Hyperlipidemia is considered as one of the major risk factors causing cardiovascular diseases. According to World Health Organisation, approximately 2.6 million deaths (4.5% of total) and one-third of ischaemic heart disease are attributable to high cholesterol.
Hyperlipidemia is a lifelong condition which refers to abnormal levels of lipids (fats) circulating in the blood. These plasma lipids include triglycerides (neutral fats), cholesterol, and plasma lipoproteins (Fat-protein complex).
Cholesterol is a wax-like substance produced naturally in the liver to aid brain functioning, hormone production and cell function. It is transported to body cells using lipoproteins.
Lipoproteins are further categorised into Very Low-Density Lipoproteins (VLDL), Low-density lipoproteins (LDL), or bad cholesterol, and high-density lipoproteins (HDL), or good cholesterol. Both VLDL and LDL remains in the bloodstream, causing damaging effects on health whereas HDL is good for health as it takes excess cholesterol back to the liver for excretion.
Triglycerides are stored in fat cells to provide energy for cell function and metabolism.
Low levels of HDL and high levels of LDL with an elevated level of cholesterol and triglycerides cause plaque deposits, which grows longer over time. These deposits clog arteries and reduce the supply of oxygen to heart, ultimately leading to atherosclerosis, heart disease and stroke.
TYPES OF HYPERLIPIDEMIA
There are several types of hyperlipidemia depending on the different types of fats involved and how each type impacts the body.
The main types of hyperlipidemia are as follow:
Type I or hyperlipidemia familial lipoprotein lipase deficiency
It is the type of hyperlipidemia prevalent in childhood. It is an inherited condition which disrupts the breakdown of fats, thereby leading to infections in the pancreas, enlargement of the liver and abdominal pain.
Type IIa or familial hypercholesterolemia, and Type IIb, or familial combined hyperlipidemia
Both these types of hyperlipidemia result in high levels of LDL. It may cause fat deposits in the skin and around eyes. It can also lead to increased risk of heart problems.
Type III, or familial dysbetalipoproteinemia
It is the type of hyperlipidemia that affects the levels of lipoproteins. It usually occurs in when levels of LDL in blood are low. A typical feature of type III is the presence of yellowish-grey plaques on the eyelids and around the eyes. It also increases the early onset of cardiovascular disease.
Type IV, or hypertriglyceridemia
It is the type of hyperlipidemia that defines the increase in levels of triglycerides leading to obesity, high blood glucose, and high insulin levels. It is not caused until early adulthood.
CAUSES OF HYPERLIPIDEMIA
Being obese or overweight with a lack of physical activity and consumption of foods rich in saturated fats and cholesterol can contribute to hyperlipidemia. Beyond diet, some other secondary factors can also increase the risk of hyperlipidemia. It includes:
- Family history of hyperlipidemia
- Unhealthy lifestyle habits such as smoking and drinking
- Certain health conditions such as diabetes, renal disease, and inherited conditions
- Certain medications such as antidepressants, diuretics and birth control pills
SYMPTOMS OF HYPERLIPIDEMIA
Most of the people with hyperlipidemia does not have any apparent symptoms, but it is discovered by routine examination. It can cause chest pain along with swelling in the liver and nodules formed on the knees.
DIAGNOSIS OF HYPERLIPIDEMIA
The diagnosis of hyperlipidemia can be made by evaluation of LDL, HDL, VLDL and triglycerides levels in the blood test. A person may have hyperlipidemia if they have one or a combination of following:
- Higher LDL and VLDL levels
- Lower HDL levels
- Higher total cholesterol levels
- Higher triglyceride levels
The following table highlights the optimal levels of triglycerides, lipoprotein and cholesterol:
PREVENTION: LIFESTYLE MODIFICATIONS TO MANAGE HYPERLIPIDEMIA
Being physically active with an improvement in diet and reduction in excess weight are the best ways to prevent and manage hyperlipidemia. Various lifestyle measures can help to prevent high cholesterol or reduce your risk of developing hyperlipidemia:
Regular exercise and physical activity help to encourage weight loss and reduce bad cholesterol levels. A total of 150 minutes of moderately intense exercise per week is recommended in patients with hyperlipidemia.
Avoid foods with saturated and trans fat
Fried foods and foods such as red meat, bacon, sausage, and full-fat dairy products should be avoided. People should switch to lean proteins like chicken, turkey, fish and low-fat or fat-free dairy. Monounsaturated fats like olive and canola oil should be used for cooking.
Eat a heart-healthy diet
A heart-healthy diet includes a variety of whole fruits, vegetables, high-quality proteins, plenty of fiber, lots of water, and whole-grain foods. This diet not only decreases cholesterol levels but also reduces the risk of cardiovascular disorders.
Maintain a healthy weight
Overweight and obesity raise levels of bad cholesterol. Losing weight can help to reduce cholesterol levels. To lose weight, adopt a low-calorie diet and increase physical activity to burn extra calories.
TREATMENT: DRUGS USED TO MANAGE HYPERLIPIDEMIA
Along with lifestyle measures, specific cholesterol and triglyceride-lowering medication are also prescribed. Currently, antihyperlipidemic drugs contain five significant classes that include statins, fibric acid derivatives, bile acid-binding resins, nicotinic acid derivatives and drugs that inhibit cholesterol absorption. Monotherapy is effective in managing hyperlipidemia, but combination therapy may also be required for a comprehensive approach.
