Long-Term Renal Function in Adult Patients with Phenylketonuria.

INTRODUCTION: In phenylketonuria (PKU), toxic phenylalanine (Phe) can harm other organs beyond the brain. Furthermore, the lifelong therapy of PKU consists of consumption of increased amounts of amino-acid mixture that provoke hyperfiltration in the glomeruli. Therefore, the adherence to therapy in PKU might influence the long-term kidney function in PKU patients. METHODS: Data from 41 adult, early treated PKU patients were analyzed in this 10-year, retrospective, monocentric study. Two subgroups were created according to their therapy adherence: one with long-term blood Phe levels in the therapeutic range (<600 µmol/L), and one with suboptimal blood Phe levels. Renal function and metabolic parameters were collected over 10 years. Kidney function parameters were compared between the two groups and associations between blood Phe levels and kidney function were tested. RESULTS: After 10 years, serum creatinine levels (p = 0.369) and estimated glomerular filtration rate (eGFR) (p = 0.723) did not change significantly from baseline in the good therapeutic group. The suboptimal therapeutic group's eGFR decreased in the same period (from 110.4 ± 14 mL/min/1.73 m2 to 94.2 ± 16 mL/min/1.73 m2, p = 0.017). At 10 years, the suboptimal therapeutic group had an increased serum creatinine level (81 ± 14.4 µmol/L vs. 71.5 ± 13 µmol/L, p = 0.038), and a decreased eGFR (94.2 ± 16 mL/min/1.73 m2 vs. 103.3 ± 13 mL/min/1.73 m2p = 0.031) compared to the good adhering group. Significant negative correlation between Phe levels and eGFR (r = -0.41, p = 0.008) was observed. CONCLUSION: Long-term suboptimal therapy adherence in PKU patients with high blood Phe levels may lead to deterioration in kidney function.

The impact of COVID-19 infection before the vaccination era on the hospitalized patients requiring hemodialysis: a single-center retrospective cohort.

Due to effective vaccinations, the COVID-19 (coronavirus disease 2019) infection that caused the pandemic has a milder clinical course. We aimed to assess the mortality of hospitalized COVID-19 patients before the vaccination era. We investigated the mortality in those patients between 1 October 2020 and 31 May 2021 who received hemodialysis treatment [patients with previously normal renal function (nCKD), patients with chronic kidney disease previously not requiring hemodialysis (CKDnonHD), chronic kidney disease (CKD), and patients on regular hemodialysis (pHD)]. In addition, participants were followed up for all-cause mortality in the National Health Service database until 1 December 2021. In our center, 83 of 108 (76.9%) were included in the analysis due to missing covariates. Over a median of 26 (interquartile range 11-266) days of follow-up, 20 of 22 (90.9%) of nCKD, 23 of 24 (95.8%) of CKDnonHD, and 17 of 37 (45.9%) pHD patients died (p < 0.001). In general, patients with nCKD had fewer comorbidities but more severe presentations. In contrast, the patients with pHD had the least severe symptoms (p < 0.001). In a model adjusted for independent predictors of all-cause mortality (C-reactive protein and serum albumin), CKDnonHD patients had increased mortality [hazard ratio (HR) 1.91, 95% confidence interval (CI), 1.02-3.60], while pHD patients had decreased mortality (HR 0.41, 95% CI 0.20-0.81) compared to nCKD patients. After further adjustment for the need for intensive care, the difference in mortality between the nCKD and pHD groups became non-significant. Despite the limitations of our study, it seems that the survival of previously hemodialysis patients was significantly better.

Urinary albumin-to-creatinine ratio and serum albumin are predictors of acute kidney injury in non-ventilated COVID-19 patients: a single-center prospective cohort study.

