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A lipoprotein(a) genetikailag meghatározott, az LDL molekuláris szerkezetéhez ha­sonló lipoproteinfrakció, amelynek fokozott az atherogenitasa, és az athero­scle­ro­ticus ere­detű érbetegségek független kockázati tényezője. Plazmakoncentrációját kör­nyezeti té­nyezők (táplálkozás, életmód) nem befolyásolják, ezért a primer és szekunder cardiovascularis prevencióban el­sősorban a gyógyszeres terápia került előtérbe. A széleskörűen alkalmazott lipidcsökkentők nem befolyásolják a lipopro­tein(a) plazmaszintjét. A közelmúltban proprotein konvertáz szubtilizin-kexin-9 (PCSK-9) elleni monoklonális antitestek (evolocumab és alirocumab), valamint az siRNS alapú inclisiran, de különösen az LPA mRNS-t megcélzó antisense oligonukleotid, a pelacarsen klinikai alkalmazása so­rán jelentős lipoprotein(a)-csökkentő ha­tást észleltek. Az atheroscleroticus eredetű vascularis betegségek mellett a kalcifikáló aor­tabillentyű-stenosis patogenezisében is meg­­határozó szerepet játszik a lipoprotein(a). A fenti biológiai terápiák alkalmazása eb­ben a kórképben is reményteljes.

A bizonyítékokon alapuló egészségügyi szakmai irányelvek az egészségügyi szakemberek és egyéb felhasználók döntéseit segítik meghatározott egészségügyi környezetben. A szisztematikus módszertannal kifejlesztett és alkalmazott egészségügyi szakmai irányelvek, tudományos vizsgálatok által igazoltan, javítják az ellátás minőségét. Az egészségügyi szakmai irányelvben megfogalmazott ajánlások sorozata az elérhető legmagasabb szintű tudományos eredmények, a klinikai tapasztalatok, az ellátottak szempontjai, valamint a magyar egészségügyi ellátórendszer sajátságainak együttes figyelembevételével kerülnek kialakításra. Az irányelv szektorsemleges módon fogalmazza meg az ajánlásokat. Bár az egészségügyi szakmai irányelvek ajánlásai a legjobb gyakorlatot képviselik, amelyek az egészségügyi szakmai irányelv megjelenésekor a legfrissebb bizonyítékokon alapulnak, nem pótolhatják minden esetben az egészségügyi szakember döntését, ezért attól indokolt esetben dokumentáltan el lehet térni.

The inadequate adherence of patients whose hyperlipidemia is treated with atorvastatin (ATR) to medical instructions presents a serious health risk. Our aim was to develop a flexible approach based on therapeutic drug monitoring (TDM), nonparametric population pharmacokinetic modeling, and Monte Carlo simulation to differentiate adherent patients from partially and nonadherent individuals in a nonrandomized, unicentric, observational study. Sixty‐five subjects were enrolled. Nonparametric, mixed‐effect population pharmacokinetic models of the sums of atorvastatin and atorvastatin lactone concentrations (ATR+ATRL) and of the concentrations of the acid and lactone forms of ATR and its 2‐ and 4‐hydroxylated pharmacologically active metabolites (ATR+MET) were elaborated by including the TDM results obtained in 128 samples collected from thirty‐nine subjects. Monte Carlo simulation was performed based on the elaborated models to establish the probabilities of attaining a specific ATR+ATRL or ATR+MET concentration in the range of 0.002–10 nmol (mg dose)−1 L−1 at 1–24 h postdose by adherent, partially adherent, and nonadherent patients. The results of the simulations were processed to allow the estimation of the adherence of further 26 subjects who were phlebotomized at sampling times of 2–20 h postdose by calculating the probabilities of attaining the ATR+ATRL and ATR+MET concentrations measured in these subjects in adherent, partially adherent, and nonadherent individuals. The best predictive values of the estimates of adherence could be obtained with sampling at early sampling times. 61.54% and 38.46% of subjects in the adherence testing set were estimated to be fully and partially adherent, respectively, while in all cases the probability of nonadherence was extremely low. The evaluation of patient adherence to ATR therapy based on pharmacokinetic modeling and Monte Carlo simulation has important advantages over the collection of trough samples and the use of therapeutic ranges., We set forth a pharmacokinetics‐based clinical laboratory procedure and decision‐making algorithm for the therapeutic monitoring of atorvastatin concentrations at any time that has passed from drug intake to sample collection.

Abstract: Introduction: Previous data showed bacterial infections among diabetic patients to be more serious and frequent, with higher mortality rates in comparison with non-diabetics. Recent investigations, however, are contradictory. Aim: The goal of our prospective, observational study was to compare patients hospitalized on a general medical ward due to community-acquired bacterial infections with type 2 diabetes mellitus (T2DM) to those of non-diabetics (K) by 1) infection localization, 2) spectrum of pathogens, 3) three-month mortality rates. Method: Patients were consecutively involved (T2DM: n = 205, K: n = 202). We characterized the infections, clinical parameters, mortalities of the two groups, and matched them to international data. Results: No difference regarding clinical details of the groups were found except for glycemic parameters and BMI. In the T2DM group the skin- and soft tissue- (37.1%), in the K patients respiratory infections (37.1%) were the most common, followed by urinary ones (31.2% and 31.7%, respectively). Skin- and soft tissue infection incidence among T2DM subjects were higher compared to international results (37.1% vs. 16%). Co-presence of Gram positive and Gram negative bacteria in the skin- and soft tissue infections (23/76 vs. 5/46, p = 0.0149), and polymicrobial origin in the urinary tract infections (34.0% vs. 15.1%, p = 0.0335) were found to be more frequent in T2DM than in K. No difference regarding mortality rates were detected. In T2DM the skin- and soft tissue while in the K group the respiratory infections had the most death counts. Conclusions: We found higher rates of skin- and soft tissue infections among T2DM patients hospitalized on a general medical ward compared to international data. In total we did not find difference regarding three-month mortality between the groups. Our results highlight the importance of primary prevention and shows its inadequacy concerning skin and soft tissue infections among type 2 diabetics in Hungary. Orv Hetil. 2019; 160(41): 1623–1632.

