underway to better determine the safety and efficacy of DPP-4 inhibitors in patients with T2DM with and without CKD.     

Interactions of serum hsCRP with apoB, apoB/AI ratio and some components of metabolic syndrome amplify the predictive values for coronary artery disease

BACKGROUND: Plasma high-sensitivity CRP (hsCRP) is a marker of inflammation, and it is reported to link with coronary artery disease (CAD). Interactions between elevated serum hsCRP and other unfavorable risk factors have been proposed to cause high risk for CAD. OBJECTIVES: To examine the potential interactions between serum hsCRP and lipids and non-lipidic risk factors. METHODS: Markers of inflammation, the profiles of serum (apo)(lipo) proteins as well as classical risk factors were determined in 270 clinically stable angiographically documented subjects. The patients were stratified into tertiles according to hsCRP distribution. RESULTS: The Framingham CAD scores, relative and absolute risk for CAD and the prevalence of diabetes mellitus and hypertension were significantly higher in 3rd relative to 1st tertile of hsCRP. Subjects with hsCRP levels in the upper tertile had significant higher levels of serum glucose, triglyceride, apolipoprotein (apo)B, apoB/apoAI ratio and the counts of total leukocyte and neutrophil and lower levels of HDL-C, albumin and the ratio of albumin/globulins. Analyses by bivariate correlation as well as linear regression showed that serum hsCRP was associated positively with the occurrence of diabetes and hypertension, the counts of total leukocyte and neutrophil and the levels of serum glucose, uric acid, apoB, apoB/apoAI ratio, alpha1- and alpha2-globulins and inversely with albumin, albumin/globulin ratio and HDL-C. By constructing dummy combined variables, elevated hsCRP accompanied with male sex, diabetes, hypertension and high levels of serum glucose, apoB, apoB/apoAI ratio and cholesterol exhibited amplified high risk for CAD. CONCLUSIONS: The results show that hsCRP does interact multiplicatively with apoB and some variables of metabolic syndrome. The simultaneous assessment of hsCRP and interactive risk factors enhances discriminating value for CAD. It is suggested to use hsCRP in conjunction with apoB or apoB/apoAI ratio instead of cholesterol ratios in global risk assessment.     

The role of inflammation factors in development of acute coronary syndrome in patients with type 2 diabetes mellitus and impaired glucose tolerance

AIM: To study the levels of inflammatory markers in acute coronary syndrome (ACS) and 6 months after its regression in patients with diabetes mellitus (DM) type 2; to evaluate effects of anxiodepressive disorders on inflammatory markers. MATERIAL AND METHODS: The levels of high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-18 (IL-18), monocyte-chemmoattractant-protein-1 (MCP-1) and soluble vascular cell adhesion molecules (sVCAM) were measured in blood samples, severity of depressive symptoms and the level of glycated haemoglobin (HbA1c) were assessed in 58 patients with type 2 DM during ACS and in 54 patients 6 months after ACS regression. RESULTS: The levels of hsCRP and IL-18 correlate significantly with severity of myocardial lesion in ACS (p < 0.002; p < 0.009). Measurement of inflammatory markers 6 months after the discharge from hospital shows significant correlation between hsCRP, IL-18 and IL-6 levels; these levels were significantly lower in patients with HbA1c < 6.5% (tight glycemic control); there were associations between severity of depressive disorders and markers of inflammation (hsCRP, IL-18); analysis of MCP-1 and sVCAM levels 6 months after ACS regression shows a decrease of markers in 32-36% cases and an increase of markers in 64-67% cases. CONCLUSION: Complex immunological reactions, chronic hyperglycemia and depresssive disorders play an important role in development of latent inflammation of the vascular wall in patients with type 2 diabetes mellitus and ACS.     

