Platelet thromboxane(11-dehydro-Thromboxane B_2) and aspirin response in patients with diabetes and coronary artery disease

Aspirin(ASA) irreversibly inhibits platelet cyclooxygenase-1(COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on thromboxane generation was evaluated in patients with diabetes(DM) and cardiovascular disease. Thromboxane inhibition was assessed by measuring the urinary excretion of 11-dehydro-thromboxane B2(11dhTxB2), a stable metabolite of thromboxane A2. The mean baseline urinary 11dhTxB2 of DM was 69.6% higher than healthy controls(P = 0.024): female subjects(DM and controls) had 50.9% higher baseline 11dhTxB2 than males(P = 0.0004), while age or disease duration had no influence. Daily ASA ingestion inhibited urinary 11dhTxB2 in both DM(71.7%) and controls(75.1%, P 0.0001). Using a pre-established cut-off of 1500 pg/mg of urinary 11dhTxB2, there were twice as many ASA poor responders(ASA "resistant") in DM than in controls(14.8% and 8.4%, respectively). The rate of ASA poor responders in two populations of acute coronary syndrome(ACS) patients was 28.6 and 28.7%, in spite of a significant(81.6%) inhibition of urinary 11dhTxB2(P 0.0001). Both baseline 11dhTxB2 levels and rate of poor ASA responders were significantly higher in DM and ACS compared to controls. Underlying systemic oxidative inflammation may maintain platelet function in atherosclerotic cardiovascular disease irrespective of COX-1 pathway inhibition and/or increase systemic generation of thromboxane from non-platelet sources.     

Insulin improves myocardial blood flow in patients with type 2 diabetes and coronary artery disease

Insulin infusion improves myocardial blood flow (MBF) in healthy subjects. Until now, the effect of insulin on myocardial perfusion in type 2 diabetic subjects with coronary artery disease (CAD) has been unknown. We studied the effects of insulin on MBF in ischemic regions evaluated by single-photon emission-computed tomography and coronary angiography and in nonischemic regions in 43 subjects (ages 63 +/- 7 years) with type 2 diabetes (HbA(1c) 7.1 +/- 0.9%). MBF was measured at fasting and during a euglycemic-hyperinsulinemic clamp at rest (n = 43) and during adenosine-induced (140 mug . kg(-1) . min(-1) for 7 min) hyperemia (n = 26) using positron emission tomography and (15)O-labeled water. MBF was significantly attenuated in ischemic regions as compared with in nonischemic regions (P < 0.0001) and was increased by insulin as compared with in the fasting state (P < 0.0001). At rest, insulin infusion increased MBF by 13% in ischemic regions (P = 0.043) and 22% in nonischemic regions (P = 0.003). During adenosine infusion, insulin enhanced MBF by 20% (P = 0.018) in ischemic regions and 18% (P = 0.045) in nonischemic regions. In conclusion, insulin infusion improved MBF similarly in ischemic and nonischemic regions in type 2 diabetic subjects with CAD. Consequently, in addition to its metabolic effects, insulin infusion may improve endothelial function and thus increase the threshold for ischemia and partly contribute to the beneficial effects found in clinical trials in these subjects.     

Independent association of type 2 diabetes and coronary artery disease with myocardial insulin resistance

