treating familial hypercholesterolemia

Question: What is the best way to treat familial hypercholesterolemia? I understand that the medication Lipitor can keep some people's cholesterol ratios within normal limits, but my cholesterol is still above 235. What else can be done to reduce my risk of early heart attack? My daughter and I both have it.

Familial hypercholesterolemia is often associated with high LDL cholesterol levels (often above 200) and can lead to premature atherosclerosis. As you've already experienced, lipid-lowering therapy can be helpful but many times does not lower cholesterol to the recommended level for the general population.

It's very important to know that cholesterol levels, although important, only account for about 30% of the variability in CAD (coronary artery disease) incidence. The good news is that other factors like diet, exercise, psychosocial issues and gender are critical, independent of cholesterol levels. So, taking good care of these other factors should reduce your risk, even if you have high LDL cholesterol. Marty Sullivan MD

apolipoproteins in the pathogenesis of atherosclerosis

Recently an international research team described the results of their studies of Lp(a) and apo(a) in the pathogenesis of atherosclerosis. They found that both substances promote vascular smooth muscle cell proliferation and migration, one of the hallmarks of atherosclerosis. Grainger et al. (Cambridge University) and Lawn et al. (Stanford University) cultured smooth muscle cells from healthy human arteries, and then exposed them to Lp(a) and purified apo(A). They found that both Lp(a) and apo(a) -- but not LDL -- caused a dose-dependent acceleration of vascular smooth muscle cell proliferation. They also found that cell-associated plasmin activity was reduced to one seventh the control level by Lp(a) and to one fifth the control level by apo(a) in both human and rat vascular smooth muscle cell cultures. Moreover, Lp(a) and apo(a) both reduced the amount of active TGF-b to 1/100 the level in control (LDL-treated) cultures. Finally, the addition of plasmin to Lp(a)-treated vascular smooth muscle cell cultures overcame the effects of Lp(a) and reduced growth rates to control levels. These results all suggest that the acceleration in smooth muscle cell proliferation is indeed due to the ability of Lp(a) and apo(a) to competitively inhibit the cleavage of plasminogen, reducing plasmin concentrations and TGF-b activation.

Thus, the homology of apo(a) with plasminogen, with subsequent inhibition of plasminogen activation, contributes to atherosclerotic plaque formation by two mechanisms: it prevents the activation of TGF-b, allowing smooth muscle cells to proliferate, and it prevents clot lysis, adding fibrin and other debris to growing atherosclerotic plaque. In addition, Lp(a) binds endothelial and macrophage cells and fibrin, and deposits its cholesterol load and other fatty debris in the vascular endothelium, another hallmark of atherosclerosis. "Both inhibition of clot lysis and enhancement of cell migration could contribute to the process of atherogenesis," concluded the Cambridge and Stanford researchers. "We suggest that Lp(a) may contribute to the growth of the arterial lesions of atherosclerosis by promoting the proliferation of vascular smooth muscle cells."
source:Grainger DJ et al. Science. 1993; 260: 1655- 1658

Eating Rye Bread May Reduce Cholesterol

The ability of dietary fiber, particularly soluble fibers found in cereals, to reduce coronary heart disease risk by improving serum lipid profiles has been demonstrated in several studies. The dietary fiber content of rye is 16.1 g/100 g, but its effects on blood lipids have been studied only in animal models. This study investigated the effects of increasing the amount of rye bread consumed in a daily diet on serum cholesterol levels in men and women in Helsinki, Finland, who had elevated cholesterol. Rye is a commonly used cereal in northern and eastern Europe.

Eighteen men and 22 women participated in the study. They had a baseline serum cholesterol concentration of 6.4 +/- 0.2 mmol/L. Each subject randomly consumed rye or wheat bread as 20% of their total energy intake for 4 weeks at a time, and then crossed over. There was an additional 4-week washout period between bread study periods. During the bread periods, subjects were asked to replace their customarily used breads and baked products with rye bread during the rye period and wheat during the wheat bread period. Test bread portions were 27.5-40.5 g for rye and 22.5-25.0 g for wheat. A minimum of 4-5 portions of the test breads had to be consumed each day. Fasting blood samples were collected at the beginning and the end of the bread periods.

Serum total cholesterol decreased by 8% in men during the rye bread period but did not change significantly in women. Wheat bread did not alter any of the lipid variables studied. Total cholesterol and LDL cholesterol decreased in men in a manner dependent on the amount of rye bread consumed. HDL cholesterol in men increased during the rye bread period, but not significantly. Neither type of bread altered blood levels of glucose and insulin significantly.

The significant reductions in total and LDL cholesterol observed in men were attributed to the fact that men consumed greater quantities of rye bread than women during the study. The greatest change in cholesterol levels occurred in men who ate about 8-10 slices of rye bread per day.

"In conclusion, rye bread is effective in reducing serum total and LDL cholesterol concentrations in men with elevated serum cholesterol," wrote the authors. "Good compliance with consuming a relatively large amount of rye bread in the usual diet indicates that rye bread offers a practical dietary means of reducing serum cholesterol in men."

Journal of Nutrition

activation of plasminogen and apolipoproteins - apo(a)

The major apolipoproteins present in Lp(a) -- the apolipoprotein B or apoB series and the apolipoprotein(a) or apo(a) series -- play different roles in health and disease. ApoB-100 is the portion of the Lp(a) molecule (the ligand) that is recognized by the receptor. Other lipid and apolipoprotein components vary considerably in the LDL complex, but they all interact to maintain the apo B molecule in a specific spatial orientation for receptor binding. The second major Lp(a) apolipoprotein is apo(a), which has been described as a giant mutant of plasminogen. This is because approximately 80% of the amino acid sequence of apo(a) is identical to that of plasminogen. Because of this homology, apo(a) is able to competitively inhibit the surface binding and activation of plasminogen. Blocking plasminogen activation prevents the formation of plasmin, a crucial component in clot lysis. Plasmin is also involved in the activation of a compound referred to as latent transforming growth factor-b (TGF-b), a potent inhibitor of smooth muscle cell growth in the vascular endothelium.
source:Grainger DJ et al. Science

