A study of nearly 488,000 adults found that people with the highest levels of chronic inflammation faced substantially greater cardiovascular risk and showed structural heart changes that may develop years before symptoms emerge.
By yourNEWS Media Newsroom
Long-running inflammation may leave measurable changes in the heart years before a person develops obvious cardiovascular symptoms, according to a large study that followed hundreds of thousands of adults and combined blood testing, heart imaging, environmental exposures and genetic data.
Researchers analyzing 488,079 participants in the UK Biobank found that adults with the highest levels of the inflammatory marker glycoprotein acetyls, or GlycA, had about a 43% higher risk of experiencing a major cardiovascular event than those with the lowest levels. The study in the European Journal of Preventive Cardiology, published Sept. 18, also linked greater chronic inflammation with smaller heart chambers, thicker heart walls, reduced blood volume pumped with each beat and impaired filling of the heart between contractions.
The findings point to a cardiovascular process that can develop quietly. Unlike inflammation caused by an infection or injury that rises and subsides, GlycA reflects activity from several inflammatory proteins and is considered a marker of persistent systemic inflammation. Researchers found cardiovascular risk remained comparatively stable at lower GlycA concentrations before increasing more sharply above the middle of the measured range.
Participants were followed for a median of 15.3 years. During that period, 74,336 experienced the study’s primary cardiovascular outcome, which included heart attack, heart failure, stroke or other cerebrovascular events, cardiac arrest and cardiovascular death. Myocardial infarctions were the most common events, followed by strokes and heart failure.
Heart Imaging Reveals Changes Before Disease Becomes Apparent
Researchers were able to examine the relationship between inflammation and heart structure in 70,809 participants who had GlycA measurements along with cardiac magnetic resonance imaging and electrocardiogram data.
Those scans revealed a consistent pattern. Higher GlycA levels were associated with reduced left ventricular chamber volume and lower stroke volume, meaning the heart expelled less blood with each contraction. Participants with greater inflammation also tended to have thicker heart walls and poorer filling between beats, while their hearts compensated partly through an increased heart rate.
The changes are important because the heart can compensate for structural and functional abnormalities for years before a person notices shortness of breath, fatigue, exercise intolerance or other signs associated with cardiovascular disease.
Imperial College London researchers said the abnormalities observed in the imaging data may develop silently before eventually progressing toward heart failure or other cardiovascular problems. The university described the research as the largest study of its kind examining chronic inflammation, heart remodeling and cardiovascular outcomes.
The analysis also identified inflammatory signaling pathways that may help explain the relationship. Researchers examined 80 circulating inflammatory proteins and found that proteins associated with interleukin and tumor necrosis factor signaling were among those statistically linked to cardiac remodeling and cardiovascular outcomes.
Interleukin-1 receptor antagonist, or IL-1RA, statistically mediated about 27% of the association between GlycA and reduced left ventricular end-diastolic volume. IL-6 showed one of the strongest statistical mediation relationships between inflammation and subsequent cardiovascular events. Those findings do not establish that the proteins directly caused the observed changes, but they provide potential biological pathways for further study.
Body Fat, Smoking and Psychological Stress Stand Out
Researchers also examined 177 environmental, lifestyle and body-composition measurements to determine which characteristics were most strongly associated with chronic inflammation.
Of those factors, 166 showed statistically significant associations with GlycA. Measures related to excess body fat were among the strongest predictors, particularly trunk fat, total fat mass and fat infiltration into muscle. Current smoking, psychological distress, depressive symptoms, visceral abdominal fat and indicators of socioeconomic disadvantage were also strongly associated with higher inflammation.
Fat concentrated around the abdominal organs is metabolically active and has long been associated with cardiovascular and metabolic risk. In the new analysis, both visceral fat and an android pattern of fat distribution — greater accumulation around the abdomen and upper body — were strongly associated with GlycA.
Smoking was another prominent factor. Current smokers had significantly higher inflammation measurements after researchers accounted for other variables.
Mental and economic circumstances also appeared repeatedly in the analysis. Psychological distress, depressive symptoms and socioeconomic disadvantage were associated with higher GlycA levels, while higher socioeconomic status was associated with lower measurements. Researchers found that socioeconomic conditions, mental health and physical activity also featured prominently when genetic cardiovascular risk was considered.
Daytime napping was among the sleep-related characteristics associated with higher GlycA. That finding does not establish that napping causes inflammation; frequent daytime sleep can also reflect poor nighttime sleep, illness, fatigue or other underlying conditions that may themselves be associated with inflammation.
