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Background and Purpose: The aim of this study was to investigate the association between daytime napping frequency and the incidence of essential hypertension or stroke as well as to validate causality in this relationship via Mendelian randomization (MR). Methods: We conducted Cox regression analysis on 358 451 participants free of hypertension or stroke from UK Biobank. To validate the results of the observational analysis, we conducted a 2-sample MR for daytime napping frequency (123 single-nucleotide polymorphisms) with essential hypertension in FinnGen Biobank, stroke, and ischemic stroke in MEGASTROKE consortium and performed a corresponding 1-sample MR on the UK Biobank data. Results: Compared with never napping, usually napping was associated with a higher risk of essential hypertension (hazard ratio, 1.12 [95% CI, 1.08–1.17]), stroke (hazard ratio, 1.24 [95% CI, 1.10–1.39], and ischemic stroke (hazard ratio, 1.20 [95% CI, 1.05–1.36]) in our prospective observational analysis. Both the 1-sample and 2-sample MR results indicated that increased daytime napping frequency was likely to be a potential causal risk factor for essential hypertension in FinnGEN (odds ratio, 1.43 [95% CI, 1.06–1.92]) and UK Biobank (odds ratio, 1.40 [95% CI, 1.28–1.58]). The 2-sample MR results supported the potential causal effect of nap frequency on ischemic stroke in MEGASTROKE (odds ratio, 1.29 [95% CI, 1.04–1.62]). Conclusions: Prospective observational and MR analyses provided evidence that increased daytime nap frequency may represent a potential causal risk factor for essential hypertension. The potential causal association of increased nap frequency with ischemic stroke was supported by 2-sample MR and prospective observational results.

Background: In preclinical models, the pannexin-1 channel has been shown to be involved in blood pressure regulation through an effect on peripheral vascular resistance. Pannexin-1 releases ATP, which can activate constrictive purinergic receptors on the smooth muscle cells. Pannexin-1 opening is proposed to be mediated by α-adrenergic receptors to potentiate sympathetic constriction. This positions pannexin-1 as a putative pharmacological target in blood pressure regulation in humans. The aim was to provide the first translational evidence for a role of pannexin-1 in essential hypertension in humans by use of an advanced invasive mechanistic approach. Methods: Middle-aged stage-1 hypertensive (n=13; 135.7±6.4 over 83.7±3.7 mm Hg) and normotensive men (n=12; 117.3±5.7 over 72.2±3.5 mm Hg) were included. Blood pressure and leg vascular resistance were determined during femoral arterial infusion of tyramine (α-adrenergic receptor stimulation), sodium nitroprusside, and acetylcholine. Measurements were made during control conditions and with pannexin-1 blockade (3000 mg probenecid). Expression of Pannexin-1, purinergic- and α-adrenergic receptors in skeletal muscle biopsies was determined by Western blot. Results: The changes in leg vascular resistance in response to tyramine (+289% versus +222%), sodium nitroprusside (−82% versus −78%) and acetylcholine (−40% versus −44%) infusion were not different between the 2 groups ( P >0.05) and pannexin-1 blockade did not alter these variables ( P >0.05). Expression of pannexin-1 and of purinergic- and α-adrenergic receptors was not different between the 2 groups ( P >0.05). Conclusions: Contrary to our hypothesis, the data demonstrate that pannexin-1 does not contribute to the elevated blood pressure in essential hypertension, a finding, which also opposes that reported in preclinical models.

Introduction. The role of hypertension in the development of cognitive impairment is emphasized in numerous works. Nearly all data were obtained from a group of old patients. Therefore it is of great importance to diagnose the cognitive impairment in hypertensive patients of working age beforehand. Objective. To determine the role of age and hypertensive anamnesis in the development of cognitive impairments in patients with essential hypertension of the 2nd degree. Materials and methods. We examined 102 patients with the second degree of essential hypertension, whose average age was 49.84 ± 0.83 years old. The patients were divided into 3 groups depending on their age and disease duration. A number of neuropsychological tests were used to study cognitive impairment. Results. Significant lowering of MoCA test results by 6.1 % were observed in the group of the patients older than 56 years old compared with those of the group with patients of 45 years old and younger. In the group with disease duration not more than 5 years cognitive impairments were absent. The results of MoCA test in patients with hypertensive disease duration more than 10 years were significantly less in comparison with the group of patients experienced disease up to 5 years and from 5 to 10 years in 9.9 % and in 4.9 %, respectively. Сonclusions. We have found that longer duration of the disease and older age in the patients of working age with essential hypertension of the second degree are associated with significant increase in cognitive impairment. An integral part of a comprehensive survey of hypertensive patients should be the identification of cognitive impairment., Актуальность. В многочисленных работах подчеркивается роль артериальной гипертензии в развитии когнитивных нарушений. Почти все данные получены на популяции лиц старшей возрастной группы, поэтому представляет интерес раннее выявление когнитивных нарушений у больных гипертонической болезнью трудоспособного возраста. Цель работы: определение роли возраста и длительности артериальной гипертензии в развитии когнитивных нарушений у больных гипертонической болезнью II стадии. Материалы и методы. Обследовано 102 больных гипертонической болезнью II стадии, средний возраст которых 49,84 ± 0,83 года. Пациенты были разделены по возрасту и длительности заболевания на 3 группы. Для изучения когнитивных нарушений применяли ряд нейропсихологических тестов. ­Результаты. Достоверное снижение показателей теста Монреальской шкалы оценки когнитивных функций (MoCA) на 6,1 % отмечается в третьей группе пациентов старше 56 лет по сравнению с пациентами до 45 лет первой группы. В группе с длительностью заболевания до 5 лет когнитивные нарушения отсутствовали. Показатели MoCA-теста в группе больных с длительностью гипертонической болезни более 10 лет достоверно меньше в сравнении с группой до 5 лет продолжительности заболевания и от 5 до 10 лет — на 9,9 и 4,9 % соответственно. Выводы. Нами установлено, что с увеличением длительности заболевания и возраста больных с гипертонической болезнью II стадии трудоспособного возраста отмечается достоверное нарастание когнитивных нарушений. Неотъемлемой частью комплексного обследования больных гипертонической болезнью должно быть выявление когнитивных нарушений., Актуальність. У численних роботах підкреслюється роль артеріальної гіпертензії в розвитку когнітивних порушень. Майже всі дані отримані на популяції осіб старшої вікової групи, тому становить інтерес раннє виявлення когнітивних порушень у хворих на гіпертонічну хворобу працездатного віку. Мета роботи: визначення ролі віку і тривалості артеріальної гіпертензії в розвитку когнітивних порушень у хворих на гіпертонічну хворобу II стадії. ­Матеріали та методи. Обстежені 102 хворі на гіпертонічну хворобу II стадії, середній вік яких 49,84 ± 0,83 року. Пацієнти були розділені за віком і тривалістю захворювання на 3 групи. Для вивчення когнітивних порушень застосовували ряд нейропсихологічних тестів. Результати. Достовірне зниження показників тесту Монреальської шкали оцінки когнітивних функцій (MoCA) на 6,1 % відзначається в третій групі пацієнтів старше 56 років порівняно з пацієнтами до 45 років першої групи. У групі з тривалістю захворювання до 5 років когнітивні порушення були відсутні. Показники MoCA-тесту в групі хворих з тривалістю гіпертонічної хвороби більше 10 років достовірно менші порівняно з групою до 5 років тривалості захворювання і від 5 до 10 років — на 9,9 і 4,9% відповідно. Висновки. Нами встановлено, що зі збільшенням тривалості захворювання і віку хворих на гіпертонічну хворобу II стадії працездатного віку відзначається достовірне наростання когнітивних порушень. Невід’ємною частиною комплексного обстеження хворих на гіпертонічну хворобу має бути виявлення когнітивних порушень.

Вивчені рівні в крові потужних активаторів ангіогенезу з прозапальною дією — васкулоендотеліального фактора росту та ангіопоетину-2 у хворих на гіпертонічну хворобу. Виявлено достовірне підвищення рівнів у крові вказаних факторів у хворих на гіпертонічну хворобу порівняно з практично здоровими особами. Встановлено, що рівні у крові ангіопоетину-2 достовірно зростають у хворих на гіпертонічну хворобу при підвищенні тяжкості гіпертензії та при наявності таких метаболічних порушень, як абдомінальне ожиріння, гіперглікемія натще, порушення толерантності до глюкози, гіперурикемія та комбінована дисліпопротеїнемія. Рівні в крові васкулоендотеліального фактора росту були достовірно більш високими у хворих на гіпертонічну хворобу зі стабільною стенокардією напруження порівняно з хворими без стенокардії. Отримані дані вказують на важливу роль активації ангіогенезу в розвитку гіпертонічної хвороби та її серцево-судинних ускладнень.

