Unmasking Hidden Risk: The EAS Lp(a) Calculator as a Roadmap for Aspirin in Primary Prevention- Dr Suhas G.C.

Looking Beyond Conventional Cardiovascular Risk: Rising Importance of Lipoprotein(a)

Lipoprotein(a) [Lp(a)] is increasingly recognised as an important piece of the cardiovascular risk puzzle, identifying inherited risk that may not be apparent from conventional risk factors such as age, smoking, blood pressure, diabetes and cholesterol. Predominantly genetically determined, elevated Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (1,2).

Current recommendations support measuring Lp(a) at least once in adulthood to identify this additional source of cardiovascular risk (1–3).

Lp(a) should be viewed as a continuous risk factor rather than simply “high” or “normal.”

The EAS consensus on Lp(a) in atherosclerotic cardiovascular disease and aortic stenosis considers <30 mg/dL (<75 nmol/L) a rule-out range, 30–50 mg/dL (75–125 nmol/L) a grey zone, and ≥50 mg/dL (≥125 nmol/L) associated with increased cardiovascular risk (2). The 2026 ACC/AHA guideline explicitly notes that equivalence between nmol/L and mg/dL is approximate (4).

The 2025 ESC/EAS focused update on the management of dyslipidaemias recognises elevated Lp(a) as a risk modifier that can help refine risk estimation and potentially reclassify patients, particularly those at moderate risk or close to treatment decision thresholds (1).

From an Lp(a) Value to Decoding the Patient's Actual CV Risk

• The clinical relevance of elevated Lp(a) is best understood in the context of a patient's baseline absolute cardiovascular risk.

• The same Lp(a) concentration may have relatively modest absolute implications in a young person with few conventional risk factors, yet substantially greater implications in someone with diabetes, hypertension, elevated LDL-C/ApoB, smoking exposure or a strong family history.

• The EAS consensus statement on Lp(a) illustrates the impact of elevated Lp(a) on an individual’s absolute ASCVD risk. An Lp(a) concentration of approximately 100 mg/dL (~250 nmol/L) may approximately double ASCVD risk, irrespective of baseline absolute risk. Thus, a baseline risk of 5% may rise to approximately 10%, whereas a baseline risk of 20% may approach 40% (2).

Lp(a)-Adjusted ASCVD Risk Calculator: How Does it Make the Hidden CV Risk Visible?

• The EAS Lp(a) Risk and Benefit Algorithm provides a practical way to visualise how much elevated Lp(a) may add to an individual's underlying cardiovascular risk (2).

• Rather than viewing an Lp(a) result in isolation, the calculator starts with estimated baseline cardiovascular risk and incorporates the patient's Lp(a) concentration to provide an Lp(a)-adjusted estimate. Its value lies in demonstrating the incremental risk that may otherwise remain unrecognised.

• For example, an individual whose estimated baseline ASCVD risk is 10% and whose Lp(a) is approximately 100 mg/dL may have an adjusted risk approaching 20%. In this scenario, elevated Lp(a) corresponds to an additional 10 percentage points of absolute cardiovascular risk.

Figure: Integrating Lp(a) for Identifying & Stratifying CV Risk

Elevated Lp(a): Rising Interest on Aspirin & Clinical Evidence

• In the Women's Health Study, carriers of the LPA rs3798220 variant had markedly elevated Lp(a) and greater cardiovascular risk, while randomisation to low-dose aspirin appeared to attenuate this excess risk (5).

• A subsequent ASPREE genetic analysis also suggested greater cardiovascular benefit from aspirin among individuals carrying Lp(a)-associated genotypes, particularly the rs3798220-C variant (6).

• Evidence based on measured Lp(a) has also emerged. In an observational analysis from the Multi-Ethnic Study of Atherosclerosis (MESA), aspirin use among participants with Lp(a) >50 mg/dL was associated with a lower risk of coronary heart disease events (7). Because aspirin exposure was observational rather than randomised, however, residual confounding cannot be excluded.

• Recent 2026 evidence further supports a cautious, risk-based individualized approach. The 2026 ACC/AHA multisociety dyslipidemia guideline recommends measuring Lp(a) at least once in all adults and recognises ≥50 mg/dL (≥125 nmol/L) as elevated, with emphasis on early and optimal control of modifiable cardiovascular risk factors. The guideline also notes that evidence suggesting aspirin benefit in elevated Lp(a) comes from post hoc analyses and that prospective trials are still required (4,9).

• In addition, a 2026 systematic review and meta-analysis found no significant overall reduction in major adverse cardiovascular events with aspirin among individuals with elevated Lp(a) or Lp(a)-raising variants, although a possible benefit signal was seen in carriers of the rs3798220-C variant (4,9).

Elevated Lp(a) is A Risk Modifier: Integrate in Overall CV Risk Assessment & Individualise

Current evidence does not support prescribing aspirin solely because a patient has elevated Lp(a) (2).

The genetic and observational findings suggest that Lp(a) may help identify patients with greater underlying cardiovascular risk, but randomised clinical-outcome evidence specifically testing aspirin in patients selected according to measured Lp(a) remains insufficient. This distinction matters because aspirin in primary prevention produces a modest reduction in cardiovascular events across broad populations but also increases major bleeding risk (8).

Lp(a) may therefore influence the expected cardiovascular-benefit side of the equation, particularly when it meaningfully raises absolute ASCVD risk, but aspirin decisions still require consideration of gastrointestinal and intracranial bleeding risk, age, comorbidities, concomitant medications and patient preference.

Elevated Lp(a) in Practice Today – How to Approach?

While dedicated Lp(a)-lowering therapies continue to be evaluated in clinical-outcome trials, identifying elevated Lp(a) already has practical implications.

• Management should focus on intensive control of modifiable cardiovascular risk factors, including appropriate LDL-C/ApoB lowering, blood-pressure optimisation, glycaemic management where relevant, smoking avoidance, healthy lifestyle measures and reassessment of overall cardiovascular risk (1-3).

• In patients with elevated Lp(a), low-dose aspirin may be considered after assessing overall cardiovascular benefit against individual bleeding risk (7).

Key Clinical Takeaways

• Lp(a) is a genetically determined, independent and continuous ASCVD risk factor and should generally be measured at least once in adulthood.
• Lp(a) can meaningfully increase absolute cardiovascular risk. The EAS Lp(a) Risk and Benefit Algorithm helps quantify this incremental risk; for example, a baseline risk of 10% may increase to approximately 20% at an Lp(a) level of ~100 mg/dL, depending on patient-specific risk factors.
• Elevated Lp(a) warrants closer attention to modifiable cardiovascular risk factors, including LDL-C/ApoB, blood pressure, glycaemia, smoking and lifestyle.
• Lp(a) can inform the aspirin risk-benefit discussion but does not independently determine treatment. Aspirin use in primary prevention remains an individualised decision based on cardiovascular benefit, bleeding risk and patient-specific factors.

Abbreviations

Lp(a)- Lipoprotein (a); ASCVD- Atherosclerotic Cardiovascular Disease; EAS- European Atherosclerosis Society; MESA- Multi-Ethnic Study of Atherosclerosis