Association of C-reactive protein with the presence and extent of angiographically verified coronary artery disease

Prospective studies have demonstrated that markers of inflammation, such as high-sensitivity C-reactive protein (hsCRP) and fibrinogen, predict future cardiovascular disease risk. However, the association between the hsCRP and fibrinogen levels and the extent of coronary stenosis in patients with coronary artery disease (CAD) remains controversial. The aim of our case-control study was to assess the association of inflammatory markers with the occurrence and extent of CAD. Serum hsCRP and plasma fibrinogen levels were measured in 138 patients with angiographically assessed CAD and in 183 healthy subjects matched according to age and gender. According to the number of significantly stenosed (>or= 50%) vessels, the patients were classified in four groups: those without stenosis (0-vessel disease) and those with 1, 2 or 3-vessel disease. The hsCRP and fibrinogen levels were significantly higher in patients than in controls (p < 0.001). Although the hsCRP and fibrinogen levels tended to increase with the number of stenotic vessels, the differences were only significant for hsCRP (p < 0.01). Regression analysis indicated hsCRP as an independent predictor for the presence (OR = 3.573, p < 0.05) and extent of CAD (beta = 1.095, p < 0.05). In conclusion, the present study is the first report concerning the frequency distribution of hsCRP in Serbian healthy subjects and CAD patients. We have shown that elevated levels of hsCRP are associated with the presence and extent of CAD.     

血清和肽素、VEGF在DN患者早期疾病严重程度的关系研究

目的 探讨血清和肽素、血管内皮细胞生长因子(VEGF)水平与早期糖尿病肾病(DN)患者疾病严重程度的关系.方法 选取2017年2月至2018年1月本院确诊的单纯2型糖尿病患者80例(T2DM组)、24 h尿清蛋白排泄率(UAER)范围30～300 mg/24 h的T2DM患者80例(微量组)、UAER＞300 mg/2...     

循环内皮脂酶阳性细胞比例与超敏C-反应蛋白在冠心病患者临床预后中的作用

目的随访检测冠心病患者内皮脂酶阳性的循环内皮细胞比例（EL＋/CECs）和超敏C-反应蛋白（hsCRP）6个月以上,探讨二者在临床预后中的作用。方法107例急性冠脉综合征（ACS）患者和69例稳定型心绞痛（SAP）患者,经冠状动脉（冠脉）造影证实有明显冠脉狭窄;经临床检查和选择性冠脉造影选择82例对照组患者。采集肘静脉血液标本,检测hsCRP,分离循环内皮细胞（CEC）,以免疫组化法检测CEC中EL的表达,并计算EL＋/CECs。所有患者进行6个月以上随访,记录心脏事件（反复心绞痛发作、非致死性心肌梗死、心源性死亡）,分析hsCRP、EL＋/CECs与心脏事件发生的关系。结果3组患者一般情况差异无统计学意义;hsCRP、EL＋/CECs差异有统计学意义（P〈0.05或P〈0.01）,其中以ACS组值最大,对照组值最小。所有研究对象随访结果发现,与低于hsCRP或EL＋/CECs均值（hsCRP为2.64mg/L,EL＋/CECs为25.27）的患者比较,高于均值的患者心脏事件的发生率显著增高（P均〈0.01）。回归分析发现,hsCRP与EL＋/CECs均可作为心脏复合事件的预测因子,二者结合起来,可显著提高预测价值。结论冠心病患者血管内皮细胞表达的EL可能参与了冠心病发病,EL＋/CECs可作为冠心病临床预后的预测因子,联合使用EL＋/CECs与hsCRP可显著提高冠心病患者预后的预测效率。     

The presence of apolipoprotein epsilon4 and epsilon2 alleles augments the risk of coronary artery disease in type 2 diabetic patients

