Cardiovascular Dysautonomia in older adults – Aetiology, Diagnosis and Health related consequences

Beskrivning

The hemodynamic homeostasis requires normal function of the cardiovascular, endocrine, and autonomic nervous systems. In cardiovascular dysautonomic states, the circulatory redistribution may lead to hypotension, thus compromising cerebral blood flow with symptoms such as blurred vision, fatigue, dizziness, and, in the most extreme cases, syncope. In classical reflex syncope, cardiovascular reflexes become transiently inappropriate while in orthostatic hypotension (OH) sympathetic efferent activity may be chronically impaired.
OH is a major manifestation of autonomic failure, and is a frequent finding in the older adults, with prevalence between 10 and 35%. The prevalence of OH increases with age and comorbidities, such as neurodegenerative, cardiovascular, metabolic and renal diseases. The presence of OH is associated with a significantly increased mortality and cardiovascular disease incidence. However, older adults who suffer unexplained syncope, presyncope or present with signs of chronic cardiovascular dysautonomia, OH and/or reflex syncope are often omitted in epidemiological and interventional studies.
The role of molecular biomarkers in the diagnosis of cardiovascular dysautonomia, OH and syncope is still debatable. Several plasma proteins, signal substances and neurohormones have been studied for their diagnostic utility in syncopal syndromes but more studies are required. The purinergic signaling system, including adenosine and adenosine triphosphate (ATP), has been recently proposed in the assessment of unexplained syncope without prodrome. According to previous studies, low plasma/adenosine level predisposes to paroxysmal AV?block and carotid sinus syndrome, whereas a high level of plasma?adenosine predisposes to hypotensive tendency and recurrent vasovagal syncope. In parallel, the adenosine/ATP provocation test has been performed to demonstrate adenosine hypersensitivity and paroxysmal cardioinhibitory propensity for selection of appropriate pacemaker candidates.
In summary, more studies on the association between cardiovascular dysautonomia and cardiovascular morbidity are needed, especially in regard to potential mechanisms linking OH with different manifestations of cardiovascular disease. Moreover, it should be remembered that therapeutic options in OH/cardiovascular dysautonomia are very limited and only a few pharmacological agents demonstrated significant but moderate effect above placebo in controlled studies.

AIMS
1) What are the characteristic features of older adults with cardiovascular dysautonomia/orthostatic hypotension?
2) How is the symptomatology of cardiovascular dysautonomia/orthostatic hypotension in older adults influenced by the diagnosis and implemented pharmacological/non?pharmacological treatment? What is the role of pacing in cardiovascular dysautonomia?
3) What is the prognostic impact of hospitalization due to syncope/orthostatic hypotension on future cardiovascular events in older adults?
4) What is the role of purinergic system in cardiovascular dysautonomia and unexplained syncope in older adults?

Subproject 1: Cardiovascular risk after hospitalisation for unexplained syncope and orthostatic hypotension.
Subproject 2: Pacing therapy in the management of unexplained syncope: a tertiary care centre prospective study.
Subproject 3: Cardiovascular autonomic dysfunction is the most common cause of syncope in paced patients.
Subproject 4: Role of implantable cardiac monitor in diagnosis of unexplained syncope. Pending project.

Period	2016 feb. 1 → 2022 mars 25
Examinerad/handledd person	Ekrem Yasa
Examination/handledning vid	Kardiovaskulär forskning - hypertoni
Omfattning	Internationell