Familial Hypercholesterolemia (FH)

Familial Hypercholesterolemia (FH) (Type II hyperlipopoteinemia, hypercholesterolemic xanthomatosis, Low lipoprotein receptor mutation 1) genetic disease related to hypercholesterolemia; Elevated or high level of low - density lipoprotein (LDL - bad cholesterol). The disease occurs about one in every 500 people. 12. During the early 1970s and 1980s

Dr. Joseph L. Goldstein and Dr. Michael S. Brown evaluated the genetic cause of FH. 16 People who have FH have serious condition, which leads to premature arteriosclerosis (arteriosclerosis - accumulation of fatty material (plaque) which collects and hardens along the walls of arteries, eventually blocking the flow of blood) of the coronary arteries, before puberty, attributing to chest pain, shortness of breath and heart attack. A piece of plaque potentially can break apart and travel through the bloodstream to cause a heart attack and stroke. 1 Hypercholesterolemia sometimes referred to as silent disease because no symptoms are detected, until chest pain of a heart attack or stroke occur. 12 Men more likely have a heart attack and die before the age of thirty compared to women. However, eighty-five percent of men in their 40's to 50's experience a heart attack by age sixty. Women are more likely to have a heart attack ten years later. Symptomatic of FH: Accumulation of waxy plaques (xanthomas) beneath the skin over the eyebrows, knees, and buttocks. Also, deposits manifest in tendons, and around the cornea of the eye. 1

Familial Hypercholesterolemia linked to a genetic abnormality in chromosome nineteen. 1 "There is a mutation in the genetic encoding for the LDL receptors (LDLR gene) that are located on the surface of the liver cells." 12 Two mutated genes inherited from mother and father, making them genetically "homozygous" (inherited from each parent 2). Those who have inherited only one copy of the mutated gene (from one parent - heterozygous) respond better to treatment, combination of diet modification (adjustment to eating habits including dietary counseling 3) achieve a reduction of fat intake to less than thirty percent of total calories consumed and prescribed statin drugs (improve blood cholesterol levels). 1 Dietary change includes decreasing the amount of pork, lamb or beef consumed and switching to low fat dairy products. Also, eliminating certain oils, such as coconut and palm oil and limiting consumption of egg yolks and organ meats. Combination with dietary change, exercise contributes to reduce weight to combat lowering cholesterol levels, help treat familial hypercholesterolemia disease. Children born in families with a history of Familial Hypercholesterolemia should be tested for FH at age two. Early diagnosis and treatment is critical to prevent early death. 3

Familial Hypercholesterolemia treatment options to reduce cholesterol include:

Lovastatin: Slowing the production of cholesterol in the body. Taken as a tablet once or twice daily with meals for extended - release. 4

Gemfibrozil: Reduces triglycerides (Chemical substance form found in which most fat exists in food and in the body 5) and increase good cholesterol (high density lipoprotein (HDL). "In one large study, gemfibrozil decreased the risk of heart attack but did not affect the overall survival of persons with high cholesterols." 6

Probucol: Lowers good and bad cholesterol (LDL and HDL), and antioxidant protection from atherosclerosis (not been proven). Probucol prescribed to patients who have not responded favorably to other medications or cannot take other medications. Most common side effect is diarrhea (10% of people). Probucol is available in Canada and Europe. 7

Bile Acid Sequestrant Resins (bile acid resins or binders): Removes from the body cholesterol by binding to bile (digestive fluid) in the small intestine and preventing it from being absorbed into circulation. 8

Beta - sitosterol: A type of organic compound found in plants, reduces cholesterol level in blood. "High levels are found in rice bran, wheat, germ, corn oil and soybeans. Peanuts and its products, such as peanut oil, peanut butter, and peanut flour, are good sources of plant sterols, particularly beta-sitosterol." 9

Fenofibrate: Prescribed medication reduces cholesterol and triglycerides in the blood. Fenofibrate combined with meals and full glass of water. Combing alcohol and fenofibrate is harmful: Increase triglyceride levels and may damage the liver. In some cases fenofibrate link to muscle pain, tenderness and weakness or flu - like symptoms. Those who have liver, kidney or gallbladder disease should consult their physician before taking fenofibrate. 10

Vytorin: In July 2004, Food and Drug Administration approved Vytorin manufactured by Merck and Schering-Plough Pharmaceuticals for the treatment of hypercholesterolemia. The medication first single treatment inhibits the production of cholesterol in the liver and blocks the absorption of cholesterol in the intestine, including cholesterol from food. "Vytorin (Inegy) lowered LDL cholesterol by 52 percent at recommended starting dose (10/20 mg) and 60 percent at the maximum does (10/80 mg)." 13

