The 3'-UTR C>T polymorphism of the oxidized LDL-receptor 1 (OLR1) gene does not associate with coronary artery disease in Italian CAD patients or with the severity of coronary disease

BACKGROUND AND AIM: Oxidized low-density lipoproteins (OxLDLs) play a critical role in endothelial dysfunction, which is implicated in the pathogenesis of atherosclerosis. Vascular endothelial cells internalize and degrade oxLDL through the endothelial lectin-like oxidized LDL receptor 1 (OLR1). OLR1 is up-regulated in several pathological conditions, including hypertension, hyperlipidemia, diabetes, atherosclerosis and inflammation, and represents therefore a good candidate for coronary artery disease (CAD). Recently, a 3'-UTR (188 C>T) SNP in the OLR1 gene has been reported to be associated with coronary artery stenosis and myocardial infarction. In the present study we investigated whether the OLR1 gene 188 C>T SNP is a genetic risk marker for CAD in Italian patients with angiographically defined coronary atherosclerosis, and assessed its relation with clinical and metabolic abnormalities, including severity of disease (classified as restenosis, single- or multiple coronary vessels disease, and MI). METHODS: The 3'-UTR C>T SNP was detected in real-time PCR in 351 subjects with CAD and in 215 control subjects. RESULTS: The OLR1-T allele frequencies were 48.9% in the CAD subjects and 47.7% in controls, with no significant difference between the two groups. Also, the 3'-UTR C>T SNP did not associate with any of the parameters of severity of disease. Furthermore, none of the other clinical and metabolic parameters were associated with the OLR1 gene SNP. CONCLUSIONS: Our observations suggest that, in our population, the 3'-UTR C>T polymorphism of the OLR1 gene is unlikely to play a role in the pathogenesis of coronary artery disease.     

Liver gene expression signature of mild fibrosis in patients with chronic hepatitis C

BACKGROUND & AIMS: The molecular mechanisms of hepatocellular carcinoma have been studied, but little is known of the changes in liver gene expression during the different stages of chronic hepatitis C virus (HCV) infection, in particular the transition from mild to moderate fibrosis. METHODS: We used real-time quantitative RT PCR to study the messenger RNA expression of 240 selected genes in 2 pools of liver specimens according to the stages of fibrosis (Metavir score; mild fibrosis = F1 and septal fibrosis = F2). Genes whose expression differed between pools (F2 vs F1) by at least 2-fold were selected. In addition, the expression level of these selected genes then was assessed in each of the 62 individual samples (F4, n = 6; F3, n = 17; F2, n = 21; vs F1, n = 18). RESULTS: The 22 genes that were up-regulated in the 21 F2 samples relative to the 18 F1 samples mainly encoded genes involved in cytoskeleton (KRT 19 and SCG 10), growth factors/cytokines (CXCL6, interleukin 8 [IL8], IL1A, IL2, and CXCL10), or growth factor receptors (CCR2, CXCR3, and CXCR4), or were involved in extracellular matrix production (COL1A1, CHI3L, and SPP1), in extracellular matrix remodeling (TIMP1, MMP7, and MMP9), and in cell junction (ITGA2 and CLDN 4). When hierarchically clustering the F2 and F1 samples according to the expression of the 11 most discriminatory genes (KRT 19, COL1A1, STMN2, CXCL6, CCR2, TIMP1, IL8, IL1A, ITGA2, CLDN 4, and IL2), the patient population was categorized into 2 subgroups: F1 and F2. Specifically, 15 of 18 F1 (83%) and 19 of 21 F2 (90%) were classified correctly (P < 10(-5)). We also studied the messenger RNA expression of these 240 selected genes in normal liver in comparison with F1. Genes dysregulated in the transition from normal liver to F1 mainly were interferon-inducible genes, and therefore were very different from those dysregulated in the transition from F1 to F2. CONCLUSIONS: Genes involved in extracellular matrix turnover and immune response are implicated in the transition from mild to moderate fibrosis. Eleven of the genes could form the basis for the gene expression signature of mild versus moderate fibrosis in patients with chronic hepatitis C.     

