What causes high cholesterol
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Causes of High Cholesterol
High cholesterol is a multifaceted condition influenced by genetic, dietary, and metabolic factors. Understanding these causes is crucial for effective management and prevention of associated diseases.
Genetic Factors and Familial Hypercholesterolemia
Familial Hypercholesterolemia (FH) is a common inherited disorder characterized by elevated levels of low-density lipoprotein (LDL) cholesterol from birth, leading to cardiovascular disease (CVD) over time. This condition is primarily caused by autosomal dominant mutations in the LDL receptor gene (LDLR), but mutations in other genes like APOB and PCSK9 also contribute, albeit less frequently. High lipoprotein(a) levels and corresponding LPA risk genotypes are also significant risk factors for clinical familial hypercholesterolemia, further increasing the risk of myocardial infarction.
Cholesteryl Ester Transfer Protein (CETP) Deficiency
CETP deficiency is another genetic factor that can influence cholesterol levels. This condition leads to increased high-density lipoprotein (HDL) cholesterol and decreased LDL cholesterol. While CETP deficiency is associated with a favorable lipoprotein profile, it is more common in certain populations, such as the Japanese, due to a founder effect. Despite elevated HDL levels, CETP deficiency does not necessarily protect against coronary heart disease (CHD).
Dietary Cholesterol and Saturated Fats
Contrary to long-held beliefs, recent research indicates that dietary cholesterol itself does not significantly impact blood cholesterol levels or increase the risk of CVD. However, foods high in cholesterol often contain saturated fatty acids, which can elevate CVD risk. Exceptions like eggs and shrimp, which are low in saturated fats, can be included in a healthy diet.
Cholesterol and Inflammation
Cholesterol accumulation in macrophages and other immune cells can trigger inflammatory responses, exacerbating conditions like atherosclerosis and obesity. This inflammation is mediated through mechanisms such as Toll-like receptor (TLR) signaling and inflammasome activation, which further promote cholesterol accumulation and inflammation.
Cholesterol-Induced Toxicity
Excess cholesterol can accumulate in various tissues and organs, contributing to the pathogenesis of multiple diseases beyond atherosclerosis. These include liver diseases, diabetes, chronic kidney disease, Alzheimer's disease, and more. This widespread cholesterol-induced toxicity underscores the importance of managing cholesterol levels to prevent a broad spectrum of diseases.
High-Density Lipoprotein Cholesterol (HDL-C) Paradox
While HDL-C is generally considered protective against CVD, extremely high levels of HDL-C have been associated with increased risks of atherosclerotic CVD mortality, particularly in certain populations and among current drinkers . This paradox highlights the complexity of cholesterol's role in cardiovascular health.
Conclusion
High cholesterol is influenced by a combination of genetic factors, dietary habits, and metabolic processes. Familial hypercholesterolemia and CETP deficiency are significant genetic contributors, while dietary cholesterol's impact is nuanced by the presence of saturated fats. Additionally, cholesterol-induced inflammation and toxicity play critical roles in disease pathogenesis. Understanding these diverse causes is essential for developing targeted strategies to manage and prevent high cholesterol and its associated health risks.
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