[Recent clinical trials in hypertensiology]. / Najnowsze badania kliniczne w hipertensjologii.

The paper presents the results of large randomized clinical trials conducted in recent years, evaluating the efficacy and safety of drugs used to treat hypertension. The results show that angiotensin converting enzyme inhibitors and/or angiotensin receptor antagonists for use as monotherapy and especially in combination with calcium antagonists are effective in controlling blood pressure and in preventing and reducing complications of drugs compared with beta-adrenolytics used as monotherapy or in combination with diuretics. Antihypertensive therapy in the elderly reduces morbidity and mortality from cardiovascular causes.

Influence of co-existing atrial fibrillation on the efficacy of atorvastatin treatment in patients with dilated cardiomyopathy: a pilot study.

INTRODUCTION: The aim of the study was to assess the influence of co-existing atrial fibrillation (AF) on inflammatory condition factors, left ventricular function, clinical course and the efficacy of statin treatment of congestive heart failure in the course of dilated cardiomyopathy (DCM). MATERIAL AND METHODS: In a prospective, randomized, open-label study, 69 patients with DCM and left ventricular ejection fraction (LVEF) < or =40% were divided into two groups, with and without AF, who were treated according to the recommended standards. 68% of patients from the group with AF and 59% of patients from the group without AF were administered atorvastatin 40 mg daily for 8 weeks and 10 mg for next 4 months. Clinical examination with the assessment of body mass index (BMI) and waist size were followed by routine laboratory tests, measurement of concentration of tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), and IL-10 in blood plasma, N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in blood serum, echocardiographic examination, and the assessment of exercise capacity in 6-minute walk test (6-MWT). After six months, morbidity rate and the number of heart failure hospitalizations were also observed. RESULTS: In the whole population of patients, a significantly higher concentration of NT-proBNP was observed in the AF group (2669 +/- 2192 vs 1540 +/- 1067, p = 0.02). After statin treatment, in patients with DCM and co-existing AF, higher values of NT-proBNP and IL-6 were observed compared to non-AF patients (1530 +/- 1054 vs 1006 +/- 1195, p = 0.04 and (14.16 +/- 13.40 vs 6.74 +/- 5.45, p = 0.02, respectively). CONCLUSION: In patients with DCM and co-existing AF, a weaker effect of atorvastatin concerning the reduction of IL-6 and NT-proBNP concentration was observed than in patients without atrial fibrillation.

The influence of atorvastatin on parameters of inflammation and function of the left ventricle in patients with dilated cardiomyopathy.

BACKGROUND: We assessed the influence of atorvastatin on selected indicators of an inflammation, function of the left ventricle and factors affecting the occurrence of rehospitalisation and mortality in patients with dilated cardiomyopathy (DCM). MATERIAL/METHODS: In a prospective, randomized study, 68 patients with DCM with LVEF

Circadian changes in the hemostatic system in healthy men and patients with cardiovascular diseases.

The highest risk of cardiovascular events is in the morning, which may be associated with circadian changes in hemostasis. There is a 10% circadian variability in von Willebrand factor (vWF). Circadian periodicity has been noted for both the number of platelets and their aggregability. The highest number of platelets was in the afternoon, while most studies observed an increase in platelet aggregation in the morning. Platelet activity has also been linked with physical activity after waking up. The highest values of coagulation system markers such as fragment 1+2, factor VIIa, and fibrinogen have been recorded in the late morning. Also, coagulation inhibitors such as protein C, antithrombin III, and a tissue factor pathway inhibitor are most active at this time of day. The levels of plasminogen and its activators (alpha 2-antiplasmin, urokinase-like plasminogen activator) do not undergo circadian periodicity, in contrast to changes in tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 levels (PAI-1). The most intensive activity of the fibrinolytic system inhibitor PAI-1 has been noted in the morning. The 24-h changes in the hemostatic system observed in healthy subjects often did not occur in individuals with health problems. The results of various studies suggest that circadian changes in the hemostatic system increase the incidence of cardiovascular events in the morning. This review considers the circadian rhythms of individual components involved in hemostasis (endothelium, platelets, coagulation, and fibrinolysis).

Polymorphism C1114G of gene encoding the cardiac regulator of G-protein signaling 2 may be associated with number of episodes of neurally mediated syncope.

