Peripheral blood natural killer cells in sarcoidosis are associated with early cardiac involvement.

AIM: To evaluate the distribution of circulating immune cell subsets in peripheral blood of patients with sarcoidosis and investigate if there is an association with an underlying cardiac involvement. METHODS AND RESULTS: Eighty-five newly diagnosed treatment-naïve patients with sarcoidosis (50 women) were included in the study. All patients underwent a thorough cardiac investigation, including cardiac magnetic resonance imaging (CMR). Of all patients, 19 (23.53%) had myocardial involvement, and the NK subpopulation in these patients in peripheral blood was significantly decreased compared to patients without (n = 63, p = 0.001 and p = 0.003 respectively). The absolute number of NKT cells (CD3+CD16/56+ ) in patients with cardiac involvement was highly correlated with T2 map increased values in MRI (r = -686, p = 0.041) showing that low NKT cell count correlates with the inflammatory process of the heart. No difference in CD19, CD3, CD4, CD8 and CD3- NK cell counts was found between groups. Lung severity was not found to correlate with the number of NK cells. CONCLUSION: We found that low NK cell count in peripheral blood of patients with sarcoidosis is associated with cardiac involvement, and the number of NK-T cells correlates with CMR findings indicative of myocardial inflammation. This finding might have a potential clinical application in detecting clinically silent cardiac involvement in sarcoidosis and may also suggest potential targets for therapeutic interventions.

Blood Pressure Deviation from the Golden Ratio φ and All-cause Mortality: A Pythagorean View of the Arterial Pulse.

INTRODUCTION: There is one mathematical element with strong historical and philosophical background that exhibits remarkable properties and applications; the golden ratio (phi). Mathematically, the golden ratio equals approximately 1.61803. A rather provocative geometrical analysis of the arterial pulse according to the golden ratio was recently described, and herein, we aim to set out the hypothesis that individuals with blood pressure (BP) values that follow the golden ratio may have different prognosis than those whose BPs deviate from the divine proportions. MATERIALS AND METHODS: We used published data from the National Health and Nutrition Examination Survey during 1999-2010. RESULTS: We found that the deviation of the BP values from the golden ratio is independently associated with all-cause mortality. CONCLUSIONS: This observation stimulates further research of the potential utility of the golden ratio of BP values on the diagnosis and prediction of BP-related abnormalities and risk.

Association of the 894G>T polymorphism in the endothelial nitric oxide synthase gene with risk of acute myocardial infarction.

BACKGROUND: This study was designed to investigate the association of the 894G>T polymorphism in the eNOS gene with risk of acute myocardial infarction (AMI), extent of coronary artery disease (CAD) on coronary angiography, and in-hospital mortality after AMI. METHODS: We studied 1602 consecutive patients who were enrolled in the GEMIG study. The control group was comprised by 727 individuals, who were randomly selected from the general adult population. RESULTS: The prevalence of the Asp298 variant of eNOS was not found to be significantly and independently associated with risk of AMI (RR = 1.08, 95%CI = 0.77-1.51, P = 0.663), extent of CAD on angiography (OR = 1.18, 95%CI = 0.63-2.23, P = 0.605) and in-hospital mortality (RR = 1.08, 95%CI = 0.29-4.04, P = 0.908). CONCLUSION: In contrast to previous reports, homozygosity for the Asp298 variant of the 894G>T polymorphism in the eNOS gene was not found to be associated with risk of AMI, extent of CAD and in-hospital mortality after AMI.

Hour-to-hour and week-to-week variability and reproducibility of wave reflection indices derived by aortic pulse wave analysis: implications for studies with repeated measurements.

