Functional condition of the endothelium in men with primary gout and initial signs of renal dysfunction

Background. Among the causes of mortality in patients with gout, cardiovascular complications and chronic renal failure are prevailed. The searching for the markers of the initial signs of endothelial and renal dysfunction is relevant for the early diagnosis of target organs damage. Objective. To determine the indicators of endothelial dysfunction in men with primary gout with normal glomerular filtration rate (GFR) and men with stage 1 chronic renal failure (CRF). Materials and methods. 30 men with primary gout and GFR > 90 ml / min, 30 men with primary gout and GFR = 89–60 ml / min and 30 healthy men were examined. We determined the concentration of endothelin-1 (ET-1), vascular cell adhesion molecule-1 (VCAM-1), total nitric oxide metabolites (NO), serum cystatin C, level of albuminuria and endothelium-dependent vasodilatation (EDVD). Results. An increase in NO, ET-1, VCAM-1, cystatin C and normal values of EDVD and albuminuria were found in men with primary gout and normal GFR in comparison to the control. In patients with gout and CRF (stage 1), a significant increase in ET-1, VCAM-1, cystatin C, albuminuria and a decrease in NO and EDVD were detected compared to the men with primary gout and GFR >90 ml / min. Conclusions. Patients with primary gout and normal GFR are characterized by NO hyperproduction providing the vasomotor endothelial function preservation. An increase in the level of cystatin C in these patients compared to the healthy men indicates the beginning of renal filtration function deterioration. Patients with gout and CRF (stage 1) are characterized by significant impairment of vasomotor endothelial function, an increased synthesis of pro-inflammatory markers and a decreased NO production

Full potential LAPW calculation of electron momentum density and related properties of Li

Electron momentum density and Compton profiles in Lithium along $$,$$, and $$ directions are calculated using Full-Potential Linear Augmented Plane Wave basis within generalized gradient approximation. The profiles have been corrected for correlations with Lam-Platzman formulation using self-consistent charge density. The first and second derivatives of Compton profiles are studied to investigate the Fermi surface breaks. Decent agreement is observed between recent experimental and our calculated values. Our values for the derivatives are found to be in better agreement with experiments than earlier theoretical results. Two-photon momentum density and one- and two-dimensional angular correlation of positron annihilation radiation are also calculated within the same formalism and including the electron-positron enhancement factor.Comment: 11 pages, 7 figures TO appear in Physical Review

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

Функціональний стан ендотелію в чоловіків, які хворі на первинну подагру з початковими ознаками ниркової дисфункції

