Natural Medicine For Cholesterol

Crunch Cholesterol Program by Colin Carmichael

Crunch Cholesterol contains several of simple yet efficient tips and remedies which are naturally proven to aid in normalizing cholesterol levels. This system is created and developed by Colin Carmichael, a respected author and consultant. Colin developed a particular interest and passion about cholesterol when his wife was found to have elevated cholesterol levels at a routine blood screening by their insurance policy. Crunch Cholesterol is divided into 14 separate chapters. You will also learn about the necessaries of HDL and how to raise it to a healthy level. After that, the author exposes some myths about cholesterol and the problems you can face. You will learn about some healthy foods to eat to manage your cholesterol level well in the chapter 6. Chapter 7 and 8 will reveal some useful tricks you will be able to use to improve your current situation. In chapter 9, you will be given some best exercises and exactly how to perform them to lower your cholesterol effectively. Crunch Cholesterol is the unique program that provides people with an exclusive cholesterol lowering diet, and detailed instructions on how to reduce cholesterol quickly and naturally without bad side effects. This program will help people avoid diseases linked to high cholesterol such as coronary heart disease, Diabetes, cardiovascular disease, and some other diseases. More here...

Natural Secrets For High Cholesterol Summary

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Author: Colin Carmichael
Official Website: getridofhighcholesterol.com
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Natural Secrets for High Cholesterol Review

Highly Recommended

All of the information that the author discovered has been compiled into a downloadable pdf so that purchasers of Natural Secrets For High Cholesterol can begin putting the methods it teaches to use as soon as possible.

When compared to other ebooks and paper publications I have read, I consider this to be the bible for this topic. Get this and you will never regret the decision.

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Lipid Disorders Involving Elevated Triglycerides

Two different genetic defects can cause the familial hyperchylomicronemia syndrome (FCS) lipoprotein lipase (LPL) deficiency and apoC-II deficiency (1). The hydrolysis of triglycerides in chylomicrons requires the action of LPL in tissue capillary beds, and apoC-II is a required cofactor for the activation of LPL. Mutations in either the LPL gene or the APOC2 gene result in functional deficiency of LPL, hypercholesterolemia Familial defective apoB-100 Autosomal recessive hypercholesterolemia Sitosterolemia Autosomal dominant hypercholesterolemia

Regulation of KLF2 Expression by Statins

Statins, which are the most commonly prescribed class of lipid-lowering agents and were originally designed as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A, have recently been discovered also to upregulate KLF2 expression in cultured human endothelial cells at pharmacologically relevant doses in vitro (Fig. 4 Parmar et al. 2005b Sen-Banerjee et al. 2005). Statins block the production of mevalonate, which forms two major downstream products known as isoprenoids farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Both of these isoprenoids can prenylate distinct sets of proteins in the cell to enable their proper localisation and signalling. The statin-mediated upregulation of KLF2 in human umbilical vein endothelial cells (HUVECs) is dependent on the depletion of GGPP (Parmar et al. 2005b Sen-Banerjee et al. 2005), which is well known to prenylate several members of the Rho superfam-ily. Importantly, upregulation of KLF2 is critical for many statin-dependent...

What About Dietary Cholesterol

I saved talking about dietary cholesterol levels to last because it's fairly obvious if you want to decrease your cholesterol levels, you should ingest less cholesterol The NCEP guidelines recommend less than 200 mg of dietary cholesterol per day. For reference, one large egg yolk has 200 mg. See Table 6.2 for the amount of cholesterol in some other foods. For some people let's call them responders blood cholesterol levels rise and fall pretty directly in relation to the amount of cholesterol and fat in their diets. In others, there's little connection. The same goes for dietary fat. A 1997 study done at the Human Nutrition Research Center on Aging at Tufts University looked at how 120 men and women responded to the same low-fat, low-cholesterol diet recommended by the NCEP. On average, LDL levels dropped. Yet though everyone ate the same thing the researchers provided the volunteers with all their food and drink the average result masked a wide range of LDL responses, ranging from a...

Reductase Inhibitors Statins

Statins are the most widely used class of cholesterol-lowering drugs. Large, randomized clinical trials have shown and continue to show that people who use statins have a 20 percent to 40 percent reduction in death from incidents of major cardiac events in studies lasting two to six years. The study that really brought statins into the limelight was called the Scandinavian Simvastatin Survival Study, or the 4S trial. It involved 4,444 men and women, ages thirty-five to seventy, who had preexisting heart disease and high total cholesterol levels. Half took the cholesterol-lowering drug simvastatin for five years, and half took placebo tablets containing no medication. By the end of the trial, LDL levels in the treatment group had fallen by 35 percent and total cholesterol dropped by 25 percent, while no change took place in the placebo group. The treatment group also had a 30 percent lower chance of dying during the trial and a 34 percent lower chance of having a major coronary event...

Elevated Triglycerides

In any case, very high triglyceride levels can cause other major health problems in the liver and pancreas, so physicians will aggressively treat these patients to lower their triglycerides. In this case, treatment would include a very low-fat diet where only 5 percent to 6 percent of calories come from fat, as opposed to the 20 percent to 30 percent we generally recommend. These individuals also get some benefit from taking fibrate medications, but the effect of the medicines is easily overwhelmed by poor dietary choices. How High Is Too High for Triglycerides triglyceride levels, stop drinking, eat healthier, and exercise. Besides contributing to weight loss, exercise also lowers triglycerides because your muscles use triglycerides as fuel.

If Your Child Has High Cholesterol

Like a lot of problems adults face, high cholesterol may start in childhood and progress into adulthood. Eating and exercise habits also carry over from younger years. This means it's especially important for kids to eat right, exercise, and not smoke. Most people don't need to get a fasting lipid profile until they hit twenty. However, the Committee on Nutrition of the American Academy of Pediatrics recommends checking the cholesterol levels of children older than two who have risk factors like a family history of early heart disease or high cholesterol. The committee recommends that doctors and parents talk about screening kids and teens who are obese, are inactive, smoke, have high blood pressure, or have diabetes. Although it's important for adults to have repeat cholesterol tests if levels are found to be high, this is even more important in children, whose levels can vary more than adults'. Table 10.1 gives the cholesterol guidelines for children.

Preventing High Cholesterol in Children

Prevention is always the best medicine, and this is definitely the case for heart disease in children. Atherosclerosis or its precursors begin in childhood, and high cholesterol during this time may play a role in causing adult atherosclerosis. If your children don't have high cholesterol, it's still a great time to get them started with a healthy lifestyle. Encourage them to exercise and eat right. Children under two should not be on fat-restrictive diets, but after that, adopting the Step 1 diet (see Table 10.2) is a good way for children and adolescents to prevent heart disease. And best of all, doing so usually means that you have to adopt these healthy habits, too.

Overthe Counter Statins

In 2004, the United Kingdom approved statins for sale over the counter. Many people began to ask if this would happen in the United States as well. Indeed, drug companies are already working on making this a possibility. I, for one, hope they do not succeed. Over-the-counter drugs are great for medical problems like a cold or headache. These are problems that a person can immediately identify and he or she can tell when they're going away. If, for example, you take a cold medicine for a runny nose and sore throat, you know that when the symptoms abate, your cold is getting better. Your results and side effects don't need to be monitored by a doctor. The same cannot be said for treating high cholesterol. First, you need a lab test to diagnose it. And, more important, you need continued lab tests to determine if your treatment is working. So if your doctor told you that you had high cholesterol and you treated yourself with an over-the-counter statin, an important part of the process...

Family History Lessons Familial Hypercholesterolemia

There are a variety of genetic disorders that affect how the body makes lipids. In terms of heart disease risk, the most detrimental lipid disorders increase LDL levels and decrease HDL levels. The majority of these disorders are caused by a few problematic genes combined with environmental factors such as obesity or a diet high in saturated fat. As far as treatment goes, it doesn't matter if your high cholesterol is caused by problematic genes or not. Medication and lifestyle changes are still prescribed based on your HDL and LDL levels. However, the discovery of these genetic problems has greatly increased researchers' understanding of lipoproteins and cholesterol. A family history of heart troubles can increase anyone's risk for heart disease, but for people with a gene mutation that causes extremely high cholesterol levels and at an early age it nearly guarantees it. The pediatricians hadn't dealt with such a high cholesterol level in a child so young, and so they referred Kelly...

Problem in Two Parts High LDL and High Triglycerides

Sometimes, though, a genetic problem can cause VLDL particles, which normally turn to LDL particles as their triglycerides are extracted for energy use, to get stuck in the middle. Like VLDL particles, these intermediate-density lipoproteins (IDL) are high in triglycerides, but they also have a relatively high content of cholesterol. So individuals with this genetic problem appear to have a combined lipid disorder (too much VLDL and LDL), when in fact they have an abnormal accumulation of IDL. If lifestyle therapies can't correct the problem, most people with a combination of high triglycerides and LDL cholesterol get started on a fibrate drug. Most of the time, they also need a statin to get their lipoproteins to desirable levels. (Some doctors prefer to reverse this order of drug use, starting with a statin and then adding a fibrate.) Though this combination of medications is very effective at getting both triglycerides and LDL levels under control, it can exacerbate the main side...