Мета дослідження : вивчити антигіпертензивну ефективність і можливість органопротекції комбінованою терапією індапамідом з амлодипіном і блокатором РААС (периндоприлом або валсартаном) в процесі 24-тижневої терапії у хворих з есенціальною гіпертонією (ЕГ) з високим і дуже високим ризиком серцево-судинних ускладнень (ССУ). Матеріали та методи. У дослідження були включені 115 хворих з ЕГ II–III ступеня (ESH/ESC, 2013) чоловічої та жіночої статі. Середній вік хворих склав 56,47 ± 9,18 року, середня тривалість захворювання — 10,20 ± 7,22 року. Проводилось офісне вимірювання артеріального тиску за методом Короткова, ЕхоКГ. Біохімічні аналізи проводили на автоаналізаторі DAYTONA. Швидкість клубочкової фільтрації (ШКФ) визначали за формулою MDRD. Контурний аналіз пульсової хвилі проводився за допомогою приладу SphygmoCor (AtCor Medical, Австралія). Результати. Застосування комбінованої терапії індапамідом з амлодипіном і блокатором РААС у хворих з ЕГ із високим і дуже високим ризиком ССУ дозволяє швидко досягти цільових показників САТ і ДАТ. Цільові значення САТ, ДАТ, АДсер. були досягнуті у 95 (82,6 %) хворих. Ступінь зниження САТ і ДАТ становила –21,61 ± 5,81 і –21,63 ± 9,58 % відповідно (р = 0,000). Антиремоделюючі ефекти індапаміда з амлодипіном і блокатором РААС асоціювалися зі зменшенням числа хворих із гіпертрофією лівого шлуночка (ГЛШ), склавши 53 (46,1 %) проти 72 (62,6 %) на початковому етапі, тобто в цілому по групі відсоток хворих з ГЛШ зменшився на 16,5 %. Спостерігалося достовірне зменшення товщини комплексу інтима-медіа (КІМ) від 1,07 ± 0,24 мм на початку до 1,01 ± 0,20 мм у динаміці (р = 0,019). Мікроальбумінурія зменшилася з 30,18 ± 59,26 мг/л на початку до 19,86 ± 37,53 мкмоль/л у динаміці (р = 0,041). Рівень креатиніну зменшився з 100,56 ± 22,29 мкмоль/л на початку до 96,01 ± 20,40 мкмоль/л у динаміці (р = 0,044). ШКФ збільшилася з 64,23 ± 13,19 мл/хв/1,73 м 2 на початку до 68,88 ± 14,94 мл/хв/1,73 м 2 у динаміці (р = 0,032). З огляду на проведену трикомпонентну комбіновану терапію відзначалися достовірне зниження центрального систолічного і пульсового тиску, тенденція до зниження центрального діастолічного тиску. Зниження аортальної аугментації та індексу аугментації відбилося на достовірному зниженні швидкості пульсової хвилі (ШПВ) з нормалізацією її показників (< 10 м/с). При цьому терапія характеризувалася доброю переносимістю. Висновки. Трикомпонентна терапія амлодипіном, індапамідом і блокатором РААС відрізняється високою антигіпертензивною ефективністю, вираженістю органопротективних ефектів, впливаючи на процеси судинного ремоделювання з нормалізацією центральної гемодинаміки, ШПХ, і зменшенням товщини КІМ загальної сонної артерії, добре переноситься, що в цілому характеризує цю комбінацію як найбільш оптимальну і ефективну у зниженні ризику ССУ у більшості хворих з АГ.

В огляді висвітлюються питання та перспективи превентивного харчування при гіпертонічній хворобі на тлі аліментарного ожиріння, роль і місце окремих нутрієнтів у дієтах, що рекомендуються пацієнтам із гіпертонічною хворобою й ожирінням високого кардіоваскулярного ризику з ішемічною хворобою серця, дисліпідеміями, порушеннями вуглеводного та пуринового обмінів. Коментуються американські та українські рекомендації з харчування і модифікації стилю життя, результати багатоцентрових досліджень при гіпертонічній хворобі й ожирінні, європейські дієтичні раціони з доведеною ефективністю (DASH-дієта, Mediterranean Diet, MIND, TLC, дієти Орніша, Polymeal, Omni Heart, клініки Майо, Paleolithic diet, Weight Watchers, дієти LCHF, South Beach, методика MEDFICTS зі скринінгу харчових жирів), особливості їх призначення при гіпертонічній хворобі, ожирінні, цукровому діабеті 2-го типу, атеросклерозі, короткі рекомендації з розширення фізичної активності в даної категорії пацієнтів.

Метою дослідження є оцінка впливу моно- та комбінованої антигіпертензивної терапії на показники системного запалення (С-реактивний протеїн (СРП), інтерлейкін (ІЛ)-6 і фактор некрозу пухлини (ФНП) α у взаємозв’язку з динамікою характеристик добового профілю артеріального тиску.Обстежено 99 хворих на гіпертонічну хворобу І–ІІ стадії 1–2-го ступеня, які були рандомізовані в 3 групи терапії: 29 пацієнтів отримували монотерапію телмісартаном у дозі 40–80 мг/добу, 27 — S-амлодипіном у дозі 5 мг/добу та 43 — фіксовану комбінацію валсартану з амлодипіном у дозі 160/5 мг/добу). Визначення вмісту СРП, ІЛ-6 і ФНП-α проводили до початку (після 7-денного безмедикаментозного періоду) та після 6 міс. терапії.Було встановлено, що лікування телмісартаном сприяє зниженню сироваткового рівня СРП на 13,9 % та ІЛ-6 — на 36,4 %, проте не впливає на вміст ФНП-α у крові хворих на гіпертонічну хворобу. Монотерапія антагоністом кальцію S-амлодипіном призводить до зменшення вмісту в крові прозапальних цитокінів: ІЛ-6 — на 39 % та ФНП-α — на 11,9 %. Застосування фіксованої комбінації валсартану з амлодипіном чинить більш суттєвий антигіпертензивний ефект, проте це не супроводжувалося більш вираженим, ніж у групах монотерапії, зниженням СРП і ІЛ-6, що становило відповідно 12,5 і 31,5 %.Було виявлено, що зниження АТ прямо пов’язане зі зменшенням активності системного запалення. Так, зменшення сироваткового вмісту ФНП-α корелює зі зниженням систолічного та діастолічного АТ у всі періоди доби під впливом лікування, а зниження рівня СРП асоціюється зі змінами середньодобового та середньоденного систолічного артеріального тиску, його добового індексу та нічної варіабельності.Отримані нами дані засвідчують зменшення активності запалення низької градації під впливом блокаторів рецепторів ангіотензину ІІ (телмісартан) та антагоністів кальцію (S-амлодипін) як при монотерапії, так і при використанні їх комбінації (валсартан із амлодипіном), яке прямо корелює зі зниженням артеріального тиску за даними амбулаторних вимірювань.

Метою дослідження є оцінка антигіпертензивної ефективності телмісартану та його впливу на активність системного запалення і показники вуглеводного та ліпідного метаболізму у хворих на гіпертонічну хворобу (ГХ). Матеріали та методи. Обстежено 29 пацієнтів із ГХ І–ІІ стадії, 1–2-го ступеня, яким після 7-денного безмедикаментозного періоду та через 6 місяців терапії телмісартаном проводили комплексне клінічне дослідження, амбулаторне моніторування артеріального тиску (АТ), визначення вмісту С-реактивного протеїну (СРП), интерлейкіну-6 (ІЛ-6) і фактора некрозу пухлини α (ФНП-α), показників вуглеводного (глюкоза, інсулін, НОМА, глікований гемоглобін (HbA1с)) та ліпідного метаболізму. Результати. Монотерапія телмісартаном дозволила досягти цільового АТ у 75,6 % пацієнтів; через 6 місяців лікування зниження систолічного АТ становило 20 мм рт.ст., діастолічного АТ — 13 мм рт.ст. Препарат сприяв відновленню нормального двофазного ритму АТ у пацієнтів з вихідними його порушеннями та зменшував варіабельність систолічного АТ в нічні години. Обговорення. Під впливом телмісартану відбулось поліпшення показників вуглеводного обміну, що проявлялось достовірним зменшенням базальної інсулінемії на 21,5 %, зниженням рівня глюкози з 5,5 ± 0,2 ммоль/л до 5,3 ± 0,1 ммоль/л (р = 0,04) і HbA1c з 5,6 ± 0,1 % до 5,4 ± 0,1 % (р = 0,04). На фоні прийому телмісартану зменшився вміст у крові тригліцеридів на 17 % (р = 0,03), спостерігалась тенденція до зниження рівня загального холестерину та холестерину ліпопротеїдів низької щільності. Встановлено, що лікування телмісартаном сприяє зниженню сироваткового рівня СРП на 13,9 % (р = 0,04) та ІЛ-6 на 36,4 % (р = 0,02), проте не впливає на вміст ФНП-α в крові хворих на ГХ. Висновки. Отримані дані свідчать про високу антигіпертензивну ефективність і сприятливі метаболічні ефекти телмісартану, а також його здатність пригнічувати активність запалення низької градації. В статті також обґрунтовано поєднане використання телмісартану та фіксованої комбінації «S-амлодипін/аторвастатин» з точки зору поліпшення прогнозу хворих на ГХ за рахунок синергізму антигіпертензивного та ліпідознижуючого потенціалу і плейотропних ефектів цих препаратів, дія яких направлена на сповільнення прогресування ГХ і атеросклерозу.

Эссенциальная гипертензия по-прежнему представляет собой наиболее распространенный фактор риска сердечно-сосудистой системы, отвечающий за большую часть глобального бремени заболеваний во всем мире. Антигипертензивная терапия, направленная на снижение уровня артериального давления (АД) в рекомендованных терапевтических целях, доказала снижение риска развития сердечно-сосудистых, цереброваскулярных и почечных осложнений. Несмотря на эти доказательства, общий уровень контроля АД остается достаточно низким в большинстве европейских и западных стран, а также в развивающихся странах, что способствует увеличению расходов на лечение и инвалидность, связанных с гипертензией. По этим причинам превентивные стратегии, направленные на улучшение уровня контроля АД у больных артериальной гипертензией (АГ), которые принимают медикаментозную терапию, и снижение АД при его высоком нормальном уровне у бессимптомных здоровых лиц могут способствовать уменьшению бремени заболеваний, связанных с гипертензией. С этой точки зрения было показано, что использование определенных питательных веществ и пищевых добавок может обеспечить благоприятные эффекты в лечении и контроле АГ, вне приема фармакологических препаратов и нефармакологических вмешательств. Их применение может эффективно и безопасно снижать уровень АД до целевых показателей и предотвращать прогрессирование заболевания с высокого нормального уровня АД к гипертензии 1-й степени. В этом консенсусном документе представлены систематический обзор и критический анализ имеющихся в настоящее время доказательств в пользу использования питательных веществ и пищевых добавок у лиц с высоким нормальным уровнем АД при различных степенях сердечно-сосудистого риска.

