Association of myeloperoxidase with cardiovascular disease risk factors in prediabetic subjects

IntroductionPrediabetes is a chronic low-grade inflammatory disease and considered as a risk factor for the development of diabetes mellitus and cardiovascular disease. Myeloperoxidase (MPO) is a leukocyte-derived enzyme, linked to both oxidative stress and inflammation and has been proposed as a possible mediator of atherosclerosis, the major cause of cardiovascular disease. The objective of the present study was to evaluate the level of MPO in prediabetic subjects and correlate it with other cardiovascular disease risk factors.Materials and methodsIn this cross-sectional study, a total of 400 subjects were recruited. Of them, 200 were prediabetic subjects and 200 were age and gender-matched controls. For each subject, blood pressure, weight, height, waist circumference, hip circumference and lipid parameters were measured. In addition, MPO was determined.ResultsMPO was significantly increased in prediabetic subjects as compared to controls. In correlation analysis, MPO was found to be significantly and positively correlated with all the cardiovascular disease risk factors i.e. age, body mass index (BMI), waist-to-hip ratio (WHR), blood pressure [both systolic blood pressure (SBP) and diastolic blood pressure (DBP)], lipid parameters except high density lipoprotein (HDL) to which it was negatively correlated.ConclusionIn conclusion, MPO is well correlated with cardiovascular disease risk factors in prediabetes. Hence, MPO could be used to detect cardiovascular risk among prediabetic subjects and also can be used as an early biomarker of oxidative stress and inflammation in prediabetes.     

Urinary albumin excretion is independently associated with carotid and femoral artery atherosclerosis in the general population.

AIMS: In diabetic patients, increased urinary albumin excretion (UAE), termed microalbuminuria when in the range between 30 and 300 mg/dL per day, is associated with a higher risk of atherosclerosis and its complications. Whether or not this notion applies to the general population is a matter of ongoing controversy because none of the few previous investigations among non-diabetics strictly represent the general community. METHODS AND RESULTS: Urinary albumin-to-creatinine ratio (uACR), a measure of UAE, was assessed from overnight spot urine samples in a population-based cohort of 684 individuals. The ratio was significantly related to age, gender, blood pressure, diabetes, markers of systemic inflammation, liver enzymes, and parathyroid hormone levels (P<0.001 each). Moreover, uACR emerged as a highly significant risk predictor of carotid and femoral artery atherosclerosis in the general community and the non-diabetic subpopulation alike (age/sex-adjusted P<0.001 each). In multivariable logistic regression analyses, odds ratios (95% CI) of carotid and femoral atherosclerosis amounted to 1.28 (1.01-1.61) and 1.44 (1.15-1.81) for a one unit increase in log(e)-transformed uACR (P=0.040 and 0.002). Corresponding odds ratios in non-diabetic subjects were 1.41 (1.09-1.84) and 1.54 (1.19-1.99) (P=0.010 and 0.001). Multivariable linear regression analyses yielded significant, or near significant, relations with carotid and femoral artery intima-media thickness and atherosclerosis scores (P=0.058-0.001). CONCLUSION: The uACR is significantly and independently associated with the presence and severity of atherosclerosis in the general population. The relation obtained was of a dose-response type and extended to levels far below what is termed microalbuminuria. The novel aspects of our study are its focus on various vascular territories and representivity of the general healthy population.     

The Dallas Heart Study: a population-based probability sample for the multidisciplinary study of ethnic differences in cardiovascular health

The decrease in cardiovascular death rates in the United States has been slower in blacks than whites, especially in patients <65 years of age. The Dallas Heart Study was designed as a single-site, multiethnic, population-based probability sample to (1) produce unbiased population estimates of biologic and social variables that pinpoint ethnic differences in cardiovascular health at the community level and (2) support hypothesis-driven research on the mechanisms causing these differences using genetics, advanced imaging modalities, social sciences, and clinical research center methods. A probability-based sample of Dallas County residents aged 18 to 65 years was surveyed with an extensive household health interview. The subset of participants 30 to 65 years of age provided in-home fasting blood and urine samples and underwent multiple imaging studies, including cardiac magnetic resonance imaging and electron beam computed tomography. Completed interviews were obtained for 6,101 subjects (54% black), phlebotomy visits for 3,398 (52% black), and clinic visits for 2,971 (50% black). Participation rates were 80.4% for interviews, 75.1% for phlebotomy visits, and 87.4% for clinic visits. Weighted population estimates of many measured variables agreed closely with those of the United States census and were relatively stable from the interview sample to the phlebotomy and clinic subsamples. Thus, the Dallas Heart Study provides a phenotypically well-characterized probability sample for multidisciplinary research that will be used to improve the mechanistic understanding and prevention of cardiovascular disease, especially in black Americans.     

