What management is recommended for elevated Lp-PLA2 levels and normal PSA levels?

From the Guidelines

Management of elevated Lp-PLA2 levels with normal PSA levels should focus on cardiovascular risk reduction through lifestyle modifications and medication therapy. The primary recommendation is to start with intensive lifestyle changes including a Mediterranean or DASH diet, regular aerobic exercise (150 minutes weekly), smoking cessation, and weight management. If lifestyle changes are insufficient, statin therapy is the first-line medication approach, with moderate to high-intensity statins like atorvastatin 20-80 mg or rosuvastatin 10-40 mg daily being most effective at reducing Lp-PLA2 levels 1. For patients who cannot tolerate statins or have inadequate response, ezetimibe 10 mg daily can be added. In high-risk patients, PCSK9 inhibitors may be considered. Regular monitoring of lipid panels every 3-6 months is recommended to assess treatment efficacy. Elevated Lp-PLA2 is an inflammatory marker associated with unstable atherosclerotic plaques and increased cardiovascular risk, independent of traditional risk factors, as supported by the 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults 1 and the European guidelines on cardiovascular disease prevention in clinical practice (version 2012) 1. The normal PSA levels indicate that prostate cancer risk is not elevated, so cardiovascular risk management should be the priority, and the management of prostate cancer is not relevant in this case, as described in the clinical practice guideline for prostate cancer screening with prostate-specific antigen (PSA) test 1. Some key points to consider in the management of elevated Lp-PLA2 levels include:

• The use of Lp-PLA2 as a marker for cardiovascular risk estimation, although it remains a ‘second-line’ marker due to the cost of the test and modest effect on risk at the level of the general population 1
• The importance of lifestyle modifications in reducing cardiovascular risk
• The role of statin therapy in reducing Lp-PLA2 levels and cardiovascular risk
• The consideration of ezetimibe and PCSK9 inhibitors in patients who cannot tolerate statins or have inadequate response.

From the Research

Management of Elevated Lp-PLA2 Levels and Normal PSA Levels

• The management of elevated Lp-PLA2 levels is influenced by various factors, including cardiac disease, comorbidities, and treatments 2.
• Studies have shown that Lp-PLA2 is an inflammatory biomarker that predicts future cardiovascular events in patients with ischemic disease and heart failure 2, 3.
• Elevated Lp-PLA2 levels are associated with an increased risk of atherosclerosis-related cardiovascular disease (ASCVD) 4.
• However, attempts to translate the inhibition of phospholipase into clinically beneficial ASCVD risk reduction have failed, highlighting the need for further research 4.

Treatment Options

• Statins have been shown to reduce plasma levels of Lp-PLA2, but their effect on Lp-PLA2 within advanced plaques is unclear 3.
• Novel inhibitors of Lp-PLA2 have been identified, and recent clinical and preclinical studies have revealed promising therapeutic effects in diabetic macular edema and Alzheimer's disease 5.
• Lipoprotein apheresis (LA) has been shown to efficiently lower Lp(a) levels, which are associated with an increased risk of cardiovascular events 6.

Monitoring and Risk Assessment

• Lp-PLA2 levels should be interpreted in the context of cardiac parameters and treatments, especially statins and ACEi/ARA2 2.
• The measurement of Lp(a) is recommended in specific clinical conditions, such as a family history of premature CVD or elevated Lp(a) 6.
• Further research is needed to establish and validate novel anti-inflammatory therapeutic strategies to fight against ASCVD development 4.