Triglycerides

The NCEP guidelines recommend aggressive treatment for elevated triglycerides. Recent studies indicate that an elevated triglyceride level is significantly linked to the degree of heart disease risk. The 2001 guidelines recommend treating even borderline-high triglyceride levels. Therapy includes weight control and physical activity and sometimes, for higher triglyceride levels, medication.

How Do Statins Work

Statins reduce the amount of cholesterol the liver makes by blocking the key protein needed in that process, HMG CoA reductase (3-hydroxy-3-methylglutaryl-coenzyme A reductase). With less cholesterol made in the liver (and remember that we typically make about 70 percent of the cholesterol in our bodies), the liver tries to recapture more of the LDL cholesterol in the circulation. When it does this by removing LDL particles from the blood, the blood LDL cholesterol level drops (see Figure 8.1). Statins tend to Q Cholesterol-lowering statin drugs work Q Cholesterol-lowering statin drugs work cholesterol synthesis is higher at night, but all of the statins can be taken once a day, even in the morning, and still work quite well. The longest-acting statins, like atorvastatin, stay in the body so long that it really doesn't matter when you take the pill. Statins have few known side effects. They are capable of damaging the liver and muscles, but such problems are rare and usually not...

HDL Cholesterol

HDL Cholesterol Level HDL Cholesterol Category terol to help identify people who need cholesterol-lowering therapy. The more HDL you have relative to total cholesterol, the smaller and healthier the ratio. one with a desirable total cholesterol of 195 mg dL who would be labeled low risk under the old system might in fact be headed for heart disease if his or her total cholesterol HDL cholesterol ratio was too high due to a low HDL level. Conversely, someone with a cholesterol level of 250 mg dL who would ordinarily be put on a treatment program might actually need little more than the usual lifestyle changes if a high HDL level (and thus a low ratio) accounted for a good proportion of the total.

Three Hundred Is a Healthy Cholesterol Level

When she went back to her doctor after two months, her cholesterol level had barely changed. Her doctor advised that she take a cholesterol-lowering pill called a statin. Mary was reluctant to follow this advice. She had never taken any medication before and didn't like the idea of having to take a pill every day. In the back of her mind she heard the voices of several of her friends who were already on cholesterol-lowering pills and who were always complaining about their cost. A few of them even said the medicines had made them feel achy and weak. Mary asked her doctor if she could get a second opinion about the need for treatment.

Selective Estrogen Receptor Modulators

These new drugs, sometimes called designer estrogens, appear to affect blood lipids in much the same way that estrogen does but possibly without the increased risk for breast cancer and endome-trial cancer associated with hormone replacement therapy. Raloxifene (Evista), one of these drugs, has been shown to decrease levels of LDL, but unlike estrogen does not reliably elevate HDL cholesterol, though it may increase one of the HDL subfractions. Also unlike estrogen, raloxifene doesn't elevate triglyceride levels. Raloxifene is approved for osteoporosis prevention, and recent preliminary studies suggest that it may be effective at reducing breast cancer risk. Like estrogen, however, it does increase the risk of blood clots in the legs. Overall, I don't use raloxifene as a pri- 33.

Interpreting New Medical Information Finding a Doctor Who Matches Your

That each of these studies worked backward, from heart disease to risk factor. The results don't mean that almost everyone with at least one of these factors will develop heart disease. But the results do make a strong case for paying attention to all four of the majors. Although the emphasis of this book is on cholesterol, the others deserve equal focus. If you have high blood pressure, high cholesterol, diabetes, a smoking habit, or any combination of these, focusing on them will help you live better and probably longer. Exercise, healthier eating habits, and getting to a healthy weight can do wonders for high blood pressure, high cholesterol, and diabetes. A variety of drugs can help get these under control and protect against their cardiovascular complications. And various approaches are helping more and more people stop smoking.

When You Visit Your Doctor

The fasting is probably the most difficult part of the full cholesterol profile for most patients. Once you get to your doctor's office, someone will draw a tube's worth of blood and you're all done Behind the scenes, the lab technician puts your blood into an automated chemical analyzer and runs the various lipid tests rapidly. If your triglyceride level is greater than 400, the lab can't calculate your LDL value. In more sophisticated labs, additional tests can be done to determine the LDL in that situation, but these require more costly and time-consuming procedures that are not always available. If that's the case, your doctor may send your blood to a national lab. LDL cholesterol can be measured directly by several different methods, each of which has its advantages and disadvantages, but all of which are more expensive than simply calculating LDL cholesterol from a standard lipid profile. So, if your LDL cholesterol can be determined by calculation, that is the preferred method...

Inaccuracies in the Tests

Although the lab should not have more than a 3 percent variation in measuring your cholesterol level, your personal level may vary a good deal more when different blood samples are compared. One study showed that total cholesterol levels can fluctuate by as much as 11 percent over the course of a year. Researchers estimated that 60 percent of that variation was caused by biological fluctuations, and the remaining 40 percent by variations in the test itself. Changes in your average daily levels may reflect changes in your diet, smoking, illness, weight, exercise routine, or certain medications. That same study found that triglyceride measurements can vary anywhere from 12.9 percent to 40.8 percent, and HDL levels from 3.6 to 12.4 percent. This is why it's important to take more than one measurement if anything looks abnormal and not to overinterpret small changes in lipid values. If you see a small rise or fall in your levels from year to year, don't worry it may not represent a real...

When to Treat Cholesterol

How do you and your doctor decide whether and how to treat your cholesterol Even though high cholesterol is clearly linked to heart disease, you shouldn't make the decision about treatment based solely on your cholesterol numbers. I know, this sounds counterintuitive, but the point of treating high cholesterol is to prevent heart disease, and other risk factors besides cholesterol come into play when determining your risk of heart disease. So two people with the same cholesterol levels may walk out of their doctors' office with completely different advice one may be told to fill a prescription for a cholesterol-lowering drug the other 90, may be told to get more exercise and eat better.

Things to Mention to Your Doctor if You Are About to Be Treated for an Abnormal Lipid Profile

If your diet was dramatically different from your typical diet in the weeks leading up to the lipid test, this is worth noting, because high alcohol or carbohydrate intake can cause a dramatic elevation in serum triglycerides. 4. If there is an abnormality (i.e., high cholesterol levels when there hadn't been in the past), ask if your cholesterol will be measured again to make sure it wasn't a fluke.

What Is Metabolic Syndrome continued

This cascade of changes isn't healthy. Damage to artery walls, high triglycerides, and increased chance of blood clots can lead to heart attacks and some strokes. Changes in the kidneys' ability to remove salt contribute to high blood pressure, another path to heart disease and stroke. And dwindling insulin production by the pancreas signals the start of type 2 diabetes, which greatly increases the chances of having a heart attack or stroke, as well as nerve, eye, and kidney damage.

Personalizing the NCEP Guidelines

Lines don't take into account, you may decide to treat your high cholesterol more aggressively than the NCEP guidelines indicate. Or if you have a lot of lifestyle risk factors that you are willing and able to change, maybe you and your doctor will want to assess your cholesterol levels again after a few months of your new habits before you try a cholesterol-lowering drug.

Diet to Lower Your Cholesterol

If the last chapter (or a discussion with your doctor) made you realize that you need to lower your cholesterol, this chapter and the next two chapters will tell you how. I'll discuss lifestyle changes first, then medications. I like to do so in this order for two reasons. One, some people might need to just change their habits to get their cholesterol levels in check. Two, even people who do need medication should also adopt these lifestyle changes. This will not only help lower your cholesterol further but will also give you many other benefits.

The Atkins Diet and Cholesterol

In fact, a study that used various equations to estimate the impact of certain diets on long-term health estimated that the Atkins diet would raise the average American's cholesterol by 51 mg dL. However, in more surprising news, some recent studies found that low-carb diets have a similar effect on cholesterol levels as low-fat diets, or in some cases even a better effect. For example, a six-month study of seventy-nine obese people found that the low-carb diet had a similar effect as a low-fat diet on HDL and LDL levels, but a more favorable impact on triglyceride levels.

Finding the Diet Thats Right for

The Tufts University study brings up an important fact about dieting in general and cholesterol lowering in particular everyone is different A diet that helped your friend lose weight and lower her cholesterol might not work for you, because of either biological or lifestyle differences. What you need to do is find a plan that works for you and stick with it. Don't get discouraged if you have to try a few different kinds before one feels right. Another good way to monitor your progress is to get your lipid profile checked after about two or three months of your new diet, and then again at six months. If you're a responder, you should see a drop in your LDL cholesterol. Once you have reached your target levels, have a follow-up every six months to make sure your cholesterol is staying at a healthy level. Depending on your cholesterol levels, if you don't see a drop in LDL cholesterol, you may need to either see a dietitian for a more thorough review of food choices and diet plans, or...

The Benefits and Risks of Exercise

Exercise's impact on heart health is amazing. Research has shown that even moderate exercise can substantially reduce the incidence of coronary events. Aerobic exercise reduces cardiac risk by lowering triglycerides and raising HDL cholesterol levels by reducing blood pressure, body fat, blood sugar, and mental stress and by moderating the blood's propensity to clot. Sedentary living, on the other hand, is the fifth major cardiac risk factor. Because it increases the risk for coronary artery disease by almost two times, a lack of exercise is nearly as dangerous as smoking, abnormal cholesterol levels, or hypertension. Regular exercise does raise your risk for minor injuries, such as shin splints or sprains and strains. But if you talk to your doctor before you start a program, choose a low-impact activity, take it slowly at first, and very gradually increase the intensity of your program, the benefits lower total cholesterol, lower triglycerides, higher HDL, lower blood pressure,...

