Hyperlipidemia, commonly known as high cholesterol, refers to abnormally elevated levels of any or all lipids and lipoproteins in the blood. Lipids include cholesterol and triglycerides, which are fatty substances that are important components of all living cells. High levels of lipids in the blood can increase the risk of various cardiovascular diseases like coronary heart disease, peripheral vascular disease, cerebrovascular disease and atherosclerosis. Hyperlipidemia is caused due to various factors like genetics, unhealthy lifestyle, obesity, diabetes, hypothyroidism etc. It is usually managed through lifestyle modifications like diet control, exercise and medication if required.
Classification
Antihyperlipidemic Drugs are classified based on their mechanism of action and the particular lipid/lipoprotein fraction they mainly act on. The major classes include:
Statins
Statins are the first line treatment for lowering LDL or "bad" cholesterol levels. They act by competitively inhibiting HMG-CoA reductase which is the rate limiting enzyme for cholesterol biosynthesis in the liver. Some commonly used statins are atorvastatin, rosuvastatin, simvastatin, pravastatin etc. Statins are very effective in reducing LDL levels by 30-60% and also reduces cardiovascular risk by 15-25%. They are well tolerated but can cause mild muscle pain in some individuals.
Fibric Acid Derivatives
Fibric acid derivatives mainly lower triglyceride levels by activating lipoprotein lipase and glucose transporter protein-4. They also increase HDL or "good" cholesterol levels. Commonly used fibrates include fenofibrate, gemfibrozil and bezafibrate. They lower triglycerides by 20-50% but have lesser effects on LDL levels. They should not be combined with statins due to increased risk of myopathy.
Bile acid sequestrants
Bile acid sequestrants work by binding bile acids in the intestine and eliminating them from the body. This causes greater breakdown of cholesterol into bile acids to make up for the loss, which leads to reduction in LDL levels by 15-30%. They include cholestyramine, colestipol and colesevelam. They are less effective than statins but useful as add-on therapy or if statins are not tolerated.
Niacin
Niacin or nicotinic acid is highly effective in raising HDL levels by 20-30% and also reduces triglycerides, LDL and total cholesterol levels when taken in high doses. However, it can cause significant side effects like flushing, itching and gastrointestinal disturbances which limits its use as monotherapy. It is now primarily used as an add-on to other drug regimens.
PSCK9 inhibitors
PCSK9 inhibitors are monoclonal antibodies that bind to proprotein convertase subtilisin/kexin type 9 (PCSK9) protein and prevent its interaction with LDL receptors. This allows greater number of LDL receptors to remain on the hepatocyte surface to clear more LDL particles from the blood, resulting in reduction in LDL levels by 50-70%. Evolocumab and alirocumab are two drugs in this class approved for treatment of high cholesterol. They are highly effective but very expensive as of now.
Lifestyle modifications for Antihyperlipidemic Drugs
In addition to drug treatment, lifestyle changes play an important role in managing high cholesterol levels:
- Diet control: Emphasize on consumption of foods low in saturated and trans fats like whole grains, fruits, vegetables, fish etc. Limit intake of fried foods and red meat.
- Weight management: Losing weight if overweight or obese through calorie restriction and exercise can aid in reducing cholesterol levels.
- Physical activity: Adults should aim for at least 30 minutes of moderate activity like walking or cycling on most days. This helps boost HDL levels.
- Avoiding alcohol: Limit intake of alcoholic drinks to recommended daily/weekly amounts.
- Smoking cessation: Smoking is directly linked to increased cardiovascular risk. Quitting smoking can benefit cholesterol levels.
- Stress management: Handle daily stress in healthy ways through yoga, meditation or other relaxation techniques. Chronic stress raises cholesterol.
- Monitoring lipids regularly: Cholesterol and triglyceride levels should be checked periodically by the doctor, even with medication and lifestyle changes, to ensure optimal control.
Using a combination of lifestyle changes, risk-factor modifications and appropriate antihyperlipidemic drugs treatment based on the lipid abnormality and cardiovascular risk status of the individual can effectively manage hyperlipidemia. Early detection and compliance with long-term management is important to prevent its associated complications. The availability of different drug classes now allows for better customized treatment approaches for hypercholesterolemia.
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