Peripheral levels of matrix metalloproteinase-9, interleukin-6, and C-reactive protein are elevated in patients with acute coronary syndromes: correlations with serum troponin I

BACKGROUND: Acute coronary syndromes (ACS) are characterized by activation of systemic and local inflammatory mediators. The interrelation between these soluble inflammatory markers and their association with markers of myocardial necrosis have not been extensively studied. HYPOTHESIS: The study was undertaken to evaluate the association of the systemic levels of matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), with C-reactive protein (CRP), interleukin-6 (IL-6), and serum troponin-I in patients admitted with ACS. METHODS: Analysis of serum concentrations of the above inflammatory markers was performed in 53 patients with unstable angina (UA) and in 15 with non-ST-segment elevation myocardial infarction (NSTEMI) within 48 h of admission, and 34 patients with stable coronary artery disease. RESULTS: Compared with patients with stable angina, those with ACS had elevated admission levels of MMP-9 (p = 0.04), CRP (p < 0.001), and IL-6 (p = 0.001), but not TIMP-1 (p = 0.55). Compared with patients with UA, those with NSTEMI also had higher levels of IL-6 (p < 0.001), CRP (p = 0.002), and MMP-9 (p = 0.05). CONCLUSIONS: In patients with ACS, the admission levels of inflammatory mediators, including MMP-9, CRP, and IL-6 are significantly elevated, specifically in association with serum troponin I. Systemic and local markers of inflammatory activity may be directly associated with myocardial injury.     

Correlation between myocardial enzyme serum levels and markers of inflammation with severity of coronary artery disease and Gensini score: A hospital-based,prospective study in Greek patients

Background

Our objective was to associate serum levels of myocardial enzymes and inflammatory biomarkers with severity of coronary artery disease (CAD).

Patients and methods

123 patients participated in our study, including 65 cases of acute myocardial infarction (MI), 27 cases of newly diagnosed CAD – without MI – and 31 controls. In all subjects, myocardial serum enzyme levels (creatine phosphokinase, aspartate aminotransferase, lactate dehydrogenase) and inflammatory indices (C-reactive protein, fibrinogen, white blood cells, and erythrocyte sedimentation rate) were measured. Patients were all submitted to coronary angiography and CAD severity was evaluated by Gensini score.

Results

Significant differences concerning enzyme serum levels and inflammatory indices were found to exist between the three study groups, being highest among patients with acute MI (p < 0.001). A significant association was demonstrated between Gensini score and serum enzyme levels as well as inflammatory biomarkers.

Conclusions

Our findings suggest that serum levels of myocardial enzymes and inflammatory indices correlate with CAD severity in Greek patients.     

生长分化因子-15和基质金属蛋白酶-9在单纯冠状动脉扩张中的作用

目的 探讨血清生长分化因子-15(GDF-15)与基质金属蛋白酶-9(MMP-9)水平的变化与单纯冠状动脉扩张(CAE)的关系.方法 筛选24例单纯CAE患者以及30例冠状动脉粥样硬化性心脏病(CAD)患者和30例冠状动脉正常(NCA)对照,检测3组人血清MMP-9、金属蛋白酶组织抑制剂-1 (TIMP-1)及GDF-15水平,并进一步研究单纯CAE患者血清MMP-9与GDF-15水平的相互关系.结果 与CAD患者和NCA对照相比,CAE患者血清MMP-9(P值分别为P=0.017和P=0.002)和GDF-15(P值分别为P＜0.001和P=0.005)水平明显增高.CAE患者TIMP-1/MMP-9比例显著低于CAD组(P =0.025)和NCA组(P =0.008).在CAE患者的分组研究中,扩张病变血管数量和冠状动脉慢血流均与血清MMP-9和GDF-15无关联.在冠状动脉正常的成年人参考组中,GDF15的上限为400 ng/L,而在CAE患者中,当GDF-15 ＜400 ng/L时,MMP-9随GDF-15升高而递增,当GDF-15 ＞400 ng/L时,MMP-9随GDF-15升高而递减,GDF-15与400 ng/L差值的绝对值与MMP-9负相关(r=-0.057,P=0.005).结论 MMP-9和GDF-15在单纯CAE疾病发展中可能存在一定的关系.     