PURPOSE: Acute kidney injury (AKI) is a frequent complication among COVID-19 patients in the intensive care unit, but it is less frequently investigated in general internal medicine wards. We aimed to examine the incidence, the predictors of AKI, and AKI-associated mortality in a prospective cohort of non-ventilated COVID-19 patients. We aimed to describe the natural history of AKI by describing trajectories of urinary markers of hemodynamic, glomerular, and tubular injury. METHODS: 141 COVID-19 patients were enrolled to the study. AKI was defined according to KDIGO guidelines. Urine and renal function parameters were followed twice a week. Multivariate logistic regression was used to determine the predictors of AKI and mortality. Trajectories of urinary markers were described by unadjusted linear mixed models. RESULTS: 19.7% patients developed AKI. According to multiple logistic regression, higher urinary albumin-to-creatinine ratio (OR 1.48, 95% CI 1.04-2.12/1 mg/mmol) and lower serum albumin (OR 0.86, 95% CI 0.77-0.94/1 g/L) were independent predictors of AKI. Mortality was 42.8% in the AKI and 8.8% in the group free from AKI (p < 0.0001). According to multiple logistic regression, older age, lower albumin, and AKI (OR 3.9, 95% CI 1.24-12.21) remained independent predictors of mortality. Urinary protein-to-creatinine trajectories were diverging with decreasing values in those without incident AKI. CONCLUSION: We found high incidence of AKI and mortality among moderately severe, non-ventilated COVID-19 patients. Its development is predicted by higher albuminuria suggesting that the originally damaged renal structure may be more susceptible for virus-associated effects. No clear relationship was found with a prerenal mechanism, and the higher proteinuria during follow-up may point toward tubular damage.

A unique case of anti-GBM disease with concomitant anti-PLA2R positivity.

BACKGROUND: Concomitant occurrence of anti-GBM disease and anti-PLA2R positive membranous nephropathy have been previously described. However, to the best of our knowledge, this is the first case report that documents the co-occurrence of the diseases proven by both serologic and histologic methods. CASE PRESENTATION: A 51-year-old woman presented to hospital with nausea, bilateral lower extremity edema, dyspnea, dark urine, and then anuria. Symptoms developed one month after an upper respiratory tract infection. Laboratory results showed acute kidney injury, and hypoalbuminemia. Immunologic examination revealed both anti-GBM and anti-PLA2R positivity. Kidney biopsy demonstrated the histological features of Goodpasture's disease and anti-PLA2R positive membranous nephropathy. Steroid, cyclophosphamide, and plasmapheresis were commenced. Despite the combined immunosuppressive, the patient remained on renal replacement therapy. CONCLUSIONS: Microbial kidney injury can trigger multiple autoimmune diseases. The simultaneous occurrence of anti-glomerular basement (anti-GBM) disease and membranous nephropathy is extremely rare. Delayed recognition leads to delayed treatment, causing worse renal and patient outcomes, as well as increased financial costs.

Hungarian consensus recommendation on the role of vitamin D in disease prevention and treatment / Magyarországi konszenzusajánlás a D-vitamin szerepérol a betegségek megelozésében és kezelésében

Nine Hungarian medical societies have developed a consensus recommendation on the preferred normal range of vitamin D, the dose of vitamin D supplementation and the method of administration. They summarized the clinical conditions and diseases the development of which may be associated with vitamin D deficiency (VDD). VDD is extremely common in Hungary, especially in late winter. The lower limit of the recommended normal range is 75 nmol/l, although the clinical significance of deficiency is evident mainly at values below 50 nmol/l, but since vitamin D supplementation at the recommended dose is safe, it is worthwhile for everyone to reduce the health risk associated with VDD. The aim of vitamin D supplementation is to prevent deficiency. The recommended normal range is 75­125 nmol/l, above which there is no clear benefit of vitamin D supplementation. To maintain the normal range, a daily intake of 2000 IU in adults is recommended during the UV-B radiation-free period. Vitamin D supplementation is also recommended for children during the same periods and conditions as for adults, but the dose varies with age. In adults, vitamin D3 supplementation at daily, weekly and monthly intervals is equally effective and safe. In severe deficiency, a loading dose is recommended, followed by maintenance supplementation. In addition to the wellknown skeletal, immunological and oncological effects of VDD, more and more data support unfavorable gyneco- logical and obstetric effects. The process of building the consensus has met the requirements of the latest Delphi criteria.

Association between affective temperaments and arterial stiffness index in chronic hypertensive patients. / Az affektív temperamentumok és az artériás érfalmerevségi index kapcsolata krónikus hypertoniás betegekben.

