Coronary Artery Disease In Type Research Articles

Screening for asymptomatic coronary artery disease in type 2 diabetes mellitus

Diabetes mellitus is a known independent risk factor for coronary artery disease (CAD) and other macrovascular complications, including stroke and peripheral vascular disease.

The protein tyrosine phosphatase receptor type f (PTPRF) locus is associated with coronary artery disease in type 2 diabetes

The protein tyrosine phosphatase receptor type f (<i>PTPRF</i>) locus is associated with coronary artery disease in type 2 diabetes

DWP4-2 Epicardial fat thickness and coronary artery disease in Type 2 diabetes mellitus

DWP4-2 Epicardial fat thickness and coronary artery disease in Type 2 diabetes mellitus

The Common −866G&amp;gt;A Variant in the Promoter of UCP2 Is Associated With Decreased Risk of Coronary Artery Disease in Type 2 Diabetic Men

Uncoupling protein 2 (UCP2) is a physiological downregulator of reactive oxygen species generation and plays an antiatherogenic role in the vascular wall. A common variant in the UCP2 promoter (-866G>A) modulates mRNA expression, with increased expression associated with the A allele. We investigated association of this variant with coronary artery disease (CAD) in two cohorts of type 2 diabetic subjects. We studied 3,122 subjects from the 6-year prospective Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events, and Ramipril (DIABHYCAR) Study (14.9% of CAD incidence at follow-up). An independent, hospital-based cohort of 335 men, 52% of whom had CAD, was also studied. We observed an inverse association of the A allele with incident cases of CAD in a dominant model (hazard risk 0.88 [95% CI 0.80-0.96]; P = 0.006). Similar results were observed for baseline cases of CAD. Stratification by sex confirmed an allelic association with CAD in men, whereas no association was observed in women. All CAD phenotypes considered--myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), and sudden death--contributed significantly to the association. Results were replicated in a cross-sectional study of an independent cohort (odds ratio 0.47 [95% CI 0.25-0.89]; P = 0.02 for a recessive model). The A allele of the -866G>A variant of UCP2 was associated with reduced risk of CAD in men with type 2 diabetes in a 6-year prospective study. Decreased risk of myocardial infarction, angina pectoris, CABG, and sudden death contributed individually and significantly to the reduction of CAD risk. This association was independent of other common CAD risk factors.

Pregnancy- associated plasma protein A and proform eosinophilic major basic protein in the detection of different types of coronary artery disease

Kryptor system was proven to be a rapid, standard method for pregnancy-associated plasma protein A and proform eosinophilic major basic protein (PAPP-A/proMBP) complex detection in coronary artery disease (CAD). No age and/or gender differences in 51 controls and 110 stable coronary artery disease (SCAD) patients were found. SCAD patients did not differ from controls and no difference in PAPP-A/proMBP levels with regards to the number of affected vessels was found. In 21 unstable angina pectoris (UAP), in 35 without and 66 with ST elevation acute myocardial infarctions (NSTEMI, STEMI respectively) patients PAPP-A/proMBP levels were increased (P=0.004 and P<0.0005, respectively). PAPP-A/proMBP levels did not correlate with cardiac troponin I (cTnI) in STEMI and NSTEMI patients. PAPP-A/ proMBP increase was more frequent than cTnI (P=0.036) within the early phase of STEMI. In NSTEMI patients PAPP-A/proMBP positivity was present in 50% of cTnI negative cases. Receiver operating characteristic (ROC) analysis revealed the highest diagnostic accuracy of PAPP-A/proMBP (0.919) in STEMI cTnI positive cases. The highest specificity/sensitivity PAPP-A/proMBP levels for particular acute coronary syndrome (ACS) types were 10.65-14.75 mIU/l. Combination of PAPP-A/proMBP with cTnI increases their diagnostic efficacy within the early phase of ACS. Our results suggest that PAPP-A/proMBP complex is involved in processes preceding vulnerable plaque development in ACS.