髓过氧化物酶在冠状动脉粥样硬化研究中的新进展

目前的研究均支持炎症在冠状动脉粥样硬化性疾病中具有举足轻重的地位,炎症细胞与血管内环境中的细胞、细胞因子、炎症介质等的相互作用极其复杂,作为中性粒细胞活化标志物的髓过氧化物酶已被发现能参与冠状动脉粥样硬化的全过程,揭示粥样斑块的早期改变,为临床的早期诊断及治疗指出了新的方向.     

High-risk plaque in the superficial femoral artery of people with peripheral artery disease: Prevalence and associated clinical characteristics

Objective

We used magnetic resonance imaging (MRI) to study the prevalence and associated clinical characteristics of high-risk plaque (defined as presence of lipid-rich necrotic core [LRNC] and intraplaque hemorrhage) in the superficial femoral arteries (SFA) among people with peripheral artery disease (PAD).

Background

The prevalence and clinical characteristics associated with high-risk plaque in the SFA are unknown.

Methods

Three-hundred-three participants with PAD underwent MRI of the proximal SFA using a 1.5 T S platform. Twelve contiguous 2.5 mm cross-sectional images were obtained.

Results

LRNC was present in 68 (22.4%) participants. Only one had intra-plaque hemorrhage. After adjusting for age and sex, smoking prevalence was higher among adults with LRNC than among those without LRNC (35.9% vs. 21.4%, p = 0.02). Among participants with vs. without LRNC there were no differences in mean percent lumen area (31% vs. 33%, p = 0.42), normalized mean wall area (0.71 vs. 0.70, p = 0.67) or maximum wall area (0.96 vs. 0.92, p = 0.54) in the SFA. Among participants with LRNC, cross-sectional images containing LRNC had a smaller percent lumen area (33% ± 1% vs. 39% ± 1%, p < 0.001), greater normalized mean wall thickness (0.25 ± 0.01 vs. 0.22 ± 0.01, p < 0.001), and greater normalized maximum wall thickness (0.41 ± 0.01 vs. 0.31 ± 0.01, p < 0.001), compared to cross-sectional images without LRNC.

Conclusions

Fewer than 25% of adults with PAD had high-risk plaque in the proximal SFA using MRI. Smoking was the only clinical characteristic associated with presence of LRNC. Further study is needed to determine the prognostic significance of LRNC in the SFA.

Clinical trial registration—URL

http://www.clinicaltrials.gov. Unique identifier: NCT00520312.     

Relation of coronary atherosclerosis determined by electron beam computed tomography and plasma levels of n-terminal pro-brain natriuretic peptide in a multiethnic population-based sample (the Dallas Heart Study)

Elevated plasma levels of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro-BNP) are seen in the setting of cardiac ischemia and are associated with adverse outcomes in patients with coronary artery disease. The mechanisms leading to natriuretic peptide elevation in patients with coronary artery disease, including the contribution of coronary atherosclerosis itself, have not been fully elucidated. Measurement of NT-pro-BNP, electron beam computed tomography, and cardiac magnetic resonance imaging were performed in 2,445 subjects from the Dallas Heart Study who were free of heart failure and renal insufficiency. Electron beam computed tomography-determined coronary artery calcium scores were categorized as none (<10), mild (> or =10 to <100), moderate (> or =100 to <400), and severe (> or =400). NT-pro-BNP levels increased significantly across increasing coronary artery calcium score categories (p <0.0001 for trend). In multivariate models adjusted for age, gender, race, body mass index, hypertension, history of myocardial infarction, angina, angiotensin-converting enzyme inhibitor use, beta-blocker use, left ventricular (LV) ejection fraction, and LV mass, higher coronary artery calcium scores remained independently associated with higher log NT-pro-BNP levels (p = 0.03). This association persisted in similar models excluding patients with low LV ejection fractions, LV hypertrophy, angina pectoris, and a history of myocardial infarction. In conclusion, these findings support the hypothesis that coronary atherosclerosis may directly influence the activation of the cardiac neurohormonal system.     

