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Clinical Autonomic Research : Official... Aug 2023
Topics: Humans; Hypertension; Autonomic Nervous System Diseases; Hypotension, Orthostatic; Blood Pressure
PubMed: 37389705
DOI: 10.1007/s10286-023-00961-x -
Hypertension (Dallas, Tex. : 1979) Oct 2023The prognostic role and the clinical significance of orthostatic hypertension (OHT) remained undefined for long because data were sparse and often inconsistent. In... (Review)
Review
The prognostic role and the clinical significance of orthostatic hypertension (OHT) remained undefined for long because data were sparse and often inconsistent. In recent years, evidence has been accumulating that OHT is associated with an increased risk of masked and sustained hypertension, hypertension-mediated organ damage, cardiovascular disease, and mortality. Most evidence came from studies in which OHT was defined using systolic blood pressure (BP) whereas the clinical relevance of diastolic OHT is still unclear. Recently, the American Autonomic Society and the Japanese Society of Hypertension defined OHT as an orthostatic systolic BP increase ≥20 mm Hg associated with a systolic BP of at least 140 mm Hg while standing. However, also smaller orthostatic BP increases have shown clinical relevance especially in people ≤45 years of age. A possible limitation of the BP response to standing is poor reproducibility. OHT concordance is better when the between-assessment interval is shorter, when OHT is evaluated using a larger number of BP readings, and if home BP measurement is used. The pathogenetic mechanisms leading to OHT are still controversial and may vary according to age. Excessive neurohumoral activation seems to be the main determinant in younger adults whereas vascular stiffness plays a more important role in older individuals. Conditions associated with higher activity of the sympathetic nervous system and/or baroreflex dysregulation, such as diabetes, essential hypertension, and aging have been found to be often associated with OHT. Measurement of orthostatic BP should be included in routine clinical practice especially in people with high-normal BP.
Topics: Adult; Humans; Aged; Reproducibility of Results; Hypertension; Blood Pressure; Blood Pressure Determination; Cardiovascular Diseases; Hypotension, Orthostatic
PubMed: 37417253
DOI: 10.1161/HYPERTENSIONAHA.123.21537 -
Frontiers in Neurology 2023Headache is a frequent symptom among patients with hypermobility spectrum disorders. This mini review focuses specifically on a challenging aspect of headache evaluation... (Review)
Review
Headache is a frequent symptom among patients with hypermobility spectrum disorders. This mini review focuses specifically on a challenging aspect of headache evaluation in all patients, but especially those with hypermobility - the orthostatic headache. While the differential for an orthostatic headache is overall limited, patients with hypermobility disorders have risk factors for all of the most commonly encountered orthostatic headache disorders. The most common conditions to produce orthostatic headaches are discussed - spontaneous intracranial hypotension, cervicogenic headache, and postural orthostatic tachycardia syndrome. Less common etiologies of orthostatic headache pertinent to any patient are presented in table format.
PubMed: 38162438
DOI: 10.3389/fneur.2023.1321350 -
Cerebellum (London, England) Oct 2023Multiple system atrophy (MSA) is a rare, adult-onset, progressive neurodegenerative disorder with major diagnostic challenges. Aiming for a better diagnostic accuracy... (Review)
Review
Multiple system atrophy (MSA) is a rare, adult-onset, progressive neurodegenerative disorder with major diagnostic challenges. Aiming for a better diagnostic accuracy particularly at early disease stages, novel Movement Disorder Society criteria for the diagnosis of MSA (MDS MSA criteria) have been recently developed. They introduce a neuropathologically established MSA category and three levels of clinical diagnostic certainty including clinically established MSA, clinically probable MSA, and the research category of possible prodromal MSA. The diagnosis of clinically established and clinically probable MSA is based on the presence of cardiovascular or urological autonomic failure, parkinsonism (poorly L-Dopa-responsive for the diagnosis of clinically established MSA), and cerebellar syndrome. These core clinical features need to be associated with supportive motor and non-motor features (MSA red flags) and absence of any exclusion criteria. Characteristic brain MRI markers are required for a diagnosis of clinically established MSA. A research category of possible prodromal MSA is devised to capture patients manifesting with autonomic failure or REM sleep behavior disorder and only mild motor signs at the earliest disease stage. There is a number of promising laboratory markers for MSA that may help increase the overall clinical diagnostic accuracy. In this review, we will discuss the core and supportive clinical features for a diagnosis of MSA in light of the new MDS MSA criteria, which laboratory tools may assist in the clinical diagnosis and which major differential diagnostic challenges should be borne in mind.
