Pregnancy-associated plasma protein a as predictor of outcome in patients with suspected acute coronary syndromes.
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Biomedical subjects
Publications and source records attributed to Felicita Andreotti.
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In severe bacterial infections, treatment failure can occur even when the infecting organism has displayed in vitro susceptibility to the antibiotics used. Several pharmacokinetic-pharmacodynamic parameters show better correlation with therapeutic outcome than susceptibility results. This study was devised to assess the relation between the inhibitory quotient (IQ), i.e., the ratio of achievable antibiotic concentration at the infection site to the minimum inhibitory concentration for the infecting organism, and both clinical and bacteriological outcomes in 290 severe bacterial infections. Multivariate analysis showed that the IQ was a strong predictor of therapeutic outcome ( P< 0.001-0.002): values <4 predicted failure, and those >or=6 cure. This simple parameter could be routinely used to guide effective antibiotic therapy.
BACKGROUND AND OBJECTIVES: The prognostic value of the G20210A prothrombin gene polymorphism in patients with a first acute coronary syndrome has not been previously assessed. We conducted a prospective study to investigate this issue. DESIGN AND METHODS: Genotyping at the 20210 prothrombin gene locus was performed in 162 patients with a first episode of myocardial infarction (MI) or unstable angina (UA) occurring before 65 years of age. Patients were stratified according to cardiovascular risk factors and to treatment strategy. The subsequent two-year relative risk (RR) of adverse events (death, MI and UA) was adjusted for possible confounders and analyzed according to genotype, risk factor category, and treatment allocation. RESULTS: In the entire study population, the prothrombin variant did not significantly increase the two-year risk of events: the adjusted RR for GA vs GG carriers was 1.82 (95% CI 0.68-4.89). However, in the absence of traditional cardiovascular risk factors the risk of events was consistently higher: among the 46 patients without hypertension, diabetes and hypercholesterolemia, GA vs GG carriership was associated with an adjusted RR at two years of 5.64 (95% CI 1.07-29.84). The gene variant also enhanced the risk of events among the 98 patients who did not undergo myocardial revascularization procedures (RR for GA vs GG: 2.89, 95% CI 1.04-8.00), but not among those who did. INTERPRETATION AND CONCLUSIONS: The present prospective study suggests that heterozygosity for the G20210A prothrombin polymorphism adversely affects prognosis after a first acute coronary syndrome in the subgroup of patients without metabolic risk factors and in those not treated by revascularization procedures.
BACKGROUND: It has been suggested that inflammation can have a role in the development of atrial arrhythmias after cardiac surgery and that a genetic predisposition to develop postoperative complications exists. This study was conceived to verify if a potential genetic modulator of the systemic inflammatory reaction to cardiopulmonary bypass (the -174 G/C polymorphism of the promoter of the Interleukin-6 gene) has a role in the pathogenesis of postoperative atrial fibrillation (AF). Patients and Results- In 110 primary isolated coronary artery bypass patients the -174G/C Interleukin-6 promoter gene variant was determined. Interleukin-6, fibrinogen and C-reactive protein plasma levels were determined preoperatively, 24, 48, and 72 hours after surgery and at discharge. Heart rate and rhythm were continuously monitored for the first 36 to 48 hours; daily 12-lead electrocardiograms were performed thereafter until discharge. GG, CT, and CC genotypes were found in 62, 38, and 10 patients, respectively. Multivariate analysis (which included genotype, age, sex, and classical risk factors for AF) identified the GG genotype as the only independent predictor of postoperative AF. The latter occurred in 33.9% of GG versus 10.4% of non-GG patients (hazard ratio 3.25, 95%CI 1.23 to 8.62). AF patients had higher blood levels of Interleukin-6 and fibrinogen after surgery (P<0.001 for difference between the area under the curve). CONCLUSIONS: The -174G/C Interleukin-6 promoter gene variant appears to modulate the inflammatory response to surgery and to influence the development of postoperative AF. These data suggest an inflammatory component of postoperative atrial arrhythmias and a genetic predisposition to this complication.
