From the Guidelines
Lipoprotein(a) levels can fluctuate due to various factors, including genetics, acute inflammation, hormonal changes, and certain medications, with the most significant influence being genetics, accounting for approximately 70-90% of the variation in Lp(a) concentrations. The fluctuations in Lipoprotein(a) (Lp(a)) levels can be attributed to several factors, as outlined in the study by 1, which lists major factors affecting the concentration of lipoprotein (a) in humans. These factors include Apo(a) size polymorphism, LDL-R, MODY (HNF-4a), acute phase, renal disease, diabetes mellitus, liver diseases, alcohol, thyroxine, pregnancy, oestrogens, progesterone, tamoxifen, tibolone, raloxifene, testosterone, anabolic steroids, ACTH, niacin, fibrates, statins, L-Carnitine, N-acetyl-cysteine, acetylsalicylic acid, and LDL/Lp(a) apheresis.
Factors Influencing Lp(a) Levels
- Genetics: Approximately 70-90% of the variation in Lp(a) concentrations is attributable to inherited factors, particularly the LPA gene 1.
- Acute inflammation: Lp(a) is an acute phase reactant that may temporarily increase during illness, infection, or after surgery 1.
- Hormonal changes: Estrogen typically lowers Lp(a) levels, while testosterone may increase them 1.
- Medications: Certain medications like niacin and PCSK9 inhibitors can modestly reduce Lp(a) levels, though these effects are generally secondary to their primary lipid-lowering actions 1.
- Liver disease: Liver disease may decrease Lp(a) since it's produced in the liver 1.
- Kidney disease: Kidney disease, particularly nephrotic syndrome, can increase Lp(a) levels 1.
Recommendations for Accurate Assessment
For accurate assessment of a person's Lp(a) status, multiple measurements taken when the individual is in good health are recommended, as this provides the most reliable indication of their baseline level. This approach helps to account for potential fluctuations due to acute inflammation, hormonal changes, or other factors. Additionally, considering the influence of genetics and other factors on Lp(a) levels, it is essential to interpret Lp(a) measurements in the context of an individual's overall health and medical history.
From the Research
Factors Influencing Lipoprotein(a) Levels
Lipoprotein(a) (Lp(a)) levels can fluctuate due to various factors. The main factors include:
- Genetics: Lipoprotein(a) levels are determined 80-90% by genetics and differ by up to 1000-fold between individuals 2.
- Non-genetic factors: These include diet, physical activity, hormones, and certain pathological conditions such as kidney and liver diseases 3.
- Inflammation: Lipoprotein(a) levels are also influenced by inflammation, as the LPA promoter contains an interleukin-6 response element; interleukin-6 released during the inflammatory response results in transient increases in plasma lipoprotein(a) levels 4.
Impact of Non-Genetic Factors on Lipoprotein(a) Levels
Non-genetic factors can modify Lp(a) levels, including:
- Diet: Diets lower in saturated fats modestly influence Lp(a) levels and often in the opposing direction to LDL cholesterol 3.
- Hormones: Hormone replacement therapy (HRT) in postmenopausal women lowers Lp(a) levels, with oral being more effective than transdermal estradiol 3.
- Kidney and liver diseases: Kidney diseases result in marked elevations in Lp(a) levels, while liver diseases result in reduced Lp(a) levels 3.
Clinical Relevance of Lipoprotein(a) Levels
Lp(a) is a critical component of the residual risk for cardiovascular and valvular heart diseases, with up to 1 billion people around the globe having an Lp(a) level that places them in a high-risk category 5. Lp(a) is strongly associated with calcific aortic valve stenosis (CAVS), coronary artery disease (CAD), peripheral arterial disease (PAD), and to a lesser extent with ischemic stroke (IS) and heart failure (HF) 5. Lp(a) levels are influenced by genetic factors, including LPA kringle IV-2 domain size, single-nucleotide polymorphisms, and interleukin-1 genotypes 4. Genetic loci beyond LPA, such as APOE and APOH, have been shown to impact lipoprotein(a) levels 4.
Variability in Lipoprotein(a) Levels
Lp(a) concentrations are generally 5% to 10% higher in women than men, and there is up to a 3-fold difference in median Lp(a) concentrations between racial and ethnic populations 4. Lp(a) levels can be screened using routine, non-fasting blood draws, making it convenient for patients 4. Several investigational, RNA-targeted agents have shown promising Lp(a)-lowering effects in clinical studies, and large-scale Lp(a) testing will be fundamental to identifying eligible patients should these agents become available 6, 4.