For more than twenty years, heart specialists have argued that inflammation inside the arteries drives heart attacks and strokes, and that a simple blood test, high-sensitivity C-reactive protein (hs-CRP), can reveal it. On 7 November 2026, at the American Heart Association's Scientific Sessions in Chicago, one of the largest tests of that idea came back neutral. In the ZEUS trial, the experimental drug ziltivekimab lowered hs-CRP by about 64%, yet people who received it had just as many heart attacks, strokes and cardiovascular deaths as those on placebo. The results were published the same day in The New England Journal of Medicine.
If your GP or cardiologist has ever ordered an hs-CRP test, or you have seen "inflammation" flagged on a heart-risk panel, here is what ZEUS found, why it does not make your result meaningless, and what to ask at your next appointment.
What the ZEUS trial tested
C-reactive protein is made by the liver when the body is inflamed. A standard CRP test picks up the large rises seen with infections. The high-sensitivity version measures much smaller amounts, in the range linked to slow, low-grade inflammation of the blood vessels. Our guide to the CRP blood test explains the difference between the two.
CRP production is switched on largely by a signalling protein called interleukin-6 (IL-6). Ziltivekimab is a monthly injectable antibody that blocks IL-6. The ZEUS trial enrolled 6,376 adults who had three things at once: established atherosclerotic cardiovascular disease (such as a previous heart attack, stroke or blocked leg arteries), chronic kidney disease, and an hs-CRP of at least 2 mg/L. Participants were randomly assigned to ziltivekimab or a placebo, on top of their usual treatment. Their average age was about 69, and more than nine in ten were already taking cholesterol-lowering medication. The trial was led by Dr Paul Ridker of Mass General Brigham and funded by Novo Nordisk, the drug's manufacturer.
What the results showed
After a median follow-up of nearly three years, the drug did exactly what it was designed to do in the blood, but that did not translate into fewer events.
| Measure | Ziltivekimab | Placebo |
|---|---|---|
| Heart attack, stroke or cardiovascular death | 561 people (17.6%) | 565 people (17.7%) |
| Change in hs-CRP compared with placebo | About 64% lower | Reference |
| Change in IL-6 compared with placebo | About 76% lower | Reference |
| Serious infections | About 20% | About 18% |
Deaths from any cause were almost identical in the two groups. According to the published report, the drug also did not slow the decline in kidney function. Serious infections were somewhat more common with ziltivekimab, which the researchers said is to be expected with a medicine that dampens the immune response.
The same morning, the Lp(a)HORIZON trial reported a similar pattern for another blood marker: a large drop in lipoprotein(a) with no reduction in events. We covered it in what the pelacarsen trial means for your Lp(a) test.
Why a lower hs-CRP did not mean fewer heart attacks
The investigators offered several explanations. The first is timing. Everyone in ZEUS already had both arterial disease and moderate to advanced kidney disease and, according to the researchers, the death rate was about twice that of comparable heart studies in people without severe kidney disease. Dr Ridker described the treatment as possibly "too little, too late" for such advanced illness.
The second is that hs-CRP is a messenger, not the culprit. It reflects inflammation, but lowering the number does not guarantee that every harmful process inside the artery wall has been switched off. Experts quoted after the results stressed that a neutral treatment trial does not disprove the link between hs-CRP and future events. In fact, the researchers noted that participants who started with higher hs-CRP or IL-6 levels remained at greater cardiovascular risk throughout the study.
Third, other anti-inflammatory approaches have worked in different groups of patients. Dr Ridker pointed out that earlier trials of canakinumab and of low-dose colchicine did reduce heart attacks and strokes. Research is now moving towards people with less advanced disease and towards blocking inflammation further upstream.
What this means for your hs-CRP test
ZEUS tested a drug, not the test. hs-CRP remains a recognised way to measure the inflammatory part of heart risk, alongside cholesterol. Results are usually read in three bands:
- Below 1 mg/L: lower inflammatory risk.
- From 1 to 3 mg/L: average risk.