OBJECTIVE: It has been suggested that there is a relationship between apolipoprotein E polymorphism and the severity of coronary artery disease in type II diabetes mellitus (T2DM). The current study specifically aimed to examine whether APOE polymorphism in association with serum lipids-lipoproteins level is a risk factor for developing coronary artery disease (CAD) in diabetic patients living in western of Iran. METHODS: The APOE genotypes were detected by PCR-RFLP in 152 angiographically documented diabetic CAD patients, 262 non-diabetic (ND) individuals with CAD and 300 unrelated controls (normal coronary artery cases without diabetes) and serum lipid level was measured enzymatically. RESULTS: The APOE-epsilon4 and epsilon2 allele frequencies were significantly higher in the CAD/T2DM and CAD/ND patients than in the control group (p<0.001). Our study demonstrated a significant association between APOE polymorphism and the level of plasma lipids with CAD/T2DM (p=0.001) and CAD/ND (p=0.026) patients. The CAD subjects with T2DM and ND patients carrying APOE-epsilon4 allele had lower plasma HDL-C level (p<0.001), (p=0.008) but had higher plasma LDL-C (p=0.01), total cholesterol (p=0.002), (p=0.03) and TG (p<0.001), (p=0.042) than that of the APOE-epsilon3 carriers, respectively. However, carriers of APOE-epsilon2 had significantly higher levels of plasma TG only. OR of APOE-epsilon4 and epsilon2 alleles in CAD/T2DM and CAD/ND patients were found to be 2.98 (p=0.001),1.86 (p=0.001), 2 (p=0.001), and 1.65 (p=0.001), respectively. CONCLUSIONS: The major finding of the present case-control study is that T2DM patients carrying APOE-epsilon2 and epsilon4 alleles have a higher risk of developing CAD than ND patients in the western population of Iran, with APOE-epsilon4 being more closely associated with CAD than the APOE-epsilon2 allele. These results indicated that carriers of APOE-epsilon4 allele have a distinct plasma lipids profile and carrier of this allele with low levels of HDL-C and with high levels of LDL-C may be susceptible to CAD and myocardial infarction specially in diabetic patients. This suggests that a therapeutic modality should be considered for these patients.     

The effect of 6 months of treatment with pravastatin on serum adiponection concentrations in Japanese patients with coronary artery disease and hypercholesterolemia: a pilot study

BACKGROUND: Pravastatin has been reported to reduce cardiovascular events and mortality in patients with coronary artery disease (CAD). Hypoadiponectinemia is a known risk factor for CAD. OBJECTIVE: This study analyzed the effects of shortterm pravastatin treatment on serum lipid and adiponectin concentrations in patients with CAD and hypercholesterolemia. METHODS: This was a multicenter, observational pilot study of the effect of 6 months of treatment with pravastatin 10 to 20 mg/d on serum adiponection concentrations in patients with documented CAD and total cholesterol (TC) levels> or =180 mg/dL. Patients from 13 medical centers in Japan were monitored at visits every 4 weeks for assessment of compliance and adverse effects. For the assessment of pravastatin's effects, patients were categorized according to baseline serum adiponectin concentrations: quartile 1 (Q1) = < 4.83 microg/mL; quartile 2 (Q2) = 4.83 to 7.20 microg/mL; (Q4) = > 10.38 microg/mL. The primary end point of the study was the percent change from baseline in adiponectin nectin concentrations at 6 months. Secondary end points were changes in lipids, high-sensitivity C-reactive protein (hsCRP), and glycosylated hemoglobin (HbA1c). RESULTS: One hundred thirty consecutive patients were enrolled; 11 were excluded and 4 discontinued due to adverse events. Thus, 115 patients were included in the study analyses (83 men, 32 women; mean age, 68 years). No patient had a cardiac event during the 6-month follow-up period. After 6 months of pravastatin treatment, 74 (64.3%) patients had increases in serum adiponectin concentrations. Median (interquartile range) adiponectin concentrations increased significantly from 7.2 (4.8-10.4) mug/mL at baseline to 7.8 (5.4-11.2) microg/mL after 6 months of pravastatin treatment (P<0.001); the mean percent increase from baseline was 16.3%. The percent increase from baseline in serum adiponection concentrations was significantly higher among patients in Q1 (39.3%) compared with those in Q3 (4.5%) and Q4 (6.3%) (P<0.003 and P<0.005, respectively). The relative increase in adiponectin concentrations was significantly correlated with the relative increase in high-density lipoprotein cholesterol (HDL-C) (f=0.47; P<0.001). After 6 months of pravastatin treatment, TC and low-density lipoprotein cholesterol levels had decreased, by 14.6% and 23.3%, respectively, and HDL-C levels had increased by 14.0% (all, P<0.001). The change in triglycerides (-13.3%) was not statistically significant. Serum hsCRP levels were significantly decreased from baseline after 6 months of pravastatin treatment (P<0.001). HbA1c did not change significantly. CONCLUSION: In this pilot study in Japanese patients with CAD and hypercholesterolemia, 6 months of treatment with pravastatin 10 to 20mg/d was associated with significant increases in serum adiponectin concentrations.     

