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In a Nutshell
- Long-term, low-grade inflammation was linked to smaller heart chambers and a heart that pumps less efficiently, changes that can set in before heart failure.
- People with the highest inflammation levels had a 43% higher risk of serious heart problems like heart attack and stroke compared with those who had the lowest levels.
- A person’s genetic makeup appeared to change how strongly things like smoking, body fat, stress, and poverty translated into inflammation and heart risk.
Long before chest pain or a diagnosis, inflammation may already be taking a toll on the heart. In a study of nearly half a million people, those with the highest levels of a blood marker called GlycA had a 43% higher risk of heart attack, stroke, and other major heart problems, along with smaller heart chambers, thicker walls, and less efficient pumping, changes that can appear before heart disease becomes clinically apparent.
Researchers analyzing data from the UK Biobank, a long-running health project that has tracked hundreds of thousands of adults in the United Kingdom since the mid-2000s, reported in the European Journal of Preventive Cardiology that this chronic, low-level inflammation was linked to subtle differences in the heart’s structure and function. Why some people suffer more heart damage than others from the same unhealthy habits has long puzzled scientists, and genetics turns out to be a big part of the answer.
Equally telling is what feeds that inflammation in the first place. Smoking, excess body fat, poor mental health, and living in poverty all raised inflammation levels in the study. But genetics changed how much those stressors actually hurt a given person, which may explain why some people seem to escape the consequences of unhealthy living while others do not.
Genes and Heart Disease Risk: A Half-Million-Person Study
Scientists at Imperial College London led the analysis, drawing on data from more than 488,000 UK Biobank participants whose blood tests measured a substance called GlycA, a marker that reflects long-term inflammation in the body. It works somewhat like C-reactive protein, or CRP, a more familiar blood test doctors already use to check for inflammation, but GlycA tends to stay steadier over time and reflects several inflammatory processes happening at once.
Participants were between 40 and 69 years old when they joined the study between 2006 and 2010, and researchers followed them for a median of more than 15 years. About 70,800 also had detailed heart scans, giving researchers a look at the structure and function of their hearts, not just their blood chemistry. A smaller group, ranging from about 8,000 to 53,000 people depending on the specific analysis, had additional blood tests for 80 different proteins tied to inflammation, letting the team narrow down which biological signals might be doing the damage.
How Inflammation Is Linked to Changes in the Heart
People with higher GlycA levels tended to have smaller heart chambers relative to their body size, thicker heart walls, and hearts that filled less efficiently with blood between beats. Their hearts also beat somewhat faster, which researchers think reflected the heart compensating for pumping less blood with each beat. These patterns held up even after accounting for sex, age, body size, and diabetes, and they showed up in both men and women.
Those structural changes carried real consequences. Higher GlycA tracked with major heart problems, among them heart attacks, strokes, heart failure, and cardiac arrest. It also predicted risk beyond what a standard cholesterol test or the CRP inflammation test could capture, meaning it may catch something those older tests miss.
To figure out what might explain the link between inflammation and heart changes, the team tested whether any of the 80 proteins could account for it. One protein, interleukin-1 receptor antagonist, a substance the body releases to help control inflammation, statistically explained about 27% of the link between overall inflammation and one measure of heart chamber size. Another protein, hepatocyte growth factor, played a similarly large role in a different heart measurement. When researchers looked at which proteins connected inflammation to actual heart attacks and strokes, a protein called interleukin-6, known for triggering inflammation throughout the body, stood out most strongly, statistically explaining about a third of the association.
Several of these proteins are already being targeted by experimental drugs in clinical trials aimed at lowering inflammation-related heart risk, a hopeful sign that this research could eventually lead to real treatments.
Genes and Heart Disease Risk: Why Habits Hit People Differently
Researchers also wanted to know what causes the inflammation in the first place. They screened 177 lifestyle and environmental factors against inflammation levels in nearly 479,000 participants. Fat around the stomach, current smoking, psychological distress, and markers of financial hardship, such as renting from a local housing authority, emerged as the strongest predictors of higher inflammation.
When the team combined this data with genetic risk scores built from multiple ancestries, they found more than 100 cases where a person’s genetic risk for heart disease changed how strongly a factor like smoking, body fat, poverty, or mental health struggles translated into inflammation. Nearly 50 of these combinations also changed how strongly inflammation translated into an actual heart attack or stroke. Seventeen patterns showed up in both analyses, most involving measures of financial hardship. In one example, a person’s employment status interacted with their genetic risk score in ways that increased its effect on both inflammation levels and the odds of a major heart event.
This research reframes heart disease risk as something shaped by habits and genes together, not one or the other. A person’s smoking habit, waistline, stress load, or financial hardship does not act on a blank slate; it acts on a body already shaped by inherited risk. That means health advice built solely around quitting smoking or losing weight, while still worth following, may miss why identical efforts pay off differently from person to person. The researchers suggest that combining blood markers of inflammation with genetic risk profiles could help doctors figure out who needs the most urgent help, rather than treating every smoker, every stressed worker, or every person living in poverty as facing the same risk.
For now, the study offers a partial answer to why two neighbors with the same bad habits can end up with very different hearts. The gap may owe less to willpower or luck than to how each person’s inherited risk collides with the smoking, stress, weight, and hardship life hands them.
Paper Notes
Limitations
Authors noted that the UK Biobank population is mostly people of White European ancestry and tends to be healthier and more socioeconomically advantaged than the general UK population, a pattern known as healthy volunteer bias, which may limit how well the findings apply to other ethnic groups or higher-risk populations. The heart-scan portion of the study also represents a smaller, selected subset of the overall Biobank group, which may introduce further selection bias. GlycA is measured using a laboratory technique not currently used in routine medical care, so its practical value compared with existing tests like CRP still needs confirmation in other populations. The 80 proteins studied represent only a slice of what circulates in blood and do not capture activity inside cells or specific organs. Environmental exposure data varied in precision and could not capture every possible factor in a person’s surroundings and lifestyle. Finally, because the protein and inflammation data were collected at a single point in time rather than tracked over time, the authors caution that the mediation findings are exploratory and cannot prove one factor directly causes another.
Funding and Disclosures
Funding came from the Medical Research Council, the British Heart Foundation, and the NIHR Imperial Biomedical Research Centre, along with a British Heart Foundation Big Beat Challenge award to a research initiative called CureHeart. One author, Declan P. O’Regan, disclosed receiving fees from Bayer AG, as well as grant funding from Bayer AG and Calico Labs.
Publication Details
Paper Title: “Gene–environment interactions shape cytokine-mediated inflammation and cardiovascular risk”
Authors: Mattia Corianò, Shamin Tahasildar, Ling Huang, Khaled Rjoob, Majid Vafaeezadeh, Soodeh Kalaie, Jin Zheng, Lara Curran, Parisa Gifani, Marc-Emmanuel Dumas, and Declan P. O’Regan.