Prevalence,characteristics, and risk stratification of electrocardiographic and symptomatic silence of myocardial ischemia despite scintigraphically evidenced ischemia in symptomatic patients presenting with severe coronary artery stenosis

Symptoms of angina pectoris and transient ST-segment depression are most commonly used to evidence acute myocardial ischemia during exercise testing. However, the diagnostic accuracy of either or both criteria in relation to clinical characteristics and the patient's exercise response has been a subject of controversy. The prevalence and severity of symptoms of angina pectoris and/or ST-segment depression were studied prospectively in 147 consecutive patients with a history of daily angina pectoris, scintigraphic evidence of exercise-induced myocardial ischemia, and coronary artery stenosis >75%. Logistic regression analysis was applied to determine absence of any or both criteria by the clinical characteristics or exercise response of the patient. During exercise testing, ST-segment response failed to prove scintigraphically evidenced myocardial ischemia in 14/147 patients (10%) and 35/147 patients (24%) when ST-segment depression ≥0.1 in either ≥1 or ≥2 ECG leads was chosen. Symptoms of angina pectoris were found to be absent in 69/147 patients (47%). Only 58 patients (40%) suffered from angina and met the ECG criterion at the time of scintigraphic myocardial ischemia. Absence of ST-segment depression was best predicted by clinical variables such as large myocardial infarction (increase: 2.6 times, p = 0.007), number of stenoses ≥2 (2.0 times, p = 0.023), and presence of diabetes mellitus (4.3 times, p = 0.035). Painless myocardial ischemia was only determined by blood response to exercising. Thus, a double product > 23 increased the risk of painless myocardial ischemia by 1.5 times (p = 0.017). In multivariate analysis, only blood pressure response, infarction size, and the number of diseased vessels were found to be independent predictors of the absence of angina pectoris or ST-segment depression during myocardial ischemia.     

青年冠心病患者冠状动脉病变特点及相关危险因素分析

目的探讨冠状动脉粥样硬化性心脏病(冠心病)的临床特点在青年与老年患者间的差异。方法回顾性分析48例青年冠心病患者与156例老年冠心病患者的临床资料,着重分析比较两组的危险因素及冠状动脉造影结果。结果青年组冠心病患者女性比例占6.25%(3/48),明显低于老年组的33.33%(52/156),差异有统计学意义(P0.01)。青年组体质量指数明显高于老年组,差异有统计学意义[(27.03±2.73)kg/m2vs.(25.16±3.05)kg/m2,P0.01]。青年组大量吸烟的比例也远高于老年组,差异有统计学意义[75.00%(36/48)vs.36.54%(57/156),P0.01]。老年组合并原发性高血压、糖尿病的发生率高于青年组,差异有统计学意义[51.28%(80/156)vs.16.67%(8/48),P0.01;30.77%(48/156)vs.6.25%(3/48),P0.01]。青年组血浆总胆固醇,低密度脂蛋白胆固醇及三酰甘油浓度与老年组比较,差异无统计学意义(P0.05)。青年组高密度脂蛋白胆固醇浓度低于老年组,差异有统计学意义[(0.85±1.80)mmol/Lvs.(1.08±0.23)mmol/L,P0.01]。青年组血浆尿酸浓度高于老年组,差异有统计学意义[(349.10±67.02)mmol/lvs.(323.77±73.82)mmol/L,P0.01]。青年组冠状动脉病变以单支病变为主,且左前降支病变发生率最高。结论男性、肥胖、大量吸烟为青年冠心病主要发病危险因素,低高密度脂蛋白胆固醇浓度和高尿酸浓度也可能为青年冠心病的危险因素;青年冠状动脉病变轻,以单支病变为主。     

Echocardiography and coronary artery disease

Echocardiography is playing an increasingly important role in the management of patients with coronary artery disease. With the addition of new digital technology and new technological advances, such as multiplane transesophageal echocardiography and intravascular ultrasound, there is every expectation that this use of cardiac ultrasound will grow even more rapidly in the near future.     

