Statins and coronary artery disease: clinical evidence and future perspective.

Many clinical trials have demonstrated the beneficial effects of statins on cardiovascular risk, both in patients with history of coronary heart disease and in healthy subjects with risk factors, because of a significant reduction in acute coronary events. The introduction of more powerful statins in the market offered the opportunity to study whether an intensive lipid lowering treatment could yields even better cardiovascular outcomes than a moderate statin therapy and several clinical trial confirmed this hypothesis. Statins have also pleiotropic effect behind their lipid lowering function: they reduce inflammation, which plays an important role in the atherosclerotic process.

Levosimendan for acute right heart failure in COVID-19: another arrow in our quiver?

OBJECTIVE: SARS-CoV-2 infection is associated with a higher risk of acute right heart failure (RHF) due to primary right ventricle (RV) dilation and systemic inflammatory response, which in turn lead to microvascular and cardiomyocytes dysfunction, local hypoxia and multi-organ failure. In this clinical setting, levosimendan could be a viable therapy thanks to its right-heart tropism and its additional pleiotropic properties. CASE REPORT: We present the case of a 72 years-old man with positive nasopharyngeal swab for SARS-CoV-2 infection, mild pulmonary involvement and clinical signs of new-onset RHF. We started a 12-hour levosimendan cycle to improve RV performance and reduce cardiac filling pressures. RESULTS: We obtained a net clinical benefit in terms of acute RHF-related signs and symptoms, progressive renal and liver function improvement and concomitant reduction of high-sensitivity C-Reactive Protein and Interleukin-6 (IL-6) levels. CONCLUSIONS: Acute RHF during SARS-CoV-2 infection could be related to a convergent widespread systemic inflammatory response. Thanks to its anti-inflammatory and anti-remodeling properties, levosimendan might represent a viable therapy in this clinical setting, contributing to the dampening of the inflammatory response.

[High-sensitivity troponin assay: biochemistry and clinical application]. / Troponine ad alta sensibilita: dalla biochimica alle applicazioni cliniche.

Cardiac troponin is the marker of choice for the diagnosis of acute coronary syndrome. Its introduction in clinical practice consistently improved both sensibility and specificity as compared with other biomarkers, as creatin-chinase MB. However traditional troponin assays show some limits: the relatively long time elapsing between the onset of ischemia and the increase in serum concentration, and the difficulty in distinguishing ischemic from non ischemic damage. An earlier diagnosis could be obtained by adopting new high sensitivity troponin assays, with a coefficient of variation ≤10% at the 99° percentile of a reference healthy population, and capable of detecting circulating troponin in the most healty subjects. The difficulty in distinguishing ischemic from non ischemic harm can be overcome considering that only a rising and falling pattern can be attributed to ischemic harm. Further studies are needed to evaluate the prognostic role of low circulating troponin levels in healthy subjects and for properly fixing cut off values. Indeed biomarker increase has always to be considered in the specific clinical context.

Free light chains a novel biomarker of cardiovascular disease. A pilot study.

OBJECTIVE: Atherosclerosis and ischemic heart disease (IHD) are the major cause of morbidity and mortality but their inflammatory pathogenesis is still unclear. In this scenario, the role of serum free light chains (sFLC) has never been fully evaluated. The aim of the present study is to assess the clinical and pathogenetic role of sFLC in patients with IHD and to propose their use as a new biomarker for cardiovascular disease. PATIENTS AND METHODS: We enrolled 117 patients, divided into 5 cohorts: 15 healthy controls, non-diabetic and without ischemic heart disease; 19 patients with type 2 diabetes (T2DM), without ischemic heart disease at recruitment; 39 patients with stable chronic angina; 27 patients with NSTEMI, 17 patients with acute STEMI. Serum sFLC and high-sensitive C-reactive protein (hs-CRP) were measured. Patients also underwent a transthoracic echocardiographic study. RESULTS: sFLC were higher in patients with IHD and T2DM. However, we did not find statistically significant differences in sFLC concentration among subgroups. No correlation resulted between sFLC and hs-CRP levels. The median value of the sFLC κ/λ ratio in the population was 0.63, therefore stratifying it into two groups according to their levels. We found that an increase in left ventricular ejection fraction at 12 months was detected in 77% of patients with κ/λ ratio higher than 0.63 and 25% of patients with κ/λ ratio lower of 0.63 (p=0.016, OR=10.0 [1.8-55.6]). CONCLUSIONS: Our study suggests that the sFLC, produced by the B-lymphocytes in the context of generalized immune activation, could play a pathogenetic role in acute coronary syndromes and that they could represent a novel risk biomarker of cardiovascular disease.