Interleukin-1 gene cluster polymorphisms and risk of coronary artery disease

BACKGROUND AND OBJECTIVES: The pro-inflammatory cytokine interleukin (IL)-1 has been suggested to play a role in atherosclerosis. Several genetic polymorphisms have been described in the genes of the IL-1 cluster and associations with coronary artery disease (CAD) have been reported, although with contrasting results. DESIGN AND METHODS: The associations of a variable number tandem repeat (86 bp) polymorphism in intron 2 of interleukin-1 receptor antagonist (IL1-RA) and of the 511 C/T polymorphism of IL-1b with the risk of CAD were studied. Three hundred and thirty-five case (CAD+) patients with angiographically documented CAD (stenosis >50% in at least one major coronary artery) were compared with 205 unrelated individuals free of CAD signs at angiogram (CAD- controls). One hundred and two (30.5%) CAD+ patients had single-vessel disease (SVD) and 233 (69.5%) multiple-vessel disease (MVD). RESULTS: There was no statistically significant difference in either genotype distribution or allele frequency of both IL-1 RA and IL-1b 511 C/T polymorphisms between CAD+ cases and CAD- controls. Moreover in multivariate analysis, adjusting for multiple comparisons and confounding factors, no difference was found in IL-1 RA genotype distribution between patients with SVD or MVD. INTERPRETATION AND CONCLUSIONS: Our study does not support the association between IL-1 RA intron 2 VNTR and IL-1b 511 C/T polymorphisms and the risk of CAD in individuals undergoing coronary angiography.     

Melatonin inhibits IL1β-induced MMP9 expression and activity in human umbilical vein endothelial cells by suppressing NF-κB activation

Matrix metalloproteinases (MMPs) have been involved in inflammatory and degradative processes in pathologic conditions. The purpose of this study was to investigate the protective effect of melatonin in human umbilical vein endothelial cell (HUVEC) monolayer permeability and the regulation of MMP9 induced by interleukin 1β (IL1β (IL1B)) in HUVECs. Protection studies were carried out with melatonin, a well-known antioxidant and antiinflammatory molecule. MMP9 expression was increased with IL1β induction in HUVECs. Melatonin showed a barrier-protective role by downregulation of MMP9 and upregulation of tissue inhibitor of metalloproteinase-1 expression in HUVECs. Meanwhile, melatonin also decreased sodium fluorescein permeability and counteracted the downregulation of vascular endothelial cadherin and occludin expression in HUVECs. During inflammatory stimulus, nuclear factor-κB (NF-κB) plays a significant role in regulating MMP genes expression, thus the function of NF-κB in HUVECs' barrier disruption was investigated. IL1β induced nuclear translocation of NF-κB in HUVECs and regulated MMP9 expression. However, NF-κB translocation into the nucleus was inhibited significantly by melatonin. Our results show that melatonin decreases the permeability of monolayer endothelial cell induced by IL1β. At the same time, melatonin decreased the expression and activity of MMP9 by a NF-κB-dependent pathway in HUVECs induced by IL1β.     

Coronary flow reserve of the angiographically normal left anterior descending coronary artery in patients with remote coronary artery disease

