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Target organ damage in hypertensive subjects. 

Target organ damage in hypertensive subjects. 

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Introduction: Subclinical brain damage in essential hypertension is more prevalent than cardiovascular or renal impairment; nevertheless, screening for nervous system involvement is difficult due to the low accessibility and high costs of these techniques. Objective: To assess the frequency of silent target organ damage in a cohort of asymptomatic...

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... can be observed that the presence of classical lesions on MRI was associated with a longer duration of hypertension and higher values of SBP. Table 3 shows the effect of essential HT on the different vascular beds in patients enrolled in the study. Heart and kidney were assessed in 28 and 29 hypertensive patients respectively, of whom 67.9% had some type of damage to the heart and 58.6% had some type of renal damage. ...

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... Five published papers regarding to the identification of subclinical brain lesions in neurologically asymptomatic subjects with vascular risk factors have been published by our group [112][113][114][115][116]. ...
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Cerebral small vessel disease (CSVD) is one of the most prevalent pathological processes affecting the structure and function of the smallest cerebral blood vessels. Depending on the location and dispersion of the lesions, it would be responsible for a quarter of all ischemic strokes, mood disturbance, cognitive impairment, motor gait disorders and is the most important contribuitor to vascular dementia. The burden of the disease is not focalized at an initial-single lesion. Lesion spreading and further disruption in structural and functional network connectivity, leads to an important clinical variability. The evolution of CSVD lesions is highly dynamic, and is not only the result of a chronic process; in addition, acute repetitive events over years contribute to the evolution of brain lesions. These can have a similar appearance on MRI studies, can progress, regress and even disappear, causing local and distal effects on brain structure and function. Advanced MRI techniques could have the potential to explore CSVD in a global conceptualization, considering its diffuse nature and the complexity of microvascular pathologies involved. The use of stronger magnetic field MRI has also assisted in the visualization and characterization of tiny and previously underappreciated lesions associated with CSVD. Additionally, the basis of the clinical-imaging dissociation observed could be influenced by brain resilience, a process which is incompletely understood. A global vision of CSVD could give a more detailed knowledge of the disease, emphasizing not only its high prevalence, but also the dynamic evolution and progression of the initial lesions.
... [31,32] Other less expensive and more available techniques have been explored, but to date none has been able to be put in practice for different reasons. Among these the most evaluated have been ambulatory blood pressure monitoring (ABPM) [12,21,[33][34][35], quantitative retinal microvascular assessment, [24,[36][37][38] quantitative electroencephalography, [20,39,40] carotid ultrasonography [41][42][43][44] and neurocognitive studies. [21,26,[45][46][47] ...
... [56] Our group reported no association of IMT with brain MRI findings in hypertensive patients; but, increased resistive index and decreased diastolic velocity were associated with classical brain MRI lesions, possibly indicating a resistive carotid flow pattern in these patients. [41] Likewise, Heliopoulos et al, in a sample of 52 hypertensive patients (mean age 71.4 years), did not find association between IMT and WMH. [42] Notwithstanding, when we calculated later the MRI total CSVD score in a larger sample of asymptomatic hypertensive patients (n=120), an association between increased intimal thickness and more severe CSVD score was recognized. ...
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Cerebral small vessel disease (CSVD) refers to a syndrome of clinical and imaging findings associated with pathologies in perforating cerebral arterioles, capillaries and venules, which include mainly white matter hyperintensities (WMHs), lacunes, recent small subcortical infarcts, enlarged perivascular spaces, cerebral microbleeds and atrophy. It is closely related to aging and vascular risk factors, tripling the risk of stroke, and majorly contributing to cognitive impairment and dementia. After aging, arterial hypertension is the major risk factor for developing CSVD, which very frequently goes unrecognized for many years (silent or asymptomatic CSVD). Brain MRI is the gold standard for diagnosis of CSVD, but it is very costly and has restricted availability at the primary care level; thus, less expensive and more available methods are necessary to screen the population at higher risks. In the present chapter we describe asymptomatic CSVD, its estimated prevalence, and main clinical and neuroimaging findings. We also review some of the most frequent methods that have been evaluated to identify silent CSVD in neurologically asymptomatic individuals. In this context, measuring brain specific proteins in the blood has been an option which has begun to be explored during the last decade with promising expectations. We review the results in this line of thought in the scientific literature and discuss our experience with neuron specific enolase, S100B protein and autoantibodies against the NR2 peptide of the NMDA receptor in hypertensive patients.
