A new study led by researchers at King's College London, in collaboration with the University of Nottingham, suggests that chronic inflammation may link frailty, social disadvantage and increased cardiovascular disease (CVD) risk.
The findings, published in Communications Medicine, could help to guide more targeted strategies to reduce CVD risk in vulnerable populations.
Frailty is a clinical condition associated with ageing, characterised by a decline in the body's ability to maintain stability and recover from physical or medical stress. It is known to increase vulnerability to a wide range of health problems, including heart disease. CVD remains a leading cause of death worldwide, and previous studies have shown that people who are frail or who live in more disadvantaged areas are more likely to experience poor cardiovascular outcomes. However, the biological mechanisms behind these links have remained poorly understood.
Inflammation is a key biological process in ageing and the development of age-related diseases. Persistent, low-grade inflammation that increases with age - known as 'inflammaging' - has been linked to increased frailty and higher levels of social deprivation. To understand this link, researchers looked at 74 inflammation-related proteins in blood samples from more than 2,000 women and explored how these were linked to frailty, area-level social deprivation, and CVD risk. The women were aged between 37 and 84 years and are part of the TwinsUK cohort.
To better understand how frailty and deprivation contribute to heart disease, we took a data-driven approach, screening a large number of inflammatory proteins in the blood. By identifying overlapping biological markers linked to both social and health vulnerability, we were able to uncover a potential shared pathway between these risk factors.
Dr Yu Lin, Research Associate in the Department of Twin Research & Genetic Epidemiology at King's College London and first author of the study.
The researchers identified ten inflammatory proteins that were associated with both frailty and living in a deprived area. Of these, four proteins that are involved in cellular signalling, growth and movement (TNFSF14, HGF, CDCP1 and CCL11) were also linked to increased risk of cardiovascular disease. One of the proteins, CDCP1, was found to be significantly associated with future heart disease events, such as narrowed or blocked arteries. These findings suggest that certain inflammatory proteins may act as a biological bridge connecting social inequality, ageing and heart disease.
The team validated their findings in an independent group of women from the Nottingham Osteoarthritis Study to ensure the results were consistent across different populations.
Frailty, social disadvantage and heart disease often go hand in hand, but the biological mechanisms linking them are not yet fully understood. Our findings suggest that the stress of socioeconomic hardship may trigger harmful inflammation that damages health over time. If confirmed, this could open up new ways to prevent disease, not only through medical treatments that reduce inflammation, but also through social policies that address health inequalities.
Dr Cristina Menni, Senior Lecturer in Molecular Epidemiology at King's College London and senior author of the study.
The proteins identified in the study may also serve as biomarkers to help clinicians identify individuals at greater risk of heart disease. The findings suggest that a dual approach to public health may offer an effective way of reducing CVD risk in vulnerable populations, by combining medical strategies that reduce inflammation with broader social policies that address inequality.
By identifying these key inflammatory proteins we've shown how these factors may connect social disadvantage and ageing to heart disease, paving the way for targeted prevention strategies to protect vulnerable populations.
Prof Ana Valdes, Professor in Genetic and Molecular Epidemiology, the School of Medicine, University of Nottingham, lead author from the University of Nottingham.
The researchers are now looking to investigate how other factors, such as the gut microbiome, may influence inflammation and cardiovascular risk. Early evidence suggests that individuals in more deprived areas may have lower microbial diversity in their gut microbiome, which could further contribute to harmful inflammation and heart disease.
This study was funded by the UKRI and Wellcome Leap Dynamic Resilience Programme (co-funded by Temasek Trust).