糖基化磷脂酰肌醇磷脂酶D与动脉粥样硬化关系的研究

目的 探讨糖基化磷脂酰肌醇特异性磷脂酶D(GPI-PLD)在动脉粥样硬化病理生理过程中的作用及其机制. 方法 分别收集102例冠心病患者和121例健康者外周血,测定其外周血GPI-PLD酶活性及其单个核细胞GPI-PLD mRNA表达.构建高表达GPI-PLD基因HUVEC细胞模型,并设立空白组和对照组,进行ox-LDL诱导,观察各组内皮细胞功能及生物学特性的改变.结果 冠心病患者和健康者其外周血GPI-PLD酶活性分别为31.80±4.21和44.32±4.50,单个核细胞GPI-PLD mRNA表达比值分别是0.92±0.16和1.53±0.14;冠心病患者组外周血GPI-PLD酶活性(t=21.31,P＜0.01)及其mRNA表达(t=30.36,P＜0.01),较健康者组分别减少28.2％和39.9％.ox-LDL诱导的各组细胞,高表达GPI-PLD细胞模型组细胞表面黏附单核细胞数、内皮素1、活性氧、丙二醛及凋亡率均低于空白组[29.59±1.40、3.51±0.45、(50.63±4.22) ng/L、0.043±0.011、(3.32±0.44) nmol/L比41.39±2.15、10.57±1.12、(59.35±4.45) ng/L、0.052±0.011、(5.01±0.69) nmol/L]和对照组[42.68±2.45、9.92±1.03、(61.11±4.12) ng/L、0.051±0.007、(4.89±0.71)nmol/L],而一氧化氮含量高于空白组[(29.88±1.37 μmol/L比(21.76±1.02) μmol/L]和对照组(23.43±0.85) μmol/L. 结论 GPI-PLD基因在冠心病患者中低表达,稳定高表达GPI-PLD有助于血管内皮细胞损伤的修复,有助于阻止动脉粥样硬化的发生和发展.     

血浆髓过氧化酶与冠心病的临床研究

目的探讨血浆髓过氧化酶（MPO）与冠状动脉粥样硬化性心脏病（CAD）的临床关系。方法利用酶联免疫法测定78例CAD患者血浆MPO、C反应蛋白（CRP）和白细胞（WBC）值，并与46例非CAD患者进行对比。结果CAD中急性冠脉综合征（Acs）组患者血浆髓过氧化酶水平显著增高，且与CRP、WBC呈正相关；而稳定型心绞痛（SAP）组MPO水平与对照组差异无统计学意义。结论血浆MPO水平可以预测冠心病ACS的危险性，对严重心血管事件的发生有一定的预警作用。     

Soluble intercellular adhesion molecule-1 is associated with carotid and femoral atherosclerosis but not with intima-media thickness in a population-based sample

Atherosclerotic vascular disease remains the single most prevalent cause of death and morbidity in the western world. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that also possesses mitogenic activity on many cell types, including vascular smooth muscle cells. Raised plasma and tissue levels of ET-1 have been described in atherosclerosis in animal models and in man, suggesting that this peptide plays a pathophysiological role in this condition. Two main ET-1 receptors have been cloned (ET_A and ET_B). Mixed ET_A/B and receptor subtype selective antagonists are now available. Since ET-1 is generally believed to be a ‘pathophysiological peptide’, we discuss the therapeutic potential of ET-1 antagonists in atherosclerosis and consider whether, at certain sites in this process, ET-1 may play a beneficial role. In such situations ET antagonism may be undesirable.     