Összefoglaló. Bevezetés: Az affektív temperamentumok (depresszív, cyclothym, hyperthym, ingerlékeny, szorongó) a személyiségnek olyan genetikailag meghatározott, felnottkorban stabil részei, amelyekkel jellemezhetok a környezeti ingerekre adott érzelmi válaszok. Az artériás érfalmerevségi index megmutatja, hogy az adott egyénnek a valóságban mért és az elvárt pulzushullám-terjedési sebessége (PWV) milyen arányban áll egymással; pozitív értéke számít kórosnak. Célkituzés: Célunk az volt, hogy az affektív temperamentumok kapcsolatát vizsgáljuk az artériás érfalmerevségi indexszel krónikus hypertoniás betegekben. Módszer: A bevont betegeknél tonometriás eszközzel (PulsePen) mértük a carotis-femoralis PWV-t, mely az artériás érfalmerevség legelfogadottabb markere. Az artériás érfalmerevségi indexet a mért és az elvárt PWV arányában határoztuk meg. Az affektív temperamentumokat a Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire kérdoív (TEMPS-A) segítségével objektivizáltuk. Eredmények: Vizsgálatunkba 185 beteget vontunk be, életkoruk 61,6 (49,5-69,8) év volt. Kortól, nemtol, diabetestol, alkoholfogyasztástól, dohányzástól, BMI-tol, systolés vérnyomástól, összkoleszterinszinttol és GFR-tol független kapcsolatot találtunk az artériás érfalmerevségi index és a depresszív (B = 0,009, 95% CI: 0,002-0,017, p = 0,018), a cyclothym (B = 0,009, 95% CI: 0,002-0,016, p = 0,012), az ingerlékeny (B = 0,013, 95% CI: 0,005-0,021, p<0,001) és a szorongó (B = 0,008, 95% CI: 0,003-0,013, p<0,001) temperamentum között. Következtetés: Újabb kapcsolatot sikerült kimutatni egy cardiovascularis rizikót jelzo paraméter és az affektív temperamentumok között, ami megerosíti ezen személyiségjegyek meghatározásának jelentoségét cardiovascularis prevenciós szempontból is az ismert pszichopatológiai vonatkozások mellett. Orv Hetil. 2022; 163(8): 312-318. INTRODUCTION: Affective temperaments (depressive, anxious, cyclothymic, hyperthymic, irritable) are genetically determined, adult-stable parts of the personality that characterize emotional responses to environmental stimuli. The arterial stiffness index demonstrates the ratio of the actually measured and expected pulse wave velocity (PWV) of a given individual. The positive value is considered to be abnormal. OBJECTIVE: The aim of this study was to investigate the relationship between affective temperaments and arterial stiffness index in chronic hypertensive patients. METHOD: Carotid-femoral PWV, the most accepted marker of arterial stiffness, was measured using a tonometric device (PulsePen). The arterial stiffness index was determined as the ratio of measured and expected PWVs. Affective temperaments were evaluated by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A). RESULTS: The study included 185 patients, with a mean age of 61.6 (49.5-69.8) years. We found association between arterial stiffness index and depressive (B = 0.009, 95% CI: 0.009-0.017, p = 0.018), cyclothymic (B = 0.009, 95% CI: 0.002-0.016, p = 0.012), irritable (B = 0.013, 95% CI: 0.005-0.021, p = 0.001), and anxious (B = 0.008, 95% CI: 0.003-0.013, p = 0.001) temperaments independent of age, sex, diabetes, alcohol consumption, smoking, BMI, systolic blood pressure, total cholesterol, and GFR. CONCLUSION: An additional relationship between a cardiovascular risk measure and affective temperaments has been demonstrated, confirming the importance of determining these personality traits aiming cardiovascular prevention in addition to their known psychopathological aspects. Orv Hetil. 2022; 163(8): 312-318.

Cross-sectional comparison of office and ambulatory pulse wave velocity by two methods, and their changes after lifestyle or medical interventions in hypertension.

OBJECTIVE: Pulse wave velocity (PWV), the most accepted biomarker of arterial stiffening can be measured by different methods and in the past decade, its 24 h monitoring has also become available. The aim of our study was to compare office and ambulatory PWVs and in a proportion of patients to compare the changes of PWVs after the initiation of lifestyle modifications or antihypertensive medication. METHODS: Office carotid-femoral PWV was measured with the tonometric PulsePen device (PP PWV), first hour and 24 h ambulatory oscillometric PWVs were evaluated with Mobil-O-Graph (MOB first hour PWV and MOB 24 h PWV, respectively). In new hypertensive patients, the measurements were repeated 3 months after the initiation of antihypertensive medication. In white-coat hypertensive patients after lifestyle modifications the measurements were repeated at 12 months. RESULTS: One hundred and five participants were involved with 22 new hypertensive and 22 white-coat hypertensive (WhHT) patients. PP PWV [8.7 (7.3-9.9) m/s] differed from MOB first hour PWV [7.3 (6.5-8.8) m/s] and MOB 24 h PWV [7.4 (6.4-8.8) m/s] as well (P < 0.05). PP PWV significantly decreased both in hypertensive [by 0.9 (0.4-1.5) m/s, P < 0.05] and WhHT patients [by 0.3 (-0.1 to 1) m/s, P < 0.05]. MOB first hour PWV did not change neither in hypertensive patients, nor in WhHT patients. MOB 24 h PWV decreased only in hypertensive patients [by 0.2 (0-0.6) m/s], which was less pronounced compared with PP PWV (P < 0.05). CONCLUSION: The significant differences observed both in the cross-sectional and in the prospective parts of our study suggests that the two methods are not interchangeable.