Coronary artery disease (CAD) has been suggested to alter coronary flow reserve (CFR; the ratio between hyperemic and baseline coronary flow velocities) not only in territories supplied by stenotic arteries but also in angiographically normal, remote regions. However, few data exist regarding the left anterior descending (LAD) coronary artery as the normal index artery. The influence of remote CAD on CFR of the angiographically normal LAD was evaluated with transthoracic Doppler ultrasound to measure CFR in the LAD during 90 seconds of venous adenosine infusion (140 microg/kg/min) in 122 subjects who were assigned to 1 group; group 1 comprised 49 controls without angiographically detectable CAD, and group 2 consisted of 73 patients with an angiographically normal LAD and remote CAD. Group 2 was divided into 4 subgroups: 16 patients with previous remote percutaneous coronary intervention (group 2A); 13 patients with significant remote stenosis (group 2B); 23 patients with previous remote myocardial infarction and percutaneous coronary intervention (group 2C); and 21 patients with previous remote myocardial infarction but no percutaneous coronary intervention (group 2D). CFR in the LAD was not significantly different in groups 1 and 2 (3.08 +/- 0.61 and 3.03 +/- 0.69, respectively, p = NS). Decreased ejection fraction and increased wall motion score index in patients with remote CAD (p < 0.00001) and multivessel CAD did not affect CFR in the LAD (group 2A 3.18 +/- 0.77; group 2B 3.05 +/- 0.65; group 2C 3.07 +/- 0.79; group 2D 2.86 +/- 0.50, respectively; F = 0.63, p = NS). In conclusion, CFR of an angiographically normal LAD is preserved in patients with remote CAD, even in the presence of previous remote myocardial infarction and wall motion abnormalities.     

Common carotid intima-media thickness is correlated with myocardial flow reserve in patients with coronary artery disease: a useful non-invasive indicator of coronary atherosclerosis

BACKGROUND: The common carotid intima-media thickness (IMT) is correlated with the angiographically determined coronary artery stenosis. However, their correlation is weak, which limits the clinical application of the IMT as a predictor of coronary artery stenosis. The IMT reflects diffuse early-phase atherosclerosis, whereas the angiographically determined coronary artery stenosis is a late-phase phenomenon. The latter is localized and rapidly progressive with plaque rupture and acute thrombosis. Instead of the angiographically determined coronary artery stenosis, we employed myocardial flow reserve (MFR) that reflects diffuse early-phase coronary atherosclerosis and impaired coronary vasodilatation function. We evaluated the relationship between the IMT and the MFR. METHODS: Twenty-three patients with angiographically diagnosed coronary artery disease (CAD) underwent B-mode ultrasound examination to measure their common carotid IMT and positron emission tomography (PET) with dipyridamole intervention to obtain their MFR. We also performed B-mode ultrasound examination in 21 patients with hypertension without CAD and in 15 control subjects. RESULTS: The common carotid IMT in patients with CAD was thickened (0.92+/-0.15 vs. 0.81+/-0.14 mm in patients with hypertension (P<0.05) and 0.69+/-0.13 mm in control subjects (P<0.01)). The IMT was inversely correlated with the MFR (r=0.51, P<0.01). The correlations between the MFR and most of the coronary risk factors (age, blood pressure, serum cholesterol level and triglyceride level, HbA1c level, smoking index) did not reach statistical significance. CONCLUSIONS: Thickened common carotid IMT is also an indicator of reduced MFR or early-phase coronary atherosclerosis.     

Aortic distensibility in post-stenotic aortic dilatation: the effect of co-existing coronary artery disease

Aortic distensibility is decreased in patients with coronary artery disease (CAD) and the angiographically normal aorta. To determine if the same is true in patients with aortic stenosis and post-stenotic dilatation, two groups were studied. Group A consisted of 15 patients with post-stenotic aortic dilatation and normal coronary arteries, and group B, 14 patients with post-stenotic aortic dilatation and CAD. The patients were compared to 18 normal subjects. The area of the first 6 cm of the aorta above the valve obtained by aortography was planimetered and the mean diameters were calculated. Distensibility was calculated using the formula: (formula; see text) Distensibility was greater in group A (2.5 +- .4 cm2.dynes-1) compared to group B (1.0 +- 8 cm2.dynes-1, p less than 0.001). Distensibility in normal subjects reported recently from this laboratory (3.4 +- .4 cm2.dynes-1) was greater compared to both groups A and B (p less than 0.001). Thus, distensibility was decreased in patients with post-stenotic aortic dilatation. The further decrease in distensibility in patients with co-existing coronary artery disease may be partially related to abnormal nutrition of the arterial wall since the vasa vasorum of the ascending aorta are derived from the coronary arteries.     

