IGF-1 and macrovascular complications of diabetes: alternative interpretations of recently published data.
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Biomarkers↗
Biomedical subjects
Filippo Crea
Publications and source records attributed to Filippo Crea.
Effects of carbon-coated coronary stents on the markers of inflammation, thrombin generation and platelet and endothelial activation.
BACKGROUND: The effects of stent carbon coating on the activation of inflammatory and endothelial cells and of coagulation were assessed in patients undergoing coronary artery stent implantation. METHODS: Forty-four consecutive patients with stable angina and an isolated significant stenosis in a native coronary vessel undergoing stent implantation were randomized to a carbon-coated stent (Carbostent, n = 23) or an uncoated stent with a similar design (Multilink, n = 21). The markers of inflammation, of hemostasis and of platelet and endothelial activation were determined before and 6, 24, 48 and 72 hours after the procedure. RESULTS: Procedural success was achieved in all cases and no patient presented with major in-hospital adverse events. In both the Carbostent and Multilink groups, the median (interquartile range) plasma levels of C-reactive protein significantly increased after the procedure (p < 0.001 and p = 0.002 vs baseline levels, respectively), reaching a peak at 48 hours, without any difference between groups (p = 0.76). Similarly, in both groups the plasma levels of fibrinogen, thrombin-antithrombin III complexes, prothrombin fragments F1 + 2, plasminogen activator inhibitor-1, soluble E-selectin, soluble P-selectin and von Willebrand factor significantly increased after the procedure (all p < 0.05 vs baseline values), without any difference between groups (all p = NS). CONCLUSIONS: This study confirms that the markers of inflammation, of endothelial and platelet activation and of thrombin generation significantly increase after successful coronary artery stent implantation. More importantly, it demonstrates that carbon coating does not modify the biologic response of the vessel wall to stent implantation.
Aged↗
Carotid plaque inflammation in a patient with unstable angina.
Coronary instability has been associated with multifocal plaque activation in the coronary circulation and in remote vascular districts, suggesting a systemic cause of instability, possibly inflammation. Magnetic resonance imaging offers a great potential for the detection of plaque inflammation. We describe the case of a 73-year-old female admitted for unstable angina, elevated levels of C-reactive protein and three-vessel disease, in whom carotid ultrasound examination revealed an atherosclerotic plaque of the left proximal internal carotid artery with an irregular profile and a heterogeneous echographic texture, determining a 50% stenosis. Magnetic resonance imaging of the plaque before and after contrast enhancement by gadolinium-DTPA showed the following signs of inflammation: an increased vessel wall thickness, an increased triple inversion recovery-fast spin-echo signal intensity indicative of tissue edema, and a homogeneous plaque contrast enhancement indicative of an increased capillary permeability and neovasculature. As the carotid stenosis was < 70% and did not give rise to any symptom, the patient was submitted to coronary bypass surgery without concomitant carotid endarterectomy. Two days later she developed an ischemic stroke with right brachiocrural hemiplegia. In the present case report, the simultaneous presence of coronary instability and a carotid plaque with magnetic resonance features suggestive of inflammation, which was probably responsible for the stroke complicating cardiac surgery, may indicate a multifocal plaque instability.
Aged↗
Sex, survival bias, and mortality following acute myocardial infarction.
Several though not all studies have found an up to 2-fold increase in 30-day mortality in women compared to men admitted to hospital for ST-elevation myocardial infarction (MI), even after adjustment for baseline variables. These data however do not take into account the pre-hospital period. Indeed, three large WHO MONICA reports that included out-of-hospital events found no significant gender difference in overall 28-day mortality from MI, with more men dying before reaching the hospital (presumably of ventricular tachyarrhythmias) and more women dying after hospital admission (presumably of heart failure). Women compared to men exhibit enhanced vagal activity, both under basal conditions and during angioplasty-induced coronary occlusion, and this may afford protection against malignant ventricular arrhythmias. Epidemiological data indicate that women dying of ischemic heart disease are less prone to sudden death than men. Taken together, the above findings suggest that, following acute MI, significant gender differences lie not so much in overall mortality, but in the timing and mechanisms of death.
