The characteristics of two LDL-cholesterol level reduction treatment strategies, "treat-to-target" and "percent reduction": an observational study without intervention.

BACKGROUND: The 2014 ACC/AHA guidelines redefined the strategy for LDL-cholesterol (LDL-C) treatment. According to data from evidence-based studies, the basis for earlier therapeutic recommendations for LDL-C target levels (2.6 and 1.8 mmol/L) may be disputed, and only the data for the percent LDL-C reduction are objective. The target is a moderate intensity (30-50%) LDL-C reduction in the high cardiovascular (CV) risk group, and a high intensity LDL-C reduction (> 50%) in the very high risk group. In our study, we analysed the success of the two types of strategies in attaining the target in the everyday routine. METHODS: Of 5652 patients suffering from hypercholesterolemia, 4302 underwent treat-to-target treatment, and 1350 patients were treated with a percent reduction strategy. Physicians were free to choose the dosage and the target treatment form. The 12-month study included three follow-up visits. RESULTS: In the high CV risk, statin-naive subgroup the percent LDL-C reduction strategy has been proven to be clearly more successful than the treat-to-target strategy, i.e. a higher proportion of patients reached the target values. We observed that the absolute value corresponding to a percent reduction target is higher if the baseline LDL-C is higher, and therefore it is easier to reach. CONCLUSION: Therefore, in this large subgroup of patients with baseline LDL-C level higher than 3.9 mmol/L may be recommended the adaptation of the percent reduction assessment.

Roles of Mac-1 and glycoprotein IIb/IIIa integrins in leukocyte-platelet aggregate formation: stabilization by Mac-1 and inhibition by GpIIb/IIIa blockers.

Circulating platelet-leukocyte hetero-aggregates play an important role in acute cardiovascular events and hypersensitivity reactions. The association involves the receptor families of selectins and integrin. The objective of this study was to investigate the role of CD11b/CD18 integrin (Mac-1) in hetero-aggregate formation and search for a counter-receptor on platelets ready to interact with Mac-1. As a model of leukocytes, Mac-1 presenting Chinese hamster ovary (CHO) cells were used to evaluate the role of Mac-1 in hetero-aggregate formation. The amount of CHO cell-bound active and inactive platelets was measured by flow cytometry, while the counter-receptors on platelets were identified via using blocking antibodies. We observed significant platelet adhesion on Mac-1-bearing cells when platelet-rich plasma or activated platelets were present. Inactive platelets did not adhere to Mac-1-bearing cells. Addition of fibrinogen, a ligand of Mac-1 significantly increased platelet binding. CD40L was demonstrated to act similarly on Mac-1. Inhibition of platelet GpIIb/IIIa completely abolished CHO cell-platelet aggregation. In our study, we have shown for the first time that Mac-1 mediates the formation of hetero-aggregates without selectin tethering when Mac-1 ligands such as fibrinogen or CD40L are present and blockers of platelet GpIIb/IIIa are able to diminish this interaction.

Correlations between prescription of anti-hypertensive medication and mortality due to stroke.

BACKGROUND: One of the most important risk factors for stroke is hypertension. A number of studies have attempted to identify the most effective anti-hypertensive therapeutic group for stroke prevention. Using an epidemiologic approach we aimed to find correlations based on Hungarian data on stroke-mortality and on prescription routine of anti-hypertensive therapeutics in three different counties, showing significant difference in stroke mortality. METHODS: We have used the official yearly reports on stroke-mortality for the period 2003-2008. Based on the significant differences in the change in mortality due to stroke three counties were selected: Baranya, Bekes and Hajdu-Bihar. The usage of antihypertensive therapeutic groups was analyzed. The correlation of stroke mortality difference and different antihypertensive treatment habits was analyzed by using normality test, time series analyses, correlation coefficient, paired samples test, one sample test and chi-square test. RESULTS: For the year 2003 stroke-mortality standardized with the county population number was highest in county Bekes, followed by county Baranya and county Hajdu-Bihar. For each year stroke mortality has shown significant (p < 0.0001) difference between the three counties and the ranking/order of the counties has been preserved over time. During the period of our study, an increase in the number of days of treatment was observed for most of the anti-hypertensive drugs listed. We have observed that the increased use of high-ceiling diuretics resulted in a mortality advantage, and the reduction in use of calcium channel blockers with direct cardiac effect had negative consequences. CONCLUSIONS: The authors acknowledge that by limiting the study to three counties the findings cannot be generalized to the whole Hungarian population. Two trends can still be identified:i) increased number of days of treatment (and therefore the probable use) of high-ceiling diuretics is associated with reduction in mortality due to stroke and its immediate complications; ii) reduction in the use of non-dihidropiridin CCBs does not seem justified, as their use appears to be advantageous in stroke prevention. Authors put emphasis on the importance of the adherence of the patients to the preventive therapies. Health care professionals could provide an important added value to the life long preventive therapies by improving the compliance of their patients, giving personalized care and advice.