Taking Your Medicine Correctly

Why did people not take their meds A small percentage of people complained of side effects, but the authors hypothesize that a lot of patients find it hard to stick with long-term therapy that isn't making them feel any different immediately. After all, until your arteries get seriously clogged with cholesterol, you can't really feel that you have a problem. But people with high cholesterol do have a major problem, and those on medication need to take it according to their doctor's orders in order to prevent heart problems. Statins are usually taken with your evening meal. Let something you do right before you eat set the table, wash your hands act as a reminder to get out your medication. You can do the same thing with medications taken at any time of day. Use brushing your teeth for cues at night or in the morning, for example.

If You Have Heart Disease

A lot of my patients wonder about the point of lowering cholesterol after a heart attack or other sign of heart disease. Isn't it a waste of time they ask. The answer is an emphatic NO. Once you've had a heart attack, you're at a much greater risk of having another. Because the risk is higher, the treatment benefits are even greater. This statement isn't my medical opinion it is one of the best-studied issues in all of medicine. The 1994 4S trial discussed earlier was the first to document the benefit of lowering choles- ,193 terol in patients who had preexisting heart disease, but even as recently as 2004, the PROVE-IT trial showed the benefit of lowering LDL to under 65 mg dL in individuals with recent heart attack symptoms. (This was one of the studies that led the NCEP to add 70 mg dL as an optional goal LDL level for people with heart disease.) In the decade that separated those two reports, many other studies that used a variety of statins have showed a benefit on either...

Plant Sterols and Stanols

Plants make kinds of alcohols known as sterols and stanols for many of the same reasons that animals make cholesterol. They're key components of cell membranes, hormones, and some vitamins. Scientists have known since the early 1950s that sterols and stanols can lower cholesterol levels. In fact, these alcohols were components of an early generation of cholesterol-lowering medications. Then they faded from sight, replaced by ones that were easier to make, less unpleasant to take, and more effective. But ,213 An influential 1995 report in the New England Journal of Medicine described the results of a trial comparing a margarine that delivered about two grams of stanols a day with a stanol-free version of the same spread among more than 150 men and women with high cholesterol. After a year, those using the stanol-enriched spread had 14 percent lower LDL and 10 percent lower total cholesterol levels. Subsequent studies have demonstrated even larger reductions, in some cases equal to the...

Bile Acid Binders Resins

Bile acid binders are synthetic resins that bind chemically with cholesterol-rich bile acids in the intestine, preventing their reabsorption. To replace the bile acids lost in this way, the body draws upon its store of cholesterol, thus lowering cholesterol levels in the blood. Medications in this class include cholestyramine (Prevalite, Questran), colesevelam (WelChol), and colestipol (Colestid). Typically, they lower LDL cholesterol by 15 percent to 30 percent, 170, depending on the daily dose. Bile acid binders are used much less commonly nowadays because of their many side effects. These include constipation, heartburn, and a bloated feeling. Bile acid binders can also interfere with the action of many drugs, especially digitalis, beta-blockers, warfarin, thiazide diuretics, anticonvulsants, and thyroid hormone supplements. And people with high triglyceride levels should not take this type of medication because it tends to elevate triglycerides. Since ezetimibe has come along,...

What Is Cholesterol

The fat in these particles is made up of cholesterol and triglycerides and a third material I won't discuss much, phospholipid, which helps make the whole particle stick together. Triglycerides are a particular type of fat that have three fatty acids attached to an alcohol called glycerol hence the name. They compose about 90 percent of the fat in the food you eat. The body needs triglycerides for energy, but as with cholesterol, too much is bad for the arteries and the heart.

Heart Disease Primer

Cholesterol seems to have taken on a life of its own in today's society. People brag about their levels or bemoan them, but often without any real understanding of the role cholesterol plays in causing heart disease. Some of my patients expend enormous emotional energy worrying about their cholesterol levels, while ignoring other issues that play an equally important role in causing the coronary arteries to be blocked. In most people, cholesterol is only one factor though a very important one in the complex process that leads to atherosclerotic heart disease. And atherosclerotic heart disease has been the number one killer of Americans every year since 1921. Lowering your blood cholesterol is one of the five basic health-care steps that will keep you from becoming a heart disease statistic, along with not smoking, eating right, exercising, and controlling your blood pressure.

High Blood Pressure

High blood pressure (or hypertension) is nearly as dangerous as high cholesterol. People with this condition are more than twice as likely to suffer a heart attack as those with normal blood pressure are. Because fifty million Americans have hypertension, it's a major cause of atherosclerosis, to say nothing of the death and disability that it brings about through stroke and other hypertensive diseases such as kidney failure.

Obesity

Because obesity is so closely linked to high blood pressure, unfavorable cholesterol levels, lack of exercise, and diabetes, it took scientists a long time to figure out whether obesity itself is an independent cardiac risk factor. Experts now agree that it is. Excess weight increases your risk for heart disease regardless of these other conditions. All forms of obesity are bad for your health, but excessive upper-body fat (an apple-shaped body) is more dangerous to the heart than lower-body obesity (the pear shape). In other words, fat stored at or above your waistline is worse than fat in your hips and thighs.

LDL Cholesterol

Your LDL levels are the most significant of the blood lipids in terms of raising your risk for heart disease, so lowering your LDL should be the primary target of therapy. For LDL cholesterol, below 100 mg dL is optimal, 100-129 mg dL is near optimal above optimal, 130-159 mg dL is borderline-high, 160-189 mg dL is high, and 190 or above is very high. The July 2004 NCEP update states that an LDL level as low as 70 is an option for people at the highest risk. The panel also noted that if you need to go on cholesterol-lowering medication, it makes sense for most people to aim for a 30 percent to 40 percent reduction in LDL cholesterol, not a smaller reduction that gets you to a particular LDL level. So if you and your doctor determine your LDL goal should be 100 mg dL, and your LDL level is currently at 115 mg dL, it doesn't make sense to take a low dose of medicine that gets you to the 100 mg dL mark. Instead, you should probably take a higher dose that gets you down to 80 mg dL or so....

Very High Risk

In 2004, the NCEP issued guidelines that made 70 mg dL an optional goal for people at the highest risk of heart disease. This is 30 mg dL lower than the previous goal for this group of people. Why the change In recent years, new studies have indicated the benefit of lowering cholesterol to levels well below 100. These studies found that for every 1 percent decline in LDL cholesterol, risk for a heart event declines by 1 percent and that this relationship applies to cholesterol levels even below 100 mg dL. Some people think that as more studies on the benefits of low cholesterol come out, LDL goals will continue to fall. The committee notes that the 70 mg dL target should be only for people in the highest risk category, meaning those with heart disease and one of the characteristics listed on page 97. If you fall into this high-risk category and have high uncontrolled cholesterol levels, you and your doctor can decide what combination of drug and lifestyle therapy is right for you. If...

Drug Treatment

Cholesterol treatment has changed dramatically over my lifetime as a physician. When I was a medical student in the 1970s, we knew that high cholesterol levels were a risk factor for coronary disease, but we did not measure cholesterol levels often, even in people who had heart attacks, and we treated people with high cholesterol even less often. Why Because we did not have any proof that lowering high cholesterol levels would make a difference to a patient's health. We also didn't have drugs that were very good at bringing the numbers down. The two types of drugs available in the 1970s are still used today (niacin and bile cholesterol-binding resins), but they typically lower LDL cholesterol by only 10 percent to 20 percent, and they have many side effects. In 1987, the first statin, lovastatin (Mevacor), was approved and the cholesterol world changed. At its highest dose, lovastatin could lower LDL cholesterol values about 40 percent, and it could be taken as a single, small pill,...

If Youre a Senior

It's especially important for seniors with high cholesterol to get treatment. Risk for heart attack increases with age, so taking care to manage other risk factors including high cholesterol has a large impact on this age group's health. Many things about lowering cholesterol, including cutoffs for healthy and unhealthy cholesterol levels, are the same for seniors ,187 as for younger adults. But some things are slightly different. For example, some studies point out that low HDL is a particularly potent risk factor in this group. A study on close to four thousand older people from the National Institutes of Health, for example, found that people with HDL levels below 35 were two and a half times more likely to die of heart disease during the six-year study than people with higher HDL levels. Other studies have shown that total cholesterol levels don't correspond with heart disease as strongly in older people as they do in younger people. This might be explained by a simple fact of...

Treating Children

Children with extremely high cholesterol levels (usually due to a genetic disorder) may need medication in order to prevent a heart attack at a very early age. A 2004 study that randomly assigned children with familial hypercholesterolemia to either pravastatin or a placebo found that the statin was effective and caused no side effects in children during the two years of the study. Personally, I try to avoid treating children with cholesterol medications. I feel treatment can usually wait because heart attacks are incredibly rare in males or females under the age of thirty. (When they do occur, there is almost always a very strong genetic predisposition to heart disease. In these cases, the young person's lipid profile is typically very abnormal and needs to be treated.) Lipid therapies take only a few years, at the longest, to confer benefits, so I believe children don't need to go on medication in all but the most severe cases. While many thoughtful physicians might disagree with...