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BACKGROUND: Platelet reactivity is increased by exercise in patients with obstructive coronary artery disease (CAD) but not in patients with syndrome X. In this study, we prospectively investigated whether the platelet response to exercise might help distinguish, among patients with angina, those with obstructive CAD from those with normal coronary arteries (NCAs). METHODS AND RESULTS: Venous blood samples were collected before and 5 minutes after exercise from 194 consecutive patients with stable angina. Platelet reactivity was measured by the platelet function analyzer (PFA)-100 system as the time for flowing whole blood to occlude a collagen-adenosine diphosphate ring (closure time). Coronary angiography showed CAD in 163 patients (84%) and NCA in 31 patients (16%). Baseline closure time was shorter in NCA patients (78.0+/-16 versus 95.5+/-23 seconds, P<0.0001). With exercise, closure time decreased in CAD patients (-15.5 seconds; 95% confidence limits [CL], -13.0 to -18.0 seconds; P<0.0001), but increased in NCA patients (12.5 seconds; 95% CL, 7.4 to 17.7 seconds; P=0.0004). An increase in closure time with exercise > or =10 seconds had 100% specificity and positive predictive value for NCAs. Similarly, a decrease > or =10 seconds had 100% specificity and positive predictive value for CAD. A closure time change (increase or decrease) > or =10 seconds allowed a correct classification of 55% of all patients. CONCLUSIONS: Among patients with stable angina, the response of platelet reactivity to exercise was predictive of normal or stenosed coronary arteries at angiography. Specifically, an increase in closure time with exercise > or =10 seconds was invariably associated with the presence of NCA.
BACKGROUND: Although some data suggest that the individual genetic predisposition for developing major or minor degrees of postoperative systemic inflammatory reaction may influence postoperative morbidity, this hypothesis has not been clinically tested to date. Methods and results The -174 G/C polymorphism of the promoter of the interleukin 6 gene was determined preoperatively in 111 consecutive patients submitted to primary isolated coronary artery bypass. The results of the genetic analysis were then correlated with the postoperative interleukin 6 levels and the development of postoperative renal and pulmonary complications. G homozygotes had significantly higher interleukin 6 levels postoperatively (P <.0001 for the difference between areas under the curve). These patients also had worse postoperative pulmonary and renal function. The mean perioperative difference in serum creatinine, potassium, and nitrogen was 0.82 +/- 0.34, 0.99 +/- 0.44, and 10.1 +/- 7.8 mg/dL versus 0.18 +/- 0.14, 0.15 +/- 0.48, and 2.6 +/- 4.1 mg/dL for GG versus non-GG carriers (P <.0001), respectively. The mean respiratory index at 6 and 12 hours was 2.9 +/- 0.8 and 2.8 +/- 0.3 versus 2.1 +/- 0.5 and 1.3 +/- 0.1, respectively (P <.0001). The mean duration of mechanical ventilation was 22.5 +/- 2.1 versus 12.7 +/- 6.7 hours (P <.01). A correlation was found between postoperative interleukin 6 levels and renal and pulmonary complications. CONCLUSION: The interleukin 6 -174 G/C polymorphism modulates postoperative interleukin 6 levels and is associated with the degree of postoperative renal and pulmonary dysfunction and in-hospital stay after coronary surgery.
BACKGROUND AND OBJECTIVE: The 4G/5G plasminogen activator inhibitor-1 (PAI-1) promoter polymorphism has been associated with basal PAI-1 levels, with ischemic heart disease, and with adverse prognosis in critically ill patients. We hypothesized it might also influence the acute-phase levels of PAI-1 following coronary bypass surgery. METHODS: In 111 consecutive patients undergoing elective coronary bypass surgery, 4G/5G genotyping and serial plasma PAI-1 activity and antigen levels were prospectively measured before surgery, daily up to 72 h, and at discharge. The inflammatory reaction was additionally assessed by white cell count, fibrinogen, interleukin-6, and C-reactive protein levels. RESULTS: PAI-1 activity and antigen concentrations increased approximately two-fold after surgery, peaking at 48 hours. Carriers of the 4G-allele, compared with 5G/5G homozygotes, showed approximately 20% higher PAI-1 activity and antigen both preoperatively ( P = 0.007 and P = 0.035) and after surgery. White cell count, fibrinogen, interleukin-6, and C-reactive protein values did not differ significantly according to genotypic groups. In multivariate analysis, the 4G/5G genotype was the only significant modulator of postoperative PAI-1 activity (P = 0.003) and the main significant modulator of postoperative PAI-1 antigen (P = 0.013). No significant interaction was found between the effects of time and genotype on postoperative PAI-1. This indicates that the association between 4G/5G and acute-phase PAI-1 levels is secondary to the genotype-related difference of baseline PAI-1. CONCLUSIONS: Postoperative PAI-1 concentrations of patients undergoing elective coronary bypass surgery are higher in carriers of the 4G-allele than in 5G/5G homozygotes as a result of higher baseline values. Knowledge of 4G/5G status may be useful to predict acute-phase PAI-1 concentrations.