Актуальность. На сегодняшний день существуют данные о влиянии повышенного индекса массы тела (ИМТ) на развитие когнитивных нарушений (КН). Цель: оценить роль повышенного артериального давления (АД) и ИМТ в возникновении КН у пациентов с гипертонической болезнью (ГБ). Материалы и методы. В исследование включены 62 пациента (1-я группа) с ГБ II–III стадии 2–3-й степени и 30 практически здоровых лиц (2-я группа) с нормальным уровнем АД. Пациенты 1-й группы были разделены на две подгруппы: 1А подгруппу составили 38 больных с ГБ и повышенным ИМТ, 1Б подгруппу — 24 больных с ГБ и нормальным ИМТ. Для изучения когнитивных функций применялась краткая шкала исследования психического статуса (MMSE). Результаты. Средний балл по шкале MMSE составил 26,9 ± 1,5 и 28,8 ± 1,1 у пациентов 1-й и 2-й группы соответственно, что свидетельствует о достоверном ухудшении когнитивных функций у пациентов с ГБ (p

Recent evidence supports a role for the gut microbiota in hypertension, but whether ambulatory blood pressure is associated with gut microbiota and their metabolites remains unclear. We characterized the function of the gut microbiota, their metabolites and receptors in untreated human hypertensive participants in Australian metropolitan and regional areas. Ambulatory blood pressure, fecal microbiome predicted from 16S rRNA gene sequencing, plasma and fecal metabolites called short-chain fatty acid, and expression of their receptors were analyzed in 70 untreated and otherwise healthy participants from metropolitan and regional communities. Most normotensives were female (66%) compared with hypertensives (35%, P Acidaminococcus spp ., Eubacterium fissicatena, and Muribaculaceae were higher, while Ruminococcus and Eubacterium eligens were lower in hypertensives. Importantly, normotensive and essential hypertensive cohorts could be differentiated based on gut microbiome gene pathways and metabolites. Specifically, hypertensive participants exhibited higher plasma acetate and butyrate, but their immune cells expressed reduced levels of short-chain fatty acid-activated GPR43 (G-protein coupled receptor 43). In conclusion, gut microbial diversity did not change in essential hypertension, but we observed a significant shift in microbial gene pathways. Hypertensive subjects had lower levels of GPR43, putatively blunting their response to blood pressure-lowering metabolites.

The rapid progression of chronic kidney disease and higher incidence of cardiovascular complications are well known in patients with hyperaldosteronism. However, detailed renal histopathologic characteristics of this disease have remained unknown. Therefore, renal biopsy specimens of 19 cases with unilateral hyperaldosteronism were compared with 22 autopsy renal cases of estimated glomerular filtration rate-matched essential hypertension without nephropathy or endocrine disorders to explore the hyperaldosteronism-specific histopathologic renal changes in this study. Global and segmental glomerulosclerosis, interstitial fibrosis, infiltration of inflammatory cells, arteriosclerosis, hyalinization of arterioles and immunoreactivity of mineralocorticoid receptor, 11β-hydroxysteroid dehydrogenase type 1 and 2, and renin were all quantitatively evaluated. The ultrastructural analysis was added in 3 hyperaldosteronism cases. Both mineralocorticoid receptor ( P P P P P =0.08). Glomerular size was significantly larger in hyperaldosteronism ( P P =0.08), and intima-to-media ratio was significantly lower ( P =0.02) in hyperaldosteronism. Arteriolar hyalinization was significantly more pronounced ( P P

Klotho has antiaging properties, and serum levels decrease with physiological aging and aging-related diseases, such as hypertension, cardiovascular, and chronic kidney disease. Klotho deficiency in mice results in accelerated aging and cardiovascular injury, whereas Klotho supplementation slows down the progression of aging-related diseases. The pleiotropic functions of Klotho include, but are not limited to, inhibition of insulin/IGF-1 (insulin-like growth factor 1) and WNT (wingless-related integration site) signaling pathways, suppression of oxidative stress and aldosterone secretion, regulation of calcium-phosphate homeostasis, and modulation of autophagy with inhibition of apoptosis, fibrosis, and cell senescence. Accumulating evidence shows an interconnection between Klotho deficiency and hypertension, and Klotho gene polymorphisms are associated with hypertension in humans. In this review, we critically review the current understanding of the role of Klotho in the development of essential hypertension and the most important underlying pathways involved, such as the FGF23 (fibroblast growth factor 23)/Klotho axis, aldosterone, Wnt5a/RhoA, and SIRT1 (Sirtuin1). Based on this critical review, we suggest avenues for further research.

At the dawn of the new decade, it is judicious to reflect on the boom of knowledge about polygenic risk for essential hypertension supplied by the wealth of genome-wide association studies. Hypertension continues to account for significant cardiovascular morbidity and mortality, with increasing prevalence anticipated. Here, we overview recent advances in the use of big data to understand polygenic hypertension, as well as opportunities for future innovation to translate this windfall of knowledge into clinical benefit.

Iron overload has been recently shown to be associated with a hyperadrenergic state in genetic hemochromatosis. Whether this is also the case in essential hypertension, characterized by sympathetic activation and frequently by body iron overload, is unknown. In 17 healthy normotensive controls (age 52.3±3.2 years, mean±SE), in 21 age-matched patients with hypertension with iron overload (HT+), defined by serum ferritin levels, and in 28 hypertensives without this condition, we measured efferent postganglionic muscle sympathetic nerve traffic (microneurography), heart rate and blood pressure variability (power spectral analysis), serum ferritin, and metabolic variables. Muscle sympathetic nerve traffic was significantly ( P r =0.51, P r =0.47, P r =0.76, P r =0.46, P

The significance of peristenotic collateral circulation (PCC) development around a stenotic renal artery is unknown. We tested the hypothesis that PCC is linked to loss of kidney function and recovery potential in patients with atherosclerotic renovascular disease (ARVD). Thirty-four patients with ARVD were assigned to medical-therapy with or without revascularization based on clinical indications. The PCC was visualized using multidetector computed tomography and defined relative to segmental arteries in patients with essential hypertension. PCC number before and 3 months after treatment was correlated with various renal parameters. Thirty-four stenotic kidneys from 30 patients were analyzed. PCC number correlated inversely with kidney volume. ARVD–stenotic kidneys with baseline PCC (collateral ARVD [C-ARVD], n=13) associated with elevated 24-hour urine protein and stenotic kidney vein level of tumor necrosis factor-α, lower single-kidney volume and blood flow, and greater hypoxia than in stenotic kidneys with no PCC (no collateral ARVD [NC-ARVD], n=17). Revascularization (but not medical-therapy alone) improved stenotic kidney function and reduced inflammation in both NC-ARVD and C-ARVD. In C-ARVD, revascularization also increased stenotic kidney volume, blood flow, and oxygenation to levels comparable to NC-ARVD, and induced PCC regression. However, revascularization improved systolic blood pressure, plasma renin activity, and filtration fraction only in NC-ARVD. Therefore, patients with C-ARVD have greater kidney dysfunction, atrophy, hypoxia, and inflammation compared with patients with NC-ARVD, suggesting that PCC does not effectively protect the stenotic kidney in ARVD. Renal artery revascularization improved in C-ARVD stenotic kidney function, but not hypertension or renin-angiotensin system activation. These observations may help direct management of patients with ARVD.

Left ventricular hypertrophy (LVH) is often seen in patients with primary aldosteronism (PA), and the prevalence of LVH is reportedly higher among patients with PA than patients with essential hypertension. However, the correlation between aldosterone levels and LVH is undefined, and how aldosterone affects LVH in patients with PA remains unclear. We, therefore, retrospectively assessed a large PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) to reveal the factors associated with LVH in patients with PA without suspected autonomous cortisol secretion. In the 1186 patients with PA studied, the basal plasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio did not significantly correlate with left ventricular LV mass index (LVMI) in single or multiple regression analyses. However, the plasma aldosterone concentration after the captopril challenge test or saline-infusion test, which are associated with autonomous aldosterone secretion, correlated significantly with LVMI, even after adjusting for patients’ backgrounds, including age and blood pressure. In addition, hypokalemia and the unilateral subtype also correlated with LVMI. Longitudinal subanalysis of medically or surgically treated patients with PA showed significant reductions in LVMI in both the surgery (63.0±18.1 to 55.3±19.5 g/m 2.7 , P 2.7 , P

For over 100 years, essential hypertension has been researched from different perspectives ranging from genetics, physiology, and immunology to more recent ones encompassing microbiology (microbiota) as a previously underappreciated field of study contributing to the cause of hypertension. Each field of study in isolation has uniquely contributed to a variety of underlying mechanisms of blood pressure regulation. Even so, clinical management of essential hypertension has remained somewhat static. We, therefore, asked if there are any converging lines of evidence from these individual fields that could be amenable for a better clinical prognosis. Accordingly, here we present converging evidence which support the view that metabolic dysfunction underlies essential hypertension.

The Asia Renal Denervation Consortium consensus conference of Asian physicians actively performing renal denervation (RDN) was recently convened to share up-to-date information and regional perspectives, with the goal of consensus on RDN in Asia. First- and second-generation trials of RDN have demonstrated the efficacy and safety of this treatment modality for lowering blood pressure in patients with resistant hypertension. Considering the ethnic differences of the hypertension profile and demographics of cardiovascular disease demonstrated in the SYMPLICITY HTN (Renal Denervation in Patients With Uncontrolled Hypertension)-Japan study and Global SYMPLICITY registry data from Korea and Taiwan, RDN might be an effective hypertension management strategy in Asia. Patient preference for device-based therapy should be considered as part of a shared patient-physician decision process. A practical population for RDN treatment could consist of Asian patients with uncontrolled essential hypertension, including resistant hypertension. Opportunities to refine the procedure, expand the therapy to other sympathetically mediated diseases, and explore the specific effects on nocturnal and morning hypertension offer a promising future for RDN. Based on available evidence, RDN should not be considered a therapy of last resort but as an initial therapy option that may be applied alone or as a complementary therapy to antihypertensive medication.