Topics: Adult; Humans; Multiple System Atrophy; Diagnosis, Differential; Parkinsonian Disorders; Magnetic Resonance Imaging; Levodopa
PubMed: 35986227
DOI: 10.1007/s12311-022-01453-w -
Journal of Clinical Medicine Jan 2024Syncope is a highly prevalent clinical condition characterized by a rapid, complete, and brief loss of consciousness, followed by full recovery caused by cerebral... (Review)
Review
Syncope is a highly prevalent clinical condition characterized by a rapid, complete, and brief loss of consciousness, followed by full recovery caused by cerebral hypoperfusion. This symptom carries significance, as its potential underlying causes may involve the heart, blood pressure, or brain, leading to a spectrum of consequences, from sudden death to compromised quality of life. Various factors contribute to syncope, and adhering to a precise diagnostic pathway can enhance diagnostic accuracy and treatment effectiveness. A standardized initial assessment, risk stratification, and appropriate test identification facilitate determining the underlying cause in the majority of cases. New technologies, including artificial intelligence and smart devices, may have the potential to reshape syncope management into a proactive, personalized, and data-centric model, ultimately enhancing patient outcomes and quality of life. This review addresses key aspects of syncope management, including pathogenesis, current diagnostic testing options, treatments, and considerations in the geriatric population.
PubMed: 38337421
DOI: 10.3390/jcm13030727 -
Hypertension (Dallas, Tex. : 1979) Nov 2023Management of orthostatic hypotension (OH) prioritizes prevention of standing hypotension, sometimes at the expense of supine hypertension. It is unclear whether supine...
BACKGROUND
Management of orthostatic hypotension (OH) prioritizes prevention of standing hypotension, sometimes at the expense of supine hypertension. It is unclear whether supine hypertension is associated with adverse outcomes relative to standing hypotension.
OBJECTIVES
To compare the long-term clinical consequences of supine hypertension and standing hypotension among middle-aged adults with and without OH.
METHODS
The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure (BP) in adults aged 45 to 64 years, without neurogenic OH, between 1987 and 1989. We defined OH as a positional drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg, supine hypertension as supine BP≥140/≥90 mm Hg, and standing hypotension as standing BP≤105/≤65 mm Hg. Participants were followed for >30 years. We used Cox regression models to examine associations with cardiovascular disease events, all-cause mortality, falls, and syncope.
RESULTS
Of 12 489 participants (55% female, 26% Black, mean age 54 years, SD 6), 4.4% had OH. Among those without OH (N=11 943), 19% had supine hypertension and 21% had standing hypotension, while among those with OH (N=546), 58% had supine hypertension and 38% had standing hypotension. Associations with outcomes did not differ by OH status (-interactions >0.25). Supine hypertension was associated with heart failure (hazard ratio, 1.83 [95% CI, 1.68-1.99]), falls (hazard ratio, 1.12 [95% CI, 1.02-1.22]), and all-cause mortality (hazard ratio, 1.45 [95% CI, 1.37-1.54]), while standing hypotension was only significantly associated with mortality (hazard ratio, 1.06 [95% CI, 1.00-1.14]).
CONCLUSIONS
Supine hypertension was associated with higher risk of adverse events than standing hypotension, regardless of OH status. This challenges conventional OH management, which prioritizes standing hypotension over supine hypertension.
Topics: Middle Aged; Humans; Adult; Female; Male; Hypertension; Cardiovascular Diseases; Blood Pressure; Hypotension, Orthostatic; Blood Pressure Determination
PubMed: 37646155
DOI: 10.1161/HYPERTENSIONAHA.123.21215 -
Europace : European Pacing,... Mar 2024The term non-cardiac syncope includes all forms of syncope, in which primary intrinsic cardiac mechanism and non-syncopal transient loss of consciousness can be ruled...
The term non-cardiac syncope includes all forms of syncope, in which primary intrinsic cardiac mechanism and non-syncopal transient loss of consciousness can be ruled out. Reflex syncope and orthostatic hypotension are the most frequent aetiologies of non-cardiac syncope. As no specific therapy is effective for all types of non-cardiac syncope, identifying the underlying haemodynamic mechanism is the essential prerequisite for an effective personalized therapy and prevention of syncope recurrences. Indeed, choice of appropriate therapy and its efficacy are largely determined by the syncope mechanism rather than its aetiology and clinical presentation. The two main haemodynamic phenomena leading to non-cardiac syncope include either profound hypotension or extrinsic asystole/pronounced bradycardia, corresponding to two different haemodynamic syncope phenotypes, the hypotensive and bradycardic phenotypes. The choice of therapy-aimed at counteracting hypotension or bradycardia-depends on the given phenotype. Discontinuation of blood pressure-lowering drugs, elastic garments, and blood pressure-elevating agents such as fludrocortisone and midodrine are the most effective therapies in patients with hypotensive phenotype. Cardiac pacing, cardioneuroablation, and drugs preventing bradycardia such as theophylline are the most effective therapies in patients with bradycardic phenotype of extrinsic cause.