Quantitative Myocardial Contrast Supine Bicycle Stress Echocardiography for Detection of Coronary Artery Disease

Background: If compared with two‐dimensional echocardiography (2DE), quantitative myocardial contrast echocardiography (MCE) improves detection of coronary artery disease (CAD) during pharmacological stress, but there is paucity of data regarding quantitative MCE performed during supine bicycle stress. Objectives: To determine the feasibility and accuracy of quantitative MCE and assess its incremental benefit over 2DE for detection of CAD during supine bicycle stress. Methods: Sixty‐one consecutive patients (47 males, 14 females, mean age 57 ± 12 years) with suspected CAD, who were scheduled for coronary angiography, underwent 2DE and MCE supine bicycle stress. The diagnosis of obstructive CAD (≥50% stenosis) was based on inducible wall‐motion and myocardial perfusion abnormalities. For quantitative myocardial perfusion analysis, A, β, and Aβ reserve were derived from myocardial contrast replenishment curves. Results: Quantitative coronary angiography revealed ≥50% stenosis in 41, ≥70% stenosis in 18, single vessel disease in 24, and multivessel disease in 17 patients. If compared with 2DE, quantitative MCE was more sensitive (71% vs. 93%; P < 0.05) and more accurate (74% vs. 89%; P < 0.05) to detect obstructive CAD. The sensitivity of 2DE and quantitative MCE was 61% and 91% (P < 0.05) in 50–69% stenosis, and 63% and 92% (P < 0.05) in single vessel disease. No difference in sensitivity between 2DE and quantitative MCE was found in subjects with ≥70% stenosis (83% vs. 94%, P = NS) and multivessel disease (82% vs. 94%, P = NS). Conclusions: Quantitative MCE enhances sensitivity and accuracy of supine bicycle stress 2DE for detection of obstructive CAD, and this incremental benefit is especially present in less severe disease.     

Effect of polymorphisms on key enzymes in homocysteine metabolism, on plasma homocysteine level and on coronary artery-disease risk in a Tunisian population

BACKGROUND: Hyperhomocysteinemia is known as an independent-risk factor for coronary-artery disease (CAD). However, the effect of homocystein metabolic enzymes polymorphisms on CAD is still controversed. We investigated the relation between homocystein metabolic key enzymes polymorphisms, homocystenemia and coronary stenosis in a Tunisian population. METHODS: Samples were collected from 251 CAD patients documented by angiography. Genotyping were performed for C677T methylene-tetrahydrofolate reductase (MTHFR), A2756G methionine-synthase (MS) and 844ins 68 cystathionine-beta-synthase (CBS). We measured fasting plasma tHcy, folate and vitamin B12. RESULTS: There was significant increase in homocysteinemia for homozygous genotypes of C677T MTHFR (p<0.001) and A2756G MS (p=0.01), but not for 844ins68 CBS (p=0.105). Potential confounders adjusted odds-ratios for significant coronary stenosis, associated with MTHFR TT, MS GG and CBS insertion, were respectively 1.78 (p=0.041); 2.33 (p=0.036) and 0.87 (p=0.823). The effect of mutated MTHFR genotype was more pronounced on homocysteinemia (21.4+/-9.1mumol/L; p<0.001) and coronary stenosis (OR=2.73; p=0.033) at low folatemia (相似文献   

冠心病与血尿酸的关系

目的　确定血尿酸是否与冠心病独立相关以及是否与性别有关。方法　 35 5例行冠状动脉 (冠脉 )造影的患者分为两组 ,以性别、年龄、体重指数、空腹血糖、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血尿酸、纤维蛋白原、吸烟量、高血压病病史、冠心病家族史等多重危险因素及冠脉评分进行多变量分析。结果　女性以血尿酸的四等分计算每组的冠脉评分 ,显示血尿酸越高 ,冠脉评分越高 ,而男性无此关系。多元logistic回归分析显示 :性别、纤维蛋白原、空腹血糖、吸烟等级与冠心病独立相关 (P值均 <0 0 5 ) ,年龄与冠心病有独立相关的趋势 (P =0 0 5 6 ) ,血尿酸与冠心病无独立相关 (P >0 0 5 )。逐步回归分析结果显示 :年龄、性别、纤维蛋白原、空腹血糖、总胆固醇与冠脉评分独立相关 (P值均 <0 0 5 ) ,血尿酸与冠脉评分无独立相关 (P >0 0 5 )。以女性病人专门进行多元逐步回归分析 ,血尿酸与冠心病及冠脉评分均无独立相关。结论　女性血尿酸越高 ,冠脉评分越高 ,但无论男女 ,血尿酸与冠心病及冠脉狭窄严重程度无独立相关。     

