January/February 2026
Study finds very high lipoprotein(a) level predicts 30-year CV risk in healthy women
By Sasha Ellery BM BCh
Healthy middle-aged women with very high lipoprotein(a) [Lp(a)] concentrations have a substantially higher 30-year risk of major cardiovascular (CV) disease, a large prospective cohort study finds.
Published in JAMA Cardiology, researchers analysed the 27,748 participants in the US Women’s Health Study who had baseline Lp(a) measure ments. These women were free of CV disease, cancer and major chronic illness, and were followed up for 30 years.
Compared with women with lower levels of Lp(a), those with levels above 30mg/dL (above the 75th percentile) had significantly higher longterm risk of major CV events (defined as incident myocardial infarction, coronary revascularisation, ischaemic stroke and CV death) and coronary heart disease. There was a stepwise increase in the risk of coronary heart disease with rising Lp(a) levels.
Lp(a) levels above 120 mg/dL (above the 99th percentile) were also associated with higher risks of ischaemic stroke and CV death.
Commenting on the study, Professor Stephen Nicholls, Cardiologist and Program Director at the Victorian Heart Hospital, Melbourne, explained: ‘Lp(a) is essentially a low-density lipoprotein (LDL)-like particle with an additional protein bound. It is more atherogenic than LDL. It is tightly regulated by the LPA gene, so diet and exercise won’t do much to the level.’
He said the implications of the study findings for primary care were immediate.
‘The data are clear that Lp(a) is a risk factor for heart disease that we have underappreciated. Knowing someone’s Lp(a) level, today, changes practice. It reclassifies risk,’ he told Medicine Today.
‘The European Atherosclerosis Society and the European Society of Cardiology guidelines are clear that Lp(a) should be tested and if it is high then we should treat the other risk factors (cholesterol, blood pressure) more intensively. The guidelines recommend that it should be measured if there is a personal or family history of premature CV disease or if family members have an elevated level.’
The researchers noted that although only a small proportion of healthy women would have an increased risk of CV disease because of high Lp(a) levels, this increased risk was comparable to that seen in familial hypercholesterolaemia and thus early identification of such patients was key.
For GPs managing patients with markedly elevated results, Professor Nicholls outlined a pragmatic approach.
‘Step one: reclassify risk; step two: intensify treatment of other risk factors.’
He noted additional options in selected patients. ‘Step three: consider aspirin in those with severe elevations. Step four: refer for consideration of clinical trials.’
Professor Nicolls said there were a number of novel therapies [targeting Lp(a)] in development, with trials of those all underway in Australia and available for Australian patients.