A 2026 study of over 60,000 people found that elevated blood levels of IL-18, an inflammation protein, were associated with increased risk of heart attacks and heart disease deaths independent of other known risk factors. However, according to Gram Research analysis, IL-18 levels alone don’t improve doctors’ ability to identify high-risk patients compared to current methods, suggesting new treatments targeting IL-18 need further testing before clinical use.
Researchers studied over 60,000 people across three countries to understand whether a protein in the blood called IL-18 could predict heart attacks and heart disease deaths. According to Gram Research analysis, they found that people with higher IL-18 levels had a greater risk of heart problems, even when accounting for other known risk factors like cholesterol and inflammation markers. However, the protein alone wasn’t helpful enough to change how doctors currently assess who’s at highest risk. The findings suggest that targeting IL-18 through new treatments might help protect people who remain at risk despite taking standard heart disease medications.
Key Statistics
A 2026 cohort study of 60,461 participants across Sweden, the UK, and Europe found that elevated IL-18 levels were independently associated with increased risk of heart attacks and cardiovascular death over 15-23 years of follow-up.
In the UK Biobank cohort of 54,219 people, elevated IL-18 remained significantly associated with heart disease risk even after adjusting for major cardiovascular risk factors including age, cholesterol, blood pressure, diabetes, and smoking.
The Swedish Malmö Diet and Cancer cohort recorded 617 heart attacks and 644 cardiovascular deaths among 4,742 participants over 23 years, with elevated IL-18 independently predicting both outcomes.
Despite its association with heart disease risk, IL-18 did not provide clinically meaningful risk reclassification in the UK Biobank cohort, meaning it doesn’t improve how doctors currently identify high-risk patients.
The Quick Take
- What they studied: Whether a blood protein called IL-18 can predict who will have a heart attack or die from heart disease
- Who participated: Over 60,000 people from Sweden, the UK, and Europe, including healthy adults and people with diabetes or existing heart disease, followed for 15-23 years
- Key finding: People with higher IL-18 levels had significantly more heart attacks and heart-related deaths, independent of other known risk factors, but the protein didn’t improve doctors’ ability to identify high-risk patients
- What it means for you: IL-18 may be a useful research target for developing new heart disease treatments, but it’s not yet ready to be used in routine medical care to assess your personal heart risk
The Research Details
Researchers followed three large groups of people over many years, measuring their blood levels of IL-18 at the start and then tracking who developed heart attacks or died from heart disease. The Swedish group (4,742 people) was followed for 23 years, the UK group (54,219 people) for 15 years, and a European group (1,500 people with diabetes or known heart disease) had their artery thickness measured by ultrasound. This approach, called a prospective cohort study, is powerful because researchers can see which people actually develop disease and compare them to those who don’t.
The researchers used a special lab technique called proximity extension assay to measure IL-18 levels accurately. They also measured other inflammation markers and traditional heart disease risk factors like cholesterol, blood pressure, and smoking. This allowed them to determine whether IL-18 provided unique information beyond what doctors already know about heart disease risk.
The study was designed to test whether IL-18 could be a useful new tool for identifying people at highest risk, particularly those already taking cholesterol-lowering medications who still have heart problems.
Following real people over many years is the gold standard for understanding disease risk because it shows what actually happens in life, not just what happens in a lab. By studying three different populations, the researchers could see if their findings held true across different countries and types of people. This approach is much stronger than simply measuring a protein once and guessing about risk.
This study is high-quality because it followed tens of thousands of people for over a decade, had detailed medical records, and carefully measured both the blood marker and heart disease outcomes. The researchers adjusted their analysis for many other factors that affect heart disease risk, making it less likely that other causes explain the findings. However, the study is observational, meaning it shows association but cannot prove that IL-18 directly causes heart disease. The findings were consistent across two large populations (Sweden and UK), which strengthens confidence in the results.
What the Results Show
In the Swedish cohort, there were 617 heart attacks and 644 deaths from heart disease over 23 years. In the UK cohort, there were 2,454 heart attacks and 1,537 deaths from heart disease over 15 years. People with elevated IL-18 levels had significantly higher risk of both outcomes in both groups. The association remained strong even after accounting for other inflammation markers like hsCRP and IL-6, suggesting IL-18 provides independent information about heart disease risk.
When researchers adjusted for major heart disease risk factors like age, cholesterol, blood pressure, diabetes, and smoking, the IL-18 association remained significant in the UK population but weakened in the Swedish population. This difference between groups suggests the relationship may vary depending on the population studied.
Interestingly, when researchers tested whether knowing someone’s IL-18 level would change how doctors classify patients as low, medium, or high risk, it didn’t meaningfully improve the classification. This means that while IL-18 is statistically associated with heart disease, it doesn’t provide practical benefit for current medical decision-making.
In the European group with existing heart disease, IL-18 was associated with thicker artery walls (a sign of advanced atherosclerosis), but this association was weaker than the association with IL-6, another inflammation marker.
