Key laboratory diagnostic biomarkers of coronary atherosclerosis

Laboratory lipid and lipoprotein biomarkers (total cholesterol - CH, triglycerides - TG, low-density and high-density lipoprotein cholesterol- LDL-CH, HDL-CH, apolipoproteins B and A1 - apoB, apoA1), carbohydrate biomarkers (plasma glucose, basal insulin), high sensitive C-reactive protein (hsCRP) and oxidative biomarkers (basal level of lipid peroxidation [LPO] products in LDL, LDL resistance to oxidation in vitro, oxidative modification of apoLDL and level of LDL lipophilic antioxidants) were studied in 388 men aged 42-70 years: 96 citizens of Western Siberia with angiographically documented coronary atherosclerosis and coronary heart disease (CHD); 292 men of population sample of citizens of Novosibirsk, including 44 men with CHD confirmed by standardized criteria and methods. Significant associations were found of coronary atherosclerosis and CHD with laboratory diagnostic biomarkers like blood levels of HDL-CH, TG, apoB, apoA1, basal insulin, hsCRP and basal level of LPO products in LDL and LDL resistance to oxidation.     

CRP, interleukin-6, secretory phospholipase A2 group IIA, and intercellular adhesion molecule-1 during the early phase of acute coronary syndromes and long-term follow-up

OBJECTIVES: The objectives of this study were to examine the time course of the inflammatory response in acute coronary syndromes (ACS) and to assess the markers of inflammation and their relation to disease severity. METHODS: We prospectively studied 134 patients with ACS who survived for at least 30 months. The patients were divided into four groups: acute myocardial infarction (MI) with (n=54) or without (n=46) ST-segment elevation and unstable angina with (n=14) or without (n=20) increased risk. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A2 group IIA (sPLA2-IIA), and intercellular adhesion molecule-1 (ICAM-1) were measured on days 1 and 4 and after 3 and 30 months. RESULTS: The highest levels of CRP and sPLA2-IIA were seen on day 4 but for IL-6 on day 1. These three markers, but not ICAM-1, were significantly related to disease severity, CKMB, and ejection fraction. Patients in Killip class II-IV had higher levels than those in Killip class I. The individual acute-phase responses correlated with marker levels at 3 and 30 months. ICAM-1 correlated with the development of congestive heart failure. CONCLUSIONS: In ACS there seems to be an individual predisposition to inflammatory response. Plasma IL-6 is the first marker to rise, while sPLA2-IIA and CRP peak later. All three markers, especially CRP, may discriminate between MI and non-MI. ICAM-1 seems to reflect other aspects of the inflammatory processes than the other markers. The results emphasize the complexity of the inflammatory response in ACS and stress the need for further studies involving multiple markers.     

Elevated levels of platelet-monocyte aggregates and related circulating biomarkers in patients with acute coronary syndrome

AimsTo investigate whether patients with acute coronary syndrome (ACS) possessed high levels of platelet–monocyte aggregates (PMAs) and related circulating biomarkers.Methods74 ACS patients, 58 stable angina pectoris (SAP) patients and 46 control patients without coronary artery disease were selected and their PMAs were measured by flow cytometry. Their plasma IL-6, IL-8, MCP-1, soluble CD40L and soluble P-selectin were also measured simultaneously by flow cytometry.ResultsPatients with ACS exhibited higher level of PMAs compared with SAP patients and the control. Furthermore, the levels of IL-6, IL-8, MCP-1, soluble CD40L, soluble P-selectin and CRP were also significantly higher in ACS patients than in SAP patients and the control group. However, there were no significant difference in the levels of IL-8, sCD40L, sP-selectin and CRP between SAP patients and the control group. Correlation analysis showed that high levels of IL-6 and sP-selectin were significantly correlated with PMAs. Logistic analysis further demonstrated that the presence of elevated CRP, IL-6 and PMAs level each confers an increased risk of ACS.ConclusionElevated levels of PMAs and related circulating biomarkers might indicate the unstable coronary syndrome in ACS patients, and the levels of PMAs, CRP and IL-6 could be used for monitoring and guiding the early intervention of ACS patients.     