冠心病患者肾动脉狭窄及其相关因素分析

目的　探讨接受冠状动脉造影及冠心病患者合并肾动脉狭窄的发生率及其危险因素。方法　对连续 15 7例接受冠状动脉造影的患者进行腹主动脉数字减影血管造影检查。结果　 15 7例患者中 ,肾动脉狭窄发生率为 14 0 % ;经冠状动脉造影证实的 81例冠心病患者中 ,肾动脉狭窄的发生率为 2 5 9% ;冠状动脉造影完全正常的 62例患者中 ,无 1例有肾动脉狭窄。多元Logistic回归分析表明 ,冠心病、糖尿病及血肌酐 >10 0 μmol/L是存在肾动脉狭窄的独立预测因素。 结论　对冠心病合并高血压、糖尿病、特别是血肌酐 >10 0 μmol/L的患者 ,冠状动脉造影时应常规进行腹主动脉造影检查 ,以尽早发现肾动脉狭窄。     

不同程度狭窄病变冠心病患者介入治疗后心肌灌注变化及临床意义

目的利用经冠状动脉超声心肌声学造影（MCE）比较单支血管不同程度狭窄病变冠心病患者经皮冠状动脉介入术（PCI）后心肌灌注的变化,并探讨其临床意义。方法62例进行PCI治疗的住院患者根据选择性冠状动脉造影结果,按血管狭窄程度分组:A组,血管狭窄75%95%;B组,血管狭窄>95%;C组,急性血管闭塞。PCI前及术后15 min进行经冠状动脉MCE,检测心肌灌注状况。其中,MCE有关定量参数分别为:造影剂峰值密度反映心肌血容量;峰值时间反映心肌灌注速度;曲线下面积反映心肌血流量。结果所有患者PC I后均达到TIMIⅢ级血流;A组术后心肌血流量较术前增加（P<0.05）;B组心肌血容量及血流量也较术前增加（P<0.05）;而C组心肌血容量、血流量及灌注速度较术前增加更显著（P<0.01）。结论不同狭窄程度病变冠心病患者,PCI后心肌灌注均得到不同程度改善,其中,以急性闭塞病变改善最明显,该类患者为PCI治疗的最大获益者。     

脑卒中患者基质金属蛋白酶基因多态性研究

目的探讨基质金属蛋白酶(MMP)-2和MMP-9基因多态性位点与脑卒中的关系。方法选择脑卒中患者348例为脑卒中组和健康体检者235例为对照组,采用限制性片段长度多态性分析技术检测MMP-2基因C1306T、C735T和MMP-9基因C1562T多态的分布特点并进行分析。根据诊断又将脑卒中患者分为脑出血组(116例)、脑梗死组(115例)、脑栓塞组(31例)、腔隙性脑梗死组(86例)。结果与对照组比较,脑卒中组收缩压、舒张压和TG水平明显升高,吸烟、颈动脉粥样硬化比例明显升高,差异有统计学意义(P<0.05)。脑出血组和脑梗死组MMP-9 C1562T的CT+TT基因型频率和T等位基因频率明显高于对照组(P<0.05)。脑梗死组MMP-2C735T的CC基因型频率和C等位基因频率明显高于对照组(P<0.05)。MMP-2、MMP-9各基因型均不是脑卒中预后影响因素。结论 MMP-2 C735T的C等位基因、MMP-9 C1562T的T等位基因是脑梗死的遗传易感基因之一,同时后者也是脑出血的遗传易感基因之一。MMP-2、MMP-9基因多态性与脑卒中预后无关。     

Increased plasma endothelin levels in angina patients with rapid coronary artery disease progression.

AIMS: To investigate the association between plasma endothelin levels and rapid coronary artery disease progression, as assessed by quantitative angiography. METHODS AND RESULTS: Changes in diameter were assessed in 224 coronary stenoses of 92 consecutive patients (62 men) with chronic stable angina pectoris who were on a waiting list for routine coronary angioplasty and underwent coronary angiography on two occasions: the first (diagnostic) angiogram was carried out at study entry and the second 5.5+/-3.0 months later, immediately prior to coronary angioplasty. A digital quantitative angiographic analysis system was used to assess differences in stenosis diameter between the first and second angiogram. Plasma immunoreactive endothelin levels were estimated by radioimmunoassay at study entry. Rapid coronary artery disease progression occurred in 29 (31.5%) patients according to pre-established criteria: 12 (41%) had a > or =10% diameter reduction of at least one pre-existing stenosis > or =50%, 10 (34%) had a > or =30% diameter reduction of a pre-existing stenosis <50%, 5 (17%) patients developed a new stenosis and 2 (7%) had progression of a lesion to total occlusion by the second angiogram. Baseline demographic, clinical and angiographic data were similar in patients with and without stenosis progression. Plasma endothelin levels were significantly higher in patients with rapid disease progression than in those without (5.7+/-2.0 pg. ml(-1)vs 3.9+/-1.6 pg. ml(-1), P<0.001). Multiple logistic regression analysis revealed that endothelin was an independent predictor of disease progression (P=0.001). Moreover, endothelin levels above 4.26 pg. ml(-1)(the median of the total endothelin concentrations) were associated with a sixfold increase in the risk of developing rapid stenosis progression. CONCLUSIONS: Plasma endothelin is raised in patients with coronary artery disease progression and may be a marker of risk of rapid stenosis progression. Endothelin may also play a pathogenic role in this process.     