Inegy: Tablets contain two ingredients, simvastatin and ezetimibe. Simvastatin is statin, reduces bad cholesterol (LDL) in the liver and decrease production of triglycerides. Ezetimibe prevents cholesterol from being absorbed from the small intestines into the bloodstream and prevents cholesterol released from the bile duct into the intestine, from being reabsorbed into the bloodstream. Excessive use of alcohol is not recommended when medication is taken. Also, avoid drinking grapefruit can affect the metabolism of simvastatin. 14

Invasive Surgery may require a liver transplant. 1

Heterozygous patients with familial hypercholesterolemia who receive early long - term drug therapy expect to be cured by gene therapy. 12

Lipid apheresis a method removes bad or LDL, cholesterol from blood. "It functions like a dialysis machine in terms of what happens. You put a needle in one arm Vein, the blood comes out, a series of filters takes out the fat, and the blood returns to the patient's other arm. It is that simple". The treatment is FDA approved and widely used in Europe during the past 20 years. When diet, exercise and medicine unable lower cholesterol, lipid apheresis offers an alternative solution for familial hypercholesterolemia. 17

In March 2008, Merck/Schering-Plough will present results of a study at the American College of Cardiology meeting regarding combination of Vytorin and Inegy medication, analysis of ENHANCE trial. The study evaluates the amount plaque reduction in arteries. Trials took place during period of twelve weeks. 15

Laboratory testing helps diagnosis and confirms familial hypercholesterolemia: Total cholesterol level exceeds 250 mg/dL (children), total plasma cholesterol greater than 300 mg/dL (adult), and elevated triglycerides. 11 "The cholesterol levels in heterozygous patients are between 350 - 500 mg/dL, and in homozygous, the levels are between 700 - 1,200 mg/dL. 12 Patients should undergo a stress test to evaluate heart function, decreased level of LDL cholesterol, and genetic testing for mutations in the LDL receptor gene. 11

References:

1.) Familial hypercholesterolemia - http://www.nlm.nih.gov/medlineplus/ency/article/000392.htm

2.) Definition of Homozygous - http://www.medterms.com/script/main/art.asp?articlekey=33676

3.) Familial Hypercholesterolemia: A Serious Inherited Condition - http://ezinearticles.com/?Familial-Hypercholesterolemia:-A-Serious-Inherited-Condition&id=403372

4.) Lovastatin - http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a688006.html

5.) Triglycerides - http://www.americanheart.org/presenter.jhtml?identifier=4778

6.) GENERIC NAME: gemfibrozil - BRAND NAME: Lopid - http://www.medicinenet.com/gemfibrozil/article.htm

7.) Probucol for high cholesterol - http://www.healthwise.org/kbase/topic/detail/drug/hw115219/detail.htm

8.) Bile Acid Sequestrants - http://cholesterol.about.com/od/bileacidsequestrants/Bile_Acid_Sequestrants.htm

9.) Beta-Sitosterol for Sports & Fitness - http://www.pccnaturalmarkets.com/health/Benefits_Sports/Beta_Sitosterol.htm

10.) Fenofibrate - http://www.healthline.com/multumcontent/fenofibrate

11.) Familial hypercholesterolemia - http://www.nlm.nih.gov/medlineplus/ency/article/000392.htm

12.) Familial Hypercholesterolemia - http://dwb.unl.edu/Teacher/NSF/C10/C10Links/www.middlebury.edu/~ch0337/ho/fh.html

13.) FDA Approves Vytorin (ezetimibe/simvastatin) for Reduction of LDL Cholesterol Reduction Through Dual Inhibition - http://www.docguide.com/dg.nsf/PrintPrint/90920F9E3ABBAC5485256EDD00476513

14.) Inegy (simvastatin and ezetimibe) - http://www.netdoctor.co.uk/medicines/100005103.html

15.) Merck/Schering-Plough Pharmaceuticals Provides Update on ENHANCE Trial - http://biz.yahoo.com/bw/071119/20071119006381.html?.v=1

16.) familial hypercholsterolemia - http://www.answers.com/topic/familial-hypercholesterolemia?cat=health

17.) Familial Hypercholesterolemia - http://www.saturdayeveningpost.com/issues/mm/7370228.shtml