Safety of a fixed-dose combination of fenofibrate/pravastatin 160 mg/40 mg in patients with mixed hyperlipidaemia: a pooled analysis from a database of clinical trials.

BACKGROUND: Fenofibrate can be prescribed concomitantly with an HMG-CoA reductase inhibitor (statin) to improve achievement of lipid goals in patients with atherogenic mixed hyperlipidaemia. However, some safety concerns, particularly an increased risk of myopathy, have been reported when these drugs are taken together. OBJECTIVE: The aim of this analysis was to assess the general safety and tolerability of a fenofibrate/pravastatin (FF/PRA) 160 mg/40 mg fixed-dose combination (FDC) capsule based on a pooled database of phase III clinical trials in patients with mixed hyperlipidaemia. METHODS: Safety data were pooled from five phase III studies (four double-blind with an uncontrolled extension and one open) of ≥12 to 64 weeks' duration. Adverse event (AE) profiles of FF/PRA 160 mg/40 mg (n=645 in the double-blind cohort) were evaluated relative to comparators (statins, n=519 or fenofibrate, n=122). Absolute incidence rates were calculated in both the double-blind cohort and the all-studies cohort (FF/PRA 160 mg/40 mg, n=1566) for all AEs, drug-related AEs, serious AEs, discontinuations due to AEs, AEs of specific interest including abnormal laboratory data, and deaths. RESULTS: The frequency and/or intensity of overall AEs, drug-related AEs, serious AEs and discontinuations due to AEs were not significantly increased for the FDC (36.0%, 12.3%, 1.7% and 5.1%, respectively) versus the statin (28.7%, 8.9%, 0.8% and 2.7%, respectively) and fenofibrate (59.0%, 21.3%, 0% and 4.9%, respectively) monotherapies. No deaths were reported during the course of treatment in clinical trials. Nevertheless, three deaths were reported more than 30 days after the patients completed the study; none of these deaths were assessed as being related to FF/PRA 160 mg/40 mg treatment. Among the AEs of special interest, no myopathy or rhabdomyolysis were reported; no patients were considered to have experienced a drug-induced liver injury; no case of pancreatitis occurred in the double-blind cohort and four patients reported pancreatitis in the all-studies cohort, two of them being study-treatment related; no case of pulmonary embolism was reported in the double-blind cohort and two patients presented with pulmonary embolism, unrelated to the study drug, in the all-studies cohort; there were more cases of decreased creatinine clearance in the FF/PRA 160 mg/40 mg group (1.7%) than in the statin group (0.6%). CONCLUSION: Within the limitations of this database (notably low percentage of very elderly patients, limited sample size of patients with mild renal insufficiency, and mode of selection in the clinical trials), no particular safety concern was raised with FF/PRA 160 mg/40 mg in the double-blind cohort as compared with statin and fenofibrate monotherapies. The acceptable long-term safety profile of FF/PRA 160 mg/40 mg was confirmed with a low frequency of AEs of interest, comparable to that observed in the 12-week double-blind cohort. Emergent effects possibly related to FF/PRA 160 mg/40 mg were mainly those attributable to fenofibrate (decrease in creatinine clearance and pancreatitis).

Comparative efficacy and safety of fenofibrate/pravastatin plus ezetimibe triple therapy and simvastatin/ezetimibe dual therapy in type 2 diabetic patients with mixed hyperlipidaemia and cardiovascular disease.