BACKGROUND: Wave reflections are implicated increasingly in clinical research. AIMS: The purpose of the present study was to investigate whether wave reflection indices are reproducible when measured repeatedly (more than twice) at longer time intervals, namely hour-to-hour and week-to-week, in healthy subjects; something that has not yet been examined. METHODS: Bland-Altman plots, the interclass correlation coefficients (ICC) and coefficient of variation were used for this purpose. Two series, with measurements repeated in triplicate, were performed in 22 healthy subjects: the first at intervals of 1 h and the second at 1-week time intervals. Augmentation index (AIx), heart rate-corrected AIx (AI@75) and arrival time of reflected waves at the central aorta (tr) were calculated by aortic pulse wave analysis. RESULTS: AIx and AI@75 presented very good to excellent reproducibility (ICC = 0.86) for hour-to-hour repeated measurements, while tr was also highly reproducible (ICC = 0.79). AIx, AI@75 and tr were substantially reproducible when measured repeatedly with 1-week intervals, providing ICCs greater than 0.70. Bland-Altman plots confirmed these results, indicating that more than 90% of AIx, AI@75 and tr measurements fell within two standard deviations of the mean difference. CONCLUSIONS: Wave reflections are substantially reproducible even when measurements repeated in triplicate are performed at longer time intervals (hours and weeks). A quantifiable amount of variation was reported, which should be taken carefully into consideration in interventional studies with repeated measurements and in observational studies investigating differences or correlations of these indices.

CARD15/NOD2, CD14, and toll-like receptor 4 gene polymorphisms in Greek patients with sarcoidosis.

BACKGROUND: Sarcoidosis, similarly to Crohn's disease (CD), is a complex inflammatory disease of unknown etiology. The belief that a genetic susceptibility to the development of sarcoidosis exists was derived from observations of familial clustering of sarcoidosis cases and racial differences in disease prevalence. Taking into account the remarkable similarity in the immunopathophysiology of sarcoidosis and CD, and in further exploring the genetic background of sarcoidosis, we study gene polymorphisms known for their implication in CD. These polymorphisms are in the CARD15/NOD2 gene (R702W, G908R and 3020insC), as well as mutations in the promoter of the CD14 gene (T/C at position -159) and in the TLR4 gene (Asp299Gly and Thr399Ile). METHODS: DNA was obtained from 100 sarcoidosis patients and 150 healthy individuals. Genotyping was performed by allele specific PCR or by PCR-RFLP analysis. RESULTS: Although CARD 15/NOD2 mutations were more frequent in cases than in controls, the difference was significant only for the G908R polymorphism (p = 0.024). Interestingly, the same was recorded with reference to the T allele (p = 0.002) and TT genotype (p = 0.017) frequencies of the CD14 promoter. No differences were observed in the 299Gly and 399Ile allele frequencies between patients and controls. Finally, the co-existence of a mutation in the CARD15/NOD2 and the CD14 genes was associated with sarcoidosis at a higher level of significance than any of these mutations separately. CONCLUSION: Our results suggest that the G908R mutation of the CARD15/NOD2 gene, as well as the T allele and TT genotype of the CD14 promoter are associated with increased susceptibility for developing sarcoidosis.

Mean arterial pressure values calculated using seven different methods and their associations with target organ deterioration in a single-center study of 1878 individuals.

To assess the differences among seven different methods for the calculation of mean arterial pressure (MAP) and to identify the formula that provides MAP values that are more closely associated with target organ deterioration as expressed by the carotid cross-sectional area (CSA), carotid-to-femoral pulse-wave velocity (cf-PWV) and left ventricular mass (LVM). The study population consisted of 1878 subjects who underwent noninvasive cardiovascular risk assessment. Blood pressure (BP) was assessed in all subjects, and MAP was calculated by direct oscillometry and six different formulas. Carotid artery ultrasound imaging was performed in 1628 subjects. The CSA of the right and left common carotid artery (CCA) were calculated and used as surrogates of arterial wall mass and hypertrophy. Aortic stiffness was evaluated in 1763 subjects by measuring the cf-PWV. Finally, 218 subjects underwent echocardiographic examination for the assessment of LVM. Among the examined methods of MAP calculation, the formula MAP1=[diastolic BP]+0.412 × [pulse pressure] yielded the strongest correlations with the LVM, cf-PWV and CSA of the right and left CCA, even after adjusting for age and gender. The MAP calculation using the 0.412 was superior compared with the traditional formula that uses the 0.33 for the discrimination of subjects with left ventricular and carotid wall hypertrophy, as well as subjects with increased aortic stiffness. MAP estimated with the 0.412 is better correlated with target organ deterioration compared with other formulas. Future studies are needed to explore the accuracy of these formulas for MAP estimation compared with direct intra-arterial BP measurement.