Apolipoproteins and Heart Disease

Lipoprotein(a), or Lp(a), is a lipid-protein complex involved in the transport of cholesterol in the circulation. Scandinavian researchers reported in 1963 that men with high levels of Lp(a) were more susceptible to coronary artery disease (CAD) than men with low levels. Unfortunately, these findings were ignored for more than 20 years because of difficulties in testing for Lp(a). Then 8 years ago, American researchers began reexamining Lp(a). They have since found that a high plasma concentration of Lp(a) is a major risk factor for atherosclerotic and thrombotic vascular disease -- including CAD, myocardial infarction, restenosis of coronary artery grafts, carotid atherosclerosis, and stroke -- and that this risk is independent of age, diet, physical activity, smoking status, ethanol consumption, and sex. Population studies indicate that abnormal plasma levels of Lp(a) may cause up to 25% of premature MIs. Elevated levels of Lp(a) are also associated with significant carotid atherosclerosis, even in the absence of clinical heart disease.
source:Schreiner PJ et al. Arterioscler Thromb.

apolipoprotein studies related to cardiovascular disease

Despite advances in diagnosis, care, and treatment, cardiovascular disease remains the number one killer in the United States and throughout the industrialized world. CAD is particularly common in males, even those less than 50 years old, and in many cases there are no clear risk factors other than a family history of heart disease. Hypercholesterolemia, for example, accounts for less than half of all MIs in the United States. Continuing research on the structure, function, pathophysiology, and heritability of apolipoproteins should lead to improvements in diagnosis, risk assessment, and treatment of cardiovascular and also cerebrovascular diseases.

apolipoprotein E gene polymorphism

Van Bockxmeer and Mamotte studied apolipoprotein E gene polymorphism in 91 Australian men 3--50 years of age with confirmed symptomatic coronary obstructive CAD who had been referred for coronary angioplasty. Each patient had at least one coronary artery with more than 50% luminal diameter obstruction (averaged from multiple views). Patients were compared with 172 healthy men. Five of the 19 CAD patients who were less than 40 years of age were homozygous for the e4 allele, representing a 16-fold increase in prevalence compared with controls. In CAD patients aged 40-50 years, e4 allele frequency was 60% higher than in controls. Moreover, CAD patients homozygous for e4 were 5 years younger, on average, than men with other genotypes (e.g., e3/e4). "Inheritance of e4 seems to confer risk of premature ischemic heart disease in males, homozygotes being especially at risk at a younger age," concluded the investigators.
source:Van Bockxmeer FM, Mamotte CDS. Lancet

Genetics, Apolipoprotein E, and Heart Disease

Apolipoprotein E (apoE) is a lipid-protein complex that plays a role in the pathogenesis of heart disease. Apo E is a protein constituent of very-low-density lipoprotein (VLDL) and chylomicrons. It is believed to mediate clearing of these lipoproteins from the circulation through specific VLDL binding to cell surface receptors, and thus it plays an important role in plasma lipid metabolism. The apoE gene is polymorphic; that is, the DNA base sequence varies slightly so that the apoE proteins produced differ from each other in just one amino acid. This substitution can lead to considerable differences in activity. The three common apoE proteins -- apoE2, apoE3, and apoE4 -- are coded for by three common genes (alleles) designated e2, e3, and e4. According to biochemists Van Bockxmeer and Mamotte, at a popula-tion level the most significant determinant of plasma lipoprotein levels found to date is polymorphism in the apoE gene.
ApoE2 has a reduced affinity for the cellular receptor, so e2/e2 carriers (homozygotes) have elevated lipids in the blood, and in 5% of cases this manifests itself as type III hyperlipidemia. The e4 allele is associated with higher total and LDL cholesterol levels. Certain populations with a high incidence of CAD (e.g., Finns) have been shown to have high serum cholesterol levels and an increased frequency of e4, while populations with a low incidence of CAD and low cholesterol levels (e.g., Orientals) have a low frequency of e4. A lower e4 frequency has been reported in octogenarians, suggesting that individuals who are free of the e4 allele are the ones who survive long enough to become octogenarians.
source:Wenham PR et al. Atherosclerosis.

What is cholesterol and how does it affect my health?

Cholesterol is an essential component in the structure of cells and is also involved in the formation of important hormones and Vitamin D. It is produced by your liver, and your body makes all the cholesterol you need.

Excess cholesterol in the bloodstream can form plaque on artery walls that narrows arteries and reduces blood flow to the heart tissue. When blood flow is restricted, chest pain or angina can occur. When blood flow to the heart is severely impaired or stops completely, a heart attack can result.

Eating foods high in saturated fat and cholesterol can raise your cholesterol levels. Being overweight or obese and not getting enough exercise are also associated with high cholesterol levels.

coronary heart disease and cholesterol levels

If you're like most women, you probably know that a high level of cholesterol in the blood increases the risk of coronary heart disease. Too often we think of coronary heart disease as something that affects only men. Not so. It just takes about ten years longer for cardiovascular disease to appear in women. Since this is the No. 1 cause of death for American women age 35 and over, it's important to get the facts and get active in reducing your risk.

what is good cholesterol and bad cholesterol?

Cholesterol moves through your bloodstream to your body's cells in special packages called lipoproteins. Low-density lipoprotein (LDL-C) cholesterol is commonly known as the "bad" cholesterol because too much LDL-C in the blood can bind or stick to the walls of your arteries, narrowing them and restricting blood flow.

High-density lipoprotein (HDL-C) is known as the "good" cholesterol because it does not collect on artery walls. It may also aid the removal of excess cholesterol from the blood and reduce the build-up of LDL-C in the arteries. In fact, high levels of this "good" cholesterol are associated with a decreased risk of heart attack. The recommended HDL-C level for women should be 45 mg/dL or higher.

