What happens if you have high cholesterol
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The Impact of High Cholesterol on Health
High Cholesterol and Disease Pathogenesis
High levels of cholesterol, particularly low-density lipoprotein (LDL) cholesterol, are widely recognized for their role in the development of atherosclerosis, a condition characterized by the buildup of fatty deposits in the arteries. However, recent research has expanded our understanding of the detrimental effects of excess cholesterol, linking it to a variety of other diseases. Elevated cholesterol levels have been implicated in liver diseases, diabetes, chronic kidney disease, Alzheimer's disease, osteoporosis, osteoarthritis, pituitary-thyroid axis dysfunction, immune disorders, and even COVID-191. This broad spectrum of cholesterol-induced toxicity underscores the importance of managing cholesterol levels to prevent a wide array of health issues.
High-Density Lipoprotein (HDL) Cholesterol: A Double-Edged Sword
Traditionally, high-density lipoprotein (HDL) cholesterol has been considered "good" cholesterol due to its role in transporting cholesterol away from the arteries and back to the liver. However, emerging evidence suggests that extremely high levels of HDL cholesterol may not be as beneficial as once thought. Studies have shown that extremely high HDL-C levels are associated with increased risks of cardiovascular disease (CVD) mortality, including coronary heart disease and ischemic stroke2 3 5. This paradoxical relationship indicates that while moderate levels of HDL-C are protective, extremely high levels can be harmful.
U-Shaped Relationship Between HDL Cholesterol and Mortality
Several studies have identified a U-shaped relationship between HDL cholesterol levels and all-cause mortality. Both low and extremely high HDL-C levels are associated with increased mortality risks. For instance, research involving large cohorts has demonstrated that men and women with extremely high HDL-C levels have higher all-cause mortality rates compared to those with moderate HDL-C levels5 7 8. This U-shaped association suggests that maintaining HDL-C levels within an optimal range is crucial for minimizing mortality risk.
The Role of Serum Uric Acid in Cholesterol Levels
Elevated serum uric acid (SUA) has been identified as a predictor for the development of high LDL cholesterol and hypertriglyceridemia. A study conducted over five years found that individuals with high baseline SUA levels were at an increased risk of developing high LDL cholesterol and hypertriglyceridemia, highlighting the interconnectedness of metabolic factors in cardiovascular health4.
Genetic Factors and Cholesterol Levels
Genetic factors also play a significant role in cholesterol levels and their associated risks. For example, cholesteryl ester transfer protein (CETP) deficiency, which leads to elevated HDL cholesterol levels, has been studied for its impact on coronary heart disease (CHD). Despite high HDL levels, individuals with CETP deficiency do not show a reduced prevalence of CHD, suggesting that genetic mutations can influence the protective effects of HDL cholesterol6.
Conclusion
High cholesterol, particularly when it involves elevated LDL or extremely high HDL levels, poses significant health risks. The association of high cholesterol with a wide range of diseases, coupled with the complex relationship between HDL levels and mortality, underscores the importance of maintaining balanced cholesterol levels. Regular monitoring and appropriate management of cholesterol can help mitigate these risks and promote overall cardiovascular health.
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Most relevant research papers on this topic
Cholesterol-induced toxicity: An integrated view of the role of cholesterol in multiple diseases.
High levels of cholesterol are generally considered to be associated with atherosclerosis. In the past two decades, however, a number of studies have shown that excess cholesterol accumulation in various tissues and organs plays a critical role in the pathogenesis of multiple diseases. Here, we summarize the effects of excess cholesterol on disease pathogenesis, including liver diseases, diabetes, chronic kidney disease, Alzheimer's disease, osteoporosis, osteoarthritis, pituitary-thyroid axis dysfunction, immune disorders, and COVID-19, while proposing that excess cholesterol-induced toxicity is ubiquitous. We believe this concept will help broaden the appreciation of the toxic effect of excess cholesterol, and thus potentially expand the therapeutic use of cholesterol-lowering medications.
Very Rigorous Journal
Highly CitedAssociation of extremely high levels of high-density lipoprotein cholesterol with cardiovascular mortality in a pooled analysis of 9 cohort studies including 43,407 individuals: The EPOCH-JAPAN study.
Extremely high levels of HDL-C are associated with an increased risk of atherosclerotic cardiovascular disease mortality, particularly in current drinkers.
Meta-AnalysisHighly CitedAssociation between extremely high-density lipoprotein cholesterol and adverse cardiovascular outcomes: a systematic review and meta-analysis
Extremely high HDL-C levels are associated with elevated risks of all-cause mortality, cardiovascular disease mortality, and stroke compared to normal HDL-C levels.
Meta-AnalysisElevated serum uric acid increases risks for developing high LDL cholesterol and hypertriglyceridemia: A five-year cohort study in Japan.
Elevated serum uric acid increases the risk for developing high LDL cholesterol and hypertriglyceridemia, potentially shedding light on its role in cardiovascular disease.
Observational Study
Rigorous JournalHighly CitedExtreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies
Extreme high HDL cholesterol levels are paradoxically associated with high all-cause mortality in both men and women.
Rigorous JournalHighly CitedA low prevalence of coronary heart disease among subjects with increased high-density lipoprotein cholesterol levels, including those with plasma cholesteryl ester transfer protein deficiency.
High HDL levels, regardless of CETP deficiency, are protective against coronary heart disease, regardless of the presence of CETP mutations.
Observational StudyHighly CitedHigh HDL (High-Density Lipoprotein) Cholesterol Increases Cardiovascular Risk in Hypertensive Patients
High HDL-C levels are associated with a U-shaped increase in cardiovascular risk in male patients with hypertension, but not in female patients.
Observational StudyVery Rigorous JournalAssociation Between High-Density Lipoprotein Cholesterol Levels and Adverse Cardiovascular Outcomes in High-risk Populations.
Very high HDL-C levels (>80 mg/dL) are paradoxically associated with higher mortality risk in individuals with coronary artery disease, particularly in men.
Observational StudyHighly CitedHigh-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.
A 1-mg/dl increment in high-density lipoprotein cholesterol is associated with a significant reduction in coronary heart disease risk in men and 3% in women, regardless of analytic methodology.
Highly CitedHigh-density lipoprotein cholesterol as an independent risk factor in cardiovascular disease: assessing the data from Framingham to the Veterans Affairs High--Density Lipoprotein Intervention Trial.
Increased HDL-C levels are a significant predictor of reduced cardiovascular disease risk, with treatment with gemfibrozil reducing death or MI by 22% and lowering total cholesterol by 4%.
RCTHighly Cited