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Aims We hypothesized that the greater the intra- or interventricular dyssynchrony (intraD, interD), the more effective cardiac resynchronization therapy (CRT) is. We sought to improve patient selection for CRT by using novel ECG dyssynchrony criteria. Methods and results Left ventricular (LV) intraD was estimated by the absolute time difference between the intrinsicoid deflections (ID) in leads aVL and aVF divided by the QRS duration (QRSd): [aVLID − aVFID]/QRSd (%). InterD was estimated from the formula: [ V 5ID − V 1ID]/QRSd (%). Their >25% value indicated electrical dyssynchrony present (ED+) and ≤25% value electrical dyssynchrony absent (ED−) diagnoses. Using the intraD + interD criteria (intra + interDC) together, if at least one of them indicated ED+ diagnosis, a final ED+ diagnosis, if both indicated ED− diagnosis, a final ED− diagnosis was made. Two authors, blinded to CRT response, retrospectively analysed pre-CRT ECGs of 124 patients with known CRT outcome. CRT response was defined as improvement of ≥ 1 NYHA class, being alive and having no hospitalizations for heart failure during 6 months of follow-up. 35/124 (28%) patients were non-responders (NRs), using the traditional criteria (TC) correct diagnosis was made in the remaining 89/124 (72%) responder (R) cases. The test accuracy (TA) of intra + interDC + TC [100/124 (81%), P

Considerable evidence suggests that “the lower the better” is a reasonable approach for reducing cardiovascular risk by lowering LDL cholesterol levels. Despite the reduction in cardiovascular events and mortality achieved by statin therapy, significant residual risk remains, especially in severe hereditary hypercholesterolemia, such as familial hypercholesterolemia. Some new strategies to achieve even lower LDL levels are now available, including the addition of cholesterol absorption inhibitor ezetimibe, and the recently available Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies. In addition, new LDL drugs may be effectively administrated in those individuals who are unable to tolerate statins. The authors summarize the efficacy and clinical indications of these new agents and review the currently available guidelines. Orv. Hetil., 2016, 157(31), 1219–1223.

The role of oxidative stress (OXS) due to myocardial nitric oxide synthase (NOS) uncoupling related to oxidative depletion of its cofactor tetrahydrobiopterin (BH4) emerged in the pathogenesis of heart failure with preserved ejection fraction. We determined the prevalence of six single nucleotide polymorphisms (SNPs) of genes encoding enzymes related to OXS, BH4 metabolism, and NOS function in ≥60-year-old 94 patients with hypertension and 18 age-matched controls with normal ejection fraction. Using echocardiography, 56/94 (60%) patients with hypertension had left ventricular (LV) diastolic dysfunction (HTDD+ group) and 38/94 (40%) patients had normal LV diastolic function (HTDD- group). Four SNPs (rs841, rs3783641, rs10483639, and rs807267) of guanosine triphosphate cyclohydrolase-1, the rate-limiting enzyme in BH4 synthesis, one (rs4880) of manganese superoxide dismutase, and one (rs1799983) of endothelial NOS genes were genotyped using real-time polymerase chain reaction method and Taqman probes. Protein carbonylation, BH4, and total biopterin levels were measured from plasma samples. No between-groups difference in minor allele frequency of SNPs was found. We calculated a genetic score indicating risk for OXS based on the minor allele frequencies of the SNPs. A high genetic risk for OXS was significantly associated with HTDD+ even after adjustment for confounding variables (odds ratio [95% confidence interval]:4.79 [1.12-20.54]; P = .035). In both patient groups protein carbonylation (P

Background Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is a rare, potentially life-threatening disorder characterized by recurrent edematous attacks. The edema formation is the consequence of interaction of bradykinin and various vasoactive peptides with endothelium. Besides these agents, danazol, a modified testosterone derivative used in these patients to prevent edematous attacks, can also affect the function of the endothelium, because it shifts the blood lipid profile to a pro-atherogenic phenotype. Objective To assess the endothelial function in C1-INH-HAE patients and in healthy matched controls. Methods To evaluate the endothelial function, we used the flow-mediated dilation method measured in the region of the brachial artery in 33 C1-INH-HAE patients and in 30 healthy matched controls. Laboratory measurements of standard biochemical parameters were performed on computerized laboratory analyzers. Results No difference was found in endothelial function (reactive hyperemia, RH) between patients (median, 9.0; 25%-75% percentile, 6.3-12.9) and controls (median, 7.37; 25%-75% percentile, 4.52-9.93). Although we found elevated cardiovascular risk (high body mass index and low-density lipoprotein/high-density lipoprotein ratio) in danazol-treated C1-INH-HAE patients, RH values did not differ between danazol-treated and nontreated patients. Furthermore, risk factors correlated with the endothelial function only in healthy controls and patients not treated with danazol. Conclusion In summary, our results did not indicate any signs of endothelial dysfunction in C1-INH-HAE patients. Moreover, the normal endothelial function in danazol-treated patients with pro-atherogenic lipid profile suggests that elevated bradykinin level or other factor(s) involved in the pathogenesis of edematous attacks may have a protective role against endothelial dysfunction and atherosclerosis.

MacIver and Townsend's hypothesis predicts, based on a mathematical model of left ventricular contraction, that preserved absolute radial wall thickening (radWT) due to left ventricular hypertrophy is responsible for the normal ejection fraction in patients with heart failure with preserved ejection fraction (HFPEF).We tested the validity of this hypothesis by detailed echocardiography including evaluation of ventricular myocardial strain (S) using speckle tracking imaging in at least 60-year-old 18 controls and 94 hypertensive patients with normal ejection fraction.Echocardiography revealed no left ventricular diastolic dysfunction in 38 out of 94 (40%) patients with hypertension (HTDD-negative group), and 56 out of 94 (60%) patients had diastolic dysfunction (HTDD-positive groups). The absolute values of global longitudinal left ventricular peak systolic S were significantly reduced in both patient groups (P 0.05 for HTDD-negative, P 0.01 for HTDD-positive groups) vs. the controls. There were no significant between-groups differences in circumferential and radial peak left ventricular systolic Ss, radWT and ejection fraction. Left ventricular mass (LVM) (P 0.001), LVM/BMI (P 0.01) increased in the HTDD-positive group and ejection fraction/LVM/BMI decreased in both patient groups (P 0.01 for HTDD-negative, P 0.001 for HTDD-positive groups) vs. the controls. LVM increased, ejection fraction/LVM/BMI decreased in the HTDD-positive group vs. the HTDD-negative group (P 0.05 and P 0.01, respectively).We demonstrated decreased longitudinal left ventricular systolic function and showed that preserved ejection fraction was due to preserved absolute radWT and not due to increased radial or circumferential systolic function in patients with hypertension and normal ejection fraction, a potential HFPEF precursor condition. Instead of ejection fraction, rather ejection fraction/LVM/BMI might be used to detect subtle left ventricular systolic dysfunction in hypertension and HFPEF.