... Эндотелиальная дисфункция является ключевым звеном в патогенезе многих заболеваний, таких как артериальная гипертензия, инсульт, сахарный диабет, метаболический синдром, эректильная дисфункция и почечная недостаточность [7][8][9]. Дисфункция эндотелия является начальной стадией морфологических изменений при этих заболеваниях [10]. Она особенно часто наблюдается у пациентов с традиционными факторами риска, включающими ожирение, гиперхолестеринемию, сахар ный диабет и артериальную гипертензию, часто еще задолго до того, как сами заболевания начинают клинически проявляться [11]. ...
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В работе подводятся некоторые итоги почти 40-летней работы авторов в области липосомологии, начатые в 80-х годах прошлого века под руководством академика НАМН Украины Александра Викторовича Стефанова.Создание нужной концентрации лекарственных веществ в органе-мишени, не затрагивая при этом не вовлеченные в патологический процесс органы и ткани, – задача непростая. За последние несколько лет предпринято множество попыток решить эту проблему, и оказалось, что лучшимипереносчиками лекарств являются именно липосомы.Преимущества липосом перед другими носителями обусловлены такими их свойствами:– сродство с природными мембранами клеток по химическому составу;– универсальность. Липосомы способны переносить разнообразные фармакологически активныевещества, а также дополнительные источники энергии для клетки и генетический материал; - липосомы сравнительно легко биодеградируют, высвобождая доставленные вещества. В пути следования липосомы надежно укрывают свое содержимое от контакта с иммунной системой и не вызывают защитных и аллергических реакций организма;– способ взаимодействия липосом с клетками, который происходит в разных формах. При этом могут изменяться свойства клеточных мембран, например: вязкость и проницаемость; величина электрического заряда; фосфолипидное окружение ферментов и ионных каналов и, соответственно, их активность (вот почему даже так называемая пустая липосома может быть биологически активным агентом).Благодаря липосомам появляется новый способ направленного воздействия на клетку, который можно назвать «мембранной инженерией», то есть, появляется возможность модифицировать клеточную мембрану в заданном направлении.Оказалось, что липосомы могут быть не только переносчиками лекарств, но и обладают самостоятельной биологической активностью. Продемонстрирована способность так называемых пустых фосфатидилхолиновых липосом (ФХЛ) оказывать влияние на электрическую и сократительную активность сосудистых гладких мышц. При гипоксии ФХЛ восстанавливают измененную для ионов проницаемость плазматических мембран гладких мышц сосудов, а у крыс со спонтанной артериальной гипертензией улучшают эндотелий-зависимые дилататорные реакции сосудов.Кроме того, было показано, что «пустые» ФХЛ эффективно восстанавливают вызванное ацетилхолином эндотелий-зависимое расслабление изолированных колец грудной аорты, нарушенное воздействием гамма-облучения. Липосомы также восстанавливают пониженную после облучения чувствительность сосудистой ткани к ацетилхолину и оксиду азота.С целью усиления антигипоксического и антиоксидантного действия липосом в их структуру был внедрен антиоксидант кверцетин. Использование липосомальной формы кверцетина приводит к полноценному восстановлению коронарного кровотока в послеокклюзионном периоде приострой субтотальной ишемии миокарда, в значительной степени уменьшает проявления характерного для репеперфузионного периода окислительного стресса и предупреждает повышение содержания лейкотриенов С4 и Е4. Синтез простациклина при этом не уменьшается. Применение липосомальной формы кверцетина приводит к уменьшению зоны некроза миокарда в два раза.Липосомальная форма кверцетина практически полностью предотвращает или в значительной степени корригирует нарушения ритма сердечных сокращений и восстанавливает сократительную активность миокарда.Липосомальная форма кверцетина эффективно восстанавливает функцию калиевых каналов большой проводимости у облученных крыс.Перспективным может оказаться включение в состав липосом цитохрома С. Липосомальная форма цитохрома С приводит к коррекции нарушений гемостаза и предотвращает развитие синдрома ДВС при острой массивной кровопотере.Многочисленные патологические процессы, такие как гипертония, атеросклероз, нарушение кровотока в центральной нервной системе, вызваны недостаточностью эндогенного синтеза/высвобождения NO. В таких случаях дополнительное введение NO может быть очень эффективнойстратегией в лечении заболеваний, связанных с указанными патологическими процессами.Разработка современных доноров оксида азота, обладающих способностью контролируемого и дозированного высвобождения действующего вещества, представляет собой чрезвычайно сложную задачу. Создание липидной системы доставки NO, способной обеспечить естественную скорость высвобождения, и разработка ее стабильной лекарственной формы стало следующей целью наших исследований.