In the FOURIER trial, 25,090 patients with stable ASCVD had baseline Lp(a) measured, and lower Lp(a) levels were linked to higher diabetes risk: prevalent diabetes rose with lower Lp(a) (adjusted OR 1.03, 95% CI 1.02-1.04) and incident diabetes also increased during follow-up (adjusted HR 1.02, 95% CI 1.01-1.03). The same analysis found no association between low Lp(a) and hemorrhagic stroke, serious bleeding, neurocognitive events, malignancy, or atrial fibrillation.

Why It Matters To Your Practice

• Lp(a)-lowering therapies are in clinical testing, so understanding whether very low Lp(a) carries safety tradeoffs matters now.

• In this secondary analysis of FOURIER, lower Lp(a) tracked with diabetes prevalence and new-onset diabetes, but not with several other major adverse safety outcomes.

• For NPs and PAs managing cardiometabolic risk, this supports closer glucose surveillance in patients with very low Lp(a), especially those with existing diabetes risk factors.

Clinical Benefits

• Low Lp(a) was not linked to higher risk of hemorrhagic stroke, serious bleeding, neurocognitive events, malignancy, or atrial fibrillation.

• That finding may reassure clinicians considering future Lp(a)-lowering strategies in high-risk ASCVD populations.

• The data help frame patient counseling: lower Lp(a) may not broadly worsen safety outcomes, but glycemic risk deserves attention.

Managing Risks

• Review baseline diabetes risk before and during intensive lipid-lowering care: A1c, fasting glucose, weight, family history, and metabolic syndrome features.

• If patients have very low Lp(a) or eventually start Lp(a)-lowering therapy, monitor for dysglycemia and reinforce lifestyle measures that reduce diabetes risk.

• Avoid overinterpreting causality for individual patients: the diabetes association was modest, and this analysis does not prove that lowering Lp(a) causes diabetes.

The Bottom Line

• Among patients with stable ASCVD in FOURIER, lower Lp(a) was associated with higher prevalent and incident diabetes risk.

• Low Lp(a) was not associated with increased risk of most other studied safety events.

• In practice, pair interest in Lp(a) lowering with routine glucose monitoring and balanced patient counseling.