Observational studies have shown that low levels of HDL-C appear to be a stronger coronary heart disease risk factor for women than for men. While national guidelines recommend an HDL-C level of 35 mg/dL or above for all adults, many experts believe this number should be 45 mg/dL or more for women.

triglycerides levels and heart attack

Triglycerides are a kind of fat found in your blood and are the most common type of fat in the body. While the role of triglycerides in coronary heart disease is unclear, moderately elevated triglycerides tend to occur in people who have suffered a heart attack. People with diabetes also frequently have elevated triglycerides. Your triglyceride level should be below 200 mg/dL.

estrogen and increased cholesterol

Research suggests that estrogen may help reduce your risk of heart attack by raising your HDL-C level and lowering your LDL-C level. The loss of estrogen that occurs at menopause has been shown to have a negative effect on heart health. When your body starts to slow its production of estrogen, your total cholesterol can increase by as much as six percent within six months of your last period.

risks of cholesterol lowering drugs

In the final analysis, taking medication to lower cholesterol is unquestionably of benefit if you have heart disease or if you are at high risk for developing heart disease and your cholesterol is high. New studies over the last two years have demonstrated that at least some of the statin drugs substantially decrease risk of heart attacks and death from heart disease. (In the future, we will look more closely at whether there are differences among the different statin drugs). Furthermore, the statins have turned out to be extraordinarily safe. If you have heart disease, you probably should be on medication for your cholesterol almost regardless of your cholesterol. Otherwise, if your cholesterol is on the high side, you should always try diet and exercise first. However, if your cholesterol remains high and especially if you are at high risk for developing heart disease, statins are very safe and potentially life-saving drugs.

risks of cholesterol lowering medication - cancer risk

The third and final issue with the statins involves the issue of whether they increase the risk of cancer. This issue received a lot of press recently when a paper was published reviewing the animal data on cholesterol-lowering medication. This paper reviewed the animal studies in which the use of very high doses of the medications was associated with tumors. Most of the tumors were benign (non-cancerous) tumors of the gastrointestinal tract, but some were malignant as well. Is this relevant to people? Most experts think the answer is probably not. There are a variety of reasons for not getting alarmed about these animal studies. The doses used in these studies were much higher than those ever used in people and perhaps most reassuringly, there has not been any evidence in the many millions of people treated with the statin drugs that there is an increase in the incidence of cancer, and none of the controlled studies in people have shown any evidence either. Can this prove that there is absolutely no increased risk associated with these medications, no matter how small? No, but common sense dictates that if your risk of having a heart attack is relatively high, the benefit of taking a medication to lower your cholesterol will far outweigh any small theoretical risk of the medication. Again, the issue comes down to what your risk really is for developing heart disease. Therefore, the overall theme of determining your risk for heart disease will continue to be a major one in the practice of medicine

risks of cholesterol lowering medication - muscle pain

The second issue involves muscle pain, or myopathy. The statins can cause muscle or joint pain relatively frequently. Very infrequently the muscle problem can progress to the level where it could be dangerous or even life-threatening. This complication is more likely to occur in people taking certain other medications, such as other cholesterol drugs or immunosuppressive drugs. The major way to prevent this complication is to be aware of the possibility -- that way if your muscles start to ache after starting a statin drug, you can stop taking the drug and call your doctor. As long as you don't keep taking the medication for many days once the muscle pains start, the chance of developing a severe problem is very low.

risks of cholesterol lowering medication - effects on liver

There are several types of cholesterol-lowering medications and to address this question they must be looked at separately. The most popular class of medications for cholesterol are known as the "statins" because their names all end in "statin": lovastatin, pravastatin, simvastatin, and fluvastatin. The bottom line is that the statins are extraordinarily safe. However, there are three issues regarding the statins which have been raised regarding safety.

• First, when lovastatin was first introduced there was concern that it could potentially affect the liver. Even today this is the first question that many people ask their doctor when a statin drug is suggested. In reality, the statins have not caused "liver damage" and this issue is no longer a significant consideration. Even the routine monitoring of liver function tests may become less routine.

Cholesterol, Atherosclerosis, and Coronary Heart Disease

Coronary Heart Disease affects close to 60 million Americans, leads to nearly half of all deaths, and costs society billions of dollars each year. One factor that contributes to coronary heart disease (CHD) is cholesterol. Cholesterol is an essential component of cell membranes and a precursor for a range of hormones; however, it is also involved in atherosclerotic plaque formation within the arterial intima. Patients with elevated levels of cholesterol, in particular, low-density lipoprotein cholesterol (LDL-C), have an increased risk for both fatal and nonfatal heart attacks. Reducing cholesterol levels with diet, exercise, and drugs has been shown to slow (and even reverse) the progression of atherosclerosis and to reduce the risk of myocardial infarction (MI). After 5 years, a 10% reduction in LDL-C results in a decrease in CHD of up to 50%.

Cholesterol circulates in the bloodstream with triglycerides and phospholipids (mostly lecithin) in small aggregates containing proteins. There are four "lipoprotein" classes: chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL).

Cholesterol lowering drugs also reduce risk of stroke

Studies on cholesterol-lowering drugs called reductase inhibitors (statin drugs), not only will these drugs help reduce your risk of heart attack, they may also reduce the risk of stroke as well.

People who take reductase inhibitors such as pravastatin, lovastatin, or simvastatin to lower their cholesterol either to prevent a heart attack or reduce the risk of a second one occurring, also get the added benefit of lowering their risk of stroke by 27% compared to those taking either a placebo or inactive medication.

Reductase inhibitors lower cholesterol levels by 20% to 40%. The analyses included data from 12 previously conducted studies involving over 20,000 people who take reductase inhibitors. The research was prompted by the need of scientists to examine data from a larger study in order to better determine the association between cholesterol lowering drugs and stroke.

Other methods of reducing heart attack risk also lower stroke risk. People who are able to get their high blood pressure under control reduce the risk of stroke by 40%; taking blood-clotting medication reduces the risk of stroke by 35%.

While scientists are not entirely clear as to why these medications help to lower stroke risk, they believe that the drugs may either reduce fatty plaques, or stabilize them, in arteries that supply blood to the brain. Approximately 70% of all strokes can be attributed to a blood clot that reduces the blood supply to the brain (ischemia). Of these ischemic strokes, about 12% are activated by a narrowing of arteries attributable to fatty plaques. The remaining 20% to 30% of all strokes are attributable to brain hemorrhages.