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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.
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OBJECTIVE: It has been suggested that a preoperative level of C-reactive protein (CRP)>5mg/l is predictive of postoperative complications in cardiac surgery patients. MATERIAL AND METHODS: Among 113 primary isolated coronary artery bypass patients, CRP was determined preoperatively and fibrinogen, interleukine 6, plasminogen activator inhibitor-1, prothrombin time, activated partial thromboplastin time, platelets and white blood cells count measured before surgery, 24, 48 and 72h thereafter and at hospital discharge. The clinical course of all cases was prospectively recorded. Data were then analysed according to the preoperative CRP level by dividing the patients into two groups (CRP>5mg/l or CRP<5mg/l). RESULTS: The in-hospital results were similar between the two patients groups. Even the postoperative haematic inflammatory markers did not significantly differ according to the preoperative CRP level. CONCLUSION: In this prospective study, a preoperative level of CRP>5mg/l did not predict in-hospital postoperative complications nor influence the extent of the inflammatory activation in primary isolated coronary bypass patients.
BACKGROUND: To better understand the mechanisms linking C reactive protein (CRP) to the risk of coronary thrombosis, we investigated the relation between inflammatory state and hemostatic response to coronary angioplasty in patients with either stable or unstable angina. METHODS: Plasma levels of von Willebrand factor (vWF) antigen, vWF collagen binding activity, vWF-cleaving-protease, CRP, and whole-blood platelet reactivity were measured before and 24 h after angioplasty in 18 patients with recent unstable angina and in 17 with stable angina. Each group was divided according to preprocedural CRP levels: >or=3 mg/l (in 9 unstable and 9 stable patients) or <3 mg/l (in 9 unstable and 8 stable patients). RESULTS: Baseline hemostatic parameters did not differ significantly among the four subgroups of patients. After angioplasty, virtually all patients with unstable angina and raised preprocedural CRP showed increased vWF antigen (P = 0.01), vWF collagen-binding (P = 0.001), CRP (P = 0.008), and platelet reactivity (P = 0.0007) compared to baseline, whereas no significant change of these variables was seen within the other three sets of patients. In the overall population, the changes in vWF antigen and vWF-collagen-binding induced by angioplasty correlated with those in CRP levels (r = 0.47, P = 0.004 and r = 0.44, P = 0.008). Baseline levels of vWF cleaving protease and modifications of this enzyme with angioplasty did not differ significantly among subgroups. CONCLUSIONS: Our data suggest that high preprocedural levels of CRP predict a significant vWF rise after angioplasty in patients with unstable angina. The rise in vWF is associated with that in CRP and with enhanced platelet reactivity. Such changes may contribute to the worse prognosis of unstable patients with raised indices of inflammation.
BACKGROUND: Despite its common acceptance in clinical practice, the effective benefits of normothermic systemic perfusion during coronary artery bypass operations are far from established. METHODS: A total of 113 patients undergoing primary isolated coronary artery bypass were randomly assigned to normothermic (37 degrees C) or hypothermic (26 degrees C) systemic perfusion. The clinical course of the patients was prospectively recorded, and several inflammatory and fibrinolytic markers (C-reactive protein, fibrinogen, interleukin 6, plasminogen activator inhibitor 1, prothrombin time, activated partial thromboplastin time, platelets, and white blood cell counts) were determined before surgical intervention; 24, 48, and 72 hours thereafter; and at hospital discharge. RESULTS: Postoperatively, 2 in-hospital deaths occurred in the normothermic series and none in the hypothermic series. Four patients had a myocardial infarction, 1 had respiratory insufficiency, 1 had to be reoperated on for graft malfunction, and none had renal insufficiency in the hypothermic group versus 1 patient with each of these complications in the normothermic series. Mean blood loss in the first 24 hours was 766 +/- 223 mL in the normothermic group and 740 +/- 220 mL in the hypothermic group. None of these differences was statistically significant. Similarly, no significant difference in the postoperative level of any of the measured variables at any time point was evident between the patients in the normothermic and hypothermic groups. CONCLUSION: Normothermic systemic perfusion does not influence the clinical course or the extent of inflammatory and hemostatic activation in patients undergoing primary isolated coronary artery bypass.