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Cholesterol... The Silent Killer. Babylyn, Tonna, Lena, & Janine. Question.

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Cholesterol...

The Silent Killer

Babylyn, Tonna, Lena, & Janine


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Question

Familial hypercholesterolemia is the most common inherited disease associated with mutations in the LDL receptor (LDLR) gene on chromosome 19. About 1 in 500 people is heterozygous for this autosomal dominant trait and are therefore genetically predisposed to having high levels of LDLs and the associated pathogenesis of heart attack or stroke. Imagine that despite lifestyle changes, both of your parents have elevated LDLs . What is your risk of also having high LDLs?


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What is

Familial Hypercholsterolemia?

  • Familial hypercholesterolemia (FH) is an inherited autosomal dominant disorder that causes severe elevations in total cholesterol and low-density lipoprotein (LDL) cholesterol. The defect concerns the cell membrane receptor for LDL. This is a binding defect due to a dysfunctional receptor.

  • Heterozygous FH occurs approximately in 1 in 500 persons.

  • Homozygous FH occurs approximately in 1 in 1,000,000 persons

  • Associated with heart attack and stroke


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Available online at http://courses.washington.edu/luca201/homework/pathway.gif


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LDL http://courses.washington.edu/luca201/homework/pathway.gif

  • LDL circles fatty acids keeping them soluble in the aqueous environment

  • LDL transports cholesterol and triglycerides from the liver and small intestine to cells and tissues which are taking up cholesterol and triglycerides

  • LDL transports cholesterol to tissues which need it


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Difference Between http://courses.washington.edu/luca201/homework/pathway.gif

Good and Bad Cholsterol

  • LDL: “Bad” Cholesterol. This is when too much LDL cholesterol in the blood can slowly build up in the inner walls of the arteries that feed the heart and brain. With other substances, it can form plaques in the arteries and will make them less flexible – artherosclerosis.

  • HDL: “Good” Cholesterol. High levels of HDL seem to protect against heart attack. It tends to carry cholesterol away from the arteries.


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What are Your Chances? http://courses.washington.edu/luca201/homework/pathway.gif

The Gene for Hypercholesterolemia is found on Chromosome 19.

Homozygous FH (LL) is extremely rare and serious. It becomes apparent in children and without aggressive treatment, most patients don’t live past 30


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Risk of Hypercholesterolemia http://courses.washington.edu/luca201/homework/pathway.gif

  • High levels of LDL can lead to premature atherosclerosis of the coronary arteries.

  • Heterozygous FH (Ll): In men, this creates an increased risk of heart attack by the age of 60. For women, they are still at high risk, but it will occur about 10 years later than in men.

  • Homozygous FH (LL): Those that inherit two mutated genes from their parents are even more at risk. They will develop waxy plaques on several areas of the skin, and will be at risk for having atherosclerosis beginning before puberty, and heart attacks before the age of 30.


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Treatment http://courses.washington.edu/luca201/homework/pathway.gif

  • Diet Change

    • Reduce fat intake to less than 30% of calories consume

    • Substituting beef, pork and lamb, with low-fat diary products.

  • Exercise

  • Drug Therapy

    • Statins-inhibit synthesis of HMG-CoA reductase, a rate limiting step in the hepatic synthesis of cholesterol. When this is limited, the liver increases the amount of LDL receptors, meaning more LDL is removed from circulation. This means that there is less cholesterol available to for atherosclerotic plaques that cause coronary heart disease (CHD)


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Analogy http://courses.washington.edu/luca201/homework/pathway.gif

Car crash on busy I-5 in Seattle. Cars in front of you are stopped, cars behind you are still going, and there are people on the sides of you. You have a slim chance of not getting into an accident. In FH, if both parents have it, there is a good chance you will get it too.

Poor little mosquito…The mosquito is being chased by a little kid, there is a spider web in front and a zapper light to the side. Will the mosquito make it?


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