Assetto lipidico e infarto del miocardio nell'anziano

GERIATRI

Off-target effects of thrombolytic drugs: apolipoprotein A-I proteolysis by alteplase and tenecteplase.

Abstract The administration of thrombolytic drugs is of proven benefit in a variety of clinical conditions requiring acute revascularization, including acute myocardial infarction (AMI), ischemic stroke, pulmonary embolism, and venous thrombosis. Generated plasmin can degrade non-target proteins, including apolipoprotein A-I (apoA-I), the major protein constituent of high-density lipoproteins (HDL). Aim of the present study was to compare the extent of apoA-I proteolytic degradation in AMI patients treated with two thrombolytic drugs, alteplase and the genetically engineered t-PA variant tenecteplase. ApoA-I degradation was evaluated in sera from 38 AMI patients treated with alteplase or tenecteplase. In vitro, apoA-I degradation was tested by incubating control sera or purified HDL with alteplase or tenecteplase at different concentrations (5-100 \u3bcg/ml). Treatment with alteplase and tenecteplase results in apoA-I proteolysis; the extent of apoA-I degradation was more pronounced in alteplase-treated patients than in tenecteplase-treated patients. In vitro, the extent of apoA-I proteolysis was higher in alteplase-treated sera than in tenecteplase-treated sera, in the whole drug concentration range. No direct effect of the two thrombolytic agents on apoA-I degradation was observed. In addition to apoA-I, apoA-IV was also degraded by the two thrombolytic agents and again proteolytic degradation was higher with alteplase than tenecteplase. In conclusion, this study indicates that both alteplase and tenecteplase cause plasmin-mediated proteolysis of apoA-I, with alteplase resulting in a greater apoA-I degradation than tenecteplase, potentially causing a transient impairment of HDL atheroprotective functions

THE PLASMA CONCENTRATION OF LPA-I:A-II PARTICLES AS A PREDICTOR OF THE INFLAMMATORY RESPONSE IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION.

Abstract Objective: To investigate the relationship between plasmaHDLat admission and the extent of the inflammatory response during anST-elevation myocardial infarction (STEMI), and to analyse structural HDL changes during STEMI as related to the extent of inflammation. Methods and results: CRP and IL-6 were monitored for 96 h in 45 patients with STEMI. Plasma apoA-II and LpA-I:A-II levels at admission, but not HDL cholesterol or other HDL-related biomarkers, were associated with the extent of the inflammatory response during STEMI, as indicated by the positive correlations with CRP AUC (apoA-II: F = 7.44, p = 0.009; LpA-I:A-II: F = 14.29, p < 0.001), and IL-6 AUC (apoAII: F = 6.98, p = 0.012; LpA-I:A-II: F = 6.67, p = 0.013). By multivariate analysis the plasma LpA-I:A-II level at admission was a powerful independent predictor of the inflammatory response, evaluated either as CRP AUC (F = 22.30, p < 0.001), or IL-6 AUC (F = 6.92, p = 0.012). During STEMI, the plasma concentration of LpA-I:A-II, but not LpA-I particles decreased, HDL became larger and progressively enriched in serum amyloid A; these changes occurred only in patients with a significant inflammatory response. Conclusion: An elevated plasma concentration of LpA-I:A-II particles was an independent predictor of a more severe inflammatory response in patients with STEMI

Off-target effects of thrombolytic drugs : apolipoprotein A-I proteolysis by alteplase and tenecteplase

