IntroductionLow socioeconomic status affects not only diagnosis rates and therapy of patients with diabetes mellitus but also their health behavior. Our primary goal was to examine diagnosis rates and therapy of individuals with diabetes living in Ormánság, one of the most deprived areas in Hungary and Europe. Our secondary goal was to examine the differences in lifestyle factors and cancer screening participation of patients with diagnosed and undiagnosed diabetes compared to healthy participants.MethodsOur study is a cross-sectional analysis using data from the “Ormánság Health Program”. The “Ormánság Health Program” was launched to improve the health of individuals in a deprived region of Hungary. Participants in the program were coded as diagnosed diabetes based on diagnosis by a physician as a part of the program, self-reported diabetes status, and self-reported prescription of antidiabetic medication. Undiagnosed diabetes was defined as elevated blood glucose levels without self-reported diabetes and antidiabetic prescription. Diagnosis and therapeutic characteristics were presented descriptively. To examine lifestyle factors and screening participation, patients with diagnosed and undiagnosed diabetes were compared to healthy participants using linear regression or multinomial logistic regression models adjusted for sex and age.ResultsOur study population consisted of 246 individuals, and 17.9% had either diagnosed (n=33) or undiagnosed (n=11) diabetes. Metformin was prescribed in 75.8% (n=25) of diagnosed cases and sodium-glucose cotransporter-2 inhibitors (SGLT-2) in 12.1% (n=4) of diagnosed patients. After adjustment, participants with diagnosed diabetes had more comorbidities (adjusted [aOR]: 3.50, 95% confidence interval [95% CI]: 1.34–9.18, p<0.05), consumed vegetables more often (aOR: 2.49, 95% CI: 1.07–5.78, p<0.05), but desserts less often (aOR: 0.33, 95% CI: 0.15–0.75, p<0.01) than healthy individuals. Patients with undiagnosed diabetes were not different in this regard from healthy participants. No significant differences were observed for cancer screening participation between groups.ConclusionsTo increase recognition of diabetes, targeted screening tests should be implemented in deprived regions, even among individuals without any comorbidities. Our study also indicates that diagnosis of diabetes is not only important for the timely initiation of therapy, but it can also motivate individuals in deprived areas to lead a healthier lifestyle.

Background Asymptomatic atherosclerosis is a common entity even at young age. Studies have suggested a strong relationship between increased arterial stiffness and asymptomatic carotid atherosclerosis (ACA) in general population, particularly in those with high cardiovascular risk, but no data exist from a younger population free from recognized cardiovascular disease. Hypothesis. We hypothesized there is an association between ACA and aortic pulse wave velocity (PWVao) in middle-aged, apparently healthy, normotensive population to reveal increased cardiovascular risk. Methods We examined the relationship between ACA and PWVao in 236 apparently healthy, asymptomatic, normotensive, middle-aged subjects (age 47 ± 8 years; 52% women). PWVao was measured with the oscillometric method (Arteriograph). ACA was assessed by carotid artery ultrasonography. Results ACA was present in 51 subjects. Subjects with ACA were older (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers ( Conclusions PWVao measured by the Arteriograph proved to be an independent marker of ACA. Our study may reveal high CV risk, detected as increased PWVao, which according to our study is related in a very high probability to asymptomatic carotid atherosclerosis in apparently healthy, young, and middle-aged subjects.

