Dyslipidemia

---

Dyslipidemia refers to abnormal levels of lipids (fats) in the blood. The main lipids measured are:

• Cholesterol - There are two main types:
• LDL or "bad" cholesterol: High levels contribute to buildup of plaque in arteries (atherosclerosis).
• HDL or "good" cholesterol: High levels help remove cholesterol from arteries. Low levels increase heart disease risk.
• Triglycerides - Elevated triglycerides also contribute to atherosclerosis and increase heart disease risk.
• Lipoprotein particles - Measuring different lipoprotein particles can provide further heart disease risk assessment. For example, small, dense LDL particles are more atherogenic than large, buoyant ones.

Causes of dyslipidemia include:

• Genetics - Some people are born with a tendency to have high cholesterol or triglycerides. Familial hypercholesterolemia is an inherited form.
• Diet - Diets high in saturated fat, trans fat, and cholesterol can elevate lipid levels. Excess sugar and carbohydrate intake raise triglycerides.
• Obesity - Excess weight and body fat leads to dyslipidemia. Losing weight can help lower lipid levels.
• Medical conditions - Hypothyroidism, diabetes, liver or kidney disease can cause dyslipidemia.
• Certain medications - Steroids, beta blockers, diuretics, etc. can raise lipid levels.
• Lifestyle - Lack of physical activity or exercise, smoking, and heavy alcohol use all contribute to dyslipidemia.

The treatment of dyslipidemia focuses on lifestyle changes and medications as needed to reach target lipid levels. Lifestyle changes include:

• Following a heart-healthy diet low in saturated fat, trans fat and cholesterol. Focus on lean proteins, whole grains, fruits and vegetables.
• Exercising regularly. Aim for at least 150 minutes per week of moderate exercise.
• Losing excess weight. Losing even 5-10 pounds can help.
• Quitting smoking.

Medications for dyslipidemia include:

• Statins - First-line treatment to lower LDL cholesterol. Examples are atorvastatin, simvastatin, rosuvastatin, etc.
• Fibrates - Used to lower triglycerides. Examples are fenofibrate and gemfibrozil.
• Niacin - Can raise HDL and lower LDL/triglycerides. Has side effects so rarely used.
• Ezetimibe - Lowers cholesterol absorption. Used alone or with statins.
• PCSK9 inhibitors - New injectable drugs to lower LDL cholesterol for high-risk patients.
• Fish oil supplements - Can modestly lower triglycerides. Dietary fish intake is preferable.

Treatment aims for LDL under 100, triglycerides under 150 and HDL over 40-50 in most patients. Aggressive treatment is needed for those with heart disease or high risk of heart disease. Follow-up and monitoring of lipid levels and potential side effects of medications are ongoing.

---

Topic Highlights:-

• Dyslipidemia is a disorder of the lipoprotein metabolism.
• This visual presentation explains dyslipidemia, discernible by presence of abnormal levels of lipids in the blood.
• Also included are segments on its causes, complications, lifestyle changes available to improve quality of life, and treatment options.

Transcript:-
Dyslipidemia derives its name from the Greek words “lipid” (meaning fat) and “emia” (meaning in the blood.) Hence dyslipidemia is a disorder of lipids or fats in the blood. Dyslipidemia may be characterized by high levels of total cholesterol in the blood. 1 in 5 adults have high cholesterol. High cholesterol is not just prevalent in older or overweight people. It can be due to heredity or an unhealthy lifestyle. The prevalence of dyslipidemia is significantly higher among men than women, and among whites than blacks.

Cholesterol is a soft, fat-like substance found in the body’s cells. It helps form certain hormones and other necessary substances. Besides being found in the body’s cells, cholesterol is also present in the blood stream where it is transported to various parts of the body. The liver produces cholesterol. The human body also receives dietary cholesterol in the form of fats from animals, especially egg yolks, meat, fish, poultry, and whole milk dairy products.

Cholesterol cannot dissolve in the blood stream, and must be transported by carriers called lipoproteins, which are synthesized in the liver. The liver produces two types of lipoprotein particles called very low-density lipoproteins (VLDL) and high-density lipoproteins (HDL). The lipoprotein particles are secreted into the bloodstream where the large VLDL particles are rapidly transformed into smaller cholesterol rich low-density lipoprotein (LDL) particles.

LDL is the major cholesterol carrier in the blood, carrying 60-80% of the body’s cholesterol. The cholesterol rich LDL, “the bad cholesterol,” is attached to the arterial wall and delivers its cholesterol into the artery. HDL, “the good cholesterol,” picks up cholesterol from the artery and transports it back to the liver. This is called reverse cholesterol transport (RCT).

