Association of gamma-glutamyl transferase with subclinical coronary atherosclerosis and cardiac outcomes in non-alcoholics.

In an asymptomatic population, we determined the relationship between serum gamma-glutamyl transferase (GGT) and subclinical atherosclerosis, using coronary computed tomography angiography (CCTA). This was a retrospective observational cohort study which analyzed 5120 consecutive asymptomatic individuals with no prior history of coronary artery disease or significant alcohol intake who voluntarily underwent CCTA as part of a general health examination. All subjects were stratified into tertiles based on GGT levels. Degree and extent of subclinical coronary atherosclerosis were evaluated using CCTA. Cardiac events were a composite of all-cause death, myocardial infarction, unstable angina, and coronary revascularization. After adjustment for cardiovascular risk factors, there were no significant differences among GGT tertiles in terms of adjusted odds ratios for non-calcified and mixed plaques. The risk of any atherosclerotic and calcified plaques, significant stenosis, multi-vessel disease, and significant stenosis in the left main or proximal left anterior descending artery was higher in the third GGT tertile than in the first tertile (all p < 0.05). Over a median 5.4-year follow-up, the third GGT tertile had significant adjusted hazards ratios for cardiac events than did the first GGT tertile, even after stepwise adjustment for cardiovascular risk factors (all p < 0.01). In asymptomatic individuals, elevated GGT was independently associated with high-risk feature atherosclerosis and poorer cardiac outcomes.

NOS3 Gene rs1799983 and rs2070744 Polymorphisms in Patients with Unstable Angina.

Acute coronary syndrome occurs when the heart muscle does not receive adequate oxygen and nutrients in a timely manner. Acute coronary syndromes are primarily due to atherosclerosis of the coronary arteries, i.e., coronary heart disease. Nitric oxide (NO) is synthesised from L-arginine in endothelial cells by the constitutive calcium-calmodulin-dependent enzyme, nitric oxide synthase (NOS), which mediates endothelium-dependent vasodilatation. Endothelial nitric oxide synthase (eNOS) is predominantly expressed in endothelial cells. Three NOS isoforms have been detected in different tissue: (1) neuronal NOS (nNOS) (NOS1), (2) eNOS (NOS2), and (3) inducible NOS (iNOS) (NOS3). These isoforms are encoded by three different genes. NOS3 is located on chromosome 7q35-36 and contains 26 exons. Previous studies have suggested that NOS3 polymorphisms may be associated with acute coronary syndromes. Therefore, the aim of the study was to examine the associations between NOS3 rs1799983 (894G/T)andrs2070744 (-786T/C) polymorphisms and unstable angina. This study included 246 patients with unstable angina, as confirmed by coronary angiography. We also included 189 healthy controls who were also assessed by this technique. There were no significant differences in genotype distributions of NOS3 rs1799983and rs2070744 polymorphisms in patients with unstable angina and healthy controls in both univariate and multivariate analyses. In patients with the NOS3 rs1799983 TT genotype, we observed a higher BMI (TT vs. GT + GG, p = 0.068), and in patients with the NOS3 rs2070744 TT genotype, we observed a higher waist circumference (TT vs. TC + CC, p = 0.023; TT vs. CC, p = 0.0053). These data suggest a lack of association between the NOS3 rs1799983andrs2070744 polymorphisms and unstable angina in our patient population. However, these polymorphisms may be associated with some obesity parameters, rs1799983 in females and rs2070744 in males.

MicroRNA 28-5p regulates ATP-binding cassette transporter A1 via inhibiting extracellular signal-regulated kinase 2.