Inflammation plays a key role in the pathogenesis of hypertension. High dietary sodium intake has been associated with inflammation in patients suffering from high blood pressure & atherosclerosis. Our lab has shown that development of hypertension in a genetic model of human essential hypertension, the Spontaneously Hypertensive Rat (SHR), is dependent on nicotinic acetylcholine receptor (nAChR) mediated renal inflammation, which leads to enhanced expression of the renal sodium-potassium chloride cotransporter (NKCC2). Based on these findings we hypothesized that sodium sensitivity may play a role in the development of cholinergic hypertension. To investigate this hypothesis, we infused young pre-hypertensive SHR and Wistar Kyoto (WKY, normotensive control) rats with either saline or nicotine (15mg/kg/day) and placed them on either low-salt (LSD, 0.01% NaCl) or high-salt (HSD, 4% NaCl) diet for 2 wks. There was no change in systolic blood pressure (SBP) in saline or nicotine infused WKY with either LSD or HSD. Similarly, there was no difference between the SBP of saline infused SHR with either LSD or HSD. Interestingly, nicotine infusion did not change SBP in LSD fed SHR, but did result in ~20% increase in SBP in HSD fed SHR (122.0 ± 0.7 vs. 146.2 ± 0.2mmHg, p= 0.01). HSD alone induced a 2.25-fold increase in renal NKCC2 expression compared to LSD in saline infused SHR (p=0.006). In comparison to saline, nicotine infusion further induced a 58% increase in renal NKCC2 expression in SHR fed HSD (p=0.004). Renal NKCC2 expression did not change in WKY with either diet or nicotine infusion. Nicotine infused SHR on a HSD also manifested a 16% sodium retention compared to saline infused SHR (2.1 ± 0.1 mM/gBW vs. 2.5 ± 0.1 mM/gBW, p = 0.017). Nicotine infused SHR had 1.7 times more renal IL-6 than saline-infused SHR (1442. ± 212 vs 826 ± 103 pg/25mg total protein, p=0.04) and 9 times more renal IL-6 than nicotine-infused WKY controls (1442. ± 212 vs 148. ± 71 pg/25mg total protein, p=0.0041) under HSD conditions. Taken together with our previously published data, we conclude that NKCC2 likely plays a role in cholinergic-mediated renal inflammation and hypertension.

Introduction: Hypertension (HTN) is one of the major public health complications throughout the world. Although progress has been made in HTN research, early diagnosis and treatment of HTN are yet to be flourished. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in many diseases including HTN. According to our previous report, there is direct evidence showing that miR-510 is involved in HTN. Hypothesis: We assessed the hypothesis that to decipher the critical pathways of miR-510 and PTEN in regulation of PI3K/AKT Pathways, so it can be used as a therapeutic pathway as well as biomarker. Finally, we intend to study how anti-miR-510 reduces the HTN in the hypertensive induced rat model. Methodology: Proliferation, migration, invasion and apoptosis capacity of miR-510, Anti-miR-510, PTEN and eNOS were evaluated in HUVEC Cells. The expression pattern of miR-510, anti-miR-510 and eNOS, PTEN are analyzed by qPCR and western blot The relationship between miR-510, Anti-miR-510 and PTEN are investigated by luciferase assay Deoxycorticosterone acetate (DOCA) of 70mg/kg and 1% NaCl salt induced hypertension model (Sprague Dawley rats) was used in this study. According to the dose dependent study, anti-miR-510 was administered intravenously. Histological analyses are performed to examine the hypertrophy by using cardiac tissues fixed in 1% paraformaldehyde. Results and conclusion: Our results suggested that miR-510 can directly influence the PTEN expressions in HUVEC cells. Furthermore, the in vitro experiments clearly indicated that miR-510/PI3K/AKT/PTEN axis involved in HTN. Anti-miR-510 delivery can reduce the progression of HTN in the hypertensive induced rat model. Though miR-510 is involved in HTN, but its molecular mechanism is almost unknown. So, these analyses suggested that the correlation between miR-510, PTEN, anti-miR-510 are the critical step in gene expression and regulations. Thus, all these analyses could lead in identification of therapeutic target and non-invasive biomarker for HTN. Our in vivo experiments suggesting that anti-miR-510 may act as a novel therapeutic molecule for HTN treatment.

Elevated plasma soluble prorenin receptor (sPRR) is associated with essential hypertension and obesity-hypertension in men. Additionally, our laboratory previously found that the infusion of mouse sPRR elevates systolic blood pressure (SBP) in high-fat (HF) fed male mice through activation of the sympathetic nervous system but did not elevate SBP in HF-fed female mice. Interestingly, mouse sPRR infusion increased renal and hepatic angiotensinogen (AGT) and plasma renin concentration in female mice fed a low-fat diet. However, whether sPRR-activates the renin angiotensin system (RAS) and increases blood pressure in low-fat fed female mice remains to be investigated. Additionally, little is known concerning the influence of human sPRR on blood pressure in women. Therefore, we developed a humanized mouse model with high circulating human sPRR. Human sPRR-Myc-tag transgenic mice were bred with mice expressing Alb/Cre recombinase to induce human sPRR release in the circulation. Control and Alb-HsPRR female mice were fed a LF-diet for 8 months (n=11/groups). Body weight and body composition were examined and blood pressure assessed by radiotelemetry. Human sPRR-Myc-tag was detected in the liver of Alb-HsPRR female mice and plasma sPRR levels increased by 50-fold (CTL: 3.6±0.5 ng/ml, HsPRR:190.5±24.4 ng/ml; P0.05). Plasma AGT and renin activity were similar between Alb-HsPRR and control female mice. Therefore, whether the local RAS or the sympathetic nervous system are involved in human sPRR-mediated increase of SBP remains to be examined. Altogether, our results suggest an important role of circulating human sPRR in blood pressure control in women.

Mineralocorticoid receptors (MRs) are implicated in the pathology of hypertension. MR blockers are recommended for the treatment of salt-sensitive or resistant hypertension. However, use of currently available MR blockers is limited by adverse events. This phase 3 multicenter, randomized, double-blind study compared the efficacy and safety of esaxerenone, a new selective nonsteroidal MR blocker, at 2.5 and 5 mg/day and eplerenone 50 mg/day in Japanese patients with essential hypertension. After a 4-week washout period, 1001 eligible adults with hypertension were randomized evenly to esaxerenone 2.5 or 5 mg/day or eplerenone 50 mg/day treatments, taken orally once daily for 12 weeks. Primary end points were changes in sitting systolic or diastolic blood pressure (BP) from baseline at the end of treatment. Esaxerenone 2.5 mg/day was noninferior to eplerenone for reductions in sitting and 24-hour BP. Reductions in BP with esaxerenone 5 mg/day were significantly greater than those with esaxerenone 2.5 mg/day. Changes in diurnal BP showed persistent 24-hour antihypertensive effects in all treatment groups. The proportions of patients achieving target sitting BP ( Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02890173.

We described the diagnostic workup and management of an obese patient with resistant hypertension, who was hospitalized for heart failure. The case was complicated by comorbidities such as diabetes mellitus. After the exclusion of pseudohypertension, renal denervation was the final treatment option. Within 1 year, the procedure led to control of blood pressure on just 2 antihypertensive agents and to normalization of the structure and function of the left ventricle. Reduction of the body mass index also contributed to maintaining a healthy condition of up to 6 years after the surgical procedure.

Primary aldosteronism (PA) is hemodynamically independently associated with arterial wall stiffness as assessed by pulse wave velocity (PWV) compared with essential hypertension. Arterial wave reflection parameters derived from pulse wave analysis, such as forward and backward wave amplitudes (Pf and Pb), are promising vascular markers to predict cardiovascular outcomes in addition to PWV. These vascular parameters have never been studied in patients with PA before. In study part A, we prospectively enrolled 67 patients with PA and 132 patients with essential hypertension. In study part B, another 54 patients with PA were enrolled. Heart-carotid PWV was measured, and carotid pressure waveforms were recorded to calculate Pf, Pb, and augmentation index at baseline (part A and B) and 6 months after treatment (part B). The results showed that the patients with PA had significantly higher Pf ( P =0.001), Pb ( P =0.01), and PWV ( P =0.021) than the patients with essential hypertension. In univariate correlation analysis, both log Pf and Pb were significantly correlated with age, office blood pressure, serum potassium level, log PWV, and the presence of PA. However, only Pb was significantly correlated with log plasma renin activity and log aldosterone to renin ratio. In multivariate analysis, log Pf was significantly correlated with the presence of PA ( P =0.001), male sex, age, and mean arterial blood pressure. Pb was significantly correlated with the presence of PA ( P =0.031), age, and mean arterial pressure. Six months after treatment, Pf and Pb decreased significantly. In conclusion, the patients with PA had significantly increased wave reflections compared with the patients with essential hypertension. Our results provide clinical evidence of aldosterone-related extensive vascular dysfunction of the arterial system.

Among ~25% of patients with essential hypertension (EH), circulating endogenous ouabain (EO) and aldosterone (Aldo) are typically coelevated and their BP is especially salt-sensitive (SS). We probed for exaggerated natriuresis in a large cohort (712) of hypertensive patients that underwent an acute 2hr (T 120 ) load with saline (0.9%/2 L). Results: Using a quartiles analysis of sodium excretion, the 4th quartile subgroups showed higher SBP and DBP at T 120 , and at 2 hrs recovery (T 240 ). Fractional sodium excretion (FE Na) was significantly higher during loading and recovery in the 4 th quartile subgroup. Plasma Aldo was suppressed after saline in all subgroups as expected. SS patients showed an increased EO. In the 4 th quartiles EO was elevated at baseline and after saline (see figure), p Manova > 0.001 and the urinary Na/K ratio output was higher. Further, increases in plasma Na + were greater in the 4 th quartile group (1.91 ± 0.15 vs 0.83 ± 0.13 mM, p