Increased levels of tumour necrosis factor-alpha (TNF-alpha) in patients with Type II diabetes mellitus after myocardial infarction are related to endothelial dysfunction

The pathophysiology of insulin resistance and atherosclerosis may share a common inflammatory basis, maintaining endothelial dysfunction, suggesting why patients with T2DM (Type II diabetes mellitus) have an impaired prognosis after an MI (myocardial infarction), but it remains unclear how these parameters are inter-related. Forty patients with an MI (20 patients with and 20 patients without T2DM) took part in this cross-sectional study. Endothelium-dependent [FMD (flow-mediated dilation)] and -independent [NTG (nitroglycerine)] vasodilatation (determined by ultrasound), S(I) (insulin sensitivity index; determined by isoglycaemic-hyperinsulinaemic clamp) and serum levels of CRP (C-reactive protein), TNF-alpha (tumour necrosis factor-alpha), IL-6 (interleukin 6), resistin and adiponectin (determined by ELISA) were measured. Associations between FMD/NTG and S(I), and CRP, TNF-alpha, IL-6, adiponectin, resistin, lipids, blood pressure, BMI (body mass index) and brachial artery diameter were then assessed. FMD (2.1 compared with 4.7%; P<0.05), NTG (14.9 compared with 21.2%; P<0.05) and S(I) [4.3 compared with 6.6 10(-4) dl.kg(-1) of body weight.min(-1).(mu-units/ml)(-1); P<0.05], and adiponectin levels (3.1 compared with 6.4 microg/ml; P<0.01) were all lower in patients with T2DM. TNF-alpha (6.9 compared with 1.8 pg/ml; P<0.01) and IL-6 (2.3 compared with 1.2 pg/ml; P<0.01) levels were higher in patients with T2DM, whereas differences in CRP and resistin levels did not attain statistical significance between the two groups. TNF-alpha concentrations and brachial artery diameter were negatively, whereas S(I) was positively, correlated with FMD. Adjustment for age weakened the association for S(I), whereas TNF-alpha and brachial artery diameter remained significantly associated with FMD after adjustment for group, age and BMI. Endothelial dysfunction and low-grade inflammation co-exist in T2DM after MI. These results suggest that the endothelium is negatively impacted in multiple ways by the diabetic state after an MI.     

Proinflammatory and proapoptotic effects of methylglyoxal on neutrophils from patients with type 2 diabetes mellitus

OBJECTIVE: To determine the effect of methylglyoxal (MG) on cytokine production by, and apoptosis of, neutrophils from type 2 diabetes mellitus (T2DM) patients. DESIGN AND METHODS: The levels of plasma MG, cytokines released by isolated neutrophils and the apoptotic status of neutrophils were determined. RESULTS: The higher level of plasma MG in T2DM patients was correlated positively with glycated hemoglobin levels, fasting plasma glucose levels and urine albumin/creatinine ratios. The basal levels of cytokines released from neutrophils were markedly higher in patients. MG treatment of the neutrophils isolated from diabetic patients either did not alter, or decreased, the production of cytokines. In contrast, MG induced the release of cytokines from neutrophils of non-diabetics. Moreover, the neutrophils from T2DM patients showed a greater proclivity for apoptosis, which was further increased by in vitro MG treatment. CONCLUSION: MG stimulated neutrophils to release more cytokines, which might play a role in the development of infection in T2DM.     