Cancer hypoxia correlates with therapeutic resistance and metastasis, suggesting that hypoxic adaptation is a critical survival advantage for cancer stem cells (CSCs). Hypoxic metabolism, however, may be a disadvantage in aerobic circulation as the extremely low incidence of metastasis-compared to the high circulating tumor-cell numbers (CTCs)-appears to suggest. As rare metastatic CSCs still survive, we searched for a mechanism that protects them from oxygen in circulation. CSCs form multicellular spheroids in vitro from virtually all cancers tested. We asked, therefore, whether cancers also form spheroids in vivo and whether circulating spheroids play a role in metastasis. We used metabolic, apoptotic and hypoxia assays, we measured aerobic barriers and calculated hypoxia vs. spheroid-size correlations. We detected metabolic/oxidative stress in spheroids, we found correlation between stem cell presence and hypoxia and we showed that the size of hypoxic spheroids is compatible with circulation. To detect spheroids in patients, we worked out a new light-scatter flow cytometry blood test and assayed 67 metastatic and control cases. We found in vivo spheroids with positive stem cell markers in cancer blood and they showed exclusive correlation with metastasis. In conclusion, our data suggest that metastatic success depends on CSC-association with in vivo spheroids. We propose that the mechanism involves a portable "micro-niche" in spheroids that may support CSC-survival/adaptation in circulation. The new assay may establish a potential early marker of metastatic progression.

Cardiac arrest causes generalized ischemia/hypoxia, and subsequent resuscitation inflicts reperfusion injury, the pathology of which is not fully understood. Moreover, predicting the prognosis of comatose, post-cardiac-arrest patients is a complex clinical challenge. We hypothesized that the extent of complement activation might be a reliable predictor of mortality in this population. Forty-six comatose cardiac arrest patients were enrolled into our prospective cohort study, conducted in a tertiary care university clinic. All subjects were cooled to 32-34 degrees C body temperature for 24 hours and then, allowed to rewarm to normothermia. All patients underwent diagnostic coronary angiography. On admission, at 6 and at 24 hrs, blood samples were taken from the arterial catheter. In these, complement products (C3a, C3, C4d, C4, SC5b9, and Bb) were measured by ELISA in blood samples. Patients were followed-up for 30 days; 22 patients (47.8%) died by the end of this period. We observed that complement activation (determined as the C3a to C3 ratio) was higher in non-survivors than in survivors at each time point. In the multivariate Cox regression analysis, the C3a/C3 ratio determined 24 hours after the initiation of therapeutic hypothermia predicted 30-day mortality regardless of age, sex, and the APACHE II score. Complement activation occurs in post-cardiac arrest patients, and its extent correlates with 30-day survival. The C3a/C3 ratio might prove useful for estimating the prognosis of comatose post-cardiac-arrest patients. This article is protected by copyright. All rights reserved.

Considerable evidence suggests that "the lower the better" is a reasonable approach for reducing cardiovascular risk by lowering LDL cholesterol levels. Despite the reduction in cardiovascular events and mortality achieved by statin therapy, significant residual risk remains, especially in severe hereditary hypercholesterolemia, such as familial hypercholesterolemia. Some new strategies to achieve even lower LDL levels are now available, including the addition of cholesterol absorption inhibitor ezetimibe, and the recently available Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies. In addition, new LDL drugs may be effectively administrated in those individuals who are unable to tolerate statins. The authors summarize the efficacy and clinical indications of these new agents and review the currently available guidelines. Orv. Hetil., 2016, 157(31), 1219-1223.

Hematological neoplasms associated with systemic mast cell disease are most frequently of myeloid origin. There are a few reports, however, of systemic mastocytosis (SM) cases associated with lymphoid or plasma cell neoplasms as well. In this report, the authors present a case of SM (with D816V mutation in the c-KIT gene) associated with JAK2 V617F mutation negative essential thrombocythemia. The leading symptom of the 78-year-old female was recurring hydrothorax that responded only to interferon alpha therapy. During the first year of therapy, the patient developed insulin-dependent diabetes and hypothyroidism. The hematological workup also revealed IgG kappa monoclonal gammopathy that was non-progressive in the following next three years. Low levels of complements without known clinical significance accompanied the entire picture.

Multiple myeloma (MM) is a heterogeneous disease group regarding prognosis, clinical course, and response to therapeutic interventions. Numerous prognostic factors have been identified however there was no consensus about the best prognostic indicators or the proper staging systems. In a previous study the A/M ratio containing albumin (A) and monoclonal component (M) emerged as reliable predictor of survival duration in patients treated with conventional chemotherapy. In the current retrospective study authors evaluated the prognostic role of this fraction in the era of novel agents. They assessed the A/M ratio prior treatment in 56 newly diagnosed MM patients from the aspect of the survival time. According to the results the A/M being

Summary Background Adequate persistence of oral antidiabetic treatment is highly important to achieve proper glycemic control in patients with type 2 diabetes. The aim of this study was to evaluate the persistence of initial treatment with metformin and/or sulphonylureas in patients with type 2 diabetes. Material/Methods The study was performed among diabetic patients (n=256,384) who were with newly prescribed oral antidiabetic drugs (metformin and/or sulphonylureas) between 2007 and 2009. For making comparison, patients with newly prescribed statin or clopidogrel therapy (with and without percutaneous coronary intervention) were investigated. The database of the Hungarian National Health Insurance Fund Administration was used. Results The 1-year persistence of initial treatment with metformin, sulphonylureas or metformin/sulphonylurea combination was 47.7%, 45.4% and 55.8%, respectively, which was significantly better than the persistence of statin therapy (26.3%) but worse than that of clopidogrel therapy in patients undergoing coronary intervention (73.2%). Within the sulphonylurea group there was a tendency of better persistence of treatment with the “modified-release” tablets at 12 months compared to the conventional sulphonylureas (47.8 vs. 42.2%). The persistence of therapy using metformin 1000 mg – 60 tablets was significantly better (60.4%) at 12 months than that of other forms of metformin therapy with lower doses and smaller boxes (with fewer tablets) analyzed together (47.7%). Conclusions The persistence of initial treatment with metformin and/or sulphonylureas is far from optimal. Better diabetic care and continuous patient education should be encouraged to achieve higher persistence of oral antidiabetic treatment in patients with type 2 diabetes.

