M. Capanni

Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study

Background  Recent studies suggest a role of n‐3 long‐chain polyunsaturated fatty acids (n‐3 PUFA) as peroxisome proliferator‐activated receptor‐α ligands in improving non‐alcoholic fatty liver disease (NAFLD) in rodents. However, data in humans are still lacking.

High Prevalence of Anti-β2 Glycoprotein I Antibodies in Patients with Ischemic Heart Disease

Ischemic cardiac manifestations have been reported in a various percentage of patients with anti-phospholipid antibodies. As concerns the relationship between anti-beta2 glycoprotein I antibodies (anti-beta2-GPI) and ischemic heart disease (IHD), it was investigated in only one coronary primary prevention study. We investigated the prevalence of anti-beta2-GPI in a well characterized group of patients with different clinical manifestation of IHD. Sera from 37 patients (mean age 62.7 +/- 9.9) with IHD (20 with unstable angina-UA and 17 with effort angina-EA) and from 40 healthy subjects, matched for age and sex, were tested for the presence of IgG and IgM anti-beta2-GPI using an ELISA technique. Eleven/37 patients (29.7%) resulted positive for anti-beta2-GPI. A positivity for IgG anti-beta2-GPI was found in 10 patients, 1 patient was positive for IgM and 1 for both isotypes. The prevalence of anti-beta2-GPI in the control group resulted significantly lower (2.5%; p < 0.005) than in patients with IHD. Positivity for anti-beta2-GPI was found in 9/20 (45%) patients with UA and only in 2/17 patients (11.8%) with EA (p = 0.0365). IgG anti-beta2-GPI levels (median 7.7U/ml, range 2.6-24.1) were significantly higher in patients with UA compared to patients with EA (median 4.6 U/ml, range 2.3-11.5; p = 0.02) and controls (median 3.15 U/ml, range 2.3-9.0; p < 0.0001); also IgM levels resulted higher in patients with unstable angina. A positivity for anti-beta2-GPI was observed in 4/13 patients (30.8%) with a previous myocardial infarction (MI) and in 7/24 (29.2%) patients without a previous MI. Our findings suggest that anti-beta2-GPI could represent an expression of the T-cell activation detectable in patients with unstable angina. The lack of a significant difference in the prevalence of these antibodies in patients with or without a previous MI suggests that anti-beta2-GPI are not induced by tissue necrosis.

Role of platelet glycoprotein PLA1/A2 polymorphism in restenosis after percutaneous transluminal coronary angioplasty ☆

This study suggests a macroheterogeneity in prevalence of platelet glycoprotein PL(A1/A2) polymorphism in different ethnic populations. In patients undergoing percutaneous transluminal coronary angioplasty, this polymorphism does not represent an independent risk factor but seems to be implicated in restenosis after percutaneous transluminal coronary angioplasty.

Postprocedural PAI-1 activity is a risk marker of subsequent clinical restenosis in patients both with and without stent implantation after elective balloon PTCA.

Stent implantation after balloon dilation of coronary arteries has improved clinical prognosis in patients undergoing transluminal coronary angioplasty (PTCA), but late restenosis remains a relevant problem. A previous study has indicated that PAI-1 activity changes immediately after PTCA without stent implantation are predictive of clinical restenosis. The present study was aimed to investigate the early PAI-1 changes and fibrin formation in patients undergoing elective PTCA with stent implantation. PAI-1 activity and D-dimer plasma levels were evaluated in two groups of patients (G1 underwent only elective balloon PTCA and G2 underwent elective PTCA with stent implantation) before and after the procedure. At the end of the procedure, PAI-1 activity significantly decreased, while D-dimer levels significantly increased in both groups. Post-PTCA D-dimer levels in the group with stent implantation were significantly higher than in the other group (P<.05). In both groups of patients, the post-PTCA PAI-1 activity was higher in patients with subsequent clinical recurrence with restenosis (P<.005 in G1 and P<.0005 in G2) than in those without, whereas no differences were found in D-dimer levels. In conclusion, our results demonstrate that fibrin formation assessed by D-dimer levels is enhanced by stent implantation. However, this behaviour is not related, differently from PAI-1 changes, to subsequent occurrence of clinical restenosis.

Need of more frequent International Normalized Ratio monitoring in elderly patients on long-term anticoagulant therapy after influenza vaccination.

