Heart attack risk: Is expanded cholesterol testing warranted?

Morgan Liotta

31/01/2023 2:41:34 PM

Some specialists say screening is needed to detect ‘bad cholesterol’ linked to heart attacks in younger people, but the RACGP is cautious.

Cholesterol blood test
Current standard cholesterol testing does not include lipoprotein(a).

Heart disease experts have recently been calling for wider testing of lipoprotein(a) – or Lp(a) – the ‘bad cholesterol’ that is believed to lead to sudden heart attacks in younger people, warning that an estimated 20% of Australians could have mild or high levels but may not be aware of it.
Elevated levels of Lp(a) have been shown to increase the risk of the inherited genetic condition atherosclerosis that causes hardening of the arteries. In addition to some lifestyle factors, elevated levels are primarily due to genetic variations in the LPA gene, while the other ‘bad’ cholesterol, low-density lipoprotein, is linked to lifestyle factors.
These factors are prompting the calls for expanded screening, with the Royal College of Pathologists of Australasia putting forward a submission to the Medical Services Advisory Committee (MSAC) for Medicare funding of Lp(a) testing as an independent predictor of cardiovascular disease (CVD).
However, the RACGP does not support the application for Lp(a) testing at this stage, saying more evidence is needed to justify the benefits of it becoming a part of standard practice.
In an October 2022 submission to MSAC, the college states that several risk modifiers will be included in the revised Australian CVD risk calculator that have ‘considerable overlap’ with indications for Lp(a) testing, rendering the proposed test ‘superfluous’.
Instead, the RACGP recommends the new draft Australian CVD risk calculator should form the basis of screening.
Professor Mark Morgan, Chair of RACGP Expert Committee – Quality Care, believes there is a need for caution to ‘avoid confusion or implied recommendation’ for Lp(a) testing.
‘There is a big difference between population screening activities and the clinical work-up of selected patients who are particular high risk,’ he told newsGP.
Using examples of population screening including mammography and FOBT for bowel cancer, Professor Morgan cites the World Health Organization (WHO) version of Wilson and Jungner’s principles of screening, recommending that there should be a recognisable ‘latent or early symptomatic’ phase and ‘an accepted treatment’ for patients with recognised disease.
‘These principles effectively state that Lp(a) screening should only be considered if there is proven beneficial treatment available for screen-detected abnormal results,’ he said.
‘Much is still to be learnt about the biology of Lp(a) and the genetics that underpin the biology.
‘PCSK9 [Proprotein convertase subtilisin/kexin type 9] inhibitors have been shown to reduce Lp(a) levels, but it is not clear where they fit in primary prevention of patients’ first cardiovascular event.’
Currently Medicare does not cover any of the costs of Lp(a) testing. However, experts calling for testing expansion say patients with a family history of early heart disease, those who have had multiple heart attacks or strokes despite treatment, and people who have developed heart disease before the age of 65, should receive subsidised access.
Speaking to The Age, Professor Jason Kovacic, Executive Director at the Victor Chang Cardiac Research Institute, said raising awareness of the risks of elevated Lp(a) and increased access to testing is important.
‘We have long wondered why healthy people with low cholesterol levels and seemingly no other major risk factors like smoking or diabetes can suffer heart attacks,’ he said.
‘But we now understand that high levels of Lp(a) could be responsible for many of these events.’
Professor Morgan says this commentary is highlighting a subset of people who have high Lp(a) as an ‘often-inherited’ risk factor.
‘There would need to be an application of WHO screening principles and some modelling to ascertain whether there should be a screening program for this inherited risk factor,’ Professor Morgan said.
‘It would be wrong to jump in with ad hoc opportunistic testing without exploring harms, costs and benefits of novel treatments.’
Professor of General Practice at the University of Tasmania Mark Nelson, who has led extensive research on statins, agrees that while GPs should be aware of the risks of high Lp(a) levels and to consider testing people displaying any symptoms, more evidence is needed before expanded screening is established.
‘There is good evidence for Lp(a) as a significant risk factor,’ he told newsGP.
‘However, it is not standard screening nor rebated as such. The critical thing at the moment is for GPs to adopt risk algorithms and treat accordingly.’
Professor Nelson recommends following the new algorithm included in the updated Guidelines for the management of absolute cardiovascular disease risk, which is due to be released this year.
Mark-Morgan-article.jpgAppropriate screening principles and further modelling is needed to determine whether screening for Lp(a) should become standard, says quality care expert Professor Mark Morgan.

The RACGP Red Book, which is undergoing revision ahead of the release of its 10th edition, states that absolute CVD risk assessment should be conducted ‘at least every two years’ in all adults aged >45 years (>35 years for Aboriginal and Torres Strait Islander peoples) who are not known to have CVD or to be at ‘clinically determined high risk’, using the patient’s:

  • age
  • sex
  • smoking status total and high-density lipoprotein-cholesterol systolic blood pressure
  • other existing conditions.
‘In adults at low absolute CVD risk, blood test results within five years may be used for review of absolute CVD risk unless there are reasons to the contrary,’ the Red Book states.
It also identifies that ‘increased frequency and early onset’ of premature ischaemic heart disease or sudden cardiac death ‘may suggest’ the presence of genetically determined disease.
Professor Morgan says along with the updated Red Book, GPs should await the updated version of the CVD risk guidelines to see whether there is a recommendation to check Lp(a), but he highlights that equivalent international guidelines do not currently recommend the test.
‘For people in their 40s to 70s who do not have medical history that immediately throws them into a high-risk category, there will be an updated risk tool that is expected to be better able to assign a risk category to inform preventive lifestyle and treatments than the existing absolute cardiovascular risk calculator,’ he said.
‘For people who have strong family history of premature heart disease and high cholesterol levels there is a need to consider familial hypercholesterolaemia, which is underdiagnosed and under treated.’
The RACGP’s Genomics in general practice also includes guidance on screening and clinical decision-making for familial hypercholesterolaemia.
Until further clinical updates and evidence arise, Professor Morgan advises that further research supporting Lp(a) testing is needed.
‘In the 2021 scientific statement from the American Heart Foundation it is clear that there are significant priority areas for more research,’ he said.
‘The statement highlighted that the reference ranges and assays for Lp(a) are not standardised and there is a poorly determined impact of ethnicity on Lp(a) levels that is a priority for further research.
‘Before doing any test it is worth asking, “How will the test alter my management recommendations?”
‘For Lp(a) this question is not clearly answered.’
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