Clustering of classical cardiovascular risk factors is insufficient to account for the excess coronary artery disease (CAD) of patients with diabetes, and chronic hyperglycemia and insulin resistance (IR) are obvious culprits. Whole-body and skeletal muscle IR is characteristic of patients with type 2 diabetes, but whether it extends to the normally contracting cardiac muscle is controversial. We investigated whether type 2 diabetes is associated with myocardial IR independent of CAD in a case-control series (n = 55) of male nondiabetic and diabetic (type 2 and type 1) patients with or without angiographically documented CAD. Baseline blood flow ((15)O-water) and insulin-stimulated glucose uptake ((18)F-fluoro-deoxyglucose) during euglycemic (5.6 mmol/l), physiological hyperinsulinemia (40 mU x min(-1) x m(-2) insulin clamp) were measured by positron emission tomography in skeletal muscle and normally contracting myocardium. Skeletal muscle glucose uptake was reduced in association with both CAD and type 2 diabetes. In regions with normal baseline perfusion, insulin-mediated myocardial glucose uptake was reduced in non-CAD type 2 diabetic (0.36 +/- 0.14 micro mol x min(-1). g(-1)) and nondiabetic CAD patients (0.44 +/- 0.15 micro mol x min(- 1) x g(-1)) in comparison with healthy control subjects (0.61 +/- 0.08) or with non-CAD type 1 diabetic patients (0.80 +/- 0.13; P < 0.001 for both CAD and diabetes). Neither basal skeletal muscle nor basal myocardial blood flow differed across groups; both skeletal muscle and myocardial IR were directly related to whole-body IR. We conclude that type 2 diabetes is specifically associated with myocardial IR that is independent of and nonadditive with angiographic CAD and proportional to skeletal muscle and whole-body IR.     

Optimal treatment for coronary artery disease in patients with diabetes: percutaneous coronary intervention,coronary artery bypass graft,and medications

There are three strategies for patients with coronary artery disease (CAD): medical therapy, coronary artery bypass graft (CABG), and percutaneous coronary intervention (PCI). With the development of drug-eluting stents, PCI is now widely used as the firstline treatment around the world. The advantage of CABG over PCI, however, remains in patients with left main coronary artery disease, three-vessel disease, and diffuse CAD. PCI and CABG do not exist in isolation because relieving the symptoms of angina is not the goal of treatment of CAD. Secondary prevention with vigorous modification of risk factors should be initiated and maintained. Among coronary risk factors, diabetes mellitus (DM) remains the most important one to predict poor early and late outcomes even in patients undergoing complete revascularization with CABG. Lowering the blood glucose level is important, but strict glycemic control is not necessarily associated with further reduction of cardiovascular events. Modification of insulin resistance with pioglitazone and metformin, lipid-lowering therapy with a statin, lowering blood pressure to <130/80 mmHg, and antiplatelet therapy should be considered in individuals with DM. A major concern is suboptimal modifications of risk factors in patients with DM and CABG in the real world. We should bear in mind this treatment gap and provide medical therapy for patients who need it most.     

Surgery for coronary artery disease in patients with diabetes mellitus

The results of surgery for occlusive coronary artery disease were studied in 600 consecutive, unselected patients who underwent aortocoronary bypass grafting between Jan. 1, 1977 and Dec. 31, 1982. Forty (7%) of these patients had diabetes mellitus, requiring medication. Sixteen of the 40 patients were insulin-dependent, the remainder required oral hypoglycemic agents. The frequency of previous myocardial infarction, hypertension and peripheral vascular disease in the groups of nondiabetic and diabetic patients was 38% and 62.5%, 12% and 22.5%, and 10.5% and 25% respectively. There was no significant difference in the rate of unstable angina, triple-vessel disease, emergency surgery, left ventricular dysfunction, myocardial infarction perioperatively and hospital morbidity or mortality in the two groups. On coronary angiography, 82% of coronary arteries in diabetic patients were graded as being small or moderate in size (less than 2 mm in diameter); at operation, 62% of these arteries were found to be 2 mm or more in diameter. At a mean follow-up of 3.9 years and 3.7 years in the nondiabetic and diabetic patients respectively (range from 1 to 6 years), no significant difference was noted with regard to relief of symptoms or survival in the two groups. It is concluded that diabetic patients with coronary artery disease can be offered bypass surgery with good short-term and medium-term results.     