Previous findings suggest the safety of influenza vaccination for patients on oral anticoagulant therapy (OAT). However, some studies reported a moderate reduction or increase of the anticoagulation. We assessed the effect of influenza vaccination on anticoagulation levels. Seventy-three patients on stable long-term OAT were recruited. Patients were compared with a control group of 72 patients observed during the same period. No differences in the anticoagulation levels were found in patients and in controls during the 3 months before and after the vaccination. However, in patients older than 70 years we observed a reduction of anticoagulation intensity achieved in the month after the vaccination, with a prolonged time spent below the therapeutic range (10% before and 27% after, P = 0.001), and this behaviour was still observed 3 months after vaccination. Influenza vaccination is safe in patients on OAT, but it is associated with a slight reduction in warfarin effect in the elderly, suggesting the need of more frequent International Normalized Ratio monitoring after vaccination in these subjects.

Lipoprotein (a) and anticardiolipin antibodies are risk factors for clinically relevant restenosis after elective balloon percutaneous transluminal coronary angioplasty

Recent reports have shown the importance of new risk factors for cardiovascular disease. We investigated the relationship between Lp(a), fibrinolytic parameters and anticardiolipin antibodies (aCL) and the occurrence of clinical recurrence owing to restenosis after elective balloon percutaneous transluminal coronary angioplasty (PTCA) without stenting. In 167 patients, undergoing PTCA, Lp(a) plasma levels, aCL, euglobulin lysis time (ELT), plasminogen activator inhibitor-1 (PAI-1) activity and tissue-type plasminogen activator (t-PA) plasma levels were evaluated before the procedure. During follow-up 29 patients underwent clinical recurrence due to restenosis. Lp(a) levels were significantly higher in patients with restenosis in comparison to those without (P<0.05); an earlier restenosis was observed in patients with Lp(a) values >450 mg/L. Kaplan-Meier survival estimate showed an earlier occurrence of restenosis in patients with base-line Lp(a)>300 mg/l associated with aCL positivity. High Lp(a) plasma levels play a role in the occurrence of clinical recurrence due to restenosis after elective balloon PTCA without stenting; the association with aCL accelerates the development of restenosis.

Impairment of early fibrinolytic activation after PTCA: a mechanism for restenosis-related clinical recurrence?

Objective: This study was aimed to investigate the acute effect of PTCA on clotting activation and fibrinolytic system and the possible role of modifications of haemostasis in relation to restenosis-related clinical recurrence after PTCA. Setting: Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy. Material and methods: In 83 unselected patients (70 men and 13 women) undergoing PTCA, blood clotting (fibrinogen, F1+2 TAT) and fibrinolytic activation (D-dimer, ELT, PAI-1, t-PA) were assayed before and immediately after PTCA. Results: At the end of the procedure there was a significant decrease in plasma levels of fibrinogen (P < 0.0001), F1+2 (P < 0.0001), TAT (P < 0.0001), PAI-1 (P < 0.0001) and t-PA (P < 0.001), a shortening of ELT (P < 0.0001) and a significant increase in D-dimer concentration (P < 0.0005). Post-procedyral PAI-1 activity levels were significantly higher in patients with subsequent clinical recurrence owing to restenosis than in those without (P < 0.0005); similarly, patients with restenosis showed lower t-PA levels (P < 0.0005) and longer ELT (P < 0.05) after PTCA than those without. An earlier occurrence of clinical recurrence owing to restenosis was observed in patients with an increase or no variation of PAI-1 levels at the end of the procedure. Conclusion: These results suggest that the early fibrinolytic response to balloon injury is a relevant determinant of the risk of clinical recurrence owing to restenosis after PTCA, possibly by determining ‘per se’ a longer local persistence of thrombus and by triggering a release of mediators involved in the proliferation of smooth muscle cells.

Low-Dose Heparin Pretreatment is not Able to Prevent Clotting Activation during Coronary Angiography

The common use of coronary angiography in the treatment of coronary artery disease has 1. Methods prompted many investigations on changes in hemostasis activation during this procedure. Many 1.1. Patients factors may interfere with the results obtained: previous pharmacological treatments, catheterization The study population consisted of 25 consecutive, procedures, drugs administered during procedures, unselected patients with coronary artery disease (21 radiographic contrast media (CM), etc. [1]. An immen and 4 women), aged 41–73 years, referred to portant issue is the role played in hemostatic changes the Institute of Internal Medicine and Cardiology for by non ionic CM, which have been shown to be pocoronary angiography. All patients were on therapy tentially thrombogenic [2–4]. A limited number of with standard antianginal drugs. No patient had prein vivo studies have indicated that both platelet and existing hemostatic defects or anticoagulant treatclotting activation occur after coronary angiography ment. Aspirin (100–325 mg/day) had been taken performed by non ionic CM [3,5,6]. Recently, Mukfor at least one month before angiography by all herjee et al. [6] observed a marked blood clotting patients. The study was carried out according to activation during coronary angiography (not prethe principles of Helsinki declaration. ceded by heparin treatment), whereas such an activation was not found after PTCA in which a heparin bolus of 20000 IU was injected. No information is 1.2. Coronary Angiography available about the occurrence of blood clotting activation during coronary angiography performed by Coronary angiography was performed through the non ionic CM when a low dose of heparin is adminisfemoral approach with a 6 F catheter. All patients during the procedure received 3000 IU of heparin intravenously (i.v). About 150–200 ml of CM were Abbrevations: CM, constrast media; SPA, spontaneous platelet aggregation; TAT, thrombin-antithrombin complexes; PRP, plateinjected into coronary arteries during each examilet-rich-plasma. nation; the CM employed was a low-osmolar non Corresponding author: Rosanna Abbate, Clinica Medica Generale ionic one, iohexol sodium (Omnipaque-Nycomed, e Cardiologia, Universita di Firenze, Viale Morgagni 85, 50134 Firenze, Italia. Tel: 139 (55) 4277954; Fax: 139 (55) 4277608. Norway).

