Role of lipid, apolipoprotein levels and apolipoprotein E genotype in young Italian patients with myocardial infarction.

BACKGROUND AND AIM: Studies of young patients with acute myocardial infarction (AMI) have demonstrated that conventional risk factors are usually responsible for their premature atherosclerosis. No account has yet been published of the risk profile of young Italians surviving an AMI. In this study, the conventional risk factors, lipids and apolipoproteins, and apolipoprotein E (APOE) allele distribution were evaluated in 98 consecutive AMI survivors (94 males, 4 females) aged 40.1 +/- 3.9 for at least three months after their acute event. These survivors were matched for age, sex, body mass index and presence of diabetes mellitus with 98 controls selected from subjects admitted to the same hospital for other reasons. METHODS AND RESULTS: Lipid profiles and APOE polymorphism were determined in both groups. Coronary angiography during hospitalization showed the absence of critical stenosis in 6.6% of the survivors, mono-vessel disease in 57.7%, and multi-vessel disease in 35.5%. The survivors had a higher frequency of smoking, hypertension, family history for coronary artery disease (CAD) and dyslipidemia, and a much greater frequency of 3 or more risk factors than the controls: Odd ratios (OR) 7.4, 95% confidence interval (CI) 2.5-18.6, p = 0.0000. Significant differences were found between the groups for triglycerides (p = 0.000002), total cholesterol (p = 0.003), LDL-cholesterol (p = 0.012), HDL-cholesterol (p = 0.0002), apolipoprotein AI (p = 0.00001), and Apolipoprotein B (p = 0.000001). No differences were observed in APOE allele distribution (APOE*4 0.11 vs 0.08, APOE*3 0.86 vs 0.89, APOE*2 0.03 vs 0.03), nor in lipid profile when both higher risk genotype (E3/4, E4/4, E2/4) and lower risk genotype groups (E2/2, E2/3, E3/3) were analysed. OR were calculated as measures of the association of the E4-positive genotypes with AMI. They indicated a non-significant increase in risk of AMI when the survivors were compared with the controls (OR 1.78, 95% CI 0.84-3.70, p = 0.13). CONCLUSIONS: This study provides further evidence that conventional coronary risk factors are usually present in young AMI patients. The APOE*4 allele was associated with a 1.8 non-significant increase in the risk of AMI in our group with premature CAD. Comparison with controls showed that the presence of three or more risk factors sharply increased the probability of premature CAD and that hyper-triglyceridemia is an independent risk factor. The data on APOE polymorphism are less certain and a larger study is needed.

[Usefulness of a protocol for carotid sinus massage in supine and erect postures in patients with syncope without other cardiovascular or neurological diseases]. / Utilità di un protocollo di massaggio del seno carotideo in clino ed ortostatismo in pazienti con sincope senza altre patologie cardiovascolari o neurologiche.

BACKGROUND: Carotid sinus massage is a first level test when investigating the cause of syncope. It is normally performed in the supine and erect positions. However, there is no standard complete protocol. So we have devised a new protocol to evaluate the utility of carotid sinus massage in different postures and the influence of patients age on the response. METHODS: Two groups of subjects were selected: a group of 167 patients (mean age 50 ys +/- 18, 105 males, 62 females) with a history of syncope without cardiovascular and neurological disease and 20 asymptomatic control subjects (mean age 52 ys +/- 13, 11 males, 9 females). Carotid sinus massage was performed supine, just after passive tilt, after 5 minutes of tilt and just after passive return to supine. If a pause > 3" was detected, the protocol was repeated after atropine i.v. injection. DEFINITIONS: Borderline vasodepressor: blood pressure reduction > 30 but < 50 mm Hg without symptoms; vasodepressor: blood pressure reduction > 50 mm Hg or > 30 mm Hg with symptoms like dizziness, vertigo or syncope; cardioinhibitory: pause > 3"; mixed: cardioinhibitory with blood pressure reduction > 30 mm Hg after atropine. RESULTS: Carotid sinus massage gave all informations in the supine position in 14 (12%) patients, after passive tilt in 67 (57%), after 5 minutes of tilt in 30 (26%), and after return to supine in 6 (5%). The responses were: 13 (8%) borderline vasodepressor, 32 (19%) vasodepressor, 2 (1%) cardioinhibitory, 70 (42%) mixed, 50 (30%) negative. Positive responses were more frequent in patients over 45 years (90% versus 43%). In the control group only 3 (15%) positive responses were elicited (2 borderline vasodepressor, and 1 vasodepressor, all in subjects over 45). CONCLUSIONS: This protocol for carotid sinus massage evidenced positive responses in 70% of patients with syncope without cardiovascular and neurological disease; cardioinhibitory responses are rare (2%); positive responses are more frequent in patients over 45 years; the protocol specificity was 85%.

Streptokinase induces intravascular release of platelet-activating factor in patients with acute myocardial infarction and stimulates its synthesis by cultured human endothelial cells.

BACKGROUND: Reocclusion of a successfully recanalized infarct-related artery may account for failure of thrombolytic therapy. Evidence suggests that the intravascular activation of platelets may limit the response to this treatment. The aim of the present study was to investigate whether platelet-activating factor (PAF), an ether lipid mediator with multiple potent biological activities, is synthesized during therapy with thrombolytic agents. Two sets of experiments were performed: (1) we extracted and quantified PAF in blood of patients with acute myocardial infarction treated or untreated with streptokinase (SK), and (2) since the endothelium/platelet interaction is thought to be at the basis of vascular reocclusion, we studied whether cultured human endothelial cells synthesize PAF after stimulation with SK or plasmin. METHODS AND RESULTS: PAF was extracted from blood samples immediately after acidification to destroy the acid-labile PAF-acetylhydrolase in 25 patients with acute myocardial infarction treated (group A, n = 14) and untreated (group B, n = 11) with intravenous infusion of SK. PAF was detected in 10 of 14 patients of group A and none of group B. PAF began to be detectable 60 to 90 minutes after SK infusion and disappeared from the circulation within 120 to 180 minutes. Percent variation of platelet count over basal values correlated negatively with the amount of PAF present in the circulation at 90 minutes (r = -.719; P < .001) and at 120 minutes (r = -.652; P < .001). Cultured human umbilical cord vein-derived endothelial cells (ECs) synthesized PAF in a dose-dependent manner in response to SK and plasmin, with a synthesis that peaked at 15 minutes and persisted up to 30 minutes for SK and 2 hours for plasmin. PAF extracted from blood samples or from ECs was quantified by bioassay performed after purification by thin-layer chromatography and high-performance liquid chromatography (HPLC). PAF-bioactive material was characterized as PAF with physicochemical and enzymatic treatments, HPLC-tandem mass spectrometry, and specific PAF-receptor antagonists. CONCLUSIONS: The observation that PAF was detectable in the blood of patients of group A only after treatment with SK and was not detectable in patients with a comparable infarct not treated with SK (group B) suggested that SK stimulates the synthesis of this mediator either directly or via plasmin generation. Indeed, cultured human ECs synthesize PAF after stimulation with both SK and plasmin. PAF production by ECs may promote platelet activation and interaction of these cells as well as of circulating leukocytes with endothelium. These events may limit the beneficial effects of thrombolytic therapy.