急性冠状动脉综合征中C反应蛋白的临床意义及阿司匹林的作用

为探讨Ｃ反应蛋白与急性冠状动脉综合征的关系及阿司匹林对其的影响,观察４６例急性心肌梗死患者、４０例不稳定性心绞痛虱及４２例稳定性心绞痛患者的Ｃ反应蛋白浓度以及不同剂量的阿司匹林对心肌梗死患者Ｃ反应蛋白浓度的影响。结果发现心肌梗死及不稳定性心绞痛患者的Ｃ反应蛋白浓度较稳定性心绞痛患者显著增高（Ｐ〈０．００１）。小剂量（每天３００ｍｇ）阿司匹林可降低心肌梗死患者的Ｃ反应蛋白浓度（Ｐ〈０．０５）。提示Ｃ反应蛋白浓度可作为评价急性冠状动脉综合征患者预后的一个参考指标。     

Independent prognostic value of C-reactive protein and troponin I in patients with unstable angina or non-Q-wave myocardial infarction.

OBJECTIVES: Elevated concentrations of C-reactive protein (CRP), a non-specific acute phase reactant, and troponin I (TnI), a cardiac-specific marker of myocardial damage, have been found to be associated with a higher risk for cardiac events in patients with an acute coronary syndrome. We evaluated CRP alone and in combination with TnI for predicting the incidence of major cardiac complications within 6 months in patients with unstable angina or non-Q-wave infarction (NQMI). METHODS: CRP and TnI was measured on admission in patients with unstable angina or NQMI, but results were kept blinded. Patients were treated according to a conservative management strategy, and the incidence of major cardiac events within 6 months was assessed. RESULTS: An abnormal CRP (> 5 mg/l) and an abnormal TnI (> 0.4 microgram/l) were more frequent in patients that suffered a major cardiac event (CRP: 93 vs. 35%, P < 0.0001; TnI: 73 vs. 26%, P < 0.001). The incidence of major cardiac events was higher in patients with an abnormal CRP than in patients with a normal CRP, both when TnI was abnormal (42 vs. 4.5%, P = 0.003) and when TnI was normal (11 vs. 0%, P = 0.014). Mean event-free survival was excellent in patients with both a normal CRP and TnI, whereas survival was poorest in patients with both an abnormal CRP and TnI (121 +/- 16 vs. 180 days, P < 0.0001). CONCLUSIONS: An abnormal CRP on admission in patients with unstable angina or NQMI is associated with increased incidence of major cardiac events within 6 months, both in patients with normal and abnormal TnI. CRP and TnI have independent and additive prognostic value in this patient group, and the combination may be useful for early risk stratification.     

Comparison of C-reactive protein and terminal complement complex in patients with unstable angina pectoris versus stable angina pectoris

Elevated C-reactive protein (CRP) can identify patients with coronary artery disease who are prone to future acute events. We investigated whether elevated CRP is related to the activation of the terminal complement cascade in 66 patients with unstable angina pectoris (UAP), in 45 patients with stable angina pectoris, and in 42 controls. CRP, additional acute phase reactants, the terminal complement complex (sC5b-9), leukocytes, and troponin T were measured. In 47 patients with UAP the CRP values were regarded as elevated (>0.3 mg/dl). In patients with UAP and elevated CRP, the plasma levels of sC5b-9 were markedly higher than in patients with UAP and lower CRP (245 +/- 14 vs 188 +/- 19 ng/ml, p <0.02) and in patients with stable angina pectoris with slightly (0.4 +/- 0.1 mg/dl) increased CRP (sC5b-9 173 +/- 21 vs 130 +/- 7 ng/ml [controls; p <0.05]). A further acute phase reaction was present only in patients with UAP and elevated CRP already on admission (p <0.01). sC5b-9 was not related to troponin release. Thus, elevated CRP levels are associated with activation of the plaque destabilizating terminal complement system in patients with UAP during the acute phase reaction. This may explain the prognostic value of CRP in acute coronary syndromes (ACS).     

