HIGH LDL? DON'T BLAME IT ALL ON GENES

High LDL? Don't blame it all on genes

Some people do have the unfortunate luck of inheriting a genetic predisposition to make truckloads of cholesterol internally. Most LDL is removed from the circulation by LDL receptors on the liver. Certain individuals inherit a tendency to produce fewer receptors, resulting in less LDL removal from the blood (predisposing them to excess LDL and atherosclerosis). With regard to receptors, we can't blame it all on the genes. The food you eat can greatly affect the density of the receptors on the liver. Ingestion of dietary cholesterol, saturated fat, and trans fat has unhealthy consequences. These foods suppress the manufacturing of cholesterol - clearing liver receptors and raise your "bad" cholesterol level. For a one-two punch against heart disease, eat a heart-healthy diet (low in saturated fat and cholesterol and devoid of trans fat) and follow the Cholesterol Down Plan, which includes foods that help augment the number of LDL receptors.

THE BODY'S CHOLESTEROL RECYCLING SYSTEM

The body's cholesterol recycling system

Think of the liver as not only a bile and lipoprotein manufacturing plant but also a cholesterol removal and recycling plant. How does the liver recycle cholesterol? The liver cells build bile acids from cholesterol. The bile acids are then secreted in bile (along with free cholesterol) into the upper section of the small intestine, where they aid in fat digestion. Once in the acidic environment of the small intestine, the bile acids convert into bile salts. Bile salts are continuously recycled from the intestine and returned to the liver. Each bile salt is actually reused about twenty times before it is excreted out of the body in the feces.

The liver, therefore, doesn't need to churn out too much new "homemade" cholesterol because it has this neat recycling program (called enterohepatic circulation) in which the bile acids (formerly cholesterol) are continuously recycled between the intestines and the liver. Almost 95 percent of the bile acids entering the intestine are recirculated and absorbed back into the bloodstream, heading straight to the liver, where they are once again secreted into the intestine in bile. This recycling system decreases the liver's requirement for new cholesterol and actually inhibits production of new bile acids from cholesterol. How much cholesterol the liver uses up each day to make bile acids depends on the return flow of bile salts from the intestine. Sequestering bile salts in the intestine so that they are excreted in waste and not recycled will force the liver to increase LDL clearance from the blood to replenish the cells' internal cholesterol stores (used for making new bile). Another class of cholesterol - lowering drugs works in this fashion. An important concept to keep in mind is that there is only one primary route out of the body for cholesterol (in the form of either free cholesterol or bile salts), and that is through the feces by way of the intestinal tract. If you block the absorption of free cholesterol or interrupt the recirculation of bile salts by trapping them in the intestine and excreting them, the end result is a drop in circulating LDL cholesterol. Several steps in the Cholesterol Down Plan work to lower LDL in this manner.

THE LIVER, A CHOLESTEROL FACTORY

The liver, a cholesterol factory

The liver is a glutton when it comes to cholesterol. Its cells work round the clock using huge amounts of cholesterol, mainly to manufacture bile. In fact, almost 80 percent of the cholesterol in the liver is used to produce bile, which is secreted into the small intestine for fat digestion. The liver also uses cholesterol for lipoprotein production, particularly VLDL (the parent molecule of LDL). The foremost source of "bad" LDL cholesterol is the liver, which indirectly functions as an LDL production facility.

HOW IS CHOLESTEROL ABSORBED FROM THE INTESTINAL POOL INTO THE BODY?

How is cholesterol absorbed from the intestinal pool into the body?

For cholesterol, the gateway into the body is a layer of cells lining the upper intestine known as enterocytes. The only way for cholesterol to get to this layer is to attach itself to a transporter called a micelle. Micelles are small, round transport packages formed by bile salts and phospholipids that carry cholesterol and fat (triglycerides) to the intestinal cell wall. The cholesterol must then take a second transport route - a protein channed called Niemann - Pick C1 Like 1, or NPC1L1 for short. The NPC1L1 traverses through the wall and into the intestinal cell where the cholesterol is packaged into chylomicrons for travel in the lymph system and ultimately the bloodstream. Zetia, the new cholesterol - lowering drug, blocks cholesterol absorption from the intestine by targeting the NPC1L1 protein.