Danazol is a drug most widely used for the prophylaxis of hereditary angioedema resulting from the deficiency of the C1-inhibitor. Potential hepatotoxic or liver tumor-inducing side effects of long-term danazol prophylaxis have been investigated during the follow-up of hereditary angioedema patients.Characteristic parameters of liver function (including bilirubin, GOT, GPT, gammaGT, total protein, ALP, LDH), as well as findings of viral serology screens and abdominal ultrasonography-determined during years 0 and 5 of follow-up of patient groups taking/not taking danazol-have been reviewed and analyzed comparatively.From a population of 126 hereditary angioedema patients, 46 subjects taking danazol and another 46 not taking danazol fulfilled the inclusion criteria. Longitudinal follow-up did not reveal any clinically relevant difference between the liver function parameters determined in years 0 and 5 in the two groups. Abdominal ultrasound did not detect neoplastic or other potentially treatment-related alterations of the liver parenchyma. There were no discontinuations of treatment during the study.Our results clearly suggest that, administered at the lowest effective dose, danazol does not induce liver injury in hereditary angioedema patients.

Background: It has been previously reported that plasma osteopontin (OPN) concentrations are increased in cardiovascular disorders. The goal of the present study was to determine plasma OPN concentrations in healthy pregnant women and preeclamptic patients, and to investigate their relationship to the clinical characteristics of the study subjects and to markers of inflammation [C-reactive protein (CRP)], endothelial activation [von Willebrand factor antigen (VWF:Ag)] or endothelial injury (fibronectin), oxidative stress [malondialdehyde (MDA)] and trophoblast debris (cell-free fetal DNA). Methods: Forty-four patients with preeclampsia and 44 healthy pregnant women matched for age and gestational age were involved in this case-control study. Plasma OPN concentrations were measured with ELISA. Serum CRP concentrations were determined with an autoanalyzer using the manufacturer's reagents. Plasma VWF:Ag was quantified by ELISA, while plasma fibronectin concentrations were measured by nephelometry. Plasma MDA concentrations were estimated by the thiobarbituric acid-based colorimetric assay. The amount of cell-free fetal DNA in maternal plasma was determined by quantitative real-time PCR analysis of the sex-determining region Y (SRY) gene. For statistical analyses, non-parametric methods were applied. Results: Serum levels of CRP, as well as plasma concentrations of VWF:Ag, fibronectin, MDA and cell-free fetal DNA were significantly higher in preeclamptic patients than in healthy pregnant women. There was no significant difference in plasma OPN concentrations between controls and the preeclamptic group. However, preeclamptic patients with plasma fibronectin concentrations in the upper quartile had significantly higher plasma OPN concentrations than those below the 75th percentile, as well as healthy pregnant women [median (interquartile range): 9.38 (8.10–11.99) vs. 7.54 (6.31–9.40) and 7.40 (6.51–8.80) ng/mL, respectively, p Conclusions: Plasma OPN concentrations are increased in preeclamptic patients with extensive endothelial injury. However, further studies are warranted to explore the relationship between OPN and endothelial damage. Clin Chem Lab Med 2010;48:181–7.

The purpose of this study was to determine serum alpha(2)-HS glycoprotein (AHSG) concentration and its diagnostic accuracy in preeclampsia. In this case-control study, the serum C-reactive protein (CRP) and AHSG levels were measured in 93 preeclamptic patients and in 127 healthy pregnant women by immunoturbidimetry and radial immunodiffusion. The serum CRP levels were significantly higher, whereas the serum AHSG concentrations were significantly lower in the preeclamptic group than in the control group (median (25th to 75th percentile), CRP: 6.71 mg l(-1) (2.76-12.69) vs. 3.38 mg l(-1) (1.69-7.27), respectively; AHSG: 660 microg ml(-1) (612-768) vs. 744 microg ml(-1) (660-816), respectively; P

It has been previously reported that circulating anti-heat-shock-protein (Hsp) antibody levels are elevated in cardiovascular disorders. The aim of the present study was to determine circulating antihuman Hsp60, antimycobacterial Hsp65, and antihuman Hsp70 antibody levels in healthy pregnant women and preeclamptic patients and to investigate their relationship to the clinical characteristics of the study subjects, as well as to the markers of inflammation (C-reactive protein (CRP)), endothelial activation (von Willebrand factor antigen), or endothelial injury (fibronectin), oxidative stress (malondialdehyde) and to serum Hsp70 levels. Ninety-three preeclamptic patients and 127 normotensive healthy pregnant women were involved in this case control study. Serum anti-Hsp60, anti-Hsp65, anti-Hsp70, and Hsp70 levels were measured with enzyme-linked immunosorbent assay (ELISA). Serum CRP levels were determined by an autoanalyzer using the manufacturer’s kit. Plasma von Willebrand factor antigen levels were quantified by ELISA, while plasma fibronectin concentration by nephelometry. Plasma malondialdehyde levels were measured by the thiobarbituric-acid-based colorimetric assay. For statistical analyses, nonparametric methods were applied. Anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibodies were detected in all of our serum samples. There were no significant differences in serum anti-Hsp60, anti-Hsp65, and anti-Hsp70 antibody levels between the control and preeclamptic groups. Serum levels of Hsp70 and CRP, as well as plasma levels of VWF antigen, fibronectin, and malondialdehyde, were significantly higher in preeclamptic patients than in normotensive healthy pregnant women. Serum anti-Hsp60 antibody levels showed significant correlations with serum anti-Hsp65 antibody levels both in the control and the preeclamptic groups (Spearman R = 0.55 and 0.59; p

Purpose: Improving the management of cardiovascular disease in Hungary represents an important clinical challenge. This article assesses the achievement of national consensus total cholesterol goals among Hungarian patients of physicians educated about the consensus guidelines and assisted in cardiovascular risk assessment. Methods and results: A total of 320 general practitioners provided data on 15,404 eligible patients. Among these individuals, 14,018 (91%) had documented atherosclerosis and the remaining 9% had ≥ 2 risk factors. Despite this, less than half of all patients received lipid-lowering therapy. Only 12% of high-risk patients attained the consensus total cholesterol target of < 4.5 mmol/L (< 175 mg/dL) and 31% of individuals at low-moderate risk achieved the consensus goal of < 5.0 mmol/L (< 194 mg/dL) at the first visit. Among patients in the high-risk group whose total cholesterol levels were above the consensus goal at the first visit, 54% received no lipid-lowering therapy and 46% receiv...