C-reactive protein increase in unstable coronary disease cause or effect?

A crucial point in understanding the clinical and pathophysiologic meaning of C-reactive protein (CRP) elevation in acute coronary syndromes (ACS) is whether CRP release is predominantly a response to even small amounts of myocardial necrosis, for which troponin is a sensitive and specific marker, or is an independent indicator of the inflammatory process occurring in that clinical condition. Whereas troponin is a good predictor of both mortality and myocardial infarction (MI), although the highest values are associated with a decreased probability of MI, CRP predicts mortality but has no relation with the early or late occurrence of MI. The large variability of CRP values in ACS may depend on the different response of this inflammation marker to various stimuli, some patients being particularly hyperresponsive, especially those with elevated CRP values at baseline. We hypothesize that myonecrosis, as detected by troponin increases, would represent the strongest stimulus for CRP increase in ACS, causing in some patients, especially those with already-elevated CRP values at baseline, a disproportionate increase of this marker. Accordingly, the highest CRP values during ACS are likely to be observed in patients with already-elevated CRP values at baseline (which would increase the probability of having death and MI in the follow-up) and the highest troponin values (which would increase the probability of death in the follow-up, but not of subsequent MI). This hypothesis would explain why high CRP levels in unstable coronary disease are good predictors of death, but not of MI.     

Projected life-expectancy gains with statin therapy for individuals with elevated C-reactive protein levels

OBJECTIVES: We sought to estimate the potential gains in life expectancy achieved with statin therapy for individuals without overt hyperlipidemia but with elevated C-reactive protein (CRP) levels. BACKGROUND: Persons with low-density lipoprotein (LDL) cholesterol levels below current treatment guidelines and elevated CRP levels are at increased risk of cardiovascular disease and may benefit from statin therapy. METHODS: We constructed a decision-analytic model to estimate the gains in life expectancy with statin therapy for individuals without overt hyperlipidemia but with elevated CRP levels. The annual risks of myocardial infarction (MI) and stroke, as well as the efficacy of statin therapy, were based on evidence from randomized trials. Estimates of prognosis after MI or stroke were derived from population-based studies. RESULTS: We estimated that 58-year-old men and women with CRP levels >or=0.16 mg/dl but LDL cholesterol <149 mg/dl would gain 6.6 months and 6.4 months of life expectancy, respectively, with statin therapy. These gains were similar to those for patients with LDL cholesterol >or=149 mg/dl (6.7 months for men and 6.6 months for women). In sensitivity analyses, we identified the baseline risk of MI and the efficacy of statin therapy for preventing MI as the most important factors in determining the magnitude of benefit with statin therapy. CONCLUSIONS: Our results suggest that individuals with elevated CRP levels, many of whom do not meet current National Cholesterol Education Program guidelines for drug treatment, may receive a substantial benefit from statin therapy. This analysis supports a crucial need for direct intervention trials aimed at subjects with elevated CRP levels.     

辛伐他汀调脂干预治疗急性冠脉综合征病人血浆CRP及NO水平的影响

目的探讨辛伐他汀对急性冠状动脉综合征(ACS)病人血浆C-反应蛋白(CRP)及血脂干预的作用。方法符合ACS诊断标准的病人73例,随机分成辛伐他汀组(治疗组)和常规组(对照组),分别在治疗前和治疗28d后,清晨空腹抽静脉血5mL,应用速率散射免疫比浊法测定血浆CRP,同时测定血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、一氧化氮(NO)等水平。结果治疗组CRP,LDL,TC,TG较对照组明显下降(P<0.05或P<0.01),而NO水平明显升高(P<0.01)。结论辛伐他汀调脂干预治疗,能够降低ACS应激反应,减轻冠状动脉粥样硬化的炎症反应和脂质过氧化损伤,改善冠状动脉内皮细胞功能。     

Apolipoprotein E genotype and circulating interleukin-10 levels in patients with stable and unstable coronary artery disease.