 Background. Among the causes of mortality in patients with gout, cardiovascular complications and chronic renal failure are prevailed. The searching for the markers of the initial signs of endothelial and renal dysfunction is relevant for the early diagnosis of target organs damage.Objective. To determine the indicators of endothelial dysfunction in men with primary gout with normal glomerular filtration rate (GFR) and men with stage 1 chronic renal failure (CRF).Materials and methods. 30 men with primary gout and GFR &gt; 90 ml / min, 30 men with primary gout and GFR = 89–60 ml / min and 30 healthy men were examined. We determined the concentration of endothelin-1 (ET-1), vascular cell adhesion molecule-1 (VCAM-1), total nitric oxide metabolites (NO), serum cystatin C, level of albuminuria and endothelium-dependent vasodilatation (EDVD).Results. An increase in NO, ET-1, VCAM-1, cystatin C and normal values of EDVD and albuminuria were found in men with primary gout and normal GFR in comparison to the control. In patients with gout and CRF (stage 1), a significant increase in ET-1, VCAM-1, cystatin C, albuminuria and a decrease in NO and EDVD were detected compared to the men with primary gout and GFR &gt;90 ml / min.Conclusions. Patients with primary gout and normal GFR are characterized by NO hyperproduction providing the vasomotor endothelial function preservation. An increase in the level of cystatin C in these patients compared to the healthy men indicates the beginning of renal filtration function deterioration. Patients with gout and CRF (stage 1) are characterized by significant impairment of vasomotor endothelial function, an increased synthesis of pro-inflammatory markers and a decreased NO production.  Среди причин смертности у больных подагрой преобладают сердечно-сосудистые осложнения и хроническая почечная недостаточность (ХПН). Поэтому для ранней диагностики поражений органов-мишеней актуальным является поиск маркеров начальных признаков эндотелиальной и почечной дисфункции.Цель работы – исследовать показатели эндотелиальной дисфункции у мужчин, больных первичной подагрой с нормальной СКФ и признаками ХПН 1 стадии.Материалы и методы. Исследовано 30 мужчин с первичной подагрой и СКФ &gt;90 мл /мин, 30 мужчин с первичной подагрой и СКФ = 89–60 мл /мин и 30 здоровых мужчин. Определяли содержание эндотелина-1 (ЭТ-1), васкулярной молекулы клеточной адгезии-1 (VCAM-1), суммарных метаболитов оксида азота (NO), цистатина С (ЦС) в сыворотке; исследовали уровень альбуминурии и эндотелий-зависимой вазодилатации (ЭЗВД).Результаты. У больных подагрой со СКФ  &gt;90 мл/мин установлено увеличение содержания NO, ЭТ-1, VCAM-1, ЦС и нормальные показатели ЭЗВД и альбуминурии по сравнению с контролем. У больных подагрой с ХПН 1 стадии отмечено увеличение ЭТ-1, VCAM-1, ЦС и альбуминурии, а также уменьшение содержания NO и показателя ЭЗВД по сравнению с больными подагрой без признаков ХПН.Выводы. У больных первичной подагрой без признаков ХПН наблюдали увеличение синтеза NO, что обеспечивает сохранение вазомоторной функции эндотелия. У больных данной категории увеличение содержания ЦС по сравнению со здоровыми свидетельствует о начале ухудшения фильтрационной способности почек. Для больных подагрой с ХПН 1 стадии характерны достоверное ухудшение вазомоторной функции эндотелия, увеличение синтеза провоспалительных маркеров и уменьшение продукции NO. Серед причин смертності у хворих на подагру переважають серцево-судинні ускладнення та хронічна ниркова недостатність (ХНН). Тому для ранньої діагностики уражень органів-мішеней актуальним є пошук маркерів початкових ознак ендотеліальної та ниркової дисфункції.Мета роботи – дослідити показники ендотеліальної дисфункції в чоловіків, які хворі на первинну подагру з нормальною ШКФ та ознаками ХНН 1 стадії.Матеріали та методи. Дослідили 30 чоловіків із первинною подагрою та ШКФ &gt; 90 мл/хв, 30 чоловіків із первинною подагрою та ШКФ = 89–60 мл/хв і 30 здорових чоловіків. Визначали вміст ендотеліну-1 (ЕТ-1), васкулярної молекули клітинної адгезії-1 (VCAM-1), сумарних метаболітів оксиду азоту (NO), цистатину С (ЦС) у сироватці; досліджували рівень альбумінурії та ендотелій-залежної вазодилатації (ЕЗВД).Результати. У осіб, які хворі на подагру зі ШКФ &gt;90 мл/хввстановлено збільшення вмісту NO, ЕТ-1, VCAM-1, ЦС і нормальні показники ЕЗВД та альбумінурії порівняно з контролем. У хворих на подагру з ХНН 1 стадії виявили збільшення ЕТ-1, VCAM-1, ЦС та альбумінурії, а також зменшення вмісту NO й показника ЕЗВД порівняно з хворими на подагру зі ШКФ &gt;90 мл/хв. Висновки. У хворих на первинну подагру без ознак ХНН спостерігається збільшення синтезу NO, що забезпечує збереження вазомоторної функції ендотелію. У хворих цієї категорії збільшення вмісту ЦС порівняно зі здоровими  свідчить про початок погіршення фільтраційної здатності нирок. Для хворих на подагру з ХНН 1 стадії характерними є вірогідне погіршення вазомоторної функції ендотелію, збільшення синтезу прозапальних маркерів, зменшення продукції NO.