BACKGROUND AND AIMS: The cardiac regulator of G-protein signaling 2 (RGS2) negatively regulates G-protein-coupled receptor signaling. The C1114G polymorphism reduces RGS2 gene expression. This molecular disorder may be one of the important factors influencing progress of neurally mediated syncope. The aim of the study was to evaluate the association between C1114G RGS2 polymorphism and tilting results and number of syncope episodes in patients with no other diseases. METHODS: Of 214 tilted patients (39% males, 39.7 +/- 17.1 years of age), genomic DNA was extracted from cellular blood components. C1114G RGS2 polymorphism was diagnosed by designed primers. Clinical variables and genetic traits were introduced into multivariate stepwise regression. Analysis was performed as follows: positive tilting n = 145 vs. negative n = 69, positive passive n = 49 vs. nitroglycerin (NTG)-positive n = 96, dominant vasodepressive n = 111 vs. cardioinhibition n = 34; and in number of syncope groups with cut-off >or=10 vs. <10. RESULTS: No relationship was found between the studied polymorphism and outcome of tilting (p >0.05). In multivariate regression model, homozygosity G/G 1114 RGS2 was the only variable associated with a reduced number of episodes of syncope (95% CI 2.3-10.9; p = 0.04). CONCLUSIONS: Our preliminary results suggest the association of G/G 1114 RGS2 genotype with the number of episodes of neurally mediated syncope. Detailed molecular mechanism of the influence of the studied polymorphism on syncopal number is probably associated with the reduced expression of RGS2 gene.

Genetic insight into syncopal tilted population with severe clinical presentation.

UNLABELLED: An impairment of cardiovascular reflexes may be the result of functional alterations in the G proteins intracellular signaling produced by functional genes' polymorphisms. The aim was to evaluate the relationships between single nucleotide polymorphisms in genes encoding G-proteins signaling pathways and syncopal patients with severe clinical manifestation. METHODS AND RESULTS: From 307 syncopal patients free from any other diseases 83 (27%) had at least one malignant episode of syncope with a significant injury as fractures. There was 1.9 malignant spells per patient. All patients were tilted and genotyped by polymerase chain reaction followed by restriction fragment length polymorphism method. 74 healthy volunteers with negative history of syncope constituted the control group were also genotyped. Following polymorphisms were detected: C393T in gene encoding the alfa-subunit of Gs-protein (GNAS1), C825T of gene for G-protein beta 3 subunit (GNB3) and C1114G for the gene of cardiac regulator of G-protein signaling (RGS2). We found an association with lower risk of malignant syncope in positive tilting patients during passive phase of the test compared to NTG-enhanced (OR 0.38; 95% CI 0.15-0.95; P=0.04). No difference between healthy controls and patients in the alleles frequency was found (P>0.05). Neither the 393T allele of GNAS1 and 825T allele of GNB3 nor 1114G allele of RGS2 was associated with enhanced risk of severe clinical manifestation (P>0.05). CONCLUSIONS: The studied single nucleotide polymorphisms of genes encoding G-proteins signaling pathways seem to be not connected with the severe clinical manifestation of syncope.

Factors associated with C-reactive protein at the early stage of acute myocardial infarction in men.

BACKGROUND: Elevation of C-reactive protein (CRP) is associated with acute coronary events. CRP is related to cardiovascular risk factors and adipokines. The aim of the study was to reveal the factors associated with elevated CRP levels in patients with ST-segment elevation acute myocardial infarction (STEMI). As there are sex-related differences in plasma levels of CRP and adipokines, our study was designed for males. METHODS: Seventy men admitted within the initial 6 hours of STEMI were categorized into 4 groups according to the quartile of CRP. Clinical data and laboratory measurements were analyzed. RESULTS: Anthropometric measurements, glucose at admission, resistin, and leptin were significantly higher, and adiponectin lower with the increase of CRP quartile. A significant positive correlation between CRP and body mass index, waist circumference, glucose at admission, resistin, and leptin and a negative relation of CRP to HDL-cholesterol and adiponectin were observed. In univariate logistic regression analysis, variables associated with a level of CRP above the fourth quartile were history of angina, obesity, diabetes, glucose at admission, resistin, leptin, and adiponectin, and independent predictors were glucose at admission and resistin. To predict the elevated CRP level the optimal cut-off for glucose at admission was 144 mg/dL (sensitivity 84%, specificity 86%) and for resistin was 21.5 ng/mL (sensitivity 79%, specificity 71%). CONCLUSIONS: Glucose at admission and resistin are independently associated with elevated levels of CRP in men during the early stage of STEMI.

