Very high hdl
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The Complex Role of Very High HDL Cholesterol in Cardiovascular Health
Introduction to HDL Cholesterol
High-density lipoprotein cholesterol (HDL-C) is often referred to as "good" cholesterol due to its role in transporting cholesterol from the arteries to the liver for excretion. Traditionally, higher levels of HDL-C have been associated with a reduced risk of cardiovascular disease (CVD). However, recent research has revealed a more nuanced picture, particularly concerning very high levels of HDL-C.
Extremely High HDL-C and Cardiovascular Mortality
Recent studies have begun to challenge the long-standing belief that higher HDL-C levels are always beneficial. A pooled analysis of nine Japanese cohort studies involving 43,407 participants found that extremely high levels of HDL-C (≥90 mg/dL) were significantly associated with increased risk of atherosclerotic CVD mortality, including coronary heart disease and ischemic stroke. This risk was particularly pronounced among current drinkers, suggesting that lifestyle factors may modulate the impact of very high HDL-C levels on cardiovascular health.
HDL Functionality vs. Quantity
The functionality of HDL, rather than its quantity, appears to play a crucial role in cardiovascular protection. HDL functionality includes its ability to promote cholesterol efflux, exhibit anti-inflammatory properties, and prevent oxidation. Studies have shown that individuals with very high HDL-C but with coronary artery disease (CAD) have reduced HDL phospholipid content and cholesterol efflux capacity compared to controls with similarly high HDL-C but no CAD. This indicates that the protective effects of HDL are more closely related to its functional properties than its concentration in the blood.
J-Shaped Relationship Between HDL-C Levels and Mortality
A meta-analysis of 37 prospective cohort studies involving over 3.5 million participants found a J-shaped relationship between HDL-C levels and mortality from all causes, cardiovascular disease, and cancer. The lowest risk was observed at HDL-C levels of 54-58 mg/dL, with both extremely high and low levels associated with increased mortality. This suggests that there is an optimal range for HDL-C levels, beyond which the benefits may diminish or even reverse.
Gender Differences in HDL-C Impact
The impact of very high HDL-C levels on mortality also appears to differ by gender. A systematic review and meta-analysis found that very high HDL-C levels (≥80 mg/dL) were associated with increased all-cause mortality in men but lower mortality in women. This gender-specific effect underscores the complexity of HDL-C's role in health and disease.
Conclusion
While HDL-C has long been considered protective against cardiovascular disease, extremely high levels of HDL-C may not confer the same benefits and could even be harmful. The functionality of HDL, including its ability to promote cholesterol efflux and exhibit anti-inflammatory properties, is crucial in mediating its protective effects. Moreover, the relationship between HDL-C levels and mortality is complex and influenced by factors such as gender and lifestyle. These findings highlight the need for a more nuanced understanding of HDL-C in cardiovascular health and the importance of focusing on HDL functionality rather than merely its quantity.
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