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The Role of Lipoprotein(a) in Cardiovascular Risk Stratification: Integrating Low-density Lipoprotein Cholesterol and
Lei Liu1, Huihui Ma2, Senwen Yang3
1Department of Cardiology, Suining Central Hospital, Suning, Sichuan, China.
Insights
High lipoprotein(a) (Lp(a)) and low-density lipoprotein cholesterol (LDL-C) synergistically increase atherosclerotic cardiovascular disease risk, especially in those with high polygenic risk scores (PRS). Dual lipid management is crucial for these individuals.
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.
Abstract:
High-density lipoprotein(a) (Lp(a)) is a well-established independent risk factor for atherosclerotic cardiovascular diseases (ASCVD). However, the interaction between Lp(a), low-density lipoprotein cholesterol (LDL-C), and polygenic risk score (PRS) in cardiovascular diseases has been the subject of relatively limited research. The present study included a total of 346,751 participants from the UK Biobank. According to the guideline of Lp(a), the study subjects were divided into 3 groups: the first group was <75 mmol/L (n = 272,643), the second group was 75 to 125 mmol/L (n = 35,792), and the third group was >125 mmol/L (n = 38,316). Elevated Lp(a) levels were associated with a progressively increased risk of overall cardiovascular events (CVEs), including ischemic stroke (IS), coronary heart disease (CHD), angina pectoris, and myocardial infarction (MI). In contrast, the risks of atrial fibrillation (AF) and heart failure (HF) decreased with higher Lp(a) levels. Additive interaction analyses revealed significant synergistic effects between Lp(a) and LDL-C for CHD (relative excess risk interaction [RERI] = 0.081, attributable proportion of interaction [AP] = 0.046, synergy index [SI] = 1.117), angina pectoris (RERI = 0.112, AP = 0.055, SI = 1.121), and MI (RERI = 0.183, AP = 0.079, SI = 1.161), with MI showing the strongest synergy. Incorporating PRS further amplified these effects, and the RERI (CHD: RERI = 0.721; angina pectoris: RERI = 0.781; MI: RERI = 1.318) and SI (CHD: SI = 2.218; angina pectoris: SI = 1.97; MI: SI = 2.326) were significantly higher than those of the interaction model containing only Lp(a) and LDL-C. In conclusion, Lp(a) and LDL-C show a significant synergistic effect in ASCVD, and this effect is more prominent in individuals with a higher PRS, suggesting that dual lipid management should be strengthened for such populations. While AF and HF may require alternative risk factor management.
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