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Lung disease puts patients at risk of developing heart conditions regardless of other risk factors

Trial in rare disease enables researchers to control for other factors and find underlying action for cardiovascular disease risk

22 March 2024
A stethoscope placed on top of an x ray of a chest cavity including lungs

Patients with lung disease are more likely to develop heart disease independent of any risk factors, according to new research.

A new study published in Orphanet Journal of Rare Diseases looked at patients who have a rare genetic condition called Alpha-1 antitrypsin deficiency (AATD) which causes lung disease similar to COPD independently of any risk factors such as smoking or age. More than 220 patients with AATD were recruited to the study alongside patients with COPD, and a control non lung disease population; and all were assessed for present cardiovascular disease (CVD) and recognised risk factors, including assessment of vascular stiffness known to increase risk for future events. Patients were then tracked for four years to see whether they developed CVD.

The patients with the rare genetic condition AATD had the highest adjusted scores among all participants for vascular stiffness, but had lowest scores for standard associated risk factors of CVD and nearly half (45%) of patients had discordant scores where one was high and other low.

....only looking at conventional factors such as age and smoking doesn’t give the full picture of the relationship between these two essential systems in the body

Professor Robert Stockley

Meanwhile, COPD and control participants had similar scores across the direct and indirect measures of CVD risk.

Furthermore, despite the AATD participants having lower risk factors associated with developing cardiovascular disease including being younger and a higher proportion who had never smoked, 12.7% of participants developed CVD after four years of follow-up.

Robert Stockley, Professor and Consultant in Acute and Respiratory Medicine at University of Birmingham and senior author of the paper said:

“This long-term study has enabled us to see the relationship between lung disease and heart disease in a unique way by following a group of patients with this rare genetic disease.

“Our study has shown that there is an increased risk for people with lung conditions of going on to develop cardiovascular conditions, and that only looking at conventional factors such as age and smoking doesn’t give the full picture of the relationship between these two essential systems in the body.”

Potential target for treatment

 

Participants also gave blood which was tested for an enzyme linked with lung damage in AATD patients.

There was a significantly higher levels of the enzyme Proteinase 3 in the AATD patients, but the study found that there was a link between elevated levels of the enzyme and vascular stiffness and hence CVD risk. The team believe that the Proteinase 3 enzyme may have a more direct impact on the development of heart and lung disease through the breakdown of fibres that support the large arteries and lungs, and that Proteinase 3 inhibitors could be a novel therapeutic to prevent cardiovascular disease especially in AATD patients.

Louise Crowley, Clinical Research Fellow and PhD researcher at the University of Birmingham and corresponding author of the paper said:

“The role of Proteinase 3 acts as a powerful link between lung and heart disease. The action that the enzyme has in attacking elastin fibres found in the lungs and major arteries suggests that inhibiting its action could have a dual effect to slow both lung and cardiovascular diseases.”

Notes for editors

  • For media enquiries please contact Tim Mayo, Press Office, University of Birmingham, tel: +44 (0)7815 607 157.

  • The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 8,000 international students from over 150 countries.
  • The University of Birmingham is a founding member of Birmingham Health Partners (BHP), a strategic alliance which transcends organisational boundaries to rapidly translate healthcare research findings into new diagnostics, drugs and devices for patients. Birmingham Health Partners is a strategic alliance between seven organisations who collaborate to bring healthcare innovations through to clinical application:
    • University of Birmingham
    • University Hospitals Birmingham NHS Foundation Trust
    • Birmingham Women's and Children's Hospitals NHS Foundation Trust
    • Aston University
    • The Royal Orthopaedic Hospital NHS Foundation Trust
    • Sandwell and West Birmingham Hospitals NHS Trust
    • West Midlands Academic Health Science Network
    • Birmingham and Solihull Mental Health NHS Foundation Trust
  • Sapey, E., Crowley, L.E., Edgar, R.G. et al.Cardiovascular disease in Alpha 1 antitrypsin deficiency: an observational study assessing the role of neutrophil proteinase activity and the suitability of validated screening tools. Orphanet J Rare Dis 19, 130 (2024). https://doi.org/10.1186/s13023-024-03124-x
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Featured staff

  • Professor Elizabeth Sapey

    Head of School of Medical Sciences

    Staff profile for Professor Elizabeth Sapey, Head of School of Medical Sciences and Consultant in Respiratory Medicine and General Internal Medicine, Department of Inflammation and Ageing, University of Birmingham.

    Phone: +44 (0)121 627 2000
    Email: e.sapey@bham.ac.uk

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