OBJECTIVES: This study was designed to assess the relation between apolipoprotein E (apoE) genotype and serum interleukin (IL)-10 levels in patients with acute coronary syndrome (ACS) and chronic stable angina (CSA). BACKGROUND: Genetic variations in the apoE gene affect the risk for coronary artery disease (i.e., carriers of the e4 allele have an increased risk). Increased levels of C-reactive protein (CRP), an inflammatory marker, correlate with an increased risk of acute coronary events, whereas increased IL-10 concentrations have an atheroprotective role. Studies have reported a negative association between the apoE e4 allele and CRP levels. METHODS: Apolipoprotein E genotypes were assessed in 166 consecutive ACS patients (119 men, mean age 68 years, interquartile range [IQR] 60 to 74 years) and 70 CSA patients (54 men, mean age 65 years, IQR 62 to 68 years). Serum IL-10 and CRP were assessed at study entry. RESULTS: Analysis of covariance showed that genetic variation in the apoE gene locus significantly influences serum IL-10 levels in both ACS (p = 0.009) and CSA patients (p = 0.013). Among ACS patients, IL-10 levels were lower in E3/E4 carriers compared with E3/E3 carriers (p = 0.01) and marginally lower compared with E2/E3 carriers (p = 0.065). Among CSA patients, IL-10 levels were lower in E3/E4 carriers compared with E2/E3 carriers (p = 0.004) and marginally lower compared with E3/E3 carriers (p = 0.086). CONCLUSIONS: The IL-10 concentrations differ in ACS and in CSA patients with different apoE genotypes. The e4 allele was associated with a trend toward lower IL-10 serum levels. Our results may provide an explanation of findings in previous studies that cardiovascular risk is higher in e4 carriers despite the presence of low CRP levels.     

Associations of plasma pro-inflammatory cytokines, fibrinogen, viscosity and C-reactive protein with cardiovascular risk factors and social deprivation: the fourth Glasgow MONICA study

Circulating inflammatory markers [plasma fibrinogen, viscosity and C-reactive protein (CRP)] have been associated with cardiovascular risk factors. In part, these associations may reflect 'upstream' changes in pro-inflammatory cytokines – interleukin (IL)-6, IL-18 and tumour necrosis factor (TNF)α. These variables were measured in 1666 men and women aged 25–64 years and their associations with risk factors were studied. All six markers increased significantly with age. IL-18 and TNFα levels were higher, and fibrinogen levels lower, in males. Oral contraceptive use increased levels of CRP, whilst postmenopausal women had elevated IL-18 levels. Inflammatory markers were also associated with components of the metabolic syndrome. Most inflammatory markers showed an increasing trend with alcohol consumption in men and a decreasing trend in women, and increasing trends with level of smoking. Inflammatory markers generally showed strong positive associations with social deprivation. After adjustment for classical risk factors, IL-6, IL-18 and TNFα retained significant associations with social deprivation only in men ( P  < 0·008). We conclude that pro-inflammatory cytokines are associated with several cardiovascular risk factors including social deprivation, and may mediate some of their associations with 'downstream' inflammatory markers (fibrinogen, viscosity and CRP).     

Inflammation,atherosclerosis and acute coronary syndromes

Inflammatory mechanisms play a pivotal role in the atherosclerotic process. At the base of atherogenesis there are complex interactions between macrophages, T lymphocytes and smooth muscle cells. A growing body of experimental evidences suggest that inflammation is involved in the pathogenesis of acute coronary syndromes (ACS) and influences their clinical evolution. In fact, in patients with ACS, coronary atherosclerotic plaques are characterized by an abundant inflammatory infiltrate. Moreover, in these patients systemic signs of inflammatory reaction can be observed: activated circulating inflammatory cells (neutrophil, monocytes and lymphocytes) and increased concentrations of pro-inflammatory cytokines, such as interleukin (IL)-1 and 6, and of acute phase reactants, in particular C-reactive protein (CRP). Recent data demonstrate that CRP is a strong independent predictor of adverse cardiac events and death in patients with ACS, but also in patients with stable ischemic heart disease and in apparently healthy men and women. Furthermore, CRP is an important prognostic index, for early and late outcome, in patients undergoing percutaneous coronary interventions, and may be useful in choosing the therapeutic management of the patient. Although the causes of inflammation in patients with ACS are not yet clear, this new line of research may open the way to a different clinical approach for these patients.     