Acute Disease↗
Immunosuppressive Therapy for the Prevention of Restenosis after Coronary Artery Stent Implantation (IMPRESS Study).
OBJECTIVES: This study tested the effect of oral prednisone on clinical and angiographic restenosis rate after successful stent implantation in patients with persistent elevation of systemic markers of inflammation after the procedure. BACKGROUND: Experimental studies have shown that corticosteroids have the potential to reduce the inflammatory response associated with stent implantation. METHODS: Eighty-three patients undergoing successful stenting with C-reactive protein (CRP) levels >0.5 mg/dl 72 h after the procedure were randomized to receive oral prednisone or placebo for 45 days. The primary clinical end point was 12-month event-free survival rate (defined as freedom from death, from myocardial infarction, and from recurrence of symptoms requiring additional revascularization). The angiographic end points were restenosis rate and late loss at six months. RESULTS: Twelve-month event-free survival rates were 93% and 65% in patients treated with prednisone and placebo, respectively (relative risk [RR] 0.18, 95% confidence intervals [CI], 0.05 to 0.61, p = 0.0063). Six-month restenosis rate and late loss were lower in prednisone-treated than in placebo-treated patients (7% vs. 33%, p = 0.001, and 0.39 +/- 0.6 mm vs. 0.85 +/- 0.6 mm, p = 0.001, respectively). CONCLUSIONS: In patients with persistently high CRP levels after successful coronary artery stent implantation, oral immunosuppressive therapy with prednisone results in a striking reduction of clinical events and angiographic restenosis rate.
Adult↗
Multicentric inflammation in epicardial coronary arteries of patients dying of acute myocardial infarction.
OBJECTIVES: We sought to test the hypothesis of whether inflammatory cell infiltration in patients dying of an acute myocardial infarction (MI) is a multifocal event involving multiple coronary branches. BACKGROUND: Coronary instability is thought to reflect local disruption of a single vulnerable plaque. However, previous postmortem studies have not addressed the question of whether activation of inflammatory cells, particularly T lymphocytes, is limited to the culprit lesion only or rather diffuse in the coronary circulation. METHODS: We performed a systematic flow cytometric study in three groups of autopsied patients (group 1 = acute MI; group 2 = old MI; group 3 = no ischemic heart disease). Cell suspensions of enzymatically digested coronary arteries were stained for flow cytometry with CD3, CD68, alpha-smooth muscle actin, and human leukocyte antigen (HLA)-DR antibodies. RESULTS: The coronary plaques showed: 1) a higher proportion of inflammatory cells in groups 1 and 2 than in group 3; 2) a higher percentage of T lymphocytes in group 1 than in group 2 (11.67 +/- 0.70% vs. 5.67 +/- 0.74%, p = 0.001) and in group 2 than in group 3 (p = 0.008); and 3) diffuse cell activation in the whole coronary tree of group 1, but not of group 2 subjects. CONCLUSIONS: Our study suggests that lymphocytes may play a key role in coronary instability by determining activation of various cellular types throughout the coronary circulation. Activated T lymphocytes and their products may well represent a new target in both the treatment and prevention of acute coronary syndromes.
Aged↗
Widespread coronary inflammation in unstable angina.
BACKGROUND: Inflammation within vulnerable coronary plaques may cause unstable angina by promoting rupture and erosion. In unstable angina, activated leukocytes may be found in peripheral and coronary-sinus blood, but it is unclear whether they are selectively activated in the vascular bed of the culprit stenosis. METHODS: We measured the content neutrophil myeloperoxidase content in the cardiac and femoral circulations in five groups of patients: two groups with unstable angina and stenosis in either the left anterior descending coronary artery (24 patients) or the right coronary artery (9 patients); 13 with chronic stable angina; 13 with variant angina and recurrent ischemia; and 6 controls. Blood samples were taken from the aorta, the femoral vein, and the great cardiac vein, which selectively drains blood from the left but not the right coronary artery. RESULTS: The neutrophil myeloperoxidase content of aortic blood was similar in both groups of patients with unstable angina (-3.9 and -5.5, with negative values representing depletion of the enzyme due to neutrophil activation) and significantly lower than in the other three groups (P<0.05). Independently of the site of the stenosis, the neutrophil myeloperoxidase content in blood from the great cardiac vein was significantly decreased in both groups of patients with unstable angina (-6.4 in those with a left coronary lesion and -6.6 in those with a right coronary lesion), but not in patients with stable angina and multiple stenoses, patients with variant angina and recurrent ischemia, or controls. There was also a significant transcoronary reduction in myeloperoxidase content in both groups with unstable angina. CONCLUSIONS: The widespread activation of neutrophils across the coronary vascular bed in patients with unstable angina, regardless of the location of the culprit stenosis, challenges the concept of a single vulnerable plaque in unstable coronary syndromes.