Background: RNAi therapeutics targeting angiotensinogen (AGT) lower blood pressure in animal models of essential hypertension, but whether this treatment is beneficial in hypertensive chronic kidney disease (CKD) is yet unknown. Our aim was to assess the effectiveness of a small interfering RNA (siRNA) targeting hepatic AGT in a rat model of hypertensive CKD. Methods: Sprague Dawley rats (n=7-12 per group) were subjected to 5/6th nephrectomy, allowed to recover for four weeks, and subsequently subjected to one of five treatments: (1) vehicle, (2) AGT siRNA (10-30 mg/kg, s.c. every 2 weeks), (3) AGT siRNA + losartan (30 mg/kg/d), (4) losartan (30 mg/kg/d), or (5) losartan + captopril (30 and 6 mg/kg/d). Mean arterial pressure (MAP) was measured by radiotelemetry for 4 weeks, glomerular filtration rate (GFR) was measured by transcutaneous FITC-sinistrin clearance. Results: AGT siRNA and AGT siRNA + losartan reduced plasma AGT by 96.5 ± 1.4% and 97.0 ± 2.3%, respectively. Over the course of 4 weeks, proteinuria increased with vehicle and this increase was abrogated by all treatments (Δ proteinuria at 4 weeks versus baseline: +0.17 [0.12, 0.23], +0.02 [-0.04, 0.05], -0.01 [-0.07, 0.06], -0.05 [-0.12, 0.00], -0.01 [-0.06, 0.11] for vehicle, AGT siRNA, AGT siRNA + losartan, losartan, losartan + captopril, P < 0.05 for all groups compared with vehicle). Similarly, heart weight was equally reduced by all treatments except vehicle. No intervention affected GFR. Over the course of 4 weeks, MAP increased (from a baseline of 154 ± 18 mmHg) during vehicle treatment and this rise was prevented by AGT siRNA (+13 ± 15 mmHg vs. -2 ± 14 mmHg, P > 0.05 for difference between groups). Combination treatment with AGT siRNA + losartan, losartan + captopril, and losartan alone caused a similar and marked reduction in MAP (-17 ± 14 mmHg, -21 ± 17 mmHg, and -33 ± 20 mmHg, P < 0.05 versus vehicle for all; differences between groups not significant). Conclusion: In experimental CKD, AGT siRNA monotherapy appears to reduce proteinuria and heart weight in a blood pressure-independent fashion, to a similar degree as losartan or combination treatment. Thus, an siRNA targeting hepatic AGT may be a potential therapeutic approach for providing renal and cardioprotection in CKD.

Essential hypertension and systemic lupus erythematosus (SLE) are devastating conditions that disproportionately affect women. SLE has heterogeneous manifestations and treatment is limited to the use of non-specific global immunosuppression. Importantly, there is an increased prevalence of hypertension in women with SLE compared to healthy controls. Isolevuglandins (IsoLGs) are oxidation products of fatty acids that form as a result of reactive oxygen species. These molecules adduct covalently to lysine residues of proteins. Adducted proteins are then presented as autoantigens to T-cells resulting in immune cell activation. Previous studies have shown an essential role of IsoLGs in immune cell activation and the development of hypertension in animal models. We hypothesize that isoLGs are important for the development of hypertension and systemic immune activation in SLE. We first examined isoLG adduct accumulation within monocytes of human subjects with SLE compared to healthy controls. By flow cytometry, we found marked accumulation of isoLG adducts within CD14 + monocytes (34.2% ± 12.4% vs 3.81% ± 2.1% of CD14 + , N = 10-11, P B6.SLE123 and NZBWF1 mouse models of SLE. Animals were treated with the isoLG scavenger 2-hydroxybenzylamine (2-HOBA) or vehicle beginning at 7 weeks and were sacrificed at 32 weeks of age. C57BL/6 and NZW were used as controls. Importantly, treatment with 2-HOBA attenuated blood pressure in both mouse models (systolic BP 136.2 ± 5.6 mmHg for B6.SLE123 vs 120.9 ± 4.46 mmHg for B6.SLE123 +2HOBA; 164.7 ± 24.4 mmHg for NZBWF1 vs 136.9 ± 14.9 mmHg for NZBWF1 +2HOBA, N = 6-8, P < 0.05). Moreover, treatment with 2-HOBA reduced albuminuria and renal injury in the B6.SLE123 model (albumin/creatinine ratio 33.8 ± 2.0 x 10 -2 μg/mg for B6.SLE123 vs 5.5 ± 0.9 x 10 -2 μg/mg for B6.SLE123 +2HOBA, N = 7-9, P < 0.05). Finally, immune cell accumulation in primary and secondary lymphoid organs is significantly attenuated by 2-HOBA. These studies suggest a critical role of isoLG adduct accumulation in both systemic immune activation and hypertension in SLE.

Hypertension, an important cause of chronic kidney disease, is characterized by peritubular capillary (PTC) loss. Circulating levels of endothelial microparticles (EMPs) reflect systemic endothelial injury. We hypothesized that systemic and urinary PTC-EMPs levels would reflect renal microvascular injury in hypertensive patients. We prospectively measured by flow cytometry renal vein, inferior vena cava, and urinary levels of EMPs in essential (n=14) and renovascular (RVH; n=24) hypertensive patients and compared them with peripheral blood and urinary levels in healthy volunteers (n=14). PTC-EMPs were identified as urinary exosomes positive for the PTC marker plasmalemmal-vesicle–associated protein. In 7 RVH patients, PTC and fibrosis were also quantified in renal biopsy, and in 18 RVH patients, PTC-EMPs were measured again 3 months after continued medical therapy with or without stenting (n=9 each). Renal vein and systemic PTC-EMPs levels were not different among the groups, whereas their urinary levels were elevated in both RVH and essential hypertension versus healthy volunteers (56.8%±12.7% and 62.8%±10.7% versus 34.0%±17.8%; both P ≤0.001). Urinary PTC-EMPs levels correlated directly with blood pressure and inversely with estimated glomerular filtration rate. Furthermore, in RVH, urinary PTC-EMPs levels correlated directly with stenotic kidney hypoxia, histological PTC count, and fibrosis and inversely with cortical perfusion. Three months after treatment, the change in urinary PTC-EMPs levels correlated inversely with a change in renal function ( r =−0.582; P =0.011). Therefore, urinary PTC-EMPs levels are increased in hypertensive patients and may reflect renal microcirculation injury, whereas systemic PTC-EMPs levels are unchanged. Urinary PTC-EMPs may be useful as novel biomarkers of intrarenal capillary loss.

Patients with primary aldosteronism (PA) have increased risk of target-organ damage, among which vascular calcification is an important indicator of cardiovascular mortality. 14, 15-Epoxyeicosatrienoic acid (14, 15-EET) has been shown to have beneficial effects in vascular remodeling. However, whether 14, 15-EET associates with vascular calcification in PA is unknown. Thus, we aimed to investigate the association between 14, 15-EET and abdominal aortic calcification (AAC) in patients with PA. Sixty-nine patients with PA and 69 controls with essential hypertension, matched for age, sex, and blood pressure, were studied. 14, 15-Dihydroxyeicosatrienoic acid (14, 15-DHET), the inactive metabolite from 14, 15-EET, was estimated to reflect serum 14, 15-EET levels. AAC was assessed by computed tomographic scanning. Compared with matched controls, the AAC prevalence was almost 1-fold higher in patients with PA (27 [39.1%] versus 14 [20.3%]; P =0.023), accompanied by significantly higher serum 14, 15-DHET levels (7.18±4.98 versus 3.50±2.07 ng/mL; P P P

There have been several clinical studies examining the factors associated with cardiovascular disease (CVD) in patients with primary aldosteronism (PA); however, their results have left it unclear whether CVD is affected by the plasma aldosterone concentration or hypokalemia. We assessed the PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) and compared the prevalence of CVD among patients with PA with that among age-, sex-, and blood pressure-matched essential hypertension patients and participants with hypertension in a general population cohort. We also performed binary logistic regression analysis to determine which parameters significantly increased the odds ratio for CVD. Of the 2582 patients with PA studied, the prevalence of CVD, including stroke (cerebral infarction, cerebral hemorrhage, or subarachnoid hemorrhage), ischemic heart disease (myocardial infarction or angina pectoris), and heart failure, was 9.4% (stroke, 7.4%; ischemic heart disease, 2.1%; and heart failure, 0.6%). The prevalence of CVD, especially stroke, was higher among the patients with PA than those with essential hypertension/hypertension. Hypokalemia (K + ≤3.5 mEq/L) and the unilateral subtype significantly increased adjusted odds ratios for CVD. Although aldosterone levels were not linearly related to the adjusted odds ratio for CVD, patients with plasma aldosterone concentrations ≥125 pg/mL had significantly higher adjusted odds ratios for CVD than those with plasma aldosterone concentrations

The diagnosis of primary aldosteronism typically requires at least one confirmatory test. The fludrocortisone suppression test is generally accepted as a reliable confirmatory test, but it is cumbersome. Evidence from accuracy studies of the saline infusion test (SIT) and the captopril challenge test (CCT) has provided conflicting results. This prospective study aimed to evaluate the diagnostic accuracy of the SIT and CCT using fludrocortisone suppression test as the reference standard. One hundred thirty-five patients diagnosed with primary aldosteronism and 101 patients diagnosed with essential hypertension who completed the 3 confirmatory tests were included for the diagnostic accuracy analysis. The areas under the receiver–operator characteristics curves of the CCT and SIT were 0.96 (95% confidence interval [CI], 0.92–0.98) and 0.96 (95% CI, 0.92–0.98), respectively, using post-test plasma aldosterone concentration (PAC) for diagnosis. However, the areas under the receiver–operator characteristics curves of the CCT decreased to 0.71 (95% CI, 0.65–0.77) when the PAC suppression percentage was used to diagnose primary aldosteronism. The optimal cutoff of PAC post-CCT was set at 11 ng/dL, resulting in a sensitivity of 0.90 (95% CI, 0.84–0.95) and a specificity of 0.90 (95% CI, 0.83–0.95), which were not significantly different from those of SIT (with PAC post-SIT set at 8 ng/dL, sensitivity: 0.85 [95% CI, 0.78–0.91], P =0.192; specificity: 0.92 [95% CI, 0.85–0.97], P =0.551). In conclusion, both CCT and SIT are accurate alternatives to the more complex fludrocortisone suppression test. Because CCT is safe and much easier to perform, it may serve as a more feasible alternative. When interpreting the results of CCT, PAC post-CCT is highly recommended.