Endothelial dysfunction in patients with noncomplicated and complicated hypertension.

Endothelial dysfunction plays an important role in the pathogenesis of hypertension. Other risk factors of atherosclerosis also affect its development. The aim of the study was to assess nitric oxide metabolites concentration (nitrites and nitrates No(x)) and endothelin (ET-1) in plasma and cyclic 3,5-guanosine monophosphate (cGMP) in 24 h-urine collection in patients with noncomplicated hypertension without risk factors of atherosclerosis and in hypertensive patients with coronary artery disease (CAD). Sixty-eight subjects were included in the study (44 men, 24 women), aged 47 +/- 76 years, allotted into four groups: I - controls (18 clinically healthy subjects); II - 12 subjects with hypertension without risk factors of atherosclerosis; III - 16 subjects with hypertension and risk factors of atherosclerosis; and IV - 22 subjects with hypertension and CAD. Plasma NO(x) concentration was determined using the Greiss method, plasma ET-1 by ELISA, and urine cGMP using the immunoenzymatic method. Plasma NO(x) concentration was 14.00 +/- 6.88 micromol/L in group I, in group II - 18.62 +/- 5.84 micromol, in group III - 9.96 +/- 4.72 micromol/L, and in group IV - 8.78 +/- 3.72 micromol/L. Statistically significant differences were between groups I and III (p < 0.05) and I and IV (p < 0.04) and groups II and III (p < 0.01) and II and IV (p < 0.01). The concentration of cGMP in 24 h urine collection was in group I - 40 +/- 24 pmol/L; in group II - 54 +/- 41 pmol/L; in group III - 38 +/- 32 pmol/L; and in group IV - 42 +/- 36 pmol/L. There were no significant differences between the groups. Plasma ET-1 concentration was 3.86 +/- 0.52 pg/mL in group I, in group II - 4.05 +/- 0.71 pg/mL, in group III - 4.22 +/- 0.79 pg/mL and in group IV - 4.38 +/- 0.75 pg/mL. Statistically significant differences were between group I and III (p < 0.05), I and IV (p < 0.03), and between group II and IV (p < 0.04). Endothelial dysfunction was not found in hypertensive patients without a family history of cardiovascular diseases and without other risk factors of atherosclerosis. Deterioration of endothelial function was observed in patients with hypertension with risk factors of atherosclerosis. It was most pronounced in those with CAD.

A novel approach to syncopal patients: association analysis of polymorphisms in G-protein genes and tilt outcome.

AIMS: G-proteins signal transduction pathways play a basic role in cardiovascular reflexes. We hypothesized that the predisposition to reflex-mediated syncope may be associated with genetic variations in G-protein genes. The aim of this study was to evaluate the effect of three single-nucleotide polymorphisms in G-protein genes on tilting outcome in syncopal patients. METHODS AND RESULTS: A total of 217 syncopal patients free from any other disease were genotyped and examined related to tilting results. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism in gene encoding the Gs-protein alpha-subunit (polymorphism C393T), the G-protein beta 3 subunit--GNB3 (polymorphism C825T)--and for the cardiac regulator of G-protein signalling RGS2 (polymorphism C1114G). In multivariate logistic regression analysis, the homozygotes 825TT GNB3 (OR 0.37; 95% CI 0.14-0.97; P < 0.05) and body mass index (OR 0.87; 95% CI 0.78-0.97; P = 0.005) were independently associated with a lower chance of positive tilting results. No relationship was found between Vasovagal Syncope International Study type of syncope and the studied genotypes or the carriage of the polymorphic alleles. CONCLUSIONS: An association between tilting results and C825T GNB3 polymorphism in syncopal patients was found. The syncopal homozygotes 825TT GNB3 had a significantly lower chance of syncope during tilt testing.

Value of blood adipose tissue hormones concentration--adiponectin, resistin and leptin in the prediction of major adverse cardiac events (MACE) in 1-year follow-up after primary percutaneous coronary intervention in ST-segment elevation acute myocardial infarction.