慢性阻塞性肺疾病患者呼出气冷凝液中髓过氧化物酶的检测及其意义

目的 检测COPD患者呼出气冷凝液（EBC）中髓过氧化物酶（MPO）浓度,探讨MPO与COPD发病发展的关系.方法 纳入49例COPD患者、18例健康体检者作为研究对象,采用EcoscrecnEBC收集仪采集标本,以酶免疫法测定EBC中MPO浓度.结果 COPD组EBC中MPO浓度显著高于健康对照组[（35.68±0.32）μg/L vs （11.72±0.34）μg/L,P＜0.05];COPD组EBC中MPO浓度与患者FEV1％ pred、呼气流量峰值呈正相关（相关系数r分别为0.418、0.327,P值均＜0.05）.结论 EBC中的MPO浓度能监测肺组织局部的炎症和氧化应激程度,能反映COPD患者病情严重程度,有助于发现COPD的病情变化,是一种较好的评价COPD病情的生物学指标.     

髓过氧化物酶在冠心病中的诊断应用

大量研究证实,炎症促进了动脉粥样硬化的形成及发展,表现为粥样硬化斑块的形成.动脉硬化引起的危重心血管事件,如心肌梗死或缺血性脑卒中,为易损斑块破裂所导致[1].血制品中的蛋白或酶类通常作为生物标记物,反映疾病状态,并提供诊断及预后价值[2].     

Carotid atherosclerosis, vascular risk profile and mortality in a population-based sample of functionally healthy elderly subjects: the Berlin ageing study

OBJECTIVES: Studies on extracranial carotid atherosclerosis have predominately been undertaken on middle-aged subjects. This study examines the prevalence of extracranial carotid atherosclerosis, its relation to vascular risk factors and its significance for survival in elderly subjects. DESIGN: Population-based cross-sectional survey. Non-modifiable vascular risk factors examined were family history of atherosclerotic disease, sex and apolipoprotein E (apoE) genotype. Potentially modifiable risk factors assessed were smoking, fibrinogen, fasting lipids, body mass index, hypertension and diabetes. SETTING AND SUBJECTS: Two hundred and twenty-five functionally healthy volunteers of the Berlin Ageing Study, aged 70-100. MAIN OUTCOME MEASURES: Presence of carotid stenosis and plaque ascertained by ultrasound imaging; 5-year mortality. RESULTS: At least one plaque was found in 144 (64%) of the volunteers; 34 (15%) had a stenosis over 50%; and nine (4%) had a stenosis over 75%. Total cholesterol > 6.5 mmol L-1, LDL cholesterol > 4.6 mmol L-1 and total cholesterol/HDL cholesterol ratio > 5 were significantly associated with presence of plaque in 70- to 80-year-old subjects, as was diabetes in subjects over 80 years. Log-linear analyses showed significant three-way interactions for high LDL cholesterol and diabetes with plaques and age. Family history, sex, apoE genotype, smoking and fibrinogen were not related to presence of plaque in the study population. Cox regression analysis revealed increased 5-year mortality rates for subjects with plaques (OR = 2. 88; 95% CI = 1.30-6.35), whereas the vascular risk profile was not associated with mortality. CONCLUSIONS: In a population-based sample of functionally healthy elderly subjects, the significance of the vascular risk profile seemed to be diminished. It had no impact on survival and only modifiable risk factors showed an age-dependent association with carotid disease.     

The association of differing measures of overweight and obesity with prevalent atherosclerosis: the Dallas Heart Study.

OBJECTIVES: This study sought to evaluate the associations between different measures of obesity and prevalent atherosclerosis in a large population-based cohort. BACKGROUND: Although obesity is associated with cardiovascular mortality, it is unclear whether this relationship is mediated by increased atherosclerotic burden. METHODS: Using data from the Dallas Heart Study, we assessed the association between gender-specific obesity measures (i.e., body mass index [BMI]; waist circumference [WC]; waist-to-hip ratio [WHR]) and prevalent atherosclerosis defined as coronary artery calcium (CAC) score >10 Agatston units measured by electron-beam computed tomography and detectable aortic plaque measured by magnetic resonance imaging. RESULTS: In univariable analyses (n = 2,744), CAC prevalence was significantly greater only in the fifth versus first quintile of BMI, whereas it increased stepwise across quintiles of WC and WHR (p trend <0.001 for each). After multivariable adjustment for standard risk factors, prevalent CAC was more frequent in the fifth versus first quintile of WHR (odds ratio 1.91, 95% confidence interval 1.30 to 2.80), whereas no independent positive association was observed for BMI or WC. Similar results were observed for aortic plaque in both univariable and multivariable-adjusted analyses. The c-statistic for discrimination of prevalent CAC was greater for WHR compared with BMI and WC in women and men (p < 0.001 vs. BMI; p < 0.01 vs. WC). CONCLUSIONS: We discovered that WHR was independently associated with prevalent atherosclerosis and provided better discrimination than either BMI or WC. The associations between obesity measurements and atherosclerosis mirror those observed between obesity and cardiovascular mortality, suggesting that obesity contributes to cardiovascular mortality via increased atherosclerotic burden.     