Akute Koronarsyndrome – ein Update Teil I: Pathogenese und medikamentöse Therapie

BACKGROUND: Unstable angina accounts for more than one million hospital admissions annually. 6-8% of patients with this condition have non-fatal myocardial infarction or die within the first year after diagnosis. Recently, the term "acute coronary syndromes" has been used to describe the spectrum of conditions that includes unstable angina, non-Q-wave myocardial infarction (which generally presents without ST-segment elevation), and Q-wave myocardial infarction (which generally presents with ST-segment elevation). PATHOGENESIS: Disruption of a formed plaque is a complex pathologic process that is central to the initiation of the acute coronary syndromes. Local thrombosis occurring after plaque disruption results from complex interactions among the lipid core, smooth-muscle cells, macrophages, and collagen. TREATMENT: Multiple huge clinical trials confirmed that aspirin reduces the risk of death from cardiac causes and fatal and non-fatal myocardial infarction by about 50-70% in patients presenting with unstable angina. Ticlopidine may be substituted for aspirin in patients with hypersensitivity to aspirin or gastrointestinal intolerance. Clopidogrel acts similarly to ticlopidin but has fewer side effects than ticlopidine and has not been reported to cause neutropenia. High-risk patients with refractory unstable angina and elevated troponin levels may have substantial benefit of glycoptotein (GP) IIb/IIIa inhibition. Current practice guidelines support the use of the combination of unfractionated heparin and aspirin for the treatment of unstable angina. Clinical studies have demonstrated that the incidence of the composite end point of death, myocardial infarction, or recurrent angina was lower with enoxaparin than with unfractionated heparin. Beta-blockers, nitrates, and calcium-channel blockers are useful for antiischemic therapy in patients with acute coronary syndromes.     

C-reactive protein is a marker for a complex culprit lesion anatomy in unstable angina.

BACKGROUND: The putative theory is that the clinical syndrome of unstable angina is caused by rupture of the atherosclerotic plaque with superimposed thrombus formation. It is characterized by angiographically complex coronary lesions in the majority of patients. HYPOTHESIS: This study aimed at assessing the correlation between C-reactive protein (CRP) and the complexity of culprit coronary lesions in unstable angina. METHODS: We identified culprit lesion complexity in 96 patients with unstable angina and normal creatine kinase (CK) and CK-MB mass. Serum concentrations of CRP (N < 5.0 mg/l) and cardiac troponin T (cTnT; N < 0.1 ng/ml) were measured on admission. RESULTS: There was a trend toward a higher grade of anatomical complexity of the culprit lesion in patients with elevated CRP (p = 0.007) and cTnT levels (p = 0.027). Patients who had intermediate- or high-grade lesion severity had a higher level of CRP (8.5 +/- 5.7 mg/l) and cTnT (0.118 +/- 0.205 ng/ml) on admission than those who had normal or low-grade lesions (5.7 +/- 4.0 mg/l, 0.017 +/- 0.021 ng/ml, respectively); Mann-Whitney U, p = 0.002 and p < 0.001, respectively. Furthermore, the likelihood of having intermediate- or high-grade complexity of the culprit lesion was higher when CRP levels were elevated in all patients (p = 0.007, odds ratio [OR] = 4.286; 95% confidence interval [CI] 1.492-12.310) and in those with normal cTnT levels (p = 0.025, OR = 3.876; 95% CI 1.185-12.678). Also, higher CRP levels strongly correlated with the need for revascularization interventions (p < 0.0005). CONCLUSION: Elevated CRP level on admission is a marker for anatomic complexity of culprit lesions and need for revascularization interventions in unstable angina.     

C-reactive protein in patients with acute coronary syndrome: correlation with diagnosis, myocardial damage, ejection fraction and angiographic findings