Markers of acute coronary syndrome in emergency room.

Acute coronary syndromes (ACS) encompasses a spectrum of coronary heart diseases, ranging in severity from unstable angina to ST-elevation myocardial infarction (STEMI). Early diagnosis and risk stratification are needed in order to address correctly hospitalization and treatment. Although the diagnosis of STEMI in the presence of typical electrocardiogram (ECG) changes and symptoms is easy and does not require the use of biomarkers, cardiac biomarkers are particularly important in the Emergency Department (ED), where about 25% of patients admitted are affected by ACS but clinical presentation is often atypical and ECG alterations may be absent. The ideal marker in the ED should have rapid release, high sensitivity and specificity and risk stratifying properties. Classic cardiac biomarkers, like myoglobin, cardiac troponin T or I and creatine kinase-MB, have a poor sensitivity, dependent on the time past from the onset of symptoms to presentation, the duration of ischemia and the amount of myocardial tissue involved. Although the serial testing of these cardiac biomarkers can improve the detection of myocardial necrosis, there is still a need for the development of early markers that can reliably rule out ACS from the ED at presentation and also detect myocardial ischemia in the absence of irreversible myocyte injury. There are several markers which represent the different features of ACS pathogenesis and that can be divided into three major groups: markers of cardiac ischemia and necrosis, markers of inflammation and coronary plaque instability and marker of cardiac function.

Increasing levels of interleukin (IL)-1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events.

BACKGROUND: A growing body of evidence suggests a role for inflammation in acute coronary syndromes. The aim of this study was to assess the role of proinflammatory cytokines, their time course, and their association with prognosis in unstable angina. METHODS AND RESULTS: We studied 43 patients aged 62+/-8 years admitted to our coronary care unit for Braunwald class IIIB unstable angina. In each patient, serum levels of interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6) (which represent sensitive markers of biologically active IL-1beta and tumor necrosis factor-alpha levels, respectively), and troponin T were measured at entry and 48 hours after admission. Troponin T-positive patients were excluded. Patients were divided a posteriori into 2 groups according to their in-hospital outcome: group 1 comprised 17 patients with an uneventful course, and group 2 comprised 26 patients with a complicated in-hospital course. In group 1, mean IL-1Ra decreased at 48 hours by 12%, and IL-6 diminished at 48 hours by 13%. In group 2, IL-1Ra and IL-6 entry levels were higher than in group 1 and increased respectively by 37% and 57% at 48 hours (P<0.01). CONCLUSIONS: These findings indicate that although they receive the same medical therapy as patients who do not experience an in-hospital event, patients with unstable angina and with complicated in-hospital courses have higher cytokine levels on admission. A fall in IL-1Ra and IL-6 48 hours after admission was associated with an uneventful course and their increase with a complicated hospital course. These findings may suggest novel therapeutic approaches to patients with unstable angina.

Enhanced response of blood monocytes to in vitro lipopolysaccharide-challenge in patients with recurrent unstable angina.

BACKGROUND: C-reactive protein (CRP) plasma levels have been associated with short- and long-term occurrence of coronary events. We investigated whether circulating inflammatory cell responsiveness to low-grade stimuli could contribute to the reported association between CRP and coronary events. METHODS AND RESULTS: We studied 32 patients with unstable angina who were followed for 24 months and were free of symptoms for 6 months (group 1): 19 patients had persistently high CRP levels (>0.3 mg/dL) (group 1A); 13 patients had normal CRP levels (group 1B). During the follow-up, 12 (63%) group 1A but no group 1B patients developed an infarction or recurrence of unstable angina (P<0.001). Eighteen patients with chronic stable angina (group 2) and 18 healthy subjects (group 3) were studied as controls. Interleukin (IL)-6 production (median, range) by peripheral blood mononuclear cells after 4 hours of in vitro stimulation with 1 ng/mL lipopolysaccharide (LPS) was significantly higher in group 1A (4526 pg/mL, 3042 to 10 583 pg/mL) than in group 1B (1752 pg/mL, 75 to 3981 pg/mL), group 2 (707 pg/mL, 41 to 3275 pg/mL), and group 3 (488 pg/mL, 92 to 3503 pg/mL) (all P<0.001). No significant differences were observed among the other groups. IL-6 production after LPS-challenge was correlated with baseline CRP levels (r=0.42, P=0.005). CONCLUSIONS: Mononuclear cells of patients with recurrent phases of instability exhibit an enhanced production of IL-6 in response to low-dose of LPS, correlated with baseline CRP levels, 6 months after the last acute event. This persisting enhanced acute-phase responsiveness may help explain the association between CRP and acute coronary events.