- Above 3 mg/L: higher risk, especially if the result is confirmed on a second test.
A single value can be thrown off by a cold, a dental infection, an injury or a hard workout. A result above 10 mg/L usually points to a short-term infection or another inflammatory condition, and the test is generally repeated once you are well. If your hs-CRP is high, see our guide to high CRP levels and what they mean.
What changes after ZEUS is the conversation about treatment. There is no reason to seek out an IL-6 blocker, and this drug is not licensed. The proven tools remain the ones that lower overall risk: cholesterol-lowering therapy (such as statins) when indicated, blood pressure and blood sugar control, not smoking, regular physical activity, a Mediterranean-style diet and a healthy weight. Ask your GP whether a persistently high hs-CRP changes your risk estimate or your treatment targets.
Which tests can monitor or screen for this?
- hs-CRP, ideally measured twice, a few weeks apart, when you are not unwell.
- A lipid profile with LDL cholesterol, and sometimes apolipoprotein B (ApoB).
- Lipoprotein(a), usually once in a lifetime.
- Kidney function: creatinine with estimated glomerular filtration rate (eGFR), plus the urine albumin test (ACR). Kidney disease raises heart risk on its own, as explained in how kidney tests help predict heart disease.
- Fasting glucose or HbA1c, to check for diabetes or prediabetes.
Recent scientific advances
ZEUS lands in the middle of a broader shift in how doctors think about inflammation and the heart.
Long-term follow-up of thousands of initially healthy American women showed that a single hs-CRP measurement in midlife helped predict heart attacks and strokes three decades later, and that combining it with LDL cholesterol and lipoprotein(a) gave the clearest picture. A separate analysis of the same women found a similar link with ischaemic stroke.
In people already taking statins, a pooled analysis of three large trials found that inflammation measured by hs-CRP predicted future events and deaths more strongly than the remaining LDL cholesterol. In 2025, the American College of Cardiology published a scientific statement calling for broad hs-CRP screening, together with cholesterol, in people both with and without known heart disease.
For people with kidney disease, a nationwide Swedish registry study published in 2026 found that raised hs-CRP was common and was linked to more heart events, heart failure, kidney injury and death, which supports monitoring it. Researchers are also developing imaging methods that measure inflammation directly around the heart's arteries on a CT scan, which may one day help identify the patients most likely to benefit from anti-inflammatory treatment.
When to see a doctor
Book an appointment with your GP if your hs-CRP stays above 3 mg/L on repeat testing, if you have kidney disease and have never had your heart risk assessed, or if you have a family history of early heart attack or stroke. Do not stop or change any prescribed medicine because of news about ZEUS. Call 999 (or 112) straight away for chest pain, sudden breathlessness, or signs of stroke such as face drooping, arm weakness or difficulty speaking.
Glossary
- High-sensitivity C-reactive protein (hs-CRP): a blood test that detects small amounts of CRP, used to estimate low-grade inflammation and heart risk.
- Interleukin-6 (IL-6): a messenger protein of the immune system that tells the liver to make CRP.
- Monoclonal antibody: a laboratory-made protein designed to attach to one specific target, here IL-6.
- Atherosclerotic cardiovascular disease (ASCVD): disease caused by fatty, inflamed plaque in the arteries, including heart attack and most strokes.
- Chronic kidney disease (CKD): a lasting loss of kidney function, usually tracked with eGFR and urine albumin.
- Residual inflammatory risk: the heart risk linked to inflammation that remains after cholesterol has been treated.
Frequently asked questions
Did ziltivekimab lower hs-CRP?
Yes. hs-CRP fell by about 64% and IL-6 by about 76% compared with placebo, but heart attacks, strokes and cardiovascular deaths did not decrease.
Does ZEUS mean my hs-CRP result does not matter?
No. People with higher hs-CRP still had more events during the trial. The result shows that this drug, in this very high-risk group, did not help, not that inflammation is harmless.
What is a normal hs-CRP level?