Aged↗
Reduced levels of insulin-like growth factor-1 in patients with angina pectoris, positive exercise stress test, and angiographically normal epicardial coronary arteries.
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Angina Pectoris↗
Chest pain after coronary artery stent implantation.
A sizeable proportion of patients who undergo successful coronary artery stent implantation experiences chest pain immediately after the procedure and/or in the following months in the absence of in-stent restenosis. We investigated this phenomenon in 57 consecutive patients with stable angina who underwent successful stent implantation. Chest pain characteristics were assessed before stent implantation and during 6-month follow-up. All patients underwent coronary angiography within 6 months of the procedure 48 hours after exercise thallium-201 perfusion scintigraphy. Patients who did not exhibit in-stent restenosis underwent an ergonovine test at the end of routine coronary angiography. During follow-up, 15 patients complained of chest pain. Six of these patients exhibited scintigraphic evidence of myocardial ischemia and in-stent restenosis at angiography. In the remaining 9 patients, chest pain occurred in the absence of in-stent restenosis at angiography. In 8 of these patients intracoronary ergonovine administration reproduced their habitual pain, whereas it did not cause any pain in the 42 patients who were completely asymptomatic at follow-up and without in-stent restenosis. Ergonovine caused more intense vasoconstriction and nitroglycerin caused more intense vasodilation of the reference coronary diameter in patients with than in patients without ergonovine-induced pain (-17 +/- 3 vs -9 +/- 3%, p <0.001; 9 +/- 6 vs 5 +/- 4%, p <0.02, respectively). In conclusion, chest pain with features similar to habitual angina occurs in the absence of in-stent restenosis in 1/5 of patients after stent implantation and appears to be associated with more intense coronary vasoreactivity.
Adult↗
Inflammatory predictors of mortality in the Scandinavian Simvastatin Survival Study.
BACKGROUND AND HYPOTHESIS: The predictive value of specific markers of infection and autoimmunity for coronary events, such as the effects of statins on inflammation, is still controversial. METHODS: A case-control design was used to compare C-reactive protein (CRP) levels, seropositivity for Chlamydia pneumoniae and Helicobacter pylori, and anti-oxidized low-density lipoprotein (oxLDL) antibody levels in prerandomization blood samples from 129 participants in the Scandinavian Simvastatin Survival Study who died (cases), and from 129 matched participants who were alive during 5-year follow-up (controls). RESULTS: Patients with CRP levels in the highest quartile had an increased risk of death compared with those in the first through third quartile (odds ratio [OR] = 2.51, 95% confidence interval [CI] 1.3-4.8). Seropositivity for Chlamydia pneumoniae or Helicobacter pylori and anti-oxLDL antibody levels were similar in cases and controls (p = NS). At a 4-month control, simvastatin reduced CRP levels (p = 0.009) while placebo did not (p = NS). However, the risk of death associated with high baseline CRP levels was similar in patients randomized to placebo (OR = 2.36, 95% CI 1.06-5.26) or simvastatin (OR = 3.13, 95% CI 1.06-9.21). CONCLUSIONS: Elevated CRP levels, but not seropositivity for Chlamydia pneumoniae or Helicobacter pylori, nor levels of anti-oxLDL antibodies, predict the risk of death in patients with stable ischemic heart disease. Simvastatin treatment reduces CRP levels, but without affecting the increased risk conferred by higher CRP levels at baseline.
Aged↗
How to search for the precipitating role of vasoconstriction and its prevalence in myocardial infarction.