Allelic distribution of −308 G > A (TNF 1/2) polymorphism of the TNF-alpha, and the +252 A > G promoter polymorphism of the LT-alpha gene, the 1267 A > G polymorphism of the HSP70-2 gene as well as the −429 T > C promoter polymorphism of the RAGE gene were tested in 94 MM cases and 141 controls. Significantly less MM patients than controls carried the TNF2 allele (p = 0.018) and the TNF2-LTA 252G haplotype (p = 0.025). The difference was, however, restricted to the females, as well as the relatively young (

Pre-eclampsia is a pregnancy-related disorder that complicates approximately 5% of all pregnancies and is cited as the primary cause of worldwide maternal and fetal mortality. The factor V Leiden mutation has been implicated in the development of severe pre-eclampsia. In order to investigate this association, a sample of 198 Hungarian women was recruited and enrolled in one of the three groups based on reproductive and health status: those as classified as pregnant and healthy (n = 71), those diagnosed as pregnant and severe pre-eclamptic (n = 69), and those found to be healthy and non-pregnant (n = 58). The presence of factor V Leiden mutation was determined by using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis (RFLP). We identified three (5.2%) heterozygous among healthy non-pregnant participants, five (7.0%) heterozygous among healthy pregnant participants and 13 (18.8%) heterozygous among pre-eclamptic women (p < 0.05, 95% CI). Our result supports the previous observation that carriers of factor V Leiden mutation are at increased risk for developing severe pre-eclampsia.

Complement activation plays an important role in ischemia/reperfusion (I/R) injury. The objective of the present study was to detect the presence and mechanism of complement activation in patients who underwent carotid endarterectomy (CEA).Complement activation products C1rsC1-inhibitor, C4d, C3a and SC5b-9 and concentrations of C-reactive protein (CRP) were measured in samples serially taken from 16 patients with eversion CEA and 10 with carotid artery stenting (CAS) in the first 24h post-surgery/intervention. MBL2 genotypes were also determined.In patients with CEA an intense increase in C3a levels were observed immediately after surgery (p0.001), accompanied by a slight elevation in SC5b-9 levels (p0.05). C3a levels remained elevated until 4h post-surgery, compared with the baseline values and with CAS patients. Peak C3a levels correlated with the time of carotid clamping (r=0.5921, p=0.02). No significant changes were detected in C1rsC1-inhibitor or C4d levels following CEA, and we found no association between the generation of C3a and MBL2 genotypes or CRP levels. Complement activation was not present in patients with CAS.Early complement activation follows CEA and correlates with the time of I/R injury. The lack of C4d generation suggests the role of the alternative and not the lectin pathway in the process.

Hereditary angioedema (HAE) is characterized by episodic edematous attacks due to the deficiency of the C1-inhibitor (C1-INH). Recently, we have described that the long-term use of danazol affects lipid metabolism, resulting in decreased high-density lipoprotein (HDL) and increased low-density lipoprotein (LDL) cholesterol levels, which might lead to accelerated, early atherosclerosis. Our aim in the present study was to investigate the impact of danazol treatment on the risk of atherosclerosis in HAE patients.The prevalence of vascular disease, as well as carotid intima-media thickness (IMT)--an objective marker of atherosclerosis--was determined in 32 HAE patients undergoing danazol prophylaxis, and compared to 25 HAE patients without danazol treatment, as well as to 20 healthy controls. Distinct atherosclerosis risk profiles were determined in addition.HAE patients with danazol prophylaxis had higher body mass index (p=0.0055 and 0.0020), creatinine (p=0.0001 and 0.0130), alanine aminotransferase (p=0.0298 and 0.0457), LDL (p=0.0060 and0.0001) and decreased HDL (p0.0001 and0.0001) levels compared to both control groups. The prevalence of vascular diseases did not differ in the two patient groups. No significant differences were observed in mean (0.43 (0.37-0.50)mm vs. 0.40 (0.35-0.49)mm, p=0.5465) carotid IMT values, when comparing patients with or without long-term danazol prophylaxis.Thickening of IMT due to danazol use was not observed in HAE patients. We hypothesize that the functional deficiency of C1-INH might confer protection against atherosclerosis in these patients.

Multiple myeloma (MM) is a B-cell lymphoma of matured plasmacytic origin. There is a well described spectrum of cutaneous diseases in MM including cell infiltration and amyloid deposition [1]. Little is known about the basic processes involved that allow malignant plasma cells or lymphomas to grow outside the bone marrow environment. Several experimental models have been used to study this issue [2]. Hedvat et al. found altered gene expression profile pattern in plasma cells growing in extramedullary sites mostly involved in angiogenesis and adhesion [3]. Identification of other tumour-specific alterations required for extramedullary growth would confer better understanding of tumour metastasis. In an earlier study authors found that histidine decarboxylase (HDC)that is the only enzyme capable of histamine synthesisis absent from B-lymphocytes infiltrating the skin in a B-cell chronic lymphocytic leukemia patient who developed cutaneous infiltrations in the course of the disease. In contrast to this, those cells that remained in the bone marrow had their HDC activity been preserved [4]. There is evidence that besides histamine being a well known mediator of allergic reactions, may also be involved in certain types of cell proliferations like wound healing, embryonic development and tumor growth [5,6]. There are data confirming that a functioning HDC gene is important in maintaining immune homeostasis [7]. The relation of histamine metabolism and metastatising human plasma cell malignancies has not been examined so far. The case reported here served an appropriate occasion for that.