Reducing heart attack risk

The current focus of much clinical research is to determine how to prevent heart attacks from occurring. Two strategies are currently used by physicians to reduce the risk of a heart attack. One strategy is aimed at inhibiting the clotting process in coronary arteries with such drugs as aspirin. Another strategy is to use cholesterol lowering drugs to prevent cholesterol build-up.

The question still remains: which individuals should have treatment with cholesterol lowering drugs? Some individuals with mild elevation of cholesterol will never get coronary disease and some individuals with cholesterol in the normal range will have a heart attack. Hopefully, new imaging techniques will prove useful for detection of coronary artery disease and screening of patients at risk for a heart attack.

One such non-invasive imaging technique is called Ultrafast CT. This radiology study identifies coronary artery cholesterol plaques by the presence of calcium in the plaques. Another imaging technique, called vascular ultrasound evaluation of the arteries in the neck, is useful because patients with cholesterol build-up in arteries in the neck and legs also tend to have cholesterol plaques in the coronary arteries. In addition, more specific blood tests to evaluate for the risk of coronary artery disease are being evaluated. Currently, the sum of risk factors is added together to provide the physician with an overall risk assessment or "heart attack scorecard" in order to determine the appropriate preventive treatment for the individual.

Cholesterol lowering and heart attack

In addition to high levels of LDL, other risk factors such as smoking, high-blood pressure and diabetes contribute to the rapid development of cholesterol plaques in heart arteries. Numerous scientific studies have been conducted over the last three decades to determine if cholesterol lowering (i.e. lowering of LDL cholesterol) reduces the progression of cholesterol plaque development. From these studies, we now know that cholesterol reduction can slow the progression of plaque development. In addition, we know that plaques that do not cause a significant obstruction to blood flow in the artery may indeed rupture and cause a heart attack. This explains why some individuals do not have significant amount of chest discomfort prior to having a heart attack.

Until recently, it was unknown whether cholesterol lowering prolongs the life of individuals with coronary artery disease. Over the last two years, several clinical studies have been published that showed that using drugs to lower cholesterol prolonged the life of individuals who have had a heart attack. Furthermore, a study conducted in Scotland and published in 1995 showed that men with high cholesterol levels who had no symptoms of heart disease suffered fewer heart attacks when taking a cholesterol lowering drug over a five year period than those who took a placebo (sugar pill).

It is now clear that patients who have had a heart attack or have been diagnosed with coronary artery disease should lower their cholesterol by reducing dietary intake and/or taking cholesterol lowering drugs to reduce the risk of further heart attacks and cardiac procedures such as angioplasty or bypass surgery.

LDL and heart attack linkage

Coronary artery disease begins in most individuals as a small area of fat in the wall of the artery during the teenage years and early twenties. This process, called atherosclerosis, involves both genetic and environmental factors. The "bad cholesterol" or low density lipoprotein (LDL) is a major risk factor for the development of atherosclerosis. Recent studies indicate that the modified form of LDL, oxidized LDL, is necessary for the cholesterol to build up in the wall of the artery.

The LDL particle has a central core of cholesterol and triglycerides as well as antioxidants such as Vitamin E. The core is surrounded by polyunsaturated fat and a protein called apo B-100. When free radicals modify the LDL by a process called lipid peroxidation, toxic products are released and change the structure of the proteins so that they are recognized as foreign by white cells in the walls of the artery macrophages. These macrophages fill up with fat and accumulate in the artery wall leading to progressive encroachment into the blood stream.

A heart attack results when the cholesterol plaque ruptures, platelets stick to the surface and a clot occludes the artery. Blood carries oxygen which is the fuel for the heart and without blood flow the heart cells are unable to survive and the muscles supplied by this artery die. Thus, a heart attack or a myocardial infarction ultimately results from a cholesterol build-up in the wall of the artery.

Stroke Reduced 29% by Statin Agents

An analysis of 16 clinical trials published over a 10-year period indicates that treatment with cholesterol-lowering statin drugs reduces the incidence of stroke by 29%. The report, covering 29,000 patients, is in this morning's JAMA

Treatment also reduced total mortality by 22%, without an attendant increase in deaths caused by noncardiovascular disease or cancer. Previous research has proven that cholesterol therapy decreases the risk of coronary-artery disease, but its effects on stroke and total mortality had been unclear. The authors conclude, "With the larger reductions in cholesterol that are achieved with statin drugs, the benefit-to-risk ratio of cholesterol lowering is clearly favorable. The issue of generalizability of findings from the overview of the statins to cholesterol lowering in general remains untested."

Gene linked to high cholesterol in black men

Certain forms of a gene called MTP cause higher cholesterol levels in African-American men, US researchers report.

Testing for the gene could identify individuals who need early intervention to prevent the health risks caused by high cholesterol, such as heart attack and stroke.

The MTP gene codes for MTP, or microsomal triglyceride transfer protein, which is involved in adding fat to certain molecules in cells. Minor variations in one site on the gene result in the existence of three common forms of the gene--GG, GT, and TT--in humans.

The GT combination has been associated with increased cholesterol levels in middle-aged men, prompting Dr. Suh-Hang Hank Juo from the National Human Genome Research Institute in Baltimore, Maryland and associates to investigate MTP forms in African-American men, who tend to have higher rates of heart disease than white men.

"This is the first study to investigate...over 10 years of the genetic effect of the MTP (forms) on lipid profiles in young African-American men," the authors note. Their report is published in Arteriosclerosis, Thrombosis, and Vascular Biology: Journal of the American Heart Association.

Out of 579 individuals tested, most had the GG or GT form of MTP. Thirty-nine men (or about 7%) carried the TT form of MTP, the team reports.

Contrary to previous research in white men, abnormal levels of cholesterol were most closely associated with the TT form of the gene, the investigators note.

African-American men with the TT gene had consistently higher levels of total cholesterol, LDL ("bad") cholesterol and apoB--all risk factors for atherosclerosis and heart disease, the report indicates. TT gene carriers also had consistently higher levels of triglycerides.