Once in the bloodstream, chylomicrons off-load lots of triglycerides to needy cells, eventually arriving at the liver as small, cholesterol-rich particles known as chylomicron remnants. These remnants signal to the liver cells that they don't have to make more cholesterol, as a new cholesterol shipment has arrived - cholesterol that may have come from your breakfast omelet. The liver extracts the cholesterol from the remnants to make whatever is required for the day. Typically, the cholesterol is converted into bile acids for its launch into the body's cholesterol recycling system. But the liver could instead package the cholesterol up as a lipoprotein (primarily VLDL) and send it back into the bloodstream, ultimately increasing the amount of "bad" LDL cholesterol. Eat a huge amount of cholesterol and you increase the delivery of cholesterol to the liver by chylomicron remnants. Therefore, you should avoid foods with high cholesterol in order to lower the amount of cholesterol in your intestinal pool. Less cholesterol overloading the liver means less VLDL exported and less LDL produced.

EATING YOUR WAY TO A HEART ATTACK

Eating your way to a heart attack

What most people don't realize is that cholesterol comes from two sources: from food and from our own cells. In fact, we actually make three times more cholesterol (about 1,000-1,200 milligrams per day) than we typically eat. So we don't need to eat cholesterol because the body is perfectly capable of manufacturing enough of this waxy substance on its own. Still, American continue to consume an appreciable amount of cholesterol from dietary sources, which can raise "bad" cholesterol levels and increase our risk of heart disease. The average American ingests approximately 300-400 milligrams of cholesterol every day from animal sources. This amount exceeds the government's cholesterol - lowering dietary recommendation of no more than 200 milligrams a day. It is simple to eat this much cholesterol: seven ounces of liver (providing 762 milligrams of cholesterol) or two egg yolks (424 milligrams) will easily put you over the top.

In the intestine is a reservoir of cholesterol called the cholesterol pool. The amount of cholesterol that enters the pool from bile is up to five times greater than the amount of cholesterol derived from our diet. Where does all that cholesterol floating around in the intestine go? About half of the approximately 2,000 milligrams in the pool is excreted and half is reabsorbed into the intestinal cells, ultimately going back to the liver. If you could block reabsorption of some of the cholesterol in the intestinal pool so that it gets excreted and not returned to the liver, then you would decrease your circulating LDL level. One class of cholesterol - lowering drugs in particular capitalizes on this concept.

WHAT DOES THIS BAD CHOLESTEROL LOOK LIKE?

What does this "bad" cholesterol look like?

LDL cholesterol is a round lipoprotein that shuttles the bulk of the cholesterol in the blood. The inner core contains oily cholesterol molecules, each with a fatty acid chain dangling from it. Also found within the core is a lesser amount of triglyceride molecules intermingling with the cholesterol esters. Seventy-five percent of the cholesterol within the LDL is in this bound-up (esterified) form, concentrated within the inner core. The greater the concentration of these "chained" cholesterol molecules in the LDL, the more susceptible the LDL molecule is to oxidation (which instigates the catastrophic events that make up the atherosclerotic process), and the higher your risk for developing heart disease.

Surrounding the fatty core of LDL is an outer shell consisting of many fat - like molecules called phospholipids, plus some "unchained" cholesterol. The entire LDL ball is encircled by one big spaghetti - like strand of protein called Apo B (apolipoprotein B-100) (Figure 2). This protein molecule plays a crucial role in mooring the LDL molecule onto LDL receptors (more on these later).

WHY IS LDL SO DANGEROUS?

Why is LDL so dangerous?

LDL is commonly referred to as the "bad" cholesterol because high levels of circulating LDL have been linked to an increased risk for atherosclerosis and cardiovascular disease. LDL is the most dangerous lipoprotein, not only because each particle is made up of mostly cholesterol (roughly 45 percent) but also because of its destination. LDL carries cholesterol to the arteries, infiltrates their walls, and goes through a series of transformation that trigger plaque buildup.