Red Yeast Rice

Though you might find red yeast rice (rice fermented by a kind of red yeast) on a menu in Asia, nowadays it's known mostly as a nutritional supplement. Studies show it lowering total cholesterol by 13 percent to 26 percent, LDL by 33 percent, and triglycerides by 13 percent to 34 percent. Some studies even show an increase in HDL cholesterol with its use. Do these results sound too good to be true for a product you can buy without a prescription at a health food store The FDA thought so. It banned the sale of red yeast rice in 2001. You see, red yeast rice works on cholesterol because it contains lovastatin, which is the same chemical compound as the statin Mevacor (and its generic counterpart). The FDA distinguishes between nutritional supplements, which are not regulated by the government, and drugs, which are. In this case, they decided red yeast rice should be monitored as a drug. However, the manufacturer won its case against the FDA, so it is available now. The problem is that...

Guggul

This extract from a tree native to Asia was used medicinally as early as 600 b.c. to fight obesity and atherosclerosis, among other things. More recently, it's been used in Asia to lower cholesterol, and it's now making its way into the medicine cabinets of Westerners as well. There are few randomized, controlled trials of this substance, and a recent one shows that guggul doesn't live up to its hype. In this 2003 study, 103 American adults with high cholesterol were assigned to take either a placebo, 1,000 mg of gug-

Soy Lecithin

Although there is a substantial amount of information on the Internet that states that soy lecithin can reduce blood cholesterol levels, there is surprisingly little published scientific information to support that conclusion. I was able to find only a single study in which soy stanol-lecithin powder was reported to reduce cholesterol absorption in the intestine and cause a 14 percent reduction in LDL cholesterol levels. This study indicates that only a specific combination of ingredients was effective for cholesterol

Vitamins C and E

A large study known as the Heart Protection Study also dampened hope that vitamin C might be a magic cholesterol-lowering bullet. Other studies had suggested that antioxidant vitamins such as C might decrease coronary disease risk, among other things. But this study of more than twenty thousand adults with diabetes or coronary or other artery disease said otherwise. Half the people were randomly assigned to receive high-dose supplements of vitamins E, C, and beta-carotene the other half received a placebo. At the end of five years, a similar number of people in each group had had coronary events, stroke, or death.

Ezetimibe

One of the newest drugs on the cholesterol-lowering block is Zetia (ezetimibe). Like a statin, ezetimibe reduces total cholesterol, LDL cholesterol, and apolipoprotein B, a protein constituent of LDL cholesterol. It works in a different way than statins, though. Instead of interfering with the body's mechanism for making cholesterol, ezetimibe interferes with the body's absorption of dietary cholesterol from the small intestine. Taking ezet-imibe along with a statin puts two different mechanisms to work, so it's more effective than taking either drug alone. In the summer of 2004, this got even easier when the drug Vytorin, a combination of ezetimibe and simvastatin, came out. Though doctors had been prescribing this combination of drugs already, Vytorin allows patients to get the two medications in one pill, which can be cheaper and more convenient. Ezetimibe can also be used as a good alternative for people who can't tolerate statins or other cholesterol-lowering agents, but ,169 it...

Policosanol Alcohol

This dietary supplement made from alcohols extracted from sugarcane shows promise as a cholesterol-lowering agent. Though we're not sure exactly how it works, policosanol alcohol seems to block the production of cholesterol. Trials have shown it lowers LDL levels moderately in people with diabetes, postmenopausal women, the elderly, and those with familial hypercholesterolemia, the genetic disorder that causes high cholesterol. That said, most of the trials have been done by one group of scientists, and there haven't been as many long-term, independent clinical trials on policosanol alcohol as I would like to see before recommending it wholeheartedly. And more important, no one knows if poli-cosanol's beneficial effects actually translate into lower incidents of heart attacks and strokes. It does appear to be safe and not interact with most medications used to treat heart disease, though a trial focused on this question needs to be done. One noteworthy side effect is that it increases...

Adynamia See asthenia

Aerobics Shortened form of aerobic exercises. Any form of repeated exercises such as jogging, swimming, or cycling that stimulates the heart and lungs, thereby increasing the intake of oxygen in the body. Aerobics are a good way to decrease cholesterol levels and build lean muscle mass, both important for HIV-infected people on a HAART regimen.

Nutritional Background

Fat diets based more on saturated fats (Dyerberg et al., 1978 Dyerberg and Bang, 1979). The crucial factor, it seems, is the effect of consumption of different fats on the proportion of serum cholesterol associated with high-density lipoproteins (HDL cholesterol) vs. that associated with low-density lipoproteins (LDL cholesterol). Thus, consumption of fats favoring a higher proportion of HDL cholesterol and or a lower proportion of LDL cholesterol, such as diets in which a higher proportion of fats consumed are polyunsat-urated (e.g., from fish or certain vegetable sources) or monounsaturated (e.g., from olive oil), tend to reduce risk from CHD (helped also by the consumption of dietary antioxidants such as Vitamin E, which blocks the oxidative modification of LDL). Conversely, a higher proportion of saturated fats in the diet tends to increase the ratio of LDL cholesterol to HDL cholesterol, thus increasing risk of CHD (Grundy, 1994). However, it is now evident that different...

Microbial Nutrients and Inhibitors

Triglycerides are hydrolyzed subsequently to liberate these acids. Generally, this hydrolysis is accepted to be the work of bacterial lipases, especially those of lipo-philic diphtheroids (7). The antimicrobial properties of fatty acids have been known for many years. For example, the saturated free fatty acid fraction of skin lipids was shown to inhibit the growth of Streptococcus pyogenes, Staphylococcus aureus, and skin micrococci, whereas Gram-negative species such as Pseudomonas aeruginosa and Escherichia coli are resistant (8). In addition to the physiological products and microbial metabolites that influence microbial growth, the vulvar area also contributes vaginal secretions and urine to the nutrient pool. Therefore, the overall microbial nutrition picture of the vulva that emerges is dynamic, and the resulting variability further contributes to the dynamic nature of the microbial ecosystem.

Replacing Standard Fats With Lowcalorie Fats

The concept of replacing fat with a low-calorie fat entered the scene in the early 1990s. By that time, the likelihood of obtaining FDA approval for the use of olestra within a short time-scale was dwindling rapidly, and, on the other hand, it was recognized that the commercially available fat mimetics did not provide an easy answer to fat replacement, and, moreover, their use was restricted, in general, to water-based food systems. In this context, the idea of using the basic structure of a triglyceride molecule, but changing the composition of the fatty acids esterified with the glycerol backbone in order to achieve caloric reduction appeared to be very plausible. Moreover, the fact that medium-chain triglycerides, which usually comprise caprylic (C8) and capric (C10) fatty acids, are GRAS ingredients with a 35-year track record in clinical medicine (e.g., for treating patients suffering from lipid malabsorption symptoms or for use in infant formulae) was a distinct advantage...

Definition of the metabolic syndrome

Three or more of the following factors (triglycerides and HDL counted separately) Triglycerides > 1.7 HDL < 0.9 (men), < 1.0 (women) > 140 90 or treated for hypertension Triglycerides > 2.0 or HDL-cholesterol < 1.0 or treated for dyslipidaemia Fasting plasma glucose > 6.1, but non-diabetic > 130 85 or treated for hypertension Triglycerides > 1.7 HDL-cholesterol < 1.0 (men), < 1.3 (women) Fasting plasma glucose > 6.1 for some other ethnic groups) and two or more of the folowing blood pressure, triglyceride and HDL-cholesterol cut-points as for the ATP-III definition and fasting plasma glucose 5.6mmol l. The application of this definition will increase the prevalence of the metabolic syndrome but its effect of risk of diabetes and cardiovascular disease has yet to be established and is not considered further here.

Selection and Interpretation of Laboratory Results

The other findings required for a diagnosis of nephrotic syndrome are low serum albumin and hyperlipidemia. Although findings vary from patient to patient, edema usually becomes apparent when the serum albumin concentration drops to around 2 g dL (20 g L). Depending on the glomerular filtration rate and the degree of protein loss, the serum albumin may even drop below 1 g dL (10 g L). When such low concentrations are reached, the amount of albuminuria may decrease because of the lower filtered load. The causes for the elevated plasma cholesterol and triglycerides include increased hepatic synthesis of lipoproteins, abnormal lipid transport, and abnormalities in function of lipolytic enzymes.2 Lipiduria may lead to the presence of oval fat bodies in the urine.

Intracellular calcium levels Decrease myocardial apoptosis post reperfusion

Finally, it is important to re-emphasize that, compared with a general population, therapy with primary angioplasty, thrombolysis, b-blockers, aspirin, ACE inhibitors, glycoprotein Ilb IIIa inhibitors, and statins are at least as effective in patients who have DM. Despite this, there is significant underuse of these proven therapies in diabetic patients 62 . Sympathetic blockade inhibits lipolysis and the generation of circulating FFA, which compromises glycolysis in ischemic and nonischemic myocardium. Therefore, it is not surprising that b-blockers are particularly beneficial in diabetic patients. Recently, more complete sympathetic blockage with carvedilol was superior to b-blocker therapy with metoprolol in reducing mortality in patients who had congestive heart failure 63 . Unlike other commercially-available b-blockers, carvedilol therapy improved insulin resistance and may be more effective in reversing left ventricular remodeling by improving myocar-dial energetics. Although...