Measurement of plasma aldosterone and renin concentration, or activity, is useful for selecting antihypertensive agents and detecting hyperaldosteronism in hypertensive patients. However, it takes several days to get results when measured by radioimmunoassay and development of more rapid assays has been long expected. We have developed chemiluminescent enzyme immunoassays enabling the simultaneous measurement of both aldosterone and renin concentrations in 10 minutes by a fully automated assay using antibody-immobilized magnetic particles with quick aggregation and dispersion. We performed clinical validation of diagnostic ability of this newly developed assay-based screening of 125 patients with primary aldosteronism from 97 patients with essential hypertension. Results of this novel assay significantly correlated with the results of radioimmunoassay (aldosterone, active renin concentration, and renin activity) and liquid chromatography–tandem mass spectrometry (aldosterone). The analytic sensitivity of this particularly novel active renin assay was 0.1 pg/mL, which was better than that of radioimmunoassay (2.0 pg/mL). The ratio of aldosterone-to-renin concentrations of 6.0 (ng/dL per pg/mL) provided 92.0% sensitivity and 76.3% specificity as a cutoff for differentiating primary aldosteronism from essential hypertension. This novel measurement is expected to be a clinically reliable alternative for conventional radioimmunoassay and to provide better throughput and cost effectiveness in diagnosis of hyperaldosteronism from larger numbers of hypertensive patients in clinical settings.

See related article, pp 129–136 Primary aldosteronism (PA), which can be detected by aldosterone-to-renin ratio in its great majority, has come to be conceived as the most frequent form of secondary hypertension constituting ≈5% to 10% of unselected hypertension. PA is also clinically known to harbor relatively higher incidences of cardiovascular events and complications. As Funder1 commented, 2 recent major breakthroughs in the research fields of PA were summarized as follows. The first one was the demonstration of much higher prevalence of PA as described earlier, and, in particular, stress-induced but undiagnosed patients of hyperaldosteronism could be present among those diagnosed with essential hypertension in general population.2 The second was the development of recent biological and pathological findings, which have indeed shed enormous insights into long studied exploration of the origins of aldosterone-producing adenomas (APAs). In particular, the sophisticated approaches using next-generation sequencing did make it possible to identify various patterns of somatic mutations associated with autonomous aldosterone overproduction in APAs. These somatic mutations occur in the genes encoding the several kinds of ion channels involved in aldosterone biosynthesis, including KCNJ5 , ATP1A1 , ATP2B3 , CACNA1D , and CTNNB1 . In particular, those of KCNJ5 , encoding the inward rectifier potassium channel, were the first identified and most prevalent one associated with APA, resulting in the persistent depolarization of the cell membrane and subsequently promoting aldosterone biosynthesis. At this juncture, more than one third of APAs are considered to harbor KCNJ5 mutations, especially in East Asian patients.3 These mutations frequently occur in the specific areas of the gene, known as hot spots, namely G151R and L168R.4 Of further particular interest, KCNJ5 somatic mutation was only detected in APA but by no means in aldosterone-producing cell clusters frequently identified in the nonpathological adrenal cortex.5 However, …

The spontaneously hypertensive rat (SHR), one of the most widely used model of essential hypertension, is predisposed to left ventricular hypertrophy, myocardial fibrosis, and metabolic disturbances. Recently, quantitative trait loci influencing blood pressure, left ventricular mass, and heart interstitial fibrosis were genetically isolated within a minimal congenic subline that contains only 7 genes, including mutant Plzf (promyelocytic leukemia zinc finger) candidate gene. To identify Plzf as a quantitative trait gene, we targeted Plzf in the SHR using the transcription activator-like effector nuclease technique and obtained SHR line harboring targeted Plzf gene with a premature stop codon. Because the Plzf targeted allele is semilethal, morphologically normal heterozygous rats were used for metabolic and hemodynamic analyses. SHR- Plzf +/− heterozygotes versus SHR wild-type controls exhibited reduced body weight and relative weight of epididymal fat, lower serum and liver triglycerides and cholesterol, and better glucose tolerance. In addition, SHR- Plzf +/− rats exhibited significantly increased sensitivity of adipose and muscle tissue to insulin action when compared with wild-type controls. Blood pressure was comparable in SHR versus SHR- Plzf +/− ; however, there was significant amelioration of cardiomyocyte hypertrophy and cardiac fibrosis in SHR- Plzf +/− rats. Gene expression profiles in the liver and expression of selected genes in the heart revealed differentially expressed genes that play a role in metabolic pathways, PPAR (peroxisome proliferator-activated receptor) signaling, and cell cycle regulation. These results provide evidence for an important role of Plzf in regulation of metabolic and cardiac traits in the rat and suggest a cross talk between cell cycle regulators, metabolism, cardiac hypertrophy, and fibrosis.

See related article, pp 457–464 Identification of all of the genes differentially expressed in essential hypertension is highly relevant to elucidation of the mechanisms involved in this complex polygenic condition. Key to this includes the tissues investigated, the genes differentially expressed in each, and sorting out whether the differences in expression in hypertension stem from (1) polymorphism(s) in regulatory DNA affecting transcription of the gene, (2) the expression change being a downstream effect of the latter, (3) a response to an environmental factor, (4) a counter-regulatory response to the elevated blood pressure (BP), or (5) another factor driving both the BP response and gene expression. Although any simple straightforward study documenting transcriptome-wide expression changes should identify the major genes that are differentially expressed in a particular tissue in hypertension, such data are, by themselves, unable to discriminate between each of the aforementioned possibilities. In the current issue of Hypertension , Huang et al1 at Augusta University, University of Helsinki, the National Heart, Lung, and Blood Institute’s Framingham Heart Study, and University of Mississippi performed a transcriptome-wide analysis of peripheral blood leukocytes of 391 twins (57% monozygous) from the Finnish Twin Cohort study, and a replication study involving the Framingham cohort, looking for transcripts whose expression was associated with BP.1 Although this study is not the first to use peripheral blood leukocytes to determine such transcriptome-wide expression differences, it not only represents an important confirmation but also distinguishes genetic and environmental influences. Huang et al1 refer to 2 previous blood transcriptome-wide expression studies. One, in 2015 by Huan et al,2 found 83 genes whose expression levels correlated with BP (73 with systolic, 31 with diastolic, and 8 with hypertension).2 They found 65 were positively correlated with BP traits and 8 were negatively correlated. After adjustment for …

Hypertension represents a major risk factor for stroke, myocardial infarction, and heart failure and affects 30% of adult population. Vascular dysfunction is crucial in hypertension pathophysiology and exhibits bidirectional relationship. Metabolic disorders and oxidative stress contribute to vascular dysfunction, and mitochondrial deacetylase Sirt3 is critical in the regulation of metabolic and antioxidant functions. We hypothesized that reduced Sirt3 expression contributes to vascular dysfunction and essential hypertension. We studied Sirt3 in arterioles from human mediastinal fat in patients with essential hypertension compared with normotensive subjects. Pathophysiological role of vascular Sirt3 depletion was studied in mice with tamoxifen-inducible endothelial specific Sirt3 depletion (Ec Sirt3KO ). For the first time, we showed a 40% decrease in vascular Sirt3 level and 400% increase in SOD2 acetylation in hypertensive subjects which was linked to increased oxidative stress measured by superoxide overproduction and vascular inflammation due to elevated NfKB activity, VCAM, ICAM and MCP-1 levels. Interestingly, global Sirt3 depletion in mice increases blood pressure, inactivates key mitochondrial antioxidant SOD2 due to acetylation, increases vascular p65, VCAM, ICAM and MCP1, and increased T cell infiltration in kidney, induces cell-senescence and promotes vascular aging while global Sirt3 overexpression prevents these deleterious effects. We tested if Ec Sirt3KO mice have vascular dysfunction and hypertension. Both basal and angiotensin II-induced blood pressure was increased in Ec Sirt3KO mice accompanied by endothelial dysfunction and vascular O 2 • overproduction. Treatment of Ec Sirt3KO mice with SOD2-mimetic mitoTEMPO reduced vascular inflammation, markers of cell-senescence and vascular aging to the wild-type control levels while treatment of Ang II-infused Ec Sirt3KO mice partially rescues from vascular inflammation and attenuates accelerated vascular aging. We suggest that Sirt3 depletion in hypertension promotes both endothelial oxidative stress and metabolic dysfunction. Our data support a therapeutic potential of targeting Sirt3 expression in vascular dysfunction and hypertension.

Obiective: To investigate the influencing factors for microalbuminuria in Tibetan hypertensive patients. Methods: The study was a cross-sectional study, which was performed at the hospital of Chengdu office of people’s government of tibet autonomous region (Chengdu, China). From 2017.3 to 2018.3, 369 consecutive essential hypertension patients without treatment were enrolled in the study, and these patients were from Tibet at an altitude of 2500-5000 m. Medical professionals did a survey according to the study protocol, including standardized questionnaire, physical examination and laboratory tests. Urine samples were collected for microalbumin detection in the morning, and microalbuminuria was defined as the albumin to creatinine ratio (ACR) ≥ 300 mg/g. Results: Compared with the negative microalbumin group (n = 303), the positive group (n = 66) had higher systolic blood pressure (SBP) (142.2 ± 18.4 vs. 139.0 ± 17.0 mm Hg, p = 0.001), diastolic blood pressure (DBP) (89.6 ± 15.9 vs. 82.5 ± 12.5 mm Hg, p = 0.001), serum uric acid (402.7 ± 108.9 vs. 364.9 ± 102.8 μmol/l, p = 0.009), total cholesterol (TC) (4.9 ± 1.1 vs. 4.4 ± 1.1 mmol/l, p = 0.001), low density lipoprotein cholesterin (LDL-C) (2.8±0.9 vs. 2.6±1.0 mmol/l, p = 0.038), erythrocyte (5.1±1.0 x10 9 vs. 4.7± 0.7 x10 9 /l, p = 0.001), hemoglobin (158.1 ± 30.9 vs.141.1 ± 20.6 g/l, p = 0.001) and homocysteine (19.1 ± 17.3 vs. 15.2 ± 8.6 μmol/L, p = 0.001) . Based on the upper reference limit of variables, these variables were divided into the low and high value groups. With the low value group as reference, univariate analysis showed that , the high value groups of hemoglobin,SBP, homocysteine and TC were positively related with microalbuminuria. After adjustmentfor confounders, multivariate analysis suggested that the high value groups of hemoglobin,SBP, homocysteine and TC,were still positively related with microalbuminuria, and the ORs were 4.08 (95% CI:1.79-9.28, p = 0.001) for hemoglobin,2.35 (95% CI:1.33-4.17, p = 0.003) for SBP, 2.14 (95% CI:1.21-3.81,p = 0.009) for homocysteine and 2.03 (95% CI:1.12-3.69, p = 0.020) for TC, respectively. Conclusion: In Tibetan plateau area, hemoglobin,SBP,homocysteine and TC were positively related with microalbuminuria in hypertensive patients.

