Age-Related Clonal Haematopoiesis and Inflammation in Heart Failure
Research type
Research Study
Full title
Age-Related Clonal Haematopoiesis and Inflammation in Heart Failure: A Prospective Cohort Study.
IRAS ID
273979
Contact name
Ninian N Lang
Contact email
Sponsor organisation
NHS Greater Glasgow and Clyde
Duration of Study in the UK
2 years, 6 months, 5 days
Research summary
Research Summary
The prevalence of heart failure (HF) continues to grow and its incidence rises substantially with age. Heart failure with preserved ejection fraction (HFpEF) accounts for over half the cases of heart failure and is more common in elderly patients.
Age-related clonal haematopoiesis (ARCH) is the development of mutations in genes involved in blood cell production. These mutations have been found in people with heart failure and heart artery disease and seem to be associated with higher levels of inflammation (the body's response to injury or infection). Both HFpEF and heart failure with reduced ejection fraction (HFrEF) are associated with elevated levels of inflammation. We would like to understand more about how ARCH is involved with inflammation and heart failure. These mutations also carry a very slight increased risk of developing disorders of the blood, including blood cancer (0.5% per year).
The prevalence of ARCH in all comers with HF is unknown and, in particular, has not been examined in patients with HFpEF. The association of ARCH and the inflammatory basis to HF is unexplored. We will investigate the prevalence of ARCH and its association with inflammatory, cardiac and vascular phenotype in patients with HF and those with coronary artery disease without heart failure or left ventricular dysfunction. We will do this using routine clinical data, assessment of ARCH status. Half of the patients recruited will also undergo a series of non-invasive assessments of blood vessel function and potential markers of inflammation.
Summary of Results
Background:
Clonal haematopoiesis of indeterminate potential (CHIP) is the accumulation of gene changes that develop over time in blood stem cells. These changes have been associated with increased levels of inflammation. Having CHIP is associated with poor outcomes in patients with chronic heart failure whose heart does not pump adequately because of heart artery disease (after heart attack). How frequently CHIP is found in the broader HF population, including in patients with heart failure whose hearts still pump out a normal amount of blood (also known as heart failure with preserved ejection fraction [HFpEF] in contrast to heart failure with reduced ejection fraction [HFrEF]), is unknown. Because inflammation may be particularly relevant in the development of HFpEF we wanted to understand how many patients with HFpEF also have CHIP and to see whether this is also linked to greater evidence of inflammation in those patients. We wanted to compare these things in people with HFpEF against those in people with HFrEF.Purpose:
To evaluate the presence of CHIP and associated clinical characteristics in patients admitted to hospital with HFrEF and HFpEF.Methods
We looked at specific changes in genes found in blood stem cells from 96 patients admitted to hospital with heart failure. 48 had HFrEF and 48 had HFpEF. CHIP gene changes and the proportion of cells displaying these changes (known asvariant allele frequency [VAF]) were analysed. Consistent with current definitions, those with VAF ≥2% were considered to have CHIP. Associations with clinical characteristics and biomarkers were assessed.Results
CHIP driver mutations (VAF≥2%) were detected in 13 patients (13.5%). The proportion of patients with CHIP increased with age from 4% in people younger than 50years to 43% in those aged over 80years. The total number of CHIP gene changes observed also increased with age. Patients with CHIP were older (75.2 years versus 69.5 years). There were no differences in baseline blood counts (eg presence or absence of anaemia) in patients with and without CHIP. CHIP was associated with higher circulating levels of markers and mediators of inflammation kown as interleukin-18, transforming growth factor-beta-2 and intercellular adhesion molecule-1. CHIP was found more frequently in people with HFpEF compared to HFrEF. Eight patients with HFpEF (17%) and five patients with HFrEF (10%) had CHIP. HFpEF patients with CHIP, when compared to HFpEF patients without CHIP were older (80.1yrs versus 70.0yrs). In comparison, HFrEF patients with CHIP, when compared to those with HFrEF without CHIP were of similar age (71.1years versus 68.9 years). The presence of CHIP was not different between patients who had heart failure because of heart artery disease in comparison to patients with heart failure caused by other things.Conclusions
This is the first study to show that the development of specific gene changes in blood stem cells occur frequently in patients admitted to hospital with heart failure and are associated with higher levels of inflammation. Whether or not the identification of these changes can be used as a marker against which anti-inflammatory drugs can be directed for the treatment of HF (particularly HFpEF) remains to be tested.REC name
West of Scotland REC 4
REC reference
20/WS/0027
Date of REC Opinion
13 Feb 2020
REC opinion
Favourable Opinion