Below 1 mg/L is considered lower risk, 1 to 3 mg/L average, and above 3 mg/L higher. Values above 10 mg/L usually reflect a temporary infection or another illness and should be rechecked.
Can I lower my hs-CRP myself?
Often, yes. Stopping smoking, losing excess weight, regular exercise and a Mediterranean-style diet tend to lower it. Statins also lower hs-CRP while they lower cholesterol.
Is there an approved anti-inflammatory heart medicine?
Low-dose colchicine is approved in the United States to reduce cardiovascular events in some adults with or at risk of heart disease. It is not suitable for everyone, so discuss it with your GP or cardiologist.
Sources
- Ridker PM, Lincoff AM, Marx N, et al. Ziltivekimab Cardiovascular Outcomes Trial (ZEUS), main results. N Engl J Med. 2026. DOI: 10.1056/NEJMoa2612126
- American Heart Association. Researchers say inflammation as a treatment target still important despite neutral results of ZEUS trial. November 7, 2026
- HCPLive. ZEUS: Ziltivekimab Fails to Reduce Cardiovascular Events in ASCVD and CKD. November 7, 2026
- Ridker PM, et al. Rationale, Design, and Baseline Clinical Characteristics of the Ziltivekimab Cardiovascular Outcomes Trial. JAMA Cardiol. 2026;11(1):89-97. DOI: 10.1001/jamacardio.2025.4491
- ClinicalTrials.gov. ZEUS, Ziltivekimab Cardiovascular Outcomes Study, NCT05021835
- Mensah GA, Arnold N, Prabhu SD, Ridker PM, Welty FK. Inflammation and Cardiovascular Disease: 2025 ACC Scientific Statement. J Am Coll Cardiol. 2025;87(11):1381-1404. DOI: 10.1016/j.jacc.2025.08.047
- American College of Cardiology. New ACC Scientific Statement Details Role of Inflammation in CVD. September 29, 2025
- Ridker PM, et al. Inflammation, Cholesterol, Lipoprotein(a), and 30-Year Cardiovascular Outcomes in Women. N Engl J Med. 2024;391(22):2087-2097. DOI: 10.1056/NEJMoa2405182
- Nordestgaard AT, et al. High-sensitivity C-reactive protein, LDL cholesterol, lipoprotein(a) and 30-year risk of stroke in healthy women. Lancet Neurol. 2025;24(11):920-930. DOI: 10.1016/S1474-4422(25)00306-0
- Ridker PM, et al. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy. Lancet. 2023;401(10384):1293-1301. DOI: 10.1016/S0140-6736(23)00215-5
- Mazhar F, et al. High sensitivity C-reactive protein and the risk of cardio-kidney outcomes in adults with moderate to severe chronic kidney disease: a nationwide study. Nephrol Dial Transplant. 2026. DOI: 10.1093/ndt/gfag240
- Prakash N S G, et al. High-sensitivity C-Reactive Protein as a Risk-Enhancing Biomarker in Patients with Chronic Kidney Disease and Atherosclerotic Cardiovascular Disease: A Narrative Review. Cardiorenal Med. 2026. DOI: 10.1159/crm/abtag019
- Avivi I, Taub PR, Ben-Yehuda O. Pericoronary adipose tissue attenuation as a dynamic marker of coronary-specific inflammation. Curr Opin Cardiol. 2026. DOI: 10.1097/HCO.0000000000001350
- Pearson TA, et al. Markers of Inflammation and Cardiovascular Disease: AHA/CDC Scientific Statement. Circulation. 2003;107(3):499-511. DOI: 10.1161/01.CIR.0000052939.59093.45
- Harvard Health Publishing. Inflammation and heart disease: A smoldering threat
- MedlinePlus. C-Reactive Protein (CRP) Test. US National Library of Medicine
Further reading
- CRP blood test: how to read your inflammation results
- High CRP levels: what your result really means
- Pelacarsen and the Lp(a)HORIZON trial
- C3 complement blood test: what ageing research adds
- Kidney function tests and heart disease
- Lipid profile: understanding your cholesterol results
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