OBJECTIVES: The objective of the study was to assess the impact of adipokines on the future major adverse cardiac events (MACE) in patients with acute myocardial infarction. METHODS: Subjects were 77 men with first, ST-segment elevation acute myocardial infarction undergoing primary percutaneous coronary intervention in whom data were available after one year follow-up. Baseline clinical and angiographic data were collected, blood level of C-reactive protein, uric acid, fasting glucose, lipid profile, adiponectin, resistin and leptin and left ventricular ejection fraction on echocardiography were assessed. MACE was defined as cardiac death, nonfatal myocardial infarction, hospitalization for angina or heart failure. RESULTS: 12% of patients experienced MACE. As revealed by univariate logistic regression analysis predictors of MACE were diabetes, multivessel disease, ejection fraction, blood C-reactive protein and adiponectin level. In multivariable analysis diabetes (OR=22.19, 95%CI 1.22-402.19; p=0.0360), lower left ventricular ejection fraction (OR=0.78, 95%CI 0.63-0.98; p=0.0298) and lower adiponectin level (OR=0.19, 95%CI 0.04-0.90; p=0.0362) were independent negative predictors of MACE. The optimal value of adiponectin for predicting MACE was 4.23 microg/ml. CONCLUSION. In male patients with myocardial infarction undergoing primary percutaneous coronary intervention, a baseline blood adiponectin but not resistin or leptin is independently predictive of MACE. The other prognostic factors are diabetes mellitus and left ventricular ejection fraction.

N-terminal pro-brain natriuretic peptide in the elderly with myocardial infarction.

BACKGROUND: The myocardial infarction (MI) results in the change of the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) in blood. In addition, attention is paid to the dependence of NT-proBNP levels on the patients' age. However, the behavior of natriuretic peptide levels has not been recognized well enough in the elderly with MI treated with invasive methods. HYPOTHESIS: The aim of the study was to estimate the effect of age on NT-proBNP levels in patients with first MI, and treated with primary percutaneous coronary intervention (PCI) with complete coronary revascularization. METHODS: One hundred and sixty-one consecutive patients with first ST-elevation MI, and treated with primary PCI with stent implantation (occlusion in infarct-related artery was the patient's only lession) were included. Determination of NT-proBNP level and echocardiography were performed on the 4th-5th day of MI. RESULTS: Thirty-seven patients (23%) aged>or=65 y were considered as a study group. The NT-proBNP levels were nearly 4-fold higher in older patients than in younger patients. Only systolic and diastolic dysfunction, mitral regurgitation, troponin T levels, and glomerular filtration rate (GFR) were independent risk factors of the occurrence of elevated NT-proBNP concentration above median. CONCLUSIONS: The patients' age was not a factor independently affecting the increase of NT-proBNP level above the median in patients with first MI and treated successfully with primary PCI. Independently associated elevated levels of NT-proBNP were as follows: presence of diastolic dysfunction, mitral regurgitation, left ventricular systolic dysfunction, troponin T concentration, and GFR.

Obesity and heart rate variability in men with myocardial infarction.

BACKGROUND: Obesity has been shown to affect heart rate variability (HRV). Adipokines (hormone-like peptides secreted by adipose tissue) display several bioactivities and have an impact on the cardiovascular system. The aim of the study was to evaluate the impact of obesity (BMI > or = 30) and adipokines (leptin, adiponectin and resistin) on HRV. METHODS: In 43 obese and 38 non-obese males with acute myocardial infarction, plasma adipokines were determined. 24-hour Holter ECG with time and frequency domain HRV analysis was performed. RESULTS: Anthropometric measurements, leptin and resistin were significantly higher and adiponectin was lower in the obese than in the non-obese group. SDNN, SDANN, SDNN-i, rMSSD, p-NN50 and HF were reduced in obese patients, whereas LF/HF was higher. Waist circumference was a better correlate of HRV parameters than body mass index. Several associations between HRV parameters and adipokines were observed: between SDNN and leptin (r = -0.32; p < 0.001) and resistin (r = -0.26; p < 0.05); SDANN and leptin (r = -0.26; p < 0.05) and resistin (r = -0.29; p < 0.001); SDNN-i and resistin (r = -0.40; p < 0.001); LF and leptin (r = 0.22; p < 0.05); HF and resistin (r = -0.22; p < 0.05); LF/HF and leptin (r = 0.46; p < 0.001) and resistin (r = 0.44; p < 0.001). CONCLUSIONS: Obesity is related to sympathovagal imbalance characterized by depressed parasympathetic tone and increased sympathetic activity. The relation between blood leptin and resistin concentration to the HRV parameters may indicate a possible link between adipokines and disturbances of the autonomic nervous system.

Effects of hypertension therapy based on eprosartan on systolic arterial blood pressure and cognitive function: primary results of the Observational Study on Cognitive function And Systolic Blood Pressure Reduction open-label study.