BACKGROUND: This study was designed to compare the efficacy and safety of a fenofibrate/pravastatin 160/40 mg fixed-dose combination plus ezetimibe 10 mg triple therapy and simvastatin 20 mg plus ezetimibe 10 mg dual therapy in patients with type 2 diabetes, mixed hyperlipidaemia and cardiovascular disease. METHOD: After a 6-week run-in period on simvastatin 20 mg, 273 patients with non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dl or low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dl were randomised to receive 12-week treatment with triple therapy or dual therapy, followed by a 12-week safety period during which all patients received the triple therapy. RESULTS: At week 12, similar significant decreases in non-HDL-C were observed with both treatments. The triple therapy has induced a greater decrease in triglycerides (between-treatment difference: -14.6%, p = 0.007) and the dual therapy a greater decrease in LDL-C (between-treatment difference: +5.3%, p = 0.05). Both treatments were generally well tolerated. CONCLUSION: The fenofibrate/pravastatin plus ezetimibe therapy improves the global atherogenic lipid profile in type 2 diabetic patients with mixed hyperlipidaemia.

Elevation of monocyte-platelet aggregates is an early marker of type 2 diabetes.

BACKGROUND: Diabetes has been shown to be an accelerating factor in the progression of atherosclerosis. The metabolic changes in diabetes contribute to modified platelet function and enhanced leukocyte-platelet aggregate formation. The attachment of activated platelets leads to the activation of leukocytes causing enhanced cytokine production and upregulation of surface adhesion molecules. Therefore, platelet-leukocyte aggregates may be of great importance in the development of cardiovascular complications. MATERIALS AND METHODS: Monocyte-platelet aggregates and monocyte Mac-1 expression were measured by flow cytometry to obtain differences between type 2 diabetic and healthy subjects. Inflammatory mediators were evaluated to assess the presence of inflammation. RESULTS: We found no signs of inflammation in type 2 diabetes; however, we observed enhanced aggregation level of monocytes and platelets. The expression of Mac-1 did not differ between diabetic and control subjects, but it was significantly higher on monocytes bearing platelets in both groups. CONCLUSIONS: Elevation of monocyte-platelet aggregates is an early marker of diabetes, which precedes the signs of inflammation. Enhanced Mac-1 expression can be observed on monocytes bearing platelets, independent from the presence of diabetes.

[Anti-atherosclerotic effect of pioglitazone--the first evidence of the role of triglyceride/HDL ratio]. / A pioglitazon antiatheroscleroticus hatása. Elso bizonyíték a triglicerid/HDL arány szerepére.

The presence of multiple risk factors can multiply exponentially the risk of cardiovascular events, thus cardiovascular diseases are more severe in diabetes mellitus. One of the challenges we face today is the application of drugs that, besides improving glucose homeostasis, also have antiatherosclerotic effect. Such candidates are glitazones, which have pleiotropic efficiency beyond their main effect: they improve distribution of adipose tissue, blood pressure and endothelial function and also have anti-inflammatory and anti-coagulation capacity. Regarding the effects on lipid metabolism, there are differences between various glitazones: improvements are mainly achieved by pioglitazone, which markedly reduces triglyceride levels, and also elevates HDL levels and decreases the ratio of small, dense LDL-particles. Studies on clinical outcomes also show the superiority of pioglitazone. Imaging of blood vessels (carotis-IMT, intracoronary ultrasound technique) also suggest a greater efficiency of pioglitazone. According to the latest analysis of the PERISCOPE study, the stability of the coronary plaque was associated only with the triglyceride/ HDL ratio in case of pioglitazone. The newest data also revealed that pioglitazone uniquely increases the cholesterol-efflux attributed to HDL-related macrophages. On the basis of the latest results, pioglitazone not only improves glucose homeostasis, but also has a remarkable anti-atherosclerotic effect, which is primarily due to its favourable lipid metabolism profile.

Fixed-dose combination fenofibrate/pravastatin 160/40 mg versus simvastatin 20 mg monotherapy in adults with type 2 diabetes and mixed hyperlipidemia uncontrolled with simvastatin 20 mg: a double-blind, randomized comparative study.