2型糖尿病患者冠状动脉钙化与骨代谢指标的相关性研究

目的 探讨2型糖尿病患者冠状动脉钙化(coronary arterial calcification,CAC)与骨质疏松症指标的相关性。方法 根据冠脉钙化积分将200例2型糖尿病患者分成冠脉钙化组和对照组,分别记录一般资料,检测血糖、血脂、钙、磷、碱性磷酸酶(alkaline phosphatase,ALP)、N端中段骨钙素(molecular fragment of osteocalcin N terminal,N-MID)、I型胶原羧基端肽交联(β-cross-linked C-telopeptide of type I collagen,β-CTX）等生化指标,同时进行骨密度(bone mineral density,BMD)和冠脉增强CT等检查,探寻BMD、骨代谢指标与CAC等指标是否存在相关性。在此基础上,进一步对冠脉钙化组患者检测指标进行相关性分析。依据冠脉增强CT结果将受试者分为冠脉狭窄组和无冠脉狭窄组,进一步探讨2型糖尿病患者冠脉狭窄与骨质疏松症的关系。结果 冠脉钙化组的年龄、ALP、腰围、体质量指数（body mass index, BMI)、空腹血糖(fasting blood glucose,FBG)高于对照组,差异有统计学意义(P<0.05)。BMD及骨代谢指标组间比较差异无统计学意义(P>0.05)。相关性分析表明,磷、25(OH)D3、β-CTX、甲状旁腺素(parathyroid hormone,PTH)与腰椎、髋部BMD均为负相关(P<0.05);有无冠心病既往史与腰椎BMD为正相关(P<0.05),绝经年限与腰椎BMD为负相关(P<0.05);年龄、绝经年限、收缩压、HDL-C、HOMA-IS与髋部BMD均为负相关(P<0.05)。CAC与各指标的Logistic回归分析表明,冠脉是否钙化与有无冠脉狭窄、有无冠心病既往史、有无颈动脉粥样硬化显著相关(P<0.05)。冠脉狭窄与各指标的Logistic回归分析显示,冠脉是否狭窄与有无冠脉钙化、有无冠心病既往史之间显著相关(P<0.05)。结论 冠脉狭窄与腰椎BMD相关,冠脉钙化与冠脉狭窄显著相关;冠脉狭窄、冠心病既往史、颈动脉粥样硬化是冠脉钙化的危险因素,冠脉钙化是冠心病的致病危险因素。2型糖尿病患者控制血糖、防治骨质疏松症的发生或可降低冠心病的发生风险。     

Cholesterol efflux capacity in vitro predicts the severity and extent of coronary artery disease in patients with and without type 2 diabetes

OBJECTIVE: To investigate the relation between severity and extent of coronary artery disease (CAD) and in vitro cholesterol efflux capacity. DESIGN: This study consisted of 46 type 2 diabetic, and 42 nondiabetic men undergoing coronary angiography. Quantitative coronary angiography was used to estimate the severity, extent, and overall "atheroma burden" of CAD. The capacity of patient plasma to induce cholesterol efflux from cultured Fu5AH rat hepatoma cells was measured in vitro. RESULTS: In the combined study population (n = 88), there was a significant inverse correlation between efflux and global atheroma burden (r = -0.23, p < 0.05). In the diabetic group, the global atheroma burden index was independently associated both with cholesterol efflux and with LpA-I levels. However, in the nondiabetic CAD group this association was lost when efflux and LpA-I levels were included in the same model. CONCLUSION: The present study demonstrated that efflux capacity was inversely associated with the severity and extent of CAD. In the diabetic group this association was independent of LpA-I levels, suggesting impaired antiatherogenic potential of these particles in type 2 diabetic patients.     

Results of surgical treatment of coronary heart disease in patients with type II diabetes mellitus

One hundred and twenty-eight patients after aorto-coronary bypass were studied, 75 of them had coronary heart disease in combination with type II diabetes mellitus (study group), 53 - coronary heart disease only (control group). The patients with diabetes were transferred on insulin before surgery, this therapy was continued during 2 weeks after surgery. Number of myocardial infarctions, degree of coronary arteries lesion, rate of complications in early postoperative period were compared in both groups. There were no significant differences. It is concluded that type II diabetes is not contraindication to aorto-coronary bypass.     