Kidney biopsy-based epidemiologic analysis shows growing biopsy rate among the elderly.

Systematic registration and examination of biopsy-related data in Central and Eastern Europe are scarce, while the health condition of the population is worse compared to other more developed countries. We aim to create a database and analyze the distribution and temporal variation of the renal biopsy diagnoses in Hungary, including the effect of the recent coronavirus pandemic. The diagnoses were standardized according to the recommendation of the European Renal Association. Native biopsy samples processed between January 1, 2006, and December 31, 2020, were analyzed. During the 15 years, 2140 native kidney biopsies were performed. The number of samples increased from 24.5 to 57.9 per million person-years and the median age from 37 to 51 years (p < 0.0001). The predominance of glomerular diseases was stable. The most frequent glomerulopathy was IgA nephropathy (21.5%), followed by focal segmental glomerulosclerosis (17.7%), and membranous nephropathy (15.7%). Trends showed the rise of ANCA-associated vasculitis. During the coronavirus pandemic, there was a decrease in the number of kidney biopsies and the proportion of membranous nephropathies. The diagnostic trends in our database showed increasing biopsy rates among the elderly and the growing frequencies of age-related diseases, which emphasizes the importance of altering medical focus according to demographic changes in this area.

Comparison of Different Cardiovascular Risk Score and Pulse Wave Velocity-Based Methods for Vascular Age Calculation.

BACKGROUND: The calculation of vascular age can help patients understand the importance of adherence to healthy lifestyle and medications. However, multiple methods are available to calculate vascular age and no comparison data is available yet. Our aim was to evaluate vascular age based on the Framingham Risk Score (FRS), the Systematic COronary Risk Evaluation (SCORE) and carotid-femoral pulse wave velocity (PWV). METHODS: Consecutive subjects between the age of 40-65 years, who took part in a screening program in three general practitioner practices were involved. PWV was measured by tonometry and was compared with normal values. Vascular age was defined based on FRS and SCORE according to literature data. RESULTS: One hundred and seventy-two (172) patients were involved. The median chronological age was 55.5 (48.8-61.2) years. The median vascular age based on FRS and SCORE were 64 (54-79) years and 55 (44.2-60.7) years, respectively (p<0.05). Based on PWV, FRS and SCORE, 40.1%, 78.5% and 32% of the subjects had increased vascular age compared with chronological age, respectively (PWV+, FRS+, SCORE+, p<0.05). Fifty-eight (58) (84%) of the PWV+ subjects were also FRS+, and this proportion was high in case of SCORE+ patients as well (n=47, 85.4%). However, only moderate overlap was found between PWV+ and SCORE+ subjects as 17 (30.9%) of SCORE+ patients were also PWV+. CONCLUSION: The differences found between the calculated vascular ages and the proportion of subjects with elevated vascular age warrants further detailed comparison of different vascular age calculation methods.

Hypercalcemia and renal insufficiency ­ where can we start? / Hypercalcaemia és veseelégtelenség - merre induljunk?