BACKGROUND: C-reactive protein (CRP) plasmatic levels increase in patients with acute coronary syndromes (ACS). Correlations between CRP levels, myocardial functional damage and cardiomyocyte lysis remain to be defined. METHODS: 192 consecutive patients with acute coronary syndromes (64.97 +/- 11.08 mean age, 71.35% male gender) were included in the study; 138 patients (71.87%) were discharged with an acute myocardial infarction (AMI) diagnosis (28 with non Q-wave AMI) and 54 with an unstable angina (UA) diagnosis (28.13%). In all patients CRP, CK, LDH, CK-MB and troponin I plasmatic concentrations were evaluated every 6 h for 48 h and every 24 h for the following 2 days from the onset of symptoms. Ejection fraction was estimated by bidimensional echocardiography and extension of myocardial lysis by cardiac enzymes plasmatic release. 92 patients (67 with AMI, 25 with UA) underwent coronary-angiography. Incidence of adverse cardiac events was recorded in a 6 months follow up. RESULTS: Mean CRP levels in Q-wave MI showed a statistically significant increase in the different blood samples with baseline. Mean CRP levels of the three groups were not statistically different at baseline and after 6, 12, and 18 h. Q-wave AMI CRP levels showed a statistically significant difference as against non Q-wave AMI at 36 (p < 0.05), 48 (p < 0.05) and 72 h (p < 0.05) and UA at 24 (p < 0.01), 30 (p < 0.01), 48 (p < 0.0001), 72 (p = 0.0001) and 96 h (p = 0.0003); non Q-wave AMI CPR levels showed a statistically significant difference as against UA at 48 h (p < 0.01). CRP peak mean levels were significantly different when comparing Q-wave AMI patients with UA patients (8.21 +/- 7.85 vs. 2.75 +/- 3.33 mg/dl, p < 0.001). In patients with Q-wave AMI there was a correlation between CRP peak concentrations and CK (r = 0.264, p = 0.008) and LDH (r = 0.32, p = 0.001), while correlation with CK-MB peak concentrations was not statistically significant (r = 0.196, p = 0.051). In the same patient group, there was also a correlation between CRP plasmatic concentrations and troponin I plasmatic concentrations from the 30th to 96th h after the onset of symptoms (r = 0.38-0.53, p < 0.05). No correlation was found between CRP levels and ejection fraction and angio-coronarography findings (number of stenotic vessels, culprit lesions, ruptured plaques). Peak CRP levels were associated in a 6 months follow up with an increased incidence of major adverse cardiac events (MACEs) in patients with Q-wave AMI (HR 1.1649, 95% C.I. 1.0197-1.3307, p < 0.05). CONCLUSIONS: CRP plasmatic concentrations showed a different release curve in patients with Q-wave AMI in comparison with patients with non Q-wave AMI and with patients with UA. CRP peak concentrations did not correlate with ejection fraction and angiographic findings, but correlate with incidence of MACE. The increase in CRP levels during Q-wave MI seems to be linked to the extension of myocardial damage rather than pre-existing inflammation.     

Acute and convalescent changes in plasma homocysteine concentrations in acute coronary syndromes

BACKGROUND—Raised plasma homocysteine is a risk factor for coronary artery disease. Patients with myocardial infarction or unstable angina show greater activation of coagulation, greater troponin release, and a worse outcome.OBJECTIVE—To examine variations in plasma homocysteine concentration in relation to C reactive protein (CRP) in patients presenting with acute coronary syndromes.METHODS—Consecutive patients presenting with acute myocardial infarction (22) and unstable angina pectoris (12) were studied. Plasma samples were obtained on admission (before clinical intervention), on days 2, 7, and 28, and again six months after admission. Plasma homocysteine, assayed by high performance liquid chromatography, and CRP were both determined at the same time points. Changes were assessed by analysis of variance.RESULTS—CRP concentrations showed a classical rise on day 2, followed by a gradual decline to normal values taken at six months from admission in both myocardial infarction (p < 0.0001) and unstable angina (p = 0.02). Homocysteine concentrations in myocardial infarction (median, 25th to 75th interquartile range) were: 11.9 (10.7 to 12.6), 11.5 (9.1 to 13.4), 12.1 (11.4 to 14.1), 12.4 (11.1 to 14.4), and 12.1 (11.2 to 14.0) µmol/l, for days 1, 2, 7, 28, and 180, respectively (p = 0.02). Significant differences were observed only between day 2 and day 7 (p < 0.05). The final homocysteine measurement was not different from the admission level. Homocysteine concentrations in unstable angina did not differ between admission and convalescence (12.5 (9.1 to 14.5) µmol/l and 12.3 (7.7 to 14.9) µmol/l, respectively).CONCLUSIONS—Plasma homocysteine concentrations are minimally influenced by acute phase variations with reliable measurements obtained on admission in patients with myocardial infarction and unstable angina.     

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 platelet-monocyte aggregates with platelet activation, systemic inflammation, and myocardial injury in patients with non-st elevation acute coronary syndromes