By 1980, it was thought that we already knew most of the major mechanisms regulating vascular tone. However, after the somewhat serendipity discovery that endothelium is involved in mediation of relaxation to acetylcholine, a whole new world opened up and we had to rewrite our concept regarding vascular function and its regulation (not to mention many other fields). The new player was an endothelium derived relaxing factor, which molecular constitution has been identified to be nitric oxide (NO). This review summarizes the major molecular steps concerning how NO is synthetized from L-arginine. Also, the fate of L-arginine is described via the arginase and methylation pathways; both of them are affecting substantially the level and efficacy of NO. In vitro and in vivo effects of L-arginine are summarized and controversial clinical findings are discussed. On the basis of the use of methylated L-arginines, the vasomotor effects of endothelial NO released to agonists and increases in flow/wall shear stress (a major biological stimulus) is summarized. In this review the role of NO in the regulation of coronary vascular resistance, hence blood flow, is delineated and the somewhat questionable clinical use of NO donors is discussed. We made an attempt to summarize the biosynthesis, role, and molecular mechanisms of endogenously produced methylated L-arginine, asymmetric dimethylarginine (ADMA) in modulating vascular resistance, affecting the function of the heart. Additionally, the relationship between ADMA level and various cardiovascular diseases is described, such as atherosclerosis, coronary artery disease (CAD), ischemia/reperfusion injuries, and different types of coronary revascularization. A novel aspect of coronary vasomotor regulation is identified in which the pericardial fluid ADMA and endothelin play putative roles. Finally, some of the open possibilities for future research on L-arginine-NO-ADMA signaling are highlighted.

Measurement of aortic pulse wave velocity (PWVao) is recommended for stratifying individual cardiovascular (CV) risk in adults. Diseases in children and adolescents might influence aortic stiffness. It is necessary to exclude overweight (OW), obese (O) subjects, and individuals with increased systolic (SBP) and/or diastolic blood pressure (DBP) from the population, when creating normal values of PWVao in children and adolescents. Body mass index (BMI), SBP/DBP cut-off values have remarkably changed in this population during the last decade. Aims of our study were to expand our previously published PWVao database and to revise it by using the recently determined normal values. PWVao was measured by an occlusive-oscillometric device (Arteriograph, TensioMed Ltd, Budapest, Hungary) in a healthy population aged 3–18 years. 7940 (4374 boys) participants were recruited, 1912 OW/O subjects and 1368 individuals with high SBP/DBP were excluded. Finally, n = 4690 (2599 boys) participants were enrolled. Mean PWVao values increased from 5.4 ± 0.6 to 6.4 ± 0.5 m/s (p < 0.05) in boys and from 5.5 ± 0.6 to 6.4 ± 0.5 m/s (p < 0.05) in girls. Mean PWVao values were significantly lower in our new study, in boys in age groups of 9–16, in girls in age groups of 11–17. This is the largest and widest age-ranged database of PWVao published to date. Due to the change of BMI and SBP/DBP reference values during the last decade, the “old” database of PWVao needed to be revised. As a result of this, normal values of PWVao decreased significantly in both sexes.

Assessment of carotid-femoral pulse wave velocity by applanation tonometry independently predicts all-cause and cardiovascular mortality. However, there has been a need for a simpler, user-independent measurement with a validated device, that is applicable even in the primary care setting. 4146 subjects (49% men) aged 35–75 years were measured in multiple centers in Hungary. Subjects visited the outpatient department of these centers on their own initiative. The measurement of aortic pulse wave velocity (PWVao) with Arteriograph was performed in addition to taking past medical history, physical examination and laboratory tests. The mean follow-up time of the study was 5.5 years. The number of events (all cause mortality) were provided by the Hungarian National Health Insurance Fund. Cox regression analyses were used to identify predictive factors for this endpoint. The mean age of the study population was 53 years, brachial systolic and diastolic blood pressure were 137±20 and 82±11 mmHg, and heart rate was 70±10 1/min. The mean value of SCORE was 3 in this large cohort. 410 subjects had a registered cerebro-or cardiovascular event before the measurement, the number of smokers was 656 (16%), 1974 subjects were treated with at least one anti-hypertensive drug (48%), while the number of subjects on lipid-lowering, antidiabetic or antiplatelet medication were 807 (19%), 352 (8%) and 398 (17%), respectively. There were 116 fatal events during a mean follow-up of 5.5 years. According to the Cox regression, PWVao is a significant and independent predictor of all cause-mortality and in univariate analysis, a 1.0 m/s increase in PWVao was associated with HR 1.7 [1.47–1.98; p<0.001], for this endpoint. Aortic pulse wave velocity measured by an invasively validated, simple, oscillometric device predicted all-cause mortality in a large cohort of relatively young subjects of the general population that may improve risk stratification even in the everyday clinical practice or primary care setting.