血清成纤维细胞生长因子-21水平与2型糖尿病患者合并冠心病的相关性研究简

目的：评价血清成纤维细胞生长因子-21（FGF-21）的水平与2型糖尿病患者合并冠心病的相关性。方法将146名2型糖尿病患者分为合并冠心病组（66例）及未合并冠心病组（80例）,采酶联免疫吸附法测定并比较两组血清FGF-21水平,采用Logistic回归分析评价FGF-21与合并冠心病的独立相关性。结果合并冠心病组高密度脂蛋白水平较未合并冠心病组明显降低,血清FGF-21水平较未合并冠心病组明显升高（t分别=3.89、-5.08,P均＜0.05）,多元Logistic回归分析结果显示高血清FGF-21水平与合并冠心病存在独立正相关关系（OR=1.65,95% CI为1.13～2.64）。结论高血清FGF-21水平是2型糖尿病患者合并冠心病的独立危险因素,FGF-21可能是评估2型糖尿病患者冠心病风险重要的生物学标记物。     

Plasma osteopontin as a predictor of coronary artery disease: association with echocardiographic characteristics of atherosclerosis

Osteopontin (OPN), a bone‐related protein, is present within the atherosclerotic plaques, most strikingly in calcified plaques. Valvular calcifications are accepted as a part of the spectrum of atherosclerosis and are associated with atherosclerotic calcification in the coronary arteries. The study aimed to evaluate the association of plasma OPN with the presence and extent of coronary stenosis, mitral annular calcification (MAC), and aortic valve sclerosis in stable angina patients. We studied 120 subjects who underwent coronary angiography because of ischemic chest pain. Coronary artery disease (CAD) was defined as ≥50% stenosis in ≥1 coronary artery. MAC and aortic valve sclerosis were detected by echocardiography. Lipid profile, high sensitive C‐reactiveprotein (hsCRP), and OPN were measured in all studied subjects. Patients with CAD had increased plasma OPN when compared with those without CAD (P<0.001). Plasma OPN levels were significantly positively correlated with atherogenic lipid profile, hsCRP, MAC grading, aortic valve sclerosis grading, and the number of stenosed coronary vessels in CAD patients. In multivariate analysis, OPN was an independent predictor of CAD (P=0.01), MAC (P=0.01), and aortic valve sclerosis (P=0.04). In conclusion, OPN is an independent predictor of MAC and aortic valve sclerosis. Plasma OPN levels reflect the extent of coronary stenosis and can be used as a biomarker to identify patients with coronary atherosclerosis. J. Clin. Lab. Anal. 24:201–206, 2010. © 2010 Wiley‐Liss, Inc.     

Safety and tolerability of voriconazole in patients with baseline renal insufficiency and candidemia

Acutely ill patients with candidemia frequently suffer from renal insufficiency. Voriconazole's intravenous formulation with sulfobutylether beta-cyclodextrin (SBECD) is restricted in patients with renal insufficiency. We evaluated the use of intravenous voriconazole formulated with SBECD in candidemic patients with renal insufficiency and compared treatment outcome and safety to those who received a short course of amphotericin B deoxycholate followed by fluconazole. We reviewed data on treatment outcome, survival, safety, and tolerability from the subset of patients with moderate (creatinine clearance [CrCl], 30 to 50 ml/min) or severe (CrCl, <30 ml/min) renal insufficiency enrolled in a trial of voriconazole compared to amphotericin B deoxycholate followed by fluconazole for treatment of candidemia in 370 patients. Fifty-eight patients with renal impairment were identified: 41 patients on voriconazole and 17 on amphotericin B/fluconazole. The median duration of treatment was 14 days for voriconazole (median, 7 days intravenous) and 11 days for amphotericin B/fluconazole, 3 days of which were for amphotericin B. Despite the short duration of exposure, worsening of renal function or newly emerged renal adverse events were reported in 53% of amphotericin B-treated patients compared to 39% of voriconazole-treated patients. During treatment, median serum creatinine decreased in the voriconazole arm, whereas creatinine increased in the amphotericin B/fluconazole arm, before return to baseline at week 3. All-cause mortality at 14 weeks was 49% in the voriconazole arm compared to 65% in the amphotericin B/fluconazole arm. Intravenous voriconazole formulated with SBECD was effective in patients with moderate or severe renal insufficiency and candidemia and was associated with less acute renal toxicity than amphotericin B/fluconazole.     

