Do statins cause apolipoprotein(a) to convert to apolipoprotein B?

From the Guidelines

No, statins do not cause Apolipoprotein (a) to turn into Apolipoprotein B. These are two distinct proteins involved in lipid transport in the bloodstream. Apolipoprotein (a) is a component of lipoprotein(a) [Lp(a)], while Apolipoprotein B is the main protein component of LDL cholesterol. Statins, which include medications like atorvastatin (Lipitor), rosuvastatin (Crestor), and simvastatin (Zocor), work by inhibiting an enzyme called HMG-CoA reductase that is involved in cholesterol production in the liver. This reduces LDL cholesterol levels in the blood.

Key Points

• While statins effectively lower LDL cholesterol and Apolipoprotein B levels, they generally have minimal to no effect on Lp(a) levels, as noted in a study published in the Journal of the American College of Cardiology 1.
• In fact, some studies suggest statins might slightly increase Lp(a) levels in some patients, which is a seeming paradox since both are associated with CV benefit 1.
• The two apolipoproteins have different genetic origins and functions, and one cannot transform into the other through medication effects or metabolic processes.
• Other interventions, such as PCSK9 inhibitors, have been shown to decrease Lp(a) levels modestly, with a 27% reduction in Lp(a) levels observed in the FOURIER trial 1.

Mechanisms and Effects

• The mechanisms through which therapeutic regimens affect Lp(a) levels are not well understood and require further research, as highlighted in the NHLBI working group recommendations 1.
• The effect of statins on Lp(a) levels is complex and may be influenced by various factors, including the balance between intact and furin-cleaved PCSK9 forms 1.
• Further studies are needed to understand the relationship between Lp(a) mass and cholesterol, particularly in varying Lp(a) levels and isoforms, as well as the effects of different treatments on Lp(a) biology 1.

From the Research

Statin Effects on Apolipoproteins

• Statin therapy does not significantly alter lipoprotein(a) [Lp(a)] levels, with a mean difference of 1.1 mg/dL (0.5-1.6, P < 0.0001) and 0.1% (-3.6% to 4.0%, P = 0.95) in absolute and percentage changes, respectively 2.
• The production rate of apolipoprotein(a) [apo(a)] is significantly higher in patients with elevated Lp(a) than in those with normal Lp(a) concentration, suggesting that elevated plasma Lp(a) concentration is a consequence of increased hepatic production of Lp(a) particles 3.
• Statin therapy alters the relationship between apolipoprotein B (apoB) and low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) targets in high-risk patients, with apoB being a more accurate measure of cardiovascular risk than LDL-C or non-HDL-C 4, 5.

Apolipoprotein B and Cardiovascular Risk

• ApoB is a more accurate measure of cardiovascular risk and a better guide to the adequacy of lipid lowering than LDL-C or non-HDL-C, with a strong endorsement by the 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines 5.
• The use of LDL-C to guide the adequacy of lipid lowering therapy represents an interpretive error of the results of the statin/ezetimibe/Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor randomized clinical trials, and apoB should be the primary metric to guide statin/ezetimibe/PCSK9 therapy 5.

Relationship Between Apolipoproteins and Statin Therapy

• Non-HDL-C may be an acceptable surrogate for direct apoB measurement during statin therapy, with a tight correlation between non-HDL-C and apoB (R(2) = 0.92) 4.
• Statin therapy does not lead to clinically important differences in Lp(a) compared to placebo in patients at risk for cardiovascular disease, suggesting that statin therapy will not change Lp(a)-associated cardiovascular disease risk 2.