Familial aggregation of coronary artery calcium in families with type 2 diabetes

Type 2 diabetes is widely recognized as a major risk factor for atherosclerotic cardiovascular disease, including subclinical atherosclerosis as measured by noninvasive procedures. However, the role of genetic factors that contribute to various measures of subclinical atherosclerosis is largely unknown. We hypothesize that subclinical atherosclerosis, measured as coronary artery calcification (CAC), will be extensive in individuals with type 2 diabetes and that its presence depends on both genetic and environmental factors. The genetic factors should result in the familial aggregation of CAC. To determine the extent of familial aggregation of CAC in the presence of type 2 diabetes, we studied 122 individuals with type 2 diabetes (mean age 60 years) and 13 individuals without diabetes in 56 families. CAC was measured by fast-gated helical computed tomography. Other measured factors included blood pressure, body size, lipids, HbA1c, and self-reported medical history. To test for an association between CAC and these factors while accounting for the potential familial correlation of CAC, generalized estimating equations were used. CAC was detectable in 80% of individuals with diabetes (median score 84, range 0-5,776). Extent of CAC, adjusted for age, was positively associated with male sex (P = 0.0003), reduced HDL (P = 0.02), albumin-to-creatinine ratio (P = 0.008), and cigarette pack-years (P = 0.03). CAC was also positively associated with a history of angina, myocardial infarction, stroke, and vascular procedures (all P < 0.01). HbA1c and fasting glucose were positively, but nonsignificantly, associated with the extent of CAC (P = 0.14 and 0.08, respectively). CAC, adjusted for age, sex, race, and diabetes status, was heritable (h2 = 0.50; P = 0.009). In multivariate analysis with additional adjustment for HDL, BMI, hypertension, and smoking, h2 = 0.40 (P = 0.038). These results suggest that strong (independent) genetic factors as well as environmental factors contribute to the variance of CAC in individuals with type 2 diabetes. In these data, CAC seems heritable and may serve as an important feature in designing studies to map genes contributing to both atherosclerosis and type 2 diabetes.     

内膜剥脱联合电熨烙术治疗弥漫性冠状动脉病变的初步探究

目的探讨内膜剥脱联合电熨烙术改善弥漫性冠状动脉病变患者的外科疗效的初步应用结果及其机制。方法2017年1月至2018年9月于我科行冠心病外科治疗并拟行前降支内膜剥脱术患者,术前充分告知电熨烙等相关手术风险,签署知情同意书并进行随机分组,两组根据样本量统计各入组150例。研究组术中内膜剥脱术毕即刻行电熨烙术,对照组单纯行内膜剥脱术,两组均常规行冠状动脉旁路移植术,术后于2、24、72、120 h行心电图及血清学检查(肌钙蛋白I、白细胞介素6、肿瘤坏死因子-α)对比两组变化差异。术后1年随访患者心电图及超声心动图结果。结果两组患者术后心电图显示,研究组术后心电图ST段抬高9例,对照组术后心电图ST段抬高25例。于术后2、24、72、120 h酶联免疫法同时检测外周血中肌钙蛋白I、肿瘤坏死因子和白细胞介素6的含量,两组患者均呈现出肌钙蛋白I、肿瘤坏死因子-α和白细胞介素6的含量持续逐渐增高的趋势,并于24 h到达顶峰,后缓慢回落;研究组术后2 h肿瘤坏死因子-α含量显著低于对照组(P=0.01),肌钙蛋白I和白细胞介素6含量水平未见明显差异;研究组术后24、72、120 h肌钙蛋白I、肿瘤坏死因子-α和白细胞介素6的含量均显著低于对照组(P<0.05)。术后1年研究组ST段改变显著低于对照组,狭窄率和心肌梗死率差异无统计学意义。结论内膜剥脱联合电熨烙术在弥漫性冠状动脉病变患者外科手术中具有防止管腔狭窄、血液湍流,使血管内壁光滑的作用;减缓外周血中炎性因子释放,同时也抑制血管中炎性因子的表达,减轻心肌损伤。短期疗效满意,长期抗炎抗血栓效果及临床疗效仍需进一步研究。     

