Identifying High-Risk Indicators for Lipoprotein(a)
The intricacies of Lipoprotein(a) [Lp(a)] measurements and how they relate to the risk of atherosclerosis and aortic valve complications.
Interpreting Lp(a) Levels:
Different consensus guidelines suggest varying thresholds for high-risk Lp(a) levels, with some indicating levels over 100 nanomoles per liter or 125 nanomoles per liter as high-risk.
Elevated Lp(a) levels are considered a significant risk factor for atherosclerosis, but it's noted that not all individuals with high Lp(a) levels will manifest atherosclerosis or aortic stenosis.
Lp(a) Risk Assessment:
High Lp(a) levels, while highly heritable and a major cause of atherosclerosis, may not always directly translate to disease manifestation in every individual.
Clinicians assessing individuals with very high Lp(a) levels should consider them at very high risk; however, advancements in additional tests may help further evaluate individual risk profiles in the future.
Lp(a) Thresholds:
Guidelines distinguish between risk thresholds based on mass concentrations (milligrams per deciliter) and molar concentrations (particle numbers).
Normal mass concentrations are considered under 30 milligrams per deciliter, with significant risk typically observed at levels of 50-70 milligrams per deciliter.
For particle counts, normal levels are under 15 nanomoles per liter, with thresholds for high risk around 100-125 nanomoles per liter, approaching the 80th and 90th percentiles of the population distribution.
Factors Influencing Risk:
Other risk factors such as high LDL cholesterol, non-HDL cholesterol, apoB levels, hypertension, smoking, coagulation disorders, diabetes, and familial history can exacerbate the risk associated with elevated Lp(a) levels.
Evaluating the collective impact of these risk factors alongside high Lp(a) levels can help gauge individual risk more comprehensively.
Genetic Influence and Drug Therapy:
Individuals with exceptional genetics or those on lipid-lowering medications can achieve low levels of Apolipoprotein B (APO B) and LDL cholesterol, indicating effective lipid management.
Despite having optimal APO B levels, there is still a need to measure Lp(a) due to its genetic abnormality and potential risk implications.
Cascade Testing and Risk Assessment:
Cascade testing can be advisable for family members to assess Lp(a) levels due to its genetic nature.
Recent trials with PCSK9 inhibitors, such as the Fier and Odyssey trials, have shown benefits in lowering both APO B and Lp(a) levels, which can further reduce cardiovascular risk and residual events.
Residual Risk and LP(a) Reduction:
Even with APO B levels at 30 or lower, there may still be residual risk, especially related to elevated Lp(a) levels.
Lowering Lp(a) levels significantly, possibly by 100 milligrams per deciliter, is suggested to mitigate atherosclerotic risk, beyond what current treatments can achieve.
Drug Development and Future Perspectives:
Existing treatments like statins may not effectively reduce Lp(a) levels, even when achieving LDL cholesterol goals, indicating the need for alternative therapies.
New drugs under development that target Lp(a) directly show promise in significantly lowering Lp(a) levels, offering potential solutions to address residual cardiovascular risk associated with elevated Lp(a).
