Don’t ignore the other killer cholesterol

Lipoprotein(a) has emerged as a possible cause of unexplained heart attacks, and statins don't help.

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More use needs to made of testing for elevated levels of lipoprotein(a), a lesser-known cholesterol that on its own increases the risk of heart attack and stroke, a leading Australian cardiologist has said. 

Professor Jason Kovacic, who is also executive director of the Victor Chang Cardiac Research Institute, wants to see the test, which costs about $40, included on the MBS.

The Royal College of Pathologists of Australasia has applied to MSAC to have the test listed on the MBS as an independent predictor of cardiovascular disease. But the RACGP has made a submission to oppose the listing.  

Professor Kovacic warned that up to 20% of Australians could have at least mildly elevated levels of lipoprotein(a), also known as Lp(a) – although many will be completely asymptomatic. 

Lp(a) is now known to be a major risk factor for atherosclerosis with evidence showing that people with raised Lp(a) levels are two to four times more likely to develop the condition. 

It has a strong genetic association, but, to date, it is not part of the routine assessment done to ascertain cardiovascular risk. 

Researcher Professor Kovacic, who is a cardiologist at St Vincent’s Hospital, Sydney, said Lp(a) should not be overlooked. 

“It is very worrying that there could be tens of thousands of Australians who are at increased risk of developing heart disease but are completely oblivious to it. We could find these people with a one-off blood test,” Professor Kovacic said. 

He said men aged 55 years and under and women aged 60 years and under who had either a heart attack or had a family history of heart attack, particularly unexplained early heart attack should consider being tested for Lp(a). Unlike regular LDL, Lp(a) is more closely influenced by genetics, not lifestyle. 

“It’s independent of LDL cholesterol, independent of smoking and overweight, blood pressure, glucose, everything,” Professor Kovacic told The Medical Republic. “It alone can cause atherosclerosis, heart attack and stroke.” 

“There are people dying from this,” he said. “It’s really important we raise awareness and start thinking about Lp(a) for our patients. 

“We’d love to see this become reimbursed for by Medicare. At the moment it’s not, it’s an out-of-pocket expense of about $40. But there have been some discussions about trying to get this listed for reimbursement. We really need that to happen.” 

A spokesman for the Department of Health and Aged Care confirmed MSAC was considering the application, but no update on this was available. 

The move to have the test listed on the MBS has not found favour with the RACGP, which made a submission in October last year to MSAC opposing the application. 

In a letter to MSAC provided to The Medical Republic, past president Adjunct Professor Karen Price, said the RACGP had endorsed the National Vascular Disease Prevention Alliance Guidelines for the management of absolute cardiovascular disease risk.  

These guidelines are currently being updated and would include a revised calculator called the Australian Cardiovascular Disease (CVD) risk calculator, she wrote.  

“The focus of MSAC application 1736 is on measuring lipoprotein(a) to establish high cardiovascular risk. The new draft Australian CVD risk calculator includes several risk modifiers, with considerable overlap with indications for lipoprotein(a) testing, making the proposed test superfluous,” Professor Price wrote. 

“The RACGP recommends the new draft Australian CVD risk calculator should form the basis of cardiovascular risk screening and, therefore, does not support this application for lipoprotein(a) testing.” 

Lp(a) was discovered about 50 years ago, but data has emerged in the past 15 years to show that elevated Lp(a) levels are almost certainly a strong and independent cause of atherosclerosis.  

A standard lipid panel usually measures total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, but not Lp(a). 

“That’s why it really it rarely gets ordered, rarely gets thought about,” he said. 

For the past decade, pharmaceutical companies have been working to develop specific targeted therapies to treat elevated Lp(a).  

Some of these therapies have come through Phase II clinical trials and “look extremely promising” Professor Kovacic said. 

In the meantime, the only treatment for the condition is plasmapheresis, a procedure that involves removing blood, filtering the cholesterol and Lp(a) and then returning the blood to the patient. Professor Kovacic said this was usually reserved for severe cases, with some patients needing the procedure every one to two weeks. 

He said it was an effective treatment, but patients needed to have their Lp(a) levels carefully monitored on an ongoing basis to ensure further treatments were given as required. 

The other treatment is evolocumab, used off-label which is a monoclonal antibody used to treat high LDL cholesterol levels. Professor Kovacic said this was an expensive treatment for patients as it was not available through the PBS. Both treatments required specialist involvement, Professor Kovacic said. 

While current measures to minimising cardiovascular risk, such as diet, exercise and ensuring blood pressure and LDL and total cholesterol levels were at recommended targets were still valid – standard cholesterol treatments did not help elevated Lp(a) levels. 

“We do know that statins … are ineffective for lowering Lp(a),” he said. 

“We sometimes give statins to people who’ve got high Lp(a) when they have high LDL and total cholesterol to bring them down, and certainly that helps in these people. But statins themselves are ineffective [in treating Lp(a)].”  

Professor Kovacic said there was a whole new class of drugs that were probably a couple of years away from becoming available. 

Associate Professor Peter Psaltis, a Royal Adelaide Hospital cardiologist who also leads the heart and vascular program at the South Australian Health and Medical Research Institute, agreed doctors should take a proactive approach to test for high Lp(a) in patients with early heart disease and those considered at increased risk. 

“While we’re waiting for these new treatments to arrive, there is still a lot we can do to make sure that people with high Lp(a) levels have their other risk factors managed more aggressively,” he said. 

“We can also monitor these individuals more closely, but we can only do that if we identify them in the first place.”