From the Guidelines
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a significant biomarker for cardiovascular health, indicating inflammation in blood vessels and helping predict heart disease risk, with elevated levels associated with increased risk of heart attacks, strokes, and coronary artery disease. This enzyme is primarily produced by inflammatory cells and circulates bound to LDL cholesterol. According to a meta-analysis of 14 studies, Lp-PLA2 was associated with an adjusted OR for CVD of 1.60 (95% CI 1.36 to 1.89) 1. The increased CVD risk of Lp-PLA2 remains after adjusting for CRP, in addition to standard CVD risk factors. Some key points to consider about Lp-PLA2 include:
- Elevated Lp-PLA2 levels are associated with increased risk of cardiovascular events
- Lp-PLA2 is vascular-specific, providing targeted information about arterial inflammation
- Testing for Lp-PLA2 can be particularly useful for patients with intermediate cardiovascular risk profiles or family histories of heart disease
- If levels are high, healthcare providers may recommend more intensive statin therapy, closer monitoring of blood pressure, stricter dietary changes, or additional medications The enzyme works by hydrolyzing oxidized phospholipids in LDL particles, creating pro-inflammatory compounds that contribute to atherosclerotic plaque formation and instability, which explains its direct mechanistic link to cardiovascular events. However, there is currently no information about whether Lp-PLA2 concentrations are clinically effective for motivating patients, guiding treatment, or improving outcomes 1. Randomized studies have demonstrated that lipid-lowering therapies reduce Lp-PLA2, although there may be some variability by medication type. Drugs under development that specifically inhibit Lp-PLA2 activity have been shown to lower Lp-PLA2 activity and inflammatory markers.
From the Research
Clinical Significance of Lp-PLA2
The clinical significance of Lipoprotein-associated phospholipase A2 (Lp-PLA2) to health is a topic of interest in the medical field.
- Lp-PLA2 is a vascular-specific inflammatory marker that is associated with low-density lipoprotein in plasma 2.
- It is recognized as a risk marker in primary or secondary prevention of atherosclerosis, with elevated Lp-PLA2 levels being associated with an increased risk for cardiovascular events, even after multivariable adjustment for traditional risk factors 2, 3, 4.
- The degree of coronary artery disease and plasma low-density lipoprotein cholesterol significantly correlates to Lp-PLA2 levels 2.
- Lp-PLA2 activity is an independent predictor of coronary heart disease and ischemic stroke in the general population 4.
Association with Cardiovascular Disease
- Lp-PLA2 is believed to contribute to atherosclerotic plaque progression and instability by promoting inflammation 5.
- A large number of epidemiologic studies have demonstrated that elevated levels of Lp-PLA2 are associated with an increased risk of cardiovascular events across diverse patient populations, independent of established risk factors including low-density lipoprotein cholesterol 5.
- Lp-PLA2 levels are significantly higher in patients with coronary heart disease than in patients without coronary heart disease 6.
- Lp-PLA2 levels are also significantly higher in patients with heart failure, sepsis, or aortic aneurysm 6.
Effect of Treatments on Lp-PLA2
- Statins and fenofibrates can reduce Lp-PLA2 concentrations in plasma 3.
- Orally active, specific Lp-PLA2 inhibitors have been developed and are in clinical trials to evaluate the potential of Lp-PLA2 as a therapeutic target 3.
- Darapladib, an inhibitor of Lp-PLA2, offers great benefit in the reduction of plaque formation when added to lipid-lowering therapy such as statins 2.
- Lp-PLA2 levels are significantly associated with treatments such as statins and ACEi/ARA2 6.