Aim: Failure to upregulate hypothalamic paraventricular nucleus (PVN) Gαi 2 proteins promotes salt sensitive hypertension (ssHTN) and central inflammation plays a role in HTN. We hypothesize that 1) PVN-specific inflammation contributes to Gαi 2 protein dependent ssHTN, and 2) GNAI2 SNPs correlate with HTN. Methods: 3-month-old male Sprague Dawley rats were implanted with I.C.V. cannulas fitted to osmotic minipumps and infused with Gαi 2 or control scrambled (SCR) oligodeoxynucleotides (ODN) (25μg/5μl/day), or ODN + minocycline (MINO) (120μg/5μl/day, HS only) and placed on a 7-day normal (NS; 0.6% NaCl) or high (HS; 4% NaCl) salt diet. Day 7 BP (femoral cannulation) and Plasma NE (ELISA) were measured. PVN and subfornical organ microglia and astrocyte activation (IHC), and PVN pro-inflammatory (PIC) and anti-inflammatory (AIC) cytokine mRNA and protein levels were analyzed. GNAI2 SNPs were examined in the UK BioBank for associations with HTN. Results: In contrast to SCR ODN infusion, Gαi 2 ODN infusion and HS evoked HTN, elevated plasma NE, PVN-specific microgliosis, upregulation of PVN PICs and downregulation of PVN IL-10. MINO co-infusion with Gαi 2 ODN and HS diet restored PIC and AIC mRNA and protein levels. Furthermore, MINO attenuated microgliosis and reduced the magnitude of ssHTN. GNAI2 SNPs rs2298952 (p=0.0411, MAF=0.103) and rs4547694 (p=0.0117, MAF=0.381) are both associated with essential HTN in BioBank subjects. Conclusion: PVN-specific microgliosis and inflammation may drive Gαi 2 protein dependent ssHTN and GNAI2 SNPs represent a potential biomarker of essential HTN.

Introduction and Aims: Growth differentiation factor-15 (GDF-15), a member of TGF-beta family, has been implicated in several pathological conditions, which include inflammation, cancer, cardiovascular, pulmonary and renal diseases. Recently it is reported that serum GDF-15 may be a marker for chronic kidney disease (CKD) and CKD progression. In present study, we evaluated whether serum GDF-15 is associated with renal vascular resistance evaluated by resistive index (RI) measured in Ultrasound, which is the marker of renal injury. Methods: Eighty patients with essential hypertension were enrolled in this study. They were evaluated on serum GDF-15 and renal RI as well as for conventional atherosclerotic risk factors. Results: Mean age of all patients was 66 ± 12 years (35 males and 45 females). Mean eGFR and renal RI was 68.9 ± 23.0ml / min / 1.73m2 and 0.71 ± 0.07 respectively. Mean serum GDF-15 was 1492 ± 1319 pg/ml. RI correlated with GDF-15 (r=0.47, P Conclusions: GDF-15 is associated with renal vascular resistance and may become a nephropathic marker in patients with hypertension.

Background: A metabolic shift in energy expenditure toward a catabolic state upon high sodium (Na + ) diet, ultimately favouring endogenous water accrual and body fluid preservation, has recently been described in a rodent model. Objective: To investigate the impact of high Na + intake on renal Na + /water handling and metabolic signatures in a large real-life cohort of patients. Methods and Results: We analysed biochemical data from 767 hypertensive patients (429 males, 55.9%; age 47 ± 13 years; BMI 25.6 [23.0-29.0] kg/m 2 ) in washout from drugs affecting the renin-angiotensin-aldosterone system at the time of screening for secondary causes and with a conclusive diagnosis of essential hypertension (2012-2017). Classes of Na + intake ( L ow ≤2.3g/d; M edium 2.3-5g/d; H igh >5g/d) were defined based on urinary 24h Na + excretion (uNaV). The fractional excretion (FE) of Na + increased with increasing Na + intake (L: 0.39% [0.30-0.47] vs H: 0.81% [0.73-0.98], p < 0.001), while FE of free water decreased (L: 1.13% [0.73-1.72] vs H: 0.89% [0.69-1.12], p = 0.015). uNaV was an independent predictor of glomerular filtration rate (GFR, estimated by creatinine clearance; H: 130 ± 33 vs M: 111 ± 52 and L: 96 ± 39 ml/min/1.73m 2 ; p < 0.001 for comparisons) after correction for age, sex, BMI, renin, aldosterone and uKV (p = 0.001). This resulted in a marked increase in the 24h tubular Na + reabsorption and, accordingly, in the estimated energy expenditure (Δ H vs L= 18 [12-24] kcal/d, p < 0.001). At non-targeted LC/MS metabolomics (n = 67), metabolites increased (p < 0.05) in H vs L Na + intake mostly entailed intermediates or end products of the urea cycle and products of protein catabolism. Urinary 24h cortisol excretion, as a potential determinant of catabolism, increased with Na + intake (n = 137; L: 63 [36-72] nmol, M: 60 [47-86] nmol, H: 86 [75-139] nmol; p < 0.001), but its strongest predictor at multivariate regression analysis was GFR (p = 0.001). Conclusions: Kidneys can effectively dissociate Na + and water handling upon high Na + diet, at the cost of glomerular hyperfiltration, enhanced glomerulotubular balance, increased tubular energy expenditure and, ultimately, protein catabolism from endogenous or excess exogenous sources. This has broad implications on global cardiovascular risk.

Sustained stimulation of β-adrenoceptors (β-ARs) and activation of renin–angiotensin–aldosterone system are common features of cardiovascular diseases with rising sympathetic activation, including essential hypertension, myocardial infarction, and heart failure. In this study, we investigated the role of AT1 receptor and mineralocorticoid receptor (MR) in the vascular alterations caused by β-AR overstimulation. β-AR overstimulation with associated cardiac hypertrophy and increased vasoconstrictor response to phenylephrine in aorta were modeled in rats by 7-day isoproterenol treatment. The increased vasoconstrictor response to phenylephrine in this model was blunted by the MR antagonist spironolactone, but not by the AT1 receptor antagonist losartan, despite the blunting of cardiac hypertrophy with both drugs. Spironolactone, but not losartan, restored NO bioavailability in association with lower endothelial nitric oxide synthase–derived superoxide production, increased endothelial nitric oxide synthase dimerization, and aortic HSP90 upregulation. MR genomic and nongenomic functions were activated in aortas from isoproterenol-treated rats. Isoproterenol did not modify plasma levels of MR ligands aldosterone and corticosterone but rather increased perivascular adipose tissue–derived corticosterone in association with increased expression of 11β-hydroxysteroid dehydrogenase type 1. The anticontractile effect of aortic perivascular adipose tissue was impaired by β-AR overstimulation and restored by MR blockade. These results suggest that activation of vascular MR signaling contributes to the vascular dysfunction induced by β-AR overstimulation associated with endothelial nitric oxide synthase uncoupling. These findings reveal an additional explanation for the protective effects of MR antagonists in cardiovascular disorders with sympathetic activation.

Mitochondrial injury contributes to renal dysfunction in several models of renal disease, but its involvement in human hypertension remains unknown. Fragments of the mitochondrial genome released from dying cells are considered surrogate markers of mitochondrial injury. We hypothesized that hypertension would be associated with increased urine mitochondrial DNA (mtDNA) copy numbers. We prospectively measured systemic and urinary copy number of the mtDNA genes cytochrome-c oxidase-3 and NADH dehydrogenase subunit-1 by quantitative polymerase chain reaction in essential (n=25) and renovascular (RVH, n=34) hypertensive patients and compared them with healthy volunteers (n=22). Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin served as indices of renal injury. Renal blood flow and oxygenation were assessed by multidetector computed tomography and blood oxygen level–dependent magnetic resonance imaging. Blood pressure, urinary neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 were similarly elevated in essential hypertension and RVH, and estimated glomerular filtration rate was lower in RVH versus healthy volunteers and essential hypertension. Renal blood flow was lower in RVH compared with essential hypertension. Urinary mtDNA copy number was higher in hypertension compared with healthy volunteers, directly correlated with urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 and inversely with estimated glomerular filtration rate. In RVH, urinary mtDNA copy number correlated directly with intrarenal hypoxia. Furthermore, in an additional validation cohort, urinary mtDNA copy number was higher in RVH compared with healthy volunteers (n=10 each). The change in serum creatinine levels and estimated glomerular filtration rate 3 months after medical therapy without or with revascularization correlated with the change in urinary mtDNA. Therefore, elevated urinary mtDNA copy numbers in hypertensive patients correlated with markers of renal injury and dysfunction, implicating mitochondrial injury in kidney damage in human hypertension.

