High Cholesterol: Causes, Implications, and Effective Management Strategies

High cholesterol is a common health concern affecting millions. Elevated cholesterol levels may contribute to an increased risk of cardiovascular diseases, which are a leading cause of health issues worldwide. Understanding the causes, implications, and management strategies for high cholesterol can help support public health. Individuals may manage their cholesterol levels and support longevity by adopting cholesterol-supportive lifestyle changes, nutraceuticals, and medications.

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What Is Cholesterol?

Cholesterol is a waxy, fat-like substance found in all the cells of the body. The liver produces most of the body's cholesterol, but it can also be obtained from dietary sources, primarily animal products like meat, dairy, and eggs.

Despite earning a bad reputation, cholesterol is essential for human life. It provides structural integrity and fluidity for cell membranes, insulates nerves, enhances brain function, and is a precursor for synthesizing steroid hormones, vitamin D, and bile acids.

Cholesterol travels through the bloodstream in lipoproteins, which are complexes of lipids and proteins. There are seven classes of lipoproteins, distinguished by their size, lipid composition, and apolipoproteins (a type of protein that binds lipids): 

• Chylomicrons
• Chylomicron remnants
• Very-low-density lipoprotein (VLDL)
• Intermediate-density lipoprotein (IDL)
• Low-density lipoprotein (LDL)
• High-density lipoprotein (HDL)
• Lipoprotein(a) (Lp(a))

Types of Cholesterol and Their Significance

A lipid panel is a blood test that measures the levels of fats in your blood. A basic lipid panel includes the following components:

• Total cholesterol (TC)
• LDL cholesterol (LDL-C)
• HDL cholesterol (HDL-C)
• VLDL cholesterol (VLDL-C)
• Triglycerides (TG)

LDL Cholesterol

LDL-C is a measurement of the amount of cholesterol carried by LDL from the liver to cells throughout the body. Low-density lipoproteins carry high amounts of cholesterol. If present in excess amounts, these particles can accumulate within arterial walls and become oxidized – the first step in atherosclerosis. 

Atherosclerosis is the thickening of the arteries caused by a buildup of plaque. This is why LDL-C is often called "bad cholesterol." Elevated levels of LDL-C are associated with an increased risk of atherosclerosis and cardiovascular diseases, such as coronary artery disease (CAD), peripheral artery disease (PAD), blood clots, heart attack, and stroke. 

HDL Cholesterol

HDL-C is a measurement of the amount of cholesterol carried by HDL. High-density lipoproteins act like a vacuum, picking up excess cholesterol in the periphery and carrying it back to the liver to be recycled and eliminated from the body. This process, called reverse cholesterol transport, helps manage the buildup of cholesterol in the arteries, which may support reduced plaque size, arterial inflammation, and the risk of cardiovascular disease (CVD). This is why HDL-C is often called the "good cholesterol."

VLDL Cholesterol and Triglycerides

Triglycerides are the most common type of fat in the body. They come from dietary fats or are made by the liver when the body needs to store excess calories, particularly those derived from carbohydrates and alcohol, that are not required for immediate energy. (40, 65)

Triglycerides are packaged into VLDLs and released into the bloodstream, where they are delivered to tissues for storage in adipose (fat) cells or for use as energy. VLDL is considered pro-atherogenic because as it circulates in the bloodstream and delivers triglycerides to cells, it is gradually converted into LDL.

High triglycerides and VLDL-C, especially when combined with high LDL-C and/or low HDL-C, are linked to an increased risk of atherosclerosis and CVD (31, 39).   

Understanding High Cholesterol

Hyperlipidemia, also called dyslipidemia, is a common medical condition affecting 93 million American adults characterized by abnormally high levels of lipids (fats) in the blood. There are different subsets of hyperlipidemia depending on which type of lipid is elevated:

• Hypercholesterolemia (high cholesterol) refers to elevations of non-HDL and LDL cholesterol in the blood.
• Mixed hyperlipidemia involves elevated levels of cholesterol and triglycerides. 

Causes of High Cholesterol

There are both genetic and acquired causes of high cholesterol. 

