Understanding the new tool that found COPD among key cardiovascular disease risk factors

Professor Mona Bafadhel tells Katherine Price about developing a new tool that has identified less obvious yet crucial cardiovascular disease risk indicators such as chronic obstructive pulmonary disease. She hopes the tool will impact health inequalities by better predicting at-risk individuals and ensuring previously under-detected populations can access preventative therapies.

Professor Mona Bafadhel is the chair of respiratory medicine at King’s College London and director of the King’s Centre for Lung Health. Her work on chronic obstructive pulmonary disease (COPD) has recently led to her working with colleagues across King’s College London and the Universities of Oxford, Nottingham, Bristol and Edinburgh to support the development of a new cardiovascular disease(CVD) predictive calculator.

COPD is the third leading cause of death worldwide, causing more than three million deaths in 2019. Nearly 90% of deaths in patients under the age of 70 occur in low- and middle-income countries, and it’s estimated that in the UK, at least 4.9% of people over the age of 40 have COPD. By 2050, it’s predicted that global COPD prevalence will approach 600 million cases and become the leading cause of death globally. ‘[This] is an important group of patients,’ stresses Professor Bafadhel.

Establishing the link between COPD and CVD risk

Among COPD patients, cause of death is often CVD, Professor Bafadhel explains. She and colleague Dr Richard Russell, head of department of the Peter Gorer Department of Immunobiology, were aware of the association between COPD and CVD based on their clinical experience and an increasing body of evidence. However, they wanted to understand more about the link between the two.

CVD is also a leading cause of death globally, responsible for an estimated 17.9 million deaths in 2019. Research into risk factors is abundant, but the tools available in clinical practice to score cardiovascular risk were unable to offer much insight into the CVD risk in a patient with COPD.

‘Indeed, it appears that current risk tools were underestimating the actual cardiovascular risk associated with patients with COPD,’ adds Professor Bafadhel.

The duo liaised with Professor Julia Hippisley-Cox from the University of Oxford and Carol Coupland from the University of Nottingham and others, who designed three iterations of QRISK – the CVD risk score that has been used across the NHS since 2009. It involves measuring patients’ blood pressure, age and medical history to identify those at high risk of developing CVD.

However, even QRISK3 does not capture several conditions that have recently been associated with increased CVD risk, including COPD, meaning it will potentially underestimate risk in these groups, who may subsequently not be offered beneficial interventions.

The new research, utilising several UK primary care databases to assess a cohort of more than 16.5 million UK citizens for derivation and validation of the algorithm, led to the development of QRISK4 or QR4, which showed that COPD was indeed a risk factor. In fact, QR4 outperformed three widely used international CVD scoring models, including QR3, due to the size and validity of the data, accurately identifying more high-risk patients.

‘The accuracy required has to be very vigorous with regard to validation tools and replication models,’ explains Professor Bafadhel. ‘It took a rigorous amount of work as standard because my collaborators Julia and Carol have experience of getting this into patient practice with QRISKs 1, 2 and 3, so we were guided and as sure as we can be that we were doing it even more rigorously for QR4.’

Addressing health inequalities

Like QR3, QR4 – if approved – would be a free-to-access web platform into which clinicians can enter details about patient health to generate a percentage risk of them developing CVD in 10 years’ time. Thresholds are also offered to inform clinicians as to when preventative treatment should be offered.

The difference is the inclusion of seven new risk factors. In addition to COPD, this includes learning disabilities, Down syndrome, four cancer types (blood, lung, oral and brain), pre-eclampsia and postnatal depression. While risk factors such as smoking and high cholesterol are well-recognised, this latest research identifies less obvious yet crucial risk indicators and highlights how other significant conditions impact on heart health.

Not only was an increased risk of severe cardiovascular events in patients with COPD identified, but the greatest effect was seen in females – a surprise for Professor Bafadhel.

Evidence previously suggested that COPD most commonly affected men, but more women appear to have COPD than first thought. What’s more, ‘it’s clear actually that women [with COPD] have more susceptibility to cardiovascular risk,’ Professor Bafadhel says, stressing that clinicians need to consider COPD as a diagnosis and confirm it with spirometry, especially in women, to mitigate these cardiovascular risks.

The risk was also highest in younger patients with COPD, which, for Professor Bafadhel, was another sign that conditions such as COPD need to be diagnosed earlier.

Optimising therapies and reducing risk

Ultimately, the research underlines the importance of prescribing therapies that reduce CVD risk, including optimising inhaled therapies, to reduce mortality.

By integrating these seven risk factors into the QR4 model, the researchers were able to develop a more nuanced and comprehensive tool for predicting CVD, ensuring preventative strategies are more personalised, inclusive and cater to the needs of a broader and more diverse population. It also provides clinicians with the clearest picture yet of individuals’ risk of developing heart and circulatory diseases.

Although the QR4 is based on UK population data, Professor Bafadhel hopes that other countries can use the research and their own population data to assess their own algorithms and tools. For countries with fewer resources, she says available tools can be used, mindful that the data may not be population relevant.

The hope is that, by providing a more accurate CVD risk estimation, QR4 should lead to significant improvements in health outcomes, particularly among populations whose risk may have previously been under-detected. If implemented, it is estimated that optimising the care of COPD patients would save more than 2,500 lives a year in the UK and promote earlier recognition of both COPD and the associated cardiovascular risk.

Driving awareness of COPD

Professor Bafadhel argues the most important impact of this research would be driving awareness of the interlinked risks of CVD and COPD across the multidisciplinary field, and of how that risk can be modified.

‘We just haven’t had enough investment and funding in [COPD]. People may not know what it is until it’s too late. We really do need to improve the global awareness of it,’ she says.

‘We need to diagnose COPD earlier and be familiar with what COPD is. We need to optimise COPD treatments, including all the available tools we have. And then we need to try and understand what causes that very close association to cardiovascular disease, and of course exacerbations.’

She also highlights the importance of preventing CVD, catastrophic events and deaths by optimising COPD pharmacological treatment as well as primary prevention.

The researchers anticipate that QR4 will supersede QR3, although there is currently no timeline for this. Nevertheless, the next five years are expected to be an exciting time in the COPD field that will further shape understanding of this debilitating condition, according to Professor Bafadhel.

While she and her colleagues are looking at platelets in patients with COPD, other multidisciplinary groups are investigating pulmonary lung-heart events in this group – research Professor Bafadhel hopes will reduce inequalities, raise standards and empower patients to ensure they get the best treatment they need, when they need it.

‘Gone are the days where we think we can’t do anything for a person with COPD,’ she says. ‘We now have multiple tools, from physiotherapy to inhaled treatments, to non-invasive and invasive surgery, and in the next few months, hopefully also biologics in COPD.’