Проведенные исследования специфического действия сконструированной липосомальной формы оксида азота (ЛФ NO) свидетельствуют о его ее чрезвычайно высокой дилататорной, антиишемической активности. Это подтверждается выраженным дозозависимым расслаблением сегментов интактной аорты крыс и продолжительной гипотензивной реакцией системного кровообращения. ЛФ NO предотвращает развитие критических нарушений насосной функции сердца и способствует сохранению его сократительной активности при субтотальной ишемии. Действие ЛФ NOпроявляется значительным также дозозависимым расслаблением полосок пещеристых тел полового члена и миометрия.Новый NO-содержащий липосомальный конструкт эффективно открывает одиночные кальцийзависимые калиевые каналы большой проводимости в сосудистых гладких мышцах и значительно увеличивает вероятность их нахождения в открытом состоянии.Таким образом, ЛФ NO обещает быть эффективной при лечении ангиопатий различного генеза (включая диабетическую), эректильной дисфункции, гиперактивного мочевого пузыря, артериальной гипертензии, геморрагического и ишемического инсульта. Учитывая возможность применения в ингаляционной форме, она может быть использована для лечения легочной гипертензии.Высказывается мнение, что потенциальные возможности липосом существенно выше пока известных нам. Мы только начали понимать, как липосомы работают с клеткой.
... Since the brain is one of the most affected target organs in hypertension [15][16][17], early damage in the cerebral microcirculation leading to a microangiopathy-Called cerebral small vessel disease (CSVD)-is present [18,19]. These vascular lesions can be symptomatic or subclinical ("silent") and have been related to essential HT in neurologically asymptomatic individuals [16,[20][21][22][23]. In neuroimaging, these lesions can be observed as lacunar infarcts, microbleeds, white matter hyperintensities (WMH) and enlarged Virchow-Robin spaces (EVRPS) [18,19]. ...
... CSVD is five times more frequent than symptomatic CVD in the general population [24], and increase significantly with advancing age and HT [25,26]. These lesions are considered potential causes of disability [27,28], with unfavorable prognosis, and their presence predicts CVD and cognitive deterioration more frequently [20,21,23,25,[29][30][31]. In fact, the annual cost, due to disability and rehabilitation for cardiovascular disease and stroke in the United States, has been estimated at 329.7 billion dollars [26]. ...
... Brain magnetic resonance imaging (MRI) has provided evidence of subclinical brain damage in asymptomatic subjects with comorbidities. Other more inexpensive and accessible biomarkers (clinical, imaging, molecular, and neurophysiological) have been explored with this objective, but studies are still inconclusive [20,21]. For this reason, the present investigation characterized CSVD in asymptomatic hypertensive patients and explored the relationship between CSVD and some indicators of subclinical vascular damage, as these indicators might be useful for screening hypertensive individuals, which are exposed to a higher risk of CVD, cognitive deterioration, and dementia. ...
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Background: Cerebral small vessel disease (CSVD) is frequent in patients with cardiovascular risk factors including arterial hypertension, and it is associated with vascular damage in other organs and the risk of stroke, cognitive impairment, and dementia. Early diagnosis of CSVD could prevent deleterious consequences. Objective: To characterize CSVD associated with indicators of subclinical vascular damage in asymptomatic hypertensive patients. Materials and Methods: Participants were hypertensive (HT) and non-hypertensive (non-HT) individuals; without signs of cerebrovascular disease, dementia, and chronic renal failure. For CSVD, white matter hyperintensities (WMH), enlarged Virchow–Robin perivascular spaces (EVRPS), lacunar infarcts, and microbleeds were investigated. Subclinical vascular damage was evaluated (hypertensive retinopathy, microalbuminuria, and extracranial carotid morphology: intima media thickness (IMT) and atheroma plaque). Results: CSVD MRI findings were more frequent in HT; as well as greater intimal thickening. The IMT + plaque was significantly associated with all MRI variables; but retinopathy was correlated with EVRPS and lacunar infarcts. Only microalbuminuria was related to the greater severity of WMH in HT. Multivariate analysis evidenced that CSVD was independently associated with the combination of indicators of vascular damage and systolic blood pressure. Conclusions: Combining indicators of subclinical vascular damage, such as carotid morphological variables, microalbuminuria, and hypertensive retinopathy for early detection of CSVD in asymptomatic hypertensive patients could prove to be useful to take actions for the prevention of irreversible brain damage, which could lead to cognitive impairment, dementia and stroke.