Background and Purpose—Recently we found that the incidence of restenosis after carotid endarterectomy was significantly higher in patients homozygous for the normal genotype of mannose-binding lectin (MBL2) than in with patients withMBL2variant genotypes. Several growth factors are also known to contribute to restenosis. Therefore, we investigated whether early postoperative changes in serum vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) concentrations andMBL2genotypes interact in the development of restenosis.Methods—Eighty-two patients who underwent carotid eversion endarterectomy and were followed up by carotid duplex scan sonography for 14 months were studied. Growth factors were measured preoperatively and 4 days after surgery.Results—Pronounced significant increases in both VEGF and PDGF predicted restenosis but only in patients who were homozygous for the normalMBL2genotype. In this group, the adjusted odds ratios of restenosis at 14 months in patients with high versus low early VEGF and PDGF increases were 27.73 (2.42 to 317.26) and 9.23 (1.45 to 58.70), respectively.Conclusions—These findings indicate that the development of restenosis depends on both complement activation regulated by theMBL2gene and pathologic processes leading to enhanced production of VEGF and PDGF during the very early postoperative period.

Background Ischemic stroke is a multifactorial disorder with genetic and environmental components. The aim of our study was to investigate whether two polymorphisms of the estrogen receptor α (ESR1) gene (ESR1 c.454-397T>C and c.454-351A>G) are associated with ischemic stroke in a Caucasian population from Hungary. Methods One hundred and ninety-eight patients with ischemic stroke and 180 control subjects were enrolled in this case–control study. Ischemic stroke subtypes were categorized according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification as large-artery atherosclerosis, small-artery occlusion, cardioembolism or stroke of other determined etiology. The ESR1 Pvu II and Xba I genotypes were determined using the PCR-RFLP method. Results There were no significant differences in the genotype, allele and haplotype frequencies of Pvu II and Xba I polymorphisms between the group of patients with ischemic stroke and the control group. Furthermore, ESR1 Pvu II and Xba I genotypes, alleles and haplotypes were not associated with any subtype of ischemic stroke. Conclusions We did not observe an association between ESR1 Pvu II and Xba I gene polymorphisms and ischemic stroke or any subtype of ischemic stroke. However, further studies are needed to explore the complex interaction between environmental factors and ESR1 gene polymorphisms in the risk of ischemic stroke, particularly in ethnically different populations.

Heat shock proteins (Hsps) are primarily known to be intracellular proteins with molecular chaperone and cytoprotective functions. However, Hsp60 and Hsp70 have been found in the serum and plasma of healthy non-pregnant individuals. We aimed to compare serum Hsp70 concentrations in healthy pregnant women with those of healthy non-pregnant women and to determine factors influencing serum Hsp70 levels in normal pregnancy. One hundred and seventy six healthy pregnant women with uncomplicated pregnancies (age, 17-44 years; gestational age, 20-41 weeks) and 81 healthy, age-matched non-pregnant women (age, 22-40 years) were enrolled in this cross-sectional study. Serum Hsp70 concentrations were measured using an enzyme-linked immunosorbent assay, and were significantly lower in healthy pregnant women than in healthy non-pregnant women (median (25-75 percentile): 0.29 (0.20-0.35)ng/ml versus 1.27 (0.86-1.72)ng/ml; p

The presence of autoantibodies to C1-inhibitor (C1-INH-Abs) is a hallmark of acquired C1-inhibitor deficiency. However, only scarce data are available on their prevalence in hereditary angioedema (HAE). In a prospective study performed between 2001 and 2004 in 95 patients with Type I or II HAE, serum samples were taken one to three times a year and clinical status of the patients was registered. Serum samples were tested for total activity of the classical pathway, C1q, C3, C4 and C1-inhibitor (C1-INH) concentration and activity levels, as well as the presence of IgG, IgA and IgM type anti-C1-inhibitor antibodies (C1-INH-Ab). Fifty-four healthy age and gender matched persons served as control. Significant differences between the patients and controls in the occurrence of elevated (2S.D. higher than mean of control) C1-INH-Abs titers was found only in the case of IgM type C1-INH-Abs. Elevated (>4.22AU/ml) IgM C1-INH-Abs levels were found in 31 and 4% of the patients and controls, respectively (p

Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T>C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p

Many recent data indicate that some alleles encoded in the central major histocompatibility complex (MHC) region (Class III) of short arm of chromosome 6 may modify the risk of cancer development. Therefore we determined 4 single nucleotide polymorphisms (SNPs) of this region (TNF-alpha -308 G > A, RAGE -429 T > C, HSP70-2 -1267 A > G, LTA 252 A > G) in genomic DNA samples from 183 Hungarian patients with colorectal cancer and 141 age matched control subjects representing the Hungarian population of the same age and gender. No significant differences were found in either SNP tested. When, however, three- or four-locus haplotypes consisting of known constituents of the so-called 8.1 ancestral haplotype (8.1AH) were considered, marked differences were observed. Frequency of TNF-alpha -308A, RAGE -429C, HSP70-2 -1267G, LTA 252G (8.1AH) haplotype was significantly (p = 0.006) more frequent (19.1%) among patients than in the controls (7.7%). Age- and gender-adjusted ratio of the 8.1AH carriers vs. non-carriers to have colorectal cancer was 2.514 (1.130-5.594). This risk was higher in

KA

Long-term dietary fatty acid intake alters the development of left ventricular hypertrophy, but the linking signaling pathways are unclear. We studied the role and underlying signaling mechanisms of dietary fat intake in the early phase of the hypertrophic process. Rats assigned for 4 weeks of high-oil, high-fat, or standard diet were subjected to angiotensin II (Ang II; 33 microg/kg/h, subcutaneous) or vehicle infusion for 24 h. The Ang II-induced increase in left ventricular mRNA levels of hypertrophy-associated genes was higher in rats fed the high-oil diet compared with the standard diet. Western blotting revealed that, in parallel with changes in gene expression, the high-oil diet increased c-Jun N-terminal kinase phosphorylation (P < 0.001). Ang II increased p38 mitogen-activated protein kinase (MAPK) phosphorylation in rats fed the high-fat diet (3-fold; P < 0.01). The increase in transcription factor activator protein-1 (AP-1) DNA binding activity in response to Ang II was higher in rats fed the high-oil diet compared with those fed the standard diet (P < 0.001). Ang II downregulated inducible nitric oxide synthase mRNA levels in fatty acid-supplemented groups compared with the standard diet group. These results show that dietary fat type modulates the early activation of hypertrophic genes in pressure-overloaded myocardium involving the distinct activation of AP-1 and MAPK signal transduction pathways.