Significant Association of Serum Albumin with Severity of Retinopathy and Neuropathy, in Addition to That of Nephropathy, in Japanese Type 2 Diabetic Patients

The aim of this study was to determine the association between serum albumin and the severity of microvascular complications and presence of coronary artery disease in type 2 diabetic patients. The presence of diabetic complications was assessed in a total of 130 Japanese patients with type 2 diabetes mellitus. Retinopathy was classified as absent, simple or proliferative diabetic retinopathy. Neuropathy was considered to be present when the patient showed absence of Achilles tendon reflex, and also evaluated by measuring the median motor nerve conduction velocity (MNCV) in the nerve conduction study. In relation to retinopathy, there were 83 patients with no retinopathy (absent), 26 with simple retinopathy and 21 with proliferative retinopathy. There was a significant difference in the serum albumin level between the "absent" group and the other two groups. In relation to nephropathy, there were 68 patients with no evidence of nephropathy, 49 with microalbuminuria and 13 with proteinuria. The results of logistic regression analysis with adjustment for three variables (age, gender, serum CRP) revealed that serum albumin was independently related to proliferative retinopathy and proteinuria. In relation to neuropathy, serum albumin was found to be significantly related to the absence of Achilles tendon reflex, MNCV, and MFWL. The results of multiple regression analysis with adjustment for three variables (age, gender, serum CRP) revealed that serum albumin was independently related to MNCV and MFWL. Serum albumin was significantly associated with the severity of retinopathy and neuropathy.

The Presence of Apolipoprotein ɛ4 and ɛ2 Alleles Augments the Risk of Coronary Artery Disease in Type 2 Diabetic Patients

The Presence of Apolipoprotein ɛ4 and ɛ2 Alleles Augments the Risk of Coronary Artery Disease in Type 2 Diabetic Patients

Risk of Coronary Artery Disease in Type 2 Diabetes and the Delivery of Care Consistent With the Chronic Care Model in Primary Care Settings

Modifiable risks for coronary heart disease (CHD) in type 2 diabetes include glucose, blood pressure, lipid control, and smoking. The chronic care model (CCM) provides an organizational framework for improving these outcomes. To examine the relationship between CHD risk attributable to modifiable risk factors among patients with type 2 diabetes and whether care delivered in primary care settings is consistent with the CCM. Approximately 30 patients in each of 20 primary care clinics. CHD risk factors were assessed by patient survey and chart abstraction. Absolute 10-year CHD risk was calculated using the UK Prospective Diabetes Study risk engine. Attributable risk was calculated by setting all 4 modifiable risk factors to guideline indicated values, recalculating the risk, and subtracting it from the absolute risk. In each clinic, the consistency of care with the CCM was evaluated using the Assessment of Chronic Illness Care (ACIC) survey. Only 15.4% had guideline-recommended control of A1c, blood pressure, and lipids. The absolute 10-year risk CHD was 16.2% (SD 16.6). One-third of this risk, 5.0% (SD 7.4), was attributable to poor risk factor control. After controlling for patient and clinic characteristics, the ACIC score was inversely associated with attributable risk: a 1 point increase in the ACIC score was associated with a 16% (95% CI, 5-26%) relative decrease in attributable risk. The degree to which care delivered in a primary care clinic conforms to the CCM is an important predictor of the 10-year risk of CHD among patients with type 2 diabetes.

The metabolic syndrome phenotype is associated with raised circulating Big endothelin-1 independently of coronary artery disease in type 2 diabetes

Summary Background and objectives Insulin modulates key regulators of vascular tone, including endothelin-1 (ET-1), hence insulin resistance (IR) and/or hyperinsulinemia may contribute to the pathogenesis of hypertension and cardiovascular disease (CVD). Imbalance in ET-1/nitric oxide may link IR to CVD. Little is known on the relation between neurohormones, metabolic syndrome (MetS) categories (1–5/5) in type 2 diabetes (T2DM). We therefore sought to assess the relationship between neurohormonal profile, CVD and MetS in a large T2DM cohort, as well as the associations between neurohormones, insulinaemia, insulin sensitivity, CVD markers and events within MetS categories. Methods In 455 consecutive T2DM patients with or without MetS [MetS (+)/(−)] defined according to AHA/NHLBI , we assessed the following: MetS categories, HOMA-S, circulating Big-endothelin-1 (Big ET-1), natriuretic peptides and macroangiopathy [Macro (+)/(−)]. Results Big ET-1 was higher by 30%, in MetS (+) (median [IQ range]): 5.2 [4.3–6.0] pg ml −1 in MetS (−) ( n = 75) versus 6.7 [5.2–9.1] pg ml −1 in MetS (+) ( n = 380; P −1 in MetS (+) 3/5; 6.9 [5.1–9.4] pg ml −1 in MetS (+) 4/5 and 7.3 [5.6–9.5] pg ml −1 in MetS (+) 5/5 (NS). The incremental difference in Big ET-1 between MetS (+) and MetS (−) was found out both in the absence or presence of macroangiopathy: 4.55 [4.03–5.25] pg ml −1 in MetS (−) Macro (−) versus 5.70 [4.60–7.50] pg ml −1 in MetS (+) Macro (−) ( P −1 in MetS (−) Macro (+) versus 7.60 [5.80–10.13] pg ml −1 in MetS (+) Macro (+) ( P Conclusions Big ET-1 is raised in T2DM patients with MetS, and its level proceeds stepwise to MetS categories. Elevated Big ET-1 is present in all categories of MetS patients, with or without macroangiopathy. The ascent in Big ET-1 found in MetS (+) without macrovascular disease is of the same magnitude as that conferred by the presence of macroangiopathy.