BACKGROUND:The no-flow region (NF) visualised by magnetic resonance imaging (MRI) in myocardial infarction (MI) has been explained as the product of reperfusion-injury-induced microvascular obstruction. However, a similar MRI phenomenon occurs in non-reperfused MI. Accordingly, our purpose was to compare the MRI and histopathologic characteristics of the NF in reperfused and non-reperfused MIs. METHODS:Reperfused (n = 7) and non-reperfused MIs (n = 7) were generated in swine by percutaneous balloon occlusion and microsphere embolisation techniques. Four days post-MI, animals underwent myocardial T2-mapping, early and serial late gadolinium enhancement MRI. MI and NF were compared between the models using the independent samples t test. Serial measurements were analysed using repeated measures analysis of variance. Triphenyltetrazolium chloride (TTC) macroscopic and microscopic histopathologic assessment was also performed. RESULTS:The MI size in the reperfused and non-reperfused groups was 17.1 ± 3.4 ml and 19.4 ± 8.1 ml, respectively (p = 0.090), in agreement with TTC assessment (p = 0.216; p = 0.484), and the NF size was 7.7 ± 2.4 ml and 8.1 ± 1.9 ml, respectively (P = 0.211). Compared to the reference 2-min post-contrast measurement, the NF size was significantly reduced at 20 min in the reperfused group and at 25 min in the non-reperfused group (both p < 0.001). Nevertheless, the NF was still detectable at 45 min after injection. No significant T2 difference was observed between the groups (p > 0.326). Histopathologic assessment revealed extensive calcification and hemosiderin deposition in the NF of the reperfused MI, but not in the non-reperfused MI. CONCLUSIONS:The NF in non-reperfused and reperfused MIs have similar characteristics on MRI despite the different pathophysiologic and underlying histopathologic conditions, indicating that the presence of the NF alone cannot differentiate between these two types of MI.

PurposeTo test whether signal intensity percent infarct mapping (SI-PIM) accurately determines the size of myocardial infarct (MI) regardless of infarct age.Materials and MethodsForty-five swine with reperfused MI underwent 1.5T late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) after bolus injection of 0.2mmol/kg Gd(DTPA) on days 2-62 following MI. Animals were classified into acute, healing, and healed groups by pathology. Infarct volume (IV) and infarct fraction (IF) were determined by two readers, using binary techniques (including 2-5 standard deviations [SD] above the remote, and full-width at half-maximum) and the SI-PIM method. Triphenyl-tetrazolium-chloride staining (TTC) was performed as reference. Bias (percent under/overestimation of IV relative to TTC) of each quantification method was calculated. Bland-Altman analysis was done to test the accuracy of the quantification methods, while intraclass correlation coefficient (ICC) analysis was done to assess intra- and interobserver agreement.ResultsBias of the MRI quantification methods do not depend on the age of the MI. Full-width at half-maximum (FWHM) and SI-PIM gave the best estimate of MI volume determined by the reference TTC (P-values for the FWHM and SI-PIM methods were 0.183, 0.26, 0.95, and 0.073, 0.091, 0.73 in Group 1, Group 2, and Group 3, respectively), while using any of the binary thresholds of 2-4 SDs above the remote myocardium showed significant overestimation. The 5 SD method, however, provided similar IV compared to TTC and was shown to be independent of the size and age of MI. ICC analysis showed excellent inter- and intraobserver agreement between the readers.ConclusionOur results indicate that the SI-PIM method can accurately determine MI volume regardless of the pathological stage of MI. Once tested, it may prove to be useful for the clinic. J. Magn. Reson. Imaging 2016;43:911-920

Cardiovascular diseases are the most common diseases worldwide. They are responsible for one third of global deaths and they are the leading cause of disability, too. The usage of different levels of prevention in combination with effective risk assessment improved these statistical data. Risk assessment based on classic risk factors has recently been supported with several new markers, such as asymmetric dimethylarginine, which is an endogenous competitive inhibitor of nitric oxide synthase. Elevated levels of asymmetric dimethylarginine have been reported in obese, smoker, hypercholesterolemic, hypertensive and diabetic patients. According to previous studies, asymmetric dimethylarginine is a suitable indicator of endothelial dysfunction, which is held to be the preceding condition before atherosclerosis. Several researches found positive correlation between higher levels of asymmetric dimethylarginine and coronary artery disease onset, or progression of existing coronary disease. According to a study involving 3000 patients, asymmetric dimethylarginine is an independent risk factor of cardiovascular mortality in patients with coronary artery disease. This article summarizes the role of asymmetric dimethylarginine in prediction of cardiovascular diseases, and underlines its importance in cardiovascular prevention.

