Lipoprotein(a), or Lp(a), is a distinct type of lipoprotein in the blood, different from the more commonly known LDL (“bad”) and HDL (“good”) cholesterol. Elevated levels of Lp(a) are an independent factor contributing to cardiovascular disease. This means high Lp(a) can increase heart risks even if other cholesterol levels appear normal.
Understanding Lipoprotein(a) and Its Significance
Lipoprotein(a) is a complex particle, structurally similar to low-density lipoprotein (LDL), but with an additional protein called apolipoprotein(a) [apo(a)]. Lp(a) is predominantly synthesized in the liver.
Elevated Lp(a) levels are an independent risk factor for various cardiovascular conditions, including atherosclerosis, heart attack, and stroke. The presence of apo(a) makes Lp(a) pro-atherogenic, pro-inflammatory, and pro-thrombotic. It contributes to plaque buildup in arteries and may interfere with the body’s natural clot-dissolving mechanisms.
Lp(a) levels are largely determined by an individual’s genetics, with the LPA gene being the primary determinant. This genetic variation accounts for 75% to 95% of the variation in Lp(a) levels among individuals. Due to this strong genetic influence, Lp(a) levels remain relatively consistent throughout a person’s life and are not significantly affected by typical lifestyle changes.
Dietary and Lifestyle Strategies
While Lp(a) levels are largely genetically determined, adopting heart-healthy dietary and lifestyle strategies remains valuable for individuals with elevated Lp(a). These approaches primarily reduce other cardiovascular risk factors, which can help offset the increased risk associated with high Lp(a). Managing overall cardiovascular health becomes more important when Lp(a) is elevated.
General heart-healthy dietary patterns, such as the Mediterranean diet, contribute to overall cardiovascular well-being. This diet emphasizes fruits, vegetables, whole grains, legumes, nuts, and olive oil, while limiting red meat and processed foods. While direct effects on Lp(a) levels from such diets are often modest, they can improve other lipid profiles, such as lowering LDL-cholesterol and triglycerides. Some research suggests that diets lower in saturated fat may even lead to a slight increase in Lp(a) levels, although more research is needed to fully understand these complex interactions.
Regular physical activity is another important component of a heart-healthy lifestyle. Exercise improves overall cardiovascular fitness and positively affects other lipid levels, such as increasing HDL cholesterol and lowering LDL cholesterol. However, moderate exercise does not significantly alter Lp(a) levels.
Maintaining a healthy weight and avoiding smoking are also important for reducing overall cardiovascular risk. Weight loss, especially in individuals with obesity, may influence Lp(a) levels, though findings vary. Quitting smoking significantly lowers the risk of heart disease and stroke, regardless of Lp(a) levels. These lifestyle modifications create a healthier environment for the cardiovascular system, which is beneficial even when Lp(a) cannot be directly lowered through these means.
Medical and Emerging Interventions
For individuals with significantly elevated Lp(a) levels and increased cardiovascular risk, medical interventions may be considered. Currently, no medications are specifically approved by the U.S. Food and Drug Administration (FDA) solely for lowering Lp(a). However, certain existing medications can have some effect on Lp(a) levels.
PCSK9 inhibitors, such as evolocumab and alirocumab, primarily lower LDL cholesterol but can also reduce Lp(a) levels by approximately 20% to 30%. The clinical significance of this Lp(a) lowering for cardiovascular outcomes is still under investigation. Niacin has been shown to lower Lp(a) levels by 20-38%, but it has not consistently reduced cardiovascular events in trials and can have notable side effects. Lipoprotein apheresis, a procedure similar to dialysis, physically removes Lp(a) from the blood. This is an option for individuals with extremely high levels and progressive cardiovascular disease despite other treatments.
Emerging therapies are specifically designed to target Lp(a) production. These include antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) therapies. Pelacarsen, an antisense oligonucleotide, works by preventing the liver from producing new Lp(a) particles. Clinical trials have shown that pelacarsen can significantly reduce Lp(a) levels, with some data suggesting reductions of up to 80%.
Small interfering RNA (siRNA) therapies, such as olpasiran and zerlasiran, also target Lp(a) production in the liver. These agents interfere with the genetic instructions for making Lp(a), leading to substantial reductions. These novel therapies are in advanced clinical trials, and their potential impact on cardiovascular outcomes is being evaluated.
Important Considerations for Management
Managing elevated Lp(a) involves several important considerations beyond specific reduction methods. Due to the strong genetic influence, significant lowering through lifestyle changes alone is challenging for many individuals, even those maintaining a healthy lifestyle.
Regular monitoring of Lp(a) levels is important, especially for individuals with a family history of high Lp(a) or early cardiovascular disease. Lp(a) testing is not part of a standard lipid panel and must be specifically requested by a healthcare provider. This testing helps assess individual risk and guide management strategies.
Given the complexity of Lp(a) and its management, consulting a healthcare professional is important for personalized risk assessment and treatment plans. A tailored approach is needed based on an individual’s overall cardiovascular risk profile, not just their Lp(a) level. Healthcare providers can integrate Lp(a) information with other risk factors to develop a comprehensive strategy for minimizing cardiovascular risk.