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Angina Pectoris, Variant↗
How to study the effects of platelet aggregation and thrombosis on coronary vasomotion and their clinical relevance.
Following arterial injury, platelets may activate and adhere to the damaged vessel wall, release vasoactive products, and produce vasoconstriction or even vasospasm. In the last few years the hypothesis of intracoronary thrombosis, triggered by plaque ulceration or fissuration, has gained wide acceptance as one of the key events in the pathophysiology of acute coronary syndromes. Following arterial injury, platelets readily adhere to the subendothelium and release a variety of chemical mediators which, apart from recruiting additional platelets from the circulation, are also powerful vasoactive substances. Platelet-induced coronary vasoconstriction may therefore contribute to the occurrence of myocardial ischemia in patients with acute coronary syndromes. Several studies have also focused on some components of the vessel wall and indicate that endothelial dysfunction in atherosclerosis plays a key role in altered vascular responses. We and others have suggested that augmented constrictor responses of atherosclerotic coronary arteries to platelet-derived substances, such as serotonin and thromboxane A2, perhaps combined with an impaired release of endothelium-derived relaxing factor, may contribute to vasoconstricting responses to aggregating platelets. The purpose of this article is to summarize recent development in knowledge relating to alteration in coronary tone associated with intracoronary platelet activation.
Animals↗
Scintigraphic results in asymptomatic myocardial infarction patients with exercise-induced ST segment elevation.
BACKGROUND: The mechanism responsible for exercise-induced ST segment elevation is debated, but heterogeneous patients were likely included in previous studies. This study was specifically aimed at investigating the clinical meaning of isolated exercise-induced ST segment elevation in asymptomatic patients with a recent acute myocardial infarction (MI). METHODS: We studied 30 patients (28 males, 2 females, mean age 62 +/- 9 years) with a recent MI who developed ST segment elevation in leads with a Q/QS wave pattern, and who did not develop angina or ST segment depression during exercise testing and did not have any history of post-infarction angina. Patients underwent bicycle 99m-Tc-sestamibi (MIBI) myocardial scintigraphy for the assessment of myocardial perfusion and of left ventricular function. RESULTS: Only 7 patients (23.3%) showed reversible perfusion defects on stress MIBI myocardial scintigraphy, which were mild and of limited extension in all. There were no statistically significant differences in the main exercise variables between groups with or without stress-related perfusion defects. Signs of exercise-related left ventricular dysfunction were detected in 6 patients (20%), 3 of whom also showed reversible perfusion defects. Again, no significant differences in the main exercise variables were found between patients with or without stress-induced scintigraphic abnormalities. CONCLUSIONS: In asymptomatic MI patients, isolated exercise-induced ST segment elevation in leads with a Q/QS wave pattern is unlikely to represent clinically relevant residual myocardial ischemia during exercise, thus suggesting that further diagnostic investigations are not necessary in these patients.
Aged↗
Combined percutaneous pulmonary valvuloplasty and patent foramen ovale closure in an adult with recurrent transient ischemic attacks.
We report the case of a 60-year-old man with a history of recurrent transient ischemic attacks, effort syncope, cyanosis, erythrocytosis and a systolic murmur. Echocardiography and catheterization showed severe pulmonary stenosis and a patent foramen ovale with a right-to-left shunt. The patient was submitted to combined percutaneous pulmonary valvuloplasty and patent foramen ovale closure using the Amplatzer device.
Cardiac Catheterization↗
The new definition of myocardial infarction: analysis of the ESC/ACC Consensus Document and reflections on its applicability to the Italian Health System.