Összefoglaló. Közleményünkben egy 63 éves férfi esetét ismertetjük, aki fáradékonyság, fogyás miatt végzett laboratóriumi vizsgálatokon igazolódó veseelégtelenség és hypercalcaemia miatt került felvételre Klinikánkra. A területen végzett röntgenvizsgálaton a koponyán frontalisan és a sacrumon csonteltérések (temporofrontalisan 13 mm-es, körülírtabb, mérsékelten intenzív árnyék és az S1-es rés sclerosisa) ábrázolódtak, ultrahangvizsgálat során lépmegnagyobbodás volt látható. Tünetei hátterében endokrin vagy malignus betegség nem igazolódott. A háttérben elsosorban myeloma multiplex merült fel, ugyanakkor azt célzott vizsgálatokkal sem megerosíteni, sem kizárni nem lehetett, így csontvelo-biopszia történt. A vesefunkció-romlás okának tisztázása végett vesebiopsziát végeztünk, melynek elozetes eredménye interstitialis nephritist véleményezett óriássejtekkel. Az angiotenzinkonvertáló enzim szérumszintjének ez okból történo vizsgálata emelkedett szintet mutatott, így esetünket Boeck-sarcoidosis extrapulmonalis manifesztációjának tartottuk. Per os szteroidkezelésre a beteg tünetei egyértelmu regressziót mutattak. A csontvelo- és vesebiopszia eredménye megerosítette a Boeck-sarcoidosis diagnózisát. A sarcoidosis ezen extrapulmonalis formája hypercalcaemiával és veseérintettséggel - de tüdoérintettség nélkül - rendkívül ritka, különös tekintettel a vesét érinto formára. Hypercalcaemia nagyjából 7,9%-ban, veseelégtelenség 1,4%-ban fordul elo. Ezen eset alapján fontos hangsúlyozni, hogy a hypercalcaemia és a veseelégtelenség hátterében a gyakoribb endokrin, malignus, hematológiai okok mellett a Boeck-sarcoidosisnak is fel kell merülnie a differenciáldiagnosztika során. Orv Hetil. 2021; 162(13): 514-518. Summary. We present the case of a 63-year-old male patient who was admitted to our Clinic with fatigue, weight loss, hypercalcemia, renal insufficiency and anemia. X-ray showed lesions on the frontal skull and sacral region. On abdominal ultrasound, splenomegaly was detected. Based on these, myeloma multiplex was the most likely initial diagnosis; this, however, could not be confirmed with targeted serum tests, therefore bone marrow biopsy was performed. To clarify the underlying cause of decreased kidney function, renal biopsy was performed, the preliminary results of which revealed interstitial nephritis accompanied by giant cells. Serum angiotensin converting enzyme level was elevated, which led to the diagnosis of Boeck sarcoidosis with extrapulmonary manifestations. Oral corticosteroid therapy was commenced that was followed by regression of the patient's symptoms and laboratory abnormalities. Both the bone marrow and the kidney biopsies supported the diagnosis of Boeck sarcoidosis. Presentation of sarcoidosis with hypercalcemia and renal insufficiency but without the involvement of the lungs is extremely rare. Hypercalcemia occurs in about 7.9% and renal insufficiency in 1.4% of the cases. Based on this case, it is important to highlight that in the background of hypercalcemia and renal failure - beside the more frequent causes such as endocrine and hematological diseases, malignancy - one is to consider the possibility of Boeck sarcoidosis as well. Orv Hetil. 2021; 162(13): 514-518.

Evaluation of affective temperaments and arterial stiffness in different hypertension phenotypes.

Affective temperaments (depressive, anxious, irritable, hyperthymic, and cyclothymic) are stable parts of personality and describe emotional reactivity to external stimuli. Their relation to psychopathological conditions is obvious, but less data are available on their relationship with cardiovascular disorders. The aim of this study was to evaluate affective temperaments and hemodynamic and arterial stiffness parameters in healthy subjects (Cont), in white-coat hypertensive (WhHT) patients, and in non-resistant (non-ResHT) and resistant hypertensive (ResHT) patients. In this cross-sectional study, 363 patients were included: 82 Cont, 44 WhHT, 200 non-ResHT, and 37 ResHT. The patients completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A), and arterial stiffness was examined with tonometry (PulsePen). Significant differences were found between the Cont, WhHT, non-ResHT and ResHT groups in pulse wave velocity (7.76 ± 0.96, 8.13 ± 1.39, 8.98 ± 1.25, and 10.18 ± 1.18 m/s, respectively, p < 0.05 between Cont and non-ResHT/ResHT; p < 0.05 between non-ResHT and ResHT). Cyclothymic affective temperament points (4 (2.25-8)) were higher (p < 0.05) in the ResHT group than in the Cont (2 (0-5)) and non-ResHT (3 (1-5)) groups. The cyclothymic temperament points of the WhHT group (4 (2-7)) were also higher than those in the Cont group. ResHT was independently associated with a cyclothymic scale score above 6 (beta = 2.59 (95% CI: 1.16-5.77)), an irritable scale score above 7 (beta = 3.17 (95% CI: 1.3-7.69)) and an anxious scale score above 9 (beta = 2.57 (95% CI: 1.08-6.13)) points. WhHT was also independently associated with cyclothymic scale scores above 6 points (beta = 2.378, 95% CI: 1.178-4.802). In conclusion, white-coat and ResHT patients have specific affective temperament patterns, and the evaluation of these patterns can help to understand the psychopathological background of these conditions.