Cardiovascular diseases are the most common diseases worldwide. They are responsible for one third of global deaths and they are the leading cause of disability, too. The usage of different levels of prevention in combination with effective risk assessment improved these statistical data. Risk assessment based on classic risk factors has recently been supported with several new markers, such as asymmetric dimethylarginine, which is an endogenous competitive inhibitor of nitric oxide synthase. Elevated levels of asymmetric dimethylarginine have been reported in obese, smoker, hypercholesterolemic, hypertensive and diabetic patients. According to previous studies, asymmetric dimethylarginine is a suitable indicator of endothelial dysfunction, which is held to be the previous state of atherosclerosis. Several researches found positive correlation between higher levels of asymmetric dimethylarginine and coronary artery disease onset, or progression of existing coronary disease. According to a study involving 3000 patients, asymmetric dimethylarginine is an independent risk factor of cardiovascular mortality in patients with coronary artery disease. This article summarizes the role of asymmetric dimethylarginine in prediction of cardiovascular diseases, and underlines its importance in cardiovascular prevention. Orv. Hetil., 2016, 157(13), 483–487.

Purpose MRI contrast agents (CA) whose contrast enhancement remains relatively high even at the higher end of the magnetic field strength range would be desirable. The purpose of this work was to demonstrate such a desired magnetic field dependency of the longitudinal relaxivity for an experimental MRI CA, Gd(ABE-DTTA). Materials and Methods The relaxivity of 0.5mM and 1mM Gd(ABE-DTTA) was measured by Nuclear Magnetic Relaxation Dispersion (NMRD) in the range of 0.0002 to 1T. Two MRI and five NMR instruments were used to cover the range between 1.5 to 20T. Parallel measurement of a Gd-DTPA sample was performed throughout as reference. All measurements were carried out at 37°C and pH 7.4. Results The relaxivity values of 0.5mM and 1mM Gd(ABE-DTTA) measured at 1.5, 3, and 7T, within the presently clinically relevant magnetic field range, were 15.3, 11.8, 12.4 s-1mM-1 and 18.1, 16.7, and 13.5 s-1mM-1, respectively. The control 4 mM Gd-DTPA relaxivities at the same magnetic fields were 3.6, 3.3, and 3.0 s-1mM-1, respectively. Conclusions The longitudinal relaxivity of Gd(ABE-DTTA) measured within the presently clinically relevant field range is three to five times higher than that of most commercially available agents. Thus, Gd(ABE-DTTA) could be a practical choice at any field strength currently used in clinical imaging including those at the higher end.

Objective This study aimed to determine the eff ect of single-bout exercise on aortic stiff ness parameters in young basketball players. Method and results A total of 108 young male subjects (mean age 14.2 ± 3.4 years) were enrolled into the study. Simultaneous measurement of aortic pulse wave velocity (PWVao) and augmentation index (AIxao) were performed with the oscillometric, occlusive device. Echocardiographic parameters of left ventricular systolic and diastolic function at rest were also measured in sportsmen. We did not fi nd signifi cant diff erences of restin PWVao in comparison with young sportsmen (S) and age-matched healthy volunteers (V): 5.82 ± 0.14 m/s vs 5.83 ± 0.12 m/s for S and V groups, respectively. The values of PWVao measured after dynamic exercise, isometric exercise, and rest were 8.0 ± 0.5 m/s, 5.86 ± 0.1 m/s and 5.82 ± 0.1 m/s, respectively. We confi rmed that values after dynamic exercise are signifi cantly diff erent from those after isometric exercise ( P <0.01) and those after rest ( P <0.01). The AIxao values exhibited a considerable, but statistically non-signifi cant, decrease during dynamic exercise in the three groups (11.7 ± 7% vs 3.8 ± 3% vs- 0.9 ± 0.9% for groups 1, 2, and 3, respectively) Conclusion We applied a feasible, clinically useful method which allowed us to measure changes in aortic PWV and AIx during acute, single-bout exercise on the basketball court in young sportsmen.