The most common genetic disorder that causes high cholesterol is called familial hypercholesterolemia, which results from mutations in the LDL-receptor, apolipoprotein B (ApoB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. These gene mutations can impact LDL clearance from circulation, resulting in LDL-C levels greater than 190 mg/dL. (45) 

The following lifestyle factors can cause the liver to produce more LDL-C and triglycerides than the body needs: 

• Diets high in saturated and trans fats, simple carbohydrates, and alcohol
• Lack of physical activity
• Smoking
• Obesity (3, 14, 45)  

Certain medications can also affect a person's lipid profile. These include, but are not limited to, birth control pills, corticosteroids, antivirals, diuretics, and immunosuppressants.

Medical conditions known to contribute to dyslipidemia include hypothyroidism, kidney disease, diabetes, liver disease, and pregnancy. (16, 42, 45)

Health Risks Associated With High Cholesterol

Hyperlipidemia is associated with a higher prevalence of atherosclerosis, which can contribute to CVD and adverse cardiovascular events, including heart attacks and strokes. 

The INTERHEART study analyzed data from 52 countries and found that dyslipidemia (characterized by high cholesterol and low HDL-C) was one of the most significant risk factors for heart attack globally. 

The Framingham Heart Study, initiated in 1948 in Framingham, Massachusetts, is a long-term, ongoing cardiovascular cohort study that has played a pivotal role in identifying risk factors for CVD, including high serum levels of TC, LDL-C, and TG.

Researchers have concluded that individuals with LDL-C levels of 130 mg/dL or greater have as much as a 50% increased risk of cardiovascular events and mortality. Those with triglycerides above 200 mg/dL are 25% more likely to experience cardiovascular issues than someone with a normal level. 

Diagnosing High Cholesterol

High cholesterol can be diagnosed with a simple blood test, such as one of the following: 

• Lipid Panel by Access Med Labs
• Lipid Panel Basic by BostonHeart Diagnostics
• Lipid Panel with Total Cholesterol/HDL Ratio by Access Labcorp Draw

Hypercholesterolemia is diagnosed when TC is greater than 200 mg/dL and/or LDL-C is greater than 100 mg/dL. Hypertriglyceridemia is diagnosed when fasting triglycerides are higher than 150 mg/dL. (18) 

The following table describes optimal, moderate, and high-risk category ranges for each of the markers included on a standard lipid panel:

The U.S. Preventive Task Force provides the following guidelines for screening individuals for lipid disorders:

• Men aged 35 and older
• Men aged 20-35 at an increased risk for coronary heart disease (CHD) 
• Women aged 20 and older at an increased risk for CHD 

Risk factors for CHD include: 

• First-degree relative with heart disease
• Smoking
• Obesity
• High blood pressure
• Prediabetes or diabetes
• Unhealthy eating habits
• Physical inactivity 

Patients diagnosed with high cholesterol should have repeat lipid measurements every 4-12 weeks until they reach goal lipid levels and every 3-12 months as needed thereafter (38). 

Strategies for Balancing and Maintaining Healthy Cholesterol Levels

Cholesterol levels are highly responsive to therapeutic interventions. Supporting healthy cholesterol levels can involve a combination of lifestyle modifications, nutraceuticals, and pharmaceuticals. The strategies for managing cholesterol should be tailored to the individual's degree of dyslipidemia and cardiovascular risk (often assessed using tools like the ASCVD Risk Estimator).

Dietary Modifications

A heart-healthy diet follows generally accepted nutritional patterns that can help manage risk factors for CVD, such as high cholesterol, blood sugar, blood pressure, and inflammation. These diets emphasize the consumption of fruits, vegetables, whole grains, and lean proteins and the avoidance of ultra-processed foods, refined sugars, processed meats, and alcohol. 

The Mediterranean diet exemplifies a heart-healthy eating plan, with research suggesting its benefits for weight management, improved glycemic control, lower blood pressure, and optimized lipid profiles. These combined advantages may contribute to a 29% lower risk of cardiovascular mortality for those who adhere to the Mediterranean diet.