Plasma matrix metalloproteinase-3 level is an independent prognostic factor in stable coronary artery disease

BACKGROUND: Recent evidence suggests the important role of matrix metalloproteinases (MMPs) in the progression of atherosclerosis and development of clinical events. We assessed the prognostic value of different plasma MMPs in patients with stable coronary artery disease (CAD). MATERIALS AND METHODS: A total of 165 consecutive nondiabetic patients with angiographically significant CAD (n = 150) or normal coronary angiograms despite exercise-induced myocardial ischemia (cardiac syndrome X, n = 15) and 17 normal subjects were evaluated. In each subject, plasma inflammatory markers including high sensitivity C-reactive protein (hsCRP) and MMP-2, 3 and 9 were measured. In CAD patients, major cardiovascular events including cardiac death, nonfatal myocardial infarction, unscheduled coronary revascularization and hospitalization as a result of unstable angina were prospectively followed up for more than 6 months. RESULTS: Plasma levels of MMPs were significantly higher in CAD patients than in those with cardiac syndrome X and in normal subjects (MMP-2: 914.76 +/- 13.20 vs. 830.79 +/- 31.95 vs. 783.08 +/- 28.40 ng mL(-1), P = 0.002; MMP-3: 129.59 +/- 4.21 vs. 116.86 +/- 8.09 vs. 91.71 +/- 9.55 ng mL(-1), P = 0.011; MMP-9: 31.42 +/- 2.84 vs. 11.40 +/- 5.49 vs. 6.71 +/- 2.89 ng mL(-1), P = 0.006). In CAD patients, there were 48 major cardiovascular events during a mean follow-up period of 17.74 +/- 0.85 months. The numbers of diseased vessels (HR = 2.19, 95% CI 1.20-1.02, P = 0.011), plasma hsCRP (HR = 2.21, 95% CI 1.18-4.11, P = 0.013) and MMP-3 level (HR = 2.46, 95% CI = 1.15-5.28, P = 0.021) were associated with the development of cardiovascular events. However, only the plasma MMP-3 level was an independent predictor of the adverse events in CAD patients (HR = 2.47, 95% CI 1.10-5.54, P = 0.028). CONCLUSIONS: Plasma MMP levels were increased in CAD patients. Plasma MMP-3 level, rather than hsCRP, was an independent prognostic marker for future cardiovascular events, suggesting its potential role in risk stratification and clinical management of stable CAD.     

Estimating kidney function and use of oral antidiabetic drugs in elderly

The prevalence of diabetes mellitus (DM) and renal impairment rises with age making regular estimation of glomerular filtration rate (eGFR) in older diabetics necessary. This study investigated the differences among available estimating equations in assessing eGFR in older diabetics and examined the use of oral antidiabetic drugs (OADs) in relation to renal function. Patients with DM were participants of the Berlin Initiative Study (BIS), a population‐based cohort study initiated in 2009 in Berlin, Germany, to evaluate kidney function in people ≥70 years. GFR was estimated with the creatinine‐based CKD‐EPI_CREA (Chronic Kidney Disease Epidemiology Collaboration), the MDRD (Modification of Diet in Renal Diseases) and the BIS1 equation and was directly measured (mGFR) with iohexol clearance as a gold standard in a subgroup (n = 137). Creatinine clearance was estimated with the Cockcroft–Gault equation (CrCl). DM prevalence was 26% (539 of 2070 overall participants). The antidiabetic drugs most commonly used among OAD patients were metformin (67%), glimepiride (27%) and glibenclamide (14%). Three of ten metformin patients had a CrCl <60 mL/min. Compared to mGFR, the mean differences of filtration rates calculated by MDRD, CKD‐EPI_CREA and BIS1 were +8.9, +6.7 and ?1.8 mL/min/1.73 m², respectively. Summing up, many patients with a CrCl <60 mL/min received metformin, although this represents a contraindication in Germany. Glibenclamide was commonly used despite its classification as potentially inappropriate medication in older adults. Finally, BIS1 performed better in estimating GFR in older diabetics than MDRD or CKD‐EPI_CREA.     