Interaction between inflammation and thrombosis in acute coronary syndrome

BACKGROUND: Inflammation and thrombosis are important in the pathogenesis of acute coronary syndrome (ACS). Cytokines [interleukin-1beta (IL-1beta) and interleukin-6 (IL-6)] are inflammation markers which play a major role in the development of coronary heart disease. Experimental data documented that an increase of cytokine and von Willebrand factor (vWF) levels in unstable angina (UA) and non-Q wave myocardial infarction (MI) predicts an adverse outcome. AIM: To examine the correlation between the IL-1beta, IL-6 and vWF levels in patients with ACS. METHODS: We examined 92 patients (74 men, 18 women, aged from 43 to 76) divided into 3 groups. The first group included 43 patients with a Q-wave MI, the second group - 33 with a non-Q-wave MI, and the third group - 18 with UA. All patients were given 125-250 mg of aspirin and bolus of 5.000 units of unfractionated heparin, followed by heparin infusion titrated to maintain an activated partial thromboplastin time of 50-75 s. Patients with a Q-wave MI received thrombolytic therapy 1.5 million units of streptokinase. The IL-1b, IL-6 and vWF levels was measured on admission and 7 as well as 21 days later. Fifteen patients with stable angina served as the control group. RESULTS: The levels of cytokines and vWF were significantly higher in patients with ACS than in control subjects. A significant correlation between vWF and IL-6 levels, measured on admission and 7 days later, was found in patients with UA (r=+0.74 and r=+0.55, respectively). Also, a significant correlation was found between vWF and IL-1beta levels measured on admission in patients with either Q-wave or non-Q wave MI (r=+0.7 and r=+0.61, respectively). CONCLUSIONS: Our data suggest that there is a positive correlation between inflammation and thrombosis markers in patients with ACS.     

Association of interleukin-6 and C-reactive protein with subclinical carotid atherosclerosis (the Rancho Bernardo Study)

Studies of interleukin-6 (IL-6) and C-reactive protein (CRP) as predictors of atherosclerosis have had mixed results. The purpose of this study was to assess the associations of IL-6 and CRP with the severity of subclinical carotid atherosclerosis measured 12 years later. Participants were 392 adults (56.9% women, mean age 63.2 years) from the Rancho Bernardo Study who had biomarkers measured from 1984 to 1987 and carotid intima-media thickness (IMT) measured from 1996 to 1998. Age-adjusted mean carotid IMT was significantly greater in men than women. After adjusting for traditional cardiovascular risk factors, carotid IMT increased significantly with increasing IL-6 quartiles (p <0.001). In similar analyses, the association between CRP quartiles and carotid IMT was weaker but remained statistically significant (p <0.05). In multiple regression analysis, IL-6 was significantly associated with carotid IMT regardless of CRP. Conversely, CRP was significantly associated with carotid IMT when IL-6 was not included in the model, but this association became nonsignificant when IL-6 was included. In conclusion, baseline IL-6 and CRP were significantly associated with carotid atherosclerosis independent of traditional cardiovascular disease risk factors. The association of IL-6 was independent of CRP, but not vice versa, suggesting an effect of IL-6 on an earlier state of atherosclerosis.     

