Cardiovascular Health Emerging Therapies and Research

The Important Role of Lipoprotein(a) in Heart Health

A purple lipoprotein particle with a coiled tail floats over a plaque-lined artery, an amber liver behind it.

What is Lipoprotein(a)?

Lipoprotein(a), or LP(a), is a lipoprotein particle consisting of a low-density lipoprotein (LDL) particle bound to a protein called apolipoprotein(a). The levels of LP(a) are determined primarily by the liver’s production rate of apolipoprotein(a).

LP(a) Levels in the Population

About 20% of people have elevated LP(a) levels, with higher rates seen in those of African ancestry. LP(a) levels are largely influenced by genetic variants in the LPA gene that codes for apolipoprotein(a). The inheritance patterns of these LPA gene variants are complex.

LP(a) and Heart Disease Risk

High LP(a) levels markedly raise a person’s risk of heart attacks, strokes, peripheral artery disease (PAD), and especially aortic valve stenosis. LP(a) likely contributes to plaque inflammation and progression inside blood vessels. The higher the LP(a) level, the greater the risk for these cardiovascular diseases.

Treatment Options for High LP(a)

Statins do not lower LP(a) levels.
Niacin only lowers LP(a) moderately.
PCSK9 inhibitor injections can lower LP(a) by about 30% on average.
Antisense oligonucleotides targeting the LPA gene can lower LP(a) by around 80% and are now in phase 3 clinical trials.

Recommendations for Those with Elevated LP(a)

Until better LP(a)-lowering drugs become available, it is vital for patients with high LP(a) levels to:

Aggressively lower LDL and ApoB levels as much as is safe and tolerable.
Get screened for aortic valve disease, which is common with very high LP(a).
Discuss adding a PCSK9 inhibitor if LDL/ApoB levels are not yet optimized.
Commit to heart-healthy lifestyle changes like a Mediterranean-style diet, regular exercise, and stress reduction techniques.

The Importance of Checking LP(a)

Since elevated LP(a) is the most common genetically-influenced risk factor for premature cardiovascular disease, patients should ask their doctor to check their LP(a) level at least once. This is especially pertinent for those with a family history of early-onset heart attacks or strokes. Detecting and addressing high LP(a) can motivate earlier and more intensive prevention efforts.

How Statins and PCSK9 Inhibitors Influence LP(a)

Statins work by boosting LDL clearance from the bloodstream but do not directly lower LP(a) production. Consequently, some studies show statins slightly increasing LP(a) levels. PCSK9 inhibitors work differently by reducing LP(a) production. Adding a PCSK9 inhibitor to a statin regimen has been shown to increase LP(a) clearance.

Exciting Potential of New LP(a)-Lowering Medications

Antisense oligonucleotides designed to block production of apolipoprotein(a) represent an exciting new approach to dramatically lower high LP(a). In clinical trials, these injectable medications lowered LP(a) levels by around 80%. Large cardiovascular outcomes trials are underway to prove whether this LP(a) reduction translates into real-world benefits like preventing heart attacks and strokes.

Improved understanding of the genetics, pathophysiology, measurement, and treatment of this unique lipoprotein over the past decade provides hope for better cardiovascular health among the 20% of people genetically predisposed to high levels.