Factors influencing the outcomes of patients with both coronary artery disease and diabetes enrolled in standard cardiac rehabilitation programs: a literature review

Currently 23.5 million working-age adults 20 years or older have had a diagnosis of both coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM), with estimates that an additional 9% of the total US population will have a diagnosis of this chronic disease combination by the year 2025. Current annual health care costs for this working-age population including medical costs, functional disability, work loss, and premature mortality currently exceed $620 billion. Prior research efforts have shown that 25% to 32% of patients requiring a coronary revascularization procedure have both CAD and T2DM. The primary intervention prescribed for these patients to regain functional ability after revascularization is enrollment in a standard outpatient cardiac rehabilitation (CR) program. These standard programs, ranging in duration from 6 to 12 weeks, have been shown to improve the physical function of CAD patients by up to 15%, but patients diagnosed with both chronic conditions of CAD and T2DM (T2DM+CAD) attending these same programs exhibit only an 8% improvement. Moreover, T2DM+CAD patients experience much lower rates of rehabilitation program appointment adherence as well as greater program attrition (T2DM+CAD: 45%-62% vs CAD: 92%). Current medical literature regarding the relationship between CAD, T2DM, and cardiac rehabilitation will be examined to identify specific factors that could influence the functional outcomes achieved by the T2DM+CAD population when enrolled in a standard CR program and help increase understanding of why the adherence and attrition differences exist.     

Clinical utility of cardiac troponin I in the diagnosis of acute coronary syndrome in patients with renal failure

To analyze sensitivity and specificity of cardiac troponin I (cTnI) in detecting obstructive coronary artery disease in African American population with renal insufficiency presenting with acute coronary syndrome. Retrospective analysis of 108 patients who underwent coronary angiography over a 3-year period in a single institution. A troponin I level of 0.1 ng/mL or higher was considered abnormal troponin I. Renal insufficiency was defined as creatinine of 1.2 mg/dL or higher. Obstructive coronary artery disease (CAD) was defined as luminal diameter reduction of 70% or more (or total occlusion) in at least 1 coronary artery. Patients were divided into group 1 (renal insufficiency without need for hemodialysis, n = 76, mean age = 65) and group 2 (patients requiring hemodialysis, n = 32, mean age = 60). Access Accu TnI method was used to quantitate cTnI where murine monoclonal antibodies specifically bind to the C-terminal end of cTnI. In group 1, 41 (54%) patients had abnormal troponin of whom 37 (90%) had CAD and 4 (10%) had normal angiogram; 35 (46%) patients had normal troponin, of whom 25 (71%) had CAD and 10 (29%) had normal angiogram yielding a sensitivity of 60% and specificity of 71% (P = 0.003; 95% confidence interval). In group 2, 20 (63%) had abnormal troponin of whom 19 (95%) had CAD and 1(5%) had normal angiogram; 12 (38%) had normal troponin of whom 7 (59%) had CAD and 5 (41%) had normal angiogram yielding a sensitivity of 73% and specificity of 83% (P = 0.06; 95% confidence interval). cTnI has a sensitivity of 60% and specificity of 71% in acute coronary syndrome patients with renal insufficiency. In patients on hemodialysis, troponin I has a sensitivity of 73% and specificity of 83% for detection of obstructive CAD.     

马来酸罗格列酮对2型糖尿病患者颈动脉内膜中层厚度的影响

目的观察在2型糖尿病(T2DM)的患者中应用马来酸罗格列酮治疗对其颈总动脉内膜中层厚度(IMT)的影响。方法T2DM患者(T2DM组)与糖耐量正常者(NGT组)各30例分别检测空腹血糖(FPG)、血胰岛素(FIns)、糖基化血红蛋白(HbA1c),计算胰岛素抵抗指数(HOMA-IR),同时测定超敏C反应蛋白(hsCRP),并应用超声仪测定IMT,然后T2DM组接受马来酸罗格列酮治疗12个月后再次检测上述指标,比较各指标的变化。结果T2DM组的FPG、FIns、HbA1c、HOMA-IR、hsCRP和IMT均显著高于NGT组(P<0.05或P<0.01);马来酸罗格列酮治疗后IGT组的上述指标与治疗前相比均显著下降(P<0.05或P<0.01)。结论马来酸罗格列酮治疗可改善T2DM患者胰岛素抵抗状态,降低炎症反应,并可能缓解动脉粥样硬化的发生和发展。