... Small vessel disease, such as silent lacunar infarcts, advanced deep white matter lesions and microbleeding, may lead to ischaemic and haemorrhagic stroke and vascular dementia in patients with hypertension. 33 In hypertensive patients, magnetic resonance imaging revealed the presence of silent cerebrovascular lesions in 44% of the patients, much more than cardiac (21%) and renal (26%) subclinical damage. 3 It has been suggested that microcirculation disorders and endothelial dysfunction may be a reason for impaired cognitive function in hypertensive patients. ...
... 35 Hypertension-induced lipohyalinosis and fibrinoid degeneration has also been found in white matter hyperintensities. 33 Role of nebivolol in reducing oxidative damage to brain Arterial hypertension may lead to brain damage. 35 Oxidative stress, inflammation and abnormalities in blood-brain barrier have been found to be underlying mechanisms for brain damage. ...
... 3,26 Active antihypertensive treatment significantly reduces vascular dementia in older patients with isolated systolic hypertension. 33,34 As nebivolol possesses significant antioxidant activity, its role in preventing cerebrovascular damage owing to ROS and inflammation may be postulated. In addition, nebivolol has also been shown to reduce arterial stiffness, which is a leading cause of vascular damage in the brain. ...
Article
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Hypertension is one of the leading risk factors for morbidity and mortality in patients with cardiovascular and cerebrovascular diseases and renal impairment. It also leads to target organ damage (TOD), which worsens organ function and the patient’s clinical status. Reactive oxygen species (ROS)-mediated oxidative stress may contribute significantly to TOD in patients with hypertension. NO (nitric oxide) is a paracrine factor derived from endothelial cells that has been shown to alleviate ROS-mediated oxidative damage. Nebivolol is a third-generation β-blocker with vasodilator activity, both actions contributing to decreased blood pressure in hypertensive patients. Its vasodilatory function is mediated by the endothelial l-arginine NO pathway. Nebivolol increases the bioavailability of NO in the vasculature. Its efficacy and safety profile is comparable to other commonly used antihypertensive agents. In this article, we review the current literature to understand TOD secondary to oxidative stress in patients with hypertension and the role of nebivolol in its prevention. A better understanding of the underlying mechanisms by which nebivolol reduces ROS-mediated TOD will not only help in the development of targeted therapies but may also improve health outcomes in hypertensive patients.
... [7] In one Cuban study of HT patients with a mean age of 44.2 years, classical silent brain lesions were detected in 40%; [17] while our group reported silent WML in 73.9% of an older cohort (mean age 59 years) of essential HT patients, [18] and more recently, classical silent MRI-detected brain lesions in 70.6% of essential HT patients. [19] In sum, WML frequency increases with age. ...
... Silent brain damage without cardiorenal impairment was observed in 11.5% (Figure 1). [19] Van Dijk demonstrated that systolic and diastolic blood pressure were positively associated with WML progression, in patients aged 60-90 years, new lesions occurring in up to 40% of patients. [20] This effect on brain lesion progression was stronger in younger patients and remained after adjusting for use of antihypertensive medications. ...
... Source: González-García, [19] ...
Article
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Arterial hypertension is the most prevalent non-communicable disease worldwide, and has long been recognized as a major risk factor for cardiovascular and cerebrovascular diseases. High blood pressure has deleterious consequences on the main target organs (heart, kidney, brain), and several studies have shown that brain damage is more frequent than heart and kidney involvement. Silent lesions can subsequently lead to cognitive decline, dementia or stroke. Nevertheless, screening for subclinical brain deterioration is rarely performed because it requires imaging techniques whose scarcity and high cost rule out routine use by primary care physicians. The challenge is thus early detection of asymptomatic brain lesions with cost-effective techniques to test thousands of patients in the community. In this review we present an update on the status of biomarkers explored as alternatives for early detection of brain damage in arterial hypertension, potentially useful to identify patients needing referrals for brain MRI: Ambulatory blood pressure monitoring, quantitative retinal microvascular assessment, quantitative electroencephalography, carotid ultrasonography, neurocognitive studies and blood-based biomarkers. We place special emphasis on blood-based biomarkers, for which our group reported the fi rst preliminary evidence of an association between serum neuron-specifi c enolase and severity of white matter lesions in patients with essential hypertension. This review consequently explores the potential for blood-based biomarkers to provide a faster, cheaper and more accessible early-detection solution, particularly benefi cial in resource-limited settings such as Cuba's.