These results suggest that the TT form of MTP could increase the risk of cardiovascular disease in these men and could be helpful in working out the genetics of heart disease, the authors conclude.

"Understanding the role of the TT gene variation could help researchers better understand what causes elevated cholesterol in the general population and may help in dealing with its potential consequences," Juo said in a news release.

"We could target individuals carrying this gene," he added, "so they could get an early start on prevention. A person with the 'bad' form could try to lower the risk by exercising, eating a low fat diet, not smoking, and taking medication to lower cholesterol."

Sources

Arteriosclerosis, Thrombosis, and Vascular Biology

Pravastatin Affects Artery Walls

Pravastatin Directly Affects Artery Walls in Monkeys

Pravastatin has been shown in three different large studies to substantially reduce the risk of heart attack and stroke. As a cholesterol-lowering drug, pravastatin was assumed by many to work primarily by lowering cholesterol levels. A new study suggests its benefits may result in part from the drug's direct effect on artery wall function.

A research team from North Carolina fed 32 monkeys a high-fat diet for 2 years. Then they put all of the monkeys on a low-fat diet and 14 of them on pravastatin as well for another 2 years. Researchers found that the concentrations of total cholesterol and the good HDL cholesterol remained similar in both groups of monkeys, Dr. J. Koudy Williams of Wake Forest University in Winston-Salem and co-workers report in the March Journal of the American College of Cardiology.

The team was not surprised to find similar cholesterol levels in the two groups, since the study was designed so that both groups of monkeys would have similar cholesterol levels at the beginning and during the study. The objective of the study was to examine the drug's effects on the artery wall.

After performing angiograms on the monkeys, the team found that the amount of plaque in the artery walls also grew the same amount in both sets of monkeys. However, the plaque in the monkeys on pravastatin was not as calcified and also had better dilation of the arterial wall, which improves blood flow in the vessels.

The authors conclude that the direct effects of pravastatin on the artery wall may account in part for the drug's reduction in the incidence of coronary events and strokes in humans.

Because the statin drugs all inhibit cholesterol synthesis and lower LDL cholesterol levels in the blood, the understandable tendency is to assume that this is all they do. However, studies in the test tube have demonstrated other effects of statin drugs and differences among the statins in some of these effects. The study reported above is the first to demonstrate the concept that pravastatin has effects on the vessel wall that are "independent" of (not directly due to) its ability to lower cholesterol. It did not compare pravastatin to any other statins and therefore comparative statements cannot be made. Nevertheless, this demonstrates that there may be more going on than we realize with some statins that is working to alter plaque and make it less likely to cause cardiovascular events. Much more research is needed before we fully understand these effects.

SOURCE: Williams, J. Koudy, "Pravastatin Has Cholesterol-Lowering Independent Effects on the Artery Wall of Atherosclerotic Monkeys", Journal of American College of Cardiology,

Cholesterol drug ads misleading

A television ad campaign for the cholesterol-lowering drug fluvastatin (Lescol) contained false and misleading information, according to a letter released Tuesday by the Food and Drug Administration (FDA).

The ads claimed that Lescol was as effective as three other cholesterol-reducing drugs: Pravachol, Mevacor, and Zocor. However, the manufacturer, Novartis Pharmaceuticals, did not provide any substantiation of those claims and has not done any head-to-head studies, according to Minnie Baylor-Henry, director of FDA's Office of Drug Marketing, Advertising and Communications.

The company also advertised Lescol as less expensive than other drugs -- a misleading claim, according to the FDA.

The ads ran in August, September, and October in Baltimore, Atlanta, St. Louis and Tampa, and the FDA asked Novartis to immediately submit a plan for undoing the damage it had done.

The federal agency is only now warning the company because it was not aware of the ads until they had finished running. Pharmaceutical manufacturers are supposed to submit advertising text, audio, or video to the FDA at the time it is first displayed or broadcast, but Novartis did not do so.

That resulted in "a significantly larger consumer audience receiving false or misleading information about the safety and effectiveness of Lescol," wrote Baylor-Henry.

Novartis advertised Lescol as costing up to 60% less than other cholesterol medications, but the company did not mention that there may be additional costs incurred for lab tests and office visits, both needed to help determine correct dosing, said the agency.

The company also did not use equivalent dosages. "In fact, because of dosing differences, Lescol may cost more than the other agents," according to the FDA.

Novartis' ads minimized risks of liver function abnormalities, and did not give patients enough information on how to learn more about side effects and other risks, the FDA said.

The campaign was a "pilot" and was last run in October, according to Anna Frable, a spokesperson for Novartis. The company "is currently reviewing the letter and we do absolutely plan on responding to the agency by their deadline," Frable said.

By February 5th, the FDA wants a complete list of TV stations that broadcast the ads, and the number of times aired. And the agency indicates that Novartis should design new ads, including, but not limited to, print ads, that "disseminate accurate and complete information to the audience that received the misleading message."

The company may even have to run new TV ads. "We think it's important to use comparable methods to reach the same audience," FDA drug advertising specialist Norm Drezin told Reuters Health.

risk factors of cholesterol

A person's risk for heart disease and elevated blood cholesterol levels is affected by many factors. First, let's look at those risk factors we cannot control: age, sex and heredity. As we get older, blood cholesterol levels naturally rise; coronary artery disease (CAD) primarily affects those older than 40. Males are more likely to develop CAD than females who are premenopausal (have not gone through menopause). Family history of heart disease is an automatic risk factor to be taken very seriously. People with a known family history of CAD can alter their lifestyles to reduce their chances of developing CAD. Family history is defined as a family member (parents, siblings, first degree relative) who develop heart disease before the age of 60, risk factors of cholesterol article

There are several risk factors that can be controlled: diet, physical activity, smoking, hypertension and diabetes. Saturated fats and foods high in cholesterol can raise your LDLs and total cholesterol levels. Decreasing blood cholesterol levels not only decreases the risk but slows the progression for those who already have been diagnosed with CAD. People who are obese have a tendency to have high LDL and low HDL levels, risk factors of cholesterol article

Likewise, physical inactivity can also worsen your cholesterol levels. Aerobic exercise and loss of body fat can improve cholesterol levels by raising the HDL levels and lowering LDL and total cholesterol levels in the blood.