Lipoprotein classification

A hydrophilic outer surface surrounds an inner hydrophobic core, allowing the transport of triglycerides and cholesterol in circulating blood. The apolipoproteins on the outer surface present to receptors on cell membranes and determine the ultimate destination for the lipoprotein molecule. Fig. 2. Lipoprotein structure. A hydrophilic outer surface surrounds an inner hydrophobic core, allowing the transport of triglycerides and cholesterol in circulating blood. The apolipoproteins on the outer surface present to receptors on cell membranes and determine the ultimate destination for the lipoprotein molecule.

Beloved Daughter at Two and a Half

We tried to start the series with relatively broad topics, such as neurohumoral antagonists in the management of heart failure, cardiovascular imaging techniques, myocarditis, and the pathogenesis of heart failure. Our plan is to gradually turn to more focused topics such as statins in heart failure, use of stem cell therapy, and myocardial architecture. We hope that you have enjoyed the attractive appearance of HFC. Audience surveys indicate that you have appreciated our unorthodox editorials, discussing one or two specific controversies related to the theme of that particular issue and highlighting manuscripts that we hope stimulated readers to think outside of the box. We have worked hard to ensure that article contents were not repetitive, which was particularly difficult because all articles revolved around a single theme. We are particularly proud of the fact that HFC was accepted by the National Library of Medicine for citation in PubMed in a very short time,...

Bidirectional transmission See transmission

Bile-acid resins A class of drugs that have been shown to reduce LDL bad cholesterol by 10 percent to 30 percent in HIV-negative people examples include cholestyramine (Questran) and colestipol (Colestid). These drugs bind with cholesterol in the intestines and prevent it from being absorbed into the bloodstream. The cholesterol is then removed from the body with each bowel movement. Bile-acid resins are often used in combination with other lipid-lowering drugs. This is because bile-acid resins can actually cause triglyceride levels to increase. Side effects of these drugs include stomachaches, bloating, flatulence (farting), heartburn, and constipation. Another problem with bile-acid resins is that they should be taken two hours before other medications, including antiretrovirals. This can be challenging for HIV-positive people who are already overwhelmed by a two- or three-times-daily medication schedule. Bile-acid resins have not yet been studied in HIV-positive patients with...

Effect of glycemic control on cardiovascular disease

Role in a variety of other metabolic abnormalities, including high levels of plasma triglycerides, low levels of high-density lipoprotein (HDL) cholesterol, hypertension, abnormal fibrinolysis, and coronary heart disease 15,16 . This cluster of abnormalities has been called the insulin resistance syndrome or the metabolic syndrome 17 . The National Cholesterol Education Program Adult Treatment Panel III recently recognized the metabolic syndrome as a secondary therapeutic target for the prevention of cardiovascular diseases 15 . Patients who have the metabolic syndrome meet at least three of the following criteria triglycerides that are greater than 150 mg dL, HDL that is less than 40 mg dL, blood pressure that is greater than 130 85 mm Hg, fasting blood glucose that is greater than 110 mg dL, and waist circumference that is greater than 40 cm in men or 50 cm in women (Table 1) 15 .

Consumer Attitudes To Diet And Health

In 1993, the Leatherhead Food Research Association (Leatherhead Food RA) in the U.K. undertook a program of qualitative and quantitative consumer research based on group discussions and in-home interviews, respectively, in order to gain a better insight into consumer issues affecting market developments in reduced-fat foods and, as a consequence, the potential market need for fat replacers (Cathro, 1993). In group discussions, respondents agreed that the high fat content of many foods was one of the most important health issues facing them today. Quantitatively, 58 of 509 respondents interviewed in the home rated dietary fat intake as the most important health issue. This was followed by additives (49 ) and sugar contained in foods (41 ), while salt and fiber were rated as the least important issues, cited by 24 and 16 of respondents, respectively. One of the most worrying aspects about fat intake and cholesterol from a consumer's point of view was that there were no outward signs of...

Treatment of Acute Rejection

Adding sirolimus to combination regimens has allowed the dose of calcineurin inhibitors to be reduced, thus decreasing the nephrotoxicity associated with calcineurin inhibitors without decreasing graft survival.33 The main side effects of sirolimus are hypercholesterolemia, leukopenia, and thrombocytopenia and, unlike calcineurin inhibitors, hypertension, nephrotoxicity, and hepatotoxicity are not common.26

Memory Loss Following Heart Surgery

Memory problems are common among people with diabetes, as well as among people with mildly impaired glucose metabolism, whose blood sugar is slightly high. In 2003, researchers at New York University School of Medicine reported that people with suboptimal glucose metabolism achieved lower scores on short-term memory tests than people with normal blood sugar. What's more, the hippocampus was smaller in people with elevated blood sugar. Suboptimal glucose metabolism (also known as reduced glucose tolerance) is one of the five characteristics of Syndrome X, a collection of risk factors for heart disease that tend to aggregate in some people. The other factors are hypertension, elevated triglyceride, low HDL (good cholesterol), and abdominal obesity.

Definition of the Disease

The cause of hypothyroidism may be primary (thyroid dysfunction), secondary (pituitary dysfunction), or tertiary (hypothalamic dysfunction). Primary hypothyroidism is 1000-fold more common than secondary or tertiary causes.1 Hypothyroidism is associated with cold intolerance, weight gain, constipation, dry skin, bradycardia, hoarseness, and slow mental processing.1 In adults, the characteristic signs and symptoms of hypothyroidism may have an insidious onset. Chronic cutaneous changes include dry, puffy skin with a yellowish complexion as well as a thickening of the subcutaneous tissues due to accumulation of mucopolysaccharides. The hair becomes dry and brittle and is often sparse. The voice may deepen in pitch, and hypoventilation has been observed. Hypothyroid patients can show decreased pulse rate, decreased cardiac stroke volume, and decreased myocar-dial contractility that causes decreased cardiac output. Since peripheral metabolism is slowed, arteriovenous oxygen may not show a...

Sometimes requires discontinuation Contraindicated in active hepatic renal and coronary artery disease

In the UKPDS, treatment with metformin (another drug that decreases hyperinsulinemia and insulin resistance) produced greater reduction in cardiovascular disease events and mortality than sulfonylureas and insulin 8 . The latter drugs decreased blood glucose level to a similar degree as metformin but did not decrease plasma insulin concentrations. This effect may have been mediated through a decrease in insulin resistance, although other effects of metformin, such as improvement in lipid profile, improved fibrinoly-sis, and prevention of weight gain, may be important 8 . Metformin has a favorable, albeit modest, effect on plasma lipids, particularly in decreasing triglycerides and low-density lipopro-tein (LDL) cholesterol however, it had little, if any, effect on HDL cholesterol levels 78 . Met-formin use was associated with decreased plas-minogen activator inhibitor (PAI-1) activity which led to improved endothelial dysfunction (see Table 1). Several studies observed the effects of...

Cranston Gonzalez National Affordable Housing

C-reactive protein (CRP) A protein released by the body in response to injury, infection, or other inflammatory stimuli. A new assay for CRP has enabled researchers to use this protein as a marker of systemic inflammation. Studies have shown a high correlation between presence of this protein and atherosclerosis. It is one of many predictors for heart disease that doctors use today. An HIVpositive person may see tests for this protein on lab reports. It is a surrogate marker of lipids in the blood that cause inflammation. It also is useful if a person is already on statin drugs, because those drugs lower inflammation, so a person with high CRP numbers after taking statins may be at high risk for further heart disease.

Monitoring health outcomes

The publication of league tables does, however, change behaviour, although it may not do so in the way intended. When some states in the USA published death rates after cardiac surgery some surgeons with poor outcomes and low operating volumes stopped operating but few other changes in practice or outcome were noted. However, it became more difficult to get poor-risk patients operated upon and the database changed as more attention was paid to recording comorbidity, etc.22 The same response is probably now underway in the UK. It is a statistical minefield fit only for trained public health clinicians, it is not what it is at present, a playground for politicians. One hopes that the interpolation of clinical czars to plan and monitor quality improvements may add the necessary insulation between politicians' aspirations and clinical reality. Public health doctors are well aware of the difficulties in the process of establishing clinical effectiveness indicators. The first stab at this...

How does atherosclerosis develop

A comprehensive description of the sequence of events in atherogenesis is beyond the focus of this review, but has been well described in several review papers 4-7 . The hallmark feature of atherosclerosis is focal and chronic inflammation in the arterial wall. Inflammation constitutes the first response of innate immunity after a threat is detected, indicating that atherosclerosis is first and foremost an immune-based disease 4 . Virtually all major and minor cellular effectors of the immune system have been shown to be present and in most cases instrumental in the development of plaque 4, 8-11 . Briefly, development of atheromata begins when lipoproteins are retained within the arterial subendothelial matrix 12 (Fig. 1). Why serum lipoproteins become trapped in the arterial subendothelium remains unclear. The Framingham Heart Study and many others unequivocally established that risk of myocardial infarction or stroke increases linearly with serum low-density lipoprotein (LDL)...