Gender specific associations between matrix metalloproteinases and inflammatory markers in post myocardial infarction patients

ObjectiveAtherothrombotic disease in the coronary arteries leads to myocardial infarction (MI) through plaque rupture or erosion of the endothelium, the former mechanism predominating in men and the latter in women. Inflammation is a key feature of these processes, and the interplay between inflammation and matrix metalloproteinases (MMPs) in this context is not fully understood. In this study, we investigated the association between inflammatory markers and MMPs in men and women.MethodsBlood samples were drawn 3 months after a first MI in 387 patients and 387 sex- and age-matched controls (82% men). C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, -18, tumour necrosis factor-α (TNF-α), macrophage chemoattractant protein-1 (MCP-1), MMP-1, -3 and -9 were measured. Coronary angiography was performed in 243 of the patients, and they were classified into 0-, 1-, 2- or 3-vessel disease groups.ResultsCRP, IL-6, -8, -18 and TNF-α were higher, and MMP-3 and -9 were lower, in patients than in controls. A greater proportion of women (49%) had 0-vessel disease than men (16%, p < 0.0001). A gender specific pattern of associations between inflammatory markers and MMPs was found as IL-6 (r_S = 0.29, p < 0.05), IL-18 (r_S = 0.34, p < 0.01) and MCP-1 (r_S = 0.35, p < 0.01) correlated with MMP-3 in female patients, whereas CRP (r_S = 0.23, p < 0.0001), IL-6 (r_S = 0.13, p < 0.05) and IL-8 (r_S = ?0.21, p < 0.01) correlated with MMP-9 in male patients.ConclusionsThe present study demonstrates different patterns of association between inflammatory markers and MMPs in men and women, strengthening the hypothesis of gender specific differences in pathophysiological mechanisms of MI.     

Role of novel biomarkers of inflammation in patients with stable coronary heart disease

Atherosclerosis is a dynamic chronic inflammatory process, and some inflammatory biomarkers have roles in this process. The levels of C-reactive protein (CRP) in patients with chronic stable coronary heart disease (CHD) have not been investigated well, and the levels of macrophage colony-stimulating factor (M-CSF) and interleukin-3 (IL-3) in patients with chronic stable CHD and the effects of these cytokines on atherogenesis are not known. To determine whether new inflammatory biomarkers have roles in atherosclerosis, the authors measured the levels of CRP, M-CSF, and IL-3 in patients with chronic stable CHD and in healthy controls. They measured plasma CRP concentrations by using a highly sensitive CRP reagent with immunonephelometric method, and plasma M-CSF and IL-3 concentrations with the help of a commercial enzyme-linked immunoassay test in 31 patients with chronic stable CHD documented by coronary angiography and in 22 age-matched healthy control subjects documented by coronary angiography. Mean plasma CRP, M-CSF, and IL-3 concentrations in patients with chronic stable CHD were significantly higher than those in controls (8.2 vs 4.6 mg/L, 195.3 vs 28.9 pg/mL, 173 vs 118 ng/mL, respectively, ppi.05). CRP, M-CSF, and IL-3 were all increased in patients with chronic stable CHD relative to controls. These findings suggest that these are new inflammatory biomarkers that may have important roles in the development of atherosclerotic lesions.     

急性冠状动脉综合征患者血清炎性细胞因子水平及临床意义

目的通过对急性冠状动脉综合征患者血清炎性细胞因子水平的测定及比较,分析炎症及细胞因子在急性冠状动脉综合征发生发展过程中的作用及临床意义。方法选择急性心肌梗死(AMI)患者44例(AMI组),不稳定性心绞痛(UAP)患者44例(UAP组),稳定性心绞痛(SAP)患者43例(SAP组),无冠心病患者35例(对照组),分别检测各组患者血清白细胞介素6(IL-6)、白细胞介素8(IL-8)、白细胞介素10(IL-10)、TNF-α、C反应蛋白(CRP)和基质金属蛋白酶9(MMP-9)浓度并进行比较。结果 AMI组患者血清IL-6、IL-8、IL-10、TNF-α、CRP和MMP-9水平均明显高于SAP组和对照组(P<0.01);AMI组患者血清IL-10、TNF-α、CRP、MMP-9水平明显高于UAP组(P<0.05);UAP组患者血清IL-6、IL-8、IL-10水平明显高于SAP组和对照组;MMP-9和CRP与IL-6呈正相关(r=0.308,r=0.384,P<0.01)。结论冠心痛与炎性反应密切相关,多种细胞因子参与了动脉粥样硬化斑块的形成和进程,血清炎性细胞因子水平的升高是冠状动脉粥样硬化斑块不稳定的标志。     