Changes in glycaemic control and risk of coronary artery disease in type 1 diabetes mellitus: findings from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC)

To complete a comparative analysis of studies that have examined the relationship between glycaemia and cardiovascular disease (CVD)/coronary artery disease (CAD) and perform a prospective analysis of the effect of change in glycosylated Hb level on CAD risk in the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) of childhood-onset type 1 diabetes mellitus (n = 469) over 16 years of two yearly follow-up. Measured values for HbA(1) and HbA(1c) from the EDC were converted to the DCCT-standard HbA(1c) for change analyses and the change in HbA(1c) was calculated (final HbA(1c) minus baseline HbA(1c)). CAD was defined as EDC-diagnosed angina, myocardial infarction, ischaemia, revascularisation or fatal CAD after medical record review. The comparative analysis suggested that glycaemia may have a stronger effect on CAD in patients without, than in those with, albuminuria. In EDC, the change in HbA(1c) differed significantly between CAD cases (+0.62 +/- 1.8%) and non-cases (-0.09 +/- 1.9%) and was an independent predictor of CAD. Discrepant study results regarding the relationship of glycaemia with CVD/CAD may, in part, be related to the prevalence of renal disease. Measures of HbA(1c) change over time show a stronger association with CAD than baseline values.

Endothelial NF-κB As a Mediator of Kidney Damage

See related article, page 268–276 In the current issue of Circulation Research Henke and coworkers demonstrate a critical role for the transcription factor nuclear factor-kappaB (NF-κB) in the genesis of renal damage caused by hypertension.1 The authors created mice in which the NF-κB superrepressor IκBαΔN was induced in the endothelium using Cre/Lox technology. They then exposed these mice and appropriate controls to a rather complex model of hypertension involving angiotensin II infusion, high salt and inhibition of endogenous nitric oxide production. Although the NF-κB superrepressor did not prevent hypertension, it markedly diminished renal injury. Albuminuria in the NF-κB suppressed mice was reduced by half, perivascular and tubular fibrosis was decreased, TNF-α levels were diminished and the renal infiltration of inflammatory cells reduced. The study illustrates a previously unappreciated role of the endothelium and specifically endothelial NF-κB in coordinating numerous aspects of hypertensive renal damage. Prevention of hypertension and its attendant end organ damage is one of the major therapeutic aims in cardiovascular medicine. A vast amount of research has been devoted to understanding the mechanisms and pathogenesis of hypertension, but for the past two decades this knowledge has not led to new treatments. Although current drugs are effective in many patients, there are still numerous patients in whom even combination therapies are not successful.2 Moreover while we focus almost solely on bringing the blood pressure levels back to normal, the mechanisms of end-organ damage are in part independent of blood pressure and are influenced by factors such as race, socioeconomic status, diabetes, dyslipidemia and other unknown factors. This is particularly true of renal failure, which occurs much more commonly in blacks and is exacerbated by diabetes. Hypertensive end organ damage is predominantly caused by inflammatory cells such as macrophages and lymphocytes infiltrating target organs. Numerous aspects of …

The presence of apolipoprotein ε4 and ε2 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-ε4 and ε2 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-ε4 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-ε3 carriers, respectively. However, carriers of APOE-ε2 had significantly higher levels of plasma TG only. OR of APOE-ε4 and ε2 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-ε2 and ε4 alleles have a higher risk of developing CAD than ND patients in the western population of Iran, with APOE-ε4 being more closely associated with CAD than the APOE-ε2 allele. These results indicated that carriers of APOE-ε4 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.

Ischaemia imaging in type 2 diabetic kidney transplant candidates is coronary angiography essential?