Smoking greatly increases your risk for developing CAD by constricting your blood vessels, reducing HDL levels and facilitating the development of CAD. Smoking is also associated with higher triglyceride and total cholesterol levels.

Hypertension (high blood pressure) is a major risk factor for heart attack. Hypertension causes the walls in your arteries to thicken and harden. It also decreases the elasticity or stretchiness in your arteries, requiring your heart to work harder. In most cases the cause of hypertension is unknown. Many people with hypertension can improve their blood pressure through diet, exercise, and limiting their consumption of alcohol. Antihypertensive medications may be prescribed for those patients who are unable to control their blood pressure through diet and exercise, risk factors of cholesterol article

Diabetes also affects our risk for CAD through the development of neuropathies and decreased circulation. Diabetic neuropathies are disorders of the peripheral nervous system that involve a loss of sensation of pain, pressure and temperature in the extremities. Weight loss and diet control can prevent the development of adult onset diabetes. Medication is often used to help some diabetics control their condition. Changing the factors that we can control can significantly decrease the risk for heart disease, risk factors of cholesterol article

Your cholesterol results can give your physician an indication of your risk level for heart disease. Your physician will look at a combination of your lab results as well as your other potential risk factors for heart disease to make a definitive diagnosis and recommendation. Be sure to discuss your lab results with your physician. Together you can come up with a plan to reduce your risk for heart disease, risk factors of cholesterol article

high LDL low HDL

Each day people are having their cholesterol screened to determine their risk for heart disease. When the lab results are presented, it can be difficult for most people to interpret them and understand whether they are at risk for heart disease. For example, the doctor tells you that your LDLs are too high, your HDLs are too low and your triglycerides aren't looking so great either. What does it all really mean?

OVERVIEW OF CHOLESTEROL
First, a quick review of cholesterol and triglycerides. Cholesterol is a fat-like substance found in your body's cells. Cholesterol comes from two sources: your liver, which produces it, and foods such as animal products that contain cholesterol and saturated fats. It travels through your bloodstream in protein coatings called lipoproteins.

HDL or high-density lipoproteins are the "good" cholesterol. They carry extra cholesterol out of the body. LDLs are the "bad" cholesterol. They are the culprits that build up plaque in your arteries and increase your risk for heart disease. It can be very confusing to remember which is good and which is bad. A good way to avoid confusion is to remember L for lousy (LDL).

Triglycerides are another type of fat found in your body. They're also both made in your body and derived from foods. Triglycerides don't directly cause heart disease but help contribute to the plaque build-up that clogs your arteries.

Cholesterol Lowering in Women - (2)

Primary cardiovascular risk prevention is of particular importance to women. Sudden cardiac death is more frequently the presenting symptom of cardiovascular disease in women than in men. In addition, women are more likely than men to die of their first MI.¹⁰ Identifying women most likely to benefit from primary intervention remains a challenge, however.

AFCAPS/TexCAPS. The Air Force Coronary Atherosclerosis Prevention Study (AFCAPS)/Texas Coronary Atherosclerosis Prevention Study (TexCAPS)¹⁵ was the only primary prevention trial with statins to include women. In it, 997 women with total cholesterol levels between 180 and 264 mg/dL, LDL cholesterol levels between 130 and 190 mg/dL, HDL cholesterol levels less than 47 mg/dL, and triglyceride levels less than 400 mg/dL were randomized to treatment with lovastatin, 20 mg/day, or placebo; the lovastatin dose was titrated to 40 mg/day if the LDL cholesterol remained above 110 mg/dL. Patients were followed up for an average of 5.2 years.

Results for the entire trial group showed a 37% reduction in risk for the primary end point of first acute major coronary event (p <.001), which included fatal or nonfatal MI, unstable angina, or sudden cardiac death. In addition, the need for revascularization was reduced by 33% (p=.001). Event rates were very low for women in this trial: 13 women in the placebo group and seven in the lovastatin group had a primary event. As a result, it is difficult to draw conclusions about the benefit of lovastatin in women.Cholesterol Lowering in Women article

AFCAPS/TexCAPS demonstrated a major clinical challenge of primary prevention: identification of women at increased risk for the development of clinical cardiovascular events. The trial included women who were at relatively low risk for a cardiovascular event. Fewer than 20% of the patients would meet current NCEP guidelines for cholesterol-lowering treatment. To reach a statistically significant conclusion about event reduction in the subgroup of women, approximately 20,000 women would have had to be included.Cholesterol Lowering in Women article

Currently, several primary prevention trials in higher risk groups are under way, including the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in the United States and a European trial in older patients. Both of these studies include women and focus on patients with high risk-factor profiles. In addition, the Women's Health Initiative will address primary cardiovascular prevention with HRT.Cholesterol Lowering in Women article

cholesterol lowering methods

In my practice in the Lipid Clinic and Cardiovascular Risk Intervention Program at the University of Pennsylvania, I face daily decisions about whom to treat with cholesterol-lowering medication and how aggressively to reduce the cholesterol level. As stated in your article, the dilemma is, "How do we target effective but costly treatments to the people most likely to benefit?" The entire medical community is in agreement that virtually all persons with known coronary heart disease should be treated with medication, even if the cholesterol level is in the "average" range.

However, the decision to use cholesterol-lowering medication in apparently healthy persons is much more difficult. The key is in the accurate determination of who is and who is not likely to be at risk of a heart attack or cardiac death. Unfortunately, analysis of traditional risk factors for coronary disease is not sufficiently precise for the identification of high risk factors for individuals. Numerous "at risk" people will remain event free for decades, whereas a large number of heart attacks occur in subjects without major risk factors, most of whom have average or only mildly elevated cholesterol levels, cholesterol lowering methods.

Fortunately, there is a relatively new tool available which provides vital information about future risk of heart disease and can therefore be used in deciding whom to treat. The American Heart Association recently concluded that Electron Beam CT scanning for coronary artery calcification identifies the presence of coronary plaque and that this finding would influence the aggressiveness with which risk factor modification is approached.Extensive studies over the past eight years demonstrate that measurement of coronary calcification correlates with coronary disease and helps predict the likelihood of future clinical coronary events even in persons without any current symptoms, cholesterol lowering methods.