Immune system activation follows inflammation in unstable angina: pathogenetic implications.

OBJECTIVES: The aim of this study was to assess the relations between inflammation, specific immune response and clinical course in unstable angina (UA). BACKGROUND: Several studies suggest that either inflammation and/or T-cell activation might have a pathogenetic role in UA, but neither their potential reciprocal connection nor their relation to the clinical course is known. METHODS: Serum levels of C-reactive protein (CRP) (inflammation), IgG, IgA, IgM, C3, C4 (humoral immunity), IL-2 and the percentage of CD4+, CD8+ and CD3+/DR+ T-cells (cell-mediated immunity) were measured in 35 patients with UA and 35 patients with chronic stable angina (CSA) during a period of 6 months. RESULTS: The CRP levels and the main specific immune markers (CD4+ and CD3+/DR+ cells, IL-2 and IgM) were higher in unstable than in stable angina. In UA, the serum levels of IgM and IL-2 and the percentage of double positive CD3+/DR+ significantly increased at 7 to 15 days, and returned to baseline at 6 months. The increment of circulating activated T cells (CD3+/ DR+) in UA was inversely related to the admission levels of CRP (r=-0.63, p=0.003) and associated with a better outcome. CONCLUSIONS: Our data suggest that the inflammatory component systemically detectable in UA may be antigen-related and that the magnitude of the immune response correlates with the clinical outcome of instability.

Intracellular neutrophil myeloperoxidase is reduced in unstable angina and acute myocardial infarction, but its reduction is not related to ischemia.

OBJECTIVES: This study sought to assess neutrophil activation in acute coronary syndromes and its relation to ischemic episodes. BACKGROUND: Neutrophil activation has been reported in unstable angina and acute myocardial infarction; however, it is not clear whether it is related exclusively to ischemia-reperfusion injury. METHODS: We measured the index of intracellular myeloperoxidase in 1) patients with unstable angina, myocardial infarction, variant angina and chronic stable angina and in normal subjects (protocol A); and 2) in patients with unstable angina and acute myocardial infarction during the first 4 days of the hospital period (protocol B). To assess whether neutrophil activation was triggered by ischemia, the myeloperoxidase intracellular index was analyzed before and after spontaneous ischemic episodes and before and after ischemia induced by an exercise stress test in 10 patients with chronic stable angina. In 11 patients with unstable angina, we also compared values of the myeloperoxidase intracellular index at entry with those after waning of symptoms. RESULTS: In protocol A, the myeloperoxidase intracellular index was significantly reduced in patients with unstable angina and acute myocardial infarction compared with patients with stable and variant angina and normal subjects (p < 0.01). In protocol B, the myeloperoxidase intracellular index did not change over time in patients with unstable angina and myocardial infarction. However, in 11 patients with waning symptoms, the myeloperoxidase intracellular index was significantly higher afer symptoms had waned (p < 0.05). In patients with unstable angina, 23 ischemic episodes were studied; no changes in the myeloperoxidase intracellular index were observed. In 10 patients with chronic stable angina and positive exercise stress test results, no significant differences in the myeloperoxidase intracellular index were observed after stress-induced ischemia. CONCLUSIONS: Our study confirms that neutrophils are activated in acute coronary syndromes but suggests that their activation may not be only secondary to ischemia-reperfusion injury.

Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty.

