How do you manage elevated Apolipoprotein B (Apo B) versus Lipoprotein(a) (Lp(a)) levels?

From the Guidelines

Managing elevated Apolipoprotein B (Apo B) and Lipoprotein(a) (Lp(a)) requires different approaches as they represent distinct cardiovascular risk factors. For elevated Apo B, which indicates an increased number of atherogenic particles, the primary treatment involves statins such as atorvastatin (20-80mg daily) or rosuvastatin (10-40mg daily) 1. If statins alone are insufficient, adding ezetimibe (10mg daily) can further reduce Apo B levels. For patients who cannot reach target levels with these medications, PCSK9 inhibitors like evolocumab (140mg every 2 weeks) or alirocumab (75-150mg every 2 weeks) may be added 1. Lifestyle modifications including a Mediterranean diet, regular exercise, weight management, and avoiding trans fats are essential components of Apo B management. For elevated Lp(a), which is largely genetically determined, treatment options are more limited. Niacin (1-3g daily) may modestly reduce Lp(a) by 20-30%, though its cardiovascular benefit is questionable 1. PCSK9 inhibitors can reduce Lp(a) by 20-30% 1. For very high Lp(a) levels, lipoprotein apheresis may be considered in specialized centers 1. A novel antisense oligonucleotide therapy targeting Lp(a) production (pelacarsen) is in late-stage clinical trials 1. Some key points to consider in the management of Apo B and Lp(a) include:

• The European Society of Cardiology (ESC) guidelines recommend measuring Lp(a) in patients at high risk of cardiovascular disease (CVD) and to target levels below 50 mg/dL 1.
• Lp(a) levels are mainly determined by genetic traits, and it is postulated that Lp(a) particles have pro-atherogenic and pro-thrombotic properties 1.
• The management approach differs because Apo B responds well to conventional lipid-lowering therapies, while Lp(a) is more resistant to these interventions and may require specialized treatments 1. It is essential to prioritize the management of Apo B and Lp(a) based on the individual patient's risk factors and response to treatment, and to consider the latest clinical guidelines and evidence-based recommendations 1.

From the Research

Management of Elevated Apolipoprotein B (Apo B) versus Lipoprotein(a) (Lp(a)) Levels

• The management of elevated Apo B and Lp(a) levels involves a combination of lipid-modifying therapies, with the primary focus on reducing low-density lipoprotein cholesterol (LDL-C) to the lowest attainable value with a high-potency statin 2.
• For patients with elevated Lp(a) levels (≥30 mg/dL) and residual LDL-C elevations (≥70-100 mg/dL) despite maximum-potency statins or combination statin therapy, the clinician may consider adding niacin (up to 2 g/d) 2.
• Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to decrease Lp(a) and cardiovascular events, particularly in high-risk patients with elevated Lp(a) 3, 4.
• The use of PCSK9 inhibitors can significantly reduce LDL-C and Lp(a) levels in patients with acute coronary syndrome (ACS) and complex higher-risk and indicated patients (CHIPs) 4.
• The addition of PCSK9 inhibitors to background niacin therapy can further lower Lp(a) levels, with a median percent reduction of -15.3% 5.

Apolipoprotein B (Apo B) as a Marker of Cardiovascular Risk

• Apo B is considered a more accurate measure of cardiovascular risk and a better guide to the adequacy of lipid lowering than LDL-C or non-high-density lipoprotein cholesterol (HDL-C) 6.
• The 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines concluded that Apo B can be measured more accurately than LDL-C or non-HDL-C, and that it should be the primary metric to guide statin/ezetimibe/PCSK9 therapy 6.

Lipoprotein(a) (Lp(a)) as a Risk Factor for Atherosclerotic Cardiovascular Disease

• Lp(a) is an independent risk factor for the development of atherosclerosis, and is closely correlated to stent thrombosis and restenosis 4.
• Elevated Lp(a) levels are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), particularly in patients with a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, or recurrent cardiovascular events 2, 3.