Gender differences in acute coronary syndrome: invasive versus conservative approach

Acute coronary syndrome (ACS) is common in women, yet we have less sex-specific data in women than in men as a result of lower enrollment in clinical trials and low rates of sex-specific reporting. Women are generally older with more comorbidities when diagnosed with ACS. Women with ACS are less likely than men to be referred for invasive evaluation and procedures and are more likely to have normal coronary arteries when they are referred for coronary angiography. For reasons that are not well understood, women have higher rates of bleeding complications compared with men. This higher bleeding rate is consistently seen in many trials. There are 3 major randomized, controlled trials that compared early invasive therapy with conservative strategy for ACS. Two of these trials found higher rates of myocardial infarction (MI) and death at 1 year in women treated with early invasive strategy, whereas the third trial found a reduction in the composite end point of rehospitalization, MI, and death at 180 days in women treated with early invasive strategy. Sex differences have also been seen in glycoprotein (GP) IIb/IIIa use in women with an increase in death and MI noted for GP use in women with ACS. Continued and increased numbers of women in clinical studies of ACS as well as increased rates of sex-specific reporting will allow us to offer optimal quality care for women and men with ACS.     

Diabetes mellitus: clinical presentation and outcome in men and women with acute coronary syndromes. Data from the Euro Heart Survey ACS.

AIMS: To study clinical presentation, in-hospital course and short-term prognosis in men and women with diabetes mellitus and acute coronary syndromes (ACS). METHODS: Men (n = 6488, 21.2% with diabetes) and 2809 women (28.7% with diabetes) < or = 80 years old, with a discharge diagnosis of ACS were prospectively enrolled in the Euro Heart Survey of ACS. RESULTS: Women with diabetes were more likely to present with ST elevation than non-diabetic women, a difference that became more marked after adjustment for differences in smoking, hypertension, obesity, medication and prior disease [adjusted odds ratio (OR) 1.46 (1.20, 1.78)], whereas there was little difference between diabetic and non-diabetic men [adjusted OR 0.99 (0.86, 1.14)]. In addition, women with diabetes were more likely to develop Q-wave myocardial infarction (MI) than non-diabetic women [adjusted OR 1.61 (1.30, 1.99)], while there was no difference between men with and without diabetes [adjusted OR 0.99 (0.85, 1.15)]. There were significant interactions between sex, diabetes and presenting with ST-elevation ACS (P < 0.001), and Q-wave MI (P < 0.001), respectively. Of the women with diabetes, 7.4% died in hospital, compared with 3.6% of non-diabetic women [adjusted OR 2.13 (1.39, 3.26)], whereas corresponding mortality rates in men with and without diabetes were 4.1% and 3.3%, respectively [OR 1.13 (0.76, 1.67)] (P for diabetes-sex interaction 0.021). CONCLUSION: In women with ACS, diabetes is associated with higher risk of presenting with ST-elevation ACS, developing Q-wave MI, and of in-hospital mortality, whereas in men with ACS diabetes is not significantly associated with increased risk of either. These findings suggest a differential effect of diabetes on the pathophysiology of ACS based on the patient's sex.     