Fibrinogen predicts ischaemic stroke and advanced atherosclerosis but not echolucent, rupture-prone carotid plaques: the Copenhagen City Heart Study.

AIMS: Whether the association between fibrinogen and cardiovascular events reflects an association with advanced atherosclerosis in general, or rupture-prone plaques in particular, is unclear. We examined whether fibrinogen predicts incidence of ischaemic stroke, advanced atherosclerosis (measured as carotid artery stenosis) and/or echolucent, rupture-prone plaques. METHODS AND RESULTS: Study 1-8755 Copenhagen City Heart Study stroke-free participants; we observed 235 ischaemic strokes during 6 years of follow-up. Study 2-318 carotid stenosis patients and 1584 age- and gender-matched controls. Study 3-159 patients with echolucent vs 159 patients with echo-rich carotid artery plaques. Fibrinogen above vs below the median value of 3 g l(-1)predicted risk of ischaemic stroke (relative risk: 1.9; 95% CI: 1.4-2.5; 235 events). Significant risk was found in men (2.7; 1.7-4.2; 113 events) and with a similar trend in women (1.4; 0.9-2.0; 122 events), in young (5.2; 1.1-26; eight events) and middle aged (2.9; 1.6-5.4; 64 events) with a similar trend in the elderly (1.4; 1.0-2.0; 163 events). Fibrinogen levels in those with and without ischaemic stroke were 3.6 and 3.1 g l(-1)(ANCOVA: P<0.0001). Likewise, in those with and without carotid artery stenosis fibrinogen levels were 4.7 and 3.1 g l(-1)(P<0.0001); equivalent values for high-sensitive C-reactive protein were 3.6 and 1.4 mg l(-1)(P<0.0001). Finally, neither fibrinogen nor high-sensitive C-reactive protein levels differed between those with echolucent and echo-rich carotid artery plaques (P=0.61 and P=0.28); the power to exclude a 15% increase in fibrinogen or a 50% increase in high-sensitive C-reactive protein was 98 and 54%, respectively. CONCLUSIONS: Elevated fibrinogen predicts future ischaemic strokes, particularly in men and in the young and middle aged. This is most likely a reflection of advanced atherosclerosis, rather than an association with rupture-prone plaques.     

Kinetics of insulin secretion following glucose infusion in patients with atherosclerotic peripheral vascular disease

Summary Kinetics of insulin secretion following an i.v. glucose infusion, according to the protocol described by Cerasi and Luft, were studied in 19 patients with angiographically documented atherosclerotic peripheral vascular disease and in a group of appropriate controls without clinical signs of disease. No significant differences were noted between patients and controls in plasma cholesterol levels and in the K value following a standard i.v. glucose tolerance test. Blood glucose levels were significantly lower in the patients, whereas mean plasma insulin and triglyceride levels were significantly higher. Analysis of the glucose and insulin responses to the glucose infusion test indicated that 31.6% of the patients had a delayed and sluggish insulin response to the glucose load, fitting the criteria suggested for the diagnosis of prediabetes, versus 10% of the appropriate controls. In particular, simulation of the plasma insulin responses by a square-wave glucose stimulus, confirmed that in a significantly higher number of patients the early insulin peak was below normal limits. The results of this study suggest that increased insulin secretion is not present in patients with atherosclerotic vascular disease, in contrast to reports by other authors, and that inefficient insulin secretory mechanisms may be observed in these patients, thus possibly contributing to the development of the atherosclerotic disease.