🧠Cardiovascular risk has been highlighted this year. As part of screening, lipoprotein A / Lp(a), which we will analyze today, became familiar to the general public.
🟢Vol. 10: Lipoprotein (a)
🧑⚕️📜Cardiovascular risk describes the likelihood of developing atherosclerotic disease (small plaques within the lumen of arteries that partially or completely obstruct blood flow) in vital arteries, such as the coronary arteries (heart) and carotid arteries (brain). This can lead to problems we all know, such as heart attack or ischemic stroke.
☢️🆘There are risk factors that favor the development of atherosclerotic disease, thereby increasing cardiovascular risk. Some of these are modifiable, meaning we can intervene and reverse their negative effects, and independent, meaning they promote atherosclerosis regardless of the presence of other risk factors.
🍔🚬🩺Classic independent, modifiable risk factors include smoking, hypertension, LDL (bad) cholesterol, and diabetes. Recent research has highlighted Lp(a) as another such factor. Let’s get to know some basics about it.
🧬🦠Its molecule is more complex than classic lipids, arising from the combination of apolipoproteins A and B, and it contains LDL cholesterol. Lp(a) levels in the blood are mainly genetically determined, meaning they are primarily influenced by the structure and function of the genes we are born with and far less by lifestyle and diet. Therefore, they do not show significant fluctuations throughout our life regardless of habits and profile (there are some exceptions, such as certain chronic inflammatory conditions).
🩸🤔Currently considered useful thresholds are 30 mg/dl (upper normal limit), 50 mg/dl, and 180 mg/dl. But how do we lower Lp(a) levels?
💊💉Classic cholesterol-lowering drugs (e.g., statins, ezetimibe) do not significantly affect Lp(a). PCSK-9 inhibitors are an exception. However, they are injectable, expensive and not easily accessible drugs. To be more specific, they are available only to very few patients who need particularly aggressive LDL reduction.
⁉️🤯So why did we measure Lp(a) in such a large part of the population if, for most people with high levels, we cannot intervene?
✅🗣For now, Lp(a) levels highlight the need for optimal management of other modifiable risk factors (e.g., smoking cessation, achieving ideal LDL and blood pressure targets), help doctors and patients decide on starting treatment in borderline cases, and may explain some cases that do not have the expected LDL reduction with diet, exercise and medication.
ℹ️🤝🆕Of course, there is ongoing research. Advanced-phase studies investigating new drugs for safety and efficacy in lowering Lp(a) are being conducted. These drugs are based on modern technologies and are intended for oral administration. The main approaches are to reduce apolipoprotein A levels and to decrease hepatic synthesis of Lp(a). Therefore, in a few years, we will be able to safely reduce Lp(a) levels.
📖References
-Reyes-Soffer G, Ginsberg HN, Berglund L, Duell PB, Heffron SP, Kamstrup PR, Lloyd-Jones DM, Marcovina SM, Yeang C, Koschinsky ML; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; and Council on Peripheral Vascular Disease. Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2022 Jan;42(1):e48-e60. doi: 10.1161/ATV.0000000000000147. Epub 2021 Oct 14. PMID: 34647487; PMCID: PMC9989949.
-Man S, Zu Y, Yang X, Deng Y, Shen D, Ma Y, Fu J, Du J, Yu C, Lv J, Li G, Wang B, Li L. Prevalence of Elevated Lipoprotein(a) and its Association With Subclinical Atherosclerosis in 2.9 Million Chinese Adults. J Am Coll Cardiol. 2025 Jun 3;85(21):1979-1992. doi: 10.1016/j.jacc.2025.02.032. Epub 2025 Apr 23. PMID: 40266173.