不同转移潜能人肝癌HCCLM3、MHCC97-L细胞系血管生成拟态基因的表达

目的采用细胞外基质与粘连分子Real-time PCR基因芯片筛选高、低转移潜能人肝癌HCCLM3、MHCC97-L细胞系差异表达的血管生成拟态基因,探讨血管生成拟态的机制。方法建立HCCLM3、MHCC97-L三维培养体系,倒置显微镜下观察其血管样结构形成情况。细胞培养24 h后,采用细胞外基质与粘连分子Real-timePCR基因芯片对HCCLM3、MHCC97-L的表达基因进行筛选。结果培养24 h,HCCLM3形成的血管样结构较MHCC97-L的长（P〈0.01）。筛选出20个差异基因,其中CD44、COL6A1、COL4A2、ECM1、ITGA1、ITGA3、MMP1、MMP2、SPP1、TNC、COL6A2、MMP7和MMP10共13个基因在HCCLM3中的表达较MHCC97-L明显上调,CTNND2、COL12A1、COL14A1、ITGAL、TIMP3、MMP16和VTN共7个基因明显下调。结论高、低转移潜能人肝癌HCCLM3、MHCC97-L细胞系体外形成血管生成拟态有差异,其原因可能与HCCLM3差异表达某些细胞外基质和粘连分子相关基因有关。     

Relation of angina pectoris to coronary artery disease in aortic valve stenosis

One hundred three patients with isolated, severe aortic stenosis (AS) were retrospectively analyzed to determine the relation of angina pectoris to angiographically significant coronary artery disease (CAD). All patients underwent coronary angiography regardless of the presence or absence of angina. Angina was significantly associated with CAD (p less than 0.002), with a sensitivity of 78% and a specificity of 53%. However, 25% of the patients without angina had angiographically significant CAD, and in these patients there was a 70% prevalence of 1-vessel disease. Patients with isolated, severe AS should undergo coronary angiography to identify coexistent CAD accurately. The absence of angina does not reliably exclude angiographically significant CAD.     

Homozygosity for angiotensinogen 235T variant increases the risk of myocardial infarction in patients with multi-vessel coronary artery disease

OBJECTIVE: Molecular variants of the angiotensinogen (AGT) and the angiotensin II type 1 receptor (ATR) genes have been associated with the risk of coronary artery disease (CAD) and myocardial infarction (MI), but data so far available are conflicting. The primary object of the paper is to verify this possible association by a rigorous, angiographically controlled study in a large sample of patients with or without multi-vessel CAD. DESIGN: We designed a large case-control study in Italian patients candidates for coronary artery bypass grafting, with angiographically documented multi-vessel CAD, compared to subjects with angiographically documented normal coronary arteries. METHODS AND RESULTS: AGT M235T and ATR A1166C gene polymorphisms were analysed in 699 subjects; 454 patients were candidates for coronary artery bypass grafting, having angiographically documented (mainly multi-vessel) CAD. An appropriate documentation of previous MI was obtained from 404/454 (89%, 247 with and 157 without MI). Subjects (n = 245) with angiographically documented normal coronary arteries, were included as control group (CAD-free group). CAD patients had a substantial burden of conventional risk factors as compared with controls free of coronary atherosclerosis. Age, gender, smoking habit and number of stenosed vessels were the only differences between patients with or without previous myocardial infarction, who were similarly exposed to the other conventional risk factors (including hypertension). AGT M235T and ATR A1166C allele and genotype frequencies were similar between CAD and CAD-free patients. In the CAD group, AGT 235T allele was found more frequently in subjects with a previous myocardial infarction (0.494 versus 0.414; P < or = 0.05). By logistic regression, homozygosity for AGT 235T variant appeared to confer 1.9-fold increased risk for MI in both the univariate and the multivariate (adjusted for age, gender, smoking habit and number of stenosed vessels) model. CONCLUSIONS: AGT 235 T homozygous patients with multivessel CAD have an increased risk of myocardial infarction as compared with subjects with clinically similar phenotype but different genotype.     