Relationship of circulating thyroid antibodies to coronary artery disease

A study of the relationship between circulating thyroid antibodies and coronary artery disease was performed. In 180 patients, the state of the coronary arteries was determined by cardiac catheterization and antithyroglobulin and antimicrosomal antibodies were measured using immunoprecipitation. The prevalence of risk factors for coronary artery disease and the mean age of the groups with and without coronary artery disease were similar. There was no significant difference in the prevalence of thyroid antibodies in patients with or without coronary artery disease.     

Low urinary 6-sulphatoxymelatonin levels in patients with coronary artery disease

A decrease in nocturnal serum melatonin levels was reported in patients with clinically uncharacterized coronary artery disease. To assess whether there was a correlation between melatonin production and disease stage, we measured the nocturnal urinary excretion of 6-sulphatoxymelatonin (an index of blood melatonin concentration) in patients with chronic stable or unstable coronary disease and in a group of age-matched controls. Three groups of individuals were studied: a) 24 healthy subjects (mean age: 63 +/- 13 yr); b) 32 patients with chronic, stable, coronary disease (62 +/- 11 yr); and c) 27 patients with unstable angina (62 +/- 12 yr). For 6-sulphatoxymelatonin measurement, urine was collected from 18:00 to 06:00 hr, within 48 hr of hospitalization in the case of unstable angina. 6-Sulphatoxymelatonin was measured by a specific radioimmunoassay. Urinary 6-sulphatoxymelatonin excretion was significantly lower in unstable angina patients than in healthy subjects or in patients with stable angina. 6-Sulphatoxymelatonin correlated negatively with age in healthy subjects, but not in coronary patients. 6-Sulphatoxymelatonin excretion in patients treated with beta-adrenoceptor blockers did not differ significantly from coronary patients not receiving beta-blockers. The results indicate that patients with coronary disease have a low melatonin production rate, with greater decreases in those with higher risk of cardiac infarction and/or death.     

Current use of beta-blockers in patients with coronary artery disease

Beta-blockers have long comprised a cornerstone in the symptomatic treatment of ischemic heart disease and in the secondary prevention of myocardial infarction and heart failure. The majority of studies underlying the evidence of a beneficial effect of beta-blockers on outcomes were conducted more than 25 years ago. In a contemporary era where treatment strategies and secondary prophylactic therapy have undergone several changes, the continued role of beta-blockers in ischemic heart disease has been questioned, especially in the absence of heart failure or a recent myocardial infarction. In summary, few randomized clinical trials are available on the effect of beta-blockers in the reperfusion era, especially on hard endpoints. Likewise, the results of numerous observational studies and meta-analysis are conflicting, emphasizing the need for additional large-scale randomized clinical trials to evaluate the role of beta-blocker therapy in current clinical practice.     

Nocturnal myocardial ischemic events and sleep-disordered breathing in patients with coronary artery disease

Objective To investigate the occurrence of nocturnal myocardial ischemia and its relationship with sleep-disordered breathing(apneas and oxygen desaturations)in patients with angina pectoris undergoing coronary an-giography.Methods Eighty-two men and 14 women referred for consideration of coronary intervention wererandomly selected.Observation by an overnight sleep monitor and Holter recording were performed to studysleep-disordered breathing(oxyhemoglobin desaturations≥4% and apnea-hypopneas),heart rates,and ST-seg-ment depressions(≥1mm,≥1 min).Results Nocturnal ST-segment depressions occurred in 37% of thepatients.ST-segment depression within 2 min after an apnea-hypopnea or desaturation occurred in 17% of thepatients.This temporal association was seen in 21% of the patients with nocturnal ST-segment depressions,morefrequendy in men(P<0.05)and more frequently in those with severe disordered breathing(P<0.05).Mostof these ST-segment depressions were preceded by a series of breathing events:repeated apnea-hypopneas or de-saturations or both in 73% of the patients.Conclusions Episodes of nocturnal myocardial ischemia are com-mon in patients with angina pectoris.A temporal relationship between sleep-disordered breathing and myocardialischemia was present in some of our patients,and occurs more frequently in men and in those with severely dis-ordered breathing.(J Geriatr Cardiol 2004;1(2):90-94.)     

