Cardiovascular disease: Getting to the heart of the matter

An estimated 22 per cent of Australia's population has heart disease. In light of this, Monash University’s Professor Stephen Nicholls – the recently appointed head of the Victorian Heart Hospital, due to open in 2022 at the University’s Clayton campus – has co-authored an important new study on heart disease medicine, published in The Lancet today.

"An estimated 22 per cent of Australia's population has heart disease."

The Lancet paper was co-written with cardiovascular and pharmacology experts from Imperial College in London, FASTA University in Argentina, and the MAC Hospital’s Cardiometabolic Centre in Mexico. Professor Nicholls is from Monash’s Cardiovascular Research Centre. The paper reviews known data on a wide range of heart disease drugs, and according to Professor Nicholls outlines “the state of play on where we are at the moment, and lays down the foundation for where the whole field is going to go”.

Heart disease – in research and in the clinic – is at a crossroads, he says. Treatments have been working, but only to a point. Heart attacks haven't been eliminated, but the chances of having one have gone down by 25-45 per cent. But the rest, which were going to happen, still happened.

The main treatment now is a statin, a class of drugs that lowers cholesterol – drugs with brand names such as Lipitor, Lescol, Pravachol or Zocor. Statins have been used for 30 years. They work by specifically targeting low-density lipoproteins, or LDL cholesterol. But since the 1980s, as the report’s authors highlight, “… additional therapies targeting different pathways in cholesterol metabolism are now available”.

Professor Nicholls explains: “What we're going to see over the next 10 to 15 years is a proliferation of a whole bunch of other therapies which not only target bad cholesterol (the LDL), but some of the other lipid factors in the blood.

“Right now, we treat everybody basically the same way, but in 10 to 15 years everyone will be treated a little differently, and that’s because we'll have a whole bunch of new therapies that target the disease in different ways, and will be able to guide the right patient to the right treatment at the right time. In the future it’s going to be about a personalised approach.”

Multiple therapies emerging

The Lancet paper analyses emerging drugs and finds the lipid field “has never been more promising, with the availability of multiple therapies that lower LDL cholesterol, as well as therapies targeting other lipid fractions, and the emergence of injectable therapies with infrequent dosing regimens.

“The challenge now,” it states, “will be how to prioritise these different approaches to optimise patient treatment.”

Genomics is one of those different approaches. “It's taken a massive step forward in the last five years,” says Professor Nicholls. “There’s been a search for the heart attack gene, but we've never found it. But we have found many genes and mutations and combinations of genes that probably contribute to a higher risk of heart attack. That’s what we call polygenic risk.” Also, he says, other emerging drugs have come from genetic discoveries. It's understood now in medicine that genes can be a cause of heart disease rather than just a bystander to it.

These emerging approaches to the health of the heart can be thought of through the idea of a simple blood test, says Professor Nicholls. ”You go to the doctor and have a blood test for cholesterol. It goes to the lab and you get four numbers back: the LDL, the low-density lipoprotein; an HDL which is the high-density lipoprotein; and a triglyceride – plus a total, but those are the three that matter. What I like to call the good, the bad, and the ugly. LDL is bad, HDL we think is good and in theory is supposed to protect you, and the triglycerides, which are thought to be the ugly player.

“The challenge now will be how to prioritise these different approaches to optimise patient treatment.”

“What we have done until now is essentially treat the LDL, with statins. We absolutely get that LDL is bad and makes you more likely to have heart attacks and strokes. But the wards are still full. This is why we’re building a heart hospital. So as good as a lot of those drugs are, heart attacks are still happening. We need to do more – we need to either lower LDL even further – and there are a number of new drugs that do that – or we need to start looking at other factors such as boosting the function of the good cholesterol, or lowering triglycerides.

“What we know,” he says, “is that for a lot of patients, statins are not a cure all. And we're now getting to the edge of where we can have drugs in the market that do something about that. We ignored it before because we didn’t have anything we could do, but now these drugs are being developed to target these factors, and that’s where the opportunity is.

“It will lead, we hope, to doctors and patients having a greater understanding of the idea that it’s not just about bad cholesterol anymore. It is about much more than that.”