The biological function of the intronic microRNA-28 (miR-28) may be associated with the biological roles of its host gene, LIM domain lipoma­preferred partner (LPP). LPP has been reported to promote smooth muscle cell migration in arterial injury and atherosclerosis. However, the mechanism of miR­28 in atherosclerosis remains unclear. In the current study, the aim was to validate the inhibitory effect of miR­28­5p on extracellular signal­regulated kinase 2 (ERK2), to investigate its biological role in atherosclerosis and its association with cardiovascular disease. Western blotting and stem­loop reverse transcription­quantitative polymerase chain reaction combined with TaqMAN microRNA analysis was conducted. The current study demonstrated that miR­28­5p upregulated the expression of ATP­binding cassette transporter A1 (ABCA1) via the inhibition of ERK2 in HepG2 cells. In addition, increased levels of plasma miR­28­5p were positively correlated with the levels of high­density lipoprotein cholesterol in patients with unstable angina. This suggests that miR-28-5p participates in atherosclerosis via ERK2-mediated upregulation of the ABCA1 pathway.

Characterization of interleukin-33 and matrix metalloproteinase-28 in serum and their association with disease severity in patients with coronary heart disease.

OBJECTIVE: To investigate serum levels of interleukin (IL)-33 and matrix metalloproteinase-28 (MMP-28) in patients with coronary heart disease (CHD) and to evaluate their association with disease severity. METHODS: A total of 103 patients with CHD, including 27 cases of acute myocardial infarction (AMI), 33 cases of unstable angina pectoris (UAP) and 43 cases of stable angina pectoris were enrolled to detect serum levels of IL-33 and MMP-28 by enzyme-linked immunosorbent assays. Forty volunteers without CHD served as the control group. RESULTS: Compared with stable angina pectoris and control groups, serum levels of IL-33 were significantly lower (P<0.01) and serum concentrations of MMP-28 were higher (P<0.05) in AMI and UAP groups. Serum levels of IL-33 in single-vessel, double-vessel and triple-vessel lesion groups were lower than that in the control group (P<0.05), and the differences among the three groups were not significant (P>0.05), whereas only levels of MMP-28 in double-vessel and triple-vessel lesion groups were higher than in the control group (P<0.05). Spearman's correlation analyses showed a negative correlation between serum levels of IL-33 and MMP-28 in AMI and UAP groups (r=-0.596, P<0.05 and r=-0.750, P<0.01). A binary logistic regression analysis showed that IL-33, low-density lipoprotein cholesterol, and MMP-28 may be independent predictors of the occurrence of acute coronary syndrome. CONCLUSION: A decreased level of IL-33 and an elevated concentration of MMP-28 were found in CHD patients and correlated with disease severity. IL-33 and MMP-28 may play important roles in the development of CHD or as markers of disease severity.

PON1 Q192R genotype influences clopidogrel responsiveness by relative platelet inhibition instead of on-treatment platelet reactivity.

BACKGROUND: paraoxonase-1 (PON1) was recently identified as the crucial enzyme for clopidogrel bioactivation, with PON1 Q192R (rs662) polymorphism determining the clopidogel antiplatelet efficacy. However, subsequent studies showed controversies over the findings. This study aimed to evaluate the impact of PON1 Q192R in parallel to that of CYP2C19*2 (rs4244285) on clopidogrel responsiveness in a cohort of Chinese patients with unstable angina pectoris. MATERIAL AND METHODS: One hundred and eighty Chinese-Han patients diagnosed with unstable angina pectoris and treated with clopidogrel were consecutively recruited. Clopidogrel responsiveness, measured by relative platelet inhibition {RI=[(pretreatment aggregation-posttreatment aggregation at 5days)/(pretreatment aggregation)] x100%}, was assessed in relation to PON1 Q192R and CYP2C19*2 genotypes. RI values were stratified into four quartiles, with patients in quartile 1 defined as individuals of clopidogrel non-responsiveness. The contributions of PON1 Q192R and CYP2C19*2 to on-treatment platelet reactivity (OTPR) at 5days maintenance dose of clopidogrel were also evaluated. RESULTS: For PON1 Q192R genotypes, RI values were significantly lower in patients with QR and RR alleles than in patients with QQ alleles (p=0.01). OTPR values at 5days maintenance dose of clopidogrel were similar across all the PON1 Q192R genotypes (p=0.41). PON1 192 QR and RR conferred increased risks for clopidogrel non-responsiveness [OR 3.64; 95% CI (1.21-10.92), p=0.02]. For CYP2C19*2 genotypes, compared to CYP2C19*1/*1 wild type carriers, CYP2C19*2 carriers showed a significantly higher OTPR (p=0.009), and a trend for lower RI values (p=0.06). An increased risk for clopidogrel non-responsiveness was found in patients with CYP2C19*2 genotype [OR 2.02; 95% CI (1.03-3.96), p=0.04]. CONCLUSIONS: Both PON1 Q192R and CYP2C19*2 genotypes influence clopidogrel responsiveness, with the impact of PON1 Q192R mainly on relative platelet inhibition instead of OTPR of clopidogrel.