Elevated levels of circulating matrix metalloproteinase-9 in non-small cell lung cancer patients

Elevated levels of matrix metalloproteinase have been implicated as playing important role in tumour progression in several types of cancers. Our aim was to determine whether these enzyme might be a useful tumour marker for lung cancer and also to evaluate the correlation of circulating levels of matrix metalloproteinase-9 (MMP-9) with tumour histology, staging, nodal status, metastasis and prognosis. Blood samples were collected from 35 nonsmall cell lung cancer patients who were diagnosed histologically, and 14 healthy controls. The MMP-9 levels were significantly higher in the cancer group (p< 0.001). However no significant correlation between several clinical features (such as histology of the tumour, staging, tumour status, or nodal status) and plasma MMP-9 levels have been observed. Though it does not show statistical significance, more patients with metastasis seemed to have higher MMP-9 levels. At the end of six month 11 patients were out of follow-up. Among the remaining 24 patients eight patients had lower MMP-9 levels, seven were survivors at the end of six months. Sixteen patients had MMP-9 levels above the threshold. Only 10 have survived to six months. In conclusion MMP-9 can serve as a marker for metastasis and can be valuable in the follow-up of lung cancer patients.     

严重冠脉病变的心电图分析

目的分析左主干、前降支近端或三支病变冠心病心绞痛患者的心电图改变。方法13例冠脉造影诊断为左主干、前降支近端或三支病变的患者,对其静息时、心绞痛发作时心电图有无aVR、V1导联的ST段抬高及临床资料进行分析。结果胸痛发作时11例出现了aVR、V1导联典型改变,静息时2例aVR、V1导联改变。结论心电图aVR、V1导联ST段抬高,尤其STaVR〉STV1,V4～V6导联ST段下移,合并Ⅱ、Ⅲ、aVF导联或Ⅰ、Ⅱ导联ST段下移与冠脉左主干、前降支近端严重狭窄及三支病变有良好的相关性。     

Association between plasma inflammatory markers and morphology of coronary artery lesion in patients with coronary artery disease

The atherosclerotic plaque vulnerability may be related to inflammation,immunity,metabolism and blood clotting.One of the key factors affecting plaque stability is inflammatory reaction.This study was to investigate the relationship between vulnerability of coronary artery plaque evaluated with coronary angiography (CAG),intravascular ultrasound (IVUS) and the levels of plasma inflammatory markers.Methods Fifty-eight consecutive patients with acute coronary syndrome who had coronary lesion of a single vessel were divided into 3 groups based on angiographic morphology of the lesions:type Ⅰ lesion group (n =16),type Ⅱ lesion group (n =25) and type Ⅲ lesion group (n =17).The control group consisted of 17 patients with stable angina.Plasma levels of high sensitivity C reaction protein (hs-CRP),matrix metalloproteinase (MMP,including MMP-2 and MMP-9),CD40 ligand (CD40L) and pregnancy associated plasma protein-A (PAPP-A) were measured by ELISA.A subgroup of 28 patients (including 18 ACS patients and 10 stable angina control patients) who underwent IVUS study,were analyzed.Results The plasma levels of MMP-2,MMP-9 and PAPP-A in type Ⅱ lesion group were significantly higher than those in other groups (all P＜0.05).In type Ⅱ lesion group,linear correlation analyses showed significant positive correlation between levels of hs-CRP and MMP-2 (r=0.508);MMP-2 and MMP-9,CD40L,PAPP-A (r=0.647,0.704 and 0.751,respectively);MMP-9 and CD40L,PAPP-A (r=0.491 and 0.639,respectively);CD40L and PAPP-A (r=0.896).IVUS subgroup analysis showed that the area of plaques and plaque burden in culprit lesion,the incidence of high-risk plaques,remodeling index (RI) and positive remodeling percentage in ACS patients were significantly greater than those in control subgroup (P=0.000,0.037,0.028,0.015 and 0.040,respectively).Compared with control subgroup,the plasma levels of hs-CRP,MMP-2,MMP-9 and PAPP-A were markedly elevated (P=0.033,0.000,0.000 and 0.027,respectively).Conclusions CAG and IVUS combined with study on plasma levels of inflammation mediators are helpful in judging the vulnerability of coronary artery plaques.(J Geriatr Cardiol 2008;5:207-211)