# Increased dipeptidyl peptidase 4 in patients with concomitant transthyretin cardiac amyloidosis and severe aortic stenosis

**Authors:** Margrethe Flesvig Holt, Annika E. Michelsen, August Flø, Kristoffer Russell, Jan Otto Beitnes, Sophie Foss Kløve, Anders Hodt, Lars Gullestad, Pål Aukrust, Einar Gude, Kaspar Broch, Thor Ueland

PMC · DOI: 10.1016/j.ijcha.2025.101820 · 2025-10-08

## TL;DR

This study found that higher levels of DPP4 in the blood may help identify patients with both aortic stenosis and ATTR-CM, and are linked to better heart function.

## Contribution

The study identifies DPP4 as a potential biomarker for detecting ATTR-CM in patients with severe aortic stenosis.

## Key findings

- DPP4 levels were significantly higher in patients with both ATTR-CM and aortic stenosis compared to those with only aortic stenosis or healthy controls.
- Lower DPP4 levels were associated with worse heart function and more severe aortic stenosis symptoms.
- High DPP4 levels were linked to better cardiac function in all aortic stenosis patients, regardless of ATTR-CM status.

## Abstract

Due to overlapping symptoms and signs, it can be challenging to diagnose transthyretin amyloid cardiomyopathy (ATTR-CM) in the setting of concomitant aortic stenosis. Biomarkers may discriminate between heart failure with ATTR-CM and heart failure without ATTR-CM, but it is not known if these markers can differentiate between AS with and AS without concomitant ATTR-CM.

In 9 patients with ATTR-CM and AS, 161 patients with lone AS, and 23 healthy controls, we measured 8 plasma proteins previously identified by proteomic analysis as potential candidates for diagnosing ATTR-CM. We assessed differences between groups and association with indices of heart failure and AS severity.

Plasma levels of dipeptidyl peptidase 4 (DPP4) were significantly higher in patients with AS and ATTR-CM than in patients with lone AS and in healthy controls. Lower levels of DPP4 were also associated with worse left ventricular function, higher New York Heart Association functional class, and low-flow, low-gradient aortic stenosis.

Our findings suggest that DPP4 may be a marker of ATTR-CM in patients with severe AS. In all AS patients, those with and without coexisting ATTR-CM, high DPP4 levels were asociated with better cardiac function.

## Linked entities

- **Proteins:** DPP4 (dipeptidyl peptidase 4)
- **Diseases:** aortic stenosis (MONDO:0042981), heart failure (MONDO:0005252)

## Full-text entities

- **Genes:** TTR (transthyretin) [NCBI Gene 7276] {aka AMYLD1, ATTR, CTS, CTS1, HEL111, HsT2651}, DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}
- **Diseases:** cardiac amyloidosis (MESH:D000686), heart failure (MESH:D006333), aortic stenosis (MESH:D001024), transthyretin amyloid cardiomyopathy (MESH:C567782)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12546798/full.md

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Source: https://tomesphere.com/paper/PMC12546798