Occurrence of Diffuse, Poorly Differentiated Hepatocellular Carcinoma During Pegylated Interferon Plus Ribavirin Combination Therapy for Chronic Hepatitis C

Abstract Interferon therapy is indicated for the treatment of chronic hepatitis C and prevention of hepatocellular carcinoma. We describe the case of a 66-year-old Italian woman who received pegylated interferon α-2a plus ribavirin combined therapy for HCV-related chronic liver disease. Preliminary hematochemical, ultrasound and bioptic investigations did not show liver cirrhosis or hepatocarcinoma. After 24 weeks of treatment transaminase serum levels were in the normal range and circulating HCVRNA was undetectable by PCR qualitative assay. On week 46 a serious adverse event occurred, with rapid transaminase increase, severe hyperpyrexia, and abdominal pain, leading to interruption of interferon and ribavirin. Liver biopsy was repeated and it revealed poorly differentiated hepatocellular carcinoma. Only palliative care could be performed and the patient died of liver failure within 2 months. The present case underlines that hepatocellular carcinoma can be misdiagnosed in spite of laboratory and instrumental follow-up. More sensitive tools are needed for tumor detection, to avoid IFN impairment of the liver, even though it eradicates HCV.

Association of plasma homocysteine with bone mineral density in postmenopausal women with osteoporosis or osteopenia affected by primary biliary cirrhosis

To the Editor: Osteoporosis is associated with fragility fractures. An increased homocysteine level has been found to be, not only a strong and independent risk factor for osteoporotic fractures, but also a player in bone metabolism. Moreover, it has been demonstrated that a Hcy-lowering therapy reduces the hip fracture rate. Osteoporosis and osteopenia are common findings in patients with primary biliary cirrhosis (PBC) and recent reports have evidenced high levels of homocysteinemia associated to low levels of folate in such population. We examined the association between plasma homocysteine levels and bone mineral density in 20 postmenopausal women with osteoporosis or osteopenia affected by PBC. Data were collected retrospectively from a database of 91 patients affected by PBC who referred to our Gastroenterology Unit. Only 20 patients had all the parameters needed for the analysis. Bone mineral density, measured by dual-energy x-ray absorptiometry, at the lumbar spine and neck of femur were examined. Subjects were classified as osteopenic if t-score at hip or lumbar spine was between 1 and 2 and osteoporotic if it was lower than 2. Fasting and after methionine loading plasma homocysteine levels, plasma folate and vitamin B12 were also recorded. Mean age and body mass index of patients were respectively 64 years (range: 50 to 75) and 24.7Kg/m (range: 18.5 to 30.4). Our PBC population was composed by: 7 patients in stage I, 5 in stage II, 6 in stage III, and 2 in stage IV. Fifty percent of patients resulted osteoporotic whereas the others were osteopenic. Mean homocysteine (fasting and after methionine oral load), folate and vitamin B12 plasma levels were 11.4 and 30.6 mg/L, 5.9 ng/mL and 435 pg/mL, respectively. Fasting and after methionine loading plasma homocysteine levels were significantly and negatively associated with bone mineral densities at neck of femur (r=0.61, P=0.01) (r=0.56, P= 0.034). This relationship was found also considering bone mineral densities of lumbar spine, but statistical significance was present for fasting plasma homocysteine levels (r=0.50, P=0.036) but not for plasma homocysteine levels after methionine loading (r=0.46, P=0.078). No significant correlation was found between folate and vitamin B12 and bone mineral densities at both neck of femur and lumbar spine. Results from this study suggest hyperhomocysteinemia is associated with low bone mineral density and may represent a risk factor for osteoporosis also in patients with PBC. Further studies are needed to confirm these findings and to clarify if a correction of homocysteine levels may decrease the progression of bone loss.