Fibrin Clot Properties and Fibrinolysis in Patients With Endocrine Hypertension Due to Aldosterone or Catecholamines Excess

Ewa Warchoł-Celińska; Aleksander Prejbisz; Piotr Dobrowolski; Ewa Wypasek; Jacek Kądziela; Sylwia Kołodziejczyk-Kruk; Marek Kabat; Anetta Undas; Andrzej Januszewicz

Disclosures

Clin Endocrinol. 2022;96(2):114-122. 

In This Article

Abstract and Introduction

Abstract

Objective: The aim of the study was to investigate a new possible background of increased risk of cardiovascular events in two forms of endocrine hypertension: in primary aldosteronism (PA) and pheochromocytoma/paraganglioma (PPGL) in comparison to essential hypertension (EHT).

Context: Prothrombotic properties of the fibrin clot structure, impaired fibrinolysis and enhanced thrombin generation have been reported to be associated with increased cardiovascular risk.

Design: Patients with PA and PPGL were evaluated at baseline and re-evaluated 3 months after causative treatment. At baseline PA and PPGL patients were compared to matched EHT patients and to healthy controls.

Patients: The study included 35 patients with PA, 16 patients with PPGL and two reference groups of patients with EHT (32 and 22 patients) and healthy controls (35 and 23 subjects).

Measurements: All subjects underwent evaluation according to the study protocol that included plasma fibrin clot permeability (Ks), clot lysis time, endogenous thrombin potential.

Results: There were no differences in clot structure and fibrinolytic activity in PA and PPGL patients as compared to matched patients with EHT, whereas all hypertensive groups were characterized by more compact fibrin clot structure, faster clot formation and enhanced thrombin generation in comparison to healthy controls. Both in PA and PPGL patients, fibrin clot properties and fibrinolytic parameters remained stable after the causative treatment.

Conclusions: Patients with PA and PPGL are at a prothrombic state comparable to patients with EHT. The results suggest the higher risk of cardiovascular events observed in hypertensive PA and PPGL as compared to EHT is not mediated through investigated prothrombic mechanisms.

Introduction

Primary aldosteronism (PA) is one of the most common forms of secondary hypertension caused by excessive secretion of aldosterone. The detrimental effects of aldosterone on the cardiovascular system were demonstrated in numerous studies conducted over recent years.[1,2] Pheochromocytoma and paraganglioma (PPGL) are neuroendocrine tumours, producing excessive amounts of catecholamines, leading to characteristic clinical signs and symptoms and increased cardiovascular morbidity and mortality.[3,4]

The fibrin clot is a spatial structure formed at the last stage of blood coagulation. Prothrombotic properties of the fibrin clot structure in combination with impaired fibrinolysis and enhanced thrombin generation have been reported to be associated with increased cardiovascular risk and progression of cardiovascular disease with its thromboembolic manifestations.[5,6] The formation of more compact fibrin clots with impaired enzymatic degradation have been reported in patients with coronary heart disease, including those with hypertension, previous myocardial infarction (MI), ischaemic stroke and atrial fibrillation (AF). It has been also observed that the unfavourably altered fibrin clot phenotype is a predictor of recurrent venous thromboembolism.[6–11]

Both patients with PPGL and with PA are at high risk for cardiovascular events and experience more cardiovascular events, which might be associated with altered fibrin clot structure (stroke, MI, AF in PA patients and MI in PPGL patients) than patients with essential hypertension (EHT) independently of blood pressure (BP).[1,2,4,5,12] It is also of note that after a causative treatment, both in patients with PA and PPGL, cardiovascular risk is comparable to the one observed in patients with EHT, therefore its increase is transient.[1,2,5]

To the best of our knowledge, there have been no published studies on the phenotype of a fibrin clot and its determinants in patients with PA and PPGL. Therefore, we investigated a new possible background of increased risk of cardiovascular events in PA and PPGL patients as compared to patients with EHT by evaluating plasma fibrin clot properties in hypertensive patients with PA and PPGL.

The aims of the study were: (1) to evaluate whether excessive catecholamine secretion may affect plasma fibrin clot characteristics, thrombin generation and fibrinolytic activity and inflammation, whereas normalisation of plasma catecholamine concentrations may alter fibrin clot parameters, blood clotting markers and fibrinolysis and (2) to assess if elevated plasma aldosterone concentration may affect the coagulation system and if the causative treatment (the surgical removal of the aldosterone-producing adenoma [APA] or pharmacological aldosterone receptor blockade in patients with bilateral hypertrophy [BAH]) can affect fibrin clot structure and fibrinolysis.

processing....