Circulating P-Selectin Glycoprotein Ligand 1 and P-Selectin Levels in Obstructive Sleep Apnea Patients.

PURPOSE: Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia which induces inflammation in blood vessels leading to the development of cardiovascular comorbidities. Several studies implicated the role of P-selectin in vascular inflammation of OSA. P-selectin glycoprotein ligand 1 (PSGL-1) is the main activator for P-selectin and is involved in immune cell trafficking. However, PSGL-1 has not been analyzed in OSA. The aim of the study was to investigate plasma PSGL-1 and P-selectin levels to have a deeper understanding on their interaction in obstructive sleep apnea. METHODS: Fifty-one untreated patients with OSA and 42 non-OSA controls were recruited. Plasma PSGL-1 levels were determined in evening and morning samples, P-selectin levels were analyzed in morning samples using commercially available ELISA kits. Polysomnography was performed in all participants. OSA was defined by an apnea-hypopnea index ≥ 5/h. RESULTS: PSGL-1 levels did not differ between controls and OSA patients either in the evening or in the morning. Although, there was no difference between controls (16.9/6.8-40.8 ng/ml) and patients with OSA (19.6/8.4-56.8, p = 0.24), patients with severe OSA had increased plasma P-selectin levels (25.6/8.4-56.8 ng/ml) compared to mild OSA patients (14.1/8.5-35.3 ng/ml, p = 0.006) and controls (p = 0.03). CONCLUSIONS: P-selectin expression relates to disease severity suggesting a pathophysiological role in endothelial cell activation. PSGL-1 levels are unaltered in OSA, suggesting an alternative activation pathway for P-selectin in OSA.

The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Assessing genetic and environmental influences on epicardial and abdominal adipose tissue quantities: a classical twin study.

BACKGROUND/OBJECTIVES: Various adipose tissue compartments play an important role in the development of cardiometabolic diseases. The quantity of different fat compartments is influenced by genetic and environmental factors. The aim of our study was to evaluate the magnitude of genetic and environmental effects on epicardial, subcutaneous and visceral adipose tissue (EAT, SAT and VAT) quantities in a cohort of adult twin pairs. SUBJECTS/METHODS: In this cross-sectional study we investigated adult twins (57 monozygotic (MZ) and 33 dizygotic (DZ) same-gender twin pairs; 180 twin subjects). We measured EAT volume using electrocardiogram-gated native computed tomography (CT) scan of the heart, and abdominal SAT and VAT areas were quantified between the third and fourth lumbar vertebra on native CT images. We calculated genetic and environmental impact on the size of various adipose tissue compartments by analyzing co-twin correlations in MZ and DZ pairs separately, and furthermore by using genetic structural equation models. RESULTS: In co-twin analysis, MZ twins had stronger correlations than DZ twins for EAT (rMZ=0.81, rDZ=0.32), similar to SAT and VAT quantities (rMZ=0.80, rDZ=0.68 and rMZ=0.79, rDZ=0.48, respectively). In multi-trait model fitting analysis, the overall contribution of genetic factors to EAT, SAT and VAT volumes were 80%, 78% and 70%, whereas environmental factors were 20%, 22% and 30%, respectively. Common pathway model analyses indicated that none of the EAT, SAT and VAT phenotypes was independent of the other two. CONCLUSIONS: Genetic factors have substantial influence, while environmental factors have only a modest impact on EAT volume, abdominal SAT and VAT quantities. There is a considerable amount of common genetic background influencing the quantities of all three adipose tissue compartments.

Different genetic impact in the development of renal length and width: a twin study.

BACKGROUND: Ultrasound measurements of renal dimensions are conventionally limited to renal length, shape and cortical thickness. These are regarded as adequate for normal therapeutic decision-making and volume measurements are reserved for a few clinical trials. However, there is no evidence concerning the degree to which renal length or volume is independently susceptible to heritable and environmental influences. AIM: We aimed to determine whether renal length or width (as a surrogate of volume) was more influenced by heritability. METHODS: A single operator measured renal length and width in 114 adult monozygotic and same-sex dizygotic Hungarian twin pairs (mean age 43.6 ± 16.3 years), using an Esaote MyLab 70X ultrasound machine with curved array transducer (1-8 MHz, CA431). RESULTS: Analysis of within-pair co-twin correlations adjusted for age and gender showed that the age- and sex-adjusted heritability of average renal length was 51% (95% confidence interval, 29-72%). Renal width showed negligible genetic influence. Common environmental effects had no influence, and unshared environments were responsible for 49-80% of the variance, mainly renal width. CONCLUSIONS: This study is the first to demonstrate the moderate heritability and limited environmental influence on renal length, and the contrasting lack of heritability of renal width, which is mainly influenced by unshared environmental components, that is lifestyle habits. Renal width therefore better represents the influence of modifiable environmental factors than renal length. The results suggest that renal width not length should be reported to facilitate early detection and monitoring of renal disease.