BACKGROUND: Platelet-monocyte aggregates (PMA) and C-reactive protein (CRP) are increased in unstable coronary disease. The interrelation of PMA with platelet activation, systemic inflammation, and their association with markers of myocardial injury has not been studied extensively. HYPOTHESIS: The study was undertaken to evaluate the association of CRP, PMA, and cardiac troponin I (cTnI) in patients admitted with non-ST elevation acute coronary syndromes (NSTE-ACS). METHODS: In all, 69 consecutive patients with NSTE-ACS, 58 patients with stable angina pectoris (SAP), and 46 control patients without coronary artery disease were selected; PMA, sP-selectin, sCD40L inter leukin, (IL)-6, CRP, and cTnI concentrations were measured in these patients at the time of admission. Patients with NSTE-ACS were classified into two groups: those with troponin normal (cTnI < 0.06 ng/ml) and those with troponin elevation (cTnI > or = 0.06 ng/ml). Their risk for clinical in-hospital cardiac events (death and nonfatal myocardial infarction) was analyzed. RESULTS: Compared with SAP and control, patients with NSTE-ACS exhibited higher levels of PMA, sP-selectin, sCD40L, IL-6, and CRP. All these parameters were found to be higher (p < 0.001 ) in patients with troponin elevation than in those with normal troponin. There was a significant relationship between PMA and CRP (r =0.628, p < 0.001) and cTnI (r = 0.557, p < 0.001) in patients with NSTE-ACS. Logistic analysis further demonstrated that the presence of elevated PMA, CRP, and cTnI levels each confers and increases risk of future cardiac events. CONCLUSIONS: Levels of PMA and CRP were significantly increased in patients with NSTE-ACS, especially in those with troponin elevation. This increase is strongly related to the risk of in-hospital cardiac events. A panel of PMA, CRP, and cTnI may provide important information additional to current laboratory data for the treatment of NSTE-ACS.     

C-reactive protein and myocardial infarction during percutaneous coronary intervention

OBJECTIVE: To evaluate the prognostic information of preprocedural C-reactive protein (CRP) levels in serum to predict myocardial infarction during percutaneous coronary interventions (PCI). DESIGN: Prospective study. SETTING: University hospital. PATIENTS: A total of 400 consecutive patients with normal serum troponin T levels (0.05 microg L-1. RESULTS: Eighty-three patients (21%) experienced a myocardial infarction during PCI. The median value of CRP before the procedure was 1.83 (0.12-99.7) mg L-1. No difference was seen in CRP levels before PCI between patients without or with myocardial infarction during PCI. Multivariate analysis identified stent implantation (OR 2.68, 95% CI 1.18-7.28, P = 0.03), procedure time (OR 2.15, 95% CI 1.28-3.67, P < 0.005) and complications during the procedure (OR 3.62, 95% CI 1.72-7.58, P < 0.001) as independent predictors of myocardial infarction during PCI. CONCLUSION: Increased CRP levels in serum before PCI were not associated with myocardial infarction during the procedure. Furthermore, patients with an expected long procedure and a high probability of stent implantation have an increased risk of developing myocardial infarction during PCI. This finding may be useful to help the operator to decide the antithrombotic regime before, during and after the procedure and the need for observation after the procedure.     

Prognostic value of C-reactive protein and troponin T level in patients with unstable angina pectoris

OBJECTIVES: The prognosis of unstable angina pectoris may be more accurately predicted by the combination of C-reactive protein (CRP), which is a known inflammation marker, and troponin T (TnT), which is used for risk assessment for the prognosis of acute coronary syndrome. The present study investigated the correlations between pathophysiology and prognosis of severe unstable angina pectoris and CRP and TnT levels. METHODS: The correlation between CRP at admission and the prognosis was studied in 367 patients with severe unstable angina pectoris (Braunwald type II and III) who were admitted to our hospital between January 1998 and December 2000. The in-hospital and long-term prognosis was investigated in TnT-positive patients. In-hospital cardiac events were defined as death, myocardial infarction, heart failure and angina attacks during hospitalization. Long-term cardiac events were defined as death, myocardial infarction, heart failure and recurrence of angina. RESULTS: The incidence of in-hospital cardiac events in all patients was 30.2%. The CRP levels were higher in patients with cardiac events (0.97 +/- 2.67 vs 0.53 +/- 1.29 mg/d/, p = 0.057), but there was no significant difference between the two groups. The incidence of long-term cardiac events was 26.8%. The mean CRP level was significantly higher in patients with cardiac events than in patients without cardiac events (1.17 +/- 1.86 vs 0.43 +/- 1.14 mg/dl, p = 0.098). In TnT-positive patients (TnT > 0.1 ng/ml, 23% of all patients), the incidence of in-hospital cardiac events was 47.6% (p < 0.0001), significantly higher than that in all patients. TnT-positive patients with CRP levels of 0.5 mg/dl or higher (8% of all patients) had a markedly higher incidence of in-hospital cardiac events of 56.7% (p = 0.001) and long-term cardiac events of 46.7% (p = 0.01). CONCLUSIONS: CRP levels were useful in prediction of the long-term prognosis. TnT levels were useful in prediction of in-hospital prognosis. The present study suggested the possibility that the combined use of these biological markers could predict the prognosis of patients with unstable angina at early stage and more accurately.     

