Background and Aims: A prospective, observational study was conducted to improve the current management of dyslipidemia in very high cardiovascular risk patients in Hungary. The study protocol was prepared and approved even before the publication of the 2019 ESC/EAS recommendation. The main objective of the study was to achieve the LDL-C target value using high-intensity rosuvastatin or rosuvastatin-ezetimibe combination during the 6 months. Methods: In our study, we analyzed the results of 3017 patients (female: 1405 (47%); age: 65+/-10 years). At the baseline 8% of the patients were statin naive and 56% on high-intensity statin monotherapy, 55.5% suffered from CAD, 35.6% from stroke, 20.4% from PAD, 2.9% from CKD, 86.1% from hypertension, 43.4% from diabetes. We calculated LDL-C by using the Martin/Hopkins estimation. After 6 months, we analyzed how many patients achieved the 1.8 or 1.4 mmol/L target LDL-C values and least a 50% reduction. Results: At the end of the study, 20.5% of the patients were treated with high-intensity rosuvastatin monotherapy and 79.5% rosuvastatin-ezetimibe combination (63.7% fix combination). The initial LDL-C level of 3.64+/-1.05 decreased to 2.03+/-0.79 mmol/L (-42%) at 6 month. 48% of patients reached the LDL-C target value of 1.8 and 19% the 1.4 mmol/L, and for rosuvastatin-ezetimibe 20/10 fix combination the target value achievement was: 55.2 and 23.4%, respectively. The LDL-C reduction of at least 50% was achieved in 41% of the patients. Conclusions: In this East-Central European real-world study, it was possible to significantly increase the prescription of the more effective rosuvastatin-ezetimibe combination in secondary prevention.

1. Zsir-szenhidrat anyagcserevaltozasok, gyulladasos es immunfolyamatok hatasa az inzulinrezisztencia alakulasara 2. Cytomegalovirus-fertőzes terhessegben 3. A statinok hepatotoxicitasa

Although triglycerides (TG) are a major risk factor for coronary artery disease (CAD), their exact role is still controversial. Recently, a T/C polymorphism in the promoter region of the apoA5 gene at position 1131 has been found that is associated with an increased plasma TG concentration. We investigated the role of this polymorphism in 308 Hungarian patients with CAD referred to coronary bypass surgery, and in 310 controls recruited from the same area. The prevalence of the apoA5-1131C allele was significantly higher among CAD patients than among controls (10.9% versus 5.7%; P<0.001, Odds ratio (OR) = 1.99 (1.30–3.04)). Controls carrying the rare C allele had in average 23.0% (P<0.001), subjects with CAD 13.8% (P<0.001) higher TG levels compared to common allele homozygotes. The polymorphism was not associated with other conventional CAD risk factors or laboratory data of the patients. In logistic regression models adjusted for age, gender, presence of diabetes, BMI, smoking, LDL-C, HDL-C and hypertension a significantly increased risk of developing CAD was found in patients carrying the apoA5-1131C allele (P<0.001; OR=1.98 (1.14–3.48)), suggesting that this allele variant is an independent genetic risk factor for CAD.

aDepartment of Medical Genetics and Child Development, Faculty of Medicine, University of Pécs, Pécs, bMTA-PTE Clinical Genetics Working Group of the Hungarian Academy of Sciences, Pécs, cDepartment of Neurology and Neurophysiology, Pándy Kálmán County Hospital, Gyula, dDepartment of Hematology, Semmelweis Hospital, Miskolc, eFirst Department of Internal Medicine, Faculty of Medicine, University of Pécs, Pécs, fDepartment of Pediatrics, Faculty of Medicine, University of Pécs, Pécs, gNational Medical Center, Department of Medicine, Budapest, hThird Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, and Research Group of Metabolism, Genetics and Immunology, Hungarian Academy of Sciences, Budapest, Hungary; iDepartment of Internal Medicine and Laboratory of Molecular Medicine, Slotervaart Hospital, Amsterdam, The Netherlands Received: June 30, 2003 Accepted: September 2, 2003

The effect of apolipoprotein E genotype and polymorphisms of lipoprotein lipase gene on plasma postprandial triglyceride levels in familial combined hyperlipidemic subjects and their relatives have not been sufficiently studied. This study included sixteen familial combined hyperlipidemic parents (G1): age: 52 ± 9 years with total-cholesterol: 7.2 ± 1.7 mmol/L, fasting triglycerides: 2.8 ± 1.4 mmol/L and sixteen children (G2) (twelve were normolipidemic): of age: 22 ± 5 years with total-cholesterol: 5.2 ± 1.1 mmol/L, fasting triglycerides: 2.06 ± 1.8 mmol/L and twelve normolipidemic, healthy controls. Blood samples were taken fasting and 2, 4, 6, 8, 10 hr postprandially after the standard fat rich test meal. We determined lipid parameters, apolipoprotein E and lipoprotein lipase HindIII and PvuII polymorphisms as well. The 6-hr critical postprandial triglyceride values were abnormal in both G1: 5.88 ± 2.7 mmol/L and G2: 3.53 ± 2.7 mmol/L (p <0.001), respectively, and differed significantly (p <0.001) from each other. The subjects of familial combined hyperlipidemic families with E4 allele in both generations exhibited significantly (p <0.001) higher and extended postprandial lipemia. We did not find significant effects of lipoprotein lipase HindIII or PvuII polymorphisms on the fasting lipid values alone, however in normolipidemic subjects from the same families the homozygosity of HindIII variation was associated with higher triglyceride postprandial peak (p <0.01). The main findings of our study are that i.) normolipidemic G2 subjects in familial combined hyperlipidemic families have already abnormal postprandial status, and ii.) the 6 h postprandial triglyceride values were correlated with fasting triglyceride levels, which showed association with the apolipoprotein E4 allele.

