From the Guidelines
For a patient with very elevated lipoprotein(a) and family history of stroke and heart attack, the next steps should focus on aggressive cardiovascular risk reduction, starting with high-intensity statin therapy to lower LDL cholesterol by at least 50%. This approach is supported by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guidelines on the management of blood cholesterol in diabetes 1. The guidelines recommend using LDL-C as the primary target for treatment and suggest that in patients at very high CV 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, as seen in the 2016 ESC/EAS guidelines for the management of dyslipidaemias 1.
Key considerations for managing such a patient include:
- Initiating high-intensity statin therapy, such as atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily, to achieve the recommended LDL-C reduction.
- Adding ezetimibe 10 mg daily if LDL goals are not met with statins alone, as suggested by the guidelines for very high-risk patients 1.
- Implementing lifestyle modifications, including a heart-healthy diet, regular exercise, smoking cessation if applicable, and weight management targeting BMI <25.
- Monitoring other cardiovascular risk factors closely, including blood pressure (target <130/80 mmHg), diabetes control if present, and addressing metabolic syndrome components.
- Scheduling regular follow-up with lipid panels every 3-6 months initially, then annually once stable.
While lipoprotein(a) levels cannot be significantly lowered with current standard therapies, reducing overall atherosclerotic risk is crucial as elevated lipoprotein(a) enhances LDL's atherogenic potential and promotes thrombosis, as noted in studies on lipoprotein(a) and cardiovascular disease risk 1. Novel therapies specifically targeting lipoprotein(a) are in development but not yet widely available for clinical use. The most recent and highest quality study guiding this recommendation is from 2020, emphasizing the importance of aggressive risk reduction in patients with elevated lipoprotein(a) and a family history of cardiovascular events 1.
From the Research
Next Steps for Patients with Elevated Lipoprotein(a) and Family History of Cerebrovascular Accident and Myocardial Infarction
The next steps for a patient presenting with severely elevated Lipoprotein(a) (Lp(a)) and a family history of cerebrovascular accident (stroke) and myocardial infarction (heart attack) include:
- Measurement of Lp(a) levels to refine cardiovascular risk assessment, as recommended by studies 2, 3
- Management with more intensive approaches to treat other modifiable cardiovascular risk factors, as suggested by 2
- Consideration of Lp(a)-lowering therapies, such as:
- PCSK9 inhibitors, which can reduce Lp(a) levels by 25-30% 4, 5
- Antisense oligonucleotides, small interfering RNAs, and microRNAs, which target RNA molecules and regulate gene expression as well as protein production levels 4, 6
- Apheresis, which is currently the most effective and tolerated treatment for patients with high Lp(a) plasma levels 4
- Cascade screening to identify elevated Lp(a) in relatives of individuals with a personal or family history of premature ASCVD, as recommended by 3
Lp(a) Measurement and Interpretation
Lp(a) level measurement poses some challenges due to the absence of a definitive reference method and the reporting of Lp(a) values as molar or mass concentrations by different assays 2. However, Lp(a) measurement is recommended to refine cardiovascular risk in specific clinical settings, such as in individuals with a family history of premature ASCVD or in patients with ASCVD not explained by standard risk factors 2, 3.
Treatment Perspectives
Several studies have found a causal and independent relationship between Lp(a) levels and cardiovascular risk 2, 4, 6, 5. Therefore, reducing Lp(a) levels is a potential therapeutic target for preventing cardiovascular disease. Newer treatment modalities, such as gene silencing via RNA interference, seem very promising 6.