I now use this rapid, non-invasive test in selected individuals in order to assist in the important decision of whether to initiate cholesterol-lowering therapy. This technology for coronary artery scanning has become increasingly available across the country at a cost of less than a six-month prescription for cholesterol-lowering drugs. Combining the power of this non-invasive detection of coronary disease with the effectiveness of the statin drugs finally allows us to focus aggressive preventative treatment on those individuals with underlying coronary atherosclerosis who are at highest risk of having future heart attacks and coronary death, cholesterol lowering methods.

what are trans fatty acids

While saturated fats raise blood cholesterol levels, monounsaturated fats lower blood cholesterol levels. But what about trans fatty acids?

WHAT ARE TRANS FATTY ACIDS?
Trans fatty acids were virtually unknown until the mid-1980’s, when the food industry started to use less saturated fats, primarily from animal and tropical oils, in processed foods. Because saturated fats cause increased levels of blood cholesterol, consumers pressured the food industry to replace harmful saturated fats with the more beneficial unsaturated fats.

Trans fatty acids are formed when liquid fats are hydrogenated, or partially hydrogenated, to become more solid at room temperature. Saturated fats have a higher melting point and less potential to become rancid. These properties are beneficial in many crackers, baked goods, and fried foods. To replace saturated fats, the food industry chose to use hydrogenated oils, creating trans fatty acids in the process.

Cholesterol Lowering in Women

After reading these articles, the reader should be able to discuss the epidemiology of coronary heart disease in women and evidence from clinical trials on the efficacy of cholesterol-lowering therapy in primary and secondary prevention of coronary events, Cholesterol Lowering in Women article.

Amid growing recognition that cardiovascular disease is the leading cause of death for women in the United States,¹ an increasing body of data is emerging on differences and similarities in coronary heart disease (CHD) in men and women. In addition, treatment options for cardiovascular risk reduction in women have been clarified, Cholesterol Lowering in Women article.

Disruption of the cholesterol plaque in a coronary artery is central to the development of symptomatic CHD in both women and men, but mechanisms of plaque disruption and stabilization may differ. Women may be more likely to develop plaque erosion than plaque rupture,² and the acute coronary syndrome in women is more likely to present as unstable angina than as acute myocardial infarction (MI).³ Another difference between the sexes is that epidemiologic studies show a strong relationship between low-density lipoprotein (LDL) cholesterol levels and cardiovascular risk in men,⁴ but the association between LDL cholesterol levels and cardiovascular mortality may be less in women⁵ , Cholesterol Lowering in Women article.

Epidemiologic studies show that hormone replacement therapy (HRT) in women reduces LDL cholesterol levels by approximately 10%, increases high-density lipoprotein (HDL) cholesterol levels by approximately 10%, and reduces the risk for cardiovascular events.^6-9 The National Cholesterol Education Program (NCEP) guidelines⁹ used epidemiologic data on HRT for recommendations for lipid lowering in women. Until recently, however, clinical trial data were not available on primary or secondary cardiovascular event reduction in women with either conventional lipid-lowering therapy or HRT. More than 50 million women in the United States have total cholesterol levels greater than 200 mg/dL,¹⁰ the desirable blood cholesterol level according to NCEP guidelines.⁹ Lipid levels in women increase with age. In women less than 45 years of age, total cholesterol levels average 185 to 207 mg/dL, whereas in women between 45 and 65 years of age, they increase to 217 to 237 mg/dL, similar to levels in men. Beyond age 70, average total cholesterol levels in women exceed those in men.¹¹¹² In parallel with this gradual rise of cholesterol levels with age, women develop cardiovascular disease, on the average, 10 years later than do men. The increase in lipid levels near menopause and the delay in onset of disease symptoms in women can be attributed to a protective effect of estrogens. Premenopausal women, with the exception of high-risk women with diabetes or strong risk-factor profiles for cardiovascular disease, are at lower risk than men for the development of CHD. Overall, 26% of American women have lipid levels that qualify for diet or drug therapy to reduce cardiovascular risk. Among those more than 55 years of age, the number rises: 51% of women 55 to 64 years old and 54% of women 65 to 74 years old qualify for lipid-lowering therapy, Cholesterol Lowering in Women article.

Women have been excluded from clinical CHD trials because of childbearing capacity, advanced age at onset of disease, and the seemingly better prognosis for women with angina.¹³ Because of a lack of clinical trial data on primary and secondary cardiovascular risk reduction in women, evidence-based recommendations have been extrapolated from data in men. Studies of lipid-lowering therapy in women with documented CHD, however, show marked undertreatment of women, despite the treatment guidelines.¹⁴ Differences in characteristics of CHD in women and lack of specific data on lipid-lowering therapy in women have contributed to the undertreatment of women with documented CHD.

A growing body of evidence now exists for both primary and secondary cardiovascular risk reduction in women using the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins). Four statin trials in a cross-section of women, with and without established CHD, have demonstrated prevention of acute coronary events. In contrast, despite large bases of epidemiologic data suggesting event reduction with HRT and basic scientific research showing the beneficial effects of HRT on the arterial wall and coronary plaque, the only prospective trial of HRT in women with established CHD did not show reduction of cardiovascular events, Cholesterol Lowering in Women article. (1)

cholesterol management

Epidemiologic studies have demonstrated a strong relationship between elevated serum cholesterol and coronary heart disease (CHD) and serve as the basis for the "cholesterol hypothesis," which maintains that a decrease in serum cholesterol will reduce atherosclerotic disease. Trials have been designed to assess the impact of cholesterol lowering on quantitative measures of atherosclerotic disease, or on clinical cardiovascular events, cholesterol management.

Because it is now recognized that most acute coronary events are caused by the disruption of a nonobstructive coronary plaque,(1) this review will focus on recent trials that have been undertaken to determine the effects of such a disruption on clinical cardiovascular events. Analysis of the five major trials with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) that have been published in the past 5 years provides important insight into the relationship between treatment of cholesterol and prevention of acute coronary events and stroke, cholesterol management.

