Non-smoker, with normal blood pressure and cholesterol levels has heart disease. Why?
Inflammation is re-emerging as a likely reason for blockages in the coronary arteries of some patients with ischaemic heart disease
Family history (genetics) is one risk factor for cardiovascular disease
Up to 25 per cent of people who experience an acute cardiac event such as a heart attack have none of the traditional risk factors for cardiovascular disease. That’s right – they have never smoked, their blood pressure is normal and they do not have elevated cholesterol levels in their blood stream.
Nor do they have diabetes or even an elevated body mass index.
In my experience many of these patients feel understandably aggrieved when they find themselves in a coronary care unit.
So what is giving these individuals heart disease?
Family history (genetics) is a factor for some. And inflammation is re-emerging from the shadows as a likely reason for blockages in the coronary arteries of at least a minority of patients with ischaemic heart disease.
The study included 10,000 patients who had previously had a heart attack
There was some excitement at the annual conference of the European Society for Cardiology in August when the results of the Cantos trial were revealed. It set out to test whether reducing inflammation in patients who had a prior heart attack could lower the risk of another cardiovascular event. The drug tested was canakinumab, a human monoclonal antibody that neutralises interleukin-1 signalling, thereby suppressing inflammation.
The study included 10,000 patients who had previously had a heart attack and had persistent, elevated levels of high sensitivity C-reactive protein (hsCRP), a marker of inflammation. All patients received aggressive standard care, which included high doses of cholesterol-lowering statins. Participants were randomised to receive canakinumab, or a placebo, administered subcutaneously once every three months. Patients were then followed for up to four years.
Results showed canakinumab reduced the risk of a cardiovascular event by 15 per cent. But there was a sting in the tail of the trial: about one in 1,000 patients developed a potentially fatal infection while taking the drug.
Naturally, this has left specialists wary: “I think the message is not about canakinumab but rather the fact that this is the first trial that shows an outcomes benefit with modification of the immune system – and with no LDL (bad cholesterol) lowering,” Dr Thomas Power, a Pittsburgh consultant cardiologist told me. He feels the drug may never be used in cardiology because, among other reasons, it is extremely expensive and not approved by the US food and drugs agency.
Inflammatory reactions increase plaque instability, possibly resulting in plaque rupture or erosion
Our understanding of the biology of atherosclerosis has always incorporated the so-called inflammatory hypothesis. Inflammatory cells and signals drive the healing response to vascular injury, allowing the initiation and growth of atherosclerotic plaque. Inflammatory reactions increase plaque instability, possibly resulting in plaque rupture or erosion and setting up the response that causes myocardial damage and heart attack.
In a bullish presentation at the ESC, principal investigator Dr Paul M Ridker, director of the Centre for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston, said : “For the first time, we’ve been able to definitively show that lowering inflammation independent of cholesterol reduces cardiovascular risk. This has far-reaching implications. By leveraging an entirely new way to treat patients – targeting inflammation – we may be able to significantly improve outcomes for certain very high risk populations.”
“In my lifetime, I’ve seen three broad eras of preventative cardiology. First we recognised the importance of diet, exercise and smoking cessation. Then we saw the tremendous value of lipid-lowering drugs such as statins. Now we’re cracking the door open on the third era. This is very exciting,” he told delegates.
It’s a case of welcome back inflammation to the heart disease frontline
However, a more measured editorial in the New England Journal of Medicine noted: “Cantos has helped move the inflammatory hypothesis of coronary artery disease forward scientifically. However, the modest absolute clinical benefit of canakinumab cannot justify its routine use in patients with previous myocardial infarction until we understand more about the efficacy and safety trade-offs and unless a price restructuring and formal cost-effectiveness evaluation supports it.”
It’s a case of welcome back inflammation to the heart disease frontline but let’s wait for a suitable drug.