Topics: Humans; Bradycardia; Syncope; Syncope, Vasovagal; Hypotension; Hypotension, Orthostatic
PubMed: 38529800
DOI: 10.1093/europace/euae073 -
International Journal of Molecular... Sep 2023Neurological disorders represent a global health problem. Current pharmacological treatments often lead to short-term symptomatic relief but have dose-dependent side... (Review)
Review
Neurological disorders represent a global health problem. Current pharmacological treatments often lead to short-term symptomatic relief but have dose-dependent side effects, such as inducing orthostatic arterial hypotension due to the blockade of alpha receptors, cardiotoxic effects due to impaired repolarization, and atrioventricular block and tachycardia, including ventricular fibrillation. These challenges have driven the medical community to seek effective treatments for this serious global health threat. Mesenchymal stem cells (MSCs) are pluripotent cells with anti-inflammatory, anti-apoptotic, and immunomodulatory properties, providing a promising alternative due to their ability to differentiate, favorable culture conditions, in vitro manipulation ability, and robust properties. Although MSCs themselves rarely differentiate into neurons at the site of injury after transplantation in vivo, paracrine factors secreted by MSCs can create environmental conditions for cell-to-cell communication and have shown therapeutic effects. Recent studies have shown that the pleiotropic effects of MSCs, particularly their immunomodulatory potential, can be attributed primarily to these paracrine factors. Exosomes derived from MSCs are known to play an important role in these effects. Many studies have evaluated the potential of exosome-based therapies for the treatment of various neurological diseases. In addition to exosomes, various miRNAs derived from MSCs have been identified to regulate genes and alleviate neuropathological changes in neurodegenerative diseases. This review explores the burgeoning field of exosome-based therapies, focusing on the effects of MSC-derived exosomes and exosomal miRNAs, and summarizes recent findings that shed light on the potential of exosomes in the treatment of neurological disorders. The insights gained from this review may pave the way for innovative and effective treatments for these complex conditions. Furthermore, we suggest the therapeutic effects of exosomes and exosomal miRNAs from MSCs, which have a rescue potential in spinal cord injury via diverse signaling pathways.
Topics: Humans; Exosomes; Stem Cells; Spinal Cord Injuries; Mesenchymal Stem Cells; Biological Transport
PubMed: 37762150
DOI: 10.3390/ijms241813849 -
NPJ Parkinson's Disease Oct 2023It remains unclear which adjunctive drug for Parkinson's disease (PD) in combination with levodopa is more effective, tolerable, and safe. We aimed to compare the...
It remains unclear which adjunctive drug for Parkinson's disease (PD) in combination with levodopa is more effective, tolerable, and safe. We aimed to compare the efficacy, tolerability, and safety among anti-PD drugs from several classes in patients with fluctuating PD who received levodopa through network meta-analysis (NMA). Twelve anti-PD drugs belonging to 4 different drug classes (dopamine agonists, monoamine oxidase type B inhibitors, catechol-O-methyl transferase inhibitors, and an adenosine A2A receptor antagonist) were selected. We systematically searched PubMed, Embase, and the Cochrane Library for eligible randomized controlled trials (RCTs) comparing placebo with anti-PD drug or among anti-PD drugs in patients with PD who experienced motor fluctuations or wearing-off and received levodopa. We included 54 RCTs in the analysis. The NMA was performed under a frequentist framework using a random-effects model. The efficacy outcome was change in daily off-time, and the tolerability outcome was discontinuation due to all causes. Safety outcomes included discontinuation due to adverse events (AEs) and the incidence of AEs, dyskinesia, hallucination, and orthostatic hypotension. According to the surface under the cumulative ranking curve (SUCRA) in the NMA, ropinirole transdermal patch (SUCRA, 0.861) ranked the highest in efficacy, followed by pramipexole (0.762), ropinirole extended release (ER) (0.750), and safinamide (0.691). In terms of tolerability, ropinirole (0.954) ranked the highest, followed by pramipexole (0.857), safinamide (0.717), and ropinirole ER (0.708). Each anti-PD drug had different SUCRA ranking profiles for the safety outcomes. These findings suggest that ropinirole, pramipexole, and safinamide are well-balanced anti-PD drugs that satisfy both efficacy and tolerability outcomes.
PubMed: 37853009
DOI: 10.1038/s41531-023-00589-8