The recent document of the ESC/ACC Committee for the redefinition of myocardial infarction (MI) has introduced the measurement of cardiac troponin as the biochemical standard for the diagnosis of MI. This change has been mainly driven by the demonstration that any amount of myocardial damage, as detected by cardiac troponins, implies a worse long-term outcome of the patient. The results of several studies consistently show that there is a continuous relationship between the degree of troponin elevation and the patient's prognosis. The new definition has important consequences on the diagnostic and therapeutic approaches to patients with acute coronary syndromes; in fact, patients with increased troponins, i.e. patients with MI, necessitate more aggressive treatment than those without troponin elevations, i.e. patients with unstable angina. The application of the new definition is expected to increase the number of cases of MI by about 30% and to decrease mortality. We believe that several aspects of the new definition need to be discussed before the new criteria for MI are used in clinical practice in Italy. The most relevant issues are the following: 1) the definition of troponin elevation should meet the analytical performance of the available assays, the diagnostic cutoff of which is frequently too imprecise. We propose that troponin elevations be defined as values exceeding the concentration corresponding to a total analytical imprecision of 10%. We disclose such a concentration for the currently available assays and suggest its use in clinical practice to mitigate the possibility of false-positive values; 2) the number of samples required for the diagnosis should be sufficient for the assessment of the changes in concentration over time. When only one sample is available, or when the temporal pattern of the changes in marker concentration is not consistent with the time elapsed from the onset of symptoms, we suggest that objective evidence that myocardial ischemia is the likely cause of myocardial damage should be obtained; 3) the diagnosis of MI after a percutaneous coronary intervention represents a unique situation. In contrast with myocardial damage occurring during spontaneous ischemia, available data do not support the concept that any troponin elevation is associated with an adverse prognosis. In the absence of conclusive studies, we suggest that the diagnosis of MI after a percutaneous coronary intervention be based on conventional criteria. Finally, we propose this summary with the aim of overcoming some of the more controversial aspects of the ESC/ACC redefinition of MI: Criteria for acute, evolving or recent MI. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: 1) elevation of biochemical markers of myocardial necrosis (preferably troponin) with at least one of the following: a) ischemic symptoms; b) development of pathologic Q waves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); d) coronary artery intervention (e.g., coronary angioplasty). Marker elevations should be accompanied by objective evidence that myocardial ischemia is the likely cause of myocardial damage when: a) only one blood sample is available; b) marker changes over time are not consistent with the onset of symptoms; 2) pathologic findings of an acute MI. Criteria for established MI. Anyone of the following criteria satisfies the diagnosis for established MI: 1) development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed; 2) pathologic findings of a healed or healing MI.
Angioplasty, Balloon, Coronary↗
[New definition of myocardial infarction: analysis of the consensus document ESC/ACC and thoughts about applicability to the Italian health situation].
The recent document of the ESC/ACC Committee for the redefinition of myocardial infarction (MI) has introduced the measurement of cardiac troponin as the biochemical standard for the diagnosis of MI. This change has been mainly driven by the demonstration that any amount of myocardial damage, as detected by cardiac troponins, implies a worse long-term outcome of the patient. The results of several studies consistently show that there is a continuous relationship between the degree of troponin elevation and the patient's prognosis. The new definition has important consequences on the diagnostic and therapeutic approaches to patients with acute coronary syndromes; in fact, patients with increased troponins, i.e. patients with MI, necessitate more aggressive treatment than those without troponin elevations, i.e. patients with unstable angina. The application of the new definition is expected to increase the number of cases of MI by about 30% and to decrease mortality. We believe that several aspects of the new definition need to be discussed before the new criteria for MI are used in clinical practice in Italy. The most relevant issues are the following: 1) the definition of troponin elevation should meet the analytical performance of the available assays, the diagnostic cut-off of which is frequently too imprecise. We propose that troponin elevations be defined as values exceeding the concentration corresponding to a total analytical imprecision of 10%. We disclose such a concentration for the currently available assays and suggest its use in clinical practice to mitigate the possibility of false-positive values; 2) the number of samples required for the diagnosis should be sufficient for the assessment of the changes in concentration over time. When only one sample is available, or when the temporal pattern of the changes in marker concentration is not consistent with the time elapsed from the onset of symptoms, we suggest that objective evidence that myocardial ischemia is the likely cause of myocardial damage should be obtained; 3) the diagnosis of MI after a percutaneous coronary intervention represents a unique situation. In contrast with myocardial damage occurring during spontaneous ischemia, available data do not support the concept that any troponin elevation is associated with an adverse prognosis. In the absence of conclusive studies, we suggest that the diagnosis of MI after a percutaneous coronary intervention be based on conventional criteria. Finally, we propose this summary with the aim of overcoming some of the more controversial aspects of the ESC/ACC redefinition of MI: Criteria for acute, evolving or recent MI. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: 1) elevation of biochemical markers of myocardial necrosis (preferably troponin) with at least one of the following: a) ischemic symptoms; b) development of pathologic Q waves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); d) coronary artery intervention (e.g., coronary angioplasty). Marker elevations should be accompanied by objective evidence that myocardial ischemia is the likely cause of myocardial damage when: a) only one blood sample is available; b) marker changes over time are not consistent with the onset of symptoms; 2) pathologic findings of an acute MI. Criteria for established MI. Anyone of the following criteria satisfies the diagnosis for established MI: 1) development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed; 2) pathologic findings of a healed or healing MI.