Education for All Handicapped Children

Efavirenz stays in the body for a long time and therefore is taken only once a day. Before replacing a protease inhibitor with efavirenz, one should remember that efavirenz can have toxicities. Efavirenz is associated with a rise in cholesterol and triglycerides, unlike other NNRTIs. First, it is not yet clear whether the lipid abnormalities observed with protease inhibitors are due to these compounds' effect on the liver or are a less obvious side effect or lingering consequence of long-term HIV infection. Besides profoundly inhibiting HIV, efavirenz does

Macrophage lipoprotein receptors

The macrophage has specific receptors which allow them to take up and digest cholesterol-containing lipoproteins, low-density lipoproteins (LDLs) (Herijgers et al., 2000), and has various mechanisms for the oxidation of lipoproteins (Guy et al., 1999 Egan and Carding, 2000). These receptor-mediated mechanisms differ from those in other cell types such as fibroblasts and smooth muscle cells. There are several types of lipoprotein receptors on macrophages the LDL receptor recognizes apolipoprotein E and apolipopro-tein B-100 and is regulated by intracellular cholesterol levels the P- VLDL (very low-density lipoprotein) receptor which is not very responsive to cellular cholesterol levels and 'scavenger' receptors. Modified (acetylated) LDLs are recognized by scavenger receptors. The macrophage scavenger receptors (Shirai et al., 1999) have an unusually broad binding specificity. Ligands include modified LDL and some polyanions. The scavenger receptor type I has three principal...

Arousal Circuits Activated By The Hypocretins

Even though the effect of the hypocretin peptides on food intake may be weak and transient, there is strong evidence demonstrating that hypocretin neurons are important sensors of metabolic signals. The connectivity between neuropeptide Y (NPY)-positive neurons in the arcuate nucleus and hypocretin neurons has been demonstrated (27,28). These studies also showed that hypocretin neurons contain leptin receptors and that they are contacted by pro-opiomelanocortin (POMC)-containing inhibitory neurons. Furthermore, hypocretin neurons are sensitive to glucose, leptin, ghrelin, and triglycerides (29-32). In an elegant study, Hara et al. (33)

Crosstalk between TLRs and lipid metabolism by liver X receptors

Interestingly, TLRs can directly interfere with cholesterol metabolism in macrophages 59 . The accumulation of cholesterol-loaded macrophages in the arterial wall is a very important event in the development of early atherosclerotic lesions 5 . Macrophages normally activate a compensatory pathway for cholesterol efflux mediated by the ABCA1 transporter in response to lipid loading but this mechanism is overwhelmed in systemic hypercholesterolemia 60 . Castrillo and co-workers recently demonstrated that activation of TLR3 and TLR4 by their corresponding ligands blocks the induction of liver X receptors (LXR) target genes, such as the cholesterol transporters ABCA1 and ABCG1 and the lipopro-tein apoE in vitro and in vivo leading to an inhibition of cholesterol efflux from macrophages 59 . However, LXR agonists also inhibit LPS- and cytokine-induced expression of proinflammatory genes 61 . New studies deepen the connection between LXR and inflammation by uncovering a protective role of...

Fetus transmission to See transmission

Fibrates A class of drugs that are antihyperli-pidimics. Fibrates are fibric acid derivatives. These drugs work by speeding up the chemical breakdown of triglyceride-rich lipoproteins that circulate in the body. They are used in particular to lower levels of triglycerides, which they control better than the statin group of drugs. They are not very effective at reducing LDL cholesterol level or raising HDL cholesterol level. The most common side effects are stomach pain, bloating, and nausea. Liver enzyme levels can also become elevated, and a myositislike syndrome, especially in patients with impaired renal function, can occur. Decreased libido and impotence have occasionally been reported. Fibrates can increase the effect of medications that thin the blood, so their use should be monitored closely by the physician. See bezafi-brate ciprofibrate fenofibrate gemfibrozil.

Tolllike receptors and atherosclerosis Genetic evidence

Several polymorphisms in the genes encoding TLRs have been investigated in the context of infectious diseases 79 , autoimmune disorders 80 , allergies 81 , periodontal disease 82 , and renal disorders 83 , but have also focused on a potential role of TLR polymorphisms on vascular disease and its clinical sequelae. Patients either heterozygous or homozygous for two different single nucleotide polymorphisms (Asp299Gly and Thr399Ile) that map to the extracellular domain of TLR4 are hyporesponsive to a challenge with LPS 84 . Atherosclerosis is characterized by chronic local inflammation 5, 85 , and thus a blunted response to LPS might place the host at a disadvantage in eradicating invading microorganisms yet could diminish cardiovascular risk because of decreased systemic inflammation. Therefore, patients harboring Asp299Gly and Thr399Ile polymorphisms might be imbued with greater cardiovascular protection. A population-based epidemiologic study did indeed show that subjects carrying...

The canadian guidelines Introduction

In 1988, the Canadian Consensus Conference of Cholesterol (CCCC) published national guidelines for patient screening and the treatment of dyslipidemia (6). In 1998, the Working Group on Hypercholesterolemia and other Dyslipidemias formed to analyze data and update these Canadian Guidelines. The committee issued updated management recommendations for dyslipidemia in 2000. In 2001, the US National Cholesterol Education Panel, Adult Treatment Panel III (NCEP ATP III) Guidelines were published followed by findings from several large clinical trials on dyslipidemia. Based on these findings, the Canadian Working Group reconvened and published an update in 2003. The guidelines were reviewed by two expert panels that included recognized specialists in the areas of CVD prevention, lipid metabolism, and diabetes along with primary care physicians (5).

Davids Medical History

In taking his medical history, I learned that David had hypertension and high cholesterol. Though he was taking medication for both conditions, they weren't being adequately controlled. He had been to a hospital emergency department five months earlier with chest pain, which turned out to be benign. A recent physical examination, blood tests, and a chest x-ray were normal. His primary care physician had also ordered a brain MRI, which was normal.

The Collaborative Atorvastatin Diabetes Study

Effects of simvastatin on first major vascular event in patients who do or do not have diabetes according to presenting features and baseline blood lipid concentrations. CI, confidence interval. The numbers in columns two and three represent the number of individuals with a given characteristic total number in that group ( of total with the given characteristic). The last column represents the proportional reduction in risk (and CIs) the size of the rectangular box varies according to the relative number of subjects. (Adaptedfrom Collins R, Armitage J, Parish S, Sleigh P, Peto R. MRC BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes a randomised placebo-controlled trial. Lancet 2003 361(9374) 2005-16 with permission.) Fig. 1. Effects of simvastatin on first major vascular event in patients who do or do not have diabetes according to presenting features and baseline blood lipid concentrations. CI, confidence interval. The numbers...

The Asymptomatic Iron

A 65-year-old Caucasian male presented to his primary care physician for a routine physical exam prior to retiring. He had enjoyed excellent health throughout his life, and did not report any new symptoms at the time. His past medical history included elevated prostate-specific antigens that had been evaluated with multiple negative prostate needle biopsies, and hypercholesterolemia treated with diet and medication. Family history was notable for cardiovascular disease, hypertension, and breast cancer. He did not smoke, and consumed less than one beer or glass of wine per week. On direct questioning, he did not acknowledge chest pain, shortness of breath, arthralgias, fatigue, cold intolerance, or decreased libido.

Triglyceride and highdensity lipoprotein intervention

Unlike the plethora of trial evidence of CHD risk reduction with statins, the evidence from drugs to decrease triglycerides or increase HDL cholesterol is sparse. A meta-analysis of 17 observational studies suggested a significant relationship of triglycerides with CHD, even after adjustment for HDL cholesterol, especially in women 33 . In the 4S trial, in post hoc analyses, patients who had the lipid triad (elevated LDL, elevated triglyceride, decreased HDL cholesterol) had the highest event rates in the placebo arm and the greatest risk reduction with simvastatin 34 . Despite a mechanistic plausibility of increased risk with these lipid abnormalities in patients who had metabolic syndrome and diabetes, few long-term randomized trials have been completed (Table 2). The largest, randomized clinical trial of fibrate therapy in patients who had diabetes was the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) 38 . In this trial, 2531 men who had CHD were...

Lipid goals in patients who have diabetes

Diabetes is a CHD-risk equivalent, as defined by the ATPIII recommendations. Based on the evidence from the LDL-lowering clinical trials that were summarized above, most patients who have diabetes should have an LDL goal of less than 100 mg dL (Table 3). If LDL is grater than 130 mg dL, treatment with LDL-lowering drugs should be initiated simultaneously with therapeutic lifestyle changes (TLC) to achieve the LDL goal 1 . The American Diabetes Association (ADA) has the same recommendations for LDL goal 42 . In addition, the ADA recommends a triglyceride goal of less than 150 mg dL and an HDL cholesterol goal of greater than 40 mg dL in men and greater than 50 mg dL in women (see Table 3). According to ATPIII, however, when triglyceride levels are elevated (200-499 mg dL) after achieving LDL goal, non-HDL cholesterol should be the secondary target of therapy. No HDL goal is specified in ATPIII because of the lack of sufficient evidence. It is recommended that if HDL remains low after...