Characterization of IL-19, -20, and -24 in acute and chronic kidney diseases reveals a pro-fibrotic role of IL-24.

BACKGROUND: Recently, the role of IL-19, IL-20 and IL-24 has been reported in renal disorders. However, still little is known about their biological role. METHODS: Localization of IL-20RB was determined in human biopsies and in the kidneys of mice that underwent unilateral ureteral obstruction (UUO). Renal Il19, Il20 and Il24 expression was determined in ischemia/reperfusion, lipopolysaccharide, streptozotocin, or UUO induced animal models of kidney diseases. The effects of H2O2, LPS, TGF-ß1, PDGF-B and IL-1ß on IL19, IL20 and IL24 expression was determined in peripheral blood mononuclear cells (PBMCs). The extents of extracellular matrix (ECM) and α-SMA, Tgfb1, Pdgfb, and Ctgf expression were determined in the kidneys of Il20rb knockout (KO) and wild type (WT) mice following UUO. The effect of IL-24 was also examined on HK-2 tubular epithelial cells and NRK49F renal fibroblasts. RESULTS: IL-20RB was present in the renal biopsies of patients with lupus nephritis, IgA and diabetic nephropathy. Amount of IL-20RB increased in the kidneys of mice underwent UUO. The expression of Il19, Il20 and Il24 increased in the animal models of various kidney diseases. IL-1ß, H2O2 and LPS induced the IL19, IL20 and IL24 expression of PBMCs. The extent of ECM, α-SMA, fibronectin, Tgfb1, Pdgfb, and Ctgf expression was lower in the kidney of Il20rb KO compared to WT mice following UUO. IL-24 treatment induced the apoptosis and TGF-ß1, PDGF-B, CTGF expression of HK-2 cells. CONCLUSIONS: Our data confirmed the significance of IL-19, IL-20 and IL-24 in the pathomechanism of renal diseases. Furthermore, we were the first to demonstrate the pro-fibrotic effect of IL-24.

The impact of currently recommended antihypertensive therapy on depression and other psychometric parameters: preliminary communication.

AIMS: Current evidence on the psychological effects of antihypertensive medications is controversial. The aim of this study was to evaluate the effect of current antihypertensive medication on different psychometric parameters and on serum brain-derived neurotrophic factor (BDNF) level. METHODS: Psychometric, haemodynamic, arterial stiffness and laboratory parameters were evaluated before and 3 months after the initiation of antihypertensive medication in untreated hypertensive patients (HT, n=31), and once in healthy controls (CONT, n=22). Subjects completed the following psychometric tests: Beck Depression Inventory (BDI), Hamilton Anxiety Scale (HAM-A), Symptom Checklist 90 Revised (SCL-90), Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire, Big Five Inventory, Pain Vigilance and Awareness Questionnaire and Berkeley Expressivity Questionnaire. Amlodipine and/or perindopril compounds were preferred medications. Serum BDNF was measured with ELISA. RESULTS: Brachial systolic blood pressure, as well as pulse wave velocity were significantly improved in the HT group over the 3-month follow-up (153.3±15.9 mmHg vs. 129.5±10.0 mmHg and 8.2±1.4 m/s vs 7.5±1.6 m/s, respectively). Similarly, we found improvements in BDI (0.73 points) and in several Scl-90 subscales. Serum BDNF was not different between CONT and HT and did not change for therapy. CONCLUSIONS: Our results indicate that initiation of currently recommended antihypertensive medications in newly diagnosed patients may have a significant impact on psychological well-being of patients and could influence quality of life as well.

The role of laser Doppler flowmetry tests, serum angiopoietin-2, asymmetric and symmetric dimethylarginine to predict outcome in chronic kidney disease.