LDL, THE DEADLY LIPOPROTEIN

LDL, the deadly lipoprotein

LDL is the chief cholesterol carrier in the blood, ferrying approximately 70 percent of all the blood cholesterol around the network of arteries. Basically, this lipoprotein is loaded with cholesterol. Unlike HDL, LDL is not directly manufactured in the liver. Instead, a different type of lipoprotein is first produced by the liver, the parent lipoprotein called VLDL. After circulating around the bloodstream, VLDL loses much of its fat (triglyceride) cache to various bodily cells to become LDL. LDL is designed to take cholesterol to cells that have run short, as cells require some cholesterol to maintain proper functioning. Typically, the LDL is taken into the cell and broken down, and then the cholesterol is used to make membranes or hormones. However, when the amount of LDL in the blood gets too high, the situation can become injurious.

HDL, THE LIFESAVING LIPOPROTEIN

HDL, the lifesaving lipoprotein

HDL is manufactured in the small intestine and the liver, its primary source. As it moves though the bloodstream, it takes in excess cholesterol that leaches out of tissue cells and, most important, excess cholesterol building up in the inner arterial wall. HDLs unload this cholesterol in the liver, where it is then excreted via bile, a process referred to as "reverse cholesterol transport." Other lipoproteins bring cholesterol into the cells, so it is this reverse transport from the cells to the liver that distinguishes HDL as the "good" cholesterol. An elevated level of HDL has been associated with a reduced risk for heart disease. HDL confers heart - protective benefits in four ways.

1. HDL circulates around the body, picking up excess cholesterol and bringing it back to the liver for disposal (reverse cholesterol transport).

2. HDL is an antioxidant, capable of dismantling rogue free radical molecules that oxidize the protein in the LDL particles - a contributing factor to atherosclerosis. (Oxidation is the same process that produces rust on metals.)

3. HDL exhibits anti-inflammatory activity (like aspirin) and can decrease the inflammation linked with the atherosclerosis process.

4. HDL lessens the ability of the blood to form clots, thus reducing the risk of heart attack or stroke.

NUMBER YOUR DOCTOR WILL BE CONCERNED ABOUT

Number your doctor will be concerned about

• High total cholesterol. This number reflects the total amount of cholesterol found in all the lipoproteins (LDL, HDL, VLDL) circulating in the blood. According to the American Heart Association, a value of less than 200 mg/dL is desirable for a relatively low risk of heart disease.

• Low HDL. To keep your heart and blood vessels in top shape, it is beneficial to have as high a concentration of HDL particles in the blood as possible. Too low an amount is unhealthy. According to the American Heart Association, a value of less than 40 mg/dL heightens your risk of heart disease.

• High LDL. The higher your LDL, the higher your risk of heart and vessel disease. As you will learn, LDL is the most telltale sign of risk. According to the American Heart Association, an optimal level of LDL cholesterol is less than 100 mg/dL.

• High triglyceride. Your triglyceride value reflects the amount of blood fats circulating. A high number is also a risk factor for heart disease. According to the American Heart Association, a normal triglyceride level is less than 150 mg/dL.

• High ratio of total cholesterol to HDL. Some physicians use the ratio of total cholesterol to HDL cholesterol to determine risk for heart disease. A high number means there is too little "good" cholesterol and too much "bad" cholesterol. According to the American Heart Association, the optimal ratio is 3:5:1 or less.

WHEN IT COMES TO LDL

When it comes to LDL, size matters

The most dangerous situation is when cholesterol is transported in a barrage of small, dense LDL particles that can slip through the cracks and congregate within the arterial wall. Numerous studies have shown that when one reverses the lipoprotein transport patterns - from a dangerous pattern of small, heavy LDL particles to a heart - healthy pattern of very few large and fluffy LDL particles - there is significantly less risk of heart attack. The steps in the Cholesterol Down Plan will help alter the size and shape of your LDL particles for maximum heart protection.