BACKGROUND: Patients with type 2 diabetes mellitus and mixed hyperlipidemia have an increased cardiovascular risk and may not achieve recommended LDL-C and non-HDL-C goals on statin monotherapy. This study was designed to obtain regulatory approval of a fenofibrate/pravastatin 160/40 mg fixed-dose combination (FDC) capsule. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of this FDC and simvastatin 20 mg in patients with type 2 diabetes. METHODS: This multicenter, randomized, double-blind, parallel-arm study was conducted in patients with type 2 diabetes and mixed hyperlipidemia, without cardiovascular disease, and who were not at lipid goals with simvastatin 20 mg monotherapy. After a 6-week run-in period during which patients received simvastatin 20 mg, those with non-HDL-C concentrations ≥130 mg/dL or LDL-C concentrations ≥100 mg/dL and triglyceride concentrations 150 to 600 mg/dL were enrolled. Eligible patients were randomly assigned to receive 12-week treatment with fenofibrate/pravastatin 160/40 mg FDC or simvastatin 20 mg once daily, followed by a 12-week open-label tolerability-assessment period during which all patients received the FDC. The primary efficacy outcome was the mean percentage change in non-HDL-C after 12 weeks. Secondary efficacy outcomes included changes in other lipid and lipoprotein parameters, fibrinogen, and high-sensitivity C-reactive protein. Tolerability was assessed based on the prevalence of adverse events and abnormal laboratory data in each treatment group. RESULTS: A total of 291 patients were randomized to receive fenofibrate/pravastatin (n= 145) or simvastatin (n = 146). The mean (SD) age of the participants was 56.6 (8.9) years, 48.1% were men, and the body mass index was 31.3 (4.6) kg/m(2). The FDC was associated with a significantly greater reduction in non-HDL-C (primary end point) compared with simvastatin monotherapy (-12.9% [1.8] vs -6.8% [1.8]; P = 0.008). Triglyceride (-28.6% [3.7] vs +5.0% [3.6]; P < 0.001), fibrinogen (-11.5% [1.6] vs +0.3% [1.6]; P < 0.001), and HDL-C (+6.3% [1.3] vs +1.8% [1.3]; P = 0.008) concentrations also were significantly improved with the FDC compared with simvastatin monotherapy. The proportions of patients who achieved the LDL-C target (<100 mg/dL) were not significantly different between the 2 groups. The proportion of patients who achieved the combined end point of non-HDL-C <130 mg/dL and LDL-C <100 mg/dL was significantly greater with fenofibrate/pravastatin compared with simvastatin monotherapy (41 [28.5%] vs 26 [17.9%]; P < 0.05). The prevalences of patients who experienced ≥1 adverse event were not statistically different between the fenofibrate/pravastatin and simvastatin groups (17.2% vs 15.1%). However, compared with simvastatin monotherapy, the combination treatment was associated with significantly greater increases in alanine aminotransferase (+9.6% vs +1.5%; P = 0.03 between groups), creatinine (+13.7% vs +6.8%; P = 0.002 between groups), and homocysteine (+36.5% vs +1.6%; P < 0.001 between groups) concentrations. CONCLUSIONS: In this selected population of adults with type 2 diabetes, the fenofibrate/pravastatin 160/40 mg FDC was associated with significantly greater changes from baseline in non-HDL-C, triglyceride, and HDL-C concentrations compared with simvastatin 20 mg. Both treatments were well tolerated.

Continued improvement of cardiovascular mortality in Hungary--impact of increased cardio-metabolic prescriptions.

BACKGROUND: During the last 35 years the poor ranking of Hungary on the list of life expectancy at birth among European countries, has not changed. In 1970 our lag behind the leading European countries was the smallest. The gap was growing between 1970 and 1993 but from 1994 onwards the life expectancy at birth in Hungary has increased continuously and somewhat faster than in other European countries. The aim of this study was to analyze the association between decreasing cardiovascular mortality rates, as a main cause of death and the increase in cardio-metabolic prescriptions and possible changes in lifestyle behavior. METHODS: Analyses were conducted on national data concerning cardiovascular mortality and the number of cardio-metabolic drug prescription per capita. The association between yearly rates of cardiovascular events and changes in antihypertensive, antilipidemic and antidiabetic prescription rates was analyzed. The changes in other cardiovascular risk factors, like lifestyle were also considered. RESULTS: We observed a remarkable decline of mortality due to stroke and acute myocardial infarction (AMI). The fall was significantly associated with all prescription rates. The proportion of each treatment type responsible for suppression of specific mortality rates is different. All treatment types comparably improved stroke mortality, while antilipidemic therapy improved AMI outcome. CONCLUSIONS: These results emphasize the importance of a comprehensive strategy that maximizes the population coverage of effective treatments. Hungary appears to be at the beginning of the fourth stage of epidemiologic transition, i.e. it has entered the stage of delayed chronic noninfectious diseases.