OBJECTIVE: The role of biochemical and functional markers of microvascular dysfunction to predict cardiovascular outcomes in nondialyzed chronic kidney disease (CKD) remains unclear. In this prospective cohort study, we assessed whether biochemical [serum level of angiopoietin-2 (Ang-2), asymmetric and symmetric dimethylarginin] and functional (laser Doppler flowmetry) measures of microvascular function predicted cardiovascular events, cardiovascular and all-cause mortality in CKD patients. METHODS: Postocclusive reactive hyperemia area (PORHHA), acetylcholine and sodium nitroprusside-mediated flow changes were estimated by laser Doppler flowmetry, and Ang-2, asymmetric and symmetric dimethylarginin were assessed in 105 CKD patients at baseline. Multiple failure time Cox-regression analyses with backward elimination were performed to determine the predictors of the combined endpoint of cardiovascular mortality and cardiovascular events or all-cause mortality and cardiovascular events during a median of 66.6 (interquartile range 39.8-80.4) months of follow-up. RESULTS: In univariate models lnAng-2 and lnPORHHA both predicted the cardiovascular outcome besides age, diabetes, baseline cardiovascular disease, brachial pulse pressure and log C-reactive protein. In multivariate analysis lnPORHHA [hazard ratio: 0.66 (95% confidence interval: 0.49-0.89) per ln(mU s)], age [1.03 (1.01-1.06) per year], log C-reactive protein [1.31 (1.06-1.64) per ln(mg/l)] and diabetes [3.33 (1.70-6.53)] remained significant predictors of the cardiovascular outcome, whereas lnAng-2 did not enter the model. Neither of the microvascular variables were an independent predictor of all-cause mortality and cardiovascular events. CONCLUSION: Among the functional and biochemical microvascular parameters PORHHA seems to improve cardiovascular risk assessment in CKD. Nevertheless the robustness of traditional risk factors seems to outweigh the role of microvascular biomarkers on all-cause mortality and cardiovascular events at this time.

Measurement of Arterial Stiffness: A Novel Tool of Risk Stratification in Hypertension.

Cardiovascular diseases are the leading causes of morbidity and mortality in industrialized countries worldwide, despite highly effective preventive treatments available. As a difference continues to exist between the estimated and true number of events, further improvement of risk stratification is an essential part of cardiovascular research.Among hypertensive patients measurement of arterial stiffness parameters, like carotid-femoral pulse wave velocity (cfPWV) or brachial-ankle pulse wave velocity (baPWV) can contribute to the identification of high-risk subpopulation of patients. This is a hot topic of vascular research including the possibility of the non-invasive measurement of central hemodynamics, wave reflections and recently, 24-h arterial stiffness monitoring as well. This chapter discusses the past and the present of this area including the scientific achievements with cfPWV, baPWV and other measures, provides a short overview of methodologies and the representation of arterial stiffness parameters in guidelines.

Hyperthymic affective temperament and hypertension are independent determinants of serum brain-derived neurotrophic factor level.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has neuroprotective, proangiogenic and myogenic effects and, therefore, possibly acts as a psychosomatic mediator. Here, we measured serum BDNF (seBDNF) level in hypertensive patients (HT) and healthy controls (CONT) and its relation to affective temperaments, depression and anxiety scales, and arterial stiffness parameters. METHODS: In this cross-sectional study, affective temperaments, anxiety, and depression were studied with questionnaires (TEMPS-A, HAM-A, and BDI, respectively). SeBDNF level and routine laboratory parameters were measured as well. Arterial stiffness was evaluated with a tonometric method. RESULTS: Allover, 151 HT, and 32 CONT subjects were involved in the study. SeBDNF level was significantly higher in HT compared to CONT (24880 ± 8279 vs 21202.6 ± 6045.5 pg/mL, p < 0.05). In the final model of regression analysis, hyperthymic temperament score (Beta = 405.8, p = 0.004) and the presence of hypertension (Beta = 6121.2, p = 0.001) were independent determinants of seBDNF. In interaction analysis, it was found that in HT, a unit increase in hyperthymic score was associated with a 533.3 (95 %CI 241.3-825.3) pg/mL higher seBDNF. This interaction was missing in CONT. CONCLUSIONS: Our results suggest a complex psychosomatic involvement of BDNF in the pathophysiology of hypertension, where hyperthymic affective temperament may have a protective role. BDNF is not likely to have an effect on large arteries.

Association of affective temperaments with blood pressure and arterial stiffness in hypertensive patients: a cross-sectional study.