OBJECTIVES: We sought to investigate whether early and late outcome after percutaneous transluminal coronary angioplasty (PTCA) could be predicted by baseline levels of acute-phase reactants. BACKGROUND: Although some risk factors for acute complications and restenosis have been identified, an accurate preprocedural risk stratification of patients undergoing PTCA is still lacking. METHODS: Levels of C-reactive protein (CRP), serum amyloid A protein (SAA) and fibrinogen were measured in 52 stable angina and 69 unstable angina patients undergoing single vessel PTCA. RESULTS: Tertiles of CRP levels (relative risk [RR] = 12.2, p < 0.001), systemic hypertension (RR = 4.3, p = 0.046) and female gender (RR = 4.1, p = 0.033) were the only independent predictors of early adverse events. Intraprocedural and in-hospital complications were observed in 22% of 69 patients with high serum levels (>0.3 mg/dl) of CRP and in none of 52 patients with normal CRP levels (p < 0.001). Tertiles of CRP levels (RR = 6.2, p = 0.001), SAA levels (RR = 6.0, p = 0.011), residual stenosis (RR = 3.2, p = 0.007) and acute gain (RR = 0.3, p = 0.01) were the only independent predictors of clinical restenosis. At one-year follow-up, clinical restenosis developed in 63% of patients with high CRP levels and in 27% of those with normal CRP levels (p < 0.001). CONCLUSIONS: Preprocedural CRP level, an easily measurable marker of acute phase response, is a powerful predictor of both early and late outcome in patients undergoing single vessel PTCA, suggesting that early complications and clinical restenosis are markedly influenced by the preprocedural degree of inflammatory cell activation.

Enhanced inflammatory response in patients with preinfarction unstable angina.

OBJECTIVES: We assessed the extent and the time course of the acute phase response following myocardial cell necrosis and its relationship with the presence of preinfarction unstable angina (UA). BACKGROUND: Elevated levels of acute phase proteins have been reported in patients with UA and in patients with acute myocardial infarction (MI). METHODS: C-Reactive Protein (CRP), serum amyloid A protein (SAA) and interleukin-6 (IL-6) were measured in 36 patients with MI admitted within 3 h from symptoms onset. All patients had normal levels of creatine kinase and of troponin T on admission, rising above diagnostic levels within 6 to 12 h. Blood samples for CRP, SAA and IL-6 measurements were taken on admission, at 6, 24, 48, 72 h and at discharge. RESULTS: Twenty of the 36 patients studied presented an unheralded MI (Group 1); the remaining 16 patients had symptoms of unstable angina in the preceding 7 days (Group 2). Group 2 patients have much higher levels of CRP and SAA on admission (median values 8.8 vs. 3 mg/L and 28 vs. 3.4 mg/L, respectively, all p<0.001). Following the necrotic insult, despite similar infarct size and clinical signs of reperfusion, Group 2 patients had strikingly higher peaks of IL-6 (median values 85.2 vs. 19 pg/ml, p<0.05), CRP (50 vs. 31.4 mg/L, p<0.05) and SAA (228 vs. 45 mg/L, p<0.001). CONCLUSIONS: Our data demonstrated that the acute phase response is greatly enhanced in patients with preinfarction UA compared with those presenting with an unheralded MI. The significant differences in acute phase response observed in these two clinical presentations of MI indicate a major difference in their underlying pathogenetic components.

Large, sustained cardiac lipid peroxidation and reduced antioxidant capacity in the coronary circulation after brief episodes of myocardial ischemia.

OBJECTIVES: We sought to investigate whether a brief episode of myocardial ischemia produces a detectable cardiac oxidative stress in patients undergoing elective coronary angioplasty (PTCA). BACKGROUND: Although cardiac oxidative stress has been clearly demonstrated in experimental models of ischemia-reperfusion, its presence in patients after transient myocardial ischemia is still unclear. METHODS: In order to evaluate oxidative stress in ischemic cardiac regions, plasma conjugated dienes (CD), lipid hydroperoxides (ROOHs) and total antioxidant capacity (TRAP), independent indexes of oxidative stress, were measured in the aorta and great cardiac vein (GCV) before (t0), 1, (t1), 5 (t5) and 15 min (t15) after first balloon inflation in 15 patients undergoing PTCA on left anterior descending coronary artery (Group 1); six patients with right coronary artery stenosis (Group 2), which is not drained by the GCV, were studied as controls. RESULTS: In Group 1 at baseline, CD and ROOHs levels were higher in GCV than in aorta (p < 0.01 for both), and TRAP levels were lower (p < 0.01). Aortic levels of CD, ROOHs and TRAP did not change at any time after to; venous levels of CD and ROOHs levels markedly increased at t1, at t5 and remained elevated at t15 (p < 0.01 for all comparisons vs. to); venous levels of TRAP decreased at t1 and t5 (p < 0.01 vs. t0) and returned to normal at t15. In Group 2, CD, ROOHs and TRAP levels were similar in the aorta and GCV and did not change throughout the study. CONCLUSIONS: Short episodes of myocardial ischemia during PTCA induce a sustained oxidative stress, which is detectable in the venous effluent of reperfused myocardium.