In contrast, greater physical activity and healthier dietary patterns were associated with lower GlycA measurements. Because the study was observational, those relationships cannot demonstrate that any single lifestyle behavior directly lowered inflammation in participants.
Inflammation Adds Another Dimension to Cardiovascular Risk
Atherosclerosis involves more than cholesterol accumulation alone. The formation and progression of arterial plaque also involve inflammatory activity within blood vessel walls, which can contribute to plaque instability and cardiovascular events.
Previous research has likewise examined inflammation markers such as C-reactive protein, or CRP, alongside conventional cardiovascular risk measurements. Research involving almost 28,000 apparently healthy American women, for example, found that CRP provided significant information about future cardiovascular risk.
GlycA differs from CRP because it reflects signals from multiple circulating proteins involved in inflammatory activity. The researchers said it also tends to exhibit less long-term variation within individuals than high-sensitivity CRP.
In the current study, GlycA remained associated with cardiovascular events after researchers adjusted for conventional cardiovascular risk factors and lipid measurements. Adding GlycA to a model that already included high-sensitivity CRP and established cardiovascular risk factors produced a modest improvement in the classification of 10-year cardiovascular risk, although researchers said prospective studies are still needed before determining its clinical usefulness.
Previous reporting from Mercola.com has also highlighted the inflammatory component of atherosclerosis and research examining relationships among chronic stress, inflammation, cardiovascular disease and metabolic disorders.
Genes May Change How Strongly People Respond
The study also found that inherited cardiovascular susceptibility may influence the degree to which environmental factors are associated with inflammation and heart disease.
Researchers used polygenic risk scores representing inherited susceptibility to cardiovascular disease, cholesterol abnormalities, diabetes, hypertension and stroke. They identified interactions suggesting that people can respond differently to similar environmental circumstances depending partly on their genetic background.
A total of 49 interactions between environmental exposures and polygenic risk scores significantly affected the relationship involving GlycA and major cardiovascular events. Seventeen genetic-environment interactions appeared in analyses of both inflammation and cardiovascular outcomes, many involving socioeconomic characteristics.
The results offer a possible explanation for why two people with broadly similar lifestyles can have different inflammatory profiles and cardiovascular outcomes. Genetics may make one person more biologically susceptible to factors such as smoking, excess body fat, psychological stress or economic hardship while another person shows a weaker inflammatory response.
That finding is consistent with decades of evidence showing a hereditary component to coronary disease. A long-running Swedish twin analysis involving 21,004 twins, for example, found a substantially elevated coronary heart disease risk among men whose identical twin died from the disease before age 55. Variants in a region of chromosome 9 have also been associated with coronary artery disease in genetic research.
Genes, however, are only one component of cardiovascular risk. The new research found that acquired and environmental factors interacted with inherited susceptibility rather than operating independently of it.
What the Findings Mean for Prevention
Many of the factors most strongly associated with inflammation in the study are potentially modifiable. Smoking cessation, regular physical activity, maintaining a healthy waist circumference and body composition, eating a nutritious diet and addressing persistent psychological stress are already established components of cardiovascular prevention.
Exercise has repeatedly been associated with cardiovascular benefits extending beyond weight control, including improvements in blood pressure, glucose regulation, blood vessel function and physical capacity. Previous research has also associated regular brisk walking with lower cardiovascular risk, including a reported reduction in heart-rhythm disorders among UK Biobank participants.
Adequate sleep is another component of cardiovascular health, though the relationship between sleep, inflammation and heart disease is complex. Sleep quality, duration, sleep disorders and underlying medical conditions can all influence cardiovascular risk.
Routine medical testing generally does not include GlycA, and the study does not establish a GlycA threshold at which otherwise healthy adults should receive treatment. Researchers said additional prospective work is needed before the marker can be incorporated widely into clinical risk assessment.
The study also did not test whether actively lowering GlycA prevents heart attacks, strokes or heart failure. Because researchers observed existing differences among participants rather than randomly assigning people to treatments designed to change inflammation, the findings demonstrate associations rather than proving that chronic inflammation directly caused the cardiac changes or later cardiovascular events.
Even with that limitation, the scale of the study allowed researchers to connect blood markers, cardiac MRI measurements, lifestyle and socioeconomic conditions, genetic susceptibility and long-term health outcomes within the same population.
The findings suggest that cardiovascular disease may be developing well before a person experiences symptoms or receives a diagnosis. For some people, persistent inflammation appears to accompany subtle remodeling of the heart while they still consider themselves healthy — placing greater emphasis on identifying and reducing modifiable cardiovascular risks before overt disease emerges.
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