The role of C-reactive protein (CRP) in atherosclerosis is controversial. It is not clear, either, if the presumed endothelium-activating effect of CRP resides in native CRP (nCRP) or in a conformational isoform of CRP known as modified CRP (mCRP). In the present study we evaluated and compared the effect of nCRP, recombinant modified CRP (rmCRP) and urea-modified CRP (umCRP) on human umbilical vein endothelial cells (HUVECs). CRP preparations were carefully analyzed by biochemical, immunological and cell biological methods in order to avoid endotoxin or sodium azide contamination as well as inappropriate conformational changes, which together had possibly been the main reason for the previously published controversial results. Neither nCRP nor mCRP showed significant cytotoxicity up to 100 microg ml(-1) at 24 h but high concentrations of CRPs induced cell death at 48 h. rmCRP but not nCRP nor umCRP showed membrane binding to HUVEC by confocal microscopy. However, none of the CRP forms induced intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin expression or IL-8 production. Monocyte chemotactic protein-1 production was weakly inhibited by high concentration of both nCRP and rmCRP, analyzed by sandwich ELISA. Neither nCRP nor mCRP could induce pro-inflammatory changes in the phenotype of HUVECs. Therefore, our present findings do not support the notion that different isoforms of CRP alone have significant effects on inflammation of the vessel wall via an interaction with endothelial cells (ECs), although one cannot exclude the possibility that there may be significant differences among various types of ECs in the response to CRP.

Our goal was to study changes in anti-cholesterol antibodies (ACHA) levels in patients with severe carotid stenosis after eversion endarterectomy. Seventy consecutive patients who underwent eversion endarterectomy at the Department of Cardiovascular Surgery, Semmelweis University, Budapest, were included in the study. Serum samples from 66 healthy volunteers served as controls. Patients had medical check up at 5.7 (4.6-8.0) weeks (median (interquartile range)), 6.8 (6.2-7.9) months as well as 13.8 (12.3-19.0) months after endarterectomy. In all patients the carotid arteries were investigated by color duplex ultrasound. ACHA concentrations were determined in the serum samples taken before operation as well as at the first and last follow-up visits by using an ELISA method. ACHA concentrations (median (interquartile range) were found to be significantly (p0.0001) lower in the sera of the patients with carotid atherosclerosis (13.5 (8.4-21.3)AU/ml) than in the healthy subjects (26.1 (20.9-33.2)AU/ml) (Mann-Whitney test). Strong negative correlation was found between the preoperative ACHA and LDL-cholesterol levels (r=-0.413, p=0.0004). Serum ACHA concentrations significantly (p0.0001) increased from the values measured before operation (13.5 (8.4-21.3)AU/ml) to 27.1 (19.9-34.7)AU/ml measured at the end of the 14 months long follow-up. Increase occurred only in patients with low or medium baseline ACHA concentration. Our present findings indicate that after surgical removal of atherosclerotic plaques from the carotid arteries the reduced baseline levels of ACHA reach normal values in 1 year. Different not mutually exclusive mechanisms (binding of ACHA to lipid/lipoproteins particles, to advanced plaques or reversibly injured endothelial cells in CNS) can be responsible for this novel finding.

Background and Purpose—Mannose-binding lectin (MBL) is thought to influence the pathophysiology of cardiovascular disease by decreasing the risk of advanced atherosclerosis and by contributing to enhanced ischemia reperfusion injury. Thus, we investigated the role of MBL in restenosis after eversion endarterectomy in patients with severe carotid atherosclerosis.Methods—In a prospective study, 123 patients who underwent carotid endarterectomy were followed-up by carotid duplex scan (CDS) sonography for 14 months. In a retrospective study, we examined 17 patients and 29 patients, respectively, who had or had not at least 50% restenosis 29 months after carotid eversion endarterectomy. MBL genotypes were analyzed by a polymerase chain reaction-based method, and MBL serum concentrations were measured.Results—In the prospective study in the patients homozygous for the normal MBL genotype, CDS values were significantly higher after 14 months of follow-up compared with the values measured 6 weeks after surgery (PP=0.007).Conclusions—These results indicate that reoccurrence of stenosis after carotid endarterectomy is partially genetically determined and imply that MBL contributes significantly to the pathophysiology of this condition.

Hereditary angioedema (HAE) is a rare disorder caused by the deficiency of the C1-inhibitor gene (C1INH) . Patients experience recurrent bouts of edema, which can occur in almost any region of the body. As regards the treatment of the disease, danazol (an attenuated androgen) is used, among other agents, for long-term prophylaxis.The aim of this study was to investigate the possible adverse effects of danazol on serum lipid profile, as well as to ascertain whether danazol treatment is associated with an increased risk of atherosclerosis.Serum concentrations of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, apolipoprotein A-I, apolipoprotein B-100, and lipoprotein(a) were compared between danazol-treated patients with HAE and 2 control groups (ie, patients who did not receive long-term danazol prophylaxis and untreated healthy subjects).Serum concentrations of HDL ( P = .0002 and P.0001) and apolipoprotein A-I ( P = .0015 and P.0001) were significantly lower, whereas LDL ( P = .0129 and P = .0127) and apolipoprotein B-100 ( P = .0456 and P = .0013) were higher in the danazol-treated patients compared with the 2 control groups, respectively. No significant difference was found in total cholesterol, triglyceride, or lipoprotein(a) levels. Patients who received danazol had an 11.6 (95% CI, 2.7-49.7) times higher risk for abnormally low HDL levels and a 4.4 (95% CI, 1.2-16.0) times lower risk for high LDL concentrations.Our findings indicate that the long-term use of danazol is associated with an increased risk for early atherosclerosis in patients with HAE. Consequently, monitoring of HDL and LDL levels at regular intervals is recommended during follow-up.

