Lipoprotein(a), or Lp(a), is a specific type of cholesterol-carrying particle in the blood that is an independent marker of cardiovascular risk. It is structurally similar to low-density lipoprotein (LDL) but carries an additional, unique protein component. An elevated Lp(a) level is a significant factor that increases the likelihood of developing heart attacks, strokes, and aortic valve stenosis. Understanding this lipoprotein and the strategies to manage its associated risk is important for heart health.
Why Lp(a) Differs From Other Cholesterol
Lp(a) is distinct from LDL cholesterol due to its unique structure and genetic origins. It consists of an LDL particle covalently bound to a protein called apolipoprotein(a), or apo(a). This apo(a) protein contributes to both the buildup of plaque in arteries and the promotion of blood clots.
The level of Lp(a) is largely determined by genetics, accounting for 70 to 90 percent of the concentration. Because of this strong genetic control, a person’s Lp(a) level remains stable throughout their lifetime, regardless of diet or exercise. Unlike high LDL cholesterol, which is often a result of lifestyle factors, a high Lp(a) level is a fixed, inherited trait. A level above 50 mg/dL (approximately 125 nmol/L) is considered a threshold for increased cardiovascular risk.
Lifestyle Steps That Provide Minimal Impact
While a heart-healthy lifestyle is beneficial for overall cardiovascular wellness, these interventions have only a modest effect on Lp(a) levels. Following a diet rich in fruits, vegetables, and whole grains, such as the Mediterranean diet, is necessary for reducing other lipid markers and managing blood pressure. However, these changes should not be relied upon to reduce high Lp(a) itself.
Aerobic exercise, while improving endothelial function and maintaining a healthy weight, does not substantially alter the genetically determined Lp(a) concentration. Dietary interventions aimed at reducing saturated fats, a standard approach for lowering LDL, can sometimes lead to a slight increase in Lp(a). This highlights Lp(a)’s resistance to traditional lifestyle modification efforts. Some dietary supplements, such as L-carnitine, Coenzyme Q10, and flaxseed, may show a mild lowering effect in small trials. However, the magnitude of this effect is usually too small to achieve the reduction needed to mitigate high-risk levels.
Established Medical Strategies for Risk Management
Since Lp(a) is difficult to lower, current medical practice focuses on aggressively managing the overall cardiovascular risk in patients with elevated levels. High-dose niacin (Vitamin B3) is one of the few established medications that can directly reduce Lp(a) mass, often by 20 to 30 percent. However, its use is uncommon due to frequent side effects like flushing and its failure to demonstrate a definitive reduction in cardiovascular events in large clinical trials.
Statins, the most commonly prescribed class of lipid-lowering drugs, are essential for reducing LDL cholesterol and are often prescribed to patients with high Lp(a) to lower overall risk. Statins have a neutral effect on Lp(a) and can sometimes cause a marginal increase in its concentration. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab and evolocumab, are highly effective at lowering LDL and provide a modest Lp(a) reduction of 15 to 30 percent. These injectable medications are used in high-risk patients who require maximal lowering of their atherogenic lipid burden. In extremely high-risk cases, lipoprotein apheresis can be used. This procedure mechanically filters Lp(a) and other lipoproteins from the blood, achieving acute reductions of 50 to 85 percent.
Highly Targeted Therapies for Significant Reduction
The future of Lp(a) management lies in therapies specifically designed to inhibit its production in the liver. These novel treatments use advanced genetic mechanisms to target the messenger RNA (mRNA) that carries instructions for making the apo(a) protein. Antisense oligonucleotides (ASOs), such as pelacarsen, bind to the specific mRNA sequence, leading to its degradation and preventing the synthesis of apo(a).
Small interfering RNAs (siRNAs), including olpasiran and lepodisiran, function similarly by silencing the gene expression of apo(a). These nucleic acid-based therapies have demonstrated high efficacy in clinical trials, achieving Lp(a) reductions ranging from 70 to over 90 percent. Several agents are currently in large-scale Phase 3 cardiovascular outcomes trials to prove that this profound reduction translates into fewer heart attacks and strokes. These targeted therapies represent the most promising avenue for directly addressing the risks associated with elevated Lp(a) levels.