The study found that IL-18’s relationship with heart disease risk was independent of IL-6 and hsCRP, two other inflammation markers that doctors sometimes measure. This suggests IL-18 captures different information about inflammation than these other markers. The association was also independent of traditional risk factors like age, sex, smoking, and diabetes in the UK population, indicating it’s not simply a marker of these known risks. However, the strength of the association varied between populations, suggesting that IL-18 may be more useful in some groups than others.
Previous research has focused heavily on IL-1β and IL-6 as inflammation markers in heart disease, with some drugs targeting these proteins showing promise. This study is among the first to carefully examine IL-18, a related protein, across large populations. The findings suggest IL-18 is associated with heart disease risk, but appears less directly useful for clinical decision-making than hoped. The results align with growing evidence that inflammation plays a role in heart disease even in people taking cholesterol-lowering drugs, supporting the idea that anti-inflammatory treatments might help.
The study is observational, meaning it shows that IL-18 and heart disease are linked but cannot prove IL-18 causes heart disease. The association was stronger in the UK population than the Swedish population, suggesting results may not apply equally to all groups. The study measured IL-18 only once at the beginning, so it couldn’t track how changes in IL-18 over time relate to heart disease risk. The European group was smaller and consisted of people with existing disease, limiting how well findings apply to healthy people. Finally, the study didn’t test whether lowering IL-18 actually reduces heart disease risk, which would require a treatment trial.
The Bottom Line
Based on current evidence, IL-18 should not be used in routine medical care to assess heart disease risk. However, the findings support continued research into whether drugs that lower IL-18 or block the inflammasome pathway could help people at high risk despite taking standard medications. If you have heart disease risk factors or existing heart disease, continue following your doctor’s recommendations about cholesterol-lowering drugs, blood pressure control, exercise, and diet. Future clinical trials will determine whether IL-18-targeting treatments provide additional benefit.
This research is most relevant to cardiologists and researchers developing new heart disease treatments. People with existing heart disease or multiple risk factors should be aware that new anti-inflammatory approaches are being studied but aren’t yet available. People taking cholesterol-lowering medications should know that researchers are working on additional treatments for residual risk. This research is not yet relevant for healthy people making personal health decisions.
IL-18-targeting treatments are still in the research phase. Even if promising drugs are identified, it typically takes 5-10 years of clinical trials before new treatments become available to patients. People should not expect IL-18 testing or IL-18-lowering treatments to be available in the near future.
Frequently Asked Questions
What is IL-18 and why does it matter for heart disease?
IL-18 is a protein in your blood that signals inflammation in your body. Research shows elevated IL-18 is associated with increased heart attack and heart disease death risk, independent of other known risk factors. However, it’s not yet used clinically to assess individual risk.
Can I get my IL-18 level tested to check my heart disease risk?
IL-18 testing is not currently recommended for routine heart disease risk assessment. While research shows it’s associated with heart disease, it doesn’t improve doctors’ ability to identify high-risk patients compared to existing methods. Talk to your doctor about proven risk assessment tools.
Are there treatments that lower IL-18 to prevent heart disease?
Drugs targeting IL-18 or the inflammasome pathway are still in research stages and not yet available for patients. This study supports continued research into these approaches for people at high risk despite taking standard heart disease medications.
Does this study prove that IL-18 causes heart disease?
No, this study shows association but not causation. The researchers followed people and found those with higher IL-18 had more heart disease, but this doesn’t prove IL-18 directly causes it. Clinical trials would be needed to test whether lowering IL-18 prevents heart disease.
Should I change my lifestyle based on this IL-18 research?
No lifestyle changes are needed based on this research alone. Continue following proven recommendations: take prescribed heart medications, exercise regularly, eat a heart-healthy diet, manage blood pressure and cholesterol, and avoid smoking. Future treatments may add to these strategies.
Want to Apply This Research?
- Track your inflammation-related symptoms and heart disease risk factors (blood pressure, cholesterol levels, exercise frequency) monthly. Note any changes in energy, chest discomfort, or shortness of breath to discuss with your doctor.
- Use the app to set reminders for taking prescribed heart disease medications consistently, log cardiovascular exercise (150 minutes weekly), and track anti-inflammatory diet choices like eating fish, vegetables, and whole grains.
- Establish a quarterly review of your cardiovascular risk profile with your doctor, including blood pressure, cholesterol, and weight. Log any new symptoms or medication changes in the app to identify patterns over time.
This research describes associations between IL-18 and heart disease risk but does not establish causation or provide medical advice. IL-18 testing is not currently recommended for routine clinical use. If you have concerns about your heart disease risk, consult with your healthcare provider about proven assessment methods and treatments. Do not make changes to your medications or treatment plan based on this research without discussing with your doctor. This article is for educational purposes and should not replace professional medical advice.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.