Relationship between total plasma homocysteine, polymorphisms of homocysteine metabolism related enzymes, risk factors and coronary artery disease in the Australian hospital-based population.

Modest elevations of circulating homocysteine are common in patients with vascular disease. We explored interrelations between total plasma homocysteine levels and mutations in genes for three key enzymes in methionine-homocysteine metabolism. Methyltetrahydrofolate reductase (MTHFR) 677C-->T, cystathionine beta synthase (CBS) 68-bp insertion at exon 8, and methionine synthase (MS) 2756A-->G were typed in 685 Australian caucasian patients aged < or =65 years with and without angiographically documented coronary artery disease (CAD). We also assessed associations between homocysteine levels and extracellular superoxide dismutase (EC-SOD) and other CAD risk factors. There were significant correlations between plasma total homocysteine, and EC-SOD (r = 0.170, p = 0.001 for men; r = 0.241, p = 0.003 for women) and LDL (r = 0.153, p = 0.001 for men; r = 0.132, p = 0.081 for women). Levels were also significantly higher among patients with unstable angina (15.30+/-0.44 micromol/l for men, 14.44+/-0.74 micromol/l for women) than those without angina (13.98+/-0.38 micromol/l for men, 13.41+/-0.98 micromol/l for women) or with stable angina (14.00+/-0.37 micromol/l for men, 12.88+/-0.71 micromol/l for women). There were no significant associations between the levels and the presence or severity of CAD. The mutant MTHFR homozygotes tended to have higher levels and those with the MS and CBS mutations tended to have lower levels. We conclude that there is a significant correlation between plasma homocysteine levels and EC-SOD suggesting that elevated homocysteine may exert oxidative stress and that levels are associated with unstable angina, but not the occurrence or extent of coronary stenosis. The contributions to total plasma homocysteine levels of the common mutations of genes coding for the enzymes controlling homocysteine metabolism are modest.     

Relationship between the extent of coronary artery disease and indicators of free radical activity.

Clinical studies have demonstrated that patients with coronary artery disease (CAD) have markers suggestive of increased free radical (FR) activity when compared with normal subjects; however, the relationship between the extent of CAD and level of FR markers is not known. The following indices of FR activity, plasma malondialdehyde (MDA), plasma thiols (PSH), red blood cell (RBC) glutathione (GSH), and RBC superoxide dismutase (SOD) were measured in 58 patients admitted for coronary angiography and in 50 matched controls. Regression analysis demonstrated no significant correlation between MDA, PSH, GSH, or SOD, and the angiographic grade which indicated the severity of the CAD. Patients with angiographically proven CAD (median 7.9 nmol/ml IQR 6.9-9.2) and patients with a history suggestive of angina pectoris but normal coronary angiograms (median 8.4 nmol/ml IQR 7.4-9.9) had significantly raised MDA levels compared with the controls (median 6.85 nmol/ml IQR 6.1-7.4), p less than 0.001 and p less than 0.005, respectively. The patients with angiographically proven CAD had significantly lower GSH levels (median 1461 microM IQR 1348-1709, p less than 0.002) compared with the controls (median 1754 microM IQR 1492-1930). Significantly raised SOD levels also were detected in patients with angiographically proven CAD (median 121.8 U/ml RBC, IQR 113.8-143.9) and in patients with a history of suggestive of angina pectoris but normal coronary angiograms (median 146 U/ml RBC, IQR 96.8-156.7) when compared with controls (median 96.3 U/ml RBC, IQR 82.4-115.6), p less than 0.001 and p less than 0.02, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic risk factors in the normolipidemic male patients with angiographically defined coronary artery disease