Endothelium and inflammation.

During the past decade, our understanding of the pathophysiology of coronary heart disease (CAD) has undergone a remarkable evolution. To date atherosclerosis is considered an inflammatory disease, whose the endothelial dysfunction represents an early key event. When the arterial endothelium encounters certain bacterial products or risk factors, such as dyslipidemia, vasoconstrictor hormones involved in hypertension, the products of glycoxidation associated with hyperglycemia, or proinflammatory cytokines derived from excess adipose tissue, these cells increase the expression of adhesion molecules that promote the sticking of blood leukocytes to the inner surface of the arterial wall. Once in the arterial intima these cells communicate with endothelium and smooth muscle cells, under the influence of mediators of inflammation and immunity, such as the cytokines and complements components, prostanoids and leukotrienes. Thus, the activated endothelium promotes the development of the atherosclerotic disease process, i.e., vascular inflammation and thrombosis by producing vasoconstrictor substances, by inducing the expression of adhesive receptors for leukocytes and platelets, the production of tissue factor and endothelin, and by increasing the production of the plasminogen activator inhibitor-1. Emerging data support the concept that assessment of endothelial vasomotion may be a useful biomarker for atherosclerotic vascular disease.

Variable response of the peripheral circulation to acetylcholine in patients with coronary artery disease.

The purpose of this study was to assess endothelium-mediated vasodilation in the peripheral circulation of patients with coronary artery disease who are free from hypertension, hypercholesterolemia, diabetes mellitus, and congestive heart failure. The vascular response of the superficial femoral artery to an endothelium-dependent (i.e., acetylcholine 10-7, 10-6, and 10-5 mol/L) and to an endothelium-independent (i.e., nitroglycerin 10-8 and 10-6 mol/L) dilator was compared in 13 patients with angiographically documented coronary artery disease and in 7 patients with normal coronary angiograms. Vascular response was assessed by Doppler ultrasonography. Whereas the vascular responses to nitroglycerin in patients with abnormal and normal findings on coronary angiograms were similar, the responses to acetylcholine were clearly different. The ratio of mean blood flow velocity (+/-SD) measured during administration of acetylcholine 10-6 mol/L and mannitol was significantly lower in patients with abnormal versus normal results of coronary angiography (1.15 +/- 0.35 vs 2.20 +/- 1.06; p < 0.05). The vascular response to acetylcholine 10-5 mol/L in patients with an abnormal finding on their coronary angiogram was highly variable when compared with that in patients with normal results. Thus, in patients with angiographically proven coronary artery disease, the response of the peripheral circulation to acetylcholine is characterized by a great variability and a reduced sensitivity, when compared with that in patients with normal findings on coronary angiography.

Role of inflammation in the pathogenesis of unstable coronary artery disease.

In this article, the clinical, angiographic, and postmortem features of unstable angina are reviewed and its pathogenesis is discussed. Coronary plaque inflammation may play a key role in the pathogenesis of unstable angina and the evidence for this assertion is examined. Finally, the therapeutic implications of the involvement of inflammation in acute coronary syndromes are outlined.

Pulsed Doppler echocardiographic analysis of mitral regurgitation after myocardial infarction.

In 72 patients with previous myocardial infarction (MI), mitral regurgitation (MR) was assessed by pulsed-wave Doppler echocardiography and compared with physical and 2-dimensional echocardiographic findings. MR was found by Doppler in 29 of 42 patients (62%) with anterior MI, 11 of 30 (37%) with inferior MI (p less than 0.01) and in none of 20 normal control subjects. MR was more frequent in patients who underwent Doppler study 3 months after MI than in those who underwent Doppler at discharge (anterior MI = 83% vs 50%, p less than 0.01; inferior MI = 47% vs 27%, p = not significant). Of 15 patients who underwent Doppler studies both times, 3 (all with anterior MI) had MR only on the second study. Of the patients with Doppler MR, 12 of 27 (44%) with a left ventricular (LV) ejection fraction (EF) greater than 30% and 1 of 13 (8%) with an EF of 30% or less (p less than 0.01) had an MR systolic murmur. Mitral prolapse or eversion and papillary muscle fibrosis were infrequent in MI patients, whether or not Doppler MR was present. The degree of Doppler MR correlated with EF (r = -0.61), LV systolic volume (r = 0.47), and systolic and diastolic mitral anulus circumference (r = 0.52 and 0.51, respectively). Doppler MR was present in 24 of 28 patients (86%) with an EF of 40% or less and in 16 of 44 (36%) with EF more than 40% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler study of precordial musical murmurs.

