Elevated lipoprotein(a) [Lp(a)] levels are genetically determined and often lead to premature heart attacks and other vascular diseases. Yet in outpatient care, this serious risk frequently goes unnoticed. This has significant implications for patients — about 20% of the population — explained nephrologist Volker Schettler, MD, PhD, co-director at the center of nephrology in Göttingen, Germany, in an interview with Coliquio, a Medscape Network platform.
Schettler, deputy chairman of the German Society for Lipidology-Lipid League, is dedicated to improving the early detection and management of Lp(a)-related disorders. Through his professional association, he seeks to raise awareness of the cardiovascular risks associated with elevated Lp(a), particularly emphasizing the crucial role of primary care physicians in identifying and managing affected patients.
Why is an elevated Lp(a) level in the serum dangerous?
Studies, including the Copenhagen Heart Study, have shown that elevated Lp(a) levels are linked to a higher risk of cardiovascular events such as heart attack, stroke, and peripheral arterial disease, sometimes even at a young age. The risk depends on concentration: Serum levels below 30 mg/dL (75 nmol/L) are generally considered safe. Levels between 30 and 50 mg/dL (75-120 nmol/L) warrant closer evaluation for familial risk, as the condition can be hereditary. Levels above 50 mg/dL (over 120 nmol/L) carry a substantially increased cardiovascular risk, making it essential to manage other risk factors — such as diabetes, hypertension, obesit
Is Lp(a) an independent risk factor, or does it simply amplify other cholesterol elevations?
Lp(a) is an independent cardiovascular risk factor, as demonstrated by Mendelian randomization studies. Its underlying biology is complex; in simplified terms, Lp(a) consists of a low-density lipoprotein (LDL) particle bound via a disulfide bridge to apolipoprotein(a). This apolipoprotein interferes with the normal cellular uptake of LDL via the LDL receptor, causing Lp(a) particles to circulate longer in the bloodstream. Over time, this leads to chemical modifications of the particle and promotes the formation of atherosclerotic lesions. Overall, Lp(a) functions as a distinct lipid particle that contributes to atherogenesis independently of other risk factors.
The Lp(a) risk seems often overlooked in daily practice, especially by primary care physicians. Despite its potential danger, elevated Lp(a) levels are rarely detected. Why isn’t it measured routinely?
Unfortunately, this is a significant problem. Routine lipid screenings ordered by most primary care physicians — including cholesterol, triglycerides, HD
It’s estimated that 20%-30% of the population has elevated Lp(a). How reliable is this figure, and what does it mean for us?
According to a Danish study, approximately 20%-24% of Caucasians have critically elevated Lp(a) levels (over 50 mg/dL or 125 nmol/L). In Germany, this corresponds to roughly 8.4 million people who have elevated Lp(a) and are potentially at cardiovascular risk. This does not mean that every patient will experience a heart attack or stroke, but their risk is substantially higher and should be accounted for. Therefore, it is crucial for individuals to know their Lp(a) levels. This recommendation was reinforced in the recently published Brussels International Declaration.
What role does the primary care physician play in preventing and managing elevated Lp(a) levels?
The primary care physician’s role is critical. Ideally, a one-time Lp(a) measurement should be conducted in childhood or adolescence — for example, during the U9 checkup at age 5-6. A single test can provide valuable information. The cost is around €20 — a minor expense compared with the potential consequences of cardiovascular disease. Moreover, Lp(a) needs to be measured only once in a lifetime. Our clear recommendation is that every adult should know their Lp(a) level. If it is elevated, all other cardiovascular risk factors should be optimally managed. Since Lp(a) cannot currently be significantly modified by medication or lifestyle, early awareness of this risk factor is especially important.
There is an extracorporeal therapy to lower dangerously high Lp(a) levels. When is it indicated?
This refers to lipoprotein apheresis. It is indicated when a patient has elevated Lp(a) and has already experienced at least one cardiovascular event, with progression of vascular deposits occurring atypically for age, despite optimal management of all other risk factors. Deposits can occur in the brain, coronary arteries, or peripheral arteries. Unfortunately, in clinical practice, initiation of lipoprotein apheresis is often significantly delayed. In my view, it is scandalous that this life-saving therapy is sometimes postponed for 4-5 years.
There are new, promising treatment approaches. When will they be available?
Yes, this represents a significant advance. Currently, two promising therapeutic strategies are in development. One involves antisense therapeutics that inhibit apolipoprotein(a) expression in cells, reducing Lp(a) production by up to 90%-98% in current studies. The other involves molecules that disrupt disulfide bridge formation, preventing apolipoprotein(a) from binding to LDL particles and effectively blocking the formation of complete Lp(a) particles. Both approaches act locally in liver cells. Initial study results are expected in 2026-2027. These therapies will need to demonstrate not only reduced morbidity but also reduced mortality, as atherosclerosis is a complex inflammatory disease extending beyond lipid abnormalities.
These novel medications will be expensive and subject to restrictive bureaucratic access. What challenges should we anticipate?
Yes, this concern is understandable. The development of highly specific Lp(a) therapies will likely involve substantial costs, and complex administrative processes for prescribing are expected. Ensuring that these therapies are accessible to a broad patient population without overburdening the healthcare system will be a major challenge. As a professional society, we are prepared to support efforts to address these challenges.
This article was translated from Coliquio.