C-reactive protein and coronary artery disease

Evidence suggests that inflammation plays a key role in the pathogenesis of atherosclerosis. The chronic inflammatory process can develop to an acute clinical event by the induction of plaque rupture and therefore cause acute coronary syndromes. The aim of this study was to determine the serum levels of the circulating acute-phase reactant C-reactive protein (CRP), which is a sensitive indicator of inflammation, in patients with chronic stable coronary artery disease (CAD) and acute coronary syndromes (ACS). We studied 56 subjects: 1) 25 consecutive patients (18 men, 7 women; mean age, 68.5 +/- 14.3 years, range, 40-86) with unstable angina (UA) or acute myocardial infarction (AMI); 2) 31 consecutive patients (25 men, 6 women; mean age 64 +/- 12.7; range, 47-83, years) with signs and symptoms of clinically stable CAD. High-sensitivity-C-reactive protein (hs-CRP) levels were determined with a commercially available enzyme-linked immunoassay method. In patients with unstable angina and AMI before reperfusion therapy, CRP levels were not significantly different to those in patients with stable CAD (5.96 +/- 2.26 versus 4.35 +/- 2.6 mg/L; P = 0.12), but tended to be higher in patients with unstable angina and AMI. Baseline CRP levels in the subgroup of patients with AMI (6.49 +/- 2.28 mg/L) were significantly higher than levels in patients with stable CAD (4.35 +/- 2.6 mg/L; P = 0.02). CRP levels in patients with unstable angina and AMI were measured four times during a 72-hour period (0, 12, 24, and 72 hours). The lowest value was observed at baseline and differed significantly from values measured at any other time of the observation period (P < 0.001; 5.96 +/- 2.26; 9.5 +/- 9.04, 18.25 +/- 11.02; 20.25 +/- 10.61). CRP levels after 12, 24, and 72 hours were also significantly different to the initial values for patients with stable CAD (P < 0.01). There was no correlation between CRP and creatine kinase (CK), CK-MB isoenzyme, or troponin I positivity as markers for the extent of the myocardial injury during the observation period. Baseline levels of serum CRP tended to be higher in patients with unstable angina or AMI but were not significantly different from levels in patients with chronic stable CAD. In the subgroup of patients with AMI, baseline CRP levels were significantly higher than the levels in patients with stable CAD. CRP as a marker of inflammation is significantly increased in patients with AMI and unstable angina shortly after the onset of symptoms (after a period of 12 hours), supporting the hypothesis of an activation of inflammatory mechanisms in patients with an acute coronary syndrome or AMI.     

Prognostic value of C-reactive protein,fibrinogen, interleukin-6, and macrophage colony stimulating factor in severe unstable angina

BACKGROUND: Inflammatory process plays an important role in the pathogenesis of acute coronary syndromes. HYPOTHESIS: The study was undertaken to evaluate whether admission levels of C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6). and macrophage colony stimulating factor (MCSF) can predict short-term prognosis in patients with unstable angina. METHODS: C-reactive protein, fibrinogen, IL-6, and MCSF were measured on admission in 141 consecutive patients, aged 59 +/- 10 years, with unstable angina (Braunwald class IIIb). Patients were divided into two groups according to their in-hospital outcome: Group 1 comprised 77 patients with a complicated course (2 died, 15 developed nonfatal myocardial infarction, and 60 had recurrence of angina), and Group 2 comprised 64 patients with an uneventful course. RESULTS: Admission median levels of CRP (8.8 vs. 3.1 mg/l, p = 0.0002). fibrinogen (392 vs. 340 mg/dl, p = 0.008), IL-6 (8.8 vs. 4.5 pg/ml, p = 0.03), and MCSF (434 vs. 307 pg/ml, p = 0.0001) were higher in Group I than in Group 2. The MCSF levels were an independent risk factor for in-hospital events, with an adjusted odds ratio for eventful in-hospital outcome of 3.3 (95% confidence interval 1-10.9, p = 0.04), and correlated with levels of IL-6 (r(s) = 0.52, p = 0.0001), CRP (r(s) = 0.43, p = 0.0001), and fibrinogen (r(s) = 0.25, p = 0.004). CONCLUSIONS: These findings suggest that among the studied inflammatory indices only increased admission levels of MCSF are strongly and independently related with adverse short-term prognosis in patients with severe unstable angina.     