心肺转流冠状动脉旁路移植术前持续服用硫酸氯吡格雷和阿司匹林的患者氨甲环酸应用的有效性和安全性

目的 评价心肺转流冠状动脉旁路移植术(CABG)术前持续服用硫酸氯吡格雷(氯吡格雷)和阿司匹林的患者氨甲环酸应用的有效性和安全性.方法 本研究为前瞻性随机对照临床研究,将110例接受择期心肺转流CABG且术前持续服用氯吡格雷和阿司匹林直至术前7d以内的患者,随机分入氨甲环酸组和标准治疗组.氨甲环酸组在麻醉诱导后给予负荷量10 mg/kg静脉滴注,继以维持量10mg· kg-1·h-1持续静脉泵入直至手术结束;标准治疗组给予等量生理盐水.主要终点评价指标为围手术期异体红细胞输注量,次要终点评价指标为术后出血量、大出血发生率、二次开胸止血率、异体红细胞输注率以及异体血浆和血小板的输注量和输注率.结果 氨甲环酸组和标准治疗组的围手术期异体红细胞输注量分别为4.0(7.5)单位和6.0(6.0)单位(W=1021,P＜0.01).两组的术后引流量分别为930(750) ml和1210(910) ml(W=1042,P＜0.01),大出血发生率分别为50.9％和76.4％(x2=7.70,P＜0.01),二次开胸止血率分别为0和9.1％(x2=5.24,P=0.02);异体血浆输注量分别为400(600) ml和600 (650) ml(W=1072,P=0.01)、输注率分别为60.0％和85.5％(x2=8.98,P＜0.01),异体血制品总输注率分别为85.5％和98.2％(x2 =5.93,P=0.01).围手术期病死率、并发症和不良事件的发生率两组没有差异.结论 在心肺转流CABG前持续服用氯吡格雷和阿司匹林的患者中,氨甲环酸可以减少术后出血和异体输血,未观察到不良反应.     

Evaluation and treatment of coronary artery disease in patients with end-stage renal disease

Evaluation and treatment of coronary artery disease in patients with end-stage renal disease. Patients with end-stage renal disease (ESRD) are at increased risk of death from coronary artery disease (CAD). The metabolic milieu that results from renal dysfunction appears to accelerate the atherosclerotic process by decades in patients with ESRD. The extremely high prevalence of atherosclerosis in patients with ESRD mandates risk factor identification and treatment. Traditionally, CAD in this patient population has been treated conservatively. Analysis of large databases has highlighted the scope and complexity of this problem; nonetheless, there is a paucity of randomized, controlled trials of CAD in patients with ESRD. In this paper the following issues related to evaluation and treatment of patients with chronic kidney disease are addressed: (1) optimal CAD risk management; (2) evaluation for CAD in patients with ESRD, including the identification of coronary calcification; (3) treatment of CAD with medical therapy and revascularization; (4) relative merits of percutaneous coronary intervention versus bypass surgery. In general, an aggressive approach to medical management of CAD is warranted, even in the setting of subclinical CAD. A low threshold for diagnostic testing should be employed in patients with ESRD. When significant CAD is identified, ESRD patients appear to benefit more from revascularization compared to conservative medical management. Thus, if clinically reasonable, patients with ESRD and CAD should be managed aggressively to improve survival and reduce the incidence of future cardiac events.     

Regional anaesthesia in patients treated with aspirin and clopidogrel

Editor—I read the recent review on coronary artery stentsand non-cardiac surgery¹ with interest. Howard-Alpe and colleaguesrefer to the difficult clinical situation in which an anaesthetistwishes to perform a central neuroaxial block on a patient treatedwith antiplatelet therapy. The authors suggest preoperativeplatelet transfusion ‘if regional neuroaxial blockadeis thought to be essential’ for emergency surgery. I wishto highlight three practical difficulties in transfusing plateletsin order to allow a central neuroaxial block to be performed. First, how many pools of platelets should be transfused? Theauthors cite French guidelines from 2003, which refer to plateletcount.² However, it is likely that patients     

Prevalence and procedural outcomes of percutaneous coronary intervention and coronary artery bypass grafting in patients with diabetes and multivessel coronary artery disease