Interleukin-33, matrix metalloproteinase-9, and tissue inhibitor [corrected] of matrix metalloproteinase-1 in myocardial infarction.

BACKGROUND/AIMS: Acute coronary syndrome (ACS) is characterized by increased inflammatory processes and endothelial activation. We investigated the association between ACS and inflammatory mediators and matrix-degrading enzymes. METHODS: We prospectively enrolled 55 consecutive patients with ACS: 25 with unstable angina (UA) and 30 with non-ST elevated myocardial infarction (NSTEMI). For comparison, 25 age- and sex-matched subjects with no significant coronary artery stenosis were included as the control group. Peripheral serum levels of interleukin (IL)-33, matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP-1, and C-reactive protein (CRP) were measured on admission, and at 12, 24, 48, and 72 hours after the initial evaluation. RESULTS: Compared to serum levels in the control group, serum levels of IL-33 decreased in the NSTEMI group (p < 0.05), and levels of MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 increased in the UA group (p < 0.01, p < 0.05, respectively) and NSTEMI group (p < 0.05, p < 0.05, respectively). IL-33 levels were significantly lower on admission than at 12 hours after the initial evaluation (p < 0.05). IL-33 levels were negatively correlated with MMP-9 levels (r = -0.461, p < 0.05) and CRP levels (r = -0.441, p < 0.05). CONCLUSIONS: Elevated levels of MMP-9, TIMP-1, and decreased levels of IL-33 play a role in the development and progression of ACS.

Novel inflammatory biomarkers in acute coronary syndrome

No abstract available.

Multiple comparisons of drug efficacy between subgroups defined by genetic polymorphisms.

In contrast to using genome-wide association studies to discover associations between genes or single-nucleotide polymorphisms in the genome with disease status or outcome, some recent pharmacogenomic studies have focused on whether polymorphisms in genes involved in metabolizing drugs significantly impact their efficacy. Whether a drug starts as an active compound and gets metabolized and eliminated from the body or starts as an inactive compound and gets metabolized to an active form, patients in subgroups separated by polymorphism of a gene needed to metabolize the drug might derive differential benefit from that drug. With the use of the Clopidogrel in Unstable Angina to Prevent Recurrent Events trial for Plavix as an example, this article proposes Multiple Comparisons with Control (Subgroup) and Multiple Comparisons with the Best (Subgroup) as methods to infer whether some subgroups of patients derive more or less benefit than wild-type patients and which subgroup or subgroups of patients derive maximum benefit or practically maximum benefit from the drug.

Association of lipoprotein-associated phospholipase A2 with characteristics of vulnerable coronary atherosclerotic plaques.