Serum amyloid A predicts early mortality in acute coronary syndromes: A TIMI 11A substudy

OBJECTIVES: We evaluated the ability of serum amyloid A (SAA), alone and in combination with a rapid qualitative assay for cardiac-specific troponin T (cTnT), to predict 14-day mortality in patients with unstable angina or non-Q wave myocardial infarction (NQMI). BACKGROUND: Elevated C-reactive protein (CRP) has been associated with adverse outcomes in unstable coronary syndromes but data regarding its acute phase counterpart, SAA, are conflicting. METHODS: Serum amyloid A measurement and a rapid cTnT assay were performed on blood obtained at enrollment into Thrombolysis in Myocardial Infarction 11A, a dose-ranging trial of enoxaparin for unstable angina and NQMI. RESULTS: Serum amyloid A was higher in patients who died compared with survivors (6.28 vs. 0.75 mg/dL, p = 0.002). Among patients with a negative rapid cTnT, mortality was higher for those in the top quintile of SAA (6.1 vs. 0.7%, p = 0.003). Patients with both an early positive rapid cTnT (< or =10 min until assay positive) and SAA in the fifth quintile had the highest mortality followed by those with either markedly elevated SAA or an early positive rapid cTnT, while patients with both a negative rapid cTnT and SAA in quintiles 1-4 were at very low risk, (9.1 vs. 3.6 vs. 0.7%, p <0.002). CONCLUSIONS: Similar to CRP, baseline elevation of SAA identifies patients hospitalized with unstable angina and NQMI at higher risk for early mortality, even among those with a negative rapid assay for cTnT. These data support further investigation of inflammatory markers used alone and in combination with cardiac troponins for risk assessment in unstable coronary syndromes.     

Kinetics of C-reactive protein release in different forms of acute coronary syndrome

INTRODUCTION AND OBJECTIVES: Better knowledge of C-reactive protein (CRP) kinetics could lead to improved clinical application of this biomarker. METHODS: We studied 110 patients: 42 had ST-elevation acute myocardial infarction (STEMI), 35 had non-ST-elevation acute myocardial infarction (NSTEMI), and 33 had unstable angina. Patients were admitted to our institution within 6 hours of symptom onset. The levels of CRP, troponin-I, and creatine kinase MB fraction (CK-MB) were measured on admission and every 6 hours during the first 48 h. The CRP level was also measured daily until hospital discharge. RESULTS: The median (interquartile range) CRP level increased relative to baseline from 6 hours after admission, from 5 (2-9) mg/L to 6 (3-10) mg/L (P=.004). Although, CRP levels on admission were similar in all groups, there was a significant difference in peak CRP level: it was 67 (36-112) mg/L in the STEMI group, 29 (20-87) mg/L in the NSTEMI group, and 18 (12-36) mg/L in the unstable angina group. The maximum CRP level was observed 49 (38-53) hours after the onset of symptoms, but occurred later in patients with STEMI. Although there was only a weak non-significant correlation between CRP and troponin levels (r=0.135) at admission, the maximum CRP level was found to be influenced by the degree of myocardial damage (r=0.496; P< .001). CONCLUSIONS: The pattern of CRP release observed was clearly different in different forms of acute coronary syndrome. Although the CRP level measured at admission was similar in all patient groups, it was influenced by the degree of early myocardial tissue necrosis. This variation in CRP kinetics should be taken into consideration when designing future studies.     

Relationship Between Minor Myocardial Damage and Inflammatory Acute-Phase Reaction in Acute Coronary Syndromes

Background: In severe acute coronary syndromes (ACS) elevation of markers of inflammation and acute phase reaction (APR) like C-reactive protein (CRP) as well as a release of troponin have been reported.Using a high sensitivity troponin T (TnT) test we investigated whether an APR occurs in ACS only in the presence of ischemic myocardial damage. Methods: In 85 patients with ACS C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, thrombin antithrombin III complexes (TAT) and kallikrein were determined vs. high sensitive TnT (0.02 ng/ml) initially and 2 d later vs. 45 patients with stable angina pectoris and 42 controls. Results: In stable angina pectoris, markers of inflammation and coagulation were slightly elevated (p < 0.05). Initially in ACS elevations of CRP to 1.2 ± 0.3 mg/dl, SAA to 4.8 ± 2.6 mg/dl and fibrinogen to 448 ± 21 mg/dl (all p < 0.01 vs. controls) were found followed by a significant APR (p < 0.01).In the subgroup of TnT positive ACS patients, an APR with increased CRP (4.1 ± 1.3 mg/dl), SAA (20.4 ± 8.3 mg/dl), and fibrinogen (641 ± 45 mg/dl) was detectable (all p < 0.05 vs. TnT negative patients). In contrast, patients without TnT release showed APR markers comparable to patients with stable angina pectoris. Conclusion: Our findings demonstrate an association between myocardial injury in ACS and acute phase reaction as evidenced by several molecular markers. A highly sensitive TnT-test identified myocardial inury in about all patients with APR while a standard TnT cut-off (0.1 ng/ml) missed 32% of these patients. Thus, the APR in patients with ACS is strongly associated with at least minor ischemic myocardial damage and prior findings of an APR independent from myocardial injury are probably based on less sensitive troponin tests.     

