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These studies suggest that the quality and functionality of HDL, rather than its quantity, are crucial for reducing cardiovascular risk and preventing diseases.
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High-density lipoprotein (HDL) is often referred to as "good cholesterol" due to its role in transporting cholesterol from the arteries to the liver, where it can be processed and removed from the body. Traditionally, higher levels of HDL cholesterol (HDL-C) have been associated with a reduced risk of coronary heart disease (CHD). However, recent research suggests that the relationship between HDL-C levels and cardiovascular health is more complex than previously thought.
Recent studies have highlighted that not all HDL particles are equally beneficial. Cholesterol-overloaded HDL, characterized by a high cholesterol-to-HDL particle ratio (HDL-C/P ratio), has been linked to an increased risk of CHD. However, the presence of apolipoprotein E (APOE)-containing HDL can mitigate this risk. In a community-based cohort study, participants with high cholesterol-overloaded HDL but also high APOE-HDL had a significantly lower risk of CHD compared to those with low APOE-HDL. This suggests that the functionality and composition of HDL particles are crucial in determining their protective effects against heart disease.
The traditional view that higher HDL-C levels are always beneficial has been challenged by recent genetic and clinical research. It is now understood that HDL functionality, rather than just HDL-C levels, plays a more critical role in cardiovascular protection. HDL's cholesterol efflux capacity (CEC), which is its ability to remove cholesterol from macrophages, is a key measure of its functionality. Studies have shown that higher CEC is strongly associated with reduced carotid intima-media thickness and a lower likelihood of coronary artery disease, independent of HDL-C levels. This indicates that enhancing HDL functionality could be more important than merely increasing HDL-C levels.
The quality of HDL, including its protein and lipid content, oxidation state, and glycation level, significantly impacts its functionality. Factors such as age, gender, lifestyle, and disease states can influence HDL quality. For instance, regular aerobic exercise and a healthy diet can improve HDL quality, while chronic inflammation and autoimmune diseases can deteriorate it. High HDL-C levels do not always correlate with good HDL quality or functionality. Dysfunctional HDL, characterized by lower apoA-I content, reduced antioxidant ability, and smaller particle size, is often associated with various diseases, including cardiovascular diseases and neurodegenerative disorders like Alzheimer's and Parkinson's.
While high HDL-C levels have traditionally been seen as protective against heart disease, recent research underscores the importance of HDL functionality and quality. Cholesterol-overloaded HDL can increase CHD risk, but this risk can be mitigated by the presence of APOE-containing HDL. Moreover, HDL's ability to efflux cholesterol and its overall quality are more critical determinants of cardiovascular health than HDL-C levels alone. Therefore, future therapeutic strategies should focus on enhancing HDL functionality and quality to effectively reduce cardiovascular risk.
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