PURPOSE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory enzyme expressed in atherosclerotic plaques. We investigated the association of circulating Lp-PLA2 with characteristics of vulnerable coronary atherosclerotic plaques. MATERIALS AND METHODS: We recruited 113 patients with either unstable angina (UA, n=59) and stable angina (SA, n=54) by coronary angiography. Thirty-six healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate the characteristics of coronary atherosclerotic plaque, and serum Lp-PLA2 concentration was measured as well. RESULTS: Lp-PLA2 concentration was significantly higher in both UA and SA patients [(396±36) µg/L and (321±39) µg/L, respectively] compared with the controls [(127 ± 49) µg/L, p<0.01], and higher in UA than SA group. IVUS findings showed that remodeling index (RI) (0.91 ± 0.15 vs. 0.85 ± 0.11, p=0.005) and eccentricity index (EI) (0.73 ± 0.16 vs. 0.65 ± 0.22, p=0.039) were larger in UA than in SA group, and fibrous caps were thicker in SA than UA group [(0.91 ± 0.23) mm vs. (0.63 ± 0.21) mm, p=0.032]. Moreover, Lp-PLA2 correlated positively with EI (r=0.439, p<0.01) and RI (r=0.592, p<0.05) in UA group. There was an inverse relationship between Lp-PLA2 and fibrous cap thickness in both UA (r=-0.587, p<0.001) and SA (r=-0.318, p<0.05) groups. The independent risk factors in UA group were Lp-PLA2 (OR=1.055, 95% CI: 1.03-1.08, p=0.013), LDL-cholesterol (OR=0.032, 95% CI: 0.00-0.05, p=0.041) and fibrous cap thickness (OR=0.008, 95% CI: 0.00-0.45, p=0.019). Lp-PLA2 was strongly associated with both EI and fibrous cap thickness in both groups. CONCLUSION: Serum level of Lp-PLA2 is associated with both eccentricity index and fibrous cap thickness in both UA and SA groups. Elevated levels of circulating Lp-PLA2 might to be a strong risk factor and more serious for unstable angina than stable angina.

The diagnostic and prognostic value of first hour glycogen phosphorylase isoenzyme BB level in acute coronary syndrome.

BACKGROUND: Evaluating patients with symptoms suggestive of acute coronary syndrome (ACS) is a time consuming, expensive and problematic process in the emergency department. This study aimed to evaluate the diagnostic and prognostic value of glycogen phosphorylase isoenzyme-BB (GP-BB) in ACS. METHODS: A total of 72 patients (mean age 61.8 ± 11.6 years) with ACS were enrolled. The ELISA method for determining GP-BB level was performed and considered positive at 〉 10 ng/mL. Duration of angina, type of ACS, demographic features, myoglobin, creatinine kinase and troponin T (cTnT) were also assessed. The cTnT levels eight hours after pain onset was considered the gold standard test for the diagnosis of myocardial infarction. RESULTS: The most sensitive biomarker at first hour of admission was GP-BB (95.8%). However, the specificity of GP-BB was low (43.7%). Receiver operating characteristics curve analysis of the GP-BB level for predicting myocardial infarction revealed the area under the curve value as 0.82 (SE 0.04; 95% CI 0.78-0.85). Positive treadmill exercise test (60% vs 17%, p = 0.047), coronary artery disease (CAD; 59% vs 19%, p = 0.007), percutaneous coronary intervention (44% vs 27%, p = 0.031) and 30-day mortality and/or readmission (33% vs 5%, p = 0.028) were found to be higher in unstable angina (UA) patients having GP-BB (+). CONCLUSIONS: GP-BB is considerably cardiosensitive at the first hour of admission in patients with ACS, but the specificity of GP-BB is lower and it is elevated in nearly half of the patients with UA. However, in this group, GP-BB predicts significant CAD and the combined end-point of mortality and re-hospitalization.

Increased expression and plasma levels of myeloperoxidase are closely related to the presence of angiographically-detected complex lesion morphology in unstable angina.

BACKGROUND: Myeloperoxidase (MPO) is a leucocyte enzyme that catalyses the formation of a number of reactive oxidant species. OBJECTIVE: The purpose of this study is to evaluate the relationship between angiographic coronary plaque morphology in patients with unstable angina pectoris (UAP) or stable angina pectoris (SAP) and MPO levels. PATIENTS AND DESIGN: Plasma MPO levels on admission were measured in 236 patients with UAP, 146 with SAP and 85 control subjects using an ELISA kit. The angiographic morphology of the culprit lesion was classified into two types, simple or complex, based on the Ambrose classification. In addition, 61 atherectomy specimens obtained from a different cohort of patients with UAP and SAP were studied immunohistochemically for MPO. RESULTS: Median (IQR) plasma MPO levels in patients with UAP with a complex lesion were significantly higher than in patients with a simple lesion (41.9 (21.7­73.7) ng/ml vs 20.5 (15.9­27.9) ng/ml, p<0.0001), but there was no significant difference between the two groups in patients with SAP. On multivariate analysis, raised plasma MPO levels and Braunwald class III were independent factors for angiographically-detected complex lesions (adjusted OR 12.49, 95% CI 3.24 to 48.17, p=0.0002). In the atherectomy specimens the number of MPO-positive cells in patients with UAP with complex lesions was significantly higher (p<0.0005) than in patients with simple lesions. Moreover, in this cohort, plasma MPO levels were positively correlated with the number of MPO-positive cells in atherectomy specimens (R=0.42, p=0.024). CONCLUSIONS: This study shows that increased expression and plasma MPO levels are closely related to the presence of angiographically-detected complex lesion morphology in patients with UAP.