Toll-like receptors: link between "danger" ligands and plaque instability.

Myocardial infarction and stroke are exaggerated by rupture of atherosclerotic lesions. Rupture-sensitive plaques have a specific composition which renders them vulnerable, but additional factors (acute infection, higher sympathetic activity, excessive increase of blood pressure or exposure to a variety of drugs) are needed to set off the event. Toll-like receptors are important components of the innate and adaptive immune system and seem to be a potential link between inflammation, infectious disease and atherosclerosis. In addition to classical bacterial and viral antigens, several endogenous ligands (HSP, ox-LDL, apoptotic cells) have also been proposed to react to TLRs. There is accumulating evidence substantiating the contribution of the TLR-signaling pathway not only in the initiation but also in the progression of atherosclerosis. TLRs also play a key role in the development of tissue ischemia. Apoptosis and inflammation comprise two important indicators of plaque instability, and trigger factors augmenting rapidly TLR signaling can lead to aggravation of plaque-rupture. Due to their multiplex involvement in ischemic conditions, Toll-like receptors may be a promising target for therapeutic intervention. In situations such as acute coronary syndrome, in which inhibition of the inflammatory cascade is warranted, the administration of TLR-blocking agents as adjuvant therapy and the clinical usefulness of this association should be considered.

Cardiovascular risk status and primary prevention in postmenopausal women: the MENOCARD study.

OBJECTIVE: Our aim was to evaluate the usefulness of screening for cardiovascular risk factors and the effect of applying professional guidelines for risk reduction in postmenopausal women, as judged by the Framingham and the high-risk systematic coronary risk evaluation (SCORE) methods. METHODS: 18 menopause clinics in Hungary participated in the study, enrolling a total of 2789 patients. Physicians were asked to follow professional guidelines for the primary prevention of cardiovascular disease. Patients were requested to attend follow-up every four months for 12 months. RESULTS: The mean age of the patients was 56.7+/-6.9 years, and the time elapsed since the last menstrual period was 9.2+/-7.2 years. Overall, 29.4% of patients attended at least one follow-up visit. At the initial visit, high total cholesterol level (>5 mmol/l) was detected in 78% of patients, high triglyceride level (>1.7 mmol/l) in 29%, high systolic and/or diastolic blood pressure (>140/90 mmHg) in 32%, fasting plasma glucose level>6.1 mmol/l in 15%. Increased waist circumference (>88 cm) was found in 85.8% of the patients; 18.3% of the patients smoked, which did not change. After 12 months, all laboratory parameters and the blood pressure had improved significantly. Both the Framingham and SCORE systems showed a significant improvement in the cardiovascular risk status, and the rate of metabolic syndrome had decreased significantly by the end of the study. CONCLUSIONS: Screening postmenopausal women for cardiovascular risk and the application of professional guidelines for primary prevention may significantly reduce the risk of coronary artery disease in this group. Patient compliance with follow-up visits needs improvement.

[Important aim of statin therapy: ischemic cardiovascular event (stroke)]. / A statinterápia fontos célpontja: ischaemiás cerebrovascularis esemény.

Statin's treatment clearly is authorized in prevention of coronary heart disease (CHD). According to the results of many studies and meta-analyses statins can inhibit the first cerebrovascular infarct (stroke). The greater the decrease of LDL-cholesterol level the more prominent the efficacy. The effect is not so robust compared to coronary vessels moreover clear pleiotropic (cholesterol independent) action takes also part. It has been nowadays revealed that high dose (80 mg) atorvastatin can confine first time the development of recurrence stroke (SPARCL study), which is an important fact in the field of secondary prevention.

