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Some studies suggest low HDL cholesterol is associated with a high risk of autoimmune disease and cardiovascular events, while other studies indicate its impact varies by region and gender.
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Low levels of high-density lipoprotein cholesterol (HDL-C) are widely recognized as a significant risk factor for coronary heart disease (CHD). HDL-C is often referred to as "good cholesterol" because it helps transport cholesterol from the arteries to the liver for excretion, a process known as reverse cholesterol transport (RCT) . However, recent studies suggest that the protective role of HDL-C may not be as straightforward as previously thought.
In individuals without a history of cardiovascular events, low HDL-C levels are inversely associated with the risk of future cardiovascular events. However, this relationship does not hold for patients with metabolic disorders or existing cardiovascular disease. This indicates that while HDL-C levels can be a useful marker in healthy individuals, they may not be as reliable in those with pre-existing conditions.
Recent research has also linked low HDL-C levels with an increased risk of autoimmune diseases. A study involving over 117,000 individuals found that those with HDL-C levels below 1.0 mmol/L (39 mg/dL) had a significantly higher risk of developing autoimmune diseases compared to those with higher HDL-C levels. This suggests that HDL-C may play a role in immune function, although the exact mechanisms remain unclear.
Low HDL-C levels have been associated with higher white blood cell counts, indicating a potential link between HDL-C and inflammation. A Mendelian randomization study found that genetically determined low HDL-C was associated with higher levels of leukocytes, lymphocytes, monocytes, and eosinophils. This supports the idea that HDL-C may have anti-inflammatory properties, which could be relevant in both cardiovascular and autoimmune diseases.
The relationship between HDL-C and cardiovascular risk factors can vary significantly between populations. For example, in sub-Saharan Africa, low HDL-C is extremely common but does not necessarily indicate increased cardiovascular risk. In these populations, low HDL-C is often associated with lower overall cholesterol levels and does not show the same relationship with adiposity and non-HDL cholesterol as seen in European populations. This suggests that the clinical significance of low HDL-C may differ based on genetic and environmental factors.
While raising HDL-C levels has been considered a potential therapeutic target, recent evidence suggests that simply increasing HDL-C may not be sufficient to reduce cardiovascular risk. Pharmacological approaches to raise HDL-C have not consistently shown reductions in cardiovascular outcomes . Instead, lifestyle changes such as smoking cessation, physical exercise, and weight loss are recommended to improve HDL-C levels and overall cardiovascular health .
Low HDL cholesterol is a complex marker with implications for cardiovascular and autoimmune diseases. While it is associated with increased risk in some populations, its role is not universally predictive, particularly in those with existing metabolic or cardiovascular conditions. Future research should focus on understanding the functional aspects of HDL and developing targeted therapies that optimize HDL function rather than merely increasing HDL-C levels.
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