These drug classes are explained as below:
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)reductase inhibitors (statins):
Statins are prescribed for lowering higher cholesterol levels. It includes drugs such as:
Other HMG-CoA reductase inhibitors include the diallyl disulfide (DADS) and diallylthiosulfinate. These drugs are described as structural analogues of HMG-coenzyme A reductase.
Mechanism of action:
They inhibit rate-limiting enzyme (HMG-coenzyme A reductase) in the biosynthesis of cholesterol in the liver. Inhibition of the enzyme results in reduced plasma levels of total cholesterol (TC), LDL and ApoB. Statins also cause a decrease in plasma triglycerides levels and a small increase in plasma level of HDL.
Efficacy and Safety:
Research studies indicate that statins can achieve 20%–50% reductions in cholesterol levels with a reduced incidence of coronary morbidity and mortality in high-risk adults. Statins are frequently well-tolerated but can cause some common adverse effects such as gastrointestinal symptoms, headache, and dizziness. These symptoms are more common with higher doses and may reduce if dose and another statin can be used.
Bile acid sequestrants
Bile acid synthesis is the primary pathway of cholesterol catabolism in the liver. It is estimated that about 500mg of cholesterol is converted into bile acid in the liver. Bile acid plays an integral role in the absorption of fats from foods. Bile acid sequestrants include:
Mechanism of action
Bile acid sequestrants are positively charged resins. They act by binding to the negatively charged
bile acids in the intestine to form a large insoluble complex. This complex is not absorbed and therefore excreted in the faeces. It also increases the excretion up to tenfold, resulting in greater conversion of cholesterol to bile acids. Furthermore, bile acid sequestrants increase HDL levels.
Efficacy and Safety
Bile acid sequestrants are rarely used as initial therapy due to poor patient tolerance. The most common adverse effects experienced are constipation, nausea, indigestion, bloating and flatulence.
Fibric acid derivatives (Fibrates)
Fibrates are a widely used class of antihyperlipidemic agents. It includes :
Mechanism of action
Fibrates exhibit multiple mechanisms of action. It acts by stimulating lipid degradation, increases hepatic fatty acid (FA) uptake and increases the removal of LDL particles and HDL production.
Efficacy and safety
Clinical trials indicated that fibrates result in a significant reduction in plasma triglycerides and a modest reduction in LDL cholesterol. It also increases the levels of HDL cholesterol level. Fibrates also decrease the progression of coronary atherosclerosis and reduce the incidence of coronary artery disease. Generally, fibrates are well-tolerated but can lead to some side effects such as gastrointestinal symptoms, skin rashes and gallstones. The use of fibrates should be avoided in patients with liver and renal dysfunction.
Nicotinic acid derivatives (Niacin)
Niacin, a type B vitamin is the oldest lipid-lowering agent used to treat hyperlipidemia proved to decrease cardiovascular morbidity and total mortality.
Mechanism of action
Niacin acts by blocking hormone-sensitive lipase, which decreases triglycerides lipid degradation. It also inhibits VLDL secretion, in turn, reduce the production of LDL. It also elevates HDL cholesterol concentrations by increasing HDL synthesis.
Efficacy and safety
Niacin effectively decreases total cholesterol, LDL cholesterol, triglycerides. Niacin treatment can lead to common side effects such as nausea, abdominal discomfort, itching and headache.
Selective cholesterol absorption inhibitor (Ezetimibe)
Ezetimibe is the first member of a group of drugs which has improved the treatment of elevated cholesterol levels.
Mechanism of action
Ezetimibe acts by selectively inhibiting the absorption of cholesterol in the small intestine, leading to a decrease in the intestinal cholesterol to the liver. It also causes an increase in the clearance of
cholesterol from the blood.
Efficacy and Safety
Research studies have indicated the effectiveness of ezetimibe in the treatment of elevated cholesterol levels. A combination of ezetimibe and statins can achieve a reduction in LDL cholesterol levels
by 25%, compared to 6% attained by doubling the statin dose. Ezetimibe is usually well tolerated but can cause headache, abdominal pain and diarrhoea in patients.
Other New potential targets and treatments:
Recent clinical trials have discovered new potential agents with promising antihyperlipidemic
activity. These drug classes act by inhibiting necessary steps in pathways involved in the formation and breakdown of cholesterol. Some of these treatments are as follow
- Acyl-CoA cholesterol acyltransferase inhibitors (ACAT) including Avasimibe and Eflucimibe
- Microsomal triglyceride transfer protein (MTP) inhibitors including Oflomitapide
- Cholesteryl ester transfer protein (CETP) inhibitors including Dalcetrapib and Anacetrapib
- Squalene synthase inhibitors including BMS-188,494 and YM-53601
- Hydroxymethylglutaryl-CoA synthase inhibitors including L-659,699
- ATP citrate lyase inhibitors including BMS-303141
- Acyl coenzyme A: diacylglycerol acyltransferase (DGAT) including T863
- Squalene epoxidase inhibitors including NB-598
- Lanosterol synthase inhibitors including U18666A and Ro 48-8071
Hyperlipidemia is an asymptomatic problem but often treatable. It should be cured as it is associated with harmful diseases like atherosclerosis, cardiovascular disorders, high blood pressure and other severe problems which seriously affect the human body. Early diagnosis and preventive measures can easily reduce the risk of developing hyperlipidemia.