̽��ֱ�� of Cambridge - Joseph Cheriyan

Anti-inflammatory drug could reduce future heart attack risk

Anonymous — Mon, 02 Sep 2024 10:52:31 +0000

A cancer drug that unlocks the anti-inflammatory power of the immune system could help to reduce the risk of future heart attacks, according to research part-funded by the British Heart Foundation. By repurposing an existing drug, researchers hope it could soon become part of routine treatment for patients after a heart attack.

̽��ֱ��findings will be presented at the European Society of Cardiology Congress in London by Dr Rouchelle Sriranjan, NIHR Clinical Lecturer in Cardiology at the ̽��ֱ�� of Cambridge.

High levels of inflammation in blood vessels are linked to an increased risk of heart disease and heart attacks. After a heart attack, the body’s immune response can aggravate existing inflammation, causing more harm and increasing risk even further. However, NICE guidelines don’t currently recommend the use of any anti-inflammatory drugs to reduce future risk.

Now, a team of researchers, led by Dr Joseph Cheriyan from Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, have found that low doses of an anti-inflammatory drug called aldesleukin, injected under the skin of patients after a heart attack, significantly reduces inflammation in arteries.

̽��ֱ��researchers are currently following up patients to investigate the longer-term impact of this fall in inflammation. To date, in the two and a half years after their treatment, there have been no major adverse cardiac events in the group that received aldesleukin, compared to seven in the group that received the placebo.

Professor Ziad Mallat, BHF Professor of Cardiovascular Medicine at the ̽��ֱ�� of Cambridge who developed the trial, said: “We associate inflammation with healing – an inbuilt response that protects us from infection and injury. But it’s now clear that inflammation is a culprit in many cardiovascular conditions.

“Early signs from our ongoing trial suggest that people treated with aldesleukin may have better long-term outcomes, including fewer heart attacks. If these findings are repeated in a larger trial, we’re hopeful that aldesleukin could become part of routine care after a heart attack within five to 10 years.”

Aldesleukin is already used to treat kidney cancer, as high doses stimulate the immune system to attack cancer cells. ̽��ֱ��Cambridge team previously found that doses one thousand times lower than those used in cancer treatment increased the number of regulatory T cells – a type of anti-inflammatory white blood cell – in patients’ blood compared to a placebo.

In the current trial at Addenbrooke's and Royal Papworth hospitals in Cambridge, 60 patients admitted to hospital with a heart attack or unstable angina received either low dose aldesleukin or placebo. Patients received an injection once a day for the first five days, then once per week over the next seven weeks. Neither the participants nor their doctors knew whether they had received the drug or placebo.

At the end of treatment, Positron Emission Tomography (PET) scans showed that inflammation in the artery involved in patients’ heart attack or angina was significantly lower in the group treated with aldesleukin, compared to those who received the placebo.

̽��ֱ��anti-inflammatory effect of aldesleukin appeared even more striking in the most inflamed arteries, leading to a larger reduction in inflammation levels in these vessels and a bigger difference between the two groups by the end of the study.

Dr Sonya Babu-Narayan, Associate Medical Director at the British Heart Foundation and consultant cardiologist said: “Thanks to research, we have an array of effective treatments to help people avoid heart attacks and strokes and save lives. But, even after successful heart attack treatment, unwanted inflammation in the coronary arteries can remain, which can lead to life-threatening complications.

“A treatment to reduce inflammation after a heart attack could be a game-changer. It would help doctors to interrupt the dangerous feedback loop that exacerbates inflammation and drives up risk. This research is an important step towards that treatment becoming a reality.”

̽��ֱ��study was predominantly funded by the Medical Research Council, with significant support from the BHF and National Institute for Health and Care Research Cambridge Biomedical Research Centre (NIHR-BRC).

Originally published by the British Heart Foundation.

Repurposed cancer drug helps to calm inflammation in arteries.

Sebastian Kaulitzki/Science Photo Library via Getty Images

Illustration of human heart

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‘Tomato pill’ improves function of blood vessels

cjb250 — Tue, 10 Jun 2014 10:49:00 +0000

̽��ֱ��incidence of cardiovascular disease varies worldwide, but is notably reduced in southern Europe, where a ‘Mediterranean diet’ consisting of a larger consumption of fruit, vegetables and olive oil predominates. Recent dietary studies suggest that this diet reduces the incidence of events related to the disease, including heart attack and stroke, in patients at high cardiovascular risk, or those who have previously had the disease.