To study the feasibility of a myocardial infarct (MI) quantification method [signal intensity-based percent infarct mapping (SI-PIM)] that is able to evaluate not only the size, but also the density distribution of the MI. In 14 male swine, MI was generated by 90 min of closed-chest balloon occlusion followed by reperfusion. Seven (n = 7) or 56 (n = 7) days after reperfusion, Gd-DTPA-bolus and continuous-infusion enhanced late gadolinium enhancement (LGE) MRI, and R1-mapping were carried out and post mortem triphenyl-tetrazolium-chloride (TTC) staining was performed. MI was quantified using binary [2 or 5 standard deviation (SD)], SI-PIM and R1-PIM methods. Infarct fraction (IF), and infarct-involved voxel fraction (IIVF) were determined by each MRI method. Bias of each method was compared to the TTC technique. The accuracy of MI quantification did not depend on the method of contrast administration or the age of the MI. IFs obtained by either of the two PIM methods were statistically not different from the IFs derived from the TTC measurements at either MI age. IFs obtained from the binary 2SD method overestimated IF obtained from TTC. IIVF among the three different PIM methods did not vary, but with the binary methods the IIVF gradually decreased with increasing the threshold limit. The advantage of SI-PIM over the conventional binary method is the ability to represent not only IF but also the density distribution of the MI. Since the SI-PIM methods are based on a single LGE acquisition, the bolus-data-based SI-PIM method can effortlessly be incorporated into the clinical image post-processing procedure.

Recently an expert consensus document advised to standardize user procedures and a new cut-off value for carotid-femoral pulse wave velocity in daily practice. Our aim was to observe aortic pulse wave velocity (PWVao) and augmentation index (AIXao) in two high cardiovascular risk groups: patients with verified coronary artery disease (CAD) or with type 2 diabetes mellitus (T2DM). We also aimed to determine the cut-off values for PWVao, AIXao in CAD and T2DM patients using oscillometric device (Arteriograph). We investigated 186 CAD and 152 T2DM patients. PWVao and AIXao increased significantly in the CAD group compared to the age-, gender-, blood pressure-, and heart rate-matched control group (10.2+/-2.3 vs. 9.3+/-1.5 m/s; p<0.001 and 34.9+/-14.6 vs. 31.9+/-12.8 %; p<0.05, respectively). When compared to the apparently healthy control subjects, T2DM patients had significantly elevated PWVao (9.7+/-1.7 vs. 9.3+/-1.5 m/s; p<0.05, respectively), however the AIXao did not differ significantly. The ROC-curves of CAD and healthy control subjects explored cut-off values of 10.2 m/s for PWVao and 33.23 % for AIXao. Our data provide supporting evidence about impaired arterial stiffness parameters in CAD and T2DM. Our findings encourage the implementation of arterial stiffness measurements by oscillometric method in daily clinical routine.

