The Role of Lipoprotein(a) in Cardiovascular Risk Stratification: Integrating Low-density Lipoprotein Cholesterol and...

Area of Science:

• Cardiovascular Medicine
• Genetics
• Lipid Metabolism

Background:

• High lipoprotein(a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascular diseases (ASCVD).
• Limited research exists on the combined impact of Lp(a), low-density lipoprotein cholesterol (LDL-C), and polygenic risk score (PRS) on cardiovascular disease risk.

Purpose of the Study:

• To investigate the interaction between Lp(a), LDL-C, and PRS in predicting cardiovascular events.
• To quantify the synergistic effects of Lp(a) and LDL-C on specific cardiovascular outcomes.
• To assess the influence of PRS on these interactions.

Main Methods:

• Analysis of 346,751 participants from the UK Biobank.
• Categorization of participants based on Lp(a) levels (<75 mmol/L, 75-125 mmol/L, >125 mmol/L).
• Additive interaction analyses to evaluate synergistic effects (RERI, AP, SI) between Lp(a), LDL-C, and PRS for various cardiovascular events.

Main Results:

• Elevated Lp(a) levels correlated with increased risk of ischemic stroke, coronary heart disease, angina pectoris, and myocardial infarction.
• Higher Lp(a) levels showed a decreased risk for atrial fibrillation and heart failure.
• Significant synergistic effects were observed between Lp(a) and LDL-C for coronary heart disease, angina pectoris, and myocardial infarction.
• Incorporating PRS amplified these synergistic effects, particularly for myocardial infarction.

Conclusions:

• Lp(a) and LDL-C exhibit a significant synergistic effect in ASCVD development.
• This synergy is more pronounced in individuals with a higher PRS, highlighting the need for intensified dual lipid management.
• Alternative risk factor management strategies may be necessary for atrial fibrillation and heart failure.