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Hypercholesterolemia

Overview

Cholesterol is a waxy substance, a type of fat the body makes. It is needed to build cell membranes (boundaries of cells), make certain hormones (steroid hormones), and produce bile acids that help fat digestion. But high cholesterol levels increase the chances of peripheral vascular disease, heart disease, and stroke. High cholesterol, also called hypercholesterolemia, deposits fat particles in the inner walls of blood vessels (atheromatous plaques), making it difficult for blood to flow through arteries. These deposits break away and form a clot (emboli) that travels to the heart or brain, leading to a heart attack or stroke. It is often a result of an unhealthy diet; in some instances, it is inherited. 

Cholesterol is insoluble, so it is carried in the blood by special proteins; the combination is called lipoproteins. These lipoproteins are of different types based on the type of cholesterol they carry. The combination that carries cholesterol from the liver to other parts of the body is called Low-density lipoprotein (LDL). It is also referred to as bad cholesterol because its excess may result in accumulation and further cause atherosclerosis. The other type that carries cholesterol from the periphery to the liver for degradation and disposal is called High-density lipoprotein (HDL), also referred to as good cholesterol. In hypercholesterolemia, either the total cholesterol or LDL is increased. Hypercholesterolemia is preventable. You need to follow a healthy diet and exercise, and adhere to your medication regimen.

Causes

Both genetic and environmental factors play a role in the occurrence of the disease. Usually, multiple genes are involved, so the condition is also referred to as polygenic. In some cases, only one gene is responsible for the disease, called familial hypercholesterolemia; it has further subtypes 

  • (1)Defective apolipoprotein B. 
  • (2) A mutation in (PCSK9) gene. 

The environmental factors responsible could be dietary, some medical conditions, medicines, etc. 

The following foods increase the level of cholesterol in your blood :

  • Egg yolk
  • Cheese 
  • Fried food 
  • Processed food 
  • Ice cream 
  • Pastries 
  • Red Meat 
  • Junk food ( fast food )

The following medications increase cholesterol in the body. The doctor needs to be aware of the cholesterol levels before prescribing any of these medicines;

  • Acne medication  
  • Cancer medication
  • Organ transplant medication
  • HIV/AIDS medication
  • High blood pressure medication. 

The following medical conditions cause an increase in the level of cholesterol 

  • Chronic kidney disease
  • Diabetes
  • HIV/AIDS
  • Hypothyroidism
  • Lupus
  • Monoclonal gammopathy
  • Dialysis therapy 
  • Nephrotic syndrome 
  • Cushing's syndrome 
  • Anorexia nervosa 
  • Alcoholism 

Risk Factors

  • An unhealthy diet. Using excess amounts of saturated fats and trans saturated fats can be harmful.
  • Obesity. A BMI of more than 30 increases the risk of high blood cholesterol.
  • Sedentary lifestyle. Exercise helps boost your body's HDL. 
  • Smoking. Cigarette smoking can lead to a lower level of HDL
  • Alcohol. Drinking a lot of alcohol can increase your total cholesterol level.
  • Age. Although young children can have unhealthy cholesterol, it's much more common in people over 40. As you age, the ability of your liver to remove LDL cholesterol decreases. Males 45 years or older and females 55 years or older are susceptible to hypercholesteremia. 
  • A positive family history Of premature atherosclerotic cardiovascular disease  (younger than 55 years in a male and younger than 65 years in a female )
  • Hypertension
  • Diabetes
  • Low HDL –cholesterol levels (less than 40 mg/dl in males and less than 55 mg/dl in females)

Epidemiology

According to the CDC, high cholesterol rates reduced to 13% in 2010, compared to 17% in 2000 in the United States. High blood cholesterol is found in around 34 million adults in the United States. It is more common in Hispanic males, followed by African Americans and white males.

Rates of coronary artery disease are high in England but low in China and Japan.

Signs And Symptoms

Hypercholesterolemia has no symptoms of its own. However, the symptoms can occur due to the complications that arise due to its accumulation and atherosclerosis. For example, atherosclerosis and atheromatous plaques in the heart vessels can cause angina attacks, in the brain vessels cause, weakness or abnormal sensations(numbness or tingling), problems with balance, temporary loss of vision, difficulty speaking, in arteries of the legs can cause pain on walking, etc

In familial hypercholesterolemia, cholesterol deposits in the skin or around tendons, known as Xanthomas. Accumulation of small fatty deposits may present as small bumps on the skin, of the hands, elbows, and knees, or as yellow deposits under the eyes or on eyelids. 

Diagnosis

Diagnosis of high cholesterol is made based on a blood test. The test is referred to as a lipid profile. Fasting of 9 to 12 hours is recommended before the test. Heart association across America recommends adults over age 20 have their cholesterol checked every 4 to 6 years. The lipid profile can give levels of;

  • Total cholesterol (Total cholesterol of 200 mg/dl is out of normal range)
  • LDL cholesterol
  • HDL cholesterol: its presence is considered good for health. Its ideal levels are more than 40 mg/dl in males and more than 55 mg/dl in females)
  • Triglycerides 
  • High cholesterol can be defined as 
  • LDL cholesterol greater than 190 mg/dl, 
  • LDL cholesterol greater than 160 mg/dl with one major risk factor, or 
  • LDL cholesterol greater than 130 mg /dl with two cardiovascular risk factors.

Differential Diagnosis

As discussed above that the levels of cholesterol can increase due to some diseases also so on finding  high blood levels of cholesterol, the following conditions should be ruled out ;

  • Alcoholism
  • Hyperlipidemia
  • Anorexia Nervosa
  • Cholestatic liver disease
  • Hypothyroidism,
  • Nephrotic syndrome, 
  • Chronic renal insufficiency
  • Anorexia
  • Obesity
  • Metabolic syndrome
  • Diabetes

Treatment

The treatment of hypercholesterolemia is through lifestyle modifications such as dietary changes and exercise and the cessation of smoking which cannot be emphasized enough. Medication is required in most instances. Statins are the first-line therapy used in hypercholesterolemia; they reduce LDL levels by blocking a specific enzyme necessary to produce cholesterol. They also lower LDL cholesterol and prevent the hardening of arteries, thus reducing the chances of heart attack and stroke. The doctor may prescribe cholesterol inhibitors or protein convertase inhibitors which ultimately lower cholesterol levels. 

Medications

  The following medications are used in the treatment of hypercholesterolemia ;

  • Statins (HMG-CoA reductase inhibitor): Atorvastatin, Fluvastatin, Lovastatin
  • Nicotinic acid: Niacin
  • Fibrates: Fenofibrate, Gemfibrozil
  • Bile acid sequestrants or Resins: Cholestyramine, Colesevelam
  • PCSK9 Inhibitors: newly approved monoclonal antibodies, Evolocumab, Alirocumab

Prognosis

If treatment is not received life expectancy of those with familial hypercholesterolemia is reduced by approximately 15 to 30 years. Cardiac events are the most significant risk in hypercholesterolemia. However, the advent of Statins has significantly reduced the mortality associated with hypercholesterolemia. Today, lowering cholesterol levels is a useful strategy for the primary prevention of heart disease.

Lifestyle Modification

Adopting the following habits will help reduce the “ bad” cholesterol (LDL cholesterol ) that builds up inside arteries

  • Exercise is a must. 
  • Choosing foods that are low in trans fats and saturated fats  
  • Adding fiber-rich fruits to diets such as bananas, pears, apples, vegetables, and whole grains. 
  • Use a diet low In salt
  • Avoiding soda and limiting alcohol intake 
  • Avoiding fried food and processed food 
  • Avoiding  or cessation of  cigarette smoking