Abstract Background: Percutaneous coronary intervention (PCI) is used with increasing frequency in patients with diabetes and multivessel disease. This study investigated evolving revascularization strategies in the State of Washington. Methods: The Clinical Outcomes Assessment Program captures all revascularization in the State of Washington and was used to compare diabetic patients with multivessel disease undergoing first‐time revascularization from 1999 to 2007. Categorical variables were compared with the chi‐squared test and continuous variables were compared with the student's t‐test. Results were risk‐adjusted using a logistic regression. Results: A total of 11,602 patients with diabetes and multivessel disease underwent revascularization from 1999 to 2007 and were nearly equally divided between coronary artery bypass grafting (CABG) (51%) and PCI (49%). Patients undergoing CABG had a higher (p < 0.0001) prevalence of congestive heart failure, cerebrovascular disease, peripheral vascular disease, three‐vessel coronary artery disease (CAD), and intraaortic balloon pump insertion, but a lower prevalence of female gender, cardiogenic shock, and emergency procedures. Patients undergoing CABG had more (p < 0.0001) three‐vessel CAD and more complete revascularization (3.7 vs. 1.5 lesions treated). Short‐term risk‐adjusted mortality was equivalent. The prevalence of PCI increased from 34.1% in 1999 to 59.4% in 2007. Conclusions: PCI is applied with increasing frequency to patients with diabetes mellitus (DM) and multivessel disease. PCI is used most commonly in two‐vessel CAD or with acute coronary syndromes with more limited and targeted revascularization. CABG is more commonly applied to extensive disease with more complete revascularization. Both the prevalence and percentage of patients undergoing PCI as primary therapy for multivessel disease with DM is increasing. A multidisciplinary approach may be warranted to ensure optimal outcomes. (J Card Surg 2011;26:1‐8)     

Ascorbic acid and cholesterol levels in patients with diabetes mellitus and coronary artery disease

Indian and black patients admitted to King Edward VIII and R. K. Khan Hospitals with a diagnosis of cardiac infarction and diabetes mellitus were studied. The mean serum cholesterol levels were higher in the indian group. This preliminary study suggests a negative correlation between leucocyte ascorbic acid and serum cholesterol levels in Indians, especially in patients with infarction. This, however, does not preclude an effect of latent ascorbic acid deficiency on the vessel wall. The possible relevance of the findings to the development of atherosclerosis is discussed.     

Risk factors for cognitive dysfunction after coronary artery bypass graft surgery in patients with type 2 diabetes

OBJECTIVES: The mechanisms of postoperative cognitive dysfunction in patients with diabetes after coronary artery bypass grafting are not fully understood. We sought to determine which type 2 diabetes-related factors contributed to postoperative cognitive dysfunction at 7 days and 6 months after coronary artery bypass grafting. METHODS: One hundred eighty patients with type 2 diabetes who were scheduled for elective coronary artery bypass grafting were studied. As a control group, 100 patients without diabetes mellitus matched for age, sex, and educational level were examined. Hemodynamic parameters (arterial and jugular venous blood gas values) were measured during cardiopulmonary bypass. All patients underwent a battery of neurologic and neuropsychologic tests the day before surgery, 7 days after surgery, and 6 months after surgery. RESULTS: Age (odds ratio 1.5, 95% confidence interval 1.3-1.8, P = .03), presence of hypertension (odds ratio 1.8, 95% confidence interval 1.3-2.0, P = .01), jugular venous oxygen saturation less than 50% time (odds ratio 1.5, 95% confidence interval 1.1-2.0, P = .045), presence of ascending aorta atherosclerosis (odds ratio 1.5, 95% confidence interval 1.1-2.6, P = .01), diabetic retinopathy (odds ratio 2.0, 95% confidence interval 1.3-3.0, P = .01), and insulin therapy (odds ratio 2.0, 95% confidence interval 1.3-3.0, P = .05), were associated with cognitive impairment at 7 days. Insulin therapy (odds ratio 2.0, 95% confidence interval 1.3-3.8, P = .01), diabetic retinopathy (odds ratio 1.3, 95% confidence interval 1.2-2.9, P < .01), and hemoglobin A 1c (odds ratio 1.9, 95% confidence interval 1.3-3.1, P = .047) were associated with cognitive impairment at 6 postoperative months. CONCLUSIONS: Insulin therapy, diabetic retinopathy, and hemoglobin A 1c were factors in cognitive impairment at 7 days and 6 months after coronary artery bypass grafting in patients with type 2 diabetes.