What is the primary focus for managing hyperlipidemia, and what role do Lipoprotein(a) (Lp(a)) levels play in treatment?

LDL-Cholesterol vs Lipoprotein(a) Testing for Hyperlipidemia Management

LDL-Cholesterol should be used as the primary lipid analysis for screening, risk estimation, diagnosis, and management of hyperlipidemia, while Lipoprotein(a) [Lp(a)] testing should be reserved for patients at high risk of cardiovascular disease. 1

Primary Target for Hyperlipidemia Management

• LDL-Cholesterol is recommended as the primary target for treatment in hyperlipidemia management according to the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guidelines 1
• A complete lipoprotein profile (total cholesterol, LDL-C, HDL-C, triglycerides) is the preferred screening method for assessing coronary heart disease risk 1
• The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines focus on LDL-C as the primary lipoprotein mediating atherosclerosis 1

Role of Lipoprotein(a) in Cardiovascular Risk Assessment

• Lipoprotein(a) [Lp(a)] is considered an emerging risk factor and should be measured in patients at high risk of cardiovascular disease 1
• The ESC guidelines recommend measuring Lp(a) in high-risk patients and targeting levels below 50 mg/dL 1
• Lp(a) has pro-atherogenic and pro-thrombotic properties, with several observational studies, meta-analyses, and genomic studies suggesting a causal association between Lp(a) levels and cardiovascular disease events 1
• Elevated Lp(a) is also associated with heart failure and calcific aortic valve stenosis in the elderly 1

Treatment Targets and Thresholds

• For patients at VERY HIGH cardiovascular risk, an LDL-C goal of < 1.8 mmol/L (70 mg/dL), or a reduction of at least 50% if the baseline LDL-C is between 1.8 and 3.5 mmol/L (70 and 135 mg/dL) is recommended 1
• For patients at HIGH cardiovascular risk, an LDL-C goal of < 2.6 mmol/L (100 mg/dL), or a reduction of at least 50% if the baseline LDL-C is between 2.6 and 5.1 mmol/L (100 and 200 mg/dL) is recommended 1
• Statins are the first-line treatment to reach LDL-C goals and should be used up to the highest recommended dose or highest tolerable dose 1

Special Considerations for Lp(a) Testing

• Lp(a) testing should be considered in patients with:
  • Premature cardiovascular disease 1
  • Familial hypercholesterolemia 1
  • Family history of premature cardiovascular disease 1
  • Recurrent cardiovascular events despite optimal lipid-lowering therapy 1
• Lp(a) levels are mainly determined by genetic traits and remain relatively stable throughout life 1
• Women younger than 40 years with low LDL-C may be at increased cardiovascular risk associated with elevated Lp(a) and apolipoprotein B levels 2

Clinical Approach to Testing

1. Begin with standard lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides) for all patients 1
2. Use LDL-C as the primary target for treatment decisions 1
3. Consider Lp(a) testing in high-risk patients or those with premature cardiovascular disease 1
4. For patients with elevated triglycerides (≥200 mg/dL), use non-HDL-C as a secondary target (goal is 30 mg/dL higher than the LDL-C goal) 1

Pitfalls and Caveats

• Lp(a) assays still suffer from poor standardization, comparability, and particle variation 3
• Current guidelines do not recommend universal Lp(a) screening in the general population 1
• Despite the association between Lp(a) and cardiovascular risk, there are currently limited therapeutic options specifically targeting Lp(a) reduction 4
• Lipoprotein apheresis may be considered for patients with severe familial hypercholesterolemia and/or Lp(a) hyperlipidemia who are intolerant or insufficiently responsive to lipid-lowering drugs 1, 3

Emerging Approaches

• PCSK9 inhibitors may provide modest Lp(a) reduction in addition to LDL-C lowering 5
• Several agents specifically targeting Lp(a) reduction are in development, with preliminary data showing reductions of up to 98% 4
• Inclusion of Lp(a) and apolipoprotein B in routine lipid testing may improve cardiovascular risk prediction in primary prevention, particularly in younger women 2