We have investigated the influence of apo(a) genetics on the relationship between interleukin (IL)-6, and lipoprotein (a) [Lp(a)] levels in 154 patients with monoclonal gammopathy and 189 healthy subjects. No significant differences in Lp(a) levels and distribution of subjects with different sizes of apo(a) isoforms were found between patients and healthy controls. Relationship between IL-6 and Lp(a) levels was strongly dependent on the size of apo(a) isoforms. In patients with high-size apo(a) isoforms Lp(a) levels positively correlated (r=0.475, P=0.0007) to IL-6 concentrations, whereas no correlation was found in patients with low apo(a) isoforms. Our present finding may provide a plausible explanation for the contradictory findings about the acute phase protein nature of Lp(a).

582 Objectives: This study was conducted to evaluate the features of brain FDG-PET in patients with PNS and its correlation with MRI brain and clinical manifestations. Methods: A total of 21 cases with a diagnosis of PNS (8 m, 13 f, age range: 44-77y) were retrospectively analyzed in this study. Among them 15 cases with complete data sets were considered for this analysis. Results: The studied population included limbic encephalitis (n=7), cerebellar degeneration (n=3), sensory motor neuropathy or cognitive decline (n=2), encephalomyelitis (n=2) and myositis (n=1). Eight patients underwent multiple FDG-PET studies in the course of their disease. Among 7 patients with limbic encephalitis, all except for 1 had hypermetabolism in one or both temporal lobes. All had MRI abnormalities restricted to one or both medial temporal lobes (hyperintensities in FLAIR and T2 sequences, with normal or mild hypointensity in T1 sequences and positive contrast enhancement). In 1 case with additional hyperactivity in the brainstem (but normal on MRI) PET correctly predicted subsequent development of central hypoventilation. Among 3 cases with cerebellar degeneration, 2 had significantly decreased activity in the cerebellum which was consistent with cerebellar atrophy and 1 patient had global reduction of FDG uptake in the cerebral cortex. Among 2 cases with sensori-motor neuropathy 1 had diffuse hypometabolism in the cortex and in the other the reduction was limited to both medial temporal lobes. Both cases of encephalomyelitis and 1 case of myositis showed a global reduction of FDG activity in the cerebral cortices. Conclusions: In the population examined, distinct patterns of uptake were observed in the limbic encephalitis and the cerebellar degeneration which were consistent with the clinical presentation in patients with PNS. In the other subtypes global reduction in the cortical FDG uptake was the most predominant feature in this disorder. Research Support (if any): Supported in part by the UICC under ACSBI fellowship.

OBJECTIVE:To evaluate the distribution of apolipoprotein E polymorphism in patients with Type 2 diabetes and their impact on plasma lipid levels.SUBJECTS:Unrelated Type 2 diabetic patients (n = 298) treated by diet and sulfonylurea and not receiving lipid-lowering regimens, elderly (n = 98) and young (n = 101)unrelated healthy control subjects in Hungary.METHODS:Apolipoprotein E genotypes were identified by PCR amplification and subsequent restriction endonuclease digestion.RESULTS:The distribution of the most frequent genotypes in the diabetes group was E2/3 8.7%, E3/3 78.2%, E3/4 12.8%, in the elderly group E2/3 9.2%, E3/3 78.6%, E3/4 12.2% and in the young group E2/3 11.9%, E3/3 62.4%, E3/4 24.8%. The frequencies of allele e4 in the diabetes and in the elderly control group were significantly lower than in the young control group (both P < 0.05). Associations were found between the e4 allele and increased triglyceride level in the diabetes group, the e2 allele and decreased total cholesterol and LDL-cholesterol levels both in the elderly and young control groups (both P < 0.01).CONCLUSION:The lower frequency of allele e4 in both the elderly and diabetes groups, may be explained by an increased morbidity and mortality in middle-aged carriers of apo e4 allele. The increased risk of e4 carriers in Type 2 diabetes may be partly mediated by a higher triglyceride level.