Heritability of arterial stiffness and carotid intima-media thickness: an Italian twin study.

BACKGROUND AND AIMS: Carotid intima-media thickness (IMT) and arterial stiffness parameters, including aortic augmentation index (AIx) and pulse wave velocity (PWV), are independent predictors of stroke and cardiovascular disease. Genetic effects on these traits were never explored in a Mediterranean country. The present study aims to quantify the contribution of genes, environment and age to carotid IMT and aortic Aix and PWV. METHODS AND RESULTS: The twin design was used. A total of 348 adult twins from the Italian Twin Register underwent measurements of carotid IMT and aortic PWV and AIx in three university hospitals located in Rome, Padua and Perugia. Carotid IMT was measured by B-mode ultrasound, aortic PWV and AIx by Arteriograph. Genetic modelling was performed to decompose total variance of traits into genetic, shared and unshared environmental and age components. For each phenotype, the best-fitting model included additive genetic, unshared environmental and age effects. For IMT, heritability was 0.32 (95% confidence interval (CI): 0.25-0.38), unshared environmental component was 0.25 (0.18-0.32) and age contribution was 0.44 (0.39-0.49). For AIx and PWV, heritabilities were 0.42 (0.29-0.55) and 0.49 (0.35-0.62), unshared environmental components were 0.31 (0.22-0.44) and 0.37 (0.26-0.51) and age contributions were 0.27 (0.16-0.39) and 0.14 (0.06-0.24), respectively. CONCLUSION: This study shows substantial genetic and unshared environmental influences on carotid intima-media thickness and arterial stiffness and confirms the relevant role of age in the aetiology of these traits. Further support is provided for prevention and health promotion strategies based on modifiable factors.

Partial absence of superior vena cava in an adult patient. Case report and literature review.

Absence of the superior vena cava (SVC) is a rare variety of vascular anomaly. The purpose of this report is to describe the computed tomography (CT) findings of the partial absence of the SVC without persistent left SVC in a patient with no evidence of congenital cardiovascular disease and no prior history of central venous instrumentation. A 77-year-old woman with a history of colon cancer underwent thoracoabdominal CT imaging because of abdominal pain of uncertain cause. No tumor recurrence was observed. A complicated"investigation" confirmed a thymoid cancer surgery back in 1976, which was accompanied by resection of the SVC and the left brachiocephalic vein because of their invasion. Owing to the absence of the SVC and bilateral brachiocephalic veins, caval hypertension developed in the patient, resulting in the dilation of cavo-caval anastomoses. In addition, new anastomoses were opened. The clinical significance and possible embryogenesis of this anomaly are discussed. The extremely rare condition of the partial absence of the SVC appeared with subcutaneous dilated, tortuous collaterals in an asymptomatic adult patient. This anomaly is becoming clinically more relevant with the increasing use of minimally invasive vascular surgery.

Effects of genetic vs. environmental factors on cardiovascular autonomic function: a twin study.

AIMS: Cardiovascular autonomic function is often assessed in patients with diabetes by measuring heart rate variability and baroreflex sensitivity, the heritability of which is not fully understood. The present study was aimed to determine the effects of genetic and environmental factors on heart rate variability and baroreflex sensitivity in monozygotic and dizygotic adult healthy twin pairs. METHODS: A total of 101 (63 monozygotic, 38 dizygotic) adult twin pairs (n = 202; mean age 44.3 years) were investigated. Anthropometric variables and serum metabolic markers were measured, while environmental characteristics were evaluated by questionnaires. Linear and spectral indices of heart rate variability and baroreflex sensitivity were determined by non-invasive methods. All measurements were adjusted for age and gender (model 1) and for all significantly relevant covariates (model 2). Heritability A-C-E structural equation models were used for characterizing the proportion of additive genetic, shared and unshared environmental influences. RESULTS: Genetic influence of different cardiovascular autonomic indices was estimated between 10.3 and 39.4%, common environmental influence was found between 0.0 and 33.2%, while unshared environmental influence was observed between 60.6 and 81.4% in model 1 analysis. In multivariable-adjusted heritability estimates (model 2), the magnitude of the genetic effects decreased to 0.0%, common environmental influence was nearly unchanged (values between 4.4 and 14.5%), while unshared environmental influence slightly increased (values between 85.5 and 96.5%). CONCLUSIONS: Unshared environmental but not genetic factors have substantial influence on cardiovascular autonomic function, suggesting that appropriate treatment of all modifiable environmental factors is of importance in order to prevent or ameliorate cardiovascular autonomic neuropathy.