Background: Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase. Increased ADMA plasma levels are associated with atherosclerosis and cardiovascular disease. In this study we investigated the plasma levels of ADMA in patients who underwent different type of coronary revascularization. Methods: Concentrations of ADMA, l-arginine, symmetric dimethylarginine (SDMA) were measured by liquid chromatography-tandem mass spectrometry in four groups: group I consisted of 16 patients with ST-elevation myocardial infarction (STEMI), and group II included 24 patients who underwent elective percutaneous coronary intervention (PCI). Before PCI and at 1 hour, 5 days and 30 days after reperfusion blood samples were taken for measurement of l-arginine, ADMA and SDMA. Group III consisted of 21 patients undergoing off-pump and group IV included 20 patients undergoing on-pump coronary artery bypass graft (CABG) surgery. The measurements were performed 24 h before, 3 times during the operation (via coronary sinus catheter), and on the 1st and 5th postoperative day. Results: In patients with elective stent implantation stenting induced a prompt and sustained depression of ADMA (F=9.594, p<0.001), however ADMA remained constant for STEMI patients after stent placement (F=2.982, p=0.069). The differences in the time-course for ADMA (F=9.431, p<0.001) proved to be significant between the two groups. We did not find significant change in the plasma concentration of ADMA during off-pump CABG surgery (F=0.416, p=0.68), however ADMA concentration increased significantly in patients who underwent on-pump surgery both in the coronary sinus (F=14.751, p<0.001) and peripheral blood (F=30.738, p<0.001). Therefore, the intersubject time effect, was significant (F=6.990, p=0.002). Conclusions: The main finding of the present study is that the response pattern of the new cardiovascular risk factor, ADMA was significantly different between the two PCI and the CABG groups. Its long-term follow-up may be suitable to monitor the improvement of coronary function after revascularisation. This method should be feasible to monitor of the ADMA metabolism during coronary revascularization.

Introduction The appearance of post-operative cognitive dysfunction as a result of open heart surgery has been proven by several studies. Focal and/or sporadic neuron damage emerging in the central nervous system may not only appear as cognitive dysfunction, but might strongly influence features of physiological tremor. Material and methods We investigated 110 patients (age: 34-73 years; 76 male, 34 female; 51 coronary artery bypass grafting (CABG), 25 valve replacement, 25 combined open heart surgery, 9 off-pump CABG) before surgery and after open-heart surgery on the 3rd to 5th post-operative day. The assessment of the physiological tremor analysis was performed with our newly developed equipment based on the Analog Devices ADXL 320 JPC integrated accelerometer chip. Recordings were stored on a PC and spectral analysis was performed by fast Fourier transformation (FFT). We compared power integrals in the 1-4 Hz, 4-8 Hz and 8-12 Hz frequency ranges and these were statistically assessed by the Wilcoxon rank correlation test. Results We found significant changes in the power spectrum of physiological tremor. The spectrum in the 8-12 Hz range (neuronal oscillation) decreased and a shift was recognised to the lower spectrum (p < 0.01). The magnitude of the shift was not significantly higher for females than for males (p < 0.157). We found no significant difference between the shift and the cross-clamp or perfusion time (p < 0.6450). Conclusions The assessment of physiological tremor by means of our novel, feasible method may provide a deeper insight into the mechanism of central nervous system damage associated with open heart surgery.

Purpose: Arterial stiffness parameters, coronary calcium score (CCS) and epicardial fat volume (EFV) are commonly used to evaluate the development of cardiovascular disease. Our aim was to compare these parameters for the estimation of cardiovascular risk. Furthermore, we determined the cut-off values for regional aortic stiffness parameters in patients with ischaemic heart disease using the pulse wave analyzer oscillometric device (Arteriograph). Methods: We evaluated 186 patients with verified coronary artery disease (CAD) and 186 age- and gender-matched apparently healthy subjects (control). The regional stiffness parameters, the aortic pulse wave velocity (PWVao) and augmentation index (AIx), were studied by oscillometric Tensioclinic Arteriograph device. We also enrolled 158 patients who underwent non-contrast cardiac CT scan (64 slice DSCT-Siemens Somatom Definition) simultaneously with the stiffness measurements, and epicardial fat volume, Agatson coronary calcium score were determined. Results: The AIx and PWVao values in CAD group proved to be significantly elevated (PWVao: 10.2±2.3 m/s versus 9.5±1.6 m/s; and AIx: 34.5±14.7% versus 30.2±12.8%, p≤0.01) compared to control group. CCS and EFV values were also significantly higher in patients with CAD (EFV: 121.1±69.8 cm3, CCS: 207 (0-1327)) versus the control (EFV: 83.7±39.3 cm3, CCS: 5.3 (0-146), p≤0.01). Furthermore, we found weak or no correlation for stiffness parameters, EFV and CCS (r values between 0.31 and 0.04, p= NS). ROC-curves of CAD and healthy control patients explored cut-off values of 10.2 m/s for PWVao and 33.18% for AIx. Conclusions: Our results suggest that arterial stiffness parameters, epicardial fat volume and coronary calcium score are important markers of coronary artery disease, however weak or no correlation was found between the observed parameters. The cut-off value for the oscillometric, aortic pulse wave velocity is in good agreement with the recently published 2012 consensus document adviced carotid-femoral PWV data (cfPWV = 10 m/s).