(1) Cerebral ischemia and reperfusion induce several changes on the endothelial cells at the microcirculatory level. (2) Vasogenic brain edema due to compromised blood-brain barrier, transformation of the endothelial cell surface from an anticoagulant to a procoagulant surface are important factors in the pathogenesis of ischemic stroke. (3) Release of prostaglandins, endothelin-1, complement proteins, and matrix metalloproteinase-9 by microvascular endothelial cells are other components in the complex mechanism of brain ischemia/hypoxia. (4) Ultrastructural studies documented the opened paracellular avenues in the course of vasogenic edema in different experimental models (5) Tight junctions of endothelial cells have been characterized with freeze fracture electron microscopy, and the process of transvesiculation was analyzed using rapid freeze and freeze substitution procedure before electron microscopy studies (6) In endothelial cell-culture experiments, we used rodent and later human brains. (7) Endothelial cells co-cultured with astroglia resulted in an elaborate tight junctional complex. (8) This co-culture technique becomes the basis of in vitro blood-brain barrier studies On endothelial cells of human brain origin, different regulatory factors found to be responsible for the complex mechanism of ischemic stroke.

Atherosclerosis is an inflammatory disease. The complement system plays an important role in the atherosclerotic process. However, lesser data is available on the possible role of C3 as a risk factor for atherosclerosis. Therefore, in a follow up study we determined C3 levels in 266 patients with pre-existing severe coronary artery disease (CAD) and compared their serum C3 concentrations with the cause of the disease. We investigated whether C3 levels predict the major complications of severe CAD during a 5-year long follow up period in patients, who have received an aorto-coronary bypass graft surgery. C3 concentrations were elevated in the patients with severe CAD compared to 182 healthy controls, and women had higher C3 concentrations than men. Pathological C3 levels (C3> or =1.8 g/L) were able to predict major complications of atherosclerosis (death by cardiac events, new acute myocardial infarction, stroke, carotid surgery and peripheral arterial disease) that developed during the follow up period only in women (OR: 4.1, 95% C.I. 1.23-13.61, p = 0.0249) independent of other risk factors for atherosclerosis. Our data supports the assumption that high C3 indicates the progression of atherosclerosis as a special marker of chronic inflammation.

Objective and design: To study changes in the levels of two acute phase proteins, plasma fibrinogen and serum C-reactive protein (hs-CRP) in patients with severe carotid stenosis after eversion endarterectomy. Material and subjects: A total of 117 consecutive patients who underwent eversion endarterectomy were included in the study. Blood samples for acute phase protein measurement were taken before operation as well as 5.7 weeks and 13.8 months (median) post-surgery. Plasma fibrinogen and serum hs-CRP concentrations were promptly determined. Results: During the follow-up period sharp, highly significant (p < 0.0001) drop occurred in the serum concentrations of both acute phase proteins. The drop in the hs-CRP levels during the follow up period was mainly due to decrease in patients with highest baseline CRP levels. Conclusions: Our present findings indicate that removal of atherosclerotic plaques from the carotid arteries markedly decreases the production of two acute phase proteins due to the decrease of the inflammatory burden or the removal of the advanced plaques able to produce these proteins.

Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.

The genetic basis for addiction to tobacco smoking--particularly that of the perception of olfactory stimuli that may be important in reinforcing smoking addiction--is largely unknown. A cluster of genes for olfactory receptors is in close proximity to the MHC region on chromosome 6. Polymorphisms of MHC class III genes (RCCX modules, TNFA promoter polymorphisms) were determined in 101 healthy subjects and 232 coronary artery disease (CAD) patients from Hungary with defined tobacco smoking habits. A highly significant association between ever smoking (past + current smokers) and a specific MHC haplotype was observed (odds ratios = 2.14-4.13; P-values = 0.012 to

OBJECTIVE: The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tIssue in correlation with adipocyte cell Volume, serum TNF-alpha, soluble TNF-receptor-2 (sTNFR-2) and indirect parameters of insulin resistance in overweight/obese and lean healthy persons. DESIGN: A cross-sectional case-control study was used. PATIENTS: Twenty-eight overweight/obese probands with normal glucose tolerance (BMI>27 kg/m(2)) and 15 lean people (BMI

OBJECTIVE—To compare the clinical parameters, C-peptide levels, pattern of islet cell-specific autoantibodies, and prevalence of predisposing genotypes in subjects with latent autoimmune diabetes in adults (LADA) and those with adult-onset type 1 diabetes with rapid progression. RESEARCH DESIGN AND METHODS—We evaluated the clinical parameters, C-peptide levels, and islet cell-specific autoantibodies in 54 LADA, 57 adult-onset type 1 diabetic, and 190 type 2 diabetic patients. Islet cell autoantibodies were also compared between subgroups of newly diagnosed patients with LADA and those with newly diagnosed adult-onset and childhood-onset type 1 diabetes. The genetic study was performed in subjects with LADA and those with adult-onset type 1 diabetes in comparison with a control population. RESULTS—There were no differences in the clinical parameters between LADA and adult-onset type 1 diabetes. Patients with LADA had lower BMI (P < 0.0001), waist-to-hip ratio (0.0029), total cholesterol (P = 0.001), and triglycerides (P = 0.001); higher HDL cholesterol levels (P < 0.0001); and lower prevalence of hypertension (P = 0.0028) compared with patients with type 2 diabetes. C-peptide levels were similar at onset (P = 0.403) but decreased less rapidly in LADA than in adult-onset type 1 diabetes (P = 0.0253). Single-autoantibody positivity was more often seen in LADA than in type 1 diabetes (P = 0.0001). The prevalence of predisposing HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 genotypes and the DR4-DQB1*0302 haplotype were increased in both LADA and adult-onset type 1 diabetic subjects compared with the control population. There were no differences in the frequencies of these risk alleles and haplotypes between the two patient groups. CONCLUSIONS—Subjects with LADA had clinical characteristics similar to those with adult-onset type 1 diabetes with rapid progression. C-peptide levels did not differ at onset but decreased less rapidly in LADA. Patients with LADA rather had single islet cell-specific autoantibody positivity. The prevalence of HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 risk alleles and the DR4-DQB1*0302 high-risk haplotype did not differ in the two forms of autoimmune diabetes.