If TGL 200 mgdL nonHDLC total C minus HDL is a secondary target of therapy with a goal of 30 mgdL higher than the LDL

HDL cholesterol ( ) Triglycerides ( ) Statins Bile acid sequestrants *, may increase in patients with high triglycerides. Adapted from Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in adults (Adult Treatment Panel III). JAMA 2001 285(19) 2486-97, with permission and Gagne C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol 2002 90(10) 1084-91 with permission. *, may increase in patients with high triglycerides. Adapted from Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in adults (Adult Treatment Panel III). JAMA 2001 285(19) 2486-97, with permission and Gagne C, Bays HE, Weiss SR, Mata P, Quinto K,...

Role of combination therapy in diabetes and dyslipidemia

Despite the known pharmacologic effects of fibrates and nicotinic acid in ameliorating the underlying defects of diabetic dyslipidemia (increased triglyceride-rich lipoproteins low HDL cholesterol small, dense LDL particles), the role of combining these agents with statins remains uncertain and further clinical trials are needed. Trials like the VA-HIT and DAIS are supportive of the potential of adding fibrates to statins because combined lipid disorders are common in patients who have insulin resistance and type 2 diabetes. In short-term studies, statins and fibrates were more effective in normalizing all lipid abnormalities than either agent alone without significant risk for adverse events, including myositis 51,52 . Caution should be exercised in patients who have potential drug interactions (eg, cyclo-sporin, antifungal agents, protease inhibitors, erythromycin) or renal disease. Long-term trials of combination therapy with statins and fenofi-brate are in progress (Table 5). In a...

Prevention Of Type 2 Diabetes

Post-challenge) Low insulin secretion Insulin resistance syndrome (low HDL-C, high triglycerides, hypertension, fibrinolytic defects, glucose intolerance) Low magnesium level Low chromium level High plasma non-esterified fatty acids Low sex hormone binding globulin Low physical activity Cigarette smoking

Meat Palaeolithic diets and health

Studies have shown that Australian Aborigines have shown significant health improvements, including a reduction in blood cholesterol levels, after returning to their natural diets, where there is a high reliance on animal foods (O'Dea, 1991). Research of macronutrient proportions in the diet of hunter-gatherer populations shows a clear relationship between high protein content and the evolution of insulin resistance, which offered a survival and reproductive advantage (BrandMiller and Colagiuri, 1994). However, the advent of agriculture saw the rise of a diet higher in carbohydrate this has meant that people were unprepared for the high glycaemic load which in turn is responsible for the current incidence of non-insulin dependent diabetes mellitus (Brand-Miller and Colagiuri, 1994). However, we must also remember that humans are not carnivores and thus we cannot exist on protein intakes above 35 energy for extended periods of time. 'A clear role for lean red meat in a healthy balanced...

Risk factors for diabetes

Elevated triglycerides HDL cholesterol metabolic syndrome. Other risk factors for type 2 diabetes mellitus include age of 45 years or older, family history of diabetes (parent or siblings), physical inactivity, ethnicity (eg, Afro-American, Hispanic, Native American, Asian American, or Pacific Islander), impaired glucose tolerance, history of gestational diabetes or delivery of a baby weighing more than 9 lbs, hypertension (blood pressure > 140 90 mm Hg in adults), high-density lipoprotein (HDL) cholesterol level below 35 mg dL and triglyceride level above 250 mg dL, polycystic ovary syndrome, and history of vascular disease 10 . Park and Edington 11 applied a prediction model using sequential multilayered perception neural network architecture. High BMI was the most significant risk factor other significant factors that predicted risk over time with variations in trajectory were elevated blood pressure, stress, elevated cholesterol levels, and fatty food intake.

Targeting Aggressive Tumors

Researchers are hopeful that the RAS family or associated pathways can become productive targets for novel therapeutics, although no such drugs are currently routinely employed in cancer patients. The frequency with which RAS mutations occur in common cancers and their association with resistance to ionizing radiation make for a potentially powerful target. Already approved for use in treating patients with hypercholesterolemia, lovastatin is a HMG-CoA reductase inhibitor that also blocks the processing of RAS (88). Application of lovastatin has been shown to increase radiosensitivity in cell lines harboring mutant RAS (89), and trials are under way to assess its applicability as an adjunctive therapy in a number of cancers. Also under way are attempts at inhibiting RAS processing by other farnesyltransferase inhibitors a necessary event in ras postranslational modification. Inhibition of this step results in the radiosensitization of cells in vivo (90). Currently in various stages of...

Limit of quantification See limit of detection

Therapeutic approaches include the use of ator-vastatin, gemfibrozil, and pravastatin to lower cholesterol and tribyceride levels. Management approaches currently under study to correct metabolic abnormalities associated with HAART include studies of statins, fibrates, and niacin, and switch studies (studies in which patients are switched from protease inhibitors to nonnucleo-side reverse transcriptase inhibitor or other agents) of the treatment of dyslipidemia and the

Chromium Supplementation And Cardiovascular Disease Risk

The observations reported for the HPFS cohort appear to be consistent with observations reported from the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer (EURAMIC). The EURAMIC was an incident, population-based, case-control study conducted in eight European countries and Israel to determine whether low toenail chromium concentrations are significantly associated with increased risk for MI. The study included 684 case subjects (men with a first diagnosis of MI within 24 hours of admission to the hospital) and 724 control subjects (men with similar demographic characteristics, but without MI). Average toenail chromium was 1.10mg kg in the case subjects versus 1.30mg kg in the control subjects. Additional analysis indicated that the adjusted ORs for MI for chromium quintiles 1-5 were 1.00, 0.82, 0.68, 0.60, and 0.59, respectively 77 . The results of EURAMIC thus indicate that toenail chromium concentration has a clearly inverse relationship...

Improvement of endothelial function

Endothelial dysfunction leads to defects in insulin-mediated glucose uptake. Blockade of vascular nitric oxide synthesis with L-arginine analogue also impairs endothelial dependent va-sodilation. Endothelial function improves with exercise, a low-fat, low-carbohydrate diet, and with use of statins and ACE inhibitors (Table 5) 29,59,67 . Angiotensin I blockade has not shown any improvement of endothelial dysfunction, but benefit has been noted with peroxisome pro-liferator activated receptor gamma (PPAR-y) stimulator, antioxidants, hormone replacement therapy, and L-arginine 66,68,69 . In addition, the ACE inhibitor quinapril significantly improved endothelial function in multiple studies, both in normotensive volunteers and in subjects with coronary artery disease 70-77 .

Clinical studies nonrandomized

Intervention consisted of unspecified dietary advice and increased physical activity conducted either in groups or individually. There were improvements in VO2max , lowered body weight, BP and serum triglycerides, greatest at one year, but maintained over the six years. Among people in the IGT group without intervention, 21.4 met criteria for diabetes (> 6.7 mmol l fasting and or > 11.1 mmol l at two hours), whereas only 10.6 had diabetes in the intervention group (RR 0.49 (CI 0.25-0.97)). Subjects who lost the most weight and improved oxygen uptake the most had the greatest improvements in glucose levels. These results were further explored in another report76 which showed that, in addition to forced vital capacity (as a correlate of fitness), insulin resistance (higher 2 h insulin level) and lower insulin secretion (40 minute insulin increment during the OGTT) predicted diabetes independently among people with normal glucose tolerance.

Man with a Tender Toe and Anemia

He was employed and smoked one pack of cigarettes and drank one pint of liquor each day. Preexisting medical problems included hypertension, hypercholesterolemia, and type 2 diabetes, but he did not consistently see a physician or take prescribed medications. Laboratory data from 3 years earlier were notable for hemoglobin 13.9 g dL and creatinine 1.3 mg dL.

Developing nutritionallyenhanced cerealbased foods 1351 Current status

Arguably, however, the key growth area has been fibre-enriched products. These products may be enriched with cereal-based dietary fibre or fibre derived from other plants, for example psyllium. As discussed in more detail elsewhere in this book, dietary fibre has been shown, or is thought to be, beneficial in managing the risk of a number of diseases. From classical times (British Nutrition Foundation, 1990) the beneficial effects of cereal fibre and in particular insoluble fibre on colonic function have been known. More recent work, such as the meta-studies of Ripsin et al (1992) have demonstrated that soluble fibres may have beneficial blood cholesterol lowering effects, particularly when eaten as part of a reduced fat diet.

Lessons and challenges of study of ethnicity in terms of disease risk

Disease patterns differ between groups that have emigrated versus groups that have stayed in their native land. A classic example is provided by migrant Japanese groups to the USA (Hawaii and California), where CHD rates in the Japanese immigrants settled overseas the longest, and in their descendants, converge to those in the host population but remain lower among the Japanese in Japan (Syme etal., 1975). It is likely that a predisposition to CVD is exacerbated by environmental factors such as exposure to Western lifestyles. For example, in the UK, Indian immigrants from Punjab had a worse risk factor profile (higher BMI, systolic blood pressure, cholesterol level, apolipoprotein-B, fasting glucose and lower HDL-cholesterol) than their siblings who continued to live in the Punjab (Bhatnagar etal., 1995). These changes in risk factors and disease among migrants provide important clues to genetic and lifestyle interactions on risk of disease.