Elevated cardiac troponin I predicts a high-risk angiographic anatomy of the culprit lesion in unstable angina

BACKGROUND: This study assessed the relation between the angiographic appearance of the culprit lesion and cardiac troponin I (cTnI) or C-reactive protein (CRP) elevations within the first 24 hours in unstable angina. Intracoronary thrombus or a complex morphology, is frequently observed on angiography in patients with unstable angina and is associated with a higher rate of spontaneous or coronary angioplasty-related complications. Biochemical parameters related to myocardial injury (eg, cTnI) or to systemic inflammation (eg, CRP) are known prognostic markers for clinical outcome and may help in angiographic risk stratification to provide new adjunctive therapy. METHODS AND RESULTS: We studied 100 patients admitted for unstable angina with angiographically proven coronary artery disease (with normal creatine kinase [CK] and CK-MB mass). Serum concentrations of cTnI (N < 0.4 ng/mL) and CRP (N < 3 mg/L) were measured at admission and 12 and 24 hours later. Multivariate analysis showed that elevated cTnI (>/=0.4 ng/mL) within 24 hours (35 patients) was an independent predictor of an angiographic appearance of the culprit lesion carrying a high risk of major cardiac events in the outcome and whether angioplasty is attempted (coronary thrombus, occlusion, or type C lesions; odds ratio 4.1, 1. 6 to 10.5). cTnI levels at admission and CRP at 0, 12, and 24 hours were not predictive of high-risk angiographic anatomy. CONCLUSIONS: In patients with unstable angina and angiographically proven coronary artery disease, increased cTnI within 24 hours of admission but not increased CRP is associated with an angiographic appearance of the culprit lesion carrying a high risk of complication, especially in the event of angioplasty.     

C-reactive protein as an independent marker of prognosis in acute coronary syndrome: comparison with troponin T

BACKGROUND: It has been suggested that inflammatory processes play a role in the pathogenesis of acute coronary syndromes (ACS). C-reactive protein (CRP) is a classic acute phase protein. It is yet unclear whether, in addition to established markers as troponin T (TnT), determination of CRP in patients admitted for ACS contributes significantly to the diagnosis and prognosis of ACS. PATIENTS AND METHODS: We investigated 50 patients with ACS (59.4 SD 13.9 years) in the first hour after admission and 4-24 h later with respect to TnT (Elecsys, Roche Diagnostics) and CRP (biokit, modified Quantex CRP plus, analytical sensitivity 0.02 mg/dL). Fifty percent of the patients were classified as having unstable angina retrospectively. All patients were followed in the 6 weeks post discharge regarding death and recurrent ACS. RESULTS: The cumulative event rate at 6 weeks after discharge was 62.5% for patients being CRP and TnT positive compared to 35.3% in TnT positive and CRP negative patients. In TnT negative patients a positive CRP test predicted 33.3% of events and 28.8% of patients negative for CRP and TnT had events at 42 days post discharge. Logistic regression analysis regarding the primary endpoint including TnT and CRP (4-24 h values), age, gender and diagnosis resulted in independent prediction of ACS or death by TnT (cutoff 0.1 microgram/L, p = 0.048, odds ratio = 7.5) and CRP (cutoff 0.862 mg/dL, p = 0.026, odds ratio = 5.3). Sensitivity/specificity for AMI diagnosis were 69.6%/75% for TnT and 12%/72% for CRP in the first hour and 91.3%/68.2% for TnT and 68%/72% for CRP 4-24 h later. CONCLUSIONS: Besides TnT, high sensitivity CRP determination has no additional value for early AMI diagnosis. The prognosis of these patients during the first 24 hours is significantly and independently predicted by CRP measurements in addition to troponin T.     