At high blood cholesterol (mainly LDL cholesterol) more and more cholesterol will be deposited in the arteries. Together with immune cells this causes the formation of atherosclerotic plaques in the arterial wall. The plaques predispose to impairment of blood flow and thrombus formation. Eventually, the growing plaques reach the clinical horizon in the form of heart attacks, stroke, or gangrene.

Causes of dyslipidemia include excessive intake of food rich in fat, uncontrolled diabetes mellitus, heredity, metabolic syndrome, overweight and obesity, under-active thyroid gland, kidney or liver problems, sedentary life style, alcohol and certain medications.

Blood lipid test includes total cholesterol, LDL, and HDL, as well as other blood lipid risk factors. Tests are carried out after a 12-hour fast. Additional risk factors for cardiovascular risk are age, being male, smoking, high blood pressure, diabetes, overweight/obesity and physical inactivity. A doctors may also order an ECG. If the test results are abnormal, a second test is recommended after a week or a couple of months.

Dyslipidemia or high cholesterol can be treated through lifestyle modifications, dietary modifications, exercise and weight reduction; or drug therapy alone or in combination with one another, depending on the causes. These basic interventions may provide sufficient treatment for up to 90 percent of persons with dyslipidemia. Improvement of lifestyle, when possible, is the cornerstone and first step of treatment of dyslipidemia. If optimal cholesterol levels are not achieved with life style modifications, lipid modifying drugs should be considered.

There are four types of drugs that are used to treat dyslipidemia. The first are a group of drugs called HMG-CoA Reductase Inhibitors, better known as Statins. Lovastatin, atorvastatin, pravastatin, simvastatin, and rosuvastatin are HMG-CoA reductase inhibitors. HMG-CoA reductase is an enzyme found in the liver. This enzyme is very vital to the manufacture or synthesis of cholesterol in the body. Statins inhibit this enzyme by competitively blocking the receptor sites that the enzyme would occupy. This stops the process of cholesterol synthesis. The reduction in the level of cholesterol in the liver cells (or hepatocytes) makes the cells produce more receptors for LDL on their surface. The LDL circulating in the blood then gets picked up by these receptors and is absorbed into the hepatocytes. This dual mechanism of action of statins results in a reduction in the levels of LDL cholesterol or “bad” cholesterol in the body. Statins may reduce the LDL levels by 20-40% (dose dependent). HDL levels may increase by 6-12 percent.

Cholesterol in the liver breaks down to form bile acids that are transported to the intestines. Bile acids help in digestion of food. The bile acid binding resins like cholestyramine and colestipol bind with the bile acids in the intestines. This binding results in an insoluble complex that cannot be reabsorbed from the intestinal walls into the blood. This insoluble complex is then excreted into the feces from the intestine. The loss of bile acids through excretion makes the liver break down more and more cholesterol to form the bile acids needed in the intestine. Thus, the cholesterol levels in the liver and hence in the blood is reduced. These agents decrease LDL cholesterol levels by up to 20 percent. These drugs are generally preferred for women in the childbearing age group or a young adult.

Ezetimibe is the new principle for lowering LDL cholesterol in blood. It reduces the reabsorption of cholesterol in the intestines and is particularly useful in combination with statins to bring about major cholesterol reduction.

The liver manufactures and secretes very low density lipoprotein or VLDL into the blood. This VLDL then gets converted into LDL or “bad” cholesterol in the blood. Nicotinic acid or Niacin acts in the liver and inhibits the manufacture or the synthesis of VLDL. This results in an increase in HDL or “good” cholesterol and reduces the levels of LDL or “bad” cholesterol. This agent increases the HDL level by 15 to 35 percent, reduces total and LDL cholesterol levels by 10 to 25 percent.

Fibric acid derivatives such as Gemfibrozil act on the liver to reduce the amount of triglyceride rich VLDL synthesis. Fibric acids are also known to increase cholesterol conversion into bile. These drugs also speed up the chemical breakdown of VLDL circulating in the blood stream. Triglyceride levels are reduced nearly 20-50% and HDL increases by 10-15%. LDL levels may decrease by 10-15%.

Regular physical activity helps control cholesterol levels. It is important to develop healthy eating habits to improve cholesterol levels, as well as blood sugar. One should maintain a healthy lifestyle, give up smoking, reduce alcohol intake and consume a low fat diet rich in fiber and whole grains. It’s also important to maintain a healthy height to weight ratio. Cholesterol levels should be checked annually since dyslipidemia does not have any symptoms and is apparent only when complications occur.