The association between fibrotic diseases and treatment resistant hypertension in England
Authors: Massen G M , Stone P W , Jenkins R G , Allen R J , Wain L V , Stewart I , Tayal U , Quint J K ,   DEMISTIFI consortium, Thorley Andrew , Duckworth Anna , Mohammadi-Nejad Ali-Reza , Aravinthan Aloysious , Harbottle Anthony , Mendez Villalon Armando , Scotton Chris , Denton Christopher , Lea Daniel , Auer Dorothee , Joof Ebrima , Cox Eleanor , Eves Elizabeth , Robertson Elizabeth , Blamont Emma , Khan Fasihul , Parcesepe Gina , Moran Gordon , Aithal Guruprasad , Longhurst Hilary , Stewart Iain , Paxton Jane , Quint Jennifer , Piper Hanley Karen , Frost Kate , Casmino Leo , Chakrabarti Lisa , Wain Louise , Roeth Margot , Kaisar Maria , Craig Martin , Nation Michael , Alireza Kisomi Mohammad , Zeybel Mujdat , Guha Neil , Selby Nicholas , Oliver Nick , Selby Nick , Leavy Olivia C , Gowland Penny , Quinlan Philip , Chambers Rachel , Allen Richard , Hubbard Richard , Slack Rob , Ploeg Rutger , Moss Sam , Fawaz Sara , Turner Scott , Quammie Shauntelle , Johnson Simon , Sotiropoulos Stamatios N , Astbury Stuart , Francis Susan , Giles Tom , Quinn Valerie , Adams Wendy , Chen Xin , Gong Zhendi 
Published: February 2025

Abstract

Background
Multimorbidity has been identified as a research priority in recent years, fibrosis (progressive organ scarring) is one mechanism which may underpin multimorbidity. Some studies suggest hypertension could be fibrotic, particularly severe hypertension (uncontrollable with medications), however it is not currently known whether severe hypertension is associated with fibrotic conditions.

Objective
To investigate whether treatment resistant hypertension is associated with fibrotic conditions.

Methods
We used the Clinical Practice Research Datalink (CPRD) Aurum primary care database to define a cohort of people with hypertension during 2015. We determined the percentage of people who had conditions with fibrotic manifestations and explored differences respective to hypertension control. We applied multivariable logistic regression to analyse associations (p&lt;0.001) between hypertension control and each fibrotic condition respectively.

Results
Of 1,340,495 people with hypertension during 2015, 83.50% (n=1,119,333) had managed hypertension either by lifestyle or medication; 16.50% (n=221,162) had treatment resistant hypertension. Fibrotic conditions were more common ((75.40% (95%CI: 75.20-75.60) vs. 68.90% (95%CI: 68.81-70.01)) in people with treatment resistant hypertension compared with those with managed hypertension. We found that treatment resistant hypertension was associated with; cardiomyopathy (ORadj:1.85, 95%CI:1.81-1.90), both type 1 and type 2 diabetes (ORadj:1.49,95%CI:1.44-1.55, ORadj:1.61,95%CI:1.60-1.63, respectively), liver fibrosis (ORadj:1.52, 95%CI: 1.46-1.58), valve fibrosis (ORadj:1.41, 95%CI:1.37-1.44) and urinary fibrosis (ORadj:1.41,95%CI:1.36-1.47).

Conclusion
The proportion of people with fibrotic conditions was greater in those with treatment resistant hypertension than managed hypertension. The identified associations between treatment resistant hypertension and fibrotic conditions may point to common disease pathways which should be further explored to understand shared mechanisms.