BACKGROUND: Recent studies have indicated a relationship between hypertension and cognitive function but therapeutic trials of antihypertensive therapy on the prevention of cognitive disorders have produced controversial findings. METHODS: The Observational Study on Cognitive function And Systolic Blood Pressure Reduction is an open-label trial in 28 countries designed to evaluate the impact of eprosartan-based therapy on cognitive function. The Mini-Mental State Examination was used as a global tool for the comprehensive assessment of cognitive function, with an intention to treat a cohort of 25 745 hypertensive patients aged at least 50 years during a follow-up interval of 6 months. Blood pressure therapy was initiated with eprosartan 600 mg/day with provision for additional medication to be introduced after 1 month in patients with insufficient blood pressure response. RESULTS: Use of eprosartan, either as monotherapy or in combination regimens, was associated with a substantial reduction in arterial blood pressure from 161.9/93.1 mmHg at baseline to 136.1/80.8 mmHg at 6 months (P < 0.0001). The overall mean Mini-Mental State Examination score at completion of follow-up was 27.9 +/- 2.9 compared with 27.1 +/- 3.4 at baseline (P < 0.0001). A significant correlation was shown between the mean absolute response of Mini-Mental State Examination and the magnitude of systolic blood pressure reduction. At the end of the study, patients with systolic blood pressure less than 140 mmHg had a larger improvement in Mini-Mental State Examination [0.88 +/- 0.01 (SEM)] than those with systolic blood pressure between 140 and 159 mmHg [0.69 +/- 0.02 (SEM); P < 0.001], or than those with systolic blood pressure of at least 160 mmHg [0.38 +/- 0.05 (SEM); P < 0.0001]. Furthermore, cognitive decline was demonstrated in multiple linear regression to be independently associated with age [odds ratio 1.19 (1.14; 1.25)], Mini-Mental State Examination at baseline [odds ratio 1.19 (1.14; 1.25)], systolic blood pressure at baseline [odds ratio 1.20 (1.13; 1.27)] and systolic blood pressure reduction [odds ratio 0.77 (0.73; 0.82)]. CONCLUSION: The results of the Observational Study on Cognitive function And Systolic Blood Pressure Reduction are supportive of the proposition that antihypertensive therapy based on drugs that target the renin-angiotensin system is associated with preservation of cognitive function.

[Clinical value of the estimation of blood pressure circadian rhythm]. / Wartosc kliniczna oceny dobowego rytmu cisnienia tetniczego.

Arterial blood pressure is one of the main factors of the development of organ vascular changes. Clinical studies have demonstrated that not only blood pressure absolute values but its 24h profile as well may be of significance for the rate and severity of organ damage. The study analyses the results and observations of the so far carried out investigations concerning the lack of nocturnal fall of blood pressure on the development of vascular changes in brain, carotid artery, myocardial hypertrophy and renal lesions. The results of the study indicate that in subjects with the lack of nocturnal fall of blood pressure the frequency of organ changes is more pronounced. Thus, for normal monitoring of the course and the treatment of arterial hypertension, its 24h monitoring seems to be an indispensable procedure. When evaluating blood pressure 24h profile age, sex, organ changes, physical activity and real sleep-wake period should be taken into account. In hypertensive patients without organ changes with nondippers blood pressure profile, repetition of 24h blood pressure monitoring seems to be an indication.

C825T G-protein beta3 subunit gene polymorphism, tilt test results and point score in syncopal patients.

We evaluated C825T polymorphism of the G-protein beta3 subunit gene in syncopal patients in regard to tilting results and the diagnostic point score (PS). In a multivariate analysis, only PS > or = -2 was associated with positive passive tilting (P < 0.05). The relationship between tilting results and this polymorphism needs further study.

Atrial fibrillation as a nonpsychiatric predictor of delirium after cardiac surgery: a pilot study.

