Core IM | Internal Medicine Podcast · Core IM Team

#174 Lp(a) and ASCVD Risk: 5 Pearls Segment

·43 min·4 clips

New Lp(a) drugs in trials could revolutionize treatment for high-risk patients within years.

This episode focuses on lipoprotein(a), or Lp(a), a genetically determined particle that increases atherosclerotic cardiovascular disease risk. Hosts Dr. Shreya Trivedi and Dr. Ian Kelly, joined by cardiologist experts, explore its clinical significance. They break down the topic into five key pearls for internal medicine practitioners. Lp(a) is a subtype of LDL with an attached apolipoprotein(a) that makes it uniquely atherogenic and thrombogenic. Dr. Steve Nissen notes a high concordance rate, where about half of first-degree relatives of someone with high Lp(a) also have elevated levels. A 1981 study found patients with Lp(a) levels over 50 mg/dL had a 2.3-fold higher heart attack risk. Proposed mechanisms for its harm include increasing phospholipid oxidation, promoting inflammation, and enhancing local thrombosis by competing with plasminogen. Dr. Greg Katz explains Lp(a) carries oxidized phospholipids and increases their oxidation rate. Apolipoprotein B (ApoB) measures the total number of atherogenic particles, while Lp(a) represents a specific high-risk type, often described as a particularly problematic "vehicle" in a traffic analogy. Testing recommendations vary, with Dr. Coco Fresh suggesting three buckets: secondary prevention patients with unexplained events, primary prevention patients with intermediate risk, and those with a strong family history of premature ASCVD. In contrast, the National Lipid Association recommends universal testing once in adulthood, citing a global prevalence of 20-25% for elevated Lp(a). Levels are largely static after age five and are minimally affected by acute illness. Interpretation uses two units: nanomoles per liter (particle concentration) or milligrams per deciliter (mass). Levels above 50 mg/dL or 125 nmol/L are generally considered elevated, with risk increasing linearly. Data from the UK Biobank study of 500,000 people over 11 years shows this continuous relationship. An equation exists to refine ASCVD risk estimates using a patient's Lp(a) level, multiplying their pooled cohort equation score by a hazard ratio. For a patient with a level of 500 nmol/L, a 5.5% estimated risk could be recalculated to roughly 15%. Current management focuses aggressively on modifying all other conventional risk factors, as no therapy directly lowers Lp(a) yet. Dr. Nissen calls this "prevention 1.5" and emphasizes getting LDL below 55 mg/dL. An elevated Lp(a) acts as a tiebreaker, encouraging more aggressive statin use and lifestyle counseling. Statins may raise Lp(a) by 10-20%, but this does not negate their cardiovascular benefit. The prothrombotic nature leads to questions about aspirin for primary prevention, but data is only from retrospective analyses and is hypothesis-generating. Promising direct therapies, like pelacarsen in the Lp(a) HORIZON trial, are in the pipeline. The tone is educational and conversational, designed for clinical learners with clear analogies and practical takeaways. It employs a structured pearl format with interactive questions and expert interviews. This episode is ideal for internists, cardiologists, and trainees seeking a nuanced, evidence-based primer on Lp(a) testing and contemporary management. Listeners looking for definitive treatment guidelines or those uncomfortable with probabilistic risk discussions might find it less immediately actionable.

As heard by us

A clear, clinically useful look at a risk marker that is easy to overlook.

The segment treats Lp(a) as a risk marker worth knowing, and it keeps the discussion grounded. Shreya Trivedi and Ian Kelly move quickly through what the number means, why nmol/L is the cleaner unit, and why the real question is often how much risk it adds, not whether it lands…

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Why you'd press play

If Lp(a) sounds abstract, this gives it a real clinical shape.

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