Using phonocardiography, continuous- and pulsed-wave Doppler, 51 patients with precordial "musical" murmurs (49 with cardiac abnormalities) and 21 patients with noisy murmurs were examined. With M-mode echocardiography, fine fluttering of the structure generating the murmur was evident in 23 patients with musical murmurs and in 5 with noisy murmurs. A continuous-wave Doppler spectral signal characterized by parallel harmonics (Doppler musical signal) was evident in all patients with musical murmurs and in none with a noisy murmur. With pulsed-wave Doppler, the musical signal had less defined spectral features because of range ambiguity. Such a signal was experimentally reproduced by activating a diapason bathed in saline solution. The source of the musical murmur was established in all 51 patients by Doppler. The musical signal was associated with a valvular regurgitation signal in 36 patients and with a ventricular septal defect in 1 patient. The musical signal always disappeared when the pulsed-wave Doppler sample volume was placed 2 cm away from the generating structure. In 11 patients with musical murmur examined by color Doppler, no abnormal bidirectional flow signal was observed in the structures generating the signal. In 6 of the patients without valvular regurgitation, no flow disturbance was found. In conclusion, Doppler is valuable in determining the source of musical murmurs, and musical murmurs are caused by a vibrating structure even in the absence of flow turbulence.

Incremental prognostic value of serum levels of troponin T and C-reactive protein on admission in patients with unstable angina pectoris.

Management of unstable angina is largely determined by symptoms, yet some symptomatic patients stabilize, whereas others develop myocardial infarction after waning of symptoms. Therefore, markers of short-term risk, available on admission, are needed. The value of 4 prognostic indicators available on admission (pain in the last 24 hours, electrocardiogram [ECG], troponin T, and C-reactive protein [CRP]), and of Holter monitoring available during the subsequent 24 hours was analyzed in 102 patients with Braunwald class IIIB unstable angina hospitalized in 4 centers. The patients were divided into 3 groups: group 1, 27 with pain during the last 24 hours and ischemic electrocardiographic changes; group 2, 45 with pain or electrocardiographic changes; group 3, 30 with neither pain nor electrocardiographic changes. Troponin T, CRP, ECG on admission, and Holter monitoring were analyzed blindly in the core laboratory. Fifteen patients developed myocardial infarction: 22% in group 1, 13% in group 2, and 10% in group 3. Twenty-eight patients underwent revascularization: 37% in group 1, 35% in group 2, and 7% in group 2 (p <0.01 between groups 1 or 2 vs group 3). Myocardial infarction was more frequent in patients with elevated troponin T (50% vs 9%, p=0.001) and elevated CRP (24% vs 4%, p= 0.01). Positive troponin T or CRP identified all myocardial infarctions in group 3. Only 1 of 46 patients with negative troponin T and CRP developed myocardial infarction. Among the indicators available on admission, multivariate analysis showed that troponin T (p=0.02) and CRP (p=0.04) were independently associated with myocardial infarction. Troponin T had the highest specificity (92%), and CRP the highest sensitivity (87%). Positive results on Holter monitoring were also associated with myocardial infarction (p=0.003), but when added to troponin T and CRP, increased specificity and positive predictive value by only 3%. Thus, in patients with class IIIB unstable angina, among data potentially available on admission, serum levels of troponin T and CRP have a significantly greater prognostic accuracy than symptoms and ECGs. Holter monitoring, available 24 hours later, adds no significant information.

Elevated levels of C-reactive protein before coronary artery bypass grafting predict recurrence of ischemic events.

C-reactive protein was measured in 86 patients undergoing coronary artery bypass graft surgery. Patients were followed up for 3.2 years (range 1 to 6). Patients with C-reactive protein > or = 3 mg/L had significantly increased risk of recurrent ischemia at 1 to 6 years after intervention.

Episodic activation of the coagulation system in unstable angina does not elicit an acute phase reaction.

The results of our study suggest that the acute phase response may be partly related to a yet unknown primary inflammatory component in unstable angina. Further studies are needed to elucidate the actual role of inflammation in unstable angina and its relation to activation of the coagulation system.