Coronary artery disease (CAD) remains the leading cause of death in type 2 diabetes mellitus (DM) patients undergoing renal transplantation. There is a high prevalence of silent CAD in these patients. Controversy exists regarding the role of dobutamine stress echocardiography (DSE) in detection of CAD. Our purpose was to compare DSE with coronary angiography (CA) for the detection of CAD in type 2 diabetic patients undergoing evaluation for renal transplantation. Forty (36 male, four female) type 2 diabetic patients with end-stage renal disease (ESRD) were subjected to DSE followed by CA as a part of their pre-renal transplant evaluation. The ability of DSE to predict 70% stenosis in one or more coronary arteries as determined by CA was evaluated. Mean age of the patients was 49.2 +/- 5 years (range 39-60 years). DSE was positive in 10 (25%) patients, while 19 patients (48%) had a more than 70% lesion in at least one epicardial vessel on CA (six patients had single vessel, three had double vessel and 10 had triple vessel disease). The sensitivity and specificity in identifying CAD was 47.3 and 95.2%, respectively, while positive predictive value and negative predictive value was 90% and 66%. Accuracy of DSE was 72.5%. All four patients with diffuse diabetic coronary artery disease had negative DSE. DSE is a poor predictor of coronary artery disease in type 2 DM patients being evaluated for renal transplantation. CA should be included in evaluation of type 2 diabetic patients who are renal transplant candidates.

Tag Polymorphisms at the A20 (TNFAIP3) Locus Are Associated With Lower Gene Expression and Increased Risk of Coronary Artery Disease in Type 2 Diabetes

A20 or tumor necrosis factor (TNF)-induced protein 3 (TNFAIP3) is a negative regulator of nuclear factor-kappaB (NF-kappaB). We have investigated whether polymorphisms in this gene are associated with increased atherosclerosis in diabetic patients. Five tag single nucleotide polymorphisms (SNPs) were typed in 479 type 2 diabetic patients from Boston, including 239 coronary artery disease (CAD)-positive case subjects and 240 CAD-negative control subjects. Two tag SNPs (rs5029930 and rs610604) were independently associated with CAD; adjusted odds ratios (ORs) for minor allele carriers were 2.3 (95% CI 1.4-3.8, P = 0.001) and 2.0 (1.3-2.9, P = 0.0008), respectively. The association with rs610604 was dependent on glycemic control, with ORs of 3.9 among subjects with A1C < or =7.0% and 1.2 for those with A1C >7.0% (P for interaction = 0.015). A similar interaction pattern was found among 231 CAD-positive and 332 CAD-negative type 2 diabetic patients from Italy (OR 2.2, P = 0.05 vs. OR 0.9, P = 0.63 in the low vs. high A1C strata, P for interaction = 0.05). Quantitative RT-PCR in blood mononuclear cells from 83 nondiabetic subjects showed that rs610604 and rs5029930 minor allele homozygotes have 30-45% lower levels of A20 mRNA than major allele homozygotes, and heterozygotes have intermediate levels (P = 0.04 and 0.028, respectively). These findings point to variability in the A20/TNFAIP3 gene as a modulator of CAD risk in type 2 diabetes. This effect is mediated by allelic differences in A20 expression.

Relationship between level of circulating modified LDL and the extent of coronary artery disease in type 2 diabetic patients

The impact of diabetes on health is due almost entirely to a series of complications that characterise the disease. It is associated with an increased incidence of macrovascular complications including coronary artery disease (CAD). The aim of the present study is to evaluate the possible relationship between the circulating levels of the modified derivatives of low-density lipoprotein (LDL) and the development of angiopathy in type 2 diabetic patients with CAD. The status of the antioxidant defences and the role of supplementation with antioxidant combinations are also studied in these patients. The study was conducted on three groups: group I (controls); group II (type 2 diabetic patients without complications – CAD[–]); and group III (including type 2 diabetic patients with stable CAD – CAD[+]). Patients in group III received adjunct treatment of antioxidant tablets for three months. The results of the present study clearly indicated that there was excessive exposure to oxidative stress in diabetic patients. The increase in free radicals was coupled with disturbance in free radical scavengers, particularly the glutathione system. The disturbance was more prominent in CAD(+) patients. The study has shown alteration in the lipid profile in diabetic groups, where the oxidised LDL (ox-LDL) levels were significantly higher than in control subjects. Diabetics with CAD had higher levels of ox-LDL than did patients without CAD. The intima/media thickness (IMT) of the carotid artery was within clinically accepted normal values if the ox-LDL level was below 100–110 u/L. Once the ox-LDL exceeded this range, IMT increased sharply with the increase in plasma ox-LDL. It seems that the level of ox-LDL should be kept below an upper limit of the 100–110 u/L range in order to avoid the serious atherosclerotic effects of this factor. The results demonstrate that plasma levels of ox-LDL correlate with the extent of coronary artery disease in type 2 diabetic patients and suggest that elevated levels of ox-LDL, can serve as an independent and significant predictor for future cardiac events in type 2 diabetic patients with CAD.