Obscure gastrointestinal bleeding and calcific aortic stenosis (Heyde's syndrome).

The coexistence of calcific aortic valve stenosis and obscure gastrointestinal bleeding secondary to intestinal angiodysplasias usually of the cecum and the ascending colon constitutes Heyde's syndrome. The pathophysiologic link between both entities has remained unclear so far but newer studies suggest that it is the result of subtle alterations in plasma coagulation factors. Cessation of the bleeding has followed replacement of the aortic valve. We describe a patient with recurrent obscure gastrointestinal bleeding, calcific aortic stenosis and intestinal angiodysplasias, and discuss the current literature.

Pattern and distribution of myocardial fibrosis in systemic sclerosis: a delayed enhanced magnetic resonance imaging study.

OBJECTIVE: To assess the prevalence and pattern of myocardial fibrosis as detected by delayed enhanced magnetic resonance imaging (DE-MRI) in patients with systemic sclerosis (SSc), and to evaluate a possible association between myocardial fibrosis and cardiac arrhythmias. METHODS: Forty-one patients with SSc underwent 24-hour Holter monitoring, Doppler echocardiography, and DE-MRI following gadolinium administration. RESULTS: Technically acceptable DE-MRIs were obtained in 36 patients with SSc. Enhancement on DE-MRI, consistent with myocardial fibrosis, was observed in 24 of these patients (66%), and it was invariably midwall with a linear pattern, mostly involving basal and midcavity segments of the left ventricle. The volume of enhancement (total volume percentage index [TVPI]) did not differ between patients with diffuse SSc and those with limited SSc (mean +/- SD 1.46 +/- 1.73% versus 1.44 +/- 1.77%; P = 0.98). Patients with a long duration (> or = 15 years) of Raynaud's phenomenon had a greater number of enhancing segments (mean +/- SD 6.55 +/- 4.93 versus 2.96 +/- 3.46; P = 0.017) and a greater TVPI (mean +/- SD 2.44 +/- 1.97% versus 1.02 +/- 1.43%; P = 0.02) than those with a duration of Raynaud's phenomenon <15 years. Nineteen patients with SSc (53%) had abnormal Holter study results. Compared with patients with normal Holter study results, those with abnormal results had a greater number of enhancing segments (mean +/- SD 5.4 +/- 4.8 versus 2.5 +/- 2.9; P < 0.05) and a greater TVPI (mean +/- SD 2.1 +/- 1.9% versus 0.8 +/- 1.2%; P < 0.05). CONCLUSION: DE-MRI can identify myocardial fibrosis in a significant percentage of patients with SSc and may be a useful noninvasive tool for determining cardiac involvement.

Lack of association between common polymorphisms in genes of the renin-angiotensin system and mortality after myocardial infarction.

The insertion/deletion (I/D) polymorphism in the ACE gene and the A1166C polymorphism in the AT1R gene have been associated with left ventricular remodelling and prognosis after acute myocardial infarction (AMI). We investigated whether these genetic variants associate with impaired left ventricular ejection fraction (LVEF) and increased risk for in-hospital mortality after AMI. Consecutive AMI patients were recruited on admission and were genotyped for the above-mentioned polymorphisms. The frequency of the studied genotypes did not differ significantly between deceased patients and those who survived. The LVEF did not differ among patients with or without the DD genotype (45 +/- 10 vs. 45 +/- 10%, p = 0.892) or the CC genotype (45 +/- 10 vs. 46 +/- 10%, p = 0.859). These data question the role of the studied genotypes in the pathogenesis of AMI and do not support the previously supported hypothesis that these genotypes influence prognosis after AMI.

New aspects on the role of blood pressure and arterial stiffness in mechanical assistance by intra-aortic balloon pump: in-vitro data and their application in clinical practice.