Cholesterol lowering margarines

Cholesterol-lowering margarines can support -- but not replace -- traditional medication- and diet-based anti-cholesterol therapies, conclude experts at the American Heart Association (AHA).

"Individuals who know that their LDL cholesterol is elevated should consult with their healthcare professional before including the new margarines in their cholesterol-lowering plan, especially if they are already taking medication," said Dr. Alice Lichtenstein, a member of the AHA's Nutrition Committee, cholesterol lowering margarines .

Two of the margarines -- McNeil's Benecol and Lipton's Take Control -- gained US Food and Drug Administration approval for sale in the US this month. McNeil Consumer Healthcare, the makers of Benecol, has announced that its product should be on grocery store shelves sometime this week. Both of the products are expected to sell for about five to six times the price of regular margarines.

Cholesterol-lowering margarines contain either sterol esters or stanol esters, plant-derived compounds that appear to reduce absorption of cholesterol within the digestive tract. Build-up of LDL ('bad') cholesterol on artery walls is a leading risk factor for heart attack and stroke.

In an AHA statement, Lichtenstein, who is also a professor of nutrition at Tufts University in Boston, Massachusetts, warned that the new products "can only lower cholesterol levels about 7% to 10%." For this reason, she says, they should be used in combination with other cholesterol-lowering measures, such as regular exercise and a low-fat, low-cholesterol diet. She also believes that "for many people... cholesterol-lowering drugs may still provide the best means of lowering LDL cholesterol levels."

AHA experts (cholesterol lowering margarines) do not recommend that individuals who are unaware of their cholesterol status use these products as a method of 'preventing' cholesterol build-up.

"While cholesterol lowering margarines may be used a part of a treatment plan, they do not prevent the underlying cause of elevated LDL cholesterol levels," according to an AHA statement.

Still, Lichtenstein believes that "for people with elevated levels of cholesterol, the new margarines can provide an effective 'boost' to a LDL cholesterol-lowering plan prescribed by a physician."

Cholesterol Screening

Cholesterol Screening: Why the Controversy? : You may have heard an opinion that doctors should stop testing or screening their patients for cholesterol. Why after all these years of talking about and studying cholesterol are doctors still arguing about who should have their cholesterol measured? Let's briefly go into the history behind this "controversy."

Conventional medical wisdom -- based upon many different studies from all over the world conducted over the last several decades -- is that high cholesterol levels are very strongly associated with risk of heart disease. Based upon this circumstantial evidence alone, however, we can not say for sure that lowering cholesterol will decrease the risk of heart disease. But, thanks to other studies specifically designed to measure effects of lowering cholesterol, we can now say definitively that lowering cholesterol does indeed decrease the risk of heart attack. This is especially true in people who have had one heart attack already; in fact, most doctors agree that people with heart disease should be treated to lower their cholesterol, cholesterol screening.

The controversy about cholesterol screening has centered around the issue of using medication to lower cholesterol in people who don't already have known heart disease. This is known as "primary prevention" because its purpose is to prevent that first heart attack. Until recently, the clinical information concerning this topic was incomplete: lowering cholesterol decreased heart attacks but not deaths from all causes and therefore its value in this setting was not completely established. However, a recent study using pravachol, one of the "statin" drugs (a class of drugs that powerfully and safely lower cholesterol ) demonstrated that both heart attacks and deaths from all causes were substantially less in persons who took the medication for five years. Therefore, it seems clear that if you are at high risk of developing heart disease and have an elevated cholesterol level that you can't control with diet, you will probably benefit from treatment to lower your cholesterol.

The recommendations about when to use medication to lower cholesterol were issued by an expert panel from the National Institutes of Health and have been endorsed by virtually all the major medical organizations, including the American Heart Association, cholesterol screening.

So where is the controversy? The controversy started when a group of physicians associated with an organization called the American College of Physicians issued guidelines recommending that cholesterol screening not be done on healthy people. The concern was that many doctors use drugs to lower cholesterol in people who shouldn't receive drug treatment. If anything, available information suggests that doctors are still not recommending cholesterol medication enough, even for patients with established heart disease. In any case, these physicians developed their own guidelines, which recommended that physicians stop screening for cholesterol levels in healthy men under 35 and women under 45, as well as in all "older" people over 65.

There are several problems with this recommendation. First, there are things you can do short of taking medication to lower your cholesterol and decrease your risk of heart disease, but only if you know you have a problem. For example, if you know that you have high cholesterol, you might be more inspired to eat better, exercise more, and lose weight.

Second, the process that causes heart disease starts well before age 35, in fact, it starts in the teen years. Why wait until it has already established itself, then try to reverse the process? Finally, there are clearly people with very high cholesterol levels who do need medication but who would never know that they had a high cholesterol unless they had been screened.

Many experts have commented on the curious fact that these recommendations came at a time when the evidence linking cholesterol- lowering with decreased heart disease risk is coming faster than ever. In fact, most major professional organizations, including the National Institutes of Health and the American Heart Association, have denounced these recommendations, cholesterol screening research.

The bottom line: experts agree that having your cholesterol measured is one of the cheapest, most reliable ways to determine your risk of heart disease and can point you toward concrete ways to decrease that risk. Don't be confused by the "controversy;" regardless of your age, you are potentially at risk for heart disease and knowing your cholesterol level can help.

heart attack & cholesterol linkage

Cholesterol is essential for the normal functioning of cells, but elevated blood levels of cholesterol, specifically LDL, can lead to the formation of atherosclerotic plaque inside the blood vessel wall. Lowering elevated cholesterol levels with diet, exercise, and drugs has been shown to slow (and in some cases even reverse) the progression of atherosclerosis and to reduce the risk of both fatal and nonfatal heart attacks and also death from noncardiac causes. All adults should know their cholesterol level, and anyone who has known heart disease or who is at high risk for heart disease should consider the possibility that medication to lower cholesterol could substantially reduce the risk of having a second or even a first heart attack by cholesterol.