What causes hypercholesterolemia (high cholesterol)?

From the Guidelines

High cholesterol is primarily caused by a combination of genetic factors, such as familial hypercholesterolemia, and lifestyle choices, including diet, physical inactivity, and obesity. Genetics play a significant role through familial hypercholesterolemia, where individuals inherit genes that reduce the liver's ability to remove LDL cholesterol from the blood 1. According to a study published in the American Family Physician in 2016, familial hypercholesterolemia occurs in approximately 1 of every 200 to 500 persons in North America and Europe and is more prevalent among populations with known founder effects 1.

Causes of High Cholesterol

• Genetic factors: Familial hypercholesterolemia is a genetic disorder that affects the liver's ability to remove LDL cholesterol from the blood 1.
• Lifestyle choices: Diet, physical inactivity, and obesity are major contributors to high cholesterol 1.
• Diet: Foods high in saturated fats (red meat, full-fat dairy) and trans fats (processed foods) can increase cholesterol levels 1.
• Physical inactivity: Prevents the body from efficiently processing fats and raising beneficial HDL cholesterol 1.
• Obesity: Increases LDL cholesterol and triglycerides while lowering HDL cholesterol 1.
• Smoking: Damages blood vessel walls, making them more prone to fat accumulation 1.
• Excessive alcohol consumption: Can raise triglyceride levels 1.
• Age and gender: Influence cholesterol levels, with levels typically rising as we age, and men generally having higher levels than premenopausal women 1.
• Medical conditions: Certain medical conditions like diabetes, hypothyroidism, and kidney disease can elevate cholesterol levels 1.
• Medications: Such as some diuretics, beta-blockers, and certain hormonal treatments can also elevate cholesterol levels 1.

Management of High Cholesterol

Managing cholesterol often requires addressing multiple factors through:

• Diet modification
• Regular exercise
• Weight management
• Sometimes medication like statins when lifestyle changes aren't sufficient 1. According to the Endocrine Society's guidelines on diagnosis and management of hypertriglyceridemia, initial treatment of patients with mild to moderate hypertriglyceridemia should include dietary counseling and weight loss in patients who are overweight or obese 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Causes of High Cholesterol

• Genetic factors: Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality 2, 3, 4.
• Environmental factors: Lifestyle factors such as alcohol consumption, physical activity, and smoking also play a role in determining high-density lipoprotein cholesterol (HDL-C) levels 5.
• Diet: The westernization of the diet has led to increased frequency of "lifestyle-related disorders" such as hyperlipidemia, diabetes mellitus, and atherosclerosis 6.
• Interaction between genetic and environmental factors: Hyperlipidemia is a complex disorder caused by multiple genetic and environmental factors, and their interaction 6.

Specific Factors Contributing to High Cholesterol

• Alcohol consumption: Associated with an increase in HDL-C levels, with an increase of 9.0-13.1 mg/dL from nondrinker to highest categories 5.
• Physical activity: Associated with a modest increase in HDL-C levels, with an increase of 3.0-3.3 mg/dL from lowest to highest categories 5.
• Smoking: Associated with a large decrement in HDL-C levels in women and a modest one in men, with a decrease of 9.9 mg/dL in women and 2.6 mg/dL in men between nonsmoker and > or =20 cigarettes per day categories 5.
• Genetic mutations: Mutations in genes such as LDLR, APOB, and PCSK9 can cause familial hypercholesterolemia, a monogenic condition 3, 4.