High cholesterol is a pervasive health issue affecting millions. Elevated cholesterol levels significantly increase the risk of cardiovascular diseases, the leading cause of death worldwide. Understanding the causes, implications, and effective management strategies for high cholesterol helps mitigate its impact on public health. Individuals can effectively manage their cholesterol levels and increase longevity by capitalizing on the health benefits of cholesterol-lowering 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, prevents the buildup of cholesterol in the arteries, reducing 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 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 negatively 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 strongly associated with a higher prevalence of atherosclerosis, which can result in 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 die from cardiovascular disease 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. Preventing and treating high cholesterol can involve a combination of lifestyle modifications, nutraceuticals, and pharmaceuticals. The strategies for managing cholesterol should be tailored to the patient'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 mitigate 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 extensive research showing its benefits for weight loss, improved glycemic control, lower blood pressure, and optimized lipid profiles. These combined advantages 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, focus on these dietary modifications to optimize lipid levels:
Foods to Eat:
- Increasing your daily servings of fruits and vegetables from two to five leads to a 12% lower risk of death from heart disease and stroke.
- Replacing saturated fats with unsaturated fats, found in olives, avocados, fish, walnuts, and flaxseeds, can reduce plaque formation and improve TG and HDL-C levels.
- Eating just ten grams of soluble fiber can 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 increase LDL-C. The American Heart Association (AHA) recommends reducing saturated fat intake to less than 6% of total daily calories to lower cholesterol levels. (64)
- Trans fats raise LDL-C, increasing the risk of CVD by at least 23%. The AHA recommends completely eliminating trans fats from the diet to reduce cholesterol levels and 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, 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 reduce 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 can lower 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 used to help manage cholesterol levels:
- Omega-3 fatty acids reduce arterial inflammation, exhibit TG-lowering effects, and can raise HDL-C levels (18, 25).
- Plant sterols and stanols (3 grams daily) can 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 can lower LDL-C, TC, and TG as effectively as a low-intensity statin with fewer statin-related side effects.
- Niacin can 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 preventing CVD.
- Key strategies that are effective for preventing and treating high cholesterol include maintaining a healthy weight, quitting smoking, moderating alcohol intake, managing stress, and taking medications and supplements that can 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 risk factors that influence cardiovascular health.
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