BACKGROUND: Affective temperaments (anxious, depressive, cyclothymic, irritable and hyperthymic) measure subclinical manifestations of major mood disorders. Furthermore, cumulating evidence suggests their involvement in somatic disorders as well. We aimed to assess associations between affective temperament scores and blood pressure and arterial stiffness parameters in hypertensive patients. METHODS: In this cross-sectional study, 173 patients with well-controlled or grade 1 chronic hypertension, with no history of depression, completed the TEMPS-A, Beck Depression Inventory (BDI) and Hamilton Anxiety Scale (HAM-A) questionnaires in three GP practices. Arterial stiffness was measured with tonometry (PulsePen). RESULTS: According to multiple linear regression analysis, cyclothymic temperament score was positively associated with brachial systolic blood pressure independently of age, sex, total cholesterol, brachial diastolic blood pressure, BDI, HAM-A and the use of alprazolam (ß = 0.529, p = 0.042), while hyperthymic temperament score was negatively related to augmentation index independent of age, sex, smoking, heart rate, BDI, HAM-A and the use of alprazolam (ß = -0.612, p = 0.013). A significant interaction was found between cyclothymic temperament score and sex in predicting brachial systolic blood pressure (p = 0.025), between irritable and anxious temperament scores and sex in predicting pulse wave velocity (p = 0.021, p = 0.023, respectively) and an interaction with borderline significance between hyperthymic temperament score and sex in predicting augmentation index (p = 0.052). CONCLUSIONS: The present findings highlight elevated blood pressure among subjects with high cyclothymic temperament as well as an increased level of arterial stiffening in subjects with low hyperthymic scores suggesting that affective temperaments may play a role in the development of hypertension and arterial stiffening and may thus represent markers of cardiovascular risk. Sex differences were also present in these associations.

Identification of hypertensive patients with dominant affective temperaments might improve the psychopathological and cardiovascular risk stratification: a pilot, case-control study.

BACKGROUND: Although mood disorders and cardiovascular diseases have widely studied psychosomatic connections, data concerning the influence of the psychopathologically important affective temperaments in hypertension are scarce. To define a possibly higher cardiovascular risk subpopulation we investigated in well-treated hypertensive patients with dominant affective temperaments (DOM) and in well-treated hypertensive patients without dominant temperaments the level of depression and anxiety, arterial stiffness and serum Brain-derived Neurotrophic Factor (seBDNF). METHODS: 175 hypertensive patients, free of the history of psychiatric diseases, completed the TEMPS-A, Beck Depression Inventory and Hamilton Anxiety Scale questionnaires in two primary care practices. Of those 175 patients, 24 DOM patients and 24 hypertensive controls (matched in age, sex and the presence of diabetes) were selected for measurements of arterial stiffness and seBDNF level. RESULTS: Beck and Hamilton scores in DOM patients were higher compared with controls. Pulse wave velocity and augmentation index did not differ between the groups while in the DOM patients decreased brachial systolic and diastolic and central diastolic blood pressures were found compared with controls. SeBDNF was lower in the DOM group than in the controls (22.4 ± 7.2 vs. 27.3 ± 7.8 ng/mL, p < 0.05). CONCLUSIONS: Although similar arterial stiffness parameters were found in DOM patients, their increased depression and anxiety scores, the decreased brachial and central diastolic blood pressures as well as the decreased seBDNF might refer to their higher vulnerability regarding the development not only of major mood disorders, but also of cardiovascular complications. These data suggest that the evaluation of affective temperaments should get more attention both with regard to psychopathology and cardiovascular health management.

[Clinical value and measurement of arterial stiffness for the assessment of cardiovascular risk in light of recent results]. / Az artériás érfalmerevség cardiovascularis kockázatértéke és mérése a legújabb eredmények tükrében.

Cardiovascular risk stratification is fundamental for the development of effective prevention and therapeutic strategies. Although there are numerous scores and risk tables available, a difference still exists between the estimated and real number of cardiovascular events. Measurement of arterial stiffness can provide additional information to risk stratification. The most widely accepted parameter of arterial stiffness is aortic pulse wave velocity, which has been included in the guideline of the European Society of Hypertension in 2007 and 2013, although American guidelines still omit it. In this review the authors summarize the evidence with regards to the different steps required for clinical application of arterial stiffness measurement and they also discuss the questions that evolved from the methodological variability of different measurement techniques.