The TL;DR
Lipoprotein(a), or Lp(a), is a specific type of cholesterol particle determined almost entirely by genetics, not diet or lifestyle. It acts like a “triple threat”: it causes plaque (atherogenic), promotes inflammation (pro-inflammatory), and promotes clotting (thrombogenic). Elevated levels affect ~20% of the population and are the leading genetic cause of early heart attacks. You only need to test it once.
Accessibility Level
Level 2 (Optimization): Not standard. Must be specifically requested. Since it is genetic, a single test in your lifetime is sufficient to know your risk status.
The Science of Lp(a)
Lp(a) is essentially an LDL particle with an extra protein tail called Apolipoprotein(a) attached to it. This “tail” is the problem.
- Sticky: It binds avidly to the arterial wall.
- Clotting: It mimics plasminogen, interfering with the body’s ability to dissolve clots.
- Oxidation: It carries oxidized phospholipids (OxPL), which act as inflammatory grenades in the vessel wall.
The Genetic Lottery
Diet and exercise have almost zero effect on Lp(a). You cannot “run off” a high Lp(a). It is an autosomal dominant trait. If you have it, your siblings and children have a 50% chance of having it.
Evidence Matrix
| Source | Verdict | Notes |
|---|---|---|
| Sotirios Tsimikas | Leading Expert | Established the causal link between Lp(a) and aortic stenosis/CVD. |
| Peter Attia | Critical Screen | Mandates testing for every patient. “The most common genetic driver of CVD we miss.” |
| Clinical Guidelines | Increasing | ESC and ACC now recommend at least once-in-a-lifetime screening for all adults. |
Risk Ranges
| Level | mg/dL | nmol/L | Risk Profile |
|---|---|---|---|
| Normal | < 30 | < 75 | Baseline risk. |
| Borderline | 30 - 50 | 75 - 125 | Mildly increased risk. |
| High | > 50 | > 125 | 2-3x risk of CVD. |
| Very High | > 100 | > 250 | Significant risk; requires aggressive management of other factors. |
(Note: Assays vary. Always check if your lab reports in mg/dL or nmol/L. They are not directly convertible by a simple factor.)
How to Manage
Since you cannot lower Lp(a) easily (yet), you must aggressively lower every other risk factor to “make room” for the risk.
- Crush ApoB: If you have high Lp(a), your ApoB target should be lower (e.g., < 40-50 mg/dL).
- Control Blood Pressure: Hypertension + High Lp(a) is a deadly multiplier.
- Therapies:
- PCSK9 Inhibitors: Can lower Lp(a) by 20-30% (off-label benefit).
- Antisense Oligonucleotides (ASOs): New drugs (Pelacarsen, Olpasiran) in Phase 3 trials specifically lower Lp(a) by 80%+. (Coming soon).
References
Tsimikas, S. (2017). A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies. Journal of the American College of Cardiology, 69(6), 692-711.
Emerging Risk Factors Collaboration. (2009). Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA, 302(4), 412-423.
O’Donoghue, M. L., et al. (2019). Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk. Circulation, 139(12), 1483-1492.