What are the implications of hypercholesterolemia (elevated cholesterol)?

From the Guidelines

Elevated cholesterol should be managed through a combination of lifestyle changes and medication when necessary, with the goal of reducing LDL cholesterol levels to less than 100 mg/dL for high-risk patients, as recommended by the National Cholesterol Education Program Adult Treatment Panel III guidelines 1.

Lifestyle Changes

Start by adopting a heart-healthy diet low in saturated fats and trans fats, focusing on fruits, vegetables, whole grains, lean proteins, and healthy fats like olive oil.

• Regular physical activity, aiming for at least 150 minutes of moderate exercise weekly, can help raise HDL (good) cholesterol and lower LDL (bad) cholesterol.
• Dietary modifications such as decreasing consumption of fat and simple sugars and increasing intake of omega-3 fatty acids (e.g., fish oil, flaxseed oil) can also help to decrease triglycerides.

Medication

If lifestyle modifications aren't sufficient, statins are typically the first-line medication, including atorvastatin (10-80mg daily), rosuvastatin (5-40mg daily), or simvastatin (10-40mg daily) 1.

• For those who cannot tolerate statins, alternatives include ezetimibe (10mg daily), PCSK9 inhibitors (evolocumab or alirocumab), or bile acid sequestrants.
• Cholesterol levels should be monitored every 3-6 months initially, then annually once stable.

Importance of Treatment

Treatment is important because elevated cholesterol, particularly LDL, contributes to atherosclerosis and increases the risk of heart attack and stroke 1.

• Statins work by inhibiting HMG-CoA reductase, the enzyme responsible for cholesterol production in the liver, while also increasing LDL receptor activity to remove more cholesterol from the bloodstream.
• Regular monitoring and adjustments to treatment as necessary can help to achieve and maintain optimal cholesterol levels, reducing the risk of cardiovascular disease.

From the FDA Drug Label

Cholestyramine for Oral Suspension, USP powder is indicated as adjunctive therapy to diet for the reduction of elevated serum cholesterol in patients with primary hypercholesterolemia (elevated low density lipoprotein [LDL] cholesterol) who do not respond adequately to diet Atorvastatin calcium tablets are used: to reduce the risk of: ... along with diet to reduce low density lipoprotein cholesterol (LDL-C) or bad cholesterol: in adults with primary hyperlipidemia

• Elevated cholesterol treatment: Cholestyramine and atorvastatin are both used to reduce elevated serum cholesterol levels.
• Primary hypercholesterolemia: Cholestyramine is indicated for patients with primary hypercholesterolemia who do not respond adequately to diet.
• LDL-C reduction: Atorvastatin is used to reduce LDL-C levels in adults with primary hyperlipidemia.
• Dietary therapy: Both cholestyramine and atorvastatin should be used in conjunction with dietary therapy to reduce cholesterol levels 2, 3.

From the Research

Treatment Options for Elevated Cholesterol

• Statins are the most potent drugs for lowering low-density lipoprotein cholesterol (LDL-C) levels and are well tolerated in most patients 4.
• The addition of a bile acid sequestrant or ezetimibe to a statin produces additional LDL-C reduction, allowing many patients to reach LDL-C targets 4.
• Ezetimibe, a cholesterol absorption inhibitor, leads to additional LDL cholesterol reduction and decreased atherosclerotic cardiovascular disease (ASCVD) risk when added to statin therapy, without raising significant safety concerns 5.
• Monoclonal antibodies of proprotein convertase subtilisin/kexin type 9 (PCSK9), such as alirocumab and evolocumab, have been approved to lower LDL cholesterol levels and decrease ASCVD risks when added to maximally tolerated statin therapy 5.

Lifestyle Modifications for Elevated Cholesterol

• Increasing physical activity has extensive benefits, including improving both blood pressure and blood cholesterol, and is a recommended lifestyle-only treatment for patients with mildly or moderately elevated blood pressure and cholesterol 6.
• Dietary composition is crucial, with replacing saturated fat with monounsaturated fatty acids (MUFAs) or n-6 polyunsaturated fatty acids (PUFAs) lowering plasma LDL cholesterol and ameliorating the LDL/HDL ratio 7.
• A multifactorial approach including multiple lifestyle changes with additive effects is the best option for controlling dyslipidemias through lifestyle modifications 7.

Combination Therapies for Elevated Cholesterol

• The combination of ezetimibe and atorvastatin is very effective in reducing atherogenic lipids and is well tolerated, making it a useful option for patients who cannot reach their lipid targets with maximally tolerated statin doses 8.
• Fixed-dose combinations, such as atorvastatin + ezetimibe, improve medication adherence and can be assumed to have greater benefits in reducing cardiovascular events due to the greater reduction in atherogenic lipids 8.