MR Diagnosis of Bone Metastases at 1.5 T and 3 T: Can STIR Imaging Be Omitted?

OBJECTIVE: To date, no prospective comparative study of the diagnostic value of STIR versus T1-weighted (T1w) sequences at both 1.5 T and 3 T has been performed with special focus on the detectability of bone metastases. MATERIALS AND METHODS: 212 oncological patients had a whole-body MRI at 1.5 T and/or at 3 T. The standard protocol comprised STIR and T1w sequences. All patients who showed typical signs of bone metastases were included in the study. Evaluation of the images was performed by the calculation of the number of metastases by three independent readers and by visual assessment on a 4-point scale. RESULTS: 86 patients fulfilled the inclusion criteria. The total number of metastases was significantly higher on T1w than on STIR images at both field strengths (p < 0.05). T1w revealed a sensitivity of 99.72% (3 T) and 100.00% (1.5 T) versus STIR with 70.99 % (3 T) and 79.34 % (1.5 T). In 53% (38/72) of all patients, STIR detected fewer bone metastases in comparison with T1w at 3 T. At 1.5 T, STIR showed inferior results in 37.5 % (18/48) of all patients. Qualitative analysis indicated a significantly better lesion conspicuity, lesion delineation and an improved image quality on T1w compared to STIR imaging at both field strengths (p < 0.05) with similar results for T1w at 1.5 T and 3 T, but inferior results for STIR especially at 3 T. CONCLUSION: The whole-body MRI protocol for the detection of bone metastases could safely be limited to the T1w sequence in adults, especially at 3 T. There is no need for an additional STIR sequence. These initial results will have a major impact on the department's workflow if confirmed by larger studies as they will help reduce examination time and therefore save financial resources. KEY POINTS: In a routine MR protocol, T1w imaging is sufficient for the detection of bone metastases. In case of differential diagnostic problems, other appropriate sequences can be added to the protocol. STIR is inferior to T1w in the detection of metastases, especially at 3 T.

A possible genetic influence in parenchyma and small airway changes in COPD: a pilot study of twins using HRCT.

UNLABELLED: Genetic effects that contribute to the risk of developing chronic obstructive pulmonary disease (COPD) have been reported. Our purpose was to estimate the possible genetic influence on CT features related to COPD in twins. METHODS: Two COPD-discordant and one COPD-concordant monozygotic (MZ) twin pair, in addition to 2 control dizygotic (DZ) twin pairs underwent a low-dose high resolution computer tomography (HRCT) in inspiration and expiration (Philips Brilliance 16). RESULTS: Monozygotic twins were more similar in lung volume expiration and in air trapping score compared to dizygotics (382 cm(3) vs. 2303 cm(3) and 17.6% vs. 26.6%, respectively). In general, MZ twin pairs showed almost identical HRCT features independently of smoking attitude and COPD status. The dizygotic twin pairs showed larger differences in HRCT features compared to MZ twins. CONCLUSIONS: Lung parenchymal and small airway changes (lung density, presence of bronchial wall thickening, bronchiectasis and/or mucus plug formation, air trapping and emphysema score) seem to be genetically associated traits, independently of smoking/COPD history. A future study with a larger sample size should confirm our findings.

Genetic effects on refraction and correlation with hemodynamic variables: a twin study.

Spherical equivalent (SE) has not been linked to increased cardiovascular morbidity. Methods: 132 Hungarian twins(age 43.3±16.9 years) underwent refraction measurements (Huvitz MRK-3100 Premium AutoRefractokeratometer)and oscillometry (TensioMed Arteriograph). Results: Heritability analysis indicated major role for genetic components in the presence of right and left SE (82.7%, 95%CI, 62.9 to 93.7%, and 89.3%, 95%CI, 72.8 to 96.6%),while unshared environmental effects accounted for 17% (95%CI, 6.3% to 37%), and 11% (95%CI, 3.4% to 26.7%)of variations adjusted for age and sex. Bilateral SE showed weak age-dependent correlations with augmentation index (AIx), aortic pulse wave velocity (r ranging between 0.218 and 0.389, all p < 0.01), aortic systolic blood pressure and pulse pressure (r between 0.188 and 0.289, p < 0.05). Conclusions: These findings support heritability of spherical equivalent, which does not coexist with altered hemodynamics (e.g. accelerated arterial aging).Accordingly, SE and the investigated hemodynamic parameters seem neither phenotypically nor genetically associated.