C-reactive protein as a marker for active coronary artery disease in patients with chest pain in the emergency room

BACKGROUND: Markers of inflammation, such as C-reactive protein (CRP), were found to be related to risk for cardiovascular disease (CVD) events in patients with angina pectoris. In addition, recent studies have shown that, in the case of atherosclerosis, increased CRP concentration reflects the inflammatory condition of the vascular wall. HYPOTHESIS: The study was undertaken to determine whether CRP levels in individuals with chest pain attending the emergency room (ER) may be used as a marker of active CVD. METHODS: Serum CRP level was measured in 226 of 326 consecutive patients (128 men, 98 women; mean age 61.3 +/- 5.9 years; range 19-87 years) referred to the ER with chest pain. The decision whether to admit orrelease the subjects was determined without taking the CRP level into account. Follow-up was then performed for 1 year. RESULTS: Eighty-four patients were admitted to the hospital. Of these, 9 with acute coronary syndrome (ACS) had very high levels of CRP (25-40 mg/l), 35 had had an acute coronary event within the preceding 3 months, with levels of CRP 14-20 mg/l. Only eight patients with nonsignificant CVD had elevated CRP levels. Twenty-eight subjects who were released from the ER had elevated CRP levels (7-14 mg/l); 8 of these, in addition to 4 subjects with normal CRP levels, had a late coronary event. CONCLUSION: This study indicates that in patients referred to the ER with chest pain and no other indication for hospitalization, a normal level of CRP suggests safe release. Most hospitalized patients with normal CRP will not have acute coronary syndrome. Patients who will develop early coronary events have very high CRP levels. High serum CRP level, after excluding other inflammatory sources, was proven to be a sensitive diagnostic and prognostic marker for significant coronary disease.     

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.     

Association of body fat with C-reactive protein in rheumatoid arthritis

OBJECTIVE: The serum C-reactive protein (CRP) concentration is commonly used in rheumatoid arthritis (RA) as a surrogate marker of systemic inflammation, presumably induced by synovitis. However, other tissues, such as adipose tissue, can induce CRP production. This study was undertaken to explore the associations between measures of adiposity and CRP levels in RA. METHODS: One hundred ninety-six men and women with RA underwent anthropometric assessment and total body dual-energy x-ray absorptiometry for measurement of total and regional body fat and lean mass. The associations between measures of fat and lean mass and serum levels of CRP and interleukin-6 (IL-6) were determined in analyses stratified by sex, with adjustment for pertinent demographic, lifestyle, and RA disease and treatment covariates as well as for the potential modifying effects of articular activity and biologic pharmacotherapeutic agents. RESULTS: All measures of adiposity were significantly associated with the level of CRP in women, but not in men. In women, the measure of adiposity that showed the strongest association with the CRP level was truncal fat, in which, in adjusted analyses, each kilogram increase was associated with a 0.101-unit increase in the logarithmically transformed CRP level (P < 0.001). Neither the level of articular activity nor the use of biologic agents significantly modified this association in women. However, in men, elevated articular involvement was associated with a decreasing CRP level as truncal fat increased. For all analyses, substitution of IL-6 for CRP produced similar findings. CONCLUSION: Adiposity is independently associated with CRP levels in women with RA, and thus may confound the estimation of RA disease activity when serum CRP concentration is used as a surrogate for systemic inflammation.     

The origins of age-related proinflammatory state

We hypothesized that the rising levels of inflammatory markers with aging is explained by cardiovascular risk factors and morbidity becoming progressively more prevalent in older persons. Information on inflammatory markers, cardiovascular risk factors, and diseases was collected in 595 men and 748 women sampled from the general population (age, 20-102 years). In both men and women, older age was associated with higher levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra), IL-18, C-reactive protein (CRP), and fibrinogen, while soluble IL-6 receptor (sIL-6r) increased significantly with age only in men. Adjusting for cardiovascular risk factors and morbidity, the age regression coefficients became substantially smaller in models predicting IL-6, IL-1ra, IL-18, and fibrinogen and larger in the model predicting sIL6r. Adjustment for cardiovascular morbidity substantially reduced the effect of age on CRP in men but not in women. Findings were confirmed in a subgroup of 51 men and 45 women with low risk profile and no cardiovascular morbidity. Part of the "proinflammatory state" in older persons is related to the high prevalence of cardiovascular risk factor and morbidity.