The relationship of plasma lipid and apolipoprotein (apo) concentrations and plasma insulin response to oral glucose load to angiographically determined coronary artery disease (CAD) was investigated in 65 normolipidemic (plasma cholesterol less than 230 mg/dl and plasma triglyceride less than 150 mg/dl) males. According to the results of coronary angiography, the patients were divided into 2 groups: patients with normal coronary artery, NCA group (n = 21); and patients with coronary artery disease, CAD group (n = 44). No significant differences in concentrations of plasma cholesterol and triglyceride were observed between the CAD and NCA groups. In the CAD group cumulative lifetime tobacco consumption was higher and high density lipoprotein (HDL) cholesterol concentration was lower than those in the NCA group. The variables that correlated with the severity of CAD, defined by the number of lesions and percent stenosis, were levels of plasma apo A-I and apo B. Prevalence of subjects with reduced oral glucose tolerance did not differ between 2 groups. However, hyperinsulinemic response to oral glucose load was present in the CAD group. HDL-cholesterol concentration, the sum of plasma insulin levels and the magnitude of the early insulin response during oral glucose challenge were accurate predictors of the presence of but not the severity of CAD. Multivariate analysis of the data confirmed the independent effect of plasma levels of apo A-I and apo B on the severity of CAD. The present data indicated that plasma levels of apo A-I and apo B were powerful discriminators in the normolipidemic CAD patients and that a high insulin response might be an indicator of enhanced susceptibility to the distinct coronary atherosclerosis.     

Lack of association of serum lipoprotein (a) levels with type-2 diabetes mellitus in patients with angiographically defined coronary artery disease

Multiple studies have demonstrated that elevated serum lipoprotein (a) [Lp(a)] levels are independent predictors for coronary artery disease (CAD) in subjects without diabetes mellitus (DM). However, their contribution in patients with DM is controversial and still requires clarification. We determined serum Lp(a) levels in 355 consecutive Caucasian patients (271 men and 84 women) with angiographically documented CAD, and in 100 control subjects (58 men and 42 women) who were clinically free of cardiovascular disease. In addition, the association of serum Lp(a) levels with type-2 DM in patients with CAD was investigated after reassigning patients according to the diagnosis of type-2 DM (61 men and 40 women with type-2 DM and 210 men and 44 women without). No gender differences in Lp(a) levels were observed between men and women (patients and control subjects). Patients with CAD had higher Lp(a) levels than the control subjects (33 (14-74) vs. 13 (9-29) mg/dl, P<0.001). Elevated Lp(a) levels (defined as >90th percentile of controls) were significantly more prevalent in men and women with CAD (35% and 28%, respectively) than in control subjects (13% and 10%, respectively). Serum Lp(a) levels correlated with LDL cholesterol (r=0.22, P<0.001) and apo B levels (r=0.18, P<0.03) in patients and control subjects. Stepwise discriminant analysis revealed that Lp(a) was an independent risk factor for the presence of CAD, independent of smoking, hypertension, type-2 DM, LDL and HDL cholesterol or apo A1 and B levels. When patients were studied according to the spread of CAD (evaluated as the number of narrowed vessels), no differences in serum Lp(a) levels were observed, nor was there a higher prevalence of elevated Lp(a) levels. Finally, when patients were re-assigned according to the diagnosis of type-2 DM, no effect of apo B and LDL-C levels on Lp(a) was found (r=0.06, P=n.s. and 40.14, P=n.s., respectively) and serum Lp(a) levels neither associated nor contributed to the extent of CAD. Our results showed that serum Lp(a) levels are increased in patients with angiographically documented CAD, but there were no significant differences between diabetic and non-diabetic patients, which indicates that elevated Lp(a) levels are specifically associated with CAD but not with type-2 DM.