Increased Serum Glycated Albumin Level is Associated With the Presence and Severity of Coronary Artery Disease in Type 2 Diabetic Patients

Glycated albumin is the predominant circulating Amadori-type glycated protein in vivo and plays a major role in the development of diabetic vascular complications. The aim of this study was to assess the relationship between increased serum glycated albumin level and the presence and severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). In a total of 320 consecutive patients with T2DM, coronary angiography revealed normal coronary arteries in 83 patients (control group) and significant coronary stenosis (> or = 70% luminal diameter narrowing) in 237, of whom 51 patients had 1-vessel disease (Group I), 80 had 2-vessel disease (Group II), and 106 had 3-vessel disease (Group III). Serum glycated albumin, hemoglobin A(1c) (HbA(1c)) and tumor necrosis factor (TNF)-alpha levels, lipid profile, and renal function were measured. Logistic regression analysis was performed to determine the relative risk of serum glycated albumin level for the presence and severity of CAD. Multivariate stepwise linear regression analysis was done to identify independent determinants of the glycated albumin level. Serum glycated albumin (21.2+/-5.3% vs 19.4+/-4.3%, p=0.005) and TNF-alpha levels (123 +/-115 pg/ml vs 65+/-59 pg/ml, p<0.001) were significantly higher in patients with CAD than in controls, but serum HbAlc level did not significantly differ between them (7.6+/-1.3% vs 7.4+/-1.2%, p=0.19). There was a significant difference in serum glycated albumin level between Groups I and III (19.5+/-3.3% vs 21.8+/-5.7%, p<0.001). The serum glycated albumin level correlated with the number of diseased arteries (Spearman r=0.205, p<0.001), and was closely related to serum levels on admission of glucose (r=0.495, p<0.001), TNF-alpha (r=0.123, p=0.028), blood urea nitrogen (r=0.167, p=0.004), triglycerides (r=0.129, p=0.021), and HbA(1c) (r=0.795, p<0.001). Multivariate analysis indicated that serum levels of glucose (p<0.0001), TNF-alpha (p=0.001), blood urea nitrogen (p=0.004) and triglycerides (p=0.035) were independent determinants for glycated albumin. Logistic regression analysis revealed that glycated albumin > or = 19% (odds ratio (OR) 2.9, p<0.001) was an independent predictor for CAD and glycated albumin > or = 21% (OR 2.3, p=0.032) for 3-vessel disease prediction. The area under the receiver-operating characteristic curve for glycated albumin (0.620, 95% confidence interval (CI) 0.548 to 0.691, p=0.001) was superior to that for HbA(1c) (0.543, 95% CI 0.473 to 0.613, p=0.243). An increased serum level of glycated albumin is associated with the presence and severity of CAD, and may be useful in screening patients with T2DM.

Common Haplotypes at the Adiponectin Receptor 1 (ADIPOR1) Locus Are Associated With Increased Risk of Coronary Artery Disease in Type 2 Diabetes

Adiponectin, an adipokine facilitating insulin action, has antiatherogenic effects. This study investigated whether common polymorphisms in the adiponectin receptor 1 (ADIPOR1) gene mediating these effects influence the risk of coronary artery disease (CAD) in type 2 diabetes. Linkage disequilibrium analysis of 28 single nucleotide polymorphisms (SNPs) spanning the entire ADIPOR1 locus revealed two haplotype blocks that could be tagged by six SNPs. These six markers were typed in two populations of CAD-positive and -negative subjects with type 2 diabetes, one from Boston (n = 411) and the other from Italy (n = 533). In the Boston population, the three tags of the more 3' block were all significantly associated with CAD (P = 0.001-0.01). A similar trend, although not significant, was found in Italian subjects. Haplotype analysis of the combined populations revealed different haplotype distributions in case and control subjects (P = 0.0002), with one common haplotype being associated in homozygotes with a greater than threefold increase in cardiovascular risk (odds ratio 3.6 [95% CI 1.8-7.2]). Some of the genotypes associated with increased cardiovascular risk were associated with 30-40% lower ADIPOR1 mRNA levels in blood mononuclear cells (n = 60) and adipose tissue biopsies (n = 28) (P = 0.001-0.014). Our findings point to genetic variability at the ADIPOR1 locus as a strong determinant of CAD susceptibility in type 2 diabetes.