Correlation between flow-mediated dilation and erectile dysfunction.

We hypothesized that there is a correlation between the magnitude of endothelial-mediated dilation of brachial artery and erectile function in patients. Thus, flow-mediated dilation of the brachial artery (FMD)-used to assess the function of endothelium-was measured in 56 patients (aged approximately 35 years) having erectile dysfunction for 6-12 months. The patients were grouped based on International Index of Erectile Dysfunction: severe (5-10), moderate (11-16), mild to moderate (17-21), and mild (22-25). As compared to the mild group (8.8 +/- 1.7%), FMD was significantly reduced in the mild-to-moderate group (5.7 +/- 1.1%), moderate group (5.3 +/- 0.8%), and severe group (4.4 +/- 0.6%). Also, there was a positive correlation between the magnitude of endothelial and erectile dysfunction. Patients were treated with the 5-phosphodiesterase inhibitor sildenafil, known to elevate vascular cGMP level and thus the vascular efficacy of internal nitric oxide, for 3 to 6 months prior to the study. The mean doses of sildenafil used were as follows: severe group, 100 mg/event; moderate group, 86.1 +/- 21.4 mg/event; mild-to-moderate group, 71.8 +/- 23.2 mg/event; mild group, 25 mg/event. We found a positive correlation between the sildenafil dose requirement and the severity of erectile dysfunction. On the bases on these findings, together with the known mechanism of action of sildenafil, we propose that vascular endothelial dysfunction could contribute to erectile dysfunction and that erectile dysfunction may be an early marker of peripheral vascular disease.

Vascular pleiosynergy--does it really work?

Cardiovascular risk increases exponentially by multiple risk factors. Similarly, by simultaneously treating these risk factors the therapeutic benefit can be multiplied. It is also relevant that some drugs exert extra benefit by acting beyond their main effect. A wide range of pleiotropic effects have been reported among lipid lowering statins and third-generation calcium channel blockers. These include an increase of endothelial nitric oxide (NO) production, inhibition of free radical formation and reduction of migration and proliferation of smooth muscle cells independently from the main therapeutic effect of these drugs. Favorable "therapeutic cross effects" due to pleiotropic mechanisms can be defined as pleiosynergy.

[Vascular pleiosynergism--a new concept?]. / Vascularis pleioszinergizmus--egy uj fogalom?

The coexistence of cardiovascular risk factors augments exponentially the relative risk value. Similarly, the parallel treatment of these risks proves multiplicative effectiveness. However, members of given drug classes show different capacity due to their variant main and other effects. Nowadays, among favorable "side" effects the pleoitropic form is in the focus of interest. In drugs with antiatherosclerotic outline the lipid lowering statins and the antihypertensive third generation calcium channel blocker amlodipin posses the widest pleiotropic profile. According to the newest molecular biological results both of them are able to enhance endothelial nitrogen-monoxid (NO) synthesis, to inhibit production of reactive oxide radicals and to reduce the migration and proliferation of smooth muscle cells, which mechanisms are independent from their main effects. Statins and amlodipin can increase the activity of eNOS by influencing the caveolin/eNOS complex. The presence of common targets in direct and indirect effects seems to be important in gaining greater efficacy. The valuable indirect therapeutical "cross reaction" can be delineated as pleiosynergism. The recent revisited results of ASCOT-LLA trial support in vitro observations. The difference in primary end points of atorvastatin/amlodipin versus atorvastatin/atenolol regimen against placebo was more than three times (3.3 x) greater in favour to amlodipin combination. The same benefits were seen in secondary end points. Because the capacity of the two schedules lowering blood pressure was very similar, the advantage can be based dominantly on the pleiosynergistic interaction between atorvastatin and amlodipin.

[Increase of homocysteine in cardiovascular diseases in Hungary]. / Magasabb homociszteinszint cardiovascularis betegségekben Magyarországon.