The myth that cholesterol-containing foods (like eggs) raise cholesterol has largely been debunked. Instead, consider these dietary modifications to support healthy lipid levels:

Foods to Eat:

• Increasing your daily servings of fruits and vegetables from two to five may lead to a 12% lower risk of heart disease and stroke. 
• Replacing saturated fats with unsaturated fats, found in olives, avocados, fish, walnuts, and flaxseeds, may help manage plaque formation and support TG and HDL-C levels.  
• Eating just ten grams of soluble fiber may help lower TC and LDL-C by at least 5-11 points. Foods rich in soluble fiber include whole grains, seeds, avocados, beans, fruits, and vegetables. 

Foods to Limit: 

• Saturated fats in meat, dairy, coconut, and palm oil may increase LDL-C. The American Heart Association (AHA) recommends reducing saturated fat intake to less than 6% of total daily calories to support healthy cholesterol levels. (64) 
• Trans fats may raise LDL-C, potentially increasing the risk of CVD by at least 23%. The AHA recommends completely eliminating trans fats from the diet to support cardiovascular health. Dietary sources of trans fats include fried foods, baked goods, snack foods, margarine, and other processed foods.
• Refined carbohydrates, especially simple sugars, may lower HDL-C and raise TG. Low-carbohydrate diets (classically defined as less than 26% of daily calories derived from carbohydrates) have been shown to support reduced inflammation and TG and increase HDL-C levels. 

Physical Activity

According to the AHA, engaging in at least 150 minutes of moderate-intensity or 75 minutes of vigorous aerobic activity per week may help support healthy cholesterol levels. Greater benefits can be observed by being active for at least five hours every week. 

Exercise also helps to raise HDL-C. Studies have shown that regular aerobic and resistance training can raise HDL-C. 

The AHA recommends that adults participate in moderate- to high-intensity resistance (strength) training at least weekly. 

Medication and Medical Interventions

Pharmacologic therapy is recommended for patients who are 40-75 years old, with LDL-C greater than 190 mg/dL, diabetes mellitus, and at sufficient ASCVD risk. 

• Statins are the first-line medications for lowering LDL-C. They work by inhibiting an enzyme involved in cholesterol production. Statins also have modest effects on TG and can raise HDL-C. 
• Ezetimibe is a medication that works in the intestines to inhibit cholesterol absorption, thereby lowering LDL-C levels. It can be used alone or in combination with statins.
• PCSK9 inhibitors are newer injectable medications that enhance the liver's ability to remove LDL cholesterol from the bloodstream. They are typically used in individuals with very high LDL-C levels or those who cannot tolerate statins.
• Drugs like cholestyramine bind bile acids in the intestines, preventing their reabsorption and promoting the excretion of cholesterol. They primarily lower LDL-C levels and can also modestly raise HDL-C.
• Fibrates primarily lower TGs but can also raise HDL-C. They are often used in individuals with hypertriglyceridemia or mixed dyslipidemia.

The following evidence-based nutraceuticals can also be considered to help manage cholesterol levels:

• Omega-3 fatty acids may help reduce arterial inflammation, exhibit TG-lowering effects, and can raise HDL-C levels (18, 25).
• Plant sterols and stanols (3 grams daily) may help lower LDL-C by 12%.
• Red yeast rice (RYR) is a natural supplement that contains monacolin K, which is chemically identical to a statin. RYR may help lower LDL-C, TC, and TG as effectively as a low-intensity statin with fewer statin-related side effects. 
• Niacin may help lower VLDL-C, LDL-C, and TG while simultaneously increasing HDL-C levels. Caution should be taken because high doses can cause flushing and liver toxicity. (18, 25) 

Lifestyle Changes and Self-Care

The following lifestyle and self-care practices can also support efforts in managing cholesterol levels:

• Maintain a healthy weight
• Quit smoking
• Drink alcohol in moderation (no more than two drinks per day for men and one drink per day for women)
• Manage stress by avoiding stressful triggers, eating a healthy diet, exercising regularly, developing healthy sleep habits, and doing activities that promote relaxation.

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Key Takeaways

• Diagnosing and managing high cholesterol is one aspect of a successful protocol for supporting cardiovascular health. 
• Key strategies that may be effective for supporting healthy cholesterol levels include maintaining a healthy weight, quitting smoking, moderating alcohol intake, managing stress, and considering medications and supplements that can help optimize lipid levels. 
• Cholesterol management is just one component of a heart-healthy lifestyle. It is important to adopt a comprehensive approach, recognizing all possible factors that influence cardiovascular health.