Predictive value of C-reactive protein and troponin T in patients with unstable angina: a comparative analysis. CAPTURE Investigators. Chimeric c7E3 AntiPlatelet Therapy in Unstable angina REfractory to standard treatment trial

OBJECTIVES: We evaluated C-reactive protein (CRP) and troponin T (TnT) for predicting six-month cardiac risk in patients with unstable angina. BACKGROUND: Troponin T is predictive of cardiac risk in patients with unstable angina. The clinical implications of elevated CRP in such patients remains controversial. METHODS: Baseline TnT and CRP values were determined in 447 patients with unstable angina enrolled in the placebo group of the Chimeric c7E3 AntiPlatelet Therapy in Unstable angina REfractory to standard treatment trial (CAPTURE) trial. All patients underwent a coronary intervention and were followed for a six month period in which 13 deaths and 47 myocardial infarctions were documented (MIs). RESULTS: Troponin T was >0.1 microg/liter in 30% and CRP was >10 mg/L in 41% of the patients. For the initial 72-h period (including coronary intervention), TnT (17.4% vs. 4.2%; p < 0.001) but not CRP (10.3% vs. 8%; p = 0.41) was predictive of mortality and MI. The TnT-positive patients displayed more frequent recurrent instability before the planned intervention (44.8% vs. 16.9%; p < 0.001), but in the CRP-positive patients, no such increase was observed (25.9% vs. 24.8%; p = 0.92). In contrast, for the six month follow-up period, CRP was predictive of cardiac risk (mortality, MI) (18.9% vs. 9.5%; p = 0.003). Using multivariate analysis, both CRP and TnT emerged as independent predictors of mortality and MI at six-month follow-up. Furthermore, the incidence of coronary restenosis during six-month follow-up was not related to TnT status (3% vs. 4.5%; p = 0.49); however, it was significantly related to CRP status (7% vs. 2.3%; p = 0.03). CONCLUSIONS: Troponin T, but not CRP, was predictive of cardiac risk during the initial 72-h period, whereas CRP was an independent predictor of both cardiac risk and repeated coronary revascularization (coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty) during six month follow-up.     

Predictive value of the markers of inflammation in acute coronary syndromes

This prospective study aims to establish the association between markers of inflammation (CRP and fibrinogen) and the severity of coronary lesions in patients with acute coronary syndromes. For this purpose, Plasma CRP, fibrinogen and troponin I were measured upon admission in 143 consecutive patients presenting with an acute coronary syndrome who underwent subsequently coronarography . Mean age is 55.5+/-11.6 years. Sex Ratio is 3.61 in favour of men; 68% of our patients presented with acute myocardial infarction with ST segment elevation; 23% with an unstable angina and 9% with an acute myocardial infarction without ST segment elevation. 31 patients (24.4%) have not any significant coronary lesion. Mean CRP level in these patients is (6.82+/-8.2 mg/l) lower than that measured in patients with significant lesions (17.4+/-26.9 mg/l; p=0.02). In patients with pathologic coronarogram, we demonstrated that the mean CRP level is higher in patients heaving one or more lesion of at least 70% of diameter stenosis than that in patients with no significant lesions (21.28+/-30.45 mg/l vs 11+/-14.2 mg/l; p=0.05). The mean CRP level grows with the number of proximal and significant stenoses. (CRP level in patients with one significant stenosis: 11+/-14.2 mg/l vs 27.45+/-39.67 mg/l in patients heaving 3 lesions; p=0.02. CRP level in patients with one proximal lesion: 14.35+/-19.8 mg/l vs 50.33+/-65 mg/l in patients heaving 3 proximal lesions; p=0.007). Fibrinogen levels measured upon admission in patients having significant lesions are higher than those measured in patients with normal coronary arteries (4.7+/-1.81 mg/l vs 3.93+/-1.69 mg/l; p=0.02). Compared with that measured in patients having distal lesions, the fibrinogen level is higher in case of proximal and multiple coronary lesions. There is a significant gradual increase in fibrinogen levels with increasing of the number of proximal coronary lesions and the degree of diameter stenosis. Multivariate logistic regression analysis showed that a CRP level higher than 10 mg/l is an independent predictive factor of the presence of the presence of significant coronary lesions (p=0.006; OR = 8.62; CI=0.7 to 7.4). We conclude that high CRP and fibrinogen plasma levels are associated with extended, severe and proximal coronary lesions.