Clinical implications

There is good evidence that a healthy lifestyle can reduce the incidence of diabetes (Hu etal., 2001), as can treating impaired glucose tolerance with lifestyle modification (Tuomilehto etal., 2001). The Finnish Diabetes Prevention Study assigned 522 middle-aged overweight men and women (mean BMI 31 kgm-2) with impaired glucose tolerance into intervention (individual counselling on diet and physical activity) and control groups. At 3.2 years of follow-up the intervention group had a 58 per cent lower incidence of diabetes, significantly greater reductions in weight and dietary fat intake and greater increases in dietary fibre and exercise (> 4h per week) reversing the changes of insulin resistance and metabolic syndrome (Tuomilehto etal., 2001). Reports of specific interventions to reverse impaired glucose tolerance in people from ethnic groups are currently lacking and are an area for future study. There is, however, good rationale to manage the presence of the metabolic syndrome...

Targeting tgrich lipoprotein reduction as a means of achieving nonhdlc goal

Clinical outcome trials with fibrate therapy have been generally supportive of a protective effect regarding cardiovascular events (20,32). However, the results are not as robust as those observed with statins. In primary and secondary prevention trials with clofibrate, gemfibrozil, bezafibrate, and fenofibrate, the median relative risk reduction for the primary outcome variable was 21 (range 4-49 ), with four of nine trials reaching statistical significance (20,32).

Clinical Immunosuppressive Protocols

Sive agents are still associated with significant side effects including organ toxicity, lifethreat-ening viral and fungal infections, and malignancies.64,65 Commonly used calcineurin inhibitors in induction and maintenance therapy have similar side effects on renal and hepatic function. Neurotoxic effects and post-transplant diabetes mellitus are higher under tacrolimus protocols, whereas the risks of hypercholesterolemia and hypertension are lower compared to those with CsA. Tacrolimus promotes nerve regeneration,66 so this agent will be preferred in CTA transplantations because nerve regeneration will be one of the goals after transplantation.

Cholesterol and Alzheimers Disease

Protein in the brain is Apolipoprotein E (ApoE), and the Apos4 allele is the only confirmed genetic risk factor for late-onset AD. ApoE and ApoJ (also called clusterin), two abundantly expressed apolipoproteins in the brain, both act as Afi chaperones and cooperatively suppress Afi levels and deposition in the brain.57 In addition to its role as a chaperone, ApoE also regulates the metabolism of Afi in the brain extracellular space.57 There are increasing genetic data (see the next section) that implicate several other genes in the cholesterol pathway, such as cholesterol 24-hydroxylase, in AD. In the cell, cholesterol impacts membrane structure, and APP, BACE1, and all four components of the y-secretase complex (presenilin 1, nicastrin, APH-1, and PEN-2) are membrane-associated proteins. Reducing cholesterol esters by inhibiting acyl-coenzyme A cholesterol acyltransferase (ACAT) reduces Afi secretion.58 Accumulation of intracellular cholesterol is accompanied by accumulation of...

Treatment and Prevention

One of the most visible treatment and prevention strategies for CHD has targeted decreasing high blood cholesterol and LDL-C. The National Cholesterol Education Program (NECP) Expert Panel in Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults published their third report (ATP III) in 2001.4 This report constitutes the guidelines for cholesterol testing and CHD risk management and is the third in a series that identifies LDL cholesterol as the primary target for therapy. The most common approach for lowering LDL is the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) inhibitors (statins), but other therapies include bile acid sequestrants, nic-otinic acid, fibric acid, and diet. The LDL-lowering therapy is tailored according to the patient's overall risk of CHD. Assessment of the overall risk for CHD is the first step in patient management. In individuals without current CHD, the number of risk factors present should be determined and the 10-year risk of CHD...

Biguanides including combinations

The metformin group showed small (-1 kg) but significant weight loss, less rise in fasting glucose, and marginally greater fall in fasting insulin, without changes in 1 h glucose or insulin. Lower LDL cholesterol, but no change in BP, triglycerides or HDL cholesterol were found. Of a number of hemostatic factors explored, the metformin group showed decreases in tissue plasminogen activator (tPA) antigen, and vonWillebrand factor109, but no change in plasminogen activator inhibitor-1 (PAI-1) activity or antigen not accounted for by weight loss. Five in the placebo group developed diabetes, versus none in the met-formin group (exact p 0.06, post-hoc analysis). The results are difficult to interpret since there was a 18 and 30 drop-out rate in the two groups at one year. While subjects who dropped out were similar to those remaining in the trial, unexplained bias could have accounted for the results. The investigators undertook a confirmatory study (BIGPRO-1.1) among 168 men who had...

Studies examining nonglycemic therapies

No area of CVD research in diabetes has received more attention than lipid management. Numerous studies in primary prevention and secondary intervention with statins and fibrate lipid-lowering agents are underway 33 . The guidelines regarding lipid management are in flux based on the rapidly evolving landscape of clinical trials that have recently and soon will be reported. Recent guidelines discussed elsewhere in this issue reinforce prior recommendations that in high-risk patients like those who have type 2 diabetes mellitus, the low-density lipoprotein cholesterol (LDL-C) goal is less than 100 mg dL, but suggest that in the highest risk patients, such as those who have acute coronary syndrome or diabetes mellitus and clinical CVD, further lowering to an LDL-C level of 70 mg dL or less is ''a therapeutic option, ie, a reasonable clinical strategy'' 34 . A remaining question is how low should one go in managing lower risk patients who have diabetes mellitus Several trials addressing...

Nitric Oxide And Progenitor Cell Mobilization

Today, NO produced by eNOS appears to be the common denominator of a variety of stimuli including VEGF (see above), HMG-CoA reductase inhibitors (statins), angiotensin converting enzyme (ACE) inhibitors, estrogen and exercise, all identified as inducers of progenitor cell mobilization. Hence, in the early post-myocardial infarction (MI) phase, an increase in ROS production and a decrease in MMP9 activity in the bone marrow are associated with the reduced EPC mobilization 23 . Interestingly, this is reversed by drugs like ACE inhibitors 23 and statins 23, 24 , in part through their capacity to increase NO production and or eNOS expression. Similarly, estradiol can increase EPC mobilization post-MI through a facilitating effect on eNOS activity and subsequent activation of MMP9 25 . These data suggest a potential benefit of hormone replacement therapy for the management of MI in postmenopausal women and have probable implications with regard to the sex discrepancy in the occurrence of...

Carbohydrate Fatty Acid Polyesters

The development of carbohydrate-based and alkyl glycoside-based fatty acid polyesters as fat substitutes to replace edible fats and oils on a one-to-one basis in food is described in detail by Akoh and Swanson (Akoh, 1994 Akoh and Swanson, 1987a and b, 1989a and b, 1990, 1994). Carbohydrate and alkyl glycoside fatty acid polyesters exhibit functional and physical properties resembling conventional triglycerides without contributing significantly to the caloric content of the diet. Digestion and absorption are reduced by saturating a carbohydrate, sugar alcohol, or an alkyl glycoside with fatty acids esterified to the available hydroxyl groups. Utilizing the wide variety of fatty acids and carbohydrate moieties naturally available, carbohydrate and alkyl glycoside fatty acid polyesters can be synthesized to incorporate desirable physical and functional properties. The carbohydrate fatty acid polyesters are macroingredients substituted for fats and oils in foods to incorporate desirable...

Other Synthetic Fat Substitutes

Trialkoxycitrate (TAC) and trialkoxyglyceryl ether (TGE) were also investigated by Hamm (1984). Because the ester bonds in TAC are reversed from corresponding esters in triglycerides, the esters in the polycarboxylic acid fat substitutes are not susceptible to lipase hydrolysis, and do not contribute calories to the diet. Polymorphic behavior is exhibited during melting and TAC viscosity and surface tension are similar to corn oil. Thermal decomposition problems may prevent TAC from being used in frying oils. Trialkoxyglyceryl ether (TGE) production on a large scale is difficult and time-consuming (Hamm, 1984 LaBarge, 1988). TGE exhibits viscosities and surface tensions similar to vegetable oils at room temperature. While functional properties may allow TGE use as a fat substitute, synthesis problems will make commercial production difficult (Artz and Hansen, 1994 Hamm, 1984 LaBarge, 1988). Esterified propoxylated glycerols (EPG) (Arco Chemical Company, Newtown Square, PA) are...

Pharmacological interventions

Statins and other cardiovascular drugs The inter-relationship between the components of the metabolic syndrome is epitomized by the actions of statins. These were employed originally to reduce the incidence of CHD because of their efficacy in lowering lipid levels. Several other actions that may be protective are now apparent (Endres and Laufs, 2004). Statins appear to improve endothelial function by promoting NO production via increased synthesis of eNOS. They also may increase NO bioavailability by reducing oxidative stress. Other actions include the observation of lower levels of inflammatory mediators such as TNF-a and IL-6 and the ability to improve arterial compliance (Endres and Laufs, 2004 Matsuo etal., 2005). These actions may be responsible for up to a 30 per cent reduction in the risk of developing type 2 diabetes (Rosenson, 1999). Angiotensin-converting enzyme (ACE) inhibitors have also been demonstrated to increase NO bioavailability (Henriksen and Jacob, 2003), and a...

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