High cholesterol
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High Cholesterol: Implications and Insights from Recent Research
High Cholesterol and Cardiovascular Disease Risk
Extremely High HDL Cholesterol and Cardiovascular Mortality
Recent studies have highlighted the complex relationship between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD). Traditionally, HDL-C is known as "good cholesterol" due to its role in reverse cholesterol transport, which helps remove cholesterol from arteries. However, extremely high levels of HDL-C have been associated with increased cardiovascular mortality. A pooled analysis of nine Japanese cohort studies involving 43,407 participants found that extremely high HDL-C levels (≥90 mg/dL) were significantly associated with increased risk of atherosclerotic CVD mortality, including coronary heart disease and ischemic stroke, particularly among current drinkers.
U-Shaped Relationship Between HDL Cholesterol and Mortality
Further supporting these findings, two large prospective cohort studies from Denmark, including over 117,000 participants, demonstrated a U-shaped association between HDL-C levels and all-cause mortality. Both extremely high and low HDL-C concentrations were linked to higher mortality rates. The optimal HDL-C levels associated with the lowest mortality were 73 mg/dL for men and 93 mg/dL for women. Men with HDL-C levels ≥116 mg/dL and women with HDL-C levels ≥135 mg/dL had significantly higher all-cause mortality risks.
Cholesterol and Broader Health Implications
Cholesterol and Type 2 Diabetes Risk
High cholesterol intake has also been linked to an elevated risk of type 2 diabetes mellitus (T2D). A meta-analysis of observational studies found that individuals with the highest dietary cholesterol intake had a 25% higher risk of developing T2D compared to those with the lowest intake. Additionally, each 100 mg/day increase in cholesterol consumption was associated with an 11% increase in T2D risk.
Cholesterol-Induced Toxicity in Multiple Diseases
Excess cholesterol accumulation is not only a risk factor for atherosclerosis but also plays a critical role in the pathogenesis of various diseases, including liver diseases, diabetes, chronic kidney disease, Alzheimer's disease, and immune disorders. This broad impact of cholesterol-induced toxicity underscores the importance of managing cholesterol levels to prevent a wide range of health issues.
Dietary Cholesterol and HDL Composition
Impact of High-Cholesterol Diets on HDL Function
Short-term increases in dietary cholesterol and fat intake can alter the biochemical composition and antioxidant properties of HDL. A clinical trial involving healthy young volunteers showed that a high-cholesterol/high-fat diet significantly increased HDL lipid hydroperoxide content and serum amyloid A levels, which are markers of dysfunctional HDL. This suggests that even short-term dietary changes can negatively impact HDL function, independent of weight changes.
Genetic Factors and HDL Cholesterol
CETP Deficiency and Coronary Heart Disease
Genetic factors, such as cholesteryl ester transfer protein (CETP) deficiency, can lead to elevated HDL-C levels. However, studies have shown that individuals with CETP deficiency and high HDL-C levels (≥80 mg/dL) have a low prevalence of coronary heart disease (CHD). This indicates that genetic causes of elevated HDL-C may not necessarily increase CHD risk, highlighting the complexity of HDL-C's role in cardiovascular health.
Conclusion
The relationship between cholesterol levels and health outcomes is multifaceted. While HDL-C is generally protective against cardiovascular disease, extremely high levels can paradoxically increase mortality risk. High dietary cholesterol intake is associated with a higher risk of type 2 diabetes and can negatively impact HDL function. Genetic factors, such as CETP deficiency, further complicate the understanding of HDL-C's role in disease risk. These insights underscore the importance of balanced cholesterol management for overall health.
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