... It has been reported to predispose the development of white matter hyperintensities (WMH), lacunar infarction and microbleeds which mostly occur silently [4]. Subclinical cerebrovascular damage has been reported to be more frequent in hypertensive subjects than cardiorrenal impairment [4][5][6][7][8]; nevertheless, evaluation of the consequences of HT on the heart and kidneys constitutes a routine procedure in clinical practice, while screening for nervous system involvement is difficult due to the low accessibility and high costs of brain magnetic resonance imaging (MRI), which is the gold standard for detecting silent brain damage [4,9]. Other alternative biomarkers which could be used for the early detection of asymptomatic lesions of the brain in essential hypertension have been explored [8,[10][11][12][13][14][15][16], but the ideal biomarker for screening at a community level still remains unavailable. ...
... Subclinical cerebrovascular damage has been reported to be more frequent in hypertensive subjects than cardiorrenal impairment [4][5][6][7][8]; nevertheless, evaluation of the consequences of HT on the heart and kidneys constitutes a routine procedure in clinical practice, while screening for nervous system involvement is difficult due to the low accessibility and high costs of brain magnetic resonance imaging (MRI), which is the gold standard for detecting silent brain damage [4,9]. Other alternative biomarkers which could be used for the early detection of asymptomatic lesions of the brain in essential hypertension have been explored [8,[10][11][12][13][14][15][16], but the ideal biomarker for screening at a community level still remains unavailable. ...
Article
The object of this work was to explore if blood based biomarkers of brain damage could predict subclinical brain lesions and clinical outcome during follow-up in asymptomatic hypertensive patients. This was a cross-sectional study including 101 patients with essential hypertension and no clinical evidence of neurological disease and 53 healthy controls, followed by a longitudinal study of 62 hypertensive patients for an average of 33 months. Serum concentrations of two brain specific proteins (S100B and neuron specific enolase - NSE) were determined at inclusion. Fundoscopic exploration, brain MRI and echocardiographic studies were also performed. Clinical outcome at follow-up was registered: transient ischemic attack (TIA), stroke, vascular headache or migraine, cardiovascular events and death. Higher serum NSE and S100B concentrations were observed in hypertensive patients; and multiple regression analysis revealed independent associations of clinical variables and more severe white matter lesions only with NSE concentration. A panel combining two clinical variables (blood pressure > 140/90 and years of hypertension > 10) and serum NSE > 13 μg/L predicted more severe white matter lesions with 80% sensitivity and 94.4% specificity. Higher NSE levels at inclusion were associated not only with the occurrence of vascular events related with the CNS (stroke, TIA and vascular headache), but also with an earlier presentation of these events during the follow-up period. Serum NSE concentration could be a useful biomarker to predict subclinical brain damage and future vascular events related with the CNS in hypertension. Blood based biomarkers could aid in filtering hypertensive patients with a higher risk of cerebrovascular disease for brain MRI scanning.
Chapter
Arterial hypertension is the most prevalent noncommunicable disease worldwide and has long been recognized as a major risk factor for stroke, cognitive decline, and dementia. The main goal for prevention is to identify high-risk patients, targeting the modifiable risk factors, and among these, hypertension is the most powerful one. Screening for subclinical brain deterioration is rarely performed because it requires very expensive and not widely available neuroimaging techniques. The main challenge is to detect asymptomatic brain lesions with noninvasive and cost-effective techniques that can be easily performed and interpreted for widespread screening in the community. In this chapter we present an update on the status of blood-based biomarkers explored as alternatives for early detection of brain damage in neurologically asymptomatic subjects (community studies, arterial hypertension, diabetes mellitus, and elderly individuals) and longitudinal studies to explore their value as long-term predictors of incident acute cerebrovascular events. This would undoubtedly have a very positive effect for primary stroke prevention. Numerous blood biomarkers have been investigated with very controversial results. Nevertheless, blood-based brain-specific biomarkers are beginning to stand out in this field and will probably be able to offer much more in the future for the detection of asymptomatic CSVD and in the long-term prediction of acute cerebrovascular events, due to the fact that they can more directly represent what is occurring in the brain.