Despite the well-known beneficial effects of the intra-aortic balloon pump (IABP) generally, there are still some clinical conditions accompanied by IABP ineffectiveness. The aim of this study was the investigation of the independent effects of arterial stiffness and blood pressure on acute IABP effectiveness. For this purpose, a mock circulatory system and 20 patients with cardiogenic shock due to acute myocardial infarction, were employed. It was shown that IABP acute efficiency was determined primarily by arterial compliance (AC) rather than blood pressure alone. IABP induced low hemodynamic effects in patients with systolic blood pressure > 80 mm Hg but with increased AC, whereas IABP resulted in greater hemodynamic effectiveness in cases with systolic pressure < 70 mm Hg but lower AC. The present study provides evidence concerning the hemodynamic conditions, which might lead to optimization of IABP or to the prediction of its acute hemodynamic performance, based on both measurements of AC and blood pressure.

P wave analysis indices in young healthy men: data from the digital electrocardiographic study in Hellenic Air Force Servicemen (DEHAS).

P wave analysis from the 12-lead ECG is a recent contribution of noninvasive electrocardiology. P wave analysis indices (maximum and minimum P wave duration, P wave dispersion [Pdis = Pmax-Pmin], adjusted P wave dispersion [APdis = Pdis/square root of measured leads], summated P wave duration [Psum], standard deviation of P wave duration [Psd], mean P wave duration [Pmean]) can predict atrial arrhythmias. However, the definitions of all these indices are based on few studies. The aim of this analysis was to define normal values of these indices and the examine possible associations between P wave indices and clinical variables. The study included 1,353 healthy men, 24 +/- 3 years of age, who answered a questionnaire and underwent a detailed physical examination and a digitized 12-lead surface ECG. All P wave indices were analyzed by two independent investigators. Mean values of the ECG indices were: Pmax: 96 +/- 11 ms, Pmin: 57 +/- 9 ms, Pdis: 38 +/- 10 ms, Psum: 924 +/- 96 ms, Psd: 12 +/- 3, APdis: 11 +/- 3 ms, and Pmean: 77 +/- 8 ms. Age was significantly related with Pmax (r = 0.277, P < 0.01), Pmin (r = 0.255, P < 0.001), Psum (r = 0.074, P < 0.01), and Pmean (r = 0.074, P < 0.01). All ECG indices were significantly associated with the R-R interval, and among each other. This study defined normal indices of wave duration and correlations among them. These markers may play an important predictive role in patients with atrial conduction abnormalities.

The paradoxical association of common polymorphisms of the renin-angiotensin system genes with risk of myocardial infarction.

BACKGROUND: The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) and the A1166C polymorphism of the angiotensin-II AT1 receptor (AT1R) have been extensively investigated as possible risk factors for myocardial infarction (MI). DESIGN AND METHODS: Genetic association, case-control study, specifically designed to investigate the association of the above-mentioned polymorphisms with risk of MI in a homogeneous, low coronary risk, Caucasian population. The study population consisted of 1603 consecutive patients with acute MI who were recruited from nine clinics, located in three cities, and 699 unrelated adults who were randomly selected from the city catalogues. RESULTS: In univariate analysis, the DD genotype was found to be more prevalent among controls (40.8 vs. 35.2%, P=0.011). In multivariate analysis adjusted for age, gender, smoking status, diabetes mellitus, hypercholesterolaemia, hypertension and family history of coronary artery disease, the presence of the DD genotype was independently and negatively associated with risk of AMI (RR=0.743, 95% CI=0.595-0.927, P=0.008). The CC genotype was not found to be significantly associated with risk of MI, either in univariate (6.2 vs. 6.4%, P=0.856), or in multivariate analysis adjusted for the same confounders (RR=0.743, 95% CI=0.473-1.167, P=0.197). CONCLUSIONS: Contrary to previous reports, in this study the DD genotype of the ACE gene, but not the CC genotype of the AT1R gene, was associated with a lower risk of MI. Our results emphasize the complexity of genotype-phenotype interactions in the pathogenesis of ischaemic heart disease and question the previously hypothesized role of the DD genotype on risk of acute myocardial infarction.