The administration of thrombolytic drugs is of proven benefit in a variety of clinical conditions requiring acute revascularization, including acute myocardial infarction (AMI), ischemic stroke, pulmonary embolism, and venous thrombosis. Generated plasmin can degrade non-target proteins, including apolipoprotein A-I (apoA-I), the major protein constituent of high-density lipoproteins (HDL). Aim of the present study was to compare the extent of apoA-I proteolytic degradation in AMI patients treated with two thrombolytic drugs, alteplase and the genetically engineered t-PA variant tenecteplase. ApoA-I degradation was evaluated in sera from 38 AMI patients treated with alteplase or tenecteplase. In vitro, apoA-I degradation was tested by incubating control sera or purified HDL with alteplase or tenecteplase at different concentrations (5-100 \u3bcg/ml). Treatment with alteplase and tenecteplase results in apoA-I proteolysis; the extent of apoA-I degradation was more pronounced in alteplase-treated patients than in tenecteplase-treated patients. In vitro, the extent of apoA-I proteolysis was higher in alteplase-treated sera than in tenecteplase-treated sera, in the whole drug concentration range. No direct effect of the two thrombolytic agents on apoA-I degradation was observed. In addition to apoA-I, apoA-IV was also degraded by the two thrombolytic agents and again proteolytic degradation was higher with alteplase than tenecteplase. In conclusion, this study indicates that both alteplase and tenecteplase cause plasmin-mediated proteolysis of apoA-I, with alteplase resulting in a greater apoA-I degradation than tenecteplase, potentially causing a transient impairment of HDL atheroprotective functions

THE PLASMA CONCENTRATION OF LPA-I:A-II PARTICLES AS A PREDICTOR OF THE INFLAMMATORY RESPONSE IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION.

Abstract Objective: To investigate the relationship between plasmaHDLat admission and the extent of the inflammatory response during anST-elevation myocardial infarction (STEMI), and to analyse structural HDL changes during STEMI as related to the extent of inflammation. Methods and results: CRP and IL-6 were monitored for 96 h in 45 patients with STEMI. Plasma apoA-II and LpA-I:A-II levels at admission, but not HDL cholesterol or other HDL-related biomarkers, were associated with the extent of the inflammatory response during STEMI, as indicated by the positive correlations with CRP AUC (apoA-II: F = 7.44, p = 0.009; LpA-I:A-II: F = 14.29, p < 0.001), and IL-6 AUC (apoAII: F = 6.98, p = 0.012; LpA-I:A-II: F = 6.67, p = 0.013). By multivariate analysis the plasma LpA-I:A-II level at admission was a powerful independent predictor of the inflammatory response, evaluated either as CRP AUC (F = 22.30, p < 0.001), or IL-6 AUC (F = 6.92, p = 0.012). During STEMI, the plasma concentration of LpA-I:A-II, but not LpA-I particles decreased, HDL became larger and progressively enriched in serum amyloid A; these changes occurred only in patients with a significant inflammatory response. Conclusion: An elevated plasma concentration of LpA-I:A-II particles was an independent predictor of a more severe inflammatory response in patients with STEMI

Usefulness of exercise test in selected patients coming to the emergency department for acute chest pain.

BACKGROUND: The management of patients with acute chest pain is a common and difficult challenge for clinicians. In our emergency department (ED) a systematic protocol that involves the use of the exercise test for the management of patients with chest pain of suspected cardiac origin is presently running. The aim of the present study was to evaluate the feasibility of such a test in this setting, in terms of the safety and satisfactory follow-up of these patients discharged home. METHODS: Patients with chest pain lasting &lt; or = 24 hours, aged &gt; 18 years, without a history of trauma or of any other evident medical cause of chest pain and without high-risk characteristics were included in the present study. These patients, defined as low-risk patients for acute coronary events on admission, were evaluated in the ED area and submitted to serial ECG and blood sampling for the determination of the creatine kinase-MB mass and troponin I serum levels on admission and at 6 and 12 hours after admission. A symptom-limited maximal exercise was performed in the patients with a negative clinical observation and typical chest pain or atypical chest pain but multiple coronary risk factors. RESULTS: In the year 2000, 1370 patients were evaluated in the ED for chest pain. In 150 (11%) an exercise test was performed. The test was positive in 24 patients (16%). The criteria for a positive test were only clinical in 3 patients, only ECG in 13 patients, and both in 8 patients. Inconclusive tests were observed in 27 patients (18%) and the test was negative in 99 patients (66%). There were no complications during the exercise test. At a median follow-up of 237 days (range 11-443 days), 11 clinical events were recorded (4 acute coronary syndromes and 7 revascularization procedures). Patients with a non-negative exercise test had a significantly shorter event-free survival (p &lt; 0.005). CONCLUSIONS: The exercise test performed in selected patients coming to the ED with acute chest pain is safe and useful for further risk assessment