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Some studies suggest that extremely high HDL cholesterol levels may be associated with increased risks of mortality and cardiovascular events, while other studies indicate that high HDL levels may not protect against cardiovascular disease and could signal other health issues.
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High-density lipoprotein (HDL) cholesterol, often referred to as "good cholesterol," plays a crucial role in transporting cholesterol from the arteries to the liver, where it can be processed and eliminated from the body. Traditionally, higher levels of HDL cholesterol have been associated with a lower risk of cardiovascular diseases, leading to the belief that more HDL is always better .
Despite the conventional wisdom, recent studies have challenged the notion that higher HDL cholesterol levels unequivocally confer cardiovascular protection. Clinical trials involving drugs designed to increase HDL levels have not demonstrated the expected reduction in heart disease risk. Additionally, genetic studies have shown that genes associated with higher HDL levels do not necessarily correlate with lower incidences of heart disease .
A large-scale study has revealed a U-shaped relationship between HDL cholesterol levels and all-cause mortality. This means that both very low and very high levels of HDL cholesterol are associated with increased mortality risks. Specifically, individuals with extremely high HDL levels showed a higher risk of death compared to those with moderately high levels.
Research has indicated that extremely high levels of HDL cholesterol may not be as protective as once thought. A longitudinal study found that while individuals with extremely high HDL levels had lower risks of all-cause mortality and cardiovascular events compared to those with low HDL levels, their risks were still higher than those with moderately high HDL levels. This suggests that there is an optimal range for HDL cholesterol, beyond which the benefits may diminish or even reverse.
The functionality of HDL particles is also a critical factor. In certain conditions, such as chronic inflammation, HDL can become dysfunctional, losing its protective properties and potentially becoming harmful. This transformation can turn HDL from an anti-atherogenic particle into a pro-atherogenic one, contributing to cardiovascular disease.
High HDL cholesterol levels have also been linked to adverse outcomes in non-cardiovascular diseases. Observational studies have found associations between high HDL levels and increased risks of age-related macular degeneration, type II diabetes, dementia, infections, and overall mortality. These findings further complicate the simplistic view of HDL as uniformly beneficial.
While HDL cholesterol has long been considered the "good cholesterol," emerging evidence suggests that extremely high levels may not be as beneficial as previously thought. Both clinical trials and observational studies indicate that there is a complex relationship between HDL levels and health outcomes, with potential risks associated with very high HDL levels. Therefore, it is essential to consider not just the quantity but also the quality and functionality of HDL cholesterol in assessing cardiovascular and overall health risks.
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