The renin–angiotensin system (RAS) is an essential regulator of blood pressure homeostasis. The primary effector molecule of the RAS is angiotensin (Ang) II, an 8-amino acid peptide that initiates tissue-specific processes via binding to the type 1 or 2 angiotensin II receptors (AT1 or AT2). The AT1 receptor is a G-protein–coupled receptor expressed in most tissues throughout the body. Although the rodent expresses 2 AT1 receptor isoforms, AT1A and AT1B, the closest functional homolog to the human AT1 receptor in most rodent tissues is AT1A. The most widely appreciated functions of Ang II signaling via the AT1 receptor are to augment global vascular tone and to promote sodium retention in the kidney, thus playing a crucial role in acute and long-term maintenance of blood pressure.1,2 Ang II elicits these effects by increasing the contractility of vascular smooth muscle, promoting the release of aldosterone from the adrenal cortex, and directly increasing the expression or activity of solute transporters in the renal tubules that promote sodium reabsorption. As such, blockade of the RAS has been a mainstay in the treatment for hypertension and its complications, including cardiovascular and kidney disease.2,3 Although the cause of essential hypertension is unclear, inhibition of the RAS is effective in reducing blood pressure in a wide variety of patients, which suggests that inappropriate RAS activation is common in the pathogenesis of this idiopathic condition. Global RAS inhibitors ameliorate hypertension by blocking the production of Ang II or by preventing activation of the AT1 receptor. These medications are global inhibitors in the sense that they disrupt AT1 receptor signaling concomitantly in all tissues. The ongoing effort to uncover novel pathogenic mechanisms of hypertension has revealed a significant role for …

Cardiovascular disease is the major factor that reduces lifespan in Turner syndrome. High blood pressure (BP) is common in Turner syndrome and is the most easily treatable cardiovascular risk factor. We studied the prevalence of elevated screening systemic BP, awareness of the problem, and its clinical associations in a large group of girls attending the annual meeting of the Turner Syndrome Society of the United States. Among 168 girls aged 2 to 17 years, 42% had elevated screening BP (systolic and diastolic), yet only 8% reported a previous diagnosis of hypertension. History of aortic coarctation repair (17%) was positively associated with elevated systolic BP (52% versus 32%; P P

Patients often have lower (white coat effect) or higher (masked effect) ambulatory/home blood pressure readings compared with clinic measurements, resulting in misdiagnosis of hypertension. The present study assessed whether blood pressure and patient characteristics from a single clinic visit can accurately predict the difference between ambulatory/home and clinic blood pressure readings (the home–clinic difference). A linear regression model predicting the home–clinic blood pressure difference was derived in 2 data sets measuring automated clinic and ambulatory/home blood pressure (n=991) using candidate predictors identified from a literature review. The model was validated in 4 further data sets (n=1172) using area under the receiver operator characteristic curve analysis. A masked effect was associated with male sex, a positive clinic blood pressure change (difference between consecutive measurements during a single visit), and a diagnosis of hypertension. Increasing age, clinic blood pressure level, and pulse pressure were associated with a white coat effect. The model showed good calibration across data sets (Pearson correlation, 0.48–0.80) and performed well-predicting ambulatory hypertension (area under the receiver operator characteristic curve, 0.75; 95% confidence interval, 0.72–0.79 [systolic]; 0.87; 0.85–0.89 [diastolic]). Used as a triaging tool for ambulatory monitoring, the model improved classification of a patient’s blood pressure status compared with other guideline recommended approaches (93% [92% to 95%] classified correctly; United States, 73% [70% to 75%]; Canada, 74% [71% to 77%]; United Kingdom, 78% [76% to 81%]). This study demonstrates that patient characteristics from a single clinic visit can accurately predict a patient’s ambulatory blood pressure. Usage of this prediction tool for triaging of ambulatory monitoring could result in more accurate diagnosis of hypertension and hence more appropriate treatment.

Primary hypertension is a growing concern in children because of the obesity epidemic largely attributable to western lifestyles. Serum uric acid is known to be influenced by dietary habits, correlates with obesity, and could represent a risk factor for hypertension. Preliminary studies in children highlighted uric acid as a potentially modifiable risk factor for the prevention and treatment of hypertension. The effect of lifestyle changes (increase of physical activity and dietary modifications) on blood pressure values, weight status, and serum uric acid levels in a cohort of 248 children referred for cardiovascular risk assessment were evaluated over a mean 1.5-year follow-up. At baseline, 48% of children were obese and 50% showed blood pressure values >90th percentile. At follow-up, a significant improvement in weight class (24% obese; P 90th percentile; P P P =0.0056), and puberty at baseline ( P =0.0048) were independently associated with higher systolic blood pressure z-score at follow-up, whereas a negative association was observed with body mass index z-score decrease during follow-up ( P =0.0033). The risk of hypertension at follow-up was associated with body mass index ( P =0.0025) and systolic blood pressure ( P P =0.0002), whereas the risk of showing hypertension ≥99th percentile was more than doubled for each baseline 1 mg/dL increase of serum uric acid ( P =0.0130). Uric acid is a powerful determinant of blood pressure over time, independent of lifestyle modifications.

The renal resistive index (RI) calculated by Doppler ultrasonography has been reported to be correlated with renal structural changes and outcomes in patients with essential hypertension or renal disease. However, little is known about this index in primary aldosteronism. In this prospective study, we examined the utility of this index to predict blood pressure (BP) outcome after adrenalectomy in patients with primary aldosteronism. We studied 94 patients with histopathologically proven aldosteronoma who underwent surgery. Parameters on renal function, including renal flow indices, were examined and followed up for 12 months postoperatively. The renal RI of the main, hilum, and interlobar arteries was significantly higher in patients with aldosteronoma compared with 100 control patients. BP, estimated glomerular filtration rate, and urinary albumin excretion significantly decreased after adrenalectomy. The resistive indices of all compartment arteries were significantly reduced 1 month after adrenalectomy and remained stable for 12 months. Patients whose interlobar RI was in the highest tertile at baseline had higher systolic BP after adrenalectomy than those whose RI was in the lowest tertile. Logistic regression analysis demonstrated that the RI of the interlobar and hilum arteries could be an independent predictive marker for intractable hypertension (systolic BP ≥140 mm Hg, increased BP, taking ≥3 antihypertensive agents, or increased number of agents) even after adrenalectomy. Therefore, in patients with aldosteronoma, the renal RI indicates partially reversible renal hemodynamics and renal structural damages that would influence postoperative BP outcome.

Актуальность. На сегодняшний день существуют данные о влиянии повышенного индекса массы тела (ИМТ) на развитие когнитивных нарушений (КН). Цель: оценить роль повышенного артериального давления (АД) и ИМТ в возникновении КН у пациентов с гипертонической болезнью (ГБ). Материалы и методы. В исследование включены 62 пациента (1-я группа) с ГБ II–III стадии 2–3-й степени и 30 практически здоровых лиц (2-я группа) с нормальным уровнем АД. Пациенты 1-й группы были разделены на две подгруппы: 1А подгруппу составили 38 больных с ГБ и повышенным ИМТ, 1Б подгруппу — 24 больных с ГБ и нормальным ИМТ. Для изучения когнитивных функций применялась краткая шкала исследования психического статуса (MMSE). Результаты. Средний балл по шкале MMSE составил 26,9 ± 1,5 и 28,8 ± 1,1 у пациентов 1-й и 2-й группы соответственно, что свидетельствует о достоверном ухудшении когнитивных функций у пациентов с ГБ (p, Актуальність. На сьогодні існують дані щодо впливу підвищеного індексу маси тіла (ІМТ) на розвиток когнітивних порушень (КП). Мета: оцінити роль підвищеного артеріального тиску (АТ) та ІМТ у виникненні КП у пацієнтів із гіпертонічною хворобою (ГХ). Матеріали та методи. У дослідження включені 62 пацієнти (1-ша група) із ГХ ІІ–ІІІ стадії 2–3-го ступеня та 30 практично здорових осіб (2-га група) із нормальним рівнем АТ. Пацієнти 1-ї групи були розподілені на дві підгрупи: 1А підгрупу становили 38 хворих із ГХ та підвищеним ІМТ, 1Б підгрупу — 24 хворі із ГХ та нормальним ІМТ. Для вивчення когнітивних функцій застосовувалась коротка шкала дослідження психічного статусу (MMSE). Результати. Середній бал за шкалою MMSE становив 26,9 ± 1,5 та 28,8 ± 1,1 у пацієнтів 1-ї та 2-ї групи відповідно, що свідчить про достовірне погіршення когнітивних функцій у пацієнтів із ГХ (p < 0,05). КП були більш вираженими в пацієнтів із ГХ та підвищеним ІМТ, середній показник цих пацієнтів за шкалою MMSE був достовірно нижчим порівняно із середнім балом хворих із нормальним ІМТ (26,4 ± 1,4 та 28,0 ± 1,2 відповідно, p < 0,05). У пацієнтів із ГХ та підвищеним ІМТ статистично достовірно вищою була частота помірних КП та деменції. Висновки. У пацієнтів із ГХ показники когнітивних функцій були достовірно нижчими порівняно з групою контролю. Надлишкова маса тіла й ожиріння зумовлювали достовірне погіршення когнітивних функцій у пацієнтів із ГХ., Background. There is growing evidence that obesity is associated with cognitive impairment. The purpose of the study was to determine the effects of high blood pressure (BP) and body mass index (BMI) on cognitive functioning in patients with essential hypertension. Materials and methods. We selected 62 patients with hypertension degrees 2–3 (group 1) and 30 apparently healthy individuals (group 2) with a normal level of BP. Hypertensive subjects were divided into two subgroups based on their BMI: subgroup 1A consisted of 38 patients with hypertension and increased BMI, subgroup 1B — of 24 patients with hypertension and normal BMI. Neuropsychological examination was carried out by Mini Mental State Examination (MMSE). Results. The average MMSE score was 26.9 ± 1.5 in group 1 and 28.8 ± 1.1 in group 2 that indicates a significant cognitive decline in hypertensive patients (p < 0.05). Obese and hypertensive patients performed more poorly than non-obese hypertensives, their average MMSE score was significantly lower (26.4 ± 1.4 and 28.0 ± 1.2, respectively, p < 0.05). Mild cognitive impairment and dementia predominated in the structure among obese hypertensives. Conclusions. Cognitive performance was significantly lower in hypertensive patients compared to the control group. And those with combination of hypertension and overweight had a significantly greater decline in cognitive functioning.

Статья посвящена профессиональной деятельности выдающегося украинского терапевта, ученого, профессора Виктора Моисеевича Коган-Ясного, который стоял у истоков современных взглядов на механизмы развития артериальной гипертензии., Статтю присвячено професійній діяльності видатного українського терапевта, вченого, професора Віктора Мойсейовича Коган-Ясного, який стояв у витоків сучасних поглядів на механізми розвитку артеріальної гіпертензії., The article deals with the professional activities of the prominent Ukrainian therapist, scientist, professor Victor Moiseiovych Kohan-Yasnyi, who was at the forefront of modern views on the pathogenesis of arterial hypertension.