Purpose: Prospective clinical trials provided firm evidence that elevated concentration of asymmetric dimethylarginine (ADMA) in the plasma and pericardial fluid (PF) is an independent predictor of worse cardiovascular events in patients undergoing coronary revascularization. Our aim was to investigate the changes of ADMA levels in patients with coronary artery disease (CAD), who underwent percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery. Methods: 64 patients who underwent PCI or CABG surgery were enrolled in this study (65.5±8.2 years). 52 patients who underwent valve replacement (VR) served as control subjects (59±6.9 years). Exercise stress test was performed on a treadmill according to the Bruce protocol. ADMA levels were determined by liquid chromatography – tandem mass spectrometry. Results: Patients in the CAD group had significantly elevated plasma concentrations of ADMA at rest, compared to the control group (0.59±0.02 μM/l vs. 0.46±0.03 μM/l; p<0.01). Serum ADMA levels exhibited similar, slight decrease in both groups during the exercise stress test on the treadmill (-0.01±0.19 for the control and -0.02±0.06 μmol/l for the CAD group; p=0.82). In the PCI group ADMA decreased substantially immediately after stent placement (Post-hoc ANOVA with factor time: F=10.8, p<0.0001) and remained low even 30 days after the intervention. ADMA levels which were collected from the coronary sinus showed a significant elevation in the group of patients who underwent cardiopulmonary bypass (CPB) (F=0.416, p=0.685 and F=14.751, p<0.001 for off-pump and CPB groups, respectively). Similarly, a significant increase of ADMA was observed in the peripheral blood (F=30.738, p<0.001) during CPB. The L-arginine/ADMA ratio of both plasma (125.4±10.7 vs. 76.7±8.7) and PF (110.4±7.2 vs. 80.8±6.04) were significantly higher in the CABG group compared to the VR group. Conclusions: The findings of this clinical study suggest that dysregulation of coronary circulation is well indicated by the altered ADMA levels and L-arginine/ADMA ratios in plasma and PF providing further evidence for the importance of the investigation of these mechanisms in patients with CAD.

OBJECTIVES Internal organ involvement reduces the life expectancy of SSc patients. Cardiopulmonary manifestations are currently the primary cause of death. We aimed to perform a systematic review and meta-analysis to define more precise effect estimates of different cardiopulmonary manifestations and to verify trends in the mortality of SSc. METHODS A systematic literature search was performed to identify relevant cohort studies. Reports analyzing the role of the organ manifestations in mortality or analysing survival compared with the control population were included. The outcome parameters were pooled with the random-effect model via generic inverse-variance weighting in conventional and cumulative meta-analysis. RESULTS Eighteen studies comprising a total of 12, 829 patients qualified. The reported causes of death were as follows: 19.7% cardiac, 16.8% interstitial pulmonary disease, 13.1% pulmonary hypertension and 13.8% renal disease. The risk of death was significantly increased in patients with cardiac involvement [hazard ratio (HR) 3.15], with pulmonary interstitial disease (HR 2.58), with pulmonary hypertension (HR 3.50) and with renal manifestations (HR 2.76). A trend for survival improvement (R2)= 0.4295, P = 0.04) was found, and the difference in survival between the diffuse and limited scleroderma subgroups was diminishing (R2)= 0.4119. P = 0.02). CONCLUSION Meta-analysis of observational studies indicates a trend for improvement over the last decades in which the life expectancy of SSc patients approaches that of the general population. A decreasing tendency in the survival differences between the limited and diffuse SSc subgroups was also verified. Internal organ involvements have similarly unfavourable predictive impact on survival.