One component of the Mediterranean diet thought to play a role in reducing this risk is lycopene, a powerful antioxidant which is ten times more potent than vitamin E. Lycopene is found in tomatoes and other fruits, and its potency appears to be enhanced when it is consumed pureed, in ketchup or in the presence of olive oil. Whilst there is strong epidemiological evidence to support the role of lycopene in reducing cardiovascular risk, the mechanism by which it does so is unclear.

In a study published in the journal PLOS One, researchers at the ̽��ֱ�� of Cambridge and the Cambridge ̽��ֱ�� Hospitals National Health Service Foundation Trust demonstrate one mechanism by which they believe lycopene reduces the risk.

Dr Joseph Cheriyan, consultant clinical pharmacologist & physician at Addenbrooke’s Hospital and Associate Lecturer at the ̽��ֱ�� of Cambridge, says: “There’s a wealth of research that suggests that the Mediterranean diet – which includes lycopene found in tomatoes and other fruit as a component – is good for our cardiovascular health. But so far, it’s been a mystery what the underlying mechanisms could be.”

̽��ֱ��researchers carried out a randomised, double blind, placebo controlled, interventional trial investigating the effects of lycopene using a gold standard method of measuring the function of blood vessels called forearm blood flow, which is predictive of future cardiovascular risk. Thirty-six cardiovascular disease patients and thirty-six healthy volunteers were given either Ateronon (an off-the-shelf supplement containing 7mg of lycopene) or a placebo treatment. As a double blind trial, neither the study participants nor the researchers dispensing the pills were aware which treatment was being provided.

̽��ֱ��patients with cardiovascular disease were all on statins (cholesterol-lowering drugs). However, despite this, they still had a relatively impaired function of the endothelium – the inner lining of blood vessels – compared to healthy volunteers. This function is determined by the response of blood vessels in the forearm to a naturally occurring molecule called acetylcholine. Endothelial function predicts future events, so having a healthy endothelium is an important factor in preventing the evolution of heart disease.

̽��ֱ��researchers found that 7mg of oral lycopene supplementation improved and normalised endothelial function in the patients, but not in healthy volunteers. Lycopene improved the responses of blood vessels to acetylcholine (which stimulates the release of an important hormone called nitric oxide which is a blood vessel dilator) by over a half (53%) compared to baseline in those taking the pill after correction for placebo effects; constriction of the blood vessels is one of the key factors that can lead to heart attack and stroke. However, the supplement had no effect on blood pressure, arterial stiffness or levels of lipids.

“We’ve shown quite clearly that lycopene improves the function of blood vessels in cardiovascular disease patients,” adds Dr Cheriyan. “It reinforces the need for a healthy diet in people at risk from heart disease and stroke. A daily ‘tomato pill’ is not a substitute for other treatments, but may provide added benefits when taken alongside other medication. However, we cannot answer if this may reduce heart disease – this would need much larger trials to investigate outcomes more carefully.”

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, says: “Impaired endothelial function is a known predictor of increased risk of future heart disease. Further work is needed to understand whether the beneficial effects seen in this small study translate into clinical benefit for at-risk patients.”

̽��ֱ��study was funded and sponsored by Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, with further support including the Wellcome Trust, the British Heart Foundation and the National Institute of Health Research Cambridge Comprehensive Biomedical Research Centre.

A daily supplement of an extract found in tomatoes may improve the function of blood vessels in patients with cardiovascular disease, according to new research from the ̽��ֱ�� of Cambridge.

There’s a wealth of research that suggests that the Mediterranean diet is good for our cardiovascular health. But so far, it’s been a mystery what the underlying mechanisms could be

Joseph Cheriyan

Marc Wellekötter

Tomatoes (cropped)

Conflict of interest

Cambridge Theranostics donated drugs and placebo to the study. Ateronon, a food supplement, is a registered trademark of CamNutra. ̽��ֱ��authors acknowledge unrestricted educational donations made by Cambridge Theranostics and CamNutra to Addenbrooke’s Charitable Trust. ̽��ֱ��donations were unrelated to the trial, which was not funded by either company. ̽��ֱ��commercial companies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

̽��ֱ��text in this work is licensed under a Creative Commons Licence. If you use this content on your site please link back to this page. For image rights, please see the credits associated with each individual image.

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