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Understanding Low HDL: Implications and Insights
Low HDL and Cardiovascular Risk
Low high-density lipoprotein cholesterol (HDL-C) is a significant marker for atherogenic dyslipidemia, which is linked to adverse lifestyle choices, impaired metabolism, and increased cardiovascular risk. Despite the epidemiological evidence, raising HDL-C levels has not proven to be a viable therapeutic target for reducing cardiovascular risk. This is partly because HDL-C levels do not necessarily reflect HDL function, which includes reverse cholesterol transport, inhibition of inflammation and oxidation, and antidiabetic properties.
Low HDL and Inflammatory Disorders
Low HDL-C is associated with increased risk of inflammatory disorders. For instance, a Mendelian randomization study found that genetically low HDL-C levels are linked to higher white blood cell counts, including leukocytes, lymphocytes, monocytes, and eosinophils, suggesting a potential causal relationship. This association underscores the role of HDL in immune regulation and inflammation.
Low HDL and Risk of Sepsis and Malignancy
Extremely low HDL levels are also associated with a higher risk of sepsis and malignancy. A retrospective analysis revealed that patients with HDL levels ≤20 mg/dL had a significantly increased risk of death, fever, and cancer compared to those with higher HDL levels. This suggests that HDL's anti-inflammatory and anti-angiogenic properties play a crucial role in protecting against these conditions.
Low HDL and Autoimmune Diseases
Low HDL-C levels are linked to a higher risk of autoimmune diseases. In a large population-based cohort study, individuals with HDL-C levels <39 mg/dL had a significantly higher risk of developing autoimmune diseases compared to those with higher HDL-C levels. This finding highlights the importance of HDL in maintaining normal immune function.
Low HDL and Coronary Artery Disease
Patients with low HDL-C and mildly elevated LDL-C often face uncertainty regarding the appropriate therapeutic goal. A study on the effects of fluvastatin therapy showed that patients with low HDL-C experienced greater angiographic and clinical benefits from LDL-C reduction compared to those with higher HDL-C. This indicates that lowering LDL-C might be more beneficial for patients with low HDL-C in managing coronary artery disease.
Weight Loss and HDL Levels
Weight loss through exercise or dieting can influence HDL levels differently based on baseline HDL levels. In a study of overweight men, those with low baseline HDL experienced smaller absolute increases in HDL levels compared to those with normal-to-high baseline HDL after weight loss through exercise. However, relative increases in HDL were more consistent across different baseline HDL levels.
Low HDL and Carotid Artery Thickness
Low HDL-C is associated with increased carotid artery intima-media thickness (IMT), a marker of atherosclerosis. In a study of asymptomatic members of low HDL-C families, lower HDL-C and HDL2-C levels were significantly inversely related to mean carotid IMT, even after adjusting for age and gender. This suggests that low HDL-C contributes to early atherosclerotic changes.
Clinical Management of Extremely Low HDL
Patients with extremely low HDL-C levels (<20 mg/dL) require careful clinical management. Secondary causes such as androgen use, malignancy, and primary monogenic disorders should be evaluated. While the association between extremely low HDL-C and atherosclerosis remains unclear, addressing reversible causes and modifying cardiovascular risk factors are essential.
Oxidative Stress and HDL Function
Individuals with low HDL-C often exhibit elevated oxidative stress and possess HDL particles with reduced antioxidative activity. This dysfunction is related to altered chemical composition of HDL particles, which may contribute to the high cardiovascular risk observed in these individuals.
Prevalence of Low HDL in Korean Adults
The prevalence of low HDL-C has increased significantly among Korean adults from 1998 to 2005. Factors such as body mass index, waist circumference, and lifestyle choices like non-alcohol consumption were associated with low HDL-C levels. This trend highlights the need for public health interventions to address modifiable risk factors.
Conclusion
Low HDL-C is a multifaceted issue linked to increased cardiovascular risk, inflammatory disorders, sepsis, malignancy, autoimmune diseases, and atherosclerosis. While raising HDL-C levels has not been a successful therapeutic target, focusing on HDL function and addressing underlying causes remain critical for managing patients with low HDL-C. Further research is needed to develop effective strategies for optimizing HDL function and improving clinical outcomes.
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