BACKGROUND: Preoperative atrial fibrillation (AF) increases the risk of cardiac surgery and the occurrence of postoperative complications, including arrhythmias, low-output syndrome, delirium, and death. The aim was to evaluate its direct influence on prognosis of patients subjected to cardiac surgery. MATERIAL/METHODS: This is a pilot study of the CODACS trial (COnsciousness Disorders After Cardiac Surgery). Two hundred sixty patients admitted for open-heart surgery were prospectively included in the study. Preoperative AF was diagnosed on the basis of multiple electrocardiographic examinations and confirmed by 24-h Holter monitoring. Diagnosis of delirium following surgical intervention was based on DSM-IV criteria. RESULTS: Preoperative AF was diagnosed in 23 patients (8.8%): in 15 patients in the nondelirious group (7%) and 8 (27.0%) in the delirious group. Preoperative AF was an independent predictor of postoperative delirium (p<0.001), increasing its risk of occurrence over sevenfold (OR=7.2). AF also increased the risk of such postoperative complications as supraventricular arrhythmia (AF: 78.3% vs. non-AF: 22.8%, p<0.001), stroke (8.7% vs. 1.3%, p<0.001), and low-output syndrome (21.7% vs. 17.3%, p=0.033) and worsened prognosis, significantly increasing the risk of death (8.7% vs. 0.8%, p<0.001). CONCLUSIONS: Preoperative AF was an independent risk factor of postoperative delirium (OR=7.2). It was also associated with significantly worse postoperative outcome (supraventricular arrhythmia, stroke, low-output syndrome, and risk of death). These results and data from available studies suggest that preoperative AF should be considered as an important predictor of postoperative outcome. This problem should be the subject of future research to establish beneficial treatment options.

Resistin increases with obesity and atherosclerotic risk factors in patients with myocardial infarction.

The objective of the study was to assess the relation of resistin to the anthropometric parameters, metabolic risk factors, and C-reactive protein (CRP) in men with myocardial infarction. Subjects were 40 obese (age, 53.6 +/- 7.39 years; body mass index, > or =30 kg/m2) and 40 lean (age, 54.4 +/- 6.62 years; body mass index, <25 kg/m2) men with first acute myocardial infarction. Waist and hip circumferences, CRP, uric acid, fasting glucose, lipid profile, and blood resistin concentration were measured. In obese patients, triglycerides, fasting glucose, and CRP were significantly higher whereas high-density lipoprotein cholesterol was lower than in lean patients. The range of blood resistin concentration was 6.0 to 70.5 ng/mL: 27.84 +/- 12.15 ng/mL in obese subjects and 17.35 +/- 11.08 ng/mL in lean subjects (P < .0001). Significant positive correlation was revealed between blood resistin concentration and each of the analyzed anthropometric parameter and with fasting glucose, low-density lipoprotein cholesterol, and CRP, whereas negative relation was observed between resistin and high-density lipoprotein cholesterol. As revealed by univariate logistic regression analysis, risk of blood resistin concentration being greater than the median value (19.75 ng/mL) was increased by obesity, high-density lipoprotein cholesterol <40 mg/dL, hypertension, and CRP. In multivariate model, independent variables associated with higher median of resistin were obesity and CRP. Obesity increased 5.5-fold the probability of blood resistin concentration being greater than 19.75 ng/mL, whereas each 1-mg/dL increase in CRP increased this probability by 13%. In patients with acute myocardial infarction, obesity is positively related to blood resistin concentration. Resistin is likely to play a major role in the atherogenesis and its complications, and this action seems to be mostly related to the inflammatory reaction.

Mutation T/C,Ile 131 of the gene encoding the alfa subunit of the human Gs protein and predisposition to vasovagal syncope.

BACKGROUND: Mutation T/C inside codon 131 of the gene encoding the alpha subunit of Gs protein (GNAS1) causes the increased activation of adenyl cyclase, which plays an important role in cardiovascular regulation. The aim of the present study was to evaluate GNAS1 T/C,Ile 131 mutation's manifestation in syncopal patients regarding head-up tilt test (HUTT) results. METHODS AND RESULTS: In 137 syncopal patients (without any other diseases) the silent T/C,Ile 131 mutation within the GNAS1 codon on chromosome 20 q was identified. This mutation consists of the presence (+) or absence (-) of a target site for endonuclease FokI (Promega). Ninety-six patients (70%) with positive HUTT had a higher FokI+ allele frequency compared with those with negative tilting results (49% vs 27%, X(2)=12.05; p<0.001). In positive tilted patients, the studied mutation had significant influence on blood pressure (p<0.05). When comparing positive HUTT with vasodepressore component, cardioinhibition results and negative HUTT, the frequencies of the FokI+ allele were decreased among these groups: 53%, 36% and 27%, respectively. CONCLUSIONS: An association between positive tilting and mutation C/T,Ile 131 within the GNAS1 codon was found. The predisposition to vasovagal syncope seems to be associated with the GNAS1 FokI+ allele.