In animal experiments the protective role of anti-cholesterol antibodies (ACHA) in the development of atherosclerosis has been demonstrated. Despite the fact that ACHA are present in the serum of healthy humans, no data on the occurrence of these antibodies in human diseases are available. We determined serum concentrations of IgG type ACHA by an enzyme immunosorbent assay in 600 patients with atherosclerotic vascular diseases (86 patients with peripheral occlusive atherosclerosis, 146 patients with cerebrovascular diseases, 341 patients with severe coronary heart disease (CHD) who received aorto-coronary by-pass, 27 patients with myocardial infarction who did not undergo by-pass operation), in 57 patient controls (complaints of CHD, without coronarographic alterations) and in 218 healthy individuals. ACHA were present in the sera of all persons tested. No serum cofactor is needed for the binding of human ACHA to solid phase cholesterol, binding can be inhibited dose-dependently by LDL and even more strongly with LDL/VLDL preparations purified from human serum. ACHA levels were found to be considerably lower in patients with peripheral occlusive atherosclerosis and cerebrovascular diseases compared with the levels in healthy individuals. By contrast, the ACHA levels of patients with CHD were considerably higher. No differences in the IgG subclass distribution and binding efficiency of ACHA in the sera of CHD patients and controls were found. Thus, our present findings indicate that both low and high ACHA production may be associated with different atherosclerotic vascular diseases.

The aim of the present study was to compare the frequencies of the F allele of C3 complement component and the Leiden mutation of coagulation factor V in patients with severe coronary heart disease (CHD) who survived myocardial infarction (MI; group A), and those who had no MI in their case history (group B). We have determined the C3 allele frequencies by electrophoresis, and Leiden mutation by PCR in 338 patients with severe CHD and in 490 and 523 healthy controls, respectively. The C3*F allele frequency was significantly (p = 0.006) higher in group A (0.213) that in group B (0.132). A significant (p = 0.045) difference was found between ≤60-year group A (0.077) and group B (0.029) patients in the frequency of Leiden mutation. These findings indicate that the C3*F allele and the Leiden mutation may be associated with an increased risk of developing myocardial infarction in CHD patients.

Background: The association between lipoprotein(a) levels, apolipoprotein(a) size and the (TTTTA)n polymorphism which is located in the 5′ non-coding region of the apo(a) gene was studied in 263 patients with severe coronary heart disease and 97 healthy subjects. Methods: Lp(a) levels were measured by ELISA, apo(a) isoform size was determined by SDS–agarose gel electrophoresis, and analysis of the (TTTTA)n was carried out by PCR. For statistical calculation, both groups were divided into low (at least one apo(a) isoform with ≤22 Kringle IV) and high (both isoforms with >22 KIV) apo(a) isoform sizes, and into low number (<10 in both alleles) and high number of (≥10 at least one allele) TTTTA repeats. Results: Lp(a) levels were higher (P=0.007), apo(a) isoforms size ≤22 KIV and TTTTA repeats ≥10 were more frequent (P=0.007 and 0.01) in cases than in controls. Lp(a) levels were found to be increased with low apo(a) weight in both groups (both P<0.0001). In multivariate logistic regression analysis, only the Lp(a) levels (P=0.005) and (TTTTA)n polymorphism (P=0.002) were found to be significantly associated with CHD. Conclusion: Nevertheless, these results indicate that in CHD patients the (TTTTA)n polymorphism has an effect on Lp(a) levels which is independent of the apo(a) size.

Endothelial dysfunction can be detected in the early phase of atherosclerosis. Two unresolved questions have been raised the wether, (1) the dyslipidemic state alone without any other risk factors can be harmful for the endothelial function measured by ultrasound, and (2) the use of the antilipidemic fibrate is sufficient to influence the endothelial functions. From 38 subjects with solitary combined dyslipidaemia 32 (84%) showed endothelial dysfunction measured by flow mediated vasodilatation (FMD) on the forearm and this group of patients was featured only by higher fibrinogen levels (no differences on BMI, serum lipid and glucose level). The patients with endothelial dysfunction were treated with 100 mg of ciprofibrate per day (12 women, 20 men, average age: 44.6 +/- 9 years, BMI 24.6 +/- 3.4 kg/m2). The pretreatment serum lipid levels were: total cholesterol 6.9 +/- 0.4, triglyceride 4.2 +/- 0.3, HDL cholesterol 1.13 +/- 0.21 mmol/l. After the 4 weeks treatment period the cholesterol and triglyceride level decreased, the concentration of HDL cholesterol increased significantly, which changes were in correspondence with significant improvement of FMD (3.9 +/- 0.7% vs. 7.0 +/- 1.6%). The level of fibrinogen also declined significantly. At the 8th week there were no significant further changes compared to the data received at the 4th week. Using the lineal regressive analysis the improved vasodilatator respond at both check points was correlated only with the fall of total cholesterol level. The ciprofibrate was suspended after the 8th week for a 4 weeks period and the triglyceride and the fibrinogen levels increased whereas the HDL cholesterol level decreased significantly. The FMD impaired significantly (to 5.8 +/- 1.2%). There were no correlations among the changes. The results demonstrated the lipid and probably non-lipid-factors are important in these early damages of endothelial functions.