Prognostic Significance of Silent Coronary Artery Disease in Type 2 Diabetes

The prevalence of obesity and diabetes is increasing rapidly. Coronary artery disease (CAD) represents the leading cause of death in diabetic patients. Diabetic patients are at a two- to fourfold risk of cardiovascular mortality compared with their nondiabetic counterparts. Silent myocardial ischemia more often occurs in diabetics than in nondiabetics. In general, the prevalence of silent CAD varies depending on the test used for patient screening and on the patient population screened. The prevalence of silent CAD is 6-23% in low-risk diabetic patients. In high-risk diabetic patients the prevalence may be as high as 60%. Over the last years it has been well recognized that silent CAD is not different from symptomatic CAD with respect to prognosis and adverse events. Particular diabetic patients therefore might benefit from routine CAD screening. CAD could be diagnosed at an earlier stage of disease and be treated accordingly. Myocardial perfusion SPECT, stress echocardiography and possibly computed tomography are emerging as effective screening tools beyond risk stratification by risk factor scoring systems alone. There are few studies suggesting that early intervention by medical or also revascularization strategies could lead to a better outcome in diabetic patients with evidence of silent CAD.

We-P11:25 Coronary artery disease in type 2 diabetes: Effects of weight loss on lipid peroxide levels, antioxidant enzyme activity and insulin sensitivity

We-P11:25 Coronary artery disease in type 2 diabetes: Effects of weight loss on lipid peroxide levels, antioxidant enzyme activity and insulin sensitivity

We-P11:26 Coronary artery disease in type 2 diabetes: Relationship between changes in LDL particle size, lipoprotein subfraction levels and insulin resistance

Atorvastatin (10 to 20 mg/day) was administered for 3 months to 15 outpatients (average age 58 ± 4 years) with hypercholesterolemia accompanied by hypertriglyceridemia without hypolipemic treatment. Changes in lipid profile, particularly oxidized low-density lipoprotein (LDL) (malondialdehyde LDL), subfractions of LDL, and remnant lipoprotein (RLP) cholesterol, were examined before and after administration. In addition, the influence of atorvastatin on lipoprotein(a) (known to be an independent risk factor for atherosclerosis), asymmetric dimethylarginine (known to be an endogenous inhibitor of nitric oxide synthase), and homocysteine (methionine metabolite) was also investigated. Administration of atorvastatin significantly decreased serum total cholesterol, LDL cholesterol, and triglycerides. Conversely, a significant increase in high-density lipoprotein cholesterol was shown. In LDL subfractions, large, buoyant LDL fractions were not influenced by treatment with atorvastatin (before administration, 99 ± 14 mg/dl; after administration, 91 ± 6 mg/dl, shown as a cholesterol content in each subfraction), but a marked decrease in small, dense LDL fractions (p <0.001) (before administration, 119 ± 17 mg/dl; after administration, 43 ± 10 mg/dl) was shown. Moreover, oxidized LDL was significantly decreased (p <0.01) (before administration, 169 ± 13 U/L; after administration, 119 ± 10 U/L) and RLP cholesterol also was significantly decreased (p <0.01) (before administration, 11.9 ± 2.0 mg/dl; after administration, 6.0 ± 0.9 mg/dl) with atorvastatin treatment. No significant change was observed in fasting plasma glucose, hemoglobin A1c, lipoprotein(a), asymmetric dimethylarginine, homocysteine, and so on. These data suggest that administration of relatively low doses of atorvastatin to patients with hypercholesterolemia accompanied with hypertriglyceridemia results in a decrease not only in LDL cholesterol and triglycerides, but also in oxidized LDL and RLP cholesterol, with an increase in high-density lipoprotein cholesterol. Furthermore, small, dense LDL decreased with a shift in LDL subfractions to large, buoyant fractions, and these changes are considered to be involved in the inhibition of the onset and progression of atherosclerosis.