UNLABELLED: There are only very few epidemiological data about homocysteine levels in patients suffering from cardiovascular (CV) disease in Hungary, however, homocysteine is a newly recognized, independent risk factor of CV diseases. AIM OF THE STUDY: Therefore, in the present study, data of 1010 East-Hungarian patients with signs of CV disease were analyzed retrospectively for correlation between the level of homocysteine and CV diseases, laboratory parameters, as well as genetic differences. PATIENTS AND METHODS: From the studied patient population a control ("healthy") group has been selected according to the following criteria: lack of previous stroke or stenosis of the carotid arteries or the lower extremities, lack of coronary artery stenosis more than 50%, no previous coronary intervention or an angiography diagnosed progression of the coronary atherosclerosis. RESULTS: The level of homocysteine showed statistically significant negative linear correlation with HDL-cholesterol and the anti-atherogenic ApoAI, and showed a positive correlation with CRP and FXIII activities in the entire patient population. When compared to the control group, homocysteine level was significantly higher in patients with previous stroke or acute myocardial infarction, coronary stenosis, progressive coronary disease, physical inactivity, MTHFR gene polymorphism, low folate or vitamin B12 level in both men and women. In patients with type II diabetes the level of homocysteine was significantly higher only in women. CONCLUSIONS: It can be concluded that the level of homocysteine in patients suffering from various CV diseases is high in Hungary. This may have a prognostic value, and shows that reduction of homocysteine level in these patients may be beneficial.

Prevalence of metabolic syndrome estimated by International Diabetes Federation criteria in a Hungarian population.

AIMS: In recent years, metabolic syndrome (MS) became a distinct pathological entity. MS is positively associated with cardiovascular mortality. The prevalence of MS is high and a continuing increase is expected. For this reason, all attempts to prevent or manage MS by interventions are extremely important. The new set of definition by International Diabetes Federation (IDF) standardizes criteria for the diagnosis of MS and facilitates its recognition. In a large sample (n = 13 383) of outpatients visiting their general practitioners, we determined the prevalence of risk factors of MS according to the earlier Adult Treatment Panel (ATP) III and the new IDF criteria. METHODS AND RESULTS: The age-standardized prevalence of MS was 14.9% in males and 8.6% in females (11.5% for all). The most prevalent factors were obesity (ATP III: 38.8% and IDF: 60%) and hypertriglyceridemia (34.1%). Hypertension dominated in men (28.7%), whereas in women obesity was the most prevalent factor (ATP III: 47.4% and IDF: 64%). CONCLUSION: The prevalence of MS depends on applied definition. The new IDF criteria offer the possibility of focusing on the importance of different components. The real comparison of prevalence among special populations has to be based on age-standardized data and the use of the same components. In our study, the dominance of obesity, hypertension and hypertriglyceridemia appears to be the major detrimental factors. The 11.5% general prevalence of MS in Hungarians, which means a 25-30% value in the middle-aged population, needs an urgent preventive approach with lifestyle changes.

The effect of ciprofibrate on flow-mediated dilation and inflammatory markers in patients with combined hyperlipidemia.

Impairment of flow-mediated dilation (FMD) has been shown to be associated with hypercholesterolemia and hypertriglyceridemia and reduction of cholesterol and/or triglyceride levels can improve FMD. In hyperlipidemia the role of inflammatory substances on endothelial function requires further clarification. In patients with combined hyperlipidemia (n = 29), the capacity of FMD was weaker whereas the levels of interleukin (IL)-lalpha, tumor necrosis factor alpha (TNFalpha), soluble intercellular adhesion molecule (sICAM), and fibrinogen were higher compared to normolipemic controls with normal FMD adjusted for age and sex. Patients were randomized to a diet-only or to a ciprofibrate treatment group. After 8 weeks FMD levels rose significantly both in the diet-only (10.2%) and the ciprofibrate treatment (79.4%) groups. In the diet-only group improvement of FMD was significantly associated with the reduction of triglyceride (by 15.9%) and cholesterol (6.9%) levels. The much larger improvement of FMD due to ciprofibrate therapy was accompanied by significant reductions of cholesterol (by 14.4%), fibrinogen, IL-1alpha, and sICAM levels and by significant increase of high-density lipoprotein (HDL) cholesterol concentration, but the change in FMD correlated only with the reduction of the cholesterol level. In line with previous data the authors emphasize that improvement of FMD in patients with combined hyperlipidemia treated with diet and/or ciprofibrate is linked directly to the reduction of cholesterol and triglyceride concentrations rather than to changes in the level of the investigated inflammatory markers.