Pharmacological inhibition of leukotriene biosynthesis: effects on the heart conductance.

Leukotrienes are lipid mediators produced via 5-lipooxygenase pathway of arachidonic acid. At least two cysteinyl-leukotrienes receptors are highly expressed in the heart, including the conduction system. Coronary angiography or angioplasty is accompanied by release of cysteinyl leukotrienes into coronary circulation and into urine. We tested the hypothesis that inhibition of leukotrienes biosynthesis would affect the conductance system function. In a double-blind placebo controlled study, patients with stable angina undergoing elective coronary catheterization or angioplasty were randomly assigned to 48 hrs treatment with a 5-lipoxgenase inhibitor (n=54) or placebo (n=49). ECG Holter recording was carried out for 24 hrs before and after the procedure and urinary leukotriene E(4) measurements were done. Inhibition of 5-lipoxygenase caused 26% reduction of urinary leukotriene E(4), associated with: 1) decrease in heart rate by about 7%, 2) enhanced heart rate variability; 3) protection against depressions in atrioventricular conductance and ventricular repolarization induced by the procedure. No effects on either arrhythmias, or ECG patterns of ischemia were noted. We conclude that pharmacological inhibition of 5-lipoxygenase, shortly before percutaneous coronary intervention, reveals specific actions of leukotrienes on the heart rhythm. Inhibitors of 5-lipoxygenase might be of interest as a novel class of cardiac drugs affecting the conductive system.

Prognostic value of myeloperoxidase in coronary artery disease: comparison of unstable and stable angina patients.

BACKGROUND: Atherosclerosis is a chronic inflammatory process, and myeloperoxidase (MPO) seems to contribute directly to the pathogenesis of acute coronary syndrome (ACS). OBJECTIVE: To compare MPO levels among the patients with stable and unstable ischemic heart disease and to evaluate their independent prognostic value for cardiovascular events. METHODS: MPO and C-reactive protein (CRP) were assessed in two cohorts of coronary artery disease patients, including 178 patients with stable angina and 130 patients with ACS evaluated at the emergency department. RESULTS: MPO and CRP levels were significantly higher among patients with ACS [MPO 93 (54-127) vs. 9.9 pmol/l (5-21) and high sensitivity-CRP 11 (3-27) vs. 2.6 mg/l (1-5)]. Among patients with stable angina, high sensitivity-CRP levels greater than 3 mg/l were associated with a three-fold risk of further cardiovascular events during a mean follow-up period of 13+/-4 months, although there was no significant association between MPO levels and outcomes. Among patients with ACS, baseline MPO level was an independent predictor of major adverse cardiac events during hospitalization, odds ratio of 3.8 (95% confidence interval: 1.2-12) for the combined endpoint (death, recurrent angina, heart failure, and arrhythmia). CRP levels were associated with hospital mortality in patients with ACS, but were not independently related to cardiovascular events. CONCLUSION: Elevated MPO levels among the ACS patients suggest that this marker may participate in plaque vulnerability and instability process, whereas higher CRP levels were predictive of cardiac events only among the stable angina patients. These findings suggest distinct role of the inflammatory markers studied in the pathophysiology of coronary artery disease.

Changes in plasma von Willebrand factor-cleaving protease (ADAMTS13) levels in patients with unstable angina.

