Postural Orthostatic Tachycardia Syndrome – The Role of Cardiovascular Dysautonomia and Inflammation

Beskrivning

Background
Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic autonomic nervous system dysfunction affecting predominantly younger females of childbearing years with great impact on life quality. In developed countries, the prevalence of POTS has been estimated at 0.2 - 1.0%. Various pathophysiological pathways are believed to interact causing great symptom diversity, prompting mandatory further exploration.

Aims and methods
Project I: The aim was to explore and compare clinical and neuroendocrine characteristics in patients among those presenting with orthostatic intolerance (orthostatic hypotension, OH, vasovagal syncope, VVS and POTS). Patients underwent head-up tilt (HUT) for autonomic testing, answered a questionnaire for symptom evaluation and had blood samples.
Project II and III: The aim was to discover biomarker footprints related to POTS using an antibody-based proteomics technique, Olink, measuring simultaneously 57 inflammatory and respectively 92 cardiovascular biomarkers. Three-hundred-and-ninety-six POTS patients were included. Project IV: The aim was to develop a novel, questionnaire -based symptom scoring system, Malmö POTS Score (MAPS), including 12 most prevalent symptoms experienced by patients with POTS. Scores in 62 POTS patients were compared with 50 healthy individuals and symptom burden related to haemodynamic changes during HUT.
Project V: The aim was to investigate the renin-angiotensin-aldosterone system (RAAS) in POTS patients compared with healthy controls without orthostatic intolerance symptoms. All participants performed active standing test for autonomic testing and blood sampling after 10 minutes supine rest.

Results
Project I: Patients with POTS were more often younger females and had higher HR during passive HUT compared with other groups, orthostatic intolerance, and negative HUT. A significant rise in norepinephrine (NE) was observed in POTS and lower resting MR-proANP in relation to VVS and OH but not to negative HUT.
Project II: Patients with POTS were predominantly females with lower BMI. Maximum HR was significantly higher compared with negative HUT patients. Proconvertase Furin, a protein that promotes proteolytic maturation of other proproteins was downregulated in POTS but not in healthy individuals.
Project III: Higher levels of growth hormone in females with POTS were observed whereas males with POTS have decreased plasma myoglobin levels compared with healthy controls.
Project IV: POTS patients reported a 5-fold higher symptom burden on MAPS score compared with controls (mean; 78±20 vs. 14±12, p<0.001). Correlation between total MAPS score and haemodynamic changes was observed in both groups though more prominent in POTS. Project V: Renin activity was decreased in POTS patients but not in healthy controls. Aldosterone levels were intact in both groups. There was an inverse correlation between renin activity and blood pressure in controls but absent in POTS patients.

Conclusions
Patients with POTS were predominantly younger females with maximal standing heart rate on average above 110 bpm during orthostatic provocation. Abnormal neuroendocrine and enzymatic responses in POTS patients were found potentially explaining symptoms experienced during orthostasis and confirming inflammatory involvement. Finally, POTS patients had significantly higher symptom scores in the newly developed questionnaire MAPS confirming their great burden of symptoms affecting life quality and offering simpler clinical diagnosis.

Period	2016 apr. 1 → 2022 nov. 18
Examinerad/handledd person
Examination/handledning vid	Kardiovaskulär forskning - hypertoni
Omfattning	Internationell