Humans↗
Prognostic value of pre-discharge exercise testing and serum C-reactive protein in patients with unstable angina.
BACKGROUND: Both exercise testing and C-reactive protein (CRP) serum levels have been shown to predict clinical events in patients with unstable angina. However, no previous study carefully compared their relative prognostic value in this clinical setting. METHODS: We reviewed data of 96 consecutive patients with unstable angina (77 males, 19 females, mean age 63.1 +/- 9.5 years), who were free from clinical events during hospital stay. A symptom/sign-limited treadmill exercise test had been performed and CRP serum levels had been measured prior to discharge in all patients. RESULTS: During an average follow-up of 2.5 years (range 0.5-5 years), there were 8 major cardiac events (death or myocardial infarction) and 11 patients had recurrent unstable angina. Both exercise-induced myocardial ischemia [relative risk (RR) 3.02, 95% confidence interval (CI) 0.58-15.5, p = 0.29], and CRP levels > or = 10 mg/l (RR 2.4, 95% CI 0.51-11.2, p = 0.25) showed a non significant association with major cardiac events. Low workload ischemia, however, was significantly associated with major cardiac events (RR 8.58, 95% CI 1.66-44.2, p = 0.01) and was also the only predictive variable for the combined endpoint of major events and recurrent angina (RR 2.57, 95% CI 1.02-4.44, p = 0.045). Among patients with low workload ischemia, the occurrence of major events was higher in those with high, compared to those with low, CRP levels, but the difference was not significant (28.6 vs 15.4%, p = 0.64). CONCLUSIONS: In this study, pre-discharge myocardial ischemia at low workload was the single most important predictor of major cardiac events during long-term follow-up among patients with stabilized unstable angina. Increased serum CRP levels did not add further significant prognostic information in this specific group of patients with unstable angina, although this issue needs to be addressed in larger studies.
Aged↗
Normal distribution of an intravascular ultrasound index of vessel remodeling.
BACKGROUND: As a consequence of plaque accumulation, coronary arteries may undergo both compensatory enlargement and paradoxical constriction. The aim of this study was to address the distribution of the different remodeling patterns in patients with obstructive coronary atherosclerosis. METHODS: Eighty-seven non-branching segments of native coronary arteries with de novo, focal, non-ostial lesions were imaged at intravascular ultrasound (IVUS). Images were acquired with a motorized pull-back at a speed of 0.5 mm/s. The cross-sectional area (CSA) circumscribed by the external elastic membrane (EEM), the plaque + media complex and the lumen area were measured at its narrowest site (CSA with the minimal lumen area) and in the reference segment (average of proximal and distal reference cross-sections, defined as the most normal looking sites). The IVUS index of vessel remodeling (VRI) was calculated using the following formula: (narrowest site EEM CSA--reference EEM CSA)/reference EEM CSA*100. The index was tested for normality using the Kolmogorov-Smirnov goodness-of-fit test. RESULTS: The frequency distribution of VRI was found to have a normal unimodal distribution (p = 0.60). VRI ranged from -60 to +164, with a mean of 9.3 +/- 28.0 and a median of 3.6. Frequency distribution of VRI slightly skewed towards right (skewness index 1.69). None of the analyzed clinical and morphological variables predicted the presence of compensatory enlargement as opposed to paradoxical constriction. CONCLUSIONS: The frequency distribution of the vascular remodeling of de novo coronary lesions is unimodal. Therefore, compensatory enlargement and paradoxical constriction represent the extremes of a continuous spectrum.
Coronary Artery Disease↗