INTRODUCTION: Increased plasma levels of von Willebrand factor (VWF) have been reported in acute myocardial infarction (AMI). Recently, we showed reduced activity of a VWF-cleaving protease (ADAMTS13) in AMI patients. However, there is no information as to whether ADAMTS13 affects the pathogenesis of unstable angina (UA). Thus, the purpose of this study was to examine changes in plasma VWF and ADAMTS13 levels in UA patients. MATERIALS AND METHODS: Plasma VWF and ADAMTS13 levels (mU/ml) were measured in 45 patients with UA, 55 with stable exertional angina (SEA) and 47 with chest pain syndrome (CPS) at the time of coronary angiography. Levels were also measured in 15 UA patients after 6 months of follow-up. RESULTS: VWF antigen levels (mU/ml) increased significantly in UA patients compared with SEA or CPS (2129.3+/-739.5, 1571.8+/-494.2 and 1569.5+/-487.0, respectively; P < 0.0001 in UA vs. SEA or CPS). ADAMTS13 antigen levels (mU/ml) were significantly lower in UA patients than SEA or CPS (737.3+/-149.5, 875.3+/-229.0 and 867.7+/-195.5, respectively; P < 0.01 in UA vs. SEA or CPS). Furthermore, there was a significant inverse correlation between VWF and ADAMTS13 antigen levels (r = -0.302, P = 0.0002). The antigen levels at 6 months of follow-up were not different compared to the acute phase in the 15 UA patients that had repeated blood sampling. CONCLUSIONS: These findings suggest that there is prolonged thrombogenicity in UA patients represented as an imbalance between VWF and ADAMTS13 activity.

Increased granzyme B production from peripheral blood mononuclear cells in patients with acute coronary syndrome.

OBJECTIVES: To clarify the role of granzyme B in acute coronary syndrome. DESIGN AND SETTING: Granzyme B is a member of the serine esterase family released from cytotoxic lymphocytes and plays an important role in cellular apoptosis by activating intracellular caspases. Granzyme B expression was compared between patients with stable and unstable angina pectoris (UAP). PATIENTS: 173 patients with coronary artery disease (CAD) were enrolled. 84 patients were found to have stable angina pectoris (SAP) and 89 patients to have UAP. METHODS: Peripheral blood was drawn from the patients. Peripheral blood mononuclear cells (PBMCs) isolated by gradient centrifugation were cultured at a density of 2x106 cells/ml for 24 hours. The supernatants were collected 24 hours after incubation and the granzyme B level was measured by enzyme-linked immunosorbent assay. Polychromic flow cytometric analysis was performed to evaluate the expression of granzyme B in the cells. RESULTS: Granzyme B production from PBMCs of UAP patients was significantly higher than from those of patients with SAP (39.1 (SEM 6.6) versus 17.0 (SEM 1.8) pg/ml, p<0.05). Granzyme B production from PBMCs increased with the increasing TIMI risk score in UAP patients. The percentage of granzyme B-positive lymphocytes to CD3-positive lymphocytes in UAP patients was significantly higher than in SAP (32.1% (SEM 1.6%) versus 18.4% (SEM 0.9%), p<0.01). CONCLUSIONS: These results suggest that granzyme B might play an important role in triggering acute coronary events by inducing apoptosis and the degradation of atherosclerotic coronary plaques.

High telomerase activity in neutrophils from unstable coronary plaques.

OBJECTIVES: We evaluated telomerase activity in circulating polymorphonuclear neutrophils (PMN) and in PMN isolated from coronary atherosclerotic plaques by a novel approach. BACKGROUND: Delayed apoptosis of PMN have been demonstrated in unstable angina (UA). These cells have a finite lifespan with low telomerase activity, a polymerase that extends telomeres, structures essential for cell aging. Reactivation of telomerase has been associated with resistance to apoptosis. METHODS: We studied 20 patients with UA and 6 patients with chronic stable angina (SA), undergoing a percutaneous coronary intervention. Circulating PMN were isolated from venous blood and PMN derived from coronary plaque were isolated from washing medium of angioplasty balloons. RESULTS: Telomerase activity was higher in coronary plaque PMN of UA patients than in coronary plaque PMN of SA patients (122.7, range 20.5 to 3,696; and 47.7, range 16 to 212.6, respectively, p = 0.001) and higher than in peripheral PMN of SA patients (122.7, range 20.5 to 3,696 vs. 59, range 16.5 to 132.5, p = 0.001). We found a statistically significant difference between venous and coronary plaque PMN telomerase activity in UA patients (z = -2.875; p = 0.004). Among UA patients, a shorter time interval from symptom onset to coronary PMN sampling was the only independent predictor of high telomerase activity in coronary plaque PMN (p < 0.001, R2 = 0.75). CONCLUSIONS: In UA patients, telomerase activity is high in coronary plaque PMN, while it is low in peripheral PMN. Telomerase reactivation in resident PMN resulting in a prolonged lifespan might play a key role in the early phases of instability.

Matrix metalloproteinase-3 and coronary remodelling: implications for unstable coronary disease.

OBJECTIVES: Matrix metalloproteinases (MMPs) are plausible candidates for prediction of unstable coronary syndromes. We hypothesised that the MMP-3 polymorphism (- 1171, 5A/6A) would relate to coronary plaque characteristics and unstable clinical presentation. METHODS AND RESULTS: Forty patients with de novo presentation of coronary artery disease (CAD) were classified into unstable coronary syndrome (n=19) or stable angina pectoris (n=21). On coronary intravascular ultrasound, patients with unstable disease had a greater plaque burden, more positive (outward) coronary remodelling, and all but one were MMP-3 6A allele carriers (p=0.027 compared with stable). The relationship between the 6A allele and unstable presentation was substantiated in a validation cohort of 161 CAD patients (58 stable and 103 unstable) and in the total population of 201 CAD patients (79 stable and 122 unstable, p=0.007), and was independent of conventional risk factors. Furthermore, 6A allele carriers had a higher plasma MMP-3 concentration (15.8+/-12.5 versus 11.7+/-7.2 ng/mL, p=0.01), maximum coronary stenosis on angiography (89+/-15% versus 80+/-23%, p=0.02), plaque area (12.0+/-5.2 versus 7.5+/-3.6 mm(2), p=0.03), percentage plaque burden (82+/-7 versus 71+/-13%, p=0.003), and remodelling ratio (1.03+/-0.23 versus 0.83+/-0.12, p=0.003). CONCLUSIONS: The MMP-3 6A allele promotes positive coronary remodelling, greater plaque burden, and increased susceptibility to unstable coronary syndromes in humans.

[Clinical implications of relationship between myeloperoxidase and acute coronary syndromes].

OBJECTIVE: To investigate the clinical implications of relationship between myeloperoxidase and acute coronary syndromes (ACS). METHODS: 176 consecutive patients who underwent coronary angiography for coronary atherosclerosis were divided into four groups according to the quartile of MPO Level. The characters and the relationship between MPO and the elements were studied in every group. RESULTS: (1) ACS rate (36.2%) in the fourth quartile group of MPO level was 6 times higher than that (5.2%) in the first quartile group of MPO level, P < 0.01. (2) Gensini score (65.6 +/- 30.3) in the fourth quartile group of MPO level was significantly higher than that (17.3 +/- 10.2) in the first quartile group (P < 0.01). WBC [(7.7 +/- 1.6) x 10(9)/L] in the fourth quartile group was also significantly higher than that [(6.6 +/- 1.8) x 10(9)/L] in the first quartile group, P < 0.05. (3) When TnI < or = 0.05 ng/ml, MPO level had a positive correlation with Gensini score (r = 0.321, P = 0.002) and WBC (r = 0.230, P = 0.025). (4) Kaplan-meier event rate curve showed that there was a significant difference of the terminus incident (death, no causing death AMI, vessel reestablish and incidence rate of CABG add up) between the groups > or = 62.9 AUU/L and < 62.9 AUU/L of MPO serum level at 6-month follow-up visit (chi(2) = 13.5, P = 0.01). CONCLUSION: Activity level of MPO in human serum seems a good biomarker for